Review of the Economics of Surgical Treatment Options for Benign Prostatic Hyperplasia.
The goal of this paper is to review the literature detailing US-based analyses for cost and cost-effectiveness of surgical treatment options for benign prostatic hypertrophy (BPH) and associated LUTS. TURP offers the greatest degree of symptom improvement with its associated costs dependent upon operating room time, equipment, and length of hospital stay. Other studied surgical treatment modalities, including transurethral laser ablative, thermal ablative, and convective water vapor modalities as well as prostatic urethral lift and transabdominal procedures, generally carry higher costs and lower cost-effectiveness in both inpatient and outpatient settings, with specific exceptions. Compared to TURP, HoLEP and Greenlight PVP have demonstrated superior cost-effectiveness for mild, moderate, and severe BPH. Convective water vapor ablation, as with transurethral microwave/thermoablative therapies, has been observed to be less expensive per procedure than TURP on average. However, it conferred lower degrees of IPSS symptom improvement. Moreover, compared to TURP, prostatic artery embolization has demonstrated lower average costs coupled with inferior objective improvement in maximal flow rate, prostate volume reduction, PSA decline and minimal improvement in IPSS subjective outcome measures. For this review, selection bias, asymmetric patient groups, issues with study aggregation, and understudied cost contributors (including retreatment costs, long-term durability of symptom relief, recovery time, and work productivity limitations) were identified as key limitations. Nevertheless, this overview takes important steps to understand the costs of surgical treatment options for BPH, allowing for more informed clinical and policy decisions.


Palladium-Catalyzed Carbonylative Synthesis of Aryl Selenoesters Using Formic Acid as an Ex Situ CO Source.
A new catalytic protocol for the synthesis of selenoesters from aryl iodides and diaryl diselenides has been developed, where formic acid was employed as an efficient, low-cost, and safe substitute for toxic and gaseous CO. This protocol presents a high functional group tolerance, providing access to a large family of selenoesters in high yields (up to 97%) while operating under mild reaction conditions, and avoids the use of selenol which is difficult to manipulate, easily oxidizes, and has a bad odor. Additionally, this method can be efficiently extended to the synthesis of thioesters with moderate-to-excellent yields, by employing for the first time diorganyl disulfides as precursors.


Management of Asymmetry.
Orthognathic surgery in asymmetric cases is challenging because of diversity and individuality. Clinical observations are of paramount importance and need to be systemically thorough. Three-dimensional diagnosis and virtual planning have been proven extremely helpful in facilitating treatment toward symmetry in difficult cases with increasing precision. Compared with orthognathic surgery in symmetric situations, asymmetries produce numerous pitfalls and provide opportunities for out-of-the-box procedures.


[Distribution of the incidence of pleural malignant tumors in Campania in the period 1988-1999 and 1995-1997].
From the comparative appraisal, an area is identified for the period 1995-1997, corresponding to the so-called inner zones, in which the "ex novo" emersion of consisting cluster of mesotheliomas is recorded. Such data are analyzed for a possible correlation with professional and/or extra professional causes.


Effects of Alt-RAMEC protocol with facemask therapy in cleft lip palate patients in a sample of Pakistani population.
The objective of the study is to evaluate the skeletal, dentoalveolar and soft tissue changes before and after treatment with Alt-RAMEC protocol and protraction headgear in comparison to the controls. A quasi experimental study was conducted in the orthodontic department on 60 patients of cleft lip and palate. These patients were divided into two groups. Group I was the Alt-RAMEC group that underwent Alt-RAMEC protocol followed by facemask therapy while group II was the control group that underwent RME and facemask therapy. Total treatment time in both the groups was approximately 6 to 7 months. Mean and standard deviation was calculated for all the quantitative variables. Pre and post treatment changes between treatment and control groups were made using paired t-test. Intergroup comparison between treatment and control group was analyzed using independent t-test. Significance for all tests was predetermined at a P-value of ≤ 0.05. The Alt-RAMEC group showed significant forward movement of maxilla and improvement in the maxillary base. A remarkable improvement in SNA was seen. The overall outcome was better maxillo-mandibular relationship as shown by positive ANB values and angle of convexity. More effect on maxilla and least effect on mandible was notified with Alt-RAMEC protocol and facemask therapy. Improvement in transverse relationship was also evident in the Alt-RAMEC group. Alt-RAMEC protocol in combination with protraction headgear is a better alternative to treat cleft lip and palate patients in comparison to the conventional protocol.


A special role for the genotype? Some comments on Keith Baverstock: "The gene: An appraisal".
There is at present uneasiness about the conceptual basis of genetics. The gene concept has become blurred and there are problems with the distinction between genotype and phenotype. In the present paper I go back to their role in the creation of modern genetics in the early twentieth century. The terms were introduced by the Danish botanist and geneticist Wilhelm Johannsen in his big textbook of 1909. Historical accounts usually concentrate on this book and his 1911 paper "The Genotype Conception of Heredity." His bean selection experiment of 1900-1903 is generally assumed to be the source of his genotype theory. The present paper examines the scientific context and meaning of this experiment, how it was received, and how the genotype theory became securely established by the early 1910s. I argue in conclusion that the genotype/phenotype distinction, which provides the empirical basis for Johannsen's gene, was scientifically well founded when introduced and still is. Keith Baverstock's criticism does not consider the force of the bean selection experiment at the time and as a paradigm for following investigations of heredity.


[Clinical criteria of the risk of oncological diseases in women as a basis for prevention of reproductive system diseases].
A multifactorial analysis was done of clinical past history of 520 female patients with cancer of the ovary, 482 patients with cancer of the endometrium, and of 513 essentially healthy women (control group). 23 historical and clinical sings were regarded as risk factors for development of cancer of the ovary and endometrium (disordered menstrual and reproductive functions, chronic inflammatory processes, benign tumours of the uterus and adnexa uteri, pretumour affections of the skin, and other pathologies). Of these, 15 sings were recognized as being of high informative value.


Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern.
Colorectal cancer liver metastases (CRC-LM) present differential histologic growth patterns (HGP) that determine the interaction between immune and tumor cells. We explored the spatial distribution of lymphocytic infiltrates in CRC-LM in the context of the HGP using multispectral digital pathology. We did not find statistically significant differences of immune cell densities in the central regions of desmoplastic (dHGP) and non-desmoplastic (ndHGP) metastases. The spatial evaluation reported that dHGP-metastases displayed higher infiltration by CD8+ and CD20+ cells in peripheral regions as well as CD4+ and CD45RO+ cells in ndHGP-metastases. However, the reactive stroma regions at the invasive margin (IM) of ndHGP-metastases displayed higher density of CD4+, CD20+, and CD45RO+ cells. The antitumor status of the TIL infiltrates measured as CD8/CD4 reported higher values in the IM of encapsulated metastases up to 400 μm towards the tumor center (p < 0.05). Remarkably, the IM of dHGP-metastases was characterized by higher infiltration of CD8+ cells in the epithelial compartment parameter assessed with the ratio CD8epithelial/CD8stromal, suggesting anti-tumoral activity in the encapsulating lesions. Taking together, the amount of CD8+ cells is comparable in the IM of both HGP metastases types. However, in dHGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in ndHGP-metastases.


[Effect of histamine on the hexokinase activity and RNA synthesis in the seminal vesicles and prostate of orchiectomized rats].
Due to orchidectomy, carried out two weeks before the experiment, in androgene-dependent rat tissues a hexokinase activity was found to be decreased several times. Within 24 hrs after administration of histamine into orchidectomized rats the hexokinase activity was increased by 96% in seminal follicles and by 160% in prostate. Incorporation of 3H-uridine into RNA of seminal follicles and prostate of castrated rat males was increased by 60% and 210%, respectively, within 3 hrs after the administration of histamine. The stimulating effects of histamine on RNA synthesis and the hexokinase activity were completely inhibited by actinomycin D. The data obtained suggest that histamine was one of mediators in the effect of testosterone on the tissues-targets.


Physico-chemical characterization of lignins from different sources for use in phenol-formaldehyde resin synthesis.
During the last decades lignin has been investigated as a promising natural alternative to petrochemicals in phenol-formaldehyde (PF) resin production, due to their structural similarity. Physico-chemical characterization of three types of lignin, namely kraft pine lignin (L1), soda-anthraquinone flax lignin (L2), and ethanol-water wild tamarind lignin (L3) has been evaluated to determine which one is the most suitable chemical structure for above purpose. Characterization has been performed using Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectrometry ((1)H NMR) to analyse the chemical structure, gel permeation chromatography (GPC) for determining molecular weight (MW) and molecular weight distribution (MWD), differential scanning calorimetry (DSC) to measure the glass transition temperature and thermogravimetric analysis (TGA) to follow the thermal degradation. Both structural and thermal characteristics suggest that kraft pine lignin (L1) would be a better phenol (P) substitute in the synthesis of lignin-phenol-formaldehyde (LPF) resins, as it presents higher amounts of activated free ring positions, higher MW and higher thermal decomposition temperature.


Hypervirulent-host-associated Citrobacter rodentium cells have poor acid tolerance.
Enhanced virulence or infectivity after passage through a mammalian host has been reported for a number of enteric food-borne pathogens. Citrobacter rodentium is a mouse pathogen that mimics many aspects of enterohemorrhagic Escherichia coli infection of humans and serves as a useful model for studying virulence mechanisms. Emergence of a hyperinfectious state after passage through mouse gastrointestinal tract was reported for C. rodentium. We wanted to investigate if increased acid tolerance could explain hypervirulence status of C. rodentium. Although we were able to observe hyperinfectious state of C. rodentium upon host passage, the cells were extremely acid sensitive. Growth under mildly acidic conditions (LB-MES, pH 5.5) induced acid tolerance of C. rodentium, but did not improve the organism's ability to establish infection. Growth under anaerobic environment on fecal components also did not induce hyperinfectious state. Thus, contrary to conventional anticipation, hypervirulent C. rodentium cells were found to be acid sensitive thereby revealing limitations of the role of mouse gastric acidity by itself in elucidating the hypervirulent phenotype.


Comparison of filtration efficiency and respiratory resistance of COVID-19 protective masks by multi-national standards.
Face masks from worldwide satisfy different standards during the COVID-19 pandemic, which led to the public misunderstanding of the concepts. We systematically evaluated the quality of face masks provided by different companies according to multi-national standards, including EN 149-2001+A1: 2009, GB 2626-2019 and NIOSH 42 CFR Part 84-2019, focusing particularly on the particulate filtration efficiency (PFE) and respiratory resistance performance. Three types of masks (planar, folding and cup type masks) were measured based on different standard protocols. The results indicated that the PFE of the mask decreased in sequence of folding mask ≈ cup type mask > planar mask. The respiratory resistance of the masks ranked as follows: cup type mask > folding mask> planar mask. Overall, when PFE was used as the quality indicator, all the masks have a higher chance of meeting criteria of the EN149-2001+A1:2009, followed by the stricter standard set by the GB2626-2019 and NIOSH 42 CFR Part84-2019. Conversely, the respiratory resistance of the masks fulfilled the highest requirement of the EN149-2001+A1:2009 standard, while it is easier to satisfied the standard of GB 2626-2019 and NIOSH 42 CFR Part 84-2019. We believe that our study provides effective guidance for customers worldwide to choose proper face masks under different epidemic situations.


Hormonal responses to fighting in hamsters: separation of physical and psychological causes.
Male Syrian hamsters were paired and allowed to interact with a conspecific for 15 min a day for 4 days. On the fifth day, the animals were again paired, but they were kept physically separated by a mesh partition that allowed visual, olfactory, and auditory contact between the animals. Controls were placed with conspecifics on each of the 5 testing days, but the partition between them was never removed. Hamsters that were submissive on days 1-4 exhibited elevated plasma adrenocorticotropin-like immunoreactivity (ACTH-LI), beta-endorphin-like immunoreactivity (B-EP-LI), and cortisol on day 5 even though no fighting occurred on that day. Dominant hamsters did not differ from controls. These data support the hypothesis that there is an important psychological component to the pituitary-adrenocortical response in defeated hamsters.


Prenatal cocaine exposure, early cannabis use, and risky sexual behavior at age 25.
Prior research on prenatal cocaine exposure (PCE) indicates that exposed children experience behavioral dysregulation resulting in risky adolescent behavior including earlier initiation of cannabis use and sexual intercourse. The goal of this study was to examine the long-term effects of PCE on adult sexual behavior. This is a prospective cohort study of the association between PCE and risky adult sexual behavior and sexually transmitted infections (STIs) in 202 young adults (mean age = 27, SD = 0.98 years). The sample was 55% female, 46% White, and 54% Black. Data from the prenatal, childhood, and adolescent phases of the study were used to delineate pathways from PCE to adult sexual behavior. The most common risky sexual behavior was having sex while drunk or high (63%). One-third of the sample reported that they "almost always" had sex while drunk or high. We found evidence for an indirect pathway from PCE to adult sex while drunk or high via early cannabis initiation. There were no other effects of PCE on adult risky sexual behavior or on risk for STIs, after controlling for sex assigned at birth, race, age at sexual initiation, and family history of drug and alcohol problems. Although PCE has been associated with earlier initiation of sex in prior studies, PCE was not directly associated with risky adult sex or history of STI. Exposed individuals were at greater risk of sex under the influence of alcohol or drugs via earlier initiation of cannabis use during adolescence.


Human Papillomavirus Vaccine: The Cancer Prevention Moonshot.
Cervical cancer is the fourth most common cancer in women worldwide with immense associated morbidity and mortality. Although most of the cervical cancer cases are caused by the human papillomavirus (HPV) and can effectively be prevented by HPV vaccination, vaccination unfortunately remains underused on a global scale with vast inequities in distribution. A vaccine as a tool to prevent cancer, cervical and others, is largely unprecedented. Then why do HPV vaccination rates globally remain so low? This article explores the burden of disease, development of the vaccine and its subsequent uptake, cost-effectiveness, and associated equity issues.


Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques.
SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.


Interaction of the B95-8 and P3HR-1 substrains of Epstein-Barr virus (EBV) with peripheral human lymphocytes.
Two substrains of the Epstein-Barr virus derived from the B95-8 and P3HR-1 cell lines were studied for their interaction with human peripheral lymphocytes. It has been previously shown that B95-8 virus has and P3HR-1 virus lacks lymphocyte-transforming ("immortalizing") properties. DNA stimulation induced by B95-8 virus showed a good correlation with the number of surface Ig-positive cells. P3HR-1 virus added before B95-8 virus completely abolished the stimulation of DNA synthesis. It also prevented EBNA induction by B95-8 virus. P3HR-1 virus added after B95-8 virus diminished DNA stimulation by the latter in a time-dependent fashion. P3HR-1 virus did not inhibit DNA stimulation by phytohaemagglutinin but was inhibitory if added before a B cell mitogen (Staphylococcus Aureus). The origin of P3HR-1 virus and its relationship to the transformation process are discussed.


Constant normal pressure, constant surface tension, and constant temperature molecular dynamics simulation of hydrated 1,2-dilignoceroylphosphatidylcholine monolayer.
A constant normal pressure, constant surface tension, and constant temperature (NP(N)gammaT) molecular dynamics (MD) simulation of the liquid condensed phase of a 1,2-dilignoceroylphosphatidylcholine (DLGPC) monolayer has been performed at 293.15 K. A DLGPC molecule has two saturated 24-carbon acyl chains, giving the hydrocarbon core thickness of the monolayer approximately 28 A, which is close to the hydrocarbon core thickness of a membrane of a living system. NP(N)gammaT ensemble was used to reproduce the experimental observations, such as area/lipid, because surface tension is an essential factor in determining the monolayer structure. Data analysis on DLGPC/water monolayer shows that various liquid condensed-phase properties of the monolayer have been well reproduced from the simulation, indicating that surface tension 22.9 mN/M used in the simulation is an appropriate condition for the condensed-phase NP(N)gammaT simulation. The simulation results suggest that this long-chain phospholipid monolayer shares many structural characteristics with typical short-chain 1,2-diacylphosphatidylcholine systems, such as DPPC/water monolayer in the condensed phase and DPPC/water bilayer in the gel phase. Furthermore, it was found that DLGPC/water monolayer has almost completely rotationally disordered acyl chains, which have not been observed so far in short-chain 1,2-diacylphosphatidylcholine/water bilayers. This study indicates the good biological relevance of the DLGPC/water monolayer which might be useful in protein/lipid studies to reveal protein structure and protein/lipid interactions in a membrane environment.


A cohort study of interstitial cystitis/bladder pain syndrome and hysterectomy.
Symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS) are often confused with uterine conditions. Gynecologists may therefore recommend hysterectomy which was inappropriate for these patients. This study investigated whether IC/BPS increases the risk of hysterectomy in a large nationwide retrospective cohort study. From the Longitudinal Health Insurance Database 2010 (LHID2010) in Taiwan, we identified women diagnosed with IC/BPS between 2002 and 2013. Those with a history of hysterectomy before IC/BPS diagnosis were excluded. All women were stratified into three subgroups (younger, middle, older age) based on the propensity scores of 15 confounding factors, including age and comorbidities. All were followed until the end of 2013 to detect the event of hysterectomy. The hazard ratio (HR) of hysterectomy in the IC/BPS cohort was compared with the non-IC/BPS cohort among the three subgroups by Cox regression after adjusting for confounding factors. In addition to the representative middle age, subgroup 2 had similar rates of comorbidities as the general population. The study was both externally and internally valid. The risk of hysterectomy in the IC/BPS cohort (n = 536) was significantly higher than in the non-IC/BPS cohort (n = 103846) in subgroup 2 (HR = 1.701, 95 % CI 1.056-2.740). The mean time to hysterectomy after diagnosis of IC/BPS was 2.97 years. In this nationwide study, we found that IC/BPS has a causal impact on hysterectomy in the middle-age subgroup in LHID 2010. The possibility of a woman having IC/BPS should be evaluated prior to hysterectomy to avoid inappropriate surgery.


Collisional spectroscopy as a screening procedure for the determination of 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole from acid hydrolysis of B-poly(L-lysine) and B-albumin.
The direct determination of 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI), present in the acid hydrolysis products of B-poly(L-lysine) and B-albumin and which appears to be a key intermediate in the physicochemical changes occurring during the incubation of protein with glucose, has been carried out by collisional spectroscopy, using a commercial double-focusing, reverse-geometry mass spectrometer and without any sample derivatization and chromatographic separation procedures.


New biomarkers for antenatal infection: MICA and MICB gene expression in preterm babies.
The human major histocompatibility complex class I chain-related gene A and B (MICA and MICB) is one of the genes in chromosome 6. As MIC expression is inducible by heat, viral infection, inflammation and DNA damage, the molecules have been thought to be stress markers for the cells. We aimed to find the level of mRNA concentrations of MICA and MICB in neonates without any evidence of early onset infection.


[The distinction of elevated alpha-fetoprotein levels in amniotic fluids for antenatal diagnosis of genetic defects].
Among 1017 amniotic fluid samples of 831 patients were 110 cases (10,8%) cases with sanguivolent amniotic fluid in the first portion and a second clear specimen. Contrary to the trend to analyse only the second clear share, we tested both samples. 110 pregnancies are analysed. The abortion risk (1,8%) in this group and the rate of prematurity (8,1%) are not increased. Retrospectively we were able to demonstrate a fetus injury in one case. The different analysis enable us to a conclusion about the fetal risk.


Cellular and molecular osmoregulatory responses to cadmium exposure in Gammarus fossarum (Crustacea, Amphipoda).
Osmoregulation represents a reliable indicator of the physiological state of crustaceans. It is mainly effected in gills via Na(+)/K(+)-ATPase (NKA) providing the major driving force for ion transport. In the present study conducted in the freshwater amphipod Gammarus fossarum, the impact of an exposure to 15 μg Cd L(-1) for 3 and 7d was investigated on the haemolymph osmolality (HO), gill structure, NKA localization in gills and its relative expression. In Cd-exposed G. fossarum, mean HO significantly decreased compared to controls. In animals exposed for 3 and 7d, high inter-individual variations in HO values were noted, resulting in their separation into unimpacted, slightly impacted and impacted animals. In unimpacted individuals, gills retained their organization, showing a thicker gill epithelium than in controls; NKA fluorescence was continuously observed along the gill epithelium and was distributed on a broader area than in controls. In slightly impacted individuals, a thinner epithelium, a slight collapse of the gill and a lower NKA fluorescence were observed compared to unimpacted specimens. In impacted individuals, dramatic alterations of the gill structure, including hyperplasia and alteration of the pillars, resulting in the collapse of the gill and the disappearance of the haemolymphatic canals were observed, as well as very limited NKA fluorescence. Therefore, the degree of gill alteration and the intensity of NKA fluorescence observed in the different groups were correlated with their respective HO levels. The relative amount of the NKA α-subunit mRNA significantly increased in specimens exposed to Cd for 3d compared to controls, and then returned to control level after 7d. The relationships between the changes in HO values, NKA immunostaining and mRNA relative expression are discussed. These results confirm that HO represents a valuable biomarker to evaluate crustacean health, and they underline the interest to assess individual responses to contaminants.


Comparison of the performance of implantable cardioverter-defibrillator leads among manufacturers.
Leads are often considered the weakest link in implantable cardioverter-defibrillator (ICD) systems, and lead dysfunction is a major concern for ICD recipients. The aim of this study was to compare the lead performance from three different manufacturers. We retrospectively reviewed consecutive patients who underwent ICD system implantation at Chiba University Hospital, Japan, between March 2008 and September 2017. The following leads were implanted in our center: Durata (St. Jude Medical, St. Paul, MN, USA, now Abbott) (n = 105), Linox and LinoxSmart (Biotronik, Berlin, Germany) (n = 66), and Sprint Quattro (Medtronic, Minneapolis, MN, USA) (n = 126). A total of 297 ICD leads were analyzed. Failure rates for Durata, Linox/LinoxSmart, and Sprint Quattro were 0.20%/patient year, 0.95%/patient year, and 1.84%/patient year, respectively, during a mean follow-up of 4.8, 6.4, and 3.0 years, respectively. The cumulative ICD lead survival probability was 98.9%, 100%, and 87.5%, after 5 years, respectively. The survival probability over the entire follow-up time as measured by the log-rank test was lower for Sprint Quattro leads than for either Durata (p = 0.011) or Linox/LinoxSmart (p = 0.028). The difference between Durata and Linox/LinoxSmart was not significant (p = 0.393). In this single-center retrospective study, the performance of Sprint Quattro was lower than the performance of Linox/LinoxSmart and Durata leads. Large-scale, multi-center studies or manufacturer-independent registries may be necessary to confirm or reject self-reported survival probabilities from manufacturers' product performance reports.


A complex of lactoferrin with monophosphoryl lipid A is an efficient adjuvant of the humoral and cellular immune response in mice.
Our recent investigations demonstrated adjuvant properties of lactoferrin (LF). Other studies proved efficacy and safety of monophosphoryl lipid A (MPL) as an adjuvant in humans. In an attempt to construct more efficient and safer adjuvants, we evaluated the activity of LF-MPL complex, formed by incubation of LF and MPL from Hafnia alvei at 20:1 w/w ratio, and verified its characteristics by SDS-PAGE analysis. Binding kinetics was determined by surface plasmon resonance analysis using a BIAcore 1000 biosensor system. The efficiency of the complex in enhancing the humoral and cellular immune responses was analyzed in BALB/c mice. The complex stimulated the humoral immune response to ovalbumin (OVA) and sheep red blood cells significantly stronger than both components separately, used at respective doses. In addition, the complex increased the serum levels of IgG, IgG2a and IgG1 OVA-specific antibodies as compared to the actions of LF or MPL alone. In the model of delayed type hypersensitivity (DTH) the strongest immune response was demonstrated with OVA administered subcutaneously, admixed with the complex. Administration of the complex in incomplete Freund's adjuvant, together with a sensitizing dose of antigen, was similarly effective as immunization with complete Freund's adjuvant. The complex also significantly enhanced the DTH response to orally administered Calmette-Guérin bacilli. In summary, the new type of adjuvant, the LF-MPL complex, was described. Its activity surpassed the adjuvant action of both constituents tested separately in the humoral and cellular immune responses in mice. The plausible mode of action of the new adjuvant is discussed.


[Connatal neuroblastoma IV-S. Clinical and therapeutic considerations on a case].
The authors describe an original case of connatal neuroblastoma (stage IV-S), observed at birth, for the presence of subcutaneous nodules, in rapid expansion. Therapeutical approach is discussed (treatment or no treatment) on the base of literature data.


Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis.
Prognosis for the occurrence of relapses in individuals with relapsing-remitting multiple sclerosis (RRMS), the most common subtype of multiple sclerosis (MS), could support individualized decisions and disease management and could be helpful for efficiently selecting patients for future randomized clinical trials. There are only three previously published prognostic models on this, all of them with important methodological shortcomings. We aim to present the development, internal validation, and evaluation of the potential clinical benefit of a prognostic model for relapses for individuals with RRMS using real-world data. We followed seven steps to develop and validate the prognostic model: (1) selection of prognostic factors via a review of the literature, (2) development of a generalized linear mixed-effects model in a Bayesian framework, (3) examination of sample size efficiency, (4) shrinkage of the coefficients, (5) dealing with missing data using multiple imputations, (6) internal validation of the model. Finally, we evaluated the potential clinical benefit of the developed prognostic model using decision curve analysis. For the development and the validation of our prognostic model, we followed the TRIPOD statement. We selected eight baseline prognostic factors: age, sex, prior MS treatment, months since last relapse, disease duration, number of prior relapses, expanded disability status scale (EDSS) score, and number of gadolinium-enhanced lesions. We also developed a web application that calculates an individual's probability of relapsing within the next 2 years. The optimism-corrected c-statistic is 0.65 and the optimism-corrected calibration slope is 0.92. For threshold probabilities between 15 and 30%, the "treat based on the prognostic model" strategy leads to the highest net benefit and hence is considered the most clinically useful strategy. The prognostic model we developed offers several advantages in comparison to previously published prognostic models on RRMS. Importantly, we assessed the potential clinical benefit to better quantify the clinical impact of the model. Our web application, once externally validated in the future, could be used by patients and doctors to calculate the individualized probability of relapsing within 2 years and to inform the management of their disease.


Vascular factors and depression.
This paper examines possible mechanisms that may explain the bi-directional relationship between vascular disease and depression. A literature review was carried out using Medline from 1996 to 2007, using relevant key words including vascular depression, and supplemented by key references to earlier work. Several mechanisms were considered including: autonomic dysfunction, platelet activation, hypothalamic pituitary axis activation, endothelial dysfunction, cytokines, omega 3 fatty acids, genetics, homocysteine and effects of treatment. The relationship between vascular disease and depression cannot solely be explained by current established risk factors or the effects of treatment for depression. Other mechanisms must apply, and there is some evidence for common genetic factors. Promising future lines of investigation include homocysteine, cytokines and endothelial dysfunction. More longitudinal studies combined with measurements of these biomarkers are needed.


Changes in Dietary Patterns through a Nutritional Intervention with a Traditional Atlantic Diet: The Galiat Randomized Controlled Trial.
Unhealthy dietary patterns (DPs) can lead to cardiovascular and other chronic diseases. We assessed the effects of a community-focused intervention with a traditional Atlantic diet on changes in DPs in families and the associations of these changes with weight loss. The Galiat study is a randomized, controlled trial conducted in 250 families (720 adults and children) and performed at a primary care setting with the cooperation of multiple society sectors. Over 6 months, families randomized to the intervention group received educational sessions, cooking classes, written supporting material, and foods that form part of the Atlantic diet, whereas those randomized to the control group followed their habitual lifestyle. At baseline, five DPs that explained 30.1% of variance were identified: "Caloric", "Frieds", "Fruits, vegetables, and dairy products", "Alcohol", and "Fish and boiled meals." Compared to the controls, the intervention group showed significant improvements in "Fruits, vegetables, and dairy products" and "Fish and boiled meals" and reductions in the "Caloric" and "Frieds". Changes in bodyweight per unit increment of "Frieds" and "Fruits, vegetables, and dairy products" scores were 0.240 kg (95% CI, 0.050-0.429) and -0.184 kg (95% CI, -0.379-0.012), respectively. We found that a culturally appropriate diet improved DPs associated with weight loss.


The reticular arousal threshold during the transition from slow wave sleep to paradoxical sleep in the rat.
The short-lasting intermediate stage of sleep occurring between slow wave sleep and paradoxical sleep showed frontal cortex spindles of higher amplitude and longer duration than during slow wave sleep, and hippocampal theta rhythm of lower frequency than during paradoxical sleep. During the intermediate stage, the mesencephalic reticular arousal threshold was slightly higher than during the slow wave sleep and much lower than in the paradoxical sleep. Thus, following this central reactivity test, the intermediate stage seems to be functionally nearer the slow wave sleep than the paradoxical sleep.


Factors affecting computed tomography image quality for assessment of mechanical aortic valves.
Evaluating mechanical valves with computed tomography (CT) can be problematic because artifacts from the metallic components of valves can hamper image quality. The purpose of this study was to determine factors affecting the image quality of cardiac CT to improve assessment of mechanical aortic valves. A total of 144 patients who underwent aortic valve replacement with mechanical valves (ten different types) and who underwent cardiac CT were included. Using a four-point grading system, the image quality of the CT scans was assessed for visibility of the valve leaflets and the subvalvular regions. Data regarding the type of mechanical valve, tube voltage, average heart rate (HR), and HR variability during CT scanning were compared between the non-diagnostic (overall image quality score ≤2) and diagnostic (overall image quality score >2) image quality groups. Logistic regression analyses were performed to identify predictors of non-diagnostic image quality. The percentage of valve types that incorporated a cobalt-chrome component (two types in total) and HR variability were significantly higher in the non-diagnostic image group than in the diagnostic group (P < 0.001 and P = 0.013, respectively). The average HR and tube voltage were not significantly different between the two groups (P > 0.05). Valve type was the only independent predictor of non-diagnostic quality. The CT image quality for patients with mechanical aortic valves differed significantly depending on the type of mechanical valve used and on the degree of HR variability.


[Chlorhexidine in the prevention of periodontal disease].
Authors considering microbiological and clinical characteristics of chlorhexidine pointing out its notable capacity to inhibit bacterial plaque formation and analyze possible collateral effects by its use.


The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care.
This study aimed at developing a shortened version of the EORTC QLQ-C30, one of the most widely used health-related quality of life questionnaires in oncology, for palliative care research. The study included interviews with 41 patients and 66 health care professionals in palliative care to determine the appropriateness, relevance and importance of the various domains of the QLQ-C30. Item response theory methods were used to shorten scales. Patients and health care professionals rated pain, physical function, emotional function, fatigue, global health status/quality of life, nausea/vomiting, appetite, dyspnoea, constipation, and sleep as most important. Therefore, these scales/items were retained in the questionnaire. Four scales were shortened without reducing measurement precision. Important dimensions not covered by the questionnaire were identified. The resulting 15-item EORTC QLQ-C15-PAL is a 'core questionnaire' for palliative care. Depending on the research questions, it may be supplemented by additional items, modules or questionnaires.


Aflatoxin induced hepatocarcinogenesis in ducks.
To assess the carcinogenic response of duck hepatic tissue, an experimental study was undertaken. Pure aflatoxin B1, was administered to twelve white pekin ducks of two to three months of age at a dose rate of 0.04165 mg/kg body weight every third day for six months. There was reduction in body weight and haemoglobin level from the third month onwards. Total serum protein, albumin and globulin had a slow and gradual reduction and ESR was significantly increased from the third month. Serum enzymes (AST, ALT, GGT and ALP) were significantly increased from the Vlllth to XVth fortnights (Two weeks). Ten ducks developed hepatic tumours by 180th day. Four of them had neoplastic nodules on the 90th day. Histo-pathologically they were hepatocellular carcinoma (6), Cholangiocellular carcinoma (4) and Chronic hepatitis (2). There was moderate to severe expression of GGT and ALP in the liver tissue during neoplastic transformation.


A comparative study of MIB-1 staining indices of gliomas measured by NIH Image analysis program and conventional manual cell counting method.
To evaluate the NIH Image measured MIB-1 staining index (SI) as a useful tool for the determination of proliferative activity of gliomas, MIB-1 immunohistochemistry was performed on paraffin sections to estimate the proliferative activity of 50 gliomas. Five to eight RGB images at 200 magnifications were acquired per sample in a Macintosh computer using a RD-175 digital camera and Adope Photoshop program, followed by conversion of the RGB image to B (blue subtracted) and R (red subtracted) images and finally automatic cell counting of more than 1000 cells per sample by the NIH Image analysis program. The mean MIB-1 staining indices by both NIH count and visually assessed (manual) count respectively were 12.7% +/- 9.9% (mean +/- standard deviation) and 12.6% +/- 9.9% in all gliomas (n = 50), 2.9% +/- 0.6% and 2.3% +/- 0.6% in grade I and II astrocytomas (n = 9), 10.7% +/- 8.9% and 11.1% +/- 9.0% in grade III gliomas (n = 17), 16.1% +/- 9.1% and 16.3% +/- 9.1% in glioblastoma multiformes (n = 20), 26.0% +/- 4.9% and 24.5% +/- 2.6% in other glial tumors (n = 4). These paired values were assumed to be identical, since the p value obtained by paired t-test in all gliomas was 0.905. We conclude that the MIB-1 staining index measured by NIH Image is reliable and universal.


"They had the lunch lady coming up to assist": The experiences of menarche and menstrual management for adolescents with physical disabilities.
Menarche is a pivotal time in an adolescent's life but can be experienced differently by those with physical disabilities. Parents typically serve as the primary educators and support for their daughters during this time. Little is known about the parent's perspective of their daughter's experience preparing for menarche and learning to manage menses. We sought to understand the parent's perspective of the experience of their daughter with a physical disability around menarche and their preferences for health care provider support. Individual semi-structured interviews were conducted with 21 parents of a daughter with a physical disability ages 7-26. Interviews were coded by 2 reviewers using Grounded Theory, with disagreements resolved by consensus. Six themes emerged regarding the parent's perception of the experiences, including 1) variation in emotional responses to menarche, 2) parent's perception of their daughter's experience with menses and menstrual symptoms, 3) cross-section of disability and menstrual management, 4) menstrual management at school, 5) parental knowledge correlating to daughter's preparation for menarche, and 6) desires for health care provider support. All parents reported that their daughters faced challenges during menarche, ranging from emotional distress to dealing with the inaccessibility of hygiene products. Managing periods at schools was particularly burdensome. Parents who were better educated about what to expect were better able to prepare their daughters, but had difficulties finding informed, supportive providers. Health care providers should provide both anticipatory guidance and holistic, respectful, and equitable options for the management of menstrual symptoms.


Directionality of PYD filament growth determined by the transition of NLRP3 nucleation seeds to ASC elongation.
Inflammasomes sense intrinsic and extrinsic danger signals to trigger inflammatory responses and pyroptotic cell death. Homotypic pyrin domain (PYD) interactions of inflammasome forming nucleotide-binding oligomerization domain (NOD)-like receptors with the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) mediate oligomerization into filamentous assemblies. We describe the cryo-electron microscopy (cryo-EM) structure of the human NLRP3PYD filament and identify a pattern of highly polar interface residues that form the homomeric interactions leading to characteristic filament ends designated as A- and B-ends. Coupling a titration polymerization assay to cryo-EM, we demonstrate that ASC adaptor protein elongation on NLRP3PYD nucleation seeds is unidirectional, associating exclusively to the B-end of the filament. Notably, NLRP3 and ASC PYD filaments exhibit the same symmetry in rotation and axial rise per subunit, allowing a continuous transition between NLRP3 and ASC. Integrating the directionality of filament growth, we present a molecular model of the ASC speck consisting of active NLRP3, ASC, and Caspase-1 proteins.


Fortified hyperbranched PEGylated chitosan-based nano-in-micro composites for treatment of multiple bacterial infections.
Bacterial resistance is a real threat to human health. One of the most common strategies used to overcome this problem is the combination therapy. This study proposes a new chitosan-based nano-in-microparticles (NIMs) antibacterial platform that can deliver multiple antibacterial therapeutics at the same time. Chitosan (CS) was PEGylated to overcome its limited water solubility. Then, the antibacterial activity of the resulting PEG-CS was fortified via conjugation with dendritic polyamidoamine hyperbranches (HB) as well as in-situ immobilization of silver nanoparticles (AgNPs) to be efficient against multiple bacterial strains. Montmorillonite nanoclay (MMT) was prepared and used to encapsulate ibuprofen (IBU) as anti-inflammatory drug to reduce any concomitant inflammatory response during bacterial infection. The successful synthesis of PEG-HBCS-AgNPs as well as IBU-MMT nanocomplex was confirmed using FTIR, 1H NMR, DSC, TGA and EDX. SEM micrographs showed a complete formation of NIM spherical particles with a size around 13 µm. Besides, the newly developed drugs-loaded CS-based NIM formulation showed a better widespread activity on the tested aerobic and anaerobic bacterial species, and it may represent, after further optimization, a promising approach for overcoming multiple-bacterial infection.


Representing logic gates over Euclidean space via heaviside step function.
Theoretical concepts asserted by Alan Turing are the basis of the computation and hence of machine intelligence. Turing Machine, the fundamental computational model, has been proven to be reducible to a logic circuit and, at the same time, portable into a computer program that can be expressed through a combination of fundamental programming language control structures. This work proposes a mathematical framework that analytically models logic gates employing Heaviside Step Function. The existence of a correspondence between a generic finite-time algorithm and the proposed mathematical formulation is proven. The proposed interpretation is given through a well-defined logical circuit analytical expression. Relevant geometrical applications, related to polygon processing, having wide implications in engineering branches are presented together with a new Penalty Method for constrained optimization problems handling. A detailed simulation campaign is conducted to assess the effectiveness of the applications derived from the proposed mathematical framework.


Parkinson's disease-associated receptor GPR37 is an ER chaperone for LRP6.
Wnt/β-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky β-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/β-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis. We conclude that GPR37 is crucial for cellular protein quality control during Wnt signaling.


Retracted: Mate Analysis of Hepatocellular Carcinoma Immune Subtypes and Their Functional Effects Based on Fuzzy Logic and Evolutionary Algorithms.
[This retracts the article DOI: 10.1155/2022/5787981.].


Histoautoradiography of central nervous system in rats with generalized tetanus due to 125I-toxin.
Rats were injected i.v. with 125I-tetanus toxin. In autoradiographs of the spinal cord radioactivity was found over the pericarya and in the surroundings of the motoneurones whereas grain density was less over their nuclear region. In addition, pericarya in the lateral horn of the thoracic region and also the bipolar cells of the spinal ganglia contained radioactivity. The central part and the dorsal horns of spinal cord, and the white substance did not show any appreciable radioactivity. Within the medulla oblongata, clusters of large cells representing motor nuclei, as well as some fibre tracts close to them, contained 125I. Forebrain and cerebellum remained free. According to its histoautoradiographic appearance, generalized tetanus can be described best as a combination of multiple local tetani.


Application of a latent variable model for a multicenter study on early effects due to mercury exposure.
A latent variable model was applied to the results of an Italian multicenter nation-wide cross-sectional study to assess the earliest health effects due to mercury (Hg) exposure caused by occupation, dental amalgams (DENTAM) and fish eating (FISH). The studied population included subjects recruited from four different geographical areas. A total number of 122 workers from chloroalkali plants and production of thermometers and neon lamps formed the occupationally exposed group, whereas 196 subjects, recruited from the same areas and not occupationally exposed to mercury, formed the control group. Neuropsychological functions were assessed with neurobehavioral testing including vigilance, motor and cognitive function, tremor measurements, and with symptoms concerning neuropsychological and mood assessment. Neuroendocrine function was examined with the measurement of prolactin (PRL) level. Parameters of immunological and renal function were also measured. The target population was characterized by the number and surface of dental amalgams and consumption of fish. In the exposed workers the average urinary mercury (U-Hg) was 10.4+/-6.9 (geometric mean 8.3, range 0.2-35.2) microg/g creatinine, whereas in the control group it was 1.9+/-2.8 (geometric mean 1.2, range 0.1-33.2) microg/g creatinine. The preliminary results indicated that finger tapping (FT) and the Branches alternate movement task (BAMT) coordination test were associated with the occupational exposure (OCCEXP). PRL was significantly decreased among the exposed workers, and inversely related to U-Hg. Among the immunological and renal parameters, cytokine serum interleuchin-8 (sIL8) and beta(2) micro globulin (beta(2)MG) were lower in the exposed group and negatively correlated to U-Hg. Small-size fish consumption was associated to a beneficial effect on symptoms reporting. No effects were observed concerning dental amalgams. After first evaluating the relationship between mercury exposure and each indicator of effect, further assessment was performed to identify the earliest effects related to mercury exposure among those who resulted in being associated in the preliminary elaboration. Two latent variables "exposure" and "effect" were identified, integrating respectively the different forms of exposure (occupational, due to dental amalgams and fish consumption) and the indicators of effects (FT, BAMT, PRL, sIL8, beta(2)MG). Confounding factors (age, alcohol, body mass index (BMI)) were considered in the same model. This further analysis showed that an inverse association of occupational exposure to mercury with PRL and BAMT, with Hg-U mediating the effect on PRL, was predominant with respect to the other form of mercury exposure, the other indicators of effect and the confounders. In conclusion, this study supports the finding of alterations of neuroendocrine secretion and motor coordination at very low occupational exposure levels of inorganic mercury, below the current ACGIH Biological Exposure Index. These changes occur at lower levels than other subtle effects on the renal function and the immunitary system. On the contrary, dental amalgams and small-size fish consumption do not seem to be associated to any adverse health effect at these exposure levels.


The m6A reader YTHDC2 inhibits lung adenocarcinoma tumorigenesis by suppressing SLC7A11-dependent antioxidant function.
The biological functions of N6-methyladenosine (m6A) RNA methylation are mainly dependent on the reader; however, its role in lung tumorigenesis remains unclear. Here, we have demonstrated that the m6A reader YT521-B homology domain containing 2 (YTHDC2) is frequently suppressed in lung adenocarcinoma (LUAD). Downregulation of YTHDC2 was associated with poor clinical outcome of LUAD. YTHDC2 decreased tumorigenesis in a spontaneous LUAD mouse model. Moreover, YTHDC2 exhibited antitumor activity in human LUAD cells. Mechanistically, YTHDC2, via its m6A-recognizing YTH domain, suppressed cystine uptake and blocked the downstream antioxidant program. Administration of cystine downstream antioxidants to pulmonary YTHDC2-overexpressing mice rescued lung tumorigenesis. Furthermore, solute carrier 7A11 (SLC7A11), the catalytic subunit of system XC-, was identified to be the direct target of YTHDC2. YTHDC2 destabilized SLC7A11 mRNA in an m6A-dependent manner because YTHDC2 preferentially bound to m6A-modified SLC7A11 mRNA and thereafter promoted its decay. Clinically, a large proportion of acinar LUAD subtype cases exhibited simultaneous YTHDC2 downregulation and SLC7A11 elevation. Patient-derived xenograft (PDX) mouse models generated from acinar LUAD showed sensitivity to system XC- inhibitors. Collectively, the promotion of cystine uptake via the suppression of YTHDC2 is critical for LUAD tumorigenesis, and blocking this process may benefit future treatment.


Two novel ergtoxins, blockers of K+-channels, purified from the Mexican scorpion Centruroides elegans elegans.
Voltage-gated potassium channels of the ether-a-go-go related gene (ERG) family are implicated in many important cellular processes. Three such genes have been cloned (erg1, erg2 and erg3) and shown to be expressed in the central nervous system (CNS) of mammalians. This communication describes the isolation and characterization of two isoforms of scorpion toxin (CeErg4 and CeErg5, systematic nomenclature gamma-KTx1.7 and gamma-KTx1.8, respectively) that can discriminate the various subtypes of ERG channels of human and rat. These peptides were purified from the venom of the Mexican scorpion Centruroides elegans elegans. They contain 42 amino acid residues, tightly folded by four disulfide bridges. Both peptides block in a reversible manner human and rat ERG1 channels, but have no effect on human ERG2. They also block completely and irreversibly the rat ERG2 and the human ERG3 channels hence are excellent tools for the discrimination of the various sub-types of ion-channels studied.


Image quality and acquisition time assessments for phase oversampling in compressed sensing sensitivity encoding: Comparison with conventional SENSE.
This study compared sensitivity encoding (SENSE) and compressed sensing sensitivity encoding (CS-SENSE) for phase oversampling distance and assessed its impact on image quality and image acquisition time. The experiment was performed with a large diameter phantom using 16-channel anterior body coils. All imaging data were divided into three groups according to the parallel imaging technique and oversampling distances: groups A (SENSE with phase oversampling distance of 150 mm), B (CS-SENSE with phase oversampling distance of 100 mm), and C (CS-SENSE with phase oversampling distance of 75 mm). No statistically significant differences were observed among groups A, B, and C regarding both T2 and T1 turbo spin-echo (TSE) sequences using an acceleration factor (AF) of 2 (p = 0.301 and 0.289, respectively). In comparison with AF 2 of group A, the scan time of AF 2 of groups B and C was reduced by 11.2% and 23.5% (T2 TSE) and 15.8% and 22.7% (T1 TSE), respectively, while providing comparable image quality. Significant image noise and aliasing artifact were more evident at AF ≥ $ \ge $ 2 in group A compared with groups B and C. CS-SENSE with a less phase oversampling distance can reduce image acquisition time without image quality degradation compared with that of SENSE, despite the increase in aliasing artifact as the AF increased in both CS-SENSE and SENSE.


MiR-490-5p inhibits the stemness of hepatocellular carcinoma cells by targeting ECT2.
To explore the targeting relationship between miR-490-5p and ECT2 in hepatocellular carcinoma (HCC) and the influences of miR-490-5p and ECT2 on the stemness of HCC cells. The expressions of miR-490-5p and ECT2 in HCC tissues and adjacent tissues were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between the expression levels of miR-490-5p/ ECT2 and the overall/disease-free survival (OS/DFS) of patients with HCC were evaluated using correlative curves. In addition, the targeting relationship between miR-490-5p and ECT2 was predicted by TargetScan and verified by dual-luciferase reporter assay. Plasmid transfection was used for overexpression of ECT2 in HepG2 cells, and transfection efficiency was verified by qRT-PCR. Cell Counting Kit-8 assay and cell sphere-formation assay were conducted to detect the proliferation and sphere-formation ability of HCC cells, respectively. Cell populations with different cell transfections were sorted using flow cytometry. The expression levels of proteins in the stem cell signaling pathway were determined using Western blot analysis. MiR-490-5p was remarkably downregulated, yet ECT2 was upregulated in HCC tissues compared with adjacent tissues. MiR-490-5p expression was positively correlated with OS and DFS of patients with HCC, which were otherwise negatively correlated with ECT2 expression. ECT2 was validated to be the downstream target of miR-490-5p. Overexpression of miR-490-5p restrained the sphere formation ability, stemness, and proliferation of HCC cells. MiR-490-5p repressed the stemness of HCC cells through inhibiting the expression of ECT2. MiR-490-5p may be an underlying therapeutic target in HCC treatment.


Dilemma of indication for thrombolysis in a patient with acute ischemic stroke treated with a novel oral anticoagulant.
Increasing age of the population is associated with a higher rate of cerebrovascular diseases, and every sixth stroke is the consequence of atrial fibrillation. In atrial fibrillation, vitamin K antagonists are routinely used to prevent cardioembolic strokes. Thrombolytic treatment recombinant tissue-type plasminogen activator (rt-PA) has established efficacy in acute ischemic stroke, but in anticoagulated patients, its use is contraindicated for those with an international normalized ratio of 1.7 or more. Recently, novel oral anticoagulants have become available. With conventional methods, however, it is difficult to assess the coagulation status of patients on these new treatments. We report the case of a patient treated with dabigatran who developed acute ischemic stroke and was considered for thrombolysis. Because of the prolonged thrombin time (TT), thrombolysis was not performed. Repeated coagulation tests 5 days after stroke, with unchanged anticoagulant (dabigatran) treatment, found 2-fold higher TT and activated partial thromboplastin time (APTT) compared with the values found in the acute stage. Routine coagulation tests (TT and APTT) do not reliably reflect the coagulation features of a patient; therefore, there is an urgent need to develop reliable biomarkers and an adequate guideline to help decision making regarding thrombolysis in those who develop their strokes while on one of these new oral anticoagulants.


Chemometric methods applied to the calibration of a Vis-NIR sensor for gas engine's condition monitoring.
This paper describes the calibration process of a Visible-Near Infrared sensor for the condition monitoring of a gas engine's lubricating oil correlating transmittance oil spectra with the degradation of a gas engine's oil via a regression model. Chemometric techniques were applied to determine different parameters: Base Number (BN), Acid Number (AN), insolubles in pentane and viscosity at 40 °C. A Visible-Near Infrared (400-1100 nm) sensor developed in Tekniker research center was used to obtain the spectra of artificial and real gas engine oils. In order to improve sensor's data, different preprocessing methods such as smoothing by Saviztky-Golay, moving average with Multivariate Scatter Correction or Standard Normal Variate to eliminate the scatter effect were applied. A combination of these preprocessing methods was applied to each parameter. The regression models were developed by Partial Least Squares Regression (PLSR). In the end, it was shown that only some models were valid, fulfilling a set of quality requirements. The paper shows which models achieved the established validation requirements and which preprocessing methods perform better. A discussion follows regarding the potential improvement in the robustness of the models.


Serum-growth hormone and free-fatty-acids levels following angiocardiography in children.
Blood-free-fatty acids (F.F.A.) and growth-hormone levels were determined in 9 children subjected to cardiac catheterization and angiography. A significant rise of growth-hormone level was recorded immediately after angiocardiography, followed by a marked increase of F.F.A. levels 2--4 hours after termination of the catheterization. These results may indicate that the high levels of F.F.A. sustained after cardiac catheterization and angiography are probably due to the increase of growth -hormone secretion during the procedure.


Cosmeceuticals: focus on topical retinoids in photoaging.
Evidence from a randomized clinical trial showed that, in spite of the many surgical procedures effective in ameliorating the clinical appearance of photoaged skin, the only medical therapy with proven benefits in photoaged skin are topical retinoids, in particular tretinoin, isotretinoin, and tazarotene. The application of retinoids might not only clinically and biochemically repair photoaged skin, but their use might also prevent photoaging. Furthermore, new evidence suggests a beneficial role of topical retinoids in the treatment of intrinsically aged skin.


Ariadne: synthetic long read deconvolution using assembly graphs.
Synthetic long read sequencing techniques such as UST's TELL-Seq and Loop Genomics' LoopSeq combine 3[Formula: see text] barcoding with standard short-read sequencing to expand the range of linkage resolution from hundreds to tens of thousands of base-pairs. However, the lack of a 1:1 correspondence between a long fragment and a 3[Formula: see text] unique molecular identifier confounds the assignment of linkage between short reads. We introduce Ariadne, a novel assembly graph-based synthetic long read deconvolution algorithm, that can be used to extract single-species read-clouds from synthetic long read datasets to improve the taxonomic classification and de novo assembly of complex populations, such as metagenomes.


Facile synthesis of MoS2@Cu2O-Pt nanohybrid as enzyme-mimetic label for the detection of the Hepatitis B surface antigen.
An ultrasensitive sandwich-type electrochemical immunosensor was proposed for quantitative detection of hepatitis B surface antigen, which is a representative biomarker of the Hepatitis B virus. First, the porous graphene oxide/Au composites with good conductive ability were employed to accelerate the electron transfer on the electrode interface. Furthermore, the amino functionalized molybdenum disulfide @ cuprous oxide hybrid with coral morphology was prepared to combine platinum nanoparticles for achieving signal amplification strategy. The resulting nanocomposites (molybdenum disulfide @ cuprous oxide - platinum) demonstrated uniform coral morphology, which effectively improved the specific surface area available for loading the secondary antibody and the number of catalytically active sites, even also increased the electrical conductivity. Based on these advantages, this composite system yielded a superior electrocatalytic current response toward the reduction of hydrogen peroxide. In addition, porous graphene oxide/Au composites were used to modify the glassy carbon electrode, thereby presenting a large surface area and becoming biocompatible, for improving the loading capacity of the primary antibody. Under optimal conditions, we obtained a linear relationship between current signal and hepatitis B surface antigen concentration in the broad range from 0.5pg/mL to 200ng/mL, with a detection limit of 0.15pg/mL (signal-to-noise ratio of 3). These values are promising towards clinical applications.


Pulsed light of near-infrared and visible light wavelengths induces the accumulation of carotenoids in tomato fruits during post-treatment time.
Pulsed light (PL) is proposed as a novel strategy for the food industry to enhance the antioxidant potential of fruits and vegetables for industrial uses. The main aim of this work is to evaluate the impact of postharvest PL treatments of different spectral ranges on the carotenoid concentration as well as quality attributes of tomatoes during post-treatment time. Doses of wide-spectrum light (180-1100 nm), full-spectrum without ultraviolet (UV)-C wavelengths (305-1100 nm), and visible (VIS) + near-infrared light (NIR) (400-1100 nm) were compared. Total carotenoids, lycopene, and chlorophyll contents were spectrophotometrically assessed just after treatments and 1, 5, and 10 days post-treatment. PL treatments accelerated the accumulation of both total carotenoids and lycopene concentrations in tomato fruits. Nevertheless, the efficacy of PL depended on the applied spectral range. Tomato subjected to VIS + NIR treatment exhibited the greatest enhancement in total carotenoids (31 %) and lycopene (35 %) content at day 5 post-treatment and quality attributes were not affected. Conversely, UV-light exposure did not enhance carotenoid concentrations. These results evidenced that VIS + NIR treatments induced a faster accumulation of carotenoids without negatively affecting tomato quality attributes. PRACTICAL APPLICATION: The integration of visible and near-infrared (VIS + NIR) light filters in pulsed light (PL) processing allows enhancing the accumulation of bioactive compounds in tomato tissues in a sustainable way, which can be processed to obtain derived products (e.g., juices, purees) with health-promoting properties. PL technology is characterized by a lack of residual compounds and the absence of applying chemicals potentially harmful to humans. Industries can attract the attention of consumers through their application, which allows offering this added value.


Design science research applied to difficulties of teaching and learning initial programming.
Learning and teaching to program is an arduous task. It requires a lot of commitment, dedication, and passion from everyone involved. Programming courses have high dropout and failure rates. Throughout time, several educational research works have been carried out to study the different learning processes and characteristics of students. With this work, we present and describe our vision and model of teaching and learning of initial programming to minimize the problems. We present a technological tool, called HTProgramming (Help To Programming), which complements the teaching and learning process. This allows students to practice a wide variety of activities with immediate feedback, directly related to content and themes for learning programming. It allows the teacher to follow the whole process and students' results. Using a machine-learning (neural network) predictive model of student failure, it will allow the teacher to anticipate possible student failure and act quickly. In this paper, we apply the Design Scientific Research Methodology to tackle teaching and learning difficulties to initial programming. We also include the results and evaluation of the application. Students consider the application an important tool for their learning process. The student failure prediction model presents very realistic values.


The experimental production of Renaut bodies.
Renaut bodies are loosely-textured whorled, cell-sparse structures found in the subperineurial space of peripheral nerves. Although described in 1881, their significance is still debated. Rats were placed in wire-mesh cages for 4 days to 6 weeks and the lateral and medial plantar nerves were sequentially removed. The initial change was the presence of endoneurial edema which dissected and displaced nerve fibers producing an endoneurial cleft. With the influx of fibroblasts, these clefts became discretely separated by circumferentially oriented processes. Over time the clefts enlarged and became filled with loosely-textured amorphous and fibrillar material as well as collagen. The Renaut bodies ranged from 15 to 80 microns in diameter. In this model the Renaut bodies formed at the maximum site of compression of the lateral plantar nerve. The fibroblasts appeared to be derived from the endoneurial connective tissue and were not the result of degenerating endoneurial structures. Renaut body formation was independent of axonal degeneration. The present study strongly suggests that Renaut bodies are a response to repeated mechanical stress.


A biased detection of the flexible genome content: missing large restriction fragments in comparative genomics.
Gene content variation between closely related bacteria is largely due to mobile elements and gene erosion. Various techniques are available to assess this variation, yet biased pools of restriction fragments have been used in several comparative genomics studies. Excluding important large restriction fragments from the actual hybridisation or from post-hybridisation amplification reactions compromise the comprehensiveness of these studies.


Development of a 3D Motion Tracking System for the Analysis of Skills in Microsurgery.
Microsurgical skills of trainee surgeons have been subjectively evaluated due to the lack of technological tools. The objective of this investigation is to present the construct validity of the mitracks3D, which is a system designed to help in the objective evaluation of microsurgery trainees. To achieve this, a stereoscopic vision system records the 3D motion of two tweezers manipulated by surgeons during microsurgery training. Using motion analysis parameters (MAPs), quantitative information about their microsurgical skills and performance is obtained. For validation, 14 participants were enrolled and divided into two groups: expert microsurgeons (3 female, 2 male) and trainee surgeons (4 female, 5 male). The 3D motion tracking was acquired while the surgeons practiced with two training models: transferring objects and suture. Twelve MAPs were used to objective assessment the skill levels of each participant. Subsequent, statistical analysis was computed to compare the scores of both groups. Validation results showed statistically significant differences in 8 of the 12 MAPs and in 10 of the 12 MAPs using the transferring and the suturing models, respectively. The capability of mitracks3D to differentiate the performance of microsurgeons by analyzing their movements was shown. The mitracks3D system was successfully validated. With this system was possible to differentiate the psychomotor microsurgical skills between the two groups of surgeons. The mitracks3D system is a suitable device for the evaluation of microsurgical skills in a variety of surgical specialties that require it during the training of their residents.


The effect of pH and blood gas correction in DPG and plasma potassium content of stored blood.
During storage of CPD preserved blood, red cell DPG decreases and plasma potassium increases, the changes becoming more marked with increasing duration of storage. Correction of the blood gas and pH alterations of stored blood decreases plasma potassium and increases red cell DPG, but they do not return to normal except in blood stored less than seven days. There is a highly significant correlation between increasing red cell DPG and decreasing plasma potassium as the pH and blood gases of stored blood are restored to physiological range.


Protein phosphatase activity is necessary for myofibrillogenesis.
During myofibrillogenesis, myosin light-chain kinase (MLCK) phosphorylates the regulatory light chain (RLC) of myosin II, enabling patterned assembly of myosin thick filaments. Aprotein phosphatase (PP) has been shown to mediate RLC dephosphorylation in adult smooth and striated muscle. A role for PP activity in regulating myofibrillogenesis during embryonic development, however, has not been investigated. Tautomycin (TM) was used to inhibit both PP1 and PP2A activities, whereas okadaic acid (OA) and fostriecin (FOS) were used to inhibit PP2A. TM affected both actin and myosin assembly at 5 nM; the IC50 value was 20 and 8.5 nM, respectively. In contrast, OA applied at 10 times above its reported Ki for PP2A caused no significant disruption. There was also no disruption when FOS was applied at a concentration 30 times above its reported Ki for PP2A. Thus, our results suggest a primary role for PP1 isoforms during myofibrillogenesis. Although rho kinase (RK) regulates PP activity in embryonic smooth and cardiac muscle, application of the RK inhibitor Y27632 did not affect actin or myosin assembly in skeletal myocytes. Collectively, our pharmacological results suggest that PP1 is involved in dynamic regulation of RLC phosphorylation. To specifically test involvement of the myosin-targeted isoform (PP1M), we used a morpholino antisense approach to knock down the myosin targeting (M) subunit of PP1. Embryos injected with morpholino targeted to the 110-kDa M targeting subunit had fewer somites, and myosin organization was significantly perturbed. The combined pharmacological and molecular results suggest a dynamic equilibrium between MLCK and PP1M activities is required for proper myofibrillogenesis.


Resilient clean cooking: Maintaining household clean cooking in Ecuador during the COVID-19 pandemic.
Decades of government subsidies for LPG and electricity have facilitated near-universal clean cooking access and use in Ecuador, placing the nation ahead of most other peer low- and middle-income countries. The widespread socio-economic impacts of the COVID-19 pandemic has threatened the resilience of clean cooking systems globally, including by altering households' ability to purchase clean fuels and policymakers' considerations about continuing subsidy programs. As such, assessing the resilience of clean cooking in Ecuador during the pandemic can offer important lessons for the international community, especially other countries looking to ensure resilient transitions to clean cooking. We study household energy use patterns using interviews, newspaper reports, government data on household electricity and LPG consumption, and household surveys [N = 200 across two rounds]. The LPG and electricity distribution systems experienced occasional disruptions to cylinder refill delivery and meter reading processes, respectively, which were associated with pandemic-related mobility restrictions. However, for the most part, supply and distribution activities by private and public companies continued without fundamental change. Survey participants reported increases in unemployment and reductions in household income as well as increased use of polluting biomass as a secondary fuel. Ecuador's LPG and electricity distribution systems were resilient throughout the pandemic, with only minimal interruption of the widespread provision of low-cost clean cooking fuels. Our findings inform the global audience concerned about the resilience of clean household energy use on the potential for clean fuel subsidies to facilitate continued clean cooking even during the COVID-19 pandemic.


A model for the interaction of two chemicals.
We describe a method for studying the interaction of two anesthetic agents, Morphine and Midazolam, acting simultaneously in the same individual. Representing the levels of the two chemicals by diffusion processes, we assume their interaction is governed by a linear combination of the separate components. Pharmacological data is used to estimate the model parameters and, in particular, to determine the coefficient in the linear combination. This leads to the conclusion that the two chemicals have a counteractive effect.


The diabetogenic antibiotic streptozotocin modifies the tryptic digest pattern for peptides of the enzyme O-GlcNAc-selective N-acetyl-beta-d-glucosaminidase that contain amino acid residues essential for enzymatic activity.
Streptozotocin (STZ) inhibits O-GlcNAc-selective N-acetyl-beta-d-glucosaminidase (O-GlcNAcase), the enzyme that removes O-GlcNAc from proteins. The active site of the enzyme was recently proposed to include aspartates 174, 175, and 177, with STZ inhibition via a transition state analog. We explored the effect of STZ on the tryptic peptide digest pattern of O-GlcNAcase. LC/MS/MS analysis demonstrated that STZ modified two areas of the enzyme. One peptide, LGCFEIAK (894-901), in a C-terminal region previously proposed to possess O-GlcNAcase activity, was methylated by STZ. Another peptide, EYEIEFIYIASPGLDITFSNPK (128-149), was detected only after treatment with STZ and was in an N-terminal region, overlapping a glutamate-rich area containing an adjacent phenylalanine residue. No covalent modification of this peptide could be demonstrated. Detection of this peptide after treatment with STZ was accompanied by the simultaneous inability to detect the nearby peptide KLDQVSQFGCR (157-167), which contains a cysteine residue recently shown to be essential for enzymatic activity. To determine which of the first two peptides might also be important for O-GlcNAcase activity, site-specific mutagenesis was performed. Mutation of the N-terminal phenylalanine and serine residues resulted in almost complete inhibition of activity. In contrast, mutation of conserved C-terminal glycine and cysteine residues caused little inhibition of enzymatic activity. Together, these data extend the region of the active site N-terminally and give independent evidence to support the idea that STZ inhibits O-GlcNAcase through formation of a transition state analog that resides in the active site of the enzyme and in doing so alters its conformation and ensuing tryptic digest pattern.


Comparison of atracurium and pancuronium in mechanically ventilated neonates.
To compare haemodynamic and gas exchange effects after either atracurium or pancuronium given to ventilated neonates with respiratory failure. In this prospective study neonates were alternately assigned to receive either atracurium or pancuronium, intravenously. Paediatric and neonatal ICU in a teaching hospital. 21 ventilated neonates with mean birth weight of 2293 g, suffering from respiratory distress syndrome, meconium aspiration syndrome or pneumonia were included in the study. Patients were entered if they were breathing out of phase with the ventilator and required FIO2 > 0.4 and peak inspiratory pressure (PIP) > 15 cm H2O. Exclusion criteria were unstable haemodynamics or a pneumothorax. Heart rate, respiratory rate, invasive blood pressure and transcutaneous oxygen tension were monitored continuously. IV atracurium (0.3 mg/kg) or pancuronium (0.1 mg/kg) were administered. Arterial blood gas analysis was performed before and 10 min after injection of muscle relaxant. Atracurium caused a significant decrease in heart rate (p < 0.05), systolic and mean blood pressure (p < 0.01). There was also a slight decrease in PaO2 and PaCO2 (n.s.). Administration of pancuronium resulted in an increase in heart rate (p < 0.01) and a slight decrease of blood pressure (n.s.). PaCO2 remained unchanged, whereas PaO2 increased slightly (n.s.). The PtcO2 index (PtcO2/PaO2) decreased after atracurium and did not change after pancuronium (both n.s.). With both drugs a slight increase in alveolar to arterial oxygen tension difference was observed (n.s.). There was one episode of hypotension and one of hypoxaemia--both after pancuronium. Both drugs may be used for muscle relaxation in neonates with respiratory failure. Atracurium however causes more cardiovascular depression, whereas the effect of pancuronium may be difficult to predict.


Oral Cavity Reconstruction.
This summary provides a concise overview of oral cavity reconstruction to optimize functional outcomes in the modern era. Soft tissue and osseous reconstruction options for a wide range of oral cavity sites including lip, oral tongue, floor of mouth, buccal, hard palate, and composite oromandibular resections are reviewed. The appropriate applications of primary closure, secondary intention, skin grafts, and dermal substitute grafts are included. Anatomic considerations, indications, contraindications, and complications of local, regional, and free flaps in oral cavity reconstruction are discussed. Specific defects and the appropriate options for reconstruction of those defects are delineated.


Clinical Tolerance of In-Neonatal Intensive Care Unit Administration of Rotavirus Vaccine.
This article determines the tolerance of neonatal intensive care unit (NICU)-based administration of RV5 in premature infants. This article also aims to compare the rate of clinically significant adverse events after RV5 immunization to the standard 2-month shot series and to historical controls who were not immunized. This is a retrospective case-control study of 201 premature infants immunized with RV5. Infants were evaluated for clinically significant events 7 days before and after immunization and were compared with events after the 2-month shot series and to 189 historical controls. Wilcoxon signed rank test and McNemar's test were used for all paired analysis. There was no increase in number of infants with clinically significant adverse events when comparing after RV5 to prior to RV5, after the 2-month shot series, or to the historical controls. RV5 is well tolerated in premature infants and does not result in clinically significant adverse events when administered in NICU-hospitalized infants.


Should the target for blood pressure control specify both a systolic and a diastolic component?
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) Report recommends, as the target for hypertension control, achieving both a systolic and diastolic goal. We suggest, however, that specifying both a systolic and a diastolic component for the blood pressure goal can be confusing to physician and patient. Furthermore, literal interpretation and application of this JNC 7 recommendation could result in overtreatment, undertreatment, or institution of treatment for hypertension when none is needed. Specific scenarios illustrating how inappropriate treatment could result from literal interpretation and application of the JNC 7 recommendations are presented. Our recommended blood pressure goal for hypertensives is: Sitting systolic blood pressure consistently in the 120s or less, if tolerated. This recommendation is evidence based, easy to understand, and achievable. Its rationale is discussed.


Are IBD Patients Underscored when Determining Postoperative VTE Risk?
Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE) following colorectal surgery and there is currently no consensus on post-surgical VTE prevention or specific VTE risk assessment tools. We sought to evaluate VTE risk after colorectal surgery and determine if known risk factors used in risk assessment tools adequate correlate with VTE risk in IBD patients. Retrospective cohort study using the National Surgical Quality Improvement Project (NSQIP) Participant User File from 2010 to 2018. A total of 27,679 patients were included; 19,015 (68.7%) had Crohn's disease (CD) and 8664 (31.3%) ulcerative colitis (UC). Of these, 16,749 (60.5%) underwent abdominopelvic procedures, 10,178 (36.8%) complex pelvic procedures, and 752 (2.7%) small bowel operations. The overall VTE rate was 2.3%. The VTE rate in patients with CD and UC was 1.8% and 3.6% (p < 0.001) respectively. Overall median time to VTE was 9 days after surgery. VTE rate was highest in patients who underwent complex pelvic procedures (3.6%; 361/10,178). A risk score was calculated using 16/40 available variables from the Caprini VTE Risk Assessment tool; risk score ranged from 3 to 12 points. Most patients that developed a VTE had a score between 3 and 5 points (75.6%), and only 24.5% had a score of 6 or higher. Patients with higher risk scores did not have a higher VTE incidence. Post-surgical VTE rates are high in IBD patients. Over half of the events occurred following discharge and in patients with an apparent low-risk score. Additional studies are warranted to define a recommended postoperative VTE prophylaxis regimen for patients with IBD.


Association of 2-Methoxyestradiol (2ME) Plasma Levels with Clinical Severity Indices and Biomarkers of Preeclampsia.
Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. The pathophysiology of preeclampsia has been extensively studied. 2ME seems to maintain placental homeostasis necessary for appropriate cytotrophoblast invasion of the maternal deciduas. We plan this study to compare its value in the plasma of normotensive and preeclamptic women and studying its correlation with the severity indices of preeclampsia. The aim of this study was to estimate plasma levels of 2ME in preeclamptic and normotensive pregnant women and correlate it with the severity in terms of clinical indices, laboratory investigations, and fetomaternal outcome. This study was a case-control study conducted in KGMU, Lucknow, August 2015-2016. Sample size was 90 pregnant women including 30 normotensive, 30 non-severe preeclampsia, and 30 severe preeclampsia patients. Plasma 2ME levels were analyzed using ELISA kit and the outcome was compared in terms of systolic and diastolic blood pressure, proteinuria, liver and renal function tests, serum LDH, uric acid, plasma 2ME levels, and fetomaternal outcome. There was a significant (p = 0.0001) difference in 2ME plasma levels among the groups (normotensive, non severe and severe preeclampsia patients). 2ME plasma levels significantly negatively correlated with SBP (r = - 0.62, p = 0.0001) and DBP (r = - 0.63, p = 0.0001). With one-unit increase in SBP, 2ME will decrease by 2445.14 units, and in one-unit increase in DBP, 2ME will decrease by 1807.28 units. The sensitivity and specificity of 2ME for preeclampsia were found to be high. It was seen that there was a statistically significant difference between plasma 2ME levels among the three groups. The ROC curve obtained showed that sensitivity was predicted to be 98.3%, specificity 76.7%, positive predictive value of 89.4%, negative predictive value of 95.8% and accuracy of 91.1%.


Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.
Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).


Impacts of chitosan oligosaccharide (COS) on angiogenic activities.
It has been proved that chitosan oligosaccharide (COS) has a more favorable therapeutic applications such as wound healing and anti-tumor treatment, and can affect angiogenesis. For better understanding the effect of COS on angiogenic activities at cellular level, COS with different concentration and degree of polymerization (DP) were used to culture human umbilical vein endothelial cells (HUVECs) in this work. Cell proliferation activity, cell morphology, cell migration and angiogenesis associated factor expression of HUVECs were evaluated. The results indicated that COS at a high concentration of 400 μg/mL (COS(400)) and DP of 6 (Chitinhexaose Hydrochloride, COS6) had inhibitory effect on angiogenic activities of HUVECs. Specifically, COS(400) and COS6 inhibited cell proliferation activity, cell migration, and vascular endothelial cell growth factor (VEGF) expression of HUVECs. While COS at a low concentration (<400 μg/mL) and suitable polymerization degrees (DP < 6) had little significant effect on cell proliferation, migration, and VEGF expression of HUVECs, showing dose-dependent effect. These findings provided insight for the potential use of COS, for broadening its future applications in biomedical fields and functional materials area. It also helped guide the design and synthesis of chitosan-based materials as an angiogenesis inhibitor for anti-angiogenic therapy.


Laboratory investigation on added-value application of the COVID-19 disposable mask in hot mix asphalt (HMA).
The outbreak of the COVID-19 pandemic has stimulated the demand for disposable masks to an unprecedented level, which also poses a significant risk to the natural environment from the improper treatment or disposal of waste masks. To lower such an environmental risk and maximize the added value of the waste masks, this paper proposed to recycle the waste mask fiber (MF) in combination with the waste cooking oil (WCO) for hot mix asphalt (HMA) application. A series of MF + WCO modified asphalt binders were first designed and fabricated. Their performance properties were then systematically measured. The physical-rheological test results showed that the incorporation of MF can significantly improve the high-temperature rutting resistance performance of asphalt binder. However, it may also lower the asphalt's low-temperature anti-cracking performance. The addition of WCO was found to compensate for this low-temperature performance loss effectively, and the MF5% + WCO3% was identified as the best combination. The Fourier transform infrared (FTIR) spectroscopy test results revealed that the asphalt modified by the MF + WCO involved only a physical modification. The performance test results indicated that the high-temperature permanent deformation resistance and low-temperature anti-cracking of MF5% + WCO3% modified HMA was greatly enhanced, while its moisture stability was slightly reduced but still met the specification requirement. The environmental benefit assessments proved that recycling the waste masks for asphalt paving can provide an enormous added value to pavement engineering in terms of carbon emission reduction and land resource saving.


A new modeling approach to the effect of antimicrobial agents on heterogeneous microbial populations.
We develop a mathematical framework to model the dynamics of the effect of antimicrobial agents on heterogeneous microbial populations of distributed antimicrobial resistance. Our framework uses the concept of cumulants of a distribution. Simplifications that result in easily usable approximation tools are presented. A case study on experimental data exemplifies shortcomings of standard methods and the usefulness of the proposed approach. Suggestions for future development are made.


Solar cheilosis: an ominous precursor: part I. Diagnostic insights.
Squamous cell carcinoma (SCC) of the lower lip is a deadly nonmelanoma skin cancer. Its precursor, a distinctive cutaneous neoplasia analogous to cervical dysplasia, is known by the confusing term actinic cheilitis. Solar cheilosis (SC) is a more appropriate designation. It represents incipient SCC in situ. SC is widely recognized as an ultraviolet light-induced precancer of the lower lip that is typically seen in light-skinned individuals and others with poorly pigmented lower lips. Lip SCC is one of the most common malignancies of the oral cavity. SCC is much more likely to metastasize from the lip than cutaneous surfaces, with a 5-year overall survival rate of less than 75%. SC results from long-term exposure to ultraviolet radiation. The occurrence of SC is dose-dependent and is influenced by the patient's solar exposure, age, genetic predisposition, geographic latitude of residence, occupation, leisure activities, and use of lip protective agents. Molecular abnormalities of SC are similar to those of actinic keratosis and facilitate the evolution to SCC. A high degree of clinical suspicion should be maintained, given the malignant nature of this condition. Ulceration and nodularity often indicate progression to SCC. We performed a Medline and Google Scholar search for all articles related to actinic cheilitis, actinic cheilosis, SC, actinic keratosis, solar keratosis, premalignant oral disease, and lip SCC, and have also evaluated many other articles and book chapters. One hundred forty-two peer-reviewed articles were identified as being of particular value. Pertinent facts were selected and analyzed.


A male infant with holoprosencephaly, associated with ring chromosome 21.
An infant with holoprosencephaly and a karyotype 46,XY,r(21) is reported. No distinctive craniofacial features suggesting holoprosencephaly were present in this infant who presented with epilepsy, microcephaly and scoliosis with hemivertebra Th 10. This is the first report which links deletion of chromosome 21q to the holoprosencephaly phenotype.


Effects of High-Dose Vitamin D Supplementation on Phase Angle and Physical Function in Patients with Prostate Cancer on ADT.
Androgen deprivation therapy (ADT) is commonly used to treat patients with advanced prostate cancer but is associated with functional decline. Bioelectrical impedance analysis (BIA)-derived phase angle may reflect frailty and functional decline in cancer patients. High-dose vitamin D supplementation may improve phase angle values and physical function. We conducted an exploratory analysis from a phase II randomized controlled trial investigating the efficacy of high-dose vitamin D supplementation in prostate cancer patients (age ≥ 60 yrs). Fifty-nine patients were randomized to high-dose vitamin D (600 IU/day plus 50,000 IU/week) or low-dose: RDA for vitamin D (600 IU/day plus placebo weekly) for 24 weeks. Phase angle was measured by BIA. Physical function measures included handgrip strength, 6-minute walk test, Short Performance Physical Battery and leg extension. All testing was completed at baseline, week 12 and week 24. Phase angle values were wider over the entire study in the high-dose vitamin D arm indicating healthier muscle cells. The low-dose vitamin D arm had phase angle values consistent with frailty cutoffs in older men (<5.7°). Patients in the high-dose vitamin D arm experienced wider phase angle values over the course of the study which may indicate less frailty. ClinicalTrials.gov ID: NCT02064946.


Analysis of serum and urinary retinol binding protein in hepato-renal syndrome.
Retinol binding protein (RBP) was analyzed in the sera and urines of 5 patients with hepato-renal syndrome (HRS), 4 with acute tubular necrosis (ATN), 20 liver cirrhosis patients with normal kidney function (NKF), 14 chronic renal failure (CRF) patients, and 19 healthy adults. All renal failure patients had high mean urine RBP (URBP): HRS, 8 mg/L; ATN, 11 mg/L; CRF, 8 mg/L respectively; p less than 0.001 vs the rest. Those with ATN and CRF had high mean serum RPB (SRBP): 146 and 149 mg/L, respectively, p less than 0.001 compared to the other groups. In HRS, in spite of renal failure, SRBP was very low (mean = 12 mg/L). The cirrhotics with NKF averaged less than 50% of the SRBP values of the healthy controls (16 vs 41 mg/L RBP, p less than 0.001); their RBP excretion was normal (mean URBP of 0.1 vs 0.06 mg/L in the control group). RBP analyses before and during HRS in two patients showed a marked increase in urine RBP during HRS (35- and 600-fold respectively) with practically unchanged serum levels. Impaired hepatic production and/or release is proposed to explain the low serum RBP in HRS, and a renal tubular injury or dysfunction to account for its high excretion. The RBP urinary loss could further compromise an already abnormal RBP metabolism and its serum levels. This combination (of low serum and high urine RBP), in the context of renal failure occurring in alcoholic liver cirrhosis, could help in the recognition of HRS.


Extended genomic sequence of the HLA-DRB1*14:04:07 and -DRB1*15:53 alleles from Gujarati individuals.
The extended genomic sequences of HLA-DRB1*14:04:07 and -DRB1*15:53 alleles were identified in the Gujarati individuals.