Hyper-parallel nonlocal CNOT operation with hyperentanglement assisted by cross-Kerr nonlinearity.
Implementing CNOT operation nonlocally is one of central tasks in distributed quantum computation. Most of previously protocols for implementation quantum CNOT operation only consider implement CNOT operation in one degree of freedom(DOF). In this paper, we present a scheme for nonlocal implementation of hyper-parallel CNOT operation in polarization and spatial-mode DOFs via hyperentanglement. The CNOT operations in polarization DOF and spatial-mode DOF can be remote implemented simultaneously with hyperentanglement assisited by cross-Kerr nonlinearity. Hyper-parallel nonlocal CNOT gate can enhance the quantum channel capacity for distributed quantum computation and long-distance quantum communication. We discuss the experiment feasibility for hyper-parallel nonlocal gate. It shows that the protocol for hyper-parallel nonlocal CNOT operation can be realized with current technology.


Genetic damage and the inhibition of 7,12-dimethylbenz[a]anthracene-induced genetic damage by the phytoestrogens, genistein and daidzein, in female ICR mice.
Populations consuming soybeans have reduced rates of breast, colon and prostate cancer possibly due, in part, to the presence in soybeans of two estrogenic isoflavones, genistein and daidzein. This study investigated the genotoxicity of these soya isoflavones and their interactions with 7,12-dimethylbenz[a]anthracene (DMBA)-induced sister chromatid exchanges (SCE) in bone marrow cells and DNA adduct formations in liver and mammary glands of mice. Groups of female ICR mice were pretreated i.p. with daidzein and/or genistein (10-20 mg/kg per day for 6 days or 50 mg/kg per 12 h for 3 days) or with the solvent, dimethylsulfoxide (DMSO). The mice were implanted with bromodeoxyuridine (BrdU) tablets s.c., and treated with DMBA (50 mg/kg) i.p. and colchicine (4 mg/kg) i.p. 24, 23, and 2 h before sacrifice, respectively. In bone marrow cells. DMBA alone induced 11.73 +/- 1.42 SCE/cell compared to 4.35 +/- 0.83 SCE/cell in the DMSO treated controls (P = 0.001). DMBA induced 20% fewer SCE (P < 0.05) in mice pretreated with daidzein, genistein or a combination of genistein and daidzein (6 x 20 mg/kg per day for 6 days) when compared to mice that received no pretreatments. Genistein at 50 mg/kg per 12 h for 3 days also inhibited DMBA-induced SCE by 20%. However, treatment for 3 days with 50 mg/kg per 12 h of genistein or daidzein alone, or a combination of daidzein plus genistein (without DMBA treatment) also induced more SCE than treatment with only the solvent (DMSO, P < 0.05). Pretreatment with both the low and the high doses of daidzein plus genistein or the high dose of genistein reduced the replication index of bone marrow cells when compared to pretreatment with DMSO (P < 0.05). Pretreatment with genistein reduced DMBA-induced DNA adduct formation by 34%, but this was only marginally significant (P = 0.08) due to the large inter-individual variability in adduct levels. These results show that genistein and daidzein suppress SCE and possibly DNA adduct formation induced by the known carcinogen, DMBA. This response to a low dose isoflavone exposure may be partly responsible for the protective effect against endocrine cancers of soya consumption.


Five-Year Cumulative Incidence and Progression of Myopic Maculopathy in a German Population.
To investigate the 5-year cumulative incidence and progression of myopic maculopathy in the general population in Germany and to analyze potential risk factors. The Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants aged 35 to 74 years at baseline. A total of 494 eyes of 323 participants (mean age, 50.2 ± 9.2 years; median, -7.25 diopters [D] myopic refractive error) without myopic maculopathy at baseline and 34 eyes of 27 subjects (mean age, 56.7 ± 9.1 years; median, -8.75 D myopic refractive error) with myopic maculopathy met the inclusion conditions, phakic eyes with spherical equivalent ≤-6 D (baseline), and had gradable fundus photographs at baseline and 5-year follow-up. Myopic maculopathy incidence and progression were assessed by grading of fundus photographs according to a recent international photographic classification system (META-PM). Multivariable logistic regression analysis was used to assess risk factors for progression of myopic maculopathy. Estimates for incidence and progression of myopic maculopathy. The 5-year cumulative incidence of myopic maculopathy was 0.3% (95% confidence interval [CI], 0.02-1.99; n = 1). Progression occurred in 17 of 34 eyes (50%) with prior myopic maculopathy over 5 years with 4 changes in category. The most common types of progression were enlargement of diffuse and patchy chorioretinal atrophy; a new pathology was present in 8 eyes. Higher intraocular pressure (IOP) (odds ratio [OR], 1.62; 95% CI, 1.51-1.59; P = 0.035) was associated with progression of myopic maculopathy. Female gender (OR, 5.54; 95% CI, 0.93-32.92; P = 0.060) and higher myopic refractive error (OR, 1.62 per diopter; 95% CI, 0.99-1.49; P = 0.063) showed a tendency toward progression. Incidence of myopic maculopathy is rare in highly myopic eyes in the general population aged 35 to 74 years in Germany. Progression of myopic maculopathy in the German population occurred in 50% of highly myopic eyes. We presented population-based 5-year follow-up data on incidence and progression of myopic maculopathy in Europe.


Computationally enhanced X-ray diffraction analysis of a gold(III) complex interacting with the human telomeric DNA G-quadruplex. Unravelling non-unique ligand positioning.
The crystal structure of the human telomeric DNA Tel24 G-quadruplex (Tel24 = TAG3(T2AG3)3T) in complex with the novel [AuL] species (with L = 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine - TPymT-α) was solved by a novel joint molecular mechanical (MM)/quantum mechanical (QM) innovative approach. The quantum-refinement crystallographic method (crystallographic refinement enhanced with quantum mechanical calculation) was adapted to treat the [AuL]/G-quadruplex structure, where each gold complex in the binding site was found spread over four equally occupied positions. The four positions were first determined by docking restrained to the crystallographically determined metal ions' coordinates. Then, the quantum refinement method was used to resolve the poorly defined density around the ligands and improve the crystallographic determination, revealing that the binding preferences of this metallodrug toward Tel24 G-quadruplex arise from a combined effect of pyrimidine stacking, metal-guanine interactions and charge-charge neutralizing action of the π-acid triazine. The occurrence of interaction in solution with the Tel24 G-quadruplex DNA was further proved through DNA melting experiments, which showed a slight destabilisation of the quadruplex upon adduct formation.


Chemical compounds causing severe acute toxicity in heavy liquids used for intraocular surgery.
Perfluorocarbon liquids (PFCLs) have been considered safe for intraocular manipulation of the retina, but since 2013 many cases of acute eye toxicity cousing blindness have been reported in various countries when using various commercial PFCLs. All these PFCLs were CE marked (Conformité Européenne), which meant they had been subjected to evaluation complying with the International Organization for Standardization (ISO) guidelines. These dramatic events raised questions about the safety of PFCLs and the validity of some cytotoxicity tests performed under ISO guidelines. Samples from toxic batches were analyzed by gas chromatography-mass spectrometry combined with Raman and infrared spectrometry. Perfluorooctanoic acid, dodecafluoro-1-heptanol, ethylbenzene and tributyltin bromide were identified and evaluated by a direct contact cytotoxicity test using ARPE-19 cell line, patented by our group (EP 3467118 A1). Perfluorooctanoic acid at a concentration of >0.06 mM and tributyltin bromide at a concentration of ≥0.016 mM were shown to be toxic, whereas the concentration found in the toxic samples reached 0.48 mM, and 0.111 mM, respectively. These finding emphasized the idea that determination of partially fluorinated compounds are not enough to guarantee the safety of these medical devices.


A biomarker of tissue damage, lactate dehydrogenase, is associated with fibulin-1 and oxidative stress in blacks: the SAfrEIC study.
Extracellular matrix (ECM) remodeling and oxidative stress is present in hypertension and associated arterial stiffness, but little is known on the physiological link among lactate dehydrogenase (LDH), fibulin-1, and reactive oxygen species (ROS). The objective of this study is to explore the link among a marker of tissue damage (LDH), fibulin-1 (as ECM biomarker), and ROS. We included 316 black and 305 white South Africans and determined the above-mentioned biomarkers along with additional cardiometabolic risk factors. LDH associated positively with fibulin-1 (β = 0.23; p < 0.001) and ROS (β = 0.11; p = 0.30) in blacks only. Our finding suggests that increased circulating levels of LDH may be due to early ECM remodeling and oxidative stress in blacks that are subjected to detrimental and uncontrolled lifestyle risk factors.


Safety of patients under the care of crisis resolution home treatment services in England: a retrospective analysis of suicide trends from 2003 to 2011.
Community care provided by crisis resolution home treatment teams is used increasingly as an alternative to admission to psychiatric wards. No systematic analysis has been done of the safety of these teams in terms of rates of suicide. We aimed to compare the rate and number of suicides among patients under the care of crisis resolution home treatment teams with those of psychiatric inpatients. We also assessed the clinical features of individuals who died by suicide in both home and hospital settings. We did a retrospective longitudinal analysis between 2003 and 2011 of all adults (aged 18 years or older) treated by the National Health Service in England who died by suicide while under the care of crisis resolution home treatment services or as a psychiatric inpatient. We obtained data from the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness and from the Mental Health Minimum Dataset. 1256 deaths by suicide (12% of all patient suicides) were recorded among patients cared for under crisis resolution home treatment teams, an average of 140 deaths per year. Different denominators meant that direct comparison between groups was difficult, but the average rate of suicide under crisis resolution home treatment services (14·6 per 10 000 episodes under crisis care) seemed higher than the average rate of suicide among psychiatric inpatients (8·8 per 10 000 admissions). The number of suicides in patients under the care of crisis resolution home treatment teams increased from an average of 80 per year (in 2003 and 2004) to 163 per year (in 2010 and 2011) and were twice as frequent as inpatient suicides in the last few years of the study. However, because of the growing number of patients under the care of crisis resolution home treatment teams, the average rate of suicide fell by 18% between the first and last 2 years of the study. 548 (44%) patients who died by suicide under the care of crisis resolution home treatment teams lived alone and 594 (49%) had had a recent adverse life event. In a third of patients (n=428) under the care of crisis resolution home treatment teams, suicide happened within 3 months of discharge from psychiatric inpatient care. Although the number of suicides under the care of crisis resolution home treatment teams has risen since 2003, the rate has fallen. However, suicide rates remain high compared with the inpatient setting, and safety of individuals cared for by crisis resolution home treatment teams should be a priority for mental health services. For some vulnerable people who live alone or have adverse life circumstances, crisis resolution home treatment might not be the most appropriate care setting. Use of crisis resolution home treatment teams to facilitate early discharge could present a risk to some patients, which should be investigated further. Healthcare Quality Improvement Partnership.


Development and validation of limited sampling models for topotecan lactone pharmacokinetic studies in children.
To develop and validate a pharmacokinetic limited sampling model (LSM) for intravenous and oral topotecan pharmacokinetic studies in children. Topotecan lactone concentration-time data from five trials were used to develop and validate LSM for intravenous and oral topotecan. Based on full sampling from one intravenous study (30 patients; 195 studies), a LSM for intravenous topotecan was determined using a modification of the D-optimality algorithm. For oral topotecan we used full sampling data from one oral topotecan study (27 patients; 47 studies) to develop an LSM. Accuracy and bias of each LSM were determined relative to the full sampling method. Predictive performance of the LSM was validated using additional data and Monte-Carlo simulations based on these data. LSM for intravenous topotecan includes: 5 min, 1.5, and 2.5 h after the end of the 30 min infusion. The median accuracy (absolute predicted error) and bias (predicted error) are < or =8% and < or =6.1%, respectively. For oral topotecan, the optimal LSM includes: 15 min, 1.5, and 6 h. The median accuracy and bias are 6% and 4%, respectively. Our results indicate that the optimal sampling times for the intravenous LSM for topotecan in children consist of: predose, and 5 min, 1.5, and 2.5 h after the end of infusion. For oral topotecan the sample times are predose, 15 min, 1.5, and 6 h after dose administration. These LSM are invaluable to children receiving topotecan because it minimizes inconvenience and blood collection.


Changes in extent and zonal distribution of prostatic adenocarcinoma in patients preoperatively treated with neoadjuvant endocrine therapy: analysis on whole-mounted prostatectomy specimens.
An increasing number of pharmacologic agents that induce reversible androgen deprivation are available for neoadjuvant endocrine therapy (NET) for prostatic adenocarcinoma (PCA). If information about the regression pattern of PCA after NET is recognized, more effective decision-making for subsequent therapies such as prostatectomy and radiotherapy, will be possible. The extent and zonal distribution of PCA with or without NET were examined in totally embedded radical prostatectomy specimens obtained from 103 patients with PCA. Seventy-nine of the 103 patients received androgen deprivation therapy (castrated). The zonal location of PCA lesions (non-transition vs transition zone), was identified in three slices from the inferior, middle and superior parts of the prostate. The area of the PCA lesions in these zones was measured. Prostatic adenocarcinoma was identified in 94 of 103 cases: 24 of 24 cases (100%) and 70 of 79 cases (87%) in the non-castrated and castrated groups, respectively. The NET induced a mean of 21% reduction of the prostate volume and lowered the serum PSA level by one eighth. The frequency of capsular penetration in the castrated cases (57%) was lower than in the non-castrated cases (83%) and confinement of the PCA lesion was found in 32% of the castrated and 17% of the non-castrated cases. The reduction rate of the extent of the PCA lesions in the non-transition and transition zone was 33% and 28%, respectively. The extent of the PCA lesions were smaller in the anterior parts, especially at the superior portion of the prostate. Neoadjuvant endocrine therapy induced involutional changes of the PCA evenly across both the non-transition and transition zones. The density of the PCA lesions was low in the anterior part of the prostate. This information is useful for decision-making in post-NET.


The Relationship between Maternal Vitamin D Deficiency and Low Birth Weight Neonates.
Maternal hypovitaminosis D may impair fetal growth and cause adverse pregnancy outcomes including intrauterine growth restriction and neonatal low birth weight. The aim of this study is to evaluate the relationship between maternal vitamin D status and neonate's birth weight. A cross-sectional, descriptive analytical study was carried out in the nursery ward of 2 hospitals (Tehran-Iran) during one year (January 2011- January 2012). One hundred and two neonates were categorized into two groups, neonates with birth weight< 2500 gr (n=52) and neonates with birth weight>2500 gr (n = 50). Data regarding medical history, physical examination and anthropometric measurements of neonates were noted in a questionnaire. Birth time blood samples of their mothers were analyzed for serum 25-(OH)-vitamin D by ELISA method. Maternal vitamin D status was compared in two groups. Mean maternal vitamin D (vit D) level was 31.46 nmol/L. Forty eight percent of mothers had vitamin D deficiency, 27.5% had vit D insufficiency and 24.5% were normal. Mean maternal vitamin D level of LBW neonates was lower than other group; 25.05 vs. 38.13 (p = 0.001). All mothers of neonates with head circumference ≤ 33 cm also had vitamin D deficiency (p = 0.007). Maternal Vitamin D deficiency may increase the risk of low birth weight neonate and modifying maternal nutrition behavior and their vit D level could be beneficial on pregnancy outcome.


Relationship between plasma growth differentiation factor-15 levels and diabetic retinopathy in individuals with type 2 diabetes.
The purpose of our study was to investigate the relationship between plasma growth differentiation factor-15 (GDF-15) concentrations and diabetic retinopathy in patients with type 2 diabetes mellitus (DM). We evaluated 235 patients with type 2 DM in a cross-sectional study. Significantly increased levels of the plasma GDF-15 were found in individuals with diabetic retinopathy versus those without. According to the degree of diabetic retinopathy, there was a significant difference in the average plasma GDF-15 levels (no diabetic retinopathy, 1114 ng/L; nonproliferative diabetic retinopathy, 1327 ng/L; proliferative diabetic retinopathy, 1445 ng/L; p for trend = 0.035) after adjustments for confounders. Logistic regression analyses indicated that plasma GDF-15 concentrations were significantly associated with diabetic retinopathy (odds ratio per 1 standard deviation increment in the log-transformed value, 1.78; 95% confidence interval, 1.05-3.03, p = 0.032). Our study showed a significant positive relationship between plasma GDF-15 concentrations and diabetic retinopathy in type 2 DM patients.


Distribution and resistance of pathogens in infected patients within 1 year after heart transplantation.
Infection is a major cause of morbidity and mortality after heart transplantation (HT). However, there have been few data on clinical manifestation, distribution, and resistance of pathogens in the infected population of heart transplant recipients. We conducted a single-center retrospective study on patients who underwent HT in Wuhan Union Hospital from August 3, 2012 to July 30, 2016. Risk factors for infections that occur within 1 year after HT were investigated by multivariable logistic regression analysis. Among 299 patients, 147 patients (49.2%) confirmed infection. The most common site of infection was the respiratory system. A total of 259 pathogens were detected in 147 patients (49.2%) with infection after HT. In all, 64 multidrug-resistant (MDR) bacteria were detected in infected patients within 1 year after HT, the most common MDR bacteria were extended-spectrum β-lactamases (ESBL) Klebsiella pneumonia and methicillin-resistant Staphylococcus aureus (MRSA). In the multivariable model, diabetes (OR 3.273 [95%CI, 1.748-6.130], and p < .001) and antibiotics treatment within 1 month before transplant (OR 1.860 [95%CI, 1.093-3.166], and p = .022) were significantly associated with infections within 1 year after HT. This study confirmed the high rate of infections within 1 year after HT. Diabetes and antibiotics treatment within 1 month before transplant were independent risk factors for infections within 1 year after HT.


Cell kinetic studies of endothelial cells in the adenocarcinoma EO 771 and the effect of cyclophosphamide.
Cell kinetic studies of endothelial cells in the adenocarcinoma EO 771 growing in C57bl/6j mice and after transplantation into Balb/c-nu/nu mice, as well as of the effect of cyclophosphamide treatment have been carried out. The 3H-thymidine labelling index of endothelial cells decreases from about 8% 3-6 days after tumour inoculation to about 3% at 18 days. This decrease parallels that of the labelling index of tumour cells, i.e. there is a positive correlation between the labelling index of endothelial cells and that of tumour cells. The labelling index of endothelial cells in the tumour periphery is two to three times as high as that in the tumour centre reflecting corresponding differences in the rate of proliferation. There is no difference in the proliferation of endothelial cells whether the tumour grows in C57bl/6j or in Balb/c-nu/nu mice. After treatment with cyclophosphamide the labelling index of endothelial cells decreases within 2 days to 1-2% and remains that low despite regrowth of the tumour with increased tumour cell proliferation, indicating that tumour relapse does not depend on tumour angiogenesis.


[Out-of-hospital cardiac arrest in children with bacterial tracheitis].
Bacterial tracheitis is a severe cause of acute infectious upper-airway obstruction. Its characteristics include thick purulent secretions with or without plaques or pseudomembrane formation. Fatal complications are infrequent if an appropriate treatment is conducted. We report on 2 cases of bacterial tracheitis revealed by out-of-hospital cardiac arrest. At presentation in winter, both children first had the symptoms of viral croup. However, no response to the appropriate therapy for this disease was observed. A cardiac arrest occurred on the second day. Bronchoscopy allowed diagnosis. Findings on initial examination were erythema, edema and purulent secretions. Bacterial cultures of tracheal secretions were positive with Staphylococcus aureus. Serology with influenza A virus was also positive. Despite antibiotics and mechanical ventilation, both children died in the pediatric intensive care unit, consecutively to irreversible ischemic brain injury. Bacterial tracheitis remains a life-threatening upper-airway infection. Prompt recognition and accurate diagnosis could lead to decreased mortality. It is essential to reassess any croup whose outcome is not rapidly favourable. Such patients should be monitored in a pediatric intensive care unit.


Separation of thymic education from antigen presenting functions of major histocompatibility complex class I molecules.
Participation of transmembrane (TM) and glycosyl-phosphatidylinositol (GPI) anchored H-2Db molecules in antigen presentation and thymic selection events was investigated using transgenic mice. Both GPI-Db and TM-Db can efficiently present H-Y antigen, influenza and lymphocytic choriomeningitis virus (LCMV) peptides to primed cytotoxic, H-2Db-restricted T cells. Transgenic mice expressing GPI-Db, although unable to reject TM-Db skin grafts, nevertheless generate secondary CTL responses which can lyse TM-Db-bearing targets, indicating that GPI-Db mice fail to delete all TM-Db-reactive T cells. Furthermore, double-transgenic mice bearing GPI-Db and a T-cell receptor (TcR) for H-2Db+LCMV do not positively select receptor positive, CD8+CD4- T cells. This paradoxical behaviour of GPI-Db molecules suggests that the structural requirements for antigen presentation and thymic selection by class I molecules are different and may explain why GPI-linked class I molecules, such as Qa-2, do not appear to function as restriction elements in vivo.


Role of soluble guanylyl cyclase in renal afferent and efferent arterioles.
Renal arteriolar tone depends considerably on the dilatory action of nitric oxide (NO) via activation of soluble guanylyl cyclase (sGC) and cGMP action. NO deficiency and hypoxia/reoxygenation are important pathophysiological factors in the development of acute kidney injury. It was hypothesized that the NO-sGC-cGMP system functions differently in renal afferent arterioles (AA) compared with efferent arterioles (EA) and that the sGC activator cinaciguat differentially dilates these arterioles. Experiments were performed in isolated, perfused mouse glomerular arterioles. Hypoxia (0.1% oxygen) was achieved by using a hypoxia chamber. Phosphodiesterase 5 (PDE5) and sGC subunits were considerably expressed on the mRNA level in AA. PDE5 inhibition with sildenafil, which blocks cGMP degradation, diminished the responses to ANG II bolus application in AA, but not significantly in EA. Vasodilation induced by sildenafil in ANG II-preconstricted vessels was stronger in EA than AA. Cinaciguat, an NO- and heme-independent sGC activator, dilated EA more strongly than AA after NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) treatment and preconstriction with ANG II. Cinaciguat-induced dilatation of l-NAME-pretreated and ANG II-preconstricted arterioles was similar to controls without l-NAME treatment. Cinaciguat also induced dilatation in iodinated contrast medium treated AA. Furthermore, it dilated EA, but not AA, after hypoxia/reoxygenation. The results reveal an important role of the NO-sGC-cGMP system for renal dilatation and that EA have a more potent sGC activated dilatory system. Furthermore, AA seem to be more sensitive to hypoxia/reoxygenation than EA under these experimental conditions.


Crystal structure of the bacteriophage P2 integrase catalytic domain.
Bacteriophage P2 is a temperate phage capable of integrating its DNA into the host genome by site-specific recombination upon lysogenization. Integration and excision of the phage genome requires P2 integrase, which performs recognition, cleavage and joining of DNA during these processes. This work presents the high-resolution crystal structure of the catalytic domain of P2 integrase, and analysis of the structure-function relationship of several previously identified non-functional P2 integrase mutants. The DNA binding area is characterized by a large positively charged patch, harboring key residues. The structure reveals potential for large dimer flexibility, likely essential for rearrangement of DNA strands upon integration and excision of the phage DNA.


Sleep duration and inflammatory mediator levels associated with long-term prognosis in temporomandibular disorders.
Sleep disturbance is a systemic symptom and at the same time a major modulating factor of temporomandibular disorders (TMD). Inflammation is known as a underlying mechanism involved in both poor sleep and increased pain. The relationship between long-term clinical characteristics and hematologic biomarkers of hypothalamic-pituitary-adrenal axis activity and inflammation in TMD patients according to sleep duration was investigated to verify the possible role of sleep disturbance and systemic inflammation in TMD. Inflammatory and stress mediator levels of venous blood samples were investigated in 63 female TMD patients along with comorbidity levels including stress, somatization, autonomic symptoms and sleep quality based on structured questionnaires. Differences in long-term clinical characteristics and hematologic variables following conservative treatment were analysed according to total sleep time as normal, short and long sleep groups. Also, clinical and hematologic indices related to favourable treatment response were sought out. Significantly less patients in the long sleep group reported pain on voluntary mandibular movement (p = .042) while depression (p = .043) and somatization levels (p = .002) were significantly higher in the short sleep group. Norepinephrine levels of the long sleep group were significantly lower than other groups. Decrease in pain intensity with treatment was smallest in the short sleep group. Erythrocyte sedimentation rate was associated with significant pain improvement at 3 months post-treatment and interleukin-1β, -4, and -8 levels could predict favourable treatment response. Short sleep is associated with more comorbidities and unfavourable long-term treatment response in TMD which may be mediated by systemic inflammation. Effective management of sleep is necessary for successful TMD management.


Can inorganic elements affect herpesvirus infections in European eels?
In combination, pollution and pathogens represent a serious threat to the health of European eels that has been increasingly recognized. Thus, the impact of contaminants, cadmium, lead, mercury, and selenium, on anguillid herpesvirus 1 infection in wild European eels has been evaluated. Despite the small sample size, results indicate that selenium and mercury concentrations may compromise the European eel immune system as herpesvirus infection was more prevalent in specimens with higher Hg and Se hepatic concentrations.


RING domain is essential for the antiviral activity of TRIM25 from orange spotted grouper.
Tripartite motif-containing 25 (TRIM25) has been demonstrated to exert crucial roles in the regulation of innate immune signaling. However, the roles of fish TRIM25 in antiviral immune response still remained uncertain. Here, a novel fish TRIM25 gene from orange spotted grouper (EcTRIM25) was cloned and its roles in grouper virus infection were elucidated. EcTRIM25 encoded a 734-aa protein which shared 68% identity to large yellow croaker (Larimichthys crocea). Amino acid alignment showed that EcTRIM25 contained three conserved domains, including a RING-finger domain, a B box/coiled-coil domain and a SPRY domain. In healthy grouper, the transcript of EcTRIM25 was predominantly detected in skin, spleen and intestine. After stimulation with Singapore grouper iridovirus (SGIV) or poly I:C, the relative expression of EcTRIM25 in grouper spleen was significantly increased at the early stage of injection. Subcellular localization analysis showed that EcTRIM25 distributed throughout the cytoplasm in grouper cells. Notably, the deletion RING domain affected its accurate localization and displayed microtubule like structures or bright aggregates in GS cells. After incubation with SGIV or red spotted grouper nervous necrosis virus (RGNNV), overexpression of full length of EcTRIM25 in vitro significantly decreased the viral gene transcription of SGIV and RGNNV. Consistently, the deletion of RING domain obviously affected the inhibitory effect of EcTRIM25. Furthermore, overexpression of EcTRIM25 significantly increased the expression level of interferon related signaling molecules, including interferon regulatory factor (IRF) 3, interferon-induced 35-kDa protein (IFP35), MXI, IRF7 and myeloid differentiation factor 88 (MyD88), suggesting that the positive regulation of interferon immune response by EcTRIM25 might affected RGNNV replication directly. Meanwhile, the expression levels of pro-inflammation cytokines were differently regulated by the ectopic expression of EcTRIM25. We proposed that the regulation of IRF7, MyD88 and pro-inflammation cytokines might contribute more important roles in SGIV infection. In addition, the RING domain of EcTRIM25 also played critical roles in the regulation of interferon immune and inflammation response. Together, our results will provide new evidences that the RING domain was essential for the antiviral action of fish TRIM25 against iridovirus and nodavirus infection.


Reconsidering the Postoperative Day 0 Visit for Retina Surgery.
This study compares outcomes of patients who were examined on postoperative (PO) day 0 and PO day 1 following retina surgery. A nonrandomized, comparative, retrospective series of one vitreoretinal surgeon was conducted on 166 patients with a PO day 0 visit (approximately 5 hours following surgery) and 428 patients with a PO day 1 visit. Among patients examined at PO day 0, 4.6% had hypotony (intraocular pressure [IOP] ≤ 5 mm Hg) and 1.8% needed intervention for elevated IOP (IOP ≥ 30 mm Hg) compared with 1.6% and 4.0% of patients, respectively, examined on PO day 1. Following retina surgery, there is a similar percentage of patients with abnormal IOP when patients are examined on PO day 0 when compared with PO day 1. However, the rate of hypotony was statistically higher on PO day 0, and there was a trend toward more elevated IOP on PO day 1. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e52-e56.].


Correlates of objectively measured physical activity in adults and older people: a cross-sectional study of population-based sample of adults and older people living in Norway.
The aims of the study were to identify correlates of objectively measured physical activity and to determine whether the explanatory power of the correlates differed with sex, weight status or level of education. Physical activity was assessed objectively in 3,867 participants, aged 20-85 years, for a consecutive 7 days using the ActiGraph GT1M activity monitor. Demographic and biological variables and levels of psychological, social environmental and physical environmental correlates were self-reported. The complete set of correlates explained 18.6 % (p < 0.001) of the variance in overall physical activity. Age and physical activity identity were the most important factors, explaining 4.8 and 3.2 % of the variance, respectively, whereas social environmental and physical environmental correlates did not significantly increase the amount of explained variance. Small interaction effects between demographic and biological variables and the correlates were observed. Self-efficacy, perceived behavioural control and physical activity identity might be important targets for intervention. Intervention efforts aimed at influencing psychological correlates of physical activity may prove equally effective regardless of sex, weight status and level of education.


Control of pMB1 replication: inhibition of primer formation by Rop requires RNA1.
The rop gene participates in the control of plasmid copy number by interfering with transcripts originating from the primer promoter. Here we show that this inhibition mechanism requires RNA1 in trans. Mutations in the RNA1 coding sequence that result in plasmids with altered incompatibility properties do not affect the ability of the molecule to participate in the Rop inhibition mechanism. Furthermore we show that the target of the Rop-RNA1 inhibitory mechanism is located, at least in part, after the 52nd nucleotide of the sequence encoding the primer transcript.


[Differential therapy of hemangiomas--when cryotherapy, laser therapy or operation?].
Hemangiomas are the most common soft tissue tumours in childhood, which arise after birth, grow for several months and regress spontaneously. Serious problems can occur with closure of the eye resulting in amblyopia or with psychologica problems due to disfiguring of the face. Therapeutic possibilities are cryo therapy, laser therapy and surgical removal. Cryotherapy can be used for small and flat hemangiomas. Bigger hemangiomas are treated with the Nd-YAG laser. Its effect is an acceleration of involution. Typical residues of hemangiomas must be secondarily corrected surgically. Indications for primary surgical therapy are hemangiomas of the eye lid and in the scalp.


Resonantly Enhanced Betatron Hard X-rays from Ionization Injected Electrons in a Laser Plasma Accelerator.
Ultrafast betatron x-ray emission from electron oscillations in laser wakefield acceleration (LWFA) has been widely investigated as a promising source. Betatron x-rays are usually produced via self-injected electron beams, which are not controllable and are not optimized for x-ray yields. Here, we present a new method for bright hard x-ray emission via ionization injection from the K-shell electrons of nitrogen into the accelerating bucket. A total photon yield of 8 × 10(8)/shot and 10(8 )photons with energy greater than 110 keV is obtained. The yield is 10 times higher than that achieved with self-injection mode in helium under similar laser parameters. The simulation suggests that ionization-injected electrons are quickly accelerated to the driving laser region and are subsequently driven into betatron resonance. The present scheme enables the single-stage betatron radiation from LWFA to be extended to bright γ-ray radiation, which is beyond the capability of 3(rd) generation synchrotrons.


HDL functionality in familial hypercholesterolemia: effects of treatment modalities and pharmacological interventions.
Recent studies have demonstrated that assessment of high-density lipoprotein (HDL) functionality indices, instead of HDL cholesterol measurement, is a more robust tool for the evaluation of the functional status of HDL and cardiovascular risk. There are qualitative abnormalities of HDL particles in familial hypercholesterolemia (FH) patients that might represent potential therapeutic targets. Despite the potential promise of optimizing HDL functionality for the treatment of FH, there has been no prior comprehensive review focusing on the impact of different lipid-modifying therapies on HDL functionality in FH patients. In the present review, we aim to fulfill this gap and provide a concise summary on the impact of different lipid-modifying therapies on HDL functionality in FH.


Engineered mutant α-ENaC subunit mRNA delivered by lipid nanoparticles reduces amiloride currents in cystic fibrosis-based cell and mice models.
Cystic fibrosis (CF) results from mutations in the chloride-conducting CF transmembrane conductance regulator (CFTR) gene. Airway dehydration and impaired mucociliary clearance in CF is proposed to result in tonic epithelial sodium channel (ENaC) activity, which drives amiloride-sensitive electrogenic sodium absorption. Decreasing sodium absorption by inhibiting ENaC can reverse airway surface liquid dehydration. Here, we inhibit endogenous heterotrimeric ENaC channels by introducing inactivating mutant ENaC α mRNA (αmutENaC). Lipid nanoparticles carrying αmutENaC were transfected in CF-based airway cells in vitro and in vivo. We observed a significant decrease in macroscopic as well as amiloride-sensitive ENaC currents and an increase in airway surface liquid height in CF airway cells. Similarly, intranasal transfection of αmutENaC mRNA decreased amiloride-sensitive nasal potential difference in CFTRKO mice. These data suggest that mRNA-based ENaC inhibition is a powerful strategy for reducing mucus dehydration and has therapeutic potential for treating CF in all patients, independent of genotype.


Laparoscopic patch repair of a Morgagni hernia in Menkes disease.
The association between Morgagni hernia and Menkes disease has not yet been described. Here, we report such a rare association in an 8-year-old boy who presented with subocclusive symptoms. He successfully underwent laparoscopic repair with a patch. The patch was fixed to the anterior abdominal wall by using transfascial sutures with extracorporeal knot tying and to the remaining edges of the diaphragmatic defect by using intracorporeal suturing and spiral tacks. At the 2-year follow-up, the child remained recurrence-free and without gastrointestinal symptoms. The potential relationship between the two conditions and the controversial use of spiral tacks to affix the mesh to the diaphragm are also discussed.


Spirulina for the food and functional food industries.
Humans are no strangers to the consumption of microalgae as already in the sixteenth century Spirulina was harvested from Lake Texcoco and consumed in markets in Tenochtitlan (today Mexico City). Nowadays, microalgae are being incorporated into many food formulations. Most of these use microalgae as a marketing strategy or as a colouring agent. However, Spirulina (and compounds derived thereof) show potential for being used as ingredients in the development of novel functional foods, which are one of the top trends in the food industry. Several human intervention studies demonstrated the potential of Spirulina for being used in the prevention or treatment of disorders related to metabolic syndrome. The aim of the current paper was to review current and potential applications of this microalga in the food and functional food industries. Health benefits associated with consuming Spirulina and/or some of the most important compounds derived from Spirulina were also discussed.


The prevalence of symptomatic and asymptomatic malaria and its associated factors in Debre Elias district communities, Northwest Ethiopia.
Malaria is a major cause of morbidity and mortality worldwide. According to the World Health Organization 2021 malaria report, it is considered to be endemic in 85 countries and territories. Malaria elimination programmes have also faced many challenges, such as widespread asymptomatic carriers in endemic regions, and they should be considered in malaria-control programmes in endemic areas for successful transmission interruption. This study aimed to assess the prevalence of symptomatic and asymptomatic malaria infections, and associated factors in Debre Elias district communities, Northwest Ethiopia from May to Jun 2018. A community-based cross-sectional study was conducted among selected kebeles in Debre Elias district, Amhara region, North-western Ethiopia. Multi-stage sampling technique was carried out to select representative households. A total of 440 randomly selected households were included, of which one individual per household was sampled for laboratory examination. Malaria prevalence was determined by light microscopy of stained blood films and using CareStart™ Malaria HRP2/pLDH (Pf/Pv) Combo rapid diagnostic test (RDT). A structured questionnaire was employed to collect socio-demographic data and associated risk factors. Data entry and analysis were carried out using Epi data 3.1 and SPSS version 23 software, respectively. The association between dependent and independent variables was explored by using bivariate and multivariate logistic regression analyses. Statistically significant association was declared at P-value of < 0.05. A total of 440 (333 asymptomatic and 107 symptomatic) individuals were included in this study. The overall prevalence of malaria was 5% with the majority (59.1%) of infections caused by Plasmodium falciparum. Among asymptomatic participants, 4.8% (n = 16, 95% CI = 2.6-7.3) and 4.2% (n = 14, 95% CI = 2.1-6.5) were diagnosed and confirmed by RDT and light microscopy respectively. Similarly, the prevalence of malaria among 107 symptomatic individuals was 7.5% (n = 8, 95% CI = 2.8-12.6) by either RDT or light microscopy. Utilization of insecticide-treated net (ITN), availability of ITN, house with eave, previous history of malaria infection, and family history of malaria infection were significantly associated with malaria infection (P < 0.05). In this study, the prevalence of asymptomatic and symptomatic malaria was moderate. Screening of both symptomatic and asymptomatic malaria in the community is very important to scale up intervention programmes.


Room Temperature Oxide Deposition Approach to Fully Transparent, All-Oxide Thin-Film Transistors.
A room temperature cathodic arc deposition technique is used to produce high-mobility ZnO thin films for low voltage thin-film transistors (TFTs) and digital logic inverters. All-oxide, fully transparent devices are fabricated on alkali-free glass and flexible polyimide foil, exhibiting high performance. This provides a practical materials platform for the low-temperature fabrication of all-oxide TFTs on virtually any substrate.


METTL1 drives tumor progression of bladder cancer via degrading ATF3 mRNA in an m7G-modified miR-760-dependent manner.
7-methylguanosine (m7G) modification is recently found to conservatively exist in RNA internal position besides mRNA caps and mediates the various RNA metabolisms. As the core confirmed transmethylase of m7G modification, METTL1 has been reported in certain human cancers. However, the role of internal m7G at miRNAs and its core writer METTL1 in bladder cancer (BCa) remains to be elucidated. Here, we demonstrated that METTL1 was indispensable for BCa proliferation and metastasis in vitro and in vivo. By combining miRNA sequencing, m7G methylated RNA immunoprecipitation (MeRIP) and RIP, we identified METTL1 promoted the processing of miR-760 in an m7G-dependent manner. Transcription sequencing suggested that METTL1 indirectly degrades tumor suppressor ATF3 mRNA mediated by miR-760. Together, we concluded a regulatory axis composed of METTL1/m7G/miR-760/ATF3 in regulating BCa progression and provided potential therapeutic targets for BCa.


Distribution of NADPH-diaphorase reactivity in the spinal cord of metamorphosing and adult Xenopus laevis.
The histochemical NADPH-diaphorase reaction has identified distinct neuronal populations in the nervous system of several species. Considerable evidence suggests that NADPH-d is a neuronal nitric oxide synthase (NOS). We examined spinal cords of adult and metamorphosing Xenopus laevis (XL) for developmental differences in NADPH-d reactivity. In adult XL, labeling was found in all dorsal root ganglia (DRGs) and in their termination sites within the dorsal horn (cutaneous afferent field) and intermediate gray (muscle afferent field). Cell bodies in the intermediate gray regions containing the autonomic preganglionic neurons were labeled in thoracic and sacral sections. Neurons located in the medial (MMC) and lateral motor columns (LMC) of the ventral horn were also stained. In metamorphosing XL, reactivity was detected in neurons in the intermediate gray, in the MMC and in the LMC as in the adult. Additionally, primary motoneurons including those innervating tail musculature were labeled. Neurons in the DRGs were stained at all stages; in the dorsal horn, the density of staining reflected the development of the sensory afferent fields. The conservation of NADPH-d reactivity in adult and metamorphosing XL spinal neurons suggests that NOS may be involved in processes independent of developmental changes occurring in XL spinal cord.


Clinical use of cyclosporine as an adjunctive therapy in the management of feline idiopathic pure red cell aplasia.
The clinical use of cyclosporine is described in a group of client-owned cats diagnosed with idiopathic pure red cell aplasia (PRCA). All 10 cats were treated with combinations of glucocorticoids and cyclosporine. Of the 10 cats, the eight for which follow-up data was available achieved and maintained remission for a median of 31 and 406 days, respectively. Therapy was reduced or discontinued in 7/8 cats; 2/7 maintained remission off therapy and 5/7 cats relapsed. Remission was reinduced in four cats, with 3/4 cats maintained long-term on low dose therapy. Adverse effects associated with cyclosporine therapy were responsive to dose reduction or drug withdrawal. Feline idiopathic PRCA was responsive to combination immunosuppressive therapy with glucocorticoids and cyclosporine. Relapse was common, particularly after drug discontinuation; therefore, most cats required maintenance long-term low dose therapy.


Current clinical propensity of laryngeal tuberculosis: review of 60 cases.
Although laryngeal tuberculosis is not frequent, it still occurs with an increasing incidence of pulmonary tuberculosis. Clinical pattern and spread mechanism of this disease have also changed as well. This study was performed to examine the current propensity seen in laryngeal tuberculosis and the clinical characteristics of this disease in patients showing atypical clinical pattern. The medical and videostroboscopic records of 60 patients with laryngeal tuberculosis diagnosed from the year 1994 to 2004 at the department of otorhinolaryngology in Severance Hospital were analyzed. The age of the patients ranged from 25 to 78 years, with their average age being 49.7 years. The ratio between men and women was 1.9:1. The major symptom encountered was hoarseness (96.6%). Clinically, granulomatous (n=22) and ulcerative types (n=11) of laryngeal tuberculosis were still prevalent, however, the incidence of atypical types such as polypoid (n=16) and nonspecific (n=11) were on the rise. Among the 27 cases that showed polypoid or nonspecific types, unilateral lesion was seen in 20 cases (74%). The most frequently affected area by this disease was true vocal cord, followed by false vocal cord, epiglottis, arytenoids and posterior commissure. Active pulmonary tuberculosis was present in 28 (46.7%), inactive pulmonary tuberculosis in 20 (33.3%), normal lung status in 12 cases (20%). Primary laryngeal tuberculosis was present in 9 cases (15%). Single lesion, polypoid and nonspecific type were prevalent in patients with inactive tuberculosis or normal lungs status. Physicians should be aware of the changes in the clinical pattern of laryngeal tuberculosis, which poses serious complications and risk of spreading.


Design, synthesis, biological evaluation and molecular docking of new 1,3,4-oxadiazole homonucleosides and their double-headed analogs as antitumor agents.
A novel series of homonucleosides and their double-headed analogs containing theophylline, 1,3,4-oxadiazole, and variant nucleobases was designed and synthesized. The new derivatives were fully characterized by HRMS, FT-IR, 1H NMR, and 13C NMR. The cytotoxic activities of all prepared compounds were screened in vitro against four cell lines, including fibrosarcoma (HT-1080), breast (MCF-7 and MDA-MB-231), and lung carcinoma (A-549). The double-headed analogue 18 showed marked growth inhibition against all the cell lines tested, specifically in HT-1080, with an IC50 values of 17.08 ± 0.97 µM. The possible mechanism of apoptosis was investigated using Annexin V staining, caspase-3/7 activity, and analysis cell cycle progression. The compound 18 induced apoptosis through caspase-3/7 activation and cell-cycle arrest in HT-1080 and A-549 cells. The molecular docking confirms that the compound 18 activated caspase-3 via the formation of hydrogen bonds and hydrophobic interactions.


[Effect of cardioplegia on nitrogen and energy metabolism of the human heart].
The interrelation between the energy and nitrogenous metabolism of the myocardium during cardioplegia has been studied in patients with congenital valvular heart disease (tetralogy of Fallot--12 patients, ventricular septal defect--5 patients). Whole body hypothermia with repeated heart reperfusion with cold cardioplegic blood perfusate was used for the protection of the myocardium. However, ATP level of the myocardium of some patients decreased by 20% and more of the baseline. This loss was accompanied by a reduction in glutamate and aspartate levels and a rise in ammonium and alanine levels in the myocardium (by 17.7 +/- 3.8; 17.6 +/- 5.9; 61.4 +/- 12.5 and 92.4 +/- 26.3% of the baseline, respectively).


[Correlation of "latent hyperthyroidism" with psychological and somatic changes].
The study reported here was undertaken to establish the degree to which a person in a preclinical state of hyperthyroidism, with (by definition) euthyroid T3 and T4 levels but suppressed TRH on testing, already exhibits psychological changes and clinical symptoms. Two groups of 20 patients each, with clear clinical and preclinical hyperthyroidism (as defined by laboratory parameters), were studied, as well as a group of 20 controls. The subjects' psychological state of mind was investigated using self-rating scales, including the state-trait-anxiety inventory (STAI), "Befindlichkeits"-Skala (Bf-S'), depression scale (D-S'), and a list of adjectives (EWL-K) with 14 different aspects of affective moods. Cognitive achievements were evaluated using the d2 test. Subjects were examined for somatic symptoms in accordance with Crooks' index of hyperthyroidism. The results clearly showed that typical psychological and somatic changes are already present in preclinical hyperthyroidism, these changes being partly identical with those of definite hyperthyroidism. In both patient groups, a significant increase in anxiety, a sense of not feeling well, and emotional irritability were found, as well as a tendency towards depressiveness, and an increased lack of vitality and activity. Attentiveness and concentration in both patient groups were lower than in the control group. Both patient groups showed the same prevalence of symptoms, such as palpitations, preference of cold over heat, excessive sweating, nervousness, fine digital tremor, and increased heart rate. With regard to the results, the diagnosis "preclinical hyperthyroidism" thus gains importance. Further prospective studies are required to answer the question whether antithyroidal treatment will influence the described psychological and somatic state of patients with preclinical hyperthyroidism.


iPSC-derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium.
We investigate the effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived progenitors and cardiomyocytes into acutely infarcted myocardium in severe combined immune deficiency mice. A total of 2 × 10(5) progenitors, cardiomyocytes or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Myocardial function was assessed at 2-week and 4-week post-infarction by using echocardiography and pressure-volume catheterization. Early myocardial remodelling was observed at 2-week with echocardiography derived stroke volume (SV) in saline (20.45 ± 7.36 μl, P < 0.05) and cardiomyocyte (19.52 ± 3.97 μl, P < 0.05) groups, but not in progenitor group (25.65 ± 3.61 μl), significantly deteriorated as compared to sham control group (28.41 ± 4.41 μl). Consistently, pressure-volume haemodynamic measurements showed worsening chamber dilation in saline (EDV: 23.24 ± 5.01 μl, P < 0.05; ESV: 17.08 ± 5.82 μl, P < 0.05) and cardiomyocyte (EDV: 26.45 ± 5.69 μl, P < 0.05; ESV: 18.03 ± 6.58 μl, P < 0.05) groups by 4-week post-infarction as compared to control (EDV: 15.26 ± 2.96 μl; ESV: 8.41 ± 2.94 μl). In contrast, cardiac progenitors (EDV: 20.09 ± 7.76 μl; ESV: 13.98 ± 6.74 μl) persistently protected chamber geometry against negative cardiac remodelling. Similarly, as compared to sham control (54.64 ± 11.37%), LV ejection fraction was preserved in progenitor group from 2-(38.68 ± 7.34%) to 4-week (39.56 ± 13.26%) while cardiomyocyte (36.52 ± 11.39%, P < 0.05) and saline (35.34 ± 11.86%, P < 0.05) groups deteriorated early at 2-week. Improvements of myocardial function in the progenitor group corresponded to increased vascularization (16.12 ± 1.49/mm(2) to 25.48 ± 2.08/mm(2) myocardial tissue, P < 0.05) and coincided with augmented networking of cardiac telocytes in the interstitial space of infarcted zone.


Localization of the peripheral-type benzodiazepine binding site to mitochondria of human glioma cells.
Subcellular fractionation was performed on human U251 glioblastoma cultures. In all subcellular fractions, the binding of the peripheral benzodiazepine ligand, [3H]PK 11195, correlated with the specific activity of monoamine oxidase (r = 0.95, p less than 0.001) and succinate dehydrogenase (r = 0.93, p less than 0.001), two mitochondrial enzymes. The specific activity of plasma membrane and nuclear markers correlated poorly with the presence of PK 11195 binding sites. These data support the mitochondrion as the primary location of peripheral-type benzodiazepine binding sites (PBBS) in human glioma cells. Mitochondria-rich preparations were then assayed for [3H]Ro5-4964 binding. Six nM [3H]Ro5-4964 failed to specifically bind to human U251 mitochondria, but bound vigorously to mitochondria from rat C6 glioma. These data indicate that the low affinity of Ro5-4864 for PBBS in human glioma cells compared to those in rat is due to interspecies receptor variation rather than impaired drug transport into human cells.


Successful treatment of non-Hodgkin lymphoma associated immune thrombocytopenia with involved field radiotherapy.
Immune thrombocytopenia complicates the course and impacts the outcome of non-Hodgkin lymphoma (NHL-ITP, non-Hodgkin lymphoma-immune thrombocytopenic purpura). The response to corticosteroids and/or intravenous immune globulins is usually short lasting, but NHL-ITP usually responds to anti-lymphoma chemotherapy. It is not clear if this success is due to the elimination of the lymphomatous tissue or to the immunosuppressor/immunomodulator effect of chemotherapy. Myelosuppressive anti-lymphoma chemotherapy carries the risk of severe thrombocytopenia that may not respond adequately to platelet transfusion support. We report on a patient with recurrent diffuse large B-cell lymphoma that coincided with immune thrombocytopenia. Both diseases completely responded to involved field radiation therapy. This supports the hypothesis that at least in some cases of NHL-ITP, the lymphomatous clone secretes the anti-platelet antibodies. This supports the therapeutic decision making for these patients.


A direct approach for function approximation on data defined manifolds.
In much of the literature on function approximation by deep networks, the function is assumed to be defined on some known domain, such as a cube or a sphere. In practice, the data might not be dense on these domains, and therefore, the approximation theory results are observed to be too conservative. In manifold learning, one assumes instead that the data is sampled from an unknown manifold; i.e., the manifold is defined by the data itself. Function approximation on this unknown manifold is then a two stage procedure: first, one approximates the Laplace-Beltrami operator (and its eigen-decomposition) on this manifold using a graph Laplacian, and next, approximates the target function using the eigen-functions. Alternatively, one estimates first some atlas on the manifold and then uses local approximation techniques based on the local coordinate charts. In this paper, we propose a more direct approach to function approximation on unknown, data defined manifolds without computing the eigen-decomposition of some operator or an atlas for the manifold, and without any kind of training in the classical sense. Our constructions are universal; i.e., do not require the knowledge of any prior on the target function other than continuity on the manifold. We estimate the degree of approximation. For smooth functions, the estimates do not suffer from the so-called saturation phenomenon. We demonstrate via a property called good propagation of errors how the results can be lifted for function approximation using deep networks where each channel evaluates a Gaussian network on a possibly unknown manifold.


Standardized protocols for microplastics determinations in environmental samples from the Gulf and marginal seas.
Microplastics are a group of ubiquitous persistent pollutants that have rapidly attracted much attention from the scientific community as well as the general public due to the growing awareness of the environmental risks they pose. However, due to limitations and variations in sampling, analytical measurement methods, and the different units used for reporting data, reliable comparisons between studies in the Gulf region and internationally are not straightforward. This study proposes standardized protocols for marine sediment, seawater, marine biota and aerosol (1) sampling, (2) sample processing, (3) sample identification and (4) reporting units to be used. An attempt has been made to highlight the limitations of the widely employed strategies for sampling microplastics in seawater, where a large portion of the microplastics is not sampled due to the mesh sizes used. The issues with the processing of biota samples and aerosols are likewise addressed, and recommendations are also made for standardization of units for reporting microplastic quantification. Protocols for collection of bottom sediments and aerosols are also proposed. These are the environmental matrixes for which there are no harmonized protocols in the Gulf region; hence if a standardized approach is adopted, it will enable and improve comparisons between the studies within this region and can be useful for similar studies in other marine areas as well.


Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds.
Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 μm porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.


Randomized Trial to Increase Speech Sound Differentiation in Infants Born Preterm.
To test whether infant-directed foreign language active learning would specifically increase speech sound differentiation to the intervention language while not decreasing differentiation in response to English. Pilot randomized controlled trial of stable infants born preterm in the newborn intensive care unit with normal auditory brainstem responses, whose parents spoke only English and had no musical training or familial hearing abnormality. Assignment was to 1 of 3 groups: passive exposure to English infant-directed lullabies and readings (English-enrichment, control group) and contingent exposure by active sucking on a sensor-equipped pacifier to either infant-directed French lullabies and readings (English environment, French-contingent learning group) or infant-directed Mandarin lullabies and readings (English environment, Chinese-contingent learning group). The main outcome measures were preintervention and postintervention event-related potentials (ERPs) in response to standardized speech syllables in each language. Forty-one subjects completed the study, including 15 in the English-enrichment control group and 13 each in the French-contingent and Chinese-contingent groups. The median gestational age at birth was 34 weeks (IQR, 8.75 weeks); postmenstrual age at intervention ranged from 36 to 46 weeks and was similar across the 3 groups. Postintervention mean ERP amplitude to pairs of English speech sounds did not differ across the 3 groups; however, ERP amplitude in French sound differentiation was greater in the French-contingent group than in the Chinese-contingent or English-enrichment groups, and ERP amplitude greater in Chinese sound differentiation was greater in the Chinese-contingent group compared with the other 2 groups. Contingent infant-directed foreign language exposure increased speech sound differentiation specific to the intervention language and did not decrease differentiation in response to English. ClinicalTrials.gov: NCT03232931.


Effects of rutin-fed caterpillars on an invertebrate predator depend on temperature.
A factorial experiment examined the effects of varying concentrations of the allelochemical rutin in caterpillars and the length of time the caterpillars had fed on the behavioral interactions of predatory stinkbugs (Podisus maculiventris) and their prey (Manduca sexta). Diet had no significant effect on defensive behavior of the caterpillars. The length of time that the caterpillars had fed (1 vs. 24 h) only influenced the frequency of caterpillars knocking the attacking stinkbugs away, with caterpillars knocking the stinkbugs away more often after 24 h of feeding. A second experiment tested the effects of diet (prey fed various concentrations of rutin), temperature (18° C and 28° C) and gender on consumption and growth parameters of fifth instar stinkbugs. At the cooler temperature, the bugs ate more, gained more weight but took twice as long to complete the stadium and consequently had reduced relative consumption and relative growth rates. Diet had no significant effect on biomass gained or stadium duration, but rutin-fed caterpillars did depress the stinkbugs' relative consumption rates. The effect of food quality on relative growth rate (RGR) was temperature dependent; rutin had no significant effect at the cooler temperature, but a high dose of rutin reduced RGR at the warmer temperature. Rutin had a greater negative impact on the females than the males. The effect of rutin on these predators was different than the effect on their prey (this study compared to Stamp (1990, 1992)): the negative effects of rutin seem to impact on the stinkbug's growth rather than on molting.


Sero-epidemiology and hemato-biochemical study of bovine leptospirosis in flood affected zone of Pakistan.
The bovine leptospirosis is an economically important zoonotic disease of flood affected areas worldwide, but scarce information is available about its epidemiology in Pakistan. This is a first study on sero-epidemiology of bovine leptospirosis in Pakistan. The objectives of this study were to investigate the sero-prevalence and associated risk factors of bovine leptospirosis in flood affected zone of Punjab, Pakistan. A total of 385 serum samples were randomly collected from four tehsils of district Muzaffargarh, Pakistan. The serum samples were subjected to indirect ELISA for the detection of anti-leptospira antibodies. The overall sero-prevalence of leptospirosis was 30.39%. The prevalence was significantly higher (p<0.001) in cattle (56.25%) than buffaloes (4.66%). The key risk factors identified based on multivariable logistic regression were; confined system of rearing, flooded area, and lesser to graduate level of education as risk factors for leptospirosis. The values of hematological parameters varied significantly (p<0.05) for Hb, TEC and PCV while there was no significant (p>0.05) difference among TLC values among sero-positive and sero-negative animals. The serum biochemical profile revealed significant differences (p<0.05) in values of ALT, AST and creatinine among the sero-positive and negative animals. Hence, it can be concluded that leptospirosis is an emerging and neglected disease in flood affected zone of Pakistan, and the disease needs to be explored comprehensively in other parts of the country to sort out solid strategies for its control and eradication.


Anti-epidermal growth factor receptor therapy for advanced head and neck squamous cell carcinoma: a meta-analysis.
To assess the efficacy and safety of anti-epidermal growth factor receptor (EGFR) therapy versus non-anti-EGFR therapy for advanced head and neck squamous cell carcinoma (HNSCC). The Cochrane Central Register of Controlled Trials, Medline, and Embase databases were searched for relevant reports. Quantitative analysis was carried out to evaluate the overall response rate (ORR), overall survival (OS), progression free survival (PFS), and grade 3-4 adverse effects. Ten reports involving 2,396 patients were included. Primary meta-analysis indicated that anti-EGFR therapy could improve ORR [relative risk (RR) 1.36, 95% confidence interval (CI) 1.12-1.67] and PFS [hazard ratio (HR) 0.63, 95% CI 0.55-0.71), but failed to improve OS (HR 0.88, 95% CI 0.74-1.03). In subgroup analyses, we found that monoclonal antibodies (Mabs) could improve ORR, OS, and PFS for both locoregionally advanced (LA) (ORR: 1.21, 1.08-1.37; OS: 0.72, 0.59-0.89; PFS: 0.66, 0.53-0.83) and recurrent/metastatic (RM) HNSCC (ORR: 1.88, 1.40-2.54; OS: 0.79, 0.67-0.94; PFS: 0.61, 0.52-0.71), while tyrosine kinase inhibitors (TKIs) did not improve any of these in patients with either LA (ORR: 1.09, 0.91-1.32; OS: 0.7, 0.31-1.63; PFS: 0.71, 0.34-1.52) or RM (ORR: 1.65, 0.84-3.24; OS: 1.13, 0.97-1.31; PFS: not available) HNSCC. Analysis of adverse effects demonstrated that rash (RR 14.34, 95% CI 5.02-41.02), diarrhea (2.36, 1.15-4.87), and anorexia (2.49, 1.11-5.56) were significantly associated with anti-EGFR therapy. Anti-EGFR Mabs are effective for both LA and RM HNSCC. In contrast, TKIs were unsuitable for treatment of advanced HNSCC. During anti-EGFR therapy, rash and some gastrointestinal reactions, such as diarrhea and anorexia, should be carefully monitored.


Improving Skin Cancer Diagnostics Through a Mobile App With a Large Interactive Image Repository: Randomized Controlled Trial.
Skin cancer diagnostics is challenging, and mastery requires extended periods of dedicated practice. The aim of the study was to determine if self-paced pattern recognition training in skin cancer diagnostics with clinical and dermoscopic images of skin lesions using a large-scale interactive image repository (LIIR) with patient cases improves primary care physicians' (PCPs') diagnostic skills and confidence. A total of 115 PCPs were randomized (allocation ratio 3:1) to receive or not receive self-paced pattern recognition training in skin cancer diagnostics using an LIIR with patient cases through a quiz-based smartphone app during an 8-day period. The participants' ability to diagnose skin cancer was evaluated using a 12-item multiple-choice questionnaire prior to and 8 days after the educational intervention period. Their thoughts on the use of dermoscopy were assessed using a study-specific questionnaire. A learning curve was calculated through the analysis of data from the mobile app. On average, participants in the intervention group spent 2 hours 26 minutes quizzing digital patient cases and 41 minutes reading the educational material. They had an average preintervention multiple choice questionnaire score of 52.0% of correct answers, which increased to 66.4% on the postintervention test; a statistically significant improvement of 14.3 percentage points (P<.001; 95% CI 9.8-18.9) with intention-to-treat analysis. Analysis of participants who received the intervention as per protocol (500 patient cases in 8 days) showed an average increase of 16.7 percentage points (P<.001; 95% CI 11.3-22.0) from 53.9% to 70.5%. Their overall ability to correctly recognize malignant lesions in the LIIR patient cases improved over the intervention period by 6.6 percentage points from 67.1% (95% CI 65.2-69.3) to 73.7% (95% CI 72.5-75.0) and their ability to set the correct diagnosis improved by 10.5 percentage points from 42.5% (95% CI 40.2%-44.8%) to 53.0% (95% CI 51.3-54.9). The diagnostic confidence of participants in the intervention group increased on a scale from 1 to 4 by 32.9% from 1.6 to 2.1 (P<.001). Participants in the control group did not increase their postintervention score or their diagnostic confidence during the same period. Self-paced pattern recognition training in skin cancer diagnostics through the use of a digital LIIR with patient cases delivered by a quiz-based mobile app improves the diagnostic accuracy of PCPs. ClinicalTrials.gov NCT05661370; https://classic.clinicaltrials.gov/ct2/show/NCT05661370.


Differentiation of F9 embryonal carcinoma cells induced by the c-jun and activated c-Ha-ras oncogenes.
The activated c-Ha-ras oncogene induced AP1-site DNA-binding activity in F9 cells. This induction appeared to be due, at least in part, to the induction of c-jun transcription. Both activated c-Ha-ras and c-jun induced the differentiation of F9 cells to endoderm-like cells. Thus, AP1 appears to play a key role in the initial stage of F9 cell differentiation.


Role of the nucleus raphe magnus in opiate analgesia as studied by the microinjection technique in the rat.
The analgesic effects of morphine (5 microgram, 0.2 microliter) microinjected into the nucleus raphé magnus (NRM) and the surrounding reticular formation of the rat were tested using vocalization after electric shock to the tail as the test for analgesia. Only sites in the NRM produced powerful analgesic effects, strongest analgesia being equivalent to 3 mg/kg i.v. morphine. The analgesia produced by the microinjection was reversed by systemic naloxone. Pretreatment with systemic cinanserin, a blocker of serotonergic receptors, led to a pronounced diminution of the analgesic effects of the morphine. The effects of microinjections of naloxone (5 microgram 0.2 microliter) were studied for their effect on analgesia produced by systemic morphine. The analgesia following 3 mg/kg i.v. morphine was diminished by the microinjection of naloxone but the naloxone almost completely reversed the analgesic effects of 1.5 mg/kg i.v. morphine. These results further substantiate the role of the NRM in analgesic mechanisms.


Design and Implementation of a Learner-Centered Self-Paced Peritoneal Oncology Education Program.
Current educational programs for peritoneal surface malignancies (PSM) are unstructured and often target advanced learners. The authors describe the design and implementation of a structured, self-paced course at a high-volume PSM center. In 2020, a learner-centered course was designed using the Canvas educational platform in consultation with the Center for Teaching at the University of Chicago. The course consisted of disease-site-specific modules, perioperative care pathways, in-built voluntary quizzes, and multimedia supplements for advanced learners. Trainees were provided access during the PSM service rotation, and engagement was compared across training levels by measuring the time spent online. Course design and management required 71 h between 2020 and 2022, with the majority of time spent in the design phase. During 3 years, 62 personnel (21 [34%] medical students, 28 [45%] residents, 8 [13%] staff, and 5 [8%] fellows) were assigned the course. The overall engagement rate was 83.9% (86% of medical students, 75% of residents, 100% of staff and fellows), and the median time spent online was 12.4 min/week (interquartile range [IQR], 2.1-53.0 min/week). Fourth-year medical students and clinical fellows spent more time online than other learners (73 min/week [IQR, 24.5-100 min/week] vs 13.3 min/week [IQR, 7.3-26.5 min/week]) (p = 0.001). The design and implementation of a PSM-specific course was feasible and sustainable using an online learning platform. Higher engagement was noted among invested learners. Non-technical factors for reduced engagement need to be ascertained further to improve the next iteration of this course.


The outcome of implant overdentures from a prosthodontic perspective: proposal for a classification protocol.
This article proposes a classification protocol for reporting the outcome of implant overdentures. Review of the literature pertaining to postinsertion prosthodontic procedures for maxillary and mandibular implant overdentures revealed a wide range in the terminology used and methods of reporting outcome, usually as a result of the use of varying designs among different implant systems. A need for comparative evaluation of the prosthodontic success of implant overdentures was identified. An existing classification protocol for implant-fixed prostheses containing six objectively defined fields was modified for implant overdentures. This new protocol, which also uses the descriptive fields of success, survival, unknown, dead, and retreatment (repair or failure), provides a method whereby postinsertion prosthodontic procedures and subsequent time to retreatment can be quantified regardless of design, method of attachment, or implant system. A ratio method for identifying prosthodontic treatment cost effectiveness of implant overdentures is included. This protocol could assist clinicians in their choices of implant overdenture therapy by providing accurate comparisons of varying implant overdenture systems and designs, and by identifying prosthodontic treatment cost effectiveness.


Bilateral robotic transabdominal adrenalectomy in a patient with intestinal malrotation.
Bilateral adrenalectomy is the preferred surgical approach for patients with failed treatments for pituitary-based Cushing's syndrome. Intestinal malrotation (IM) is a rare congenital anatomic variant that rarely affects adults. The abnormal abdominal anatomy is concerning to surgeons planning elective procedures in such patients. Here, we describe a bilateral robotic transabdominal adrenalectomy (RTA) in a patient with IM. A 29-year-old female presented with refractory pituitary-based Cushing's syndrome and was found to have IM on preoperative CT scan. The RTA was performed using one 10-12 mm camera trocar, two 8 mm robotic trocars per side and two midline 5 mm assistant ports. The 8 mm robotic cardiere forceps and the 8 mm robotic cautery hook were used on the left and right ports, respectively. Total operation time was 165 min (62 min on the right, 93 min on the left and 21 min for re-positioning). Total console time was 114 min (45 min on the right and 69 min on the left). Blood loss was minimal and there were no complications. She was discharged on post-operative day one. Anatomic variations were noted and the procedure modified. To our knowledge, this is the first reported case of bilateral RTA in a patient with IM. Surgeons should always review the anatomy on preoperative imaging. During the procedure, care should be taken to avoid damage to the multiple loops of small bowel located in the right upper quadrant. On the left side, the colonic splenic flexure is not encountered making access to the underlying left adrenal and kidney easier. The vascular anatomy was normal.


TERT promoter mutations and rs2853669 polymorphism: prognostic impact and interactions with common alterations in glioblastomas.
TERT promoter (TERTp) mutation is the most common mutation in glioblastomas. It creates a putative binding site for Ets/TCF transcription factors, enhancing telomerase expression and activity, whereas the rs2853669 variant disrupts another Ets/TCF binding. We explore here the interaction between these two alterations, tumor genomic profile and the impact on prognosis. The TERTp and rs2853669 statuses were determined and confronted with the outcome and molecular profile, i.e., loss of chromosome 10q, CDKN2A deletion, IDH mutation, EGFR amplification, MGMT promoter methylation. 651 glioblastomas were selected (sex ratio = 1.35, median age 60.4 years, median survival 13.5 months). The TERTp mutation found in 481 patients (74 %) was independent from rs2853669 genotypes. TERTp mutation, but not rs2853669 status, was associated with older age (61.4 vs. 52.8 years). rs2853669 status had no impact on overall survival (OS) either in mutated TERTp or wild-type TERTp. Neither rs2736100 (TERT, 5q15.33) nor rs192011116 (TERC, 3q26.2) status had any impact on survival or showed any association with a TERTp mutation. The TERTp mutation was associated with EGFR amplification chromosome 10q loss, CDKN2A deletion and IDH wt. EGFR amplification was associated with a better outcome in TERTp mutated GBM, and a worse outcome in TERTp WT. This study-the largest analyzing the TERTp mutation and the rs2853669 polymorphism-fails to find any prognostic impact of rs2853669. It confirms the dual prognostic impact of EGFR amplification depending on TERTp status.


Effects of preconditioning on the resistance to acute hypobaric hypoxia and their correction with selective antagonists of nicotinic receptors.
Hypobaric hypoxic preconditioning increased the resistance of low resistant and highly resistant rats to acute hypobaric hypoxia at a critical height. Intergroup differences in the resistance of rats to acute hypobaric hypoxia were not observed after hypobaric hypoxia and one variational series with a wide range of resistance (4.5-24.5 min) appeared. Methyllycaconitine, an antagonist of subtype α(7) nicotinic cholinergic receptors, abolished the influence of hypobaric hypoxia on low resistant rats, but had no effect on highly resistant animals. Mecamylamine, a preferential antagonist of subtype α(4)β(2) and α(3)-containing cholinergic receptors, did not modulate the effect of hypobaric hypoxia. By contrast, hypobaric hypoxia abolished the effect of mecamylamine on the resistance of rats that were not trained under conditions of hypobaric hypoxia (low resistant and highly resistant animals with low sensitivity to hypobaric hypoxia). We conclude that the same effect of hypobaric hypoxia is mediated by various mechanisms, which involve different nicotinic cholinergic receptors. They differ from the resistance mechanisms in non-trained rats.


Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome.
The HIE syndrome is a rare disorder characterized by extremely high serum IgE levels; recurrent serious infections, primarily involving the skin and sinopulmonary tract; and chronic eczematoid dermatitis dating from early infancy. The most common organisms that infect these patients are S. aureus and C. albicans. In addition, they have increased susceptibility to infection with H. influenzae, S. pneumoniae, enteric gram-negative rods, herpesviruses, and a variety of fungal organisms. The infections are frequently deep-seated, with abscess formation in the case of skin infection and pneumatocele formation in the case of pneumonias. Osteomyelitis, septic arthritis, and visceral abscesses are also seen but less frequently. Associated features of this syndrome are coarse facies, growth retardation, osteoporosis, keratoconjunctivitis, and eosinophilia. The immunologic basis of the HIE syndrome is still speculative. It is believed that the elevated IgE levels reflect a T-cell imbalance characterized by T-cell activation and a deficiency of suppressor T cells to inhibit IgE production. The propensity for recurrent infection may be related to a unique abnormality in the humoral immune system: excessive production of IgE directed to S. aureus and other infectious organisms with a concurrent deficit in their ability to synthesize protective IgG antibody against the same organisms. The fluctuating neutrophil chemotactic abnormality found in these patients may be secondary to the underlying T-cell defect with secretion of chemotactic inhibitor substances from mononuclear cells. Alternatively, the interaction of infectious agents with IgE on the surface of Fc epsilon R-bearing immune effector cells results in the release of inflammatory mediators that impair local host immune response. Activation of the immune system may also contribute to the associated features in this syndrome via the secretion of mediators that regulate connective tissue production and bone mineralization. Further studies will be needed before we completely understand the pathogenesis of HIE syndrome. Therapy primarily involves use of prophylactic anti-S. aureus antibiotics and the use of intravenous antibiotics, antifungal agents, or antiviral agents during acute infections. Surgical drainage or resection of deep-seated infections are frequently indicated. In patients who do not respond to conservative management, there may be a role for intravenous gammaglobulin and/or plasmapheresis.


Correction: Stimulation of the left dorsolateral prefrontal cortex with slow rTMS enhances verbal memory formation.
[This corrects the article DOI: 10.1371/journal.pbio.3001363.].


The role of continuous versus fractionated physical training on muscle oxidative stress parameters and calcium-handling proteins in aged rats.
Age-associated decline in skeletal muscle mass and strength is associated with oxidative stress and Ca(2+) homeostasis disturbance. Exercise should be considered a viable modality to combat aging of skeletal muscle. This study aimed to investigate whether continuous and fractionated training could be useful tools to attenuate oxidative damage and retain calcium-handling proteins. We conducted the study using 24-month-old male Wistar rats, divided into control, continuous, and fractionated groups. Animals ran at 13 m min(-1) for five consecutive days (except weekends) for 6 weeks, for a total period of 42 days. Each session comprised 45 min of exercise, either continuous or divided into three daily sessions of 15 min each. Metabolic and oxidative stress markers, protein levels of mitochondrial transcription factors, and calcium-handling proteins were analyzed. Continuous exercise resulted in reduced ROS production as well as showed a decrease in TBARS levels and carbonyl content. On the other hand, fractionated training increased the antioxidant enzyme activities. The ryanodine receptor and phospholamban protein were regulated by continuous training while sodium calcium exchange protein was increased by the fractionated training. These data suggest that intracellular Ca(2+) can be modulated by various training stimuli. In addition, the modulation of oxidative stress by continuous and fractionated training may play an important regulatory role in the muscular contraction mechanism of aged rats, due to changes in calcium metabolism.


Photoenzymatic decarboxylation: A promising way to produce sustainable aviation fuels and fine chemicals.
As one of the fastest-growing carbon emission sources, the aviation sector is severely restricted by carbon emission reduction targets. Sustainable aviation fuel (SAF) has emerged as the most potential alternative to traditional aviation fuel, but harsh production technologies limit its commercialization. Fatty acids photodecarboxylase from Chlorella variabilis NC64A (CvFAP), the latest discovered photoenzyme, provides promising approaches to produce various carbon-neutral biofuels and fine chemicals. This review highlights the state-of-the-art strategies to enhance the application of CvFAP in carbon-neutral biofuel and fine chemicals production, including supplementing alkane as decoy molecular, screening efficient CvFAP variants with directed evolution, constructing genetic strains, employing biphasic catalytic system, and immobilizing CvFAP in an efficient photobioreactor. Furthermore, future opportunities are suggested to enhance photoenzymatic decarboxylation and explore the catalytic mechanism of CvFAP. This review provides a broad context to improve CvFAP catalysis and advance its potential applications.


Between Always and Never: Evaluating Uncertainty in Radiology Reports Using Natural Language Processing.
The ideal radiology report reduces diagnostic uncertainty, while avoiding ambiguity whenever possible. The purpose of this study was to characterize the use of uncertainty terms in radiology reports at a single institution and compare the use of these terms across imaging modalities, anatomic sections, patient characteristics, and radiologist characteristics. We hypothesized that there would be variability among radiologists and between subspecialities within radiology regarding the use of uncertainty terms and that the length of the impression of a report would be a predictor of use of uncertainty terms. Finally, we hypothesized that use of uncertainty terms would often be interpreted by human readers as "hedging." To test these hypotheses, we applied a natural language processing (NLP) algorithm to assess and count the number of uncertainty terms within radiology reports. An algorithm was created to detect usage of a published set of uncertainty terms. All 642,569 radiology report impressions from 171 reporting radiologists were collected from 2011 through 2015. For validation, two radiologists without knowledge of the software algorithm reviewed report impressions and were asked to determine whether the report was "uncertain" or "hedging." The relationship between the presence of 1 or more uncertainty terms and the human readers' assessment was compared. There were significant differences in the proportion of reports containing uncertainty terms across patient admission status and across anatomic imaging subsections. Reports with uncertainty were significantly longer than those without, although report length was not significantly different between subspecialities or modalities. There were no significant differences in rates of uncertainty when comparing the experience of the attending radiologist. When compared with reader 1 as a gold standard, accuracy was 0.91, sensitivity was 0.92, specificity was 0.9, and precision was 0.88, with an F1-score of 0.9. When compared with reader 2, accuracy was 0.84, sensitivity was 0.88, specificity was 0.82, and precision was 0.68, with an F1-score of 0.77. Substantial variability exists among radiologists and subspecialities regarding the use of uncertainty terms, and this variability cannot be explained by years of radiologist experience or differences in proportions of specific modalities. Furthermore, detection of uncertainty terms demonstrates good test characteristics for predicting human readers' assessment of uncertainty.


[Changes and the clinical significance of muscle strength after different proportion tibial neurotomy].
To study the changes of the muscle strength after the selective tibial neurotomy and the relationship between the changes and the quantities of neurotomy, and to discuss the clinical significances. Twenty-four normal SD rats were divided into 4 groups with 6 in each. In group A, the left tibia nerve were cut off by 80%. 60% in group B, 40% in group C, 20% in group D, with the right as the control side. After 6 weeks measure the strength of the crural triceps and the weight of them. In all the groups muscle weight and muscle strength decreased. 88.2% strength decreased on the average in group A, 54.2% in group B, 19.5% in group C, 4.7% in group D. It will not damage strength of the crural triceps to cut off below 40% tibial nerve in SD rats.


Accommodating Indigenous Nurse-Initiated and Managed Antiretroviral Therapy (NIMART) Reporting in a Developing Country Context.
Financial reporting represents a critical tool in eliminating HIV across Papua New Guinea (PNG). Using the tenets of the theory of indigenous alternative reporting, this paper considers how the PNG Nursing Council may accommodate nurse-initiated and managed antiretroviral therapy (NIMART) reporting. Textual analysis of indigenous reporting expectations placed on the PNG Nursing Council are examined in a NIMART context to examine levels of reporting compliance exercised by council administrators from year-end reports (1980 to 2016) to accommodate NIMART reporting. The study revealed that the 2014 annual report of the PNG Nursing Council generated a 40% NIMART compliance rate, offering encouraging signs of financial reporting that could make room for NIMART reporting. The study suggested that local mechanisms could be used to meet local indigenous reporting expectations in order to adopt NIMART reporting. The study also has far-reaching implications for other developing country nursing councils wanting to develop NIMART reporting.


Compact, broadband, and low-loss power splitters using MZI based on Bézier bends.
We experimentally demonstrate wavelength-independent couplers (WICs) based on an asymmetric Mach-Zehnder interferometer (MZI) on a monolithic silicon-photonics platform in a commercial, 300-mm, CMOS foundry. We compare the performance of splitters based on MZIs consisting of circular and 3rd order (cubic) Bézier bends. A semi-analytical model is constructed in order to accurately calculate each device's response based on their specific geometry. The model is successfully tested via 3D-FDTD simulations and experimental characterization. The obtained experimental results demonstrate uniform performance across different wafer sites for various target splitting ratios. We also confirm the superior performance of the Bézier bend-based structure, compared to the circular bend-based structure both in terms of insertion loss (0.14 dB), and performance consistency throughout different wafer dies. The maximum deviation of the optimal device's splitting ratio is 0.6%, over a wavelength span of 100 nm. Moreover, the devices have a compact footprint of 36.3 × 3.8 μ m 2.


Prevalence of and factors associated with root decay in older adults in Canada.
We collected data on the oral health status and treatment needs of a random sample of persons aged 50 years and over. Data on root decay were obtained from the 183 subjects who were dentate. All remaining teeth were examined for root decay and restorations, whether root surfaces were affected by recession or not. Analysis was undertaken by case and root surface, with separate analyses of decayed (DS), and decayed and filled (DFS) root surfaces. One or more root surfaces with untreated decay were found in 37.2% of subjects, while one or more decayed or filled root surfaces were found in 56.8%. The mean number of decayed surfaces was 1.3 per person, and the mean number of decayed and filled root surfaces was 2.6. Multiple and logistic regression analyses showed that oral health variables were more important predictors of the presence and severity of root decay than demographic, general health, or dental care factors.


The burden of pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunization (EPI) in 1974: a systematic review protocol.
Vaccine against pertussis has been in use for several decades. Despite the widespread use of pertussis vaccine, evidence shows resurgence of pertussis in high-income countries. Pertussis surveillance data is largely missing from low- and middle-income countries (LMICs). Without data on trends of pertussis, it is difficult to review and amend pertussis control policies in any country. We propose conducting a systematic review to evaluate the burden and trends of pertussis in LMICs since 1974. Common and medical subject heading (MeSH) terms for pertussis and LMICs will be used to search electronic databases for the relevant literature published between 1974 and December 2014. Only studies from LMICs that fulfils World Health Organisation (WHO) or CDC pertussis case definitions will be included. The studies must have a clear numerator and denominator in a well-defined population. Risk of bias will be evaluated by assessing all qualifying full-text articles for quality and eligibility using a modified quality score assessment tool. Standardised data extraction will be carried out after which descriptions of trends in the prevalence, incidence, as well as mortality rate and case fatality rate, will be done. Where sufficient data is available, the results will be stratified by age group, geography, location, vaccination and HIV status. The systematic review proposed by this protocol seeks to address the knowledge gap in the epidemiology of pertussis in LMICs for the first time. It is anticipated that the background epidemiological trends of pertussis in LMICs that our study will provide could be used in the planning for the control of pertussis. PROSPERO CRD42015015159.


An inducible model for genetic manipulation and fate-tracing of PDGFRβ-expressing fibrogenic cells in the liver.
Myofibroblasts are the source of extracellular matrix protein during liver fibrogenesis. Fibroblasts, hepatic stellate cells (HSCs) and vascular smooth muscle cells are mesenchymal subpopulations in the liver that are characterized by the expression of PDGFRβ and contribute to the pool of these myofibroblasts. Conditional knockout models are important to better understand the function of specific liver cell populations including mesenchymal cells. While there is a limited number of constitutive mouse models for liver mesenchymal cell specific transgene expression, there is no established model for inducible gene targeting in HSCs or PDGFRβ-expressing mesenchymal cell populations in the liver. To address this, we investigated whether the tamoxifen inducible PDGFRβ-P2A-CreERT2 mouse can be used as a reliable tool to specifically express transgens in liver mesenchymal cells. Our data demonstrate, that PDGFRβ-P2A-CreERT2 specifically and efficiently marks over 90% of retinoid positive HSCs in healthy and fibrotic liver in mice upon tamoxifen injection, and that those cells give rise to Col1a1-expressing myofibroblasts in different models of liver fibrosis. Together with a negligible background recombination of only about 0.33%, this confirms that the PDGFRβ-P2A-CreERT2 mouse is nearly as efficient as established constitutive LratCre and PDGFRβ-Cre mouse models for recombination in HSCs, and that it is a powerful model for mesenchymal liver cell studies that require an inducible Cre approach.


ED ultrasound diagnosis of a type B aortic dissection using the suprasternal view.
Aortic dissection (AD) is one of the most challenging diagnoses in emergency medicine. This is due, in part, to its variable presentation, ranging from abrupt tearing chest pain in a hemodynamically unstable patient to back pain in a stable patient, as well as its high mortality rates. (1) With the expanding role of ultrasound (U/S) performed by emergency physicians, it is possible to make the diagnosis of AD at the bedside before any other imaging modality has been accessed. (2) In this case report, we describe the use of emergency department (ED) bedside U/S and specifically highlight the use of the suprasternal view in the diagnosis of AD.


Immunotherapy: Treating with Fewer Allergens?
Polysensitization, sensitization to more than one allergen, is a common feature of patients with allergic rhinitis, and may be a risk factor for subsequent development of allergic diseases, especially allergic asthma. However, a polysensitized patient does not necessarily have polyallergy, a documented, causal relationship between exposure to 2 or more specific, sensitizing allergens and the subsequent occurrence of relevant clinical symptoms of allergy. Allergen immunotherapy treatment strategy for the polysensitized patient in Europe is to treat the single or 2 most clinically relevant allergen(s), whereas patients in the United States are usually treated for all potential clinically relevant allergens.


B cells secrete GABA, which provokes a pro-tumor immune microenvironment.
In a recent publication in Nature, Zhang et al. report that foreign antigen stimulation elicits bountiful changes in lymphatic metabolite production-changes that include B cells secreting GABA, which reprograms macrophages and limits T cell cytotoxicity. This signifies a new mechanism by which B cells regulate immune suppression and facilitate tumor progression.