Class prediction and discovery using gene microarray and proteomics mass spectroscopy data: curses, caveats, cautions.
Two practical realities constrain the analysis of microarray data, mass spectra from proteomics, and biomedical infrared or magnetic resonance spectra. One is the 'curse of dimensionality': the number of features characterizing these data is in the thousands or tens of thousands. The other is the 'curse of dataset sparsity': the number of samples is limited. The consequences of these two curses are far-reaching when such data are used to classify the presence or absence of disease. Using very simple classifiers, we show for several publicly available microarray and proteomics datasets how these curses influence classification outcomes. In particular, even if the sample per feature ratio is increased to the recommended 5-10 by feature extraction/reduction methods, dataset sparsity can render any classification result statistically suspect. In addition, several 'optimal' feature sets are typically identifiable for sparse datasets, all producing perfect classification results, both for the training and independent validation sets. This non-uniqueness leads to interpretational difficulties and casts doubt on the biological relevance of any of these 'optimal' feature sets. We suggest an approach to assess the relative quality of apparently equally good classifiers.


Mechanical insights into ribosomal progression overcoming RNA G-quadruplex from periodical translation suppression in cells.
G-quadruplexes formed on DNA and RNA can be roadblocks to movement of polymerases and ribosome on template nucleotides. Although folding and unfolding processes of the G-quadruplexes are deliberately studied in vitro, how the mechanical and physical properties of the G-quadruplexes affect intracellular biological systems is still unclear. In this study, mRNAs with G-quadruplex forming sequences located either in the 5' untranslated region (UTR) or in the open reading frame (ORF) were constructed to evaluate positional effects of the G-quadruplex on translation suppression in cells. Periodic fluctuation of translation suppression was observed at every three nucleotides within the ORF but not within the 5' UTR. The results suggested that difference in motion of ribosome at the 5' UTR and the ORF determined the ability of the G-quadruplex structure to act as a roadblock to translation in cells and provided mechanical insights into ribosomal progression to overcome the roadblock.


PLGA nanoparticles loaded with KMP-11 stimulate innate immunity and induce the killing of Leishmania.
We recently demonstrated that immunization with polyester poly(lactide-co-glycolide acid) (PLGA) nanoparticles loaded with the 11-kDa Leishmania vaccine candidate kinetoplastid membrane protein 11 (KMP-11) significantly reduced parasite load in vivo. Presently, we explored the ability of the recombinant PLGA nanoparticles to stimulate innate responses in macrophages and the outcome of infection with Leishmania braziliensis in vitro. Incubation of macrophages with KMP-11-loaded PLGA nanoparticles significantly decreased parasite load. In parallel, we observed the augmented production of nitric oxide, superoxide, TNF-α and IL-6. An increased release of CCL2/MCP-1 and CXCL1/KC was also observed, resulting in macrophage and neutrophil recruitment in vitro. Lastly, the incubation of macrophages with KMP-11-loaded PLGA nanoparticles triggered the activation of caspase-1 and the secretion of IL-1β and IL-18, suggesting inflammasome participation. Inhibition of caspase-1 significantly increased the parasite load. We conclude that KMP-11-loaded PLGA nanoparticles promote the killing of intracellular Leishmania parasites through the induction of potent innate responses. In this novel study, KMP-11-loaded PLGA nanoparticles are demonstrated to promote the killing of intracellular Leishmania parasites through enhanced innate immune responses by multiple mechanisms. Future clinical applications would have a major effect on our efforts to address parasitic infections.


Familial translocation t(10;21)(q22;q22).
A family is described with a translocation t(10;21)(q22;q22) transmitted through three generations. This family was studied for the apparition of several miscarriages and two sisters with multiple malformations. Both children had a probably partial trisomy of chromosome 10 and a monosomy of chromosome 21 due to a maternal adjacent-2 meiotic segregation.


Trends in the incidence of oral cancer in Saudi Arabia from 1994 to 2015.
Oral cancer is one of the most common non-communicable diseases worldwide. This paper presents an evaluation of the trends and geographical distributions of oral cancers in the Saudi Arabian population. Data from Saudi Cancer Registry reports were used in this analysis, which assessed the period between 1994 and 2015. All cancer cases are recorded in these reports, as well as the age, gender, region and histological cancer sites for each patient. Age-standardised and age-specific incidence rates were calculated in these reports. For the purposes of this paper, only cancers of the lips, tongue and mouth were considered oral cancers. Between 1994 and 2015, the Saudi Cancer Registry identified 172,424 cancer cases in total. Of these, 3184 were oral cancer. The mean age-standardised rate of oral cancer for the study period was 2.9 per 100,000 people; for females, it was 1.5, and for males, it was 1.4. The incidence of oral cancer varied by region, with Jazan displaying the highest age-standardised rate and Hail displaying the lowest. A positive correlation was observed between oral cancer incidence and age. The overall trend of the age-standardised rate for both sexes remained constant from 1994 to 2015. However, the oral cancer incidence in Saudi Arabia varies by region. Studying this variation in more detail will help to guide awareness programmes in the regions that are most in need.


Behaviors and Advocacy Related to COVID-19 among Cancer Patients: The Health Belief Model and Opportunities for Messaging and Education.
Cancer patients have an increased risk of severe COVID-19 outcomes and were recommended to be vaccinated, wear a mask, practice social distancing, and increase hand hygiene. We used the Health Belief Model (HBM) to identify constructs that were associated with the likelihood of adhering to and advocating for CDC COVID-19 prevention recommendations. We surveyed adult cancer patients who had an onsite appointment at the Penn State Cancer Institute or at the Hematology and Oncology Associates of Northeastern Pennsylvania. Survey measures included adherence to and informing others of COVID-19 recommendations as well as HBM constructs. Relationships between HBM constructs and outcomes were assessed with Spearman's correlation and multivariable ordinal logistic regression. Of the 106 participants who completed the survey for our objectives of interest, 76% always wore a mask, 29% always practiced social distancing, and 24% washed their hands at least 10 times a day. Limited advocacy behaviors were captured for the COVID-19 vaccine (30%), social distancing (36%), and wearing masks (27%). Perceived benefits, perceived barriers, and cues-to-action were positively associated with the likelihood of adherence or advocacy of COVID-19 recommendations among cancer patients, whereas perceived susceptibility and self-efficacy were negatively associated with the likelihood of adherence or advocacy of COVID-19 recommendations among cancer patients. Perceived benefits may be the strongest predictor for adherence and advocacy for specific COVID-19 guidelines. Future messaging and educational campaigns focused on improving adherence to or advocacy of specific health behaviors should be informed by the HBM and originate from multiple outlets.


Image Exchange in Canada: Examples from the Province of Ontario.
An increased number of healthcare providers across the continuum of care share responsibility for providing treatment and care to the patient. Treatment is often provided at community-based facilities and not necessarily at the hospital that performed the imaging. As a result, there is an increased dependency on readily available access to a patient's longitudinal imaging records. The ways in which diagnostic images and results are exchanged among providers within a patient's circle of care have expanded. This article explores three varieties of image exchange. First, we examine image exchange patterns within a regional Diagnostic Imaging Repository and identify missed sharing opportunities. Secondly, we explore the use of a regional clinical viewer widely used in southwestern Ontario, called ClinicalConnect™, and examine the adoption of the viewer by providers. Finally, the paper provides a high-level look at how patients can leverage patient portals to view their imaging data to empower their healthcare experience.


Effects of non-haemorrhagic injury on the cardiovascular response to tilting in the rat.
In the unanaesthetized uninjured rat a head-up tilt elicited a pressor response, the magnitude of which was directly related to the angle of tilt. The pressor response was reduced by a 4 h period of bilateral hind-limb ischaemia and by a non-fatal scald, although the slope of the regression line relating percentage rise in mean arterial blood pressure to the angle of tilt was unaltered. The degree of impairment of the response was directly related to the severity of the injury. In the uninjured rat there was a sigmoid relationship between the angle of tilt and the mean heart rate during the tilt. No relationship could be demonstrated between angle of tilt and heart rate in the injured rats.


Significance of Serum Cytokeratin-18 in Prediction of Hepatocellular Carcinoma in Chronic Hepatitis C Infected Egyptian Patients.
Hepatitis C virus is one of the most common etiologic agents of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma in which there is continuous inflammation and regeneration of hepatocytes. Cytokeratin-18 (CK18) has been suggested to play an important role in tumorigenesis of epithelial cancers. Estimation of CK18 serum levels in patients with chronic viral hepatitis C (CHCV) and hepatocellular carcinoma (HCC) and find the relationship between their levels, the severity of the disease and the development of HCC. We measured serum levels of CK18 in 60 Egyptian patients (30 with CHCV & 30 with HCC) and 30 healthy controls. Patients with HCC had highly significant increased CK18 levels compared with CHCV patients, healthy controls. Cytokeratin-18 among the three classes of Child-Pugh classification show highly significant gradual increase from child A to C. Furthermore, In HCC there were positive correlations between CK18 and with RBCs, ESR, and AFP. CK18 is a sensitive indicator of the severity of liver disease. Patients with CHCV infection can be followed up by measurement of its serum level which can predict the development of HCC. The combination of AFP and CK18 increased the sensitivity of detection for HCC.


Gold-coated capillary based 2,4-dichlorophenoxyacetic acid chemi-luminescent assays: possibilities towards multianalysis.
The application of gold-coated glass capillaries for the design of a sensitive chemiluminescent immunoassay for 2,4-dichlorophenoxyacetic acid (2,4-D) is reported. The gold coating on the glass capillaries has been partially characterized and its effect on enhancing the signal intensity has been measured. A simple photo-multiplier tube-based photon detector is used for this purpose. At least three times improvement in the signal intensity is observed compared to uncoated glass capillaries, with a consequent improvement in the sensitivity of detection. Using such gold-coated glass capillaries, 2,4-D in the range 10(-9) to 10(-13) mol/l is detectable at a precision of +/-15% (CV%) and a limit of detection of 10(-15) mol/l is achievable. The possibility of using such gold-coated capillaries with a portable multianalytical set-up for field studies is also demonstrated.


Assessment of health related quality of life in polish patients with primary biliary cirrhosis.
Most patients with primary biliary cirrhosis (PBC) have impaired health related quality of life (HRQoL), as assessed by PBC-specific HRQoL (PBC-40) and generic (SF-36) questionnaires. Data on the applicability of PBC-27, a shorter version of PBC-40, have been limited. To assess HRQoL in Polish PBC patients, applying PBC-40, PBC-27 and SF-36 and to associate clinical or laboratory parameters with HRQoL factors. A total of 205 PBC patients (188 females) were analyzed using PBC-40, PBC-27 and SF-36; 85 disease-free demographically matched (in terms of age, gender, ethnicity) individuals were used as normal controls. When compared to controls, PBC patients had significantly impaired HRQoL across all the domains of SF-36. HRQoL impairment by PBC-40 and PBC-27 was comparable between cirrhotics and non-cirrhotics, except for significantly worse Itch in cirrhotics (6.5±4.9 vs 5.1±4.3; P=0.03). In PBC-40/27, alkaline phosphatase (ALP) levels correlated with itch (P=0.0003). Female patients had marginally impaired cognitive function compared to males by PBC-40 (P=0.06). Other gender-related differences were not found. Anti-gp210 positive, as well as AMA negative PBC patients, had worse HRQoL features in itch and social/emotional domains of PBC-40/PBC-27 questionnaires. Very strong correlations (P<0.0001) between PBC-40/PBC-27 and SF-36 were seen for several domains. HRQoL is significantly impaired in Polish patients with PBC, independently of gender and disease severity. PBC-40 and PBC-27 questionnaires are efficient in detecting HRQoL impairment in Polish PBC patients. The striking correlation between PBC-40/PBC-27 and SF-36 confirms the usefulness of the former HRQoL measures in PBC patients from Central-Eastern Europe.


Lessons learned from early experience of per oral endoscopic myotomy in children.
Achalasia cardia (AC) is rare in children, and the standard treatment is open or Laparoscopic Heller's myotomy with or without fundoplication if pneumatic dilatation has failed. Per oral endoscopic myotomy (POEM) is a novel technique for management of achalasia with good results in adults. We report POEM in four children and the outcome with special emphasis on the technique and management of intra-operative complications. Four children aged 7-15 years presenting with progressive dysphagia, cough, night-time aspirations, and weight loss of six months to one year were investigated with upper GI contrast study, flexible endoscopy and biopsy, oesophageal manometry, and a diagnosis of Type 1 & 2 AC was made. An experienced adult endoscopist in collaboration with the paediatric surgical team performed POEM. POEM was performed successfully using ERBE HYBRID knife setup and waterjet injection for the submucosal tunnelling. Operative time was 25-40 min (mean 31 min). The hospital stay was 3-8 days with last 3 patients discharged on day three. No major intraoperative or post-operative complications were seen. The Eckardt score changed from above 4 to 0 at one-month follow-up. All four are well at one year post-operatively and beyond. Two patients had subcutaneous emphysema post-operatively. One developed pneumoperitoneum intra-operatively. POEM was successfully performed with only minor adverse events in experienced hands. Anticipation and preparation for potential intraoperative complications and assigned responsibilities to each team helped the safe completion in the shortest time. Rectifying pneumoperitoneum concurrently without interruption of the operation exemplified teamwork. III.


Efficacy of remotely-delivered cognitive behavioural therapy for obsessive-compulsive disorder: An updated meta-analysis of randomised controlled trials.
Despite remotely-delivered cognitive behavioural therapy (CBT) being an emerging field, the evidence of its efficacy in obsessive-compulsive disorder (OCD) is limited. We aimed to estimate the efficacy of remotely-delivered CBT for OCD, compared to face-to-face CBT and non-CBT control conditions. Randomised clinical trials (RCTs) identified through a systematic literature search of PubMed, Ovid/PsychINFO and Web of Science until 21/06/2021. Eligible studies included individuals with OCD evaluating at least one form of remotely-delivered CBT versus a control condition. Random-effects meta-analyses, sub-analyses, meta-regressions, heterogeneity analyses, publication bias assessment and quality assessment. Twenty-two RCTs were included (n = 1796, mean age = 27.7 years, females = 59.1 %). Remotely-delivered CBT was more efficacious than non-CBT control conditions for OCD symptoms (g = 0.936 95 % CI = 0.597-1.275, p < .001), depressive symptoms (g = 0.358, 95 % CI = 0.125-0.590, p = .003) and anxiety symptoms (g = 0.468, 95 % CI = 0.135-0.800, p = .006). There were no significant differences in efficacy between remotely-delivered CBT and face-to-face CBT for OCD symptoms (g = -0.104 95 % CI = -0.391-0.184, p = .479), depressive symptoms (g = 0.138, 95 % CI = -0.044-0.320, p = .138), anxiety symptoms (g = 0.166, 95 % CI = -0.456-0.780, p = .601) or quality of life (g = 0.057, 95 % CI = -0.178-0.292, p = .489). Higher baseline severity of OCD symptoms was associated with a lower efficacy of remotely-delivered CBT compared to face-to-face CBT (β = -0.092, p = .036). The quality of the included studies was mostly identified as "low risk of bias" (45.5 %) or "some concerns" (45.5 %). Heterogeneity and limited evidence for some outcomes. Remotely-delivered CBT appears efficacious in reducing OCD symptoms and other relevant outcomes and is therefore a viable option for increasing treatment access. Preliminary evidence suggests some individuals with severe OCD may benefit more from face-to-face than remotely-delivered CBT.


Factors influencing the growth and maintenance of tubed cultures of embryonic chick cells.
An analysis was made of factors influencing the culture of embryonic chick cells. The procedures found to be optimal resulted in monolayers which survived for about 15 days.


Disseminated Sporotrichosis: An Important Differential Diagnosis for Venous Ulcers.
The authors present the case of a 45-year-old immunosuppressed man with lower extremity ulcers. Initially treated as venous ulcers, the wounds were later correctly diagnosed as cutaneous disseminated sporotrichosis. After appropriate treatment with systemic antifungals was initiated, the patient healed within 4 months.


Effect of temperature and relative humidity on ultraviolet (UV 254) inactivation of airborne porcine respiratory and reproductive syndrome virus.
The objective of this research was to estimate the effects of temperature and relative humidity on the inactivation of airborne porcine reproductive and respiratory syndrome (PRRS) virus by ultraviolet light (UV(254)). Aerosols of PRRS virus were exposed to one of four doses of UV(254) under nine combinations of temperature (n=3) and relative humidity (n=3). Inactivation constants (k), defined as the absolute value of the slope of the linear relationship between the survival fraction of the microbial population and the UV(254) exposure dose, were estimated using the random coefficient model. The associated UV(254) half-life dose for each combination of environmental factors was determined as (log(10)2/k) and expressed as UV(254) mJ per unit volume. The effects of UV(254) dose, temperature, and relative humidity were all statistically significant, as were the interactions between UV(254) dose × temperature and UV(254) dose × relative humidity. PRRS virus was more susceptible to ultraviolet as temperature decreased; most susceptible to ultraviolet inactivation at relative humidity between 25% and 79%, less susceptible at relative humidity ≤ 24%, and least susceptible at ≥ 80% relative humidity. The current study allows for calculating the dose of UV(254) required to inactivate airborne PRRS virus under various laboratory and field conditions using the inactivation constants and UV(254) half-life doses reported therein.


An examination of Ball's desaturation of intermittent monochromatic light in two patients with retinitis pigmentosa.
In 1971, Walters hypothesized that Bartley's brightness enhancement, the Broca-Sülzer phenomenon, and the desaturation of intermittent trains of short-wavelength monochromatic light (the Ball effect) were all the result of scotopic involvement at photopic levels. In support of this hypothesis, ERG data were presented showing the presence of a scotopic B-wave under conditions which normally did not produce them. In the present paper, data are presente from two patients with retinitis pigmentosa that seem to contradict Walters' hypothesis and to suggest the possibility of a more complex mechanism.


Development criteria for a Benchmark test program.
A Benchmark test program cannot only be used as a tool in the process of comparing the capabilities of different EDP systems, to make the decision for a new computer. Benchmark tests can serve also as a source of dynamic information on the development of performance and to predict bottlenecks with increasing workload. To gain these advantages each computer center should develop a representative model for its typical computer workload. Criteria for the development of such a Benchmark test program are described, especially for the important simulation of terminal sessions and detailed in an example.


Computers in a human perspective: an alternative way of teaching informatics to health professionals.
An alternative way of teaching informatics, especially health informatics, to health professionals of different categories has been developed and practiced. The essentials of human competence and skill in handling and processing information are presented parallel with the essentials of computer-assisted methodologies and technologies of formal language-based informatics. Requirements on how eventually useful computer-based tools will have to be designed in order to be well adapted to genuine human skill and competence in handling tools in various work contexts are established. On the basis of such a balanced knowledge methods for work analysis are introduced. These include how the existing problems at a workplace can be identified and analyzed in relation to the goals to be achieved. Special emphasis is given to new ways of information analysis, i.e. methods which even allow the comprehension and documentation of those parts of the actually practiced 'human' information handling and processing which are normally overlooked, as e.g. non-verbal communication processes and so-called 'tacit knowledge' based information handling and processing activities. Different ways of problem solving are discussed involving in an integrated human perspective--alternative staffing, enhancement of the competence of the staff, optimal planning of premises as well as organizational and technical means. The main result of this alternative way of education has been a considerably improved user competence which in turn has led to very different designs of computer assistance and man-computer interfaces. It is the purpose of this paper to give a brief outline of the teaching material and a short presentation of the above mentioned results.(ABSTRACT TRUNCATED AT 250 WORDS)


Enhanced and stabilized arsenic retention in microcosms through the microbial oxidation of ferrous iron by nitrate.
Magnetite strongly retains As, and is relatively stable under Fe(III)-reducing conditions common in aquifers that release As. Here, laboratory microcosm experiments were conducted to investigate a potential As remediation method involving magnetite formation, using groundwater and sediments from the Vineland Superfund site. The microcosms were amended with various combinations of nitrate, Fe(II) (aq) (as ferrous sulfate) and lactate, and were incubated for more than 5 weeks. In the microcosms enriched with 10 mM nitrate and 5 mM Fe(II) (aq), black magnetic particles were produced, and As removal from solution was observed even under sustained Fe(III) reduction stimulated by the addition of 10 mM lactate. The enhanced As retention was mainly attributed to co-precipitation within magnetite and adsorption on a mixture of magnetite and ferrihydrite. Sequential chemical extraction, X-ray absorption spectroscopy and magnetic susceptibility measurements showed that these minerals formed at pH 6-7 following nitrate-Fe(II) addition, and As-bearing magnetite was stable under reducing conditions. Scanning electron microscopy and X-ray diffraction indicated that nano-particulate magnetite was produced as coatings on fine sediments, and no aging effect was detected on morphology over the course of incubation. These results suggest that a magnetite based strategy may be a long-term remedial option for As-contaminated aquifers.


Working memory is a core executive function supporting dual-task locomotor performance across childhood and adolescence.
Most daily-life ambulatory tasks involve dual tasking, for example, talking while walking. In children, the evidence supporting the effects of age on dual tasking is confounded by the difficulty of the cognitive task and lack of adjustment to suit individual cognitive abilities. To address this issue, the current study examined the effects of age, cognitive load, and executive functioning on the degree of dual-task gait interference across childhood and adolescence. We tested 120 typically developing children aged 6-11 years, adolescents aged 12-16 years, and young adults aged 18-25 years. Participants were asked to walk while performing a visuospatial working memory task at two levels of cognitive load (easy and difficult) adjusted to suit each participant's cognitive ability. Spatiotemporal characteristics and intra-individual variability of gait were measured using a GAITRite electronic walkway. Irrespective of the cognitive load level, children aged 6 to 11 years showed greater dual-task gait interference for selective spatiotemporal gait characteristics; however, the younger children showed a trade-off pattern in gait variability whereby they prioritized gait stability at the expense of cognitive performance. Our results also showed that age and working memory capacity were significant predictors of dual-task interference for a range of complementary gait parameters in the combined sample. Importantly, working memory capacity was part of a moderating relationship between age and dual-task gait interference. These findings emphasize the importance of dual-task prioritization strategies in younger children and highlight the role of individual differences in working memory capacity in performance in dual-task gait situations.


Thiol content of spruce needles at forest limits.
We determined the water-soluble thiol (SH) content and the osmolality of the cell sap in spruce trees of both low- and high-altitude origin that were transplanted to two test areas at different altitudes (400 m and 1700 m). There was little or no significant difference in SH content and osmotic value between trees of low- or high-altitude origin at the same altitude, but the sulfhydryl (SH) content varied with the altitude of cultivation, being higher at 1700 m than at 400 m. SH content and osmotic value were higher in winter, independent of altitude and provenance. The annual pattern of water-soluble and protein-bound SH content and glutathione reductase activity was measured in spruce trees at 1700 m; these values also peaked in winter and were lowest in summer.


Neurometabolite correlates with personality and stress in healthy emerging adults: A focus on sex differences.
Personality traits have been linked with both brain structure and function. However, the exact relationship between personality traits and other behavioural measures with neurometabolites, measured with proton magnetic resonance spectroscopy, is not clear. Here we investigated the association between behavioural measures (i.e., personality traits, resilience, perceived stress, self-esteem, hopelessness, psychological distress) and metabolite ratios (i.e., of choline-containing compounds [Cho], creatine and phosphocreatine [Cr], and N-acetyl-aspartate [NAA]) in the posterior cingulate cortex (pCC) and the dorsal anterior cingulate cortex (dACC) and surrounding white matter (WM) regions in healthy emerging adults (N = 57, 26 women, mean age=23.40 years, SD=2.50). The pCC and the dACC were selected for their known involvement as important brain network hubs and their association to five factor personality dimensions and other psychological measures. Spectral analysis as well as statistics for demographic, clinical, and imaging data were performed. Correlation and multiple regression analyses were used to test the relationship between metabolite ratios and behavioural scores in the entire sample as well as in female and male participants separately. The entire sample showed significant (p<0.05) negative correlates of stress with the NAA/Cr ratio in the pCC, and of extraversion with WM metabolite ratios. In regards of sex differences, a significantly higher NAA/Cho ratio in the pCC (p<0.05), the dACC (p<0.01), and in the left and right posterior WM matter (p<0.05), and a lower Cho/Cr ratio in the dACC (p<0.01) was detected in women. Moreover, the two sexes differed in regards of metabolite correlates of openness, conscientiousness, extraversion, agreeableness, neuroticism, stress, hopelessness, and self-esteem, and in multiple regression model predictions. Our results point to a role of the ACC in conscientiousness through its involvement in higher-order cognitive control as part of the salience network and internally directed thoughts as part of the default mode network (DMN). Furthermore, the two sexes differ in terms of metabolite correlates of openness and conscientiousness in the pCC, suggesting mental process involvement through the DMN, and of agreeableness in the dACC, possibly through involvement in social cognitive processes, particularly in women. Additionally, our results suggest that the ACC is linked to the so-called Alpha-factor of personality. Our findings on stress correlates contribute to the existing literature of the involvement of the ACC as part of the limbic system. In addition, our results suggest a possible role of the pCC in stress-regulatory processes through a possible co-involvement of stress, hopelessness, and self-esteem in the pCC in men, where higher self-esteem may help to cope with stress.


Free nitrous acid serving as a pretreatment method for alkaline fermentation to enhance short-chain fatty acid production from waste activated sludge.
Alkaline condition (especially pH 10) has been demonstrated to be a promising method for short-chain fatty acid (SCFA) production from waste activated sludge anaerobic fermentation, because it can effectively inhibit the activities of methanogens. However, due to the limit of sludge solubilization rate, long fermentation time is required but SCFA yield is still limited. This paper reports a new pretreatment method for alkaline fermentation, i.e., using free nitrous acid (FNA) to pretreat sludge for 2 d, by which the fermentation time is remarkably shortened and meanwhile the SCFA production is significantly enhanced. Experimental results showed the highest SCFA production of 370.1 mg COD/g VSS (volatile suspended solids) was achieved at 1.54 mg FNA/L pretreatment integration with 2 d of pH 10 fermentation, which was 4.7- and 1.5-fold of that in the blank (uncontrolled) and sole pH 10 systems, respectively. The total time of this integration system was only 4 d, whereas the corresponding time was 15 d in the blank and 8 d in the sole pH 10 systems. The mechanism study showed that compared with pH 10, FNA pretreatment accelerated disruption of both extracellular polymeric substances and cell envelope. After FNA pretreatment, pH 10 treatment (1 d) caused 38.0% higher substrate solubilization than the sole FNA, which indicated that FNA integration with pH 10 could cause positive synergy on sludge solubilization. It was also observed that this integration method benefited hydrolysis and acidification processes. Therefore, more SCFA was produced, but less fermentation time was required in the integrated system.


Outcomes after stent implantation for the treatment of congenital and postoperative pulmonary vein stenosis in children.
Pulmonary vein stenosis (PVS) is a rare condition that can lead to worsening pulmonary hypertension and cardiac failure in children, and it is frequently lethal. Surgical and transcatheter approaches are acutely successful but restenosis is common and rapid. We reviewed outcomes among patients who underwent transcatheter pulmonary vein stent implantation for congenital or postoperative PVS at <18 years of age. A total of 74 pulmonary veins were stented with bare metal, drug-eluting, or covered stents in 47 patients. Primary diagnoses included PVS associated with anomalous venous return in 51%, PVS associated with other congenital cardiovascular defects in 36%, and congenital ("de novo") PVS in 13% of patients. Median age at the time of pulmonary vein stent implantation was 1.4 years. During a median cross-sectional follow-up of 3.1 years, 21 patients died. Estimated survival was 62±8% at 1 year and 50±8% at 5 years after pulmonary vein stent implantation. Stent placement acutely relieved focal obstruction in all veins. Of the 54 stents reexamined with catheterization, 32 underwent reintervention. Freedom from reintervention was 62±7% at 6 months and 42±7% at 1 year. Stent occlusion was documented in 9 cases and significant in-stent stenosis in 17 cases. Stent implantation diameter ≥7 mm was associated with longer freedom from reintervention (hazard ratio, 0.32; P=0.015) and from significant in-stent stenosis (hazard ratio, 0.14; P=0.002). Major acute complications occurred in 5 cases. Transcatheter stent implantation can acutely relieve PVS in children, but reintervention is common. Larger stent lumen size at implantation is associated with longer stent patency and a lower risk of reintervention.


Antibodies to ribosomes in chronic active hepatitis.
A recently developed Farr-type radioimmunoassay for the detection of antibodies to tritium-labeled HeLa cell cytoplasmic ribosomes was evaluated as a serologic test in a variety of liver diseases. Ribosomal antibodies were detected in the sera of 31.4% of 70 patients with chronic active hepatitis (CAH) and primary biliary cirrhosis compared with only 4.2% of patients with chronic persistent hepatitis, acute viral hepatitis, alcoholic liver disease, and miscellaneous liver diseases (X2 = 17.89, P less than 0.001). The level of ribosomal binding activity was also significantly higher in sera of patients with CAH and primary biliary cirrhosis (15.4% vs 6.5%; t = 5.61, P less than 0.001). The antibodies were observed almost exclusively in HBsAg-negative CAH with autoimmune features and infrequently at lower titer in HBsAg-positive CAH or CAH without HBsAg or autoantibodies. Inhibition experiments with purified ribosomal RNA suggested that the ribosomal antibodies are in part reactive with ribosomal RNA. Ribosomal antibodies appear to represent another example of the exaggerated immune response associated with CAH and primary biliary cirrhosis.


[Preliminary study on arsenic trioxide induced Tca8113 cell apoptosis].
To explore the possibility of arsenic trioxide inducing the apoptosis in the treatment of oral squamous cell carcinoma. Human tongue squamous cell carcinoma cell line Tca8113 was used for in vitro studies. The effect of arsenic trioxide on oral squamous cell carcinoma was studied by using flow cytometry, fluoroscope and electric microscope. Arsenic trioxide induced Tca8113 cell apoptosis, while inhibiting the growth and survival. Arsenic trioxide might be one drug of inducing apoptosis in the treatment of oral squamous cell carcinoma.


Ca2+ binding effects on protein conformation and protein interactions of canine cardiac calsequestrin.
Calsequestrin is a Ca2+-binding protein located intraluminally in the junctional sarcoplasmic reticulum (SR) of striated muscle. In this study, Ca2+ binding to cardiac calsequestrin was assessed directly by equilibrium dialysis and correlated with effects on protein conformation and calsequestrin's ability to interact with other SR proteins. Cardiac calsequestrin bound 800-900 nmol of Ca2+/mg of protein (35-40 mol of Ca2+/mol of calsequestrin). Associated with Ca2+ binding to cardiac calsequestrin was a loss in protein hydrophobicity, as revealed with use of absorbance difference spectroscopy, fluorescence emission spectroscopy, and photoaffinity labeling with the hydrophobic probe 3-(trifluoromethyl)-3-(m-[125]iodophenyl)diazirine. Ca2+ binding to cardiac calsequestrin also caused a large change in its hydrodynamic character, almost doubling the sedimentation coefficient. We observed that cardiac calsequestrin was very resistant to several proteases after binding Ca2+, consistent with a global effect of Ca2+ on protein conformation. Moreover, Ca2+ binding to cardiac calsequestrin completely prevented its interaction with several calsequestrin-binding proteins, which we identified in cardiac junctional SR vesicles for the first time. The principal calsequestrin-binding protein identified in junctional SR vesicles exhibited an apparent Mr of 26,000 in sodium dodecyl sulfate-polyacrylamide gels. This 26-kDa calsequestrin-binding protein was greatly reduced in free SR vesicles and absent from sarcolemmal vesicles and was different from phospholamban, an SR regulatory protein exhibiting a similar molecular weight. Our results suggest that the specific interaction of calsequestrin with this 26-kDa protein may be regulated by Ca2+ concentration in intact cardiac muscle, when the Ca2+ concentration inside the junctional SR falls to submillimolar levels during coupling of excitation to contraction.


The effect of intravitreal brolucizumab on choroidal thickness in patients with neovascular age-related macular degeneration.
In this study we evaluated the effect of intravitreal brolucizumab injections on choroidal thickness in patients with neovascular age-related macular degeneration (nAMD) who previously showed an incomplete response to anti-vascular endothelial growth factor treatment. A total of thirty-four eyes from 34 patients were included in this study. The patients received an average of 2.4 ± 1.1 brolucizumab injections with the mean follow-up period of 4.9 ± 2.0 months. After their first brolucizumab treatment, the central foveal thickness (CFT) and subfoveal choroidal thickness (SFCT) were significantly decreased from 431.6 ± 190.0 μm and 193.9 ± 75.1 μm to 274.6 ± 109.4 μm (P < 0.001) and 169.4 ± 71.1 μm (P < 0.001), respectively. However, there were no improvements in visual acuity. Patients were divided into three subgroups according to the number of brolucizumab treatments: one, two, and three or more injections. In all three subgroups, the CFT and SFCT were significantly reduced compared to baseline at all time points of brolucizumab injections. In conclusion, choroidal thickness was significantly reduced after intravitreal brolucizumab injections as a switching treatment in patients with nAMD.


Prophylactic Anticonvulsants in Intracerebral Hemorrhage.
Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome. We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score. We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95-0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76-4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40-3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51-6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10-5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4-6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication. Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.


Comparison of the effects of general and epidural anaesthesia for caesarean section on the neurobehavioural responses of newborn infants.
Thirty-one neonates delivered by elective caesarean section were evaluated at the ages of 3 h, 1 day, 2 days and 4-5 days using Scanlon's Early Neonatal Neurobehavioural Scale and tests for orientation. Thirteen of the mothers received general anaesthesia and 18 epidural anaesthesia. All the mothers were healthy and not in labour. All the neonates weighed 2500 g or more and had Apgar scores of 7 or more at 1, 5 and 15 min. The neonates delivered with epidural anaesthesia scored significantly lower on rooting at the age of 3 h than those delivered with general anaesthesia, but the latter scored significantly lower on habituation to sound and orientation to both animate and inanimate visual stimuli. General anaesthesia seemed to depress the infants' interactive processes (orientation items), and their ability to make an appropriate response to repetitive stimuli (habituation) more than did epidural anaesthesia, indicating greater global depression. This depression was short-lived, however, and there were no differences between the groups on any of the parameters after 24 h.


Role of calcineurin in the VTA in rats behaviorally sensitized to methamphetamine.
Chronic psychostimulant administration increases locomotor activity, which is referred to as locomotor sensitization. Calcineurin has been suggested to participate in psychostimulant-induced sensitization, but the underlying neurobiological mechanism is poorly understood. This study was designed to examine whether calcineurin activity and its substrates participate in methamphetamine (METH)-induced locomotor sensitization in rats. Two weeks daily METH (1 mg/kg, i.p.) was administrated to rats to induce locomotor sensitization, activity of calcineurin and its substrates Synapsin and glycogen synthase kinase-3β (GSK-3β) were detected. The initiation and expression of locomotor sensitization were tested by inhibition of calcineurin activity systematically or locally in the ventral tegmental area (VTA). Expression of the calcineurin A subunit (catalytic subunit) increased in the VTA but not prefrontal cortex, nucleus accumbens, or hippocampus in rats sensitized to METH. The calcineurin inhibitor cyclosporine A, systemically administered or microinfused into the VTA, suppressed the initiation but not expression of METH-induced locomotor sensitization. Chronic METH exposure upregulated the expression of the calcineurin A subunit in the VTA, which was negatively associated with downregulation of the phosphorylation of Synapsin and GSK-3β. Moreover, the related molecular changes were blocked by systemically administered cyclosporine A or microinjections into the VTA. These data elucidate the critical role of calcineurin in the neurobiological mechanism underlying METH-induced locomotor sensitization, suggesting that calcineurin might participate in the initiation of METH-induced locomotor sensitization by negatively regulating the activity of Synapsin and GSK-3β in the VTA.


Contraception and preconception counseling in women with autoimmune disease.
Appropriate contraception and preconception counseling are critical for women of reproductive age with systemic autoimmune diseases (AIDs) because clinical diagnosis, rheumatology medications, and disease activity may impact the safety or efficacy of certain contraceptives as well as the risk of adverse pregnancy outcomes. The presence of antiphospholipid (aPL) antibodies (anticardiolipin, anti-β2 glycoprotein I, and lupus anticoagulant) is the most important determinant of contraception choice, as women with these antibodies should not receive estrogen-containing contraceptives because of the increased risk of thrombosis. Prepregnancy counseling generally includes the assessment of preexisting disease-related organ damage, current disease activity, aPL antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies, and medication safety in pregnancy. Quiescent AID for six months on pregnancy-compatible medications optimizes maternal and fetal/neonatal outcomes for most patients.


Correction to: Relationship between Toxoplasma gondii seropositivity and schizophrenia in the Lebanese population: potential implication of genetic polymorphism of MMP-9.
An amendment to this paper has been published and can be accessed via the original article.


In vitro processing of recombinant G protein gamma subunits. Requirements for assembly of an active beta gamma complex.
The gamma subunits of the heterotrimeric G proteins (G gamma) are subject to carboxyl-terminal processing. This processing involves prenylation of a cysteine residue initially 4 amino acids from the carboxyl terminus, endoproteolytic truncation of the 3 terminal amino acids, and methylation of the now carboxyl-terminal prenylcysteine residue. The significance of each of these modifications in the ultimate properties of G proteins is not yet clear. We have developed in vitro systems for the production of the three processing intermediates (unmodified, prenylated, and truncated-prenylated) for two G gamma subunits, one which is subject to farnesylation (G gamma 1) and one which is geranylgeranylated (G gamma 2). Assessment of the functional consequences of the processing of G gamma was found to require reconstitution of the polypeptides with a G protein beta subunit (G beta). The ability of recombinant G beta, produced in Sf9 cells, to assemble into stable beta gamma complexes (G beta gamma) with each of the G gamma processing intermediates was assessed. Both prenylated and unprenylated G gamma subunits formed stable complexes with G beta, but surprisingly, neither of the truncated-prenylated G gamma subunits were competent for this assembly. The G beta gamma complexes which were formed were examined for their ability to interact with a G protein alpha subunit (G alpha). Only those G beta gamma complexes containing a prenylated G gamma subunit were functional in this assay. These data indicate that: 1) prenylation of G gamma is not required for G beta gamma assembly; 2) assembly of the G beta gamma complex occurs prior to the proteolytic processing of G gamma; and 3) G beta gamma complexes require prenylated G gamma for interaction with G alpha.


Co-delivery of paclitaxel and curcumin by biodegradable polymeric nanoparticles for breast cancer chemotherapy.
Multi-drug chemotherapy has been one of the most popular strategies for the treatment of malignant tumors, and has achieved desirable therapeutic outcomes. The objective of the present study is to develop biodegradable PCEC nanoparticles (NPs) for the co-delivery of paclitaxel (PTX) and curcumin (CUR), and investigate the antitumor effect of the drug delivery system (DDS: PTX-CUR-NPs) against breast cancer both in vitro and in vivo. The prepared PTX-CUR-NPs had a small size of 27.97 ± 1.87 nm with a low polydispersity index (PDI, 0.197 ± 0.040). The results exhibited slow release of PTX and CUR from the DDS without any burst effect. Further, the PTX-CUR-NPs displayed a dose-dependent cytotoxicity in MCF-7 cells with a higher apoptosis rate (64.29% ± 1.97%) as compared to that of free drugs (PTX + CUR, 34.21% ± 0.81%). The cellular uptake study revealed that the drug loaded PCEC polymeric nanoparticles were more readily uptaken by tumor cells in vitro. To evaluate the in vivo anti-tumor effect, the PTX-CUR-NPs were intravenously administered to BALB/c nude mouse xenografted with MCF-7 cells and the results exhibited significant inhibition of tumor growth with prolonged survival time and reduced side effect when compared with free drugs (PTX + CUR). Moreover, the administration of PTX-CUR-NPs treatment led to lower Ki67 expression (p < 0.05), and enhanced TUNEL positivity (higher apoptosis, p < 0.01) in tumor cells as compared to other treatment groups, suggesting the therapeutic efficacy of the DDS. Altogether, the present study suggests that the DDS PTX-CUR-NPs could be employed for the effective treatment of breast cancers in near future.


Importance of cytochrome P450-mediated metabolism in the mechanism of action of vitamin D analogs.
The elucidation of the metabolic pathway for vitamin D, including the delineation of the specific cytochrome P450s (CYPs) involved in activation and catabolism, has emphasized the overall importance of metabolic considerations in vitamin D analog design. This short review attempts to summarize recent findings with isolated CYPs and animal models in which CYPs are genetically manipulated to draw attention to structural features of vitamin D analogs that make them more or less resistant to metabolic enzymes. We conclude by placing metabolic considerations in the context of the other important aspects of vitamin D analogs.


A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease.
Currently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S-adenosyl-L-methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease. A total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention. After adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (- 34 ± 5 dB/m vs. - 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men. Our results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis. Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021-retrospectively registered, https://doi.org/10.1186/ISRCTN70887063.


Differences in energy expenditure for conventional and femtosecond-assisted cataract surgery using 2 different phacoemulsification systems.
To compare the mean cumulative dissipated energy (CDE) in patients having femtosecond laser-assisted or conventional phacoemulsification cataract surgery using 2 different phacoemulsification platforms. Bascom Palmer Eye Institute, Miami, Florida, USA. Prospective comparative nonrandomized clinical study. Consecutive patients were scheduled to have femtosecond laser-assisted cataract surgery with the Lensx laser or conventional phacoemulsification using an active-fluidics torsional platform (Centurion) or torsional platform (Infiniti). The mean CDE and cataract grade were recorded. The study comprised 570 eyes (570 patients). There was no statistically significant difference in mean age (P = .41, femtosecond group; P = .33, conventional group) or cataract grade (P = .78 and P = .45, respectively) between the active-fluidics and gravity-fluidics platforms. In femtosecond cases (145 eyes), the mean CDE (percent-seconds) was 5.18 ± 4.58 (SD) with active fluidics and 7.00 ± 6.85 with gravity fluidics; in conventional cases (425 eyes), the mean CDE was 7.77 ± 6.97 and 11.43 ± 9.12, respectively. In both femtosecond cases and conventional cases, the CDE was lower with the active-fluidics platform than with the gravity-fluidics platform (P = .029, femtosecond group; P < .001 conventional group). With both fluidics platforms, the mean CDE was significantly lower in the femtosecond group than in the conventional group (both P < .001). The active-fluidics phacoemulsification platform achieved lower CDE values than the gravity-fluidics platform for conventional cataract extraction. Femtosecond laser pretreatment with the active-fluidics platform further reduced CDE.


Studies on cryoprotectant equilibration in the intact rat liver using nuclear magnetic resonance spectroscopy: a noninvasive method to assess distribution of dimethyl sulfoxide in tissues.
Nuclear magnetic resonance (NMR) spectroscopy was used in the study of rat livers following flushing with a clinically used preservation solution containing either 12 or 30% (v/v) Me2SO. The extent of equilibration of Me2SO in the tissue after 10-15 min of perfusion with Me2SO and again after subsequent washout with Me2SO-free medium was assessed by 1H NMR spectroscopy. 31P NMR spectroscopy was used to follow the changes in ATP, ADP, inorganic phosphate, and tissue pH. The data show that 1H NMR spectroscopy can be used as a sensitive and rapid method of assessing the equilibration and concentration of compounds such as Me2SO, since these compounds are likely to be present at concentrations greatly in excess of other constituents of the medium and will therefore give rise to strong, easily detected signals. At the same time, 31P NMR spectroscopy can be used to monitor the metabolic status of the tissue reflected in the levels of ATP, ADP, and inorganic phosphate, as well as being a noninvasive monitor of intracellular pH. The possibility of determining the tissue pH in the presence of solutes such as Me2SO is discussed.


A randomized trial of a minimal intervention for sexual concerns after cancer: a comparison of self-help and professionally delivered modalities.
Information and discussion of sexual changes with a health professional is a high priority for many cancer patients in order to assist with sexual changes and ensure that sexual intimacy does not cease post-cancer. The PLISSIT model is widely recommended as a framework for providing sexual information and support, allowing for the discussion of sexual changes at various levels of increasing intensity. The aim of the present study is to evaluate the early stages of the PLISSIT model by examining the relative efficacy of written information provision about cancer related sexual changes, and information provision accompanied by a single session of counselling, for people with cancer and their partners, across a range of cancer types. Eighty-eight people with cancer and 53 partners across a range of sexual and non-sexual cancers, took part in a randomised trial which adopted mixed method analysis to examine changes in psychological wellbeing, quality of life, relationship satisfaction and communication, and sexual functioning, following written information provision about cancer related sexual changes (self-help condition; SH), or written information accompanied by a single session of counselling (health professional condition; HP). Ratings of the usefulness and efficacy of the SH and HP interventions, collected through analysis of Likert scales, open ended survey items and interviews, indicated that both conditions were found to be useful and efficacious by the majority of participants, serving to increase awareness of sexuality, improve couple communication about sex, and help in the management of sexual changes, through the exploration of non-coital sexual practices. In contrast, the quantitative analysis of standardized instruments found no significant improvements in psychological wellbeing, quality of life, relationship satisfaction and communication, or sexual functioning. There were significant reductions in self-silencing in the HP condition, and a trend towards increases in sexual satisfaction across both conditions. These results offer support for the early stages of the PLISSIT model, in terms of normalization and increased awareness of sexual changes after cancer, increased couple communication about sexual changes, and legitimation of exploration of a range of non-coital sexual practices and intimacy. However, more complex and intensive interventions are needed to address sexual functioning and psychological wellbeing. The findings provide support for the proposition that providing permission to discuss sexuality should be the core feature underpinning all stages of interventions designed to provide sexuality information and support for people with cancer and their partners, and also demonstrate the potential importance of limited information and specific suggestions. This study was registered in the Australian New Zealand Clinical Trials Registry. ( ACTRN12615000399594 ) on 29 April 2015.


Nanoscale surface electrical properties of zinc oxide films investigated by conducting atomic force microscopy.
In this study, conducting atomic force microscopy was employed to investigate the nanoscale surface electrical properties of zinc oxide (ZnO) films prepared by pulsed laser deposition (PLD) at different substrate temperatures for use as anode materials in polymer light-emitting diodes. The results show that the surface conductivity distribution of ZnO is related to its surface structure. At substrate temperatures of 150-200 degrees C, the conducting regions may cover over 90% of the ZnO thin-film surface, thus providing the best local conductivity. Moreover, heating at substrate temperatures of above 250 degrees C can effectively make the conductivity on the ZnO surface uniform. In particular, at substrate temperatures of around 300 degrees C, the conducting regions where currents are between 1 and 2 muA may cover as much as 83% of the surface, and furthermore, the transmission ratio in the visible range is higher than 80%. This is a rather ideal production temperature for the PLD for ZnO films.


The Prevalence and Distribution of Neurodegenerative Compound-Producing Soil Streptomyces spp.
Recent work from our labs demonstrated that a metabolite(s) from the soil bacterium Streptomyces venezuelae caused dopaminergic neurodegeneration in Caenorhabditis elegans and human neuroblastoma cells. To evaluate the capacity for metabolite production by naturally occurring streptomycetes in Alabama soils, Streptomyces were isolated from soils under different land uses (agriculture, undeveloped, and urban). More isolates were obtained from agricultural than undeveloped soils; there was no significant difference in the number of isolates from urban soils. The genomic diversity of the isolates was extremely high, with only 112 of the 1509 isolates considered clones. A subset was examined for dopaminergic neurodegeneration in the previously established C. elegans model; 28.3% of the tested Streptomyces spp. caused dopaminergic neurons to degenerate. Notably, the Streptomyces spp. isolates from agricultural soils showed more individual neuron damage than isolates from undeveloped or urban soils. These results suggest a common environmental toxicant(s) within the Streptomyces genus that causes dopaminergic neurodegeneration. It could also provide a possible explanation for diseases such as Parkinson's disease (PD), which is widely accepted to have both genetic and environmental factors.


Avoiding adverse effects of cycloplegics in infants and children.
Cycloplegics are very safe and useful medications. To avoid the unpleasant side effects of these medications, six precautions are considered. They are: 1. dosage, 2. cycloplegic selection, 3. toxic reaction, 4. biologic variations, 5. topical anesthesia, 6. environmental temperature and humidity.


Mutational Signatures in Cancer: Laboratory Considerations and Emerging Applications.
Patterns of somatic mutations have emerged from the broad sequencing of human cancer genomes. These mutational signatures reflect mechanisms of mutagenesis and DNA repair defects and represent an emerging class of cancer biomarkers. The appropriate interpretation of mutational signatures from sequencing assays holds implications in the reporting of molecular diagnostic results for patients with cancer. This brief review describes the scientific principles, laboratory considerations, and emerging clinical applications of mutational signature analysis from clinical cancer genomes.


Review of Anemone raddeana Rhizome and its pharmacological effects.
The chemical compositions of Anemone raddeana Rhizome, a kind of traditional Chinese medicine, were reviewed, along with its bioactivity and pharmacological properties and method improvements of extracting and detecting triterpenoid saponins. A. raddeana Rhizome is used to treat neuralgia and rheumatism, and is rich in triterpenoid saponins, most of which are pentacyclic, with oleanane as the nucleus. So far, 37 triterpenoid saponins have been determined from the herb. Its reported bioactivity and pharmacological properties have been described as anticancerous, antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsive, antihistaminic, and sedative. It has also been used for the induction of the humoral immune response and treatment of liver fibrosis in chronic hepatitis. However, the herb also has hemolytic effects and can be toxic, which limits its clinical application. Further studies are needed on the pharmaceutical functions, mechanisms, and immunological responses to contribute to the herb's clinical applications.


A test of the self-help model and use of complementary and alternative medicine among Hispanic women during treatment for breast cancer.
To describe the relationships in Braden's Self-Help Model of side-effect burden to uncertainty, complementary and alternative medicine (CAM), self-care, and quality of life (QOL) in Hispanic women during breast cancer treatment. Descriptive, correlational; convenience sample; cross-sectional design. An outpatient oncology clinic in a public setting of a metropolitan community in southern Texas. 137 Hispanic women receiving or completing treatment for breast cancer. Participants completed a comprehensive set of instruments. Analyses included a correlation of variables and multiple regressions to examine variables for potential theoretical relationships. CAM use, uncertainty, and enabling skills. CAM use as a resource to reduce uncertainty for Hispanic women during breast cancer treatment was not supported. As a type of self-care, CAM was minimally effective in improving QOL. The greater the side-effect burden that Hispanic women experienced, the more uncertainty and depression and lower QOL scores were found. In contrast, women who were involved in CAM self-care had higher QOL scores. The study results provide valuable information about understanding CAM's role during breast cancer therapy among Hispanic women. The model-testing findings indicated strong support for a predicted pattern in Braden's Self-Help Model with a slight trend for CAM as a special type of self-care. The findings further inform the concept development of CAM and model building. Additional research with a longitudinal design is needed to understand how CAM is used throughout the breast cancer treatment trajectory and will contribute to knowledge guiding nurses in facilitating self-care interventions for Hispanic women.


Malnutrition, inflamation and atherosclerosis (MIA syndrome) in patients with end stage renal disease on maintenance hemodialysis (a single centre experience).
Inflammation and malnutrition play an important role in endothelial dysfunction, atherosclerosis and excessive cardiovascular morbidity and mortality in ESRD patients AIM OF THE STUDY: The primary objective is to determine the prevalence of inflammation, malnutrition and atherosclerosis in patients on maintenance haemodialysis. Secondary objective was to determine the association for atherosclerosis with inflammation and malnutrition. One hundred and one adult patients with end stage renal disease on maintenance haemodialysis who are met with the exclusion criteria were enrolled in this cross sectional study from haemodialysis unit of Baghdad teaching hospital over the period of July/2015 - June 2016. All patients were thoroughly examined and many variables were evaluated (age, gender, blood pressure, diabetes mellitus, serum lipid profile, smoking habits, serum albumin, CRP, calcium, Phosphate, Parathyroid hormone and haemoglobin measurements). All patients underwent a carotid Doppler ultrasound study. Atherosclerosis was present in 65.3%: 58.4% of patients had malnutrition and 43.6% had inflammation. The association for atherosclerosis and high CRP and low serum albumin is strong and independent of other atherosclerosis risk factors. There is significant inverse and independent correlation between CRP and albumin. Inflammation (high serum CRP) and malnutrition (low serum albumin) in patients on haemodialysis are significantly associated with carotid atherosclerosis. Inflammation was more prevalent in the malnourished patients than in those with normal nutritional status.


Vertical disparity nulling in random-dot stereograms.
Vertical alignment of monocularly visible structures has profound influence on a binocular system's ability to fuse high spatial frequencies of a random-dot stereogram. We show that monocular objects "capture" the vertical alignment: often less than 5% of the total stereogram area determines the state of the vertical alignment and can prevent fusion of the fine scale detail. This suggests that the human binocular system uses a heuristic in which, when monocularly salient information is available, stereomatching is attempted only at vertical alignment settings determined by the monocular structures.


Qualitative Patient Interviews to Characterize the Human Burden of Advanced Basal Cell Carcinoma Following Hedgehog Pathway Inhibitor Treatment.
Evidence of patients' experiences of living with advanced basal cell carcinoma (aBCC) are limited, particularly after hedgehog pathway inhibitor (HHI) treatment. We explored the burden of aBCC on symptoms and patients' everyday lives post HHI treatment. In-depth, semi-structured, approximately 1-h qualitative interviews of US patients with aBCC and prior HHI treatment were conducted. Data were assessed using thematic analysis with NVivo 1.0 software. Saturation analysis was performed to ensure all concepts were captured. Fifteen patients (median age, 63 years; locally advanced BCC, n = 9; metastatic BCC, n = 6) were interviewed. A patient-led conceptual model was developed from the responses using 10 symptoms and 15 impact categories (comprising emotional/psychological, physical, and social domains) identified as most commonly discussed and important to patients. Overall, reported impacts were discussed more commonly than reported symptoms. Impacts most commonly discussed were related to emotions (e.g., anxiety, worry, fear [n = 14; 93%]; low mood, depression [n = 12; 80%]) and physical function (e.g., hobbies or leisure activities [n = 13; 87%]). Symptoms most commonly discussed were fatigue and tiredness (n = 14; 93%) and itch (n = 13; 87%). Out of all reported impacts and symptoms, fatigue and tiredness (n = 7, 47%) and anxiety, worry, and fear (n = 6; 40%) were most bothersome to patients. As a descriptive exercise, participant responses were mapped to commonly used patient-reported outcome scales in aBCC clinical trials. Most expressed concepts were captured across two common measures in oncology/skin conditions (European Organization for Research and Treatment of Cancer Quality of Life-Core 30 [EORTC QLQ-C30] and Skindex-16 questionnaires), but sun avoidance and others' perception of skin cancer were not explicitly mentioned by these instruments. Patients with aBCC experienced a significant disease burden post first-line HHI therapy, including major emotional and lifestyle impacts. Accordingly, through this study, patients with aBCC highlighted a significant unmet need for second-line treatment options post HHI therapy.


Assessment of more than 1,000 implanted percutaneous bone conduction devices: skin reactions and implant survival.
This study assesses soft tissue reactions and implant stability of 1,132 percutaneous titanium implants (970 patients) for bone conduction devices (BCDs). In addition, it examines BCD usage and comparisons between different patient groups. Retrospective survey. Mean follow-up time of 4.6 years. Tertiary care referral center. The surveyed cohort was divided into 3 different age groups (children, adults, and the elderly). In addition, 4 groups with variable loading times (i.e., the time between placement of the implant and loading the BCD sound processor) were identified as well as a subgroup of patients with mental retardation. Soft tissue reactions around the percutaneous implants as classified by the Holgers grading system, implant failure, and revision surgery rates. In 95.5% of the 7,415 observations of 1,132 implants, there were no adverse soft tissue reactions. Implant loss was 8.3%. Significantly more soft tissue reactions and implant failures were observed in children compared with adults and the elderly (p < 0.05). Implant survival was lower in patients with mental retardation compared with patients without mental retardation (p = 0.001). The loading time did not influence the occurrence of soft tissue reactions and implant survival rates. Children and patients with mental retardation are the most vulnerable to soft tissue reactions and implant losses. Additional and more frequent care needs to be given during outpatient consultations. Because loading as early as 3 to 5 weeks did not negatively affect skin reactions or implant survival, full BCD installation can occur earlier without risk.


Effect of paraquat administered intraperitoneally on the nonpolar lipids of rabbits.
Rabbits were injected intraperitoneally with 3, 6, or 12 mg of paraquat/kg/day for a period of 3, 7, or 14 days. Rabbits receiving 3 or 6 mg of paraquat/kg/day showed a significant loss of body weight at 7 days of the treatment. Liver, kidney, heart, and lungs demonstrated a significant decrease in their weights in the first 3 days of paraquat treatment. A decrease in total lipids, total triglycerides, and total cholesterol of both liver and kidney was observed. This decrease was accompanied by a significant increase in plasma total triglycerides and total cholesterol at 7 days of paraquat treatment. The ratio of cholesterol to cholesterol esters in liver decreased after 3 days of paraquat treatment after which it showed a consistent increase until the 14th day of the paraquat treatment. In kidney, this ratio increased for up to 7 days of paraquat treatment followed by a decrease at the 14th day. These results indicate, contrary to earlier reports, that rabbits are susceptible to paraquat toxicity.


Clinical practice recommendations for the diagnosis and management of human herpesvirus-6B encephalitis after allogeneic hematopoietic stem cell transplantation: the Japan Society for Hematopoietic Cell Transplantation.
Reactivation of human herpesvirus (HHV)-6B is relatively common after allogeneic hematopoietic stem cell transplantation (HSCT) and HHV-6B diseases may consequently develop. Among them, HHV-6B encephalitis is a serious and often fatal complication. The aim of these clinical practice recommendations is to provide diagnostic and therapeutic guidance for HHV-6B encephalitis after allogeneic HSCT. In this evidence-based review, we critically evaluated data from the published literature. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assist in generating recommendations. We have summarized the findings that contribute to decision-making and we have provided our recommendations. In cases where rigorous clinical data are unavailable, recommendations have been developed in discussions with physicians who have relevant expertize.


Differential excretion of xenobiotic acyl-esters of carnitine due to administration of pivampicillin and valproate.
The fate of supplemental carnitine was studied in human subjects treated with drugs known to cause carnitine deficiency. Six children were treated with pivampicillin and equimolar L-carnitine for 7 days. On the last day of treatment, the plasma levels of total and free carnitine were decreased, but acylcarnitine levels were increased. A 12-fold increase in urinary excretion of acylcarnitines was found; it increased from 188.5 +/- 82.7 to 2218.4 +/- 484.1 mumole/day, and 84% was pivaloylcarnitine. Free carnitine excretion was reduced. Ten epileptic children on chronic valproate treatment received equimolar carnitine for a 2-week period. Plasma carnitine levels were elevated on the last day of treatment. A 3.4-fold increase in urinary acylcarnitines was found, but most of the excreted carnitines were free (64.5-fold increases). These data show that pivalate is readily converted to carnitine esters, in contrast to the limited conversion of valproate to acylcarnitines in humans.


Conducting research during the COVID-19 pandemic.
The highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected every aspect of medical practice and has all but ceased clinical, translational and basic science research. Pregnant women appear to be similarly affected by the virus as non-pregnant adults. As obstetricians, not only do we have a duty to care for pregnant women and their fetuses, but to continue to conduct research, inclusive of that which would guide us in delivering care during a pandemic. Conducting such research has its challenges. The objective of this chapter is to review the impact of SARS-CoV-2 on ongoing and new pregnancy research during the pandemic, describe the challenges encountered and summarize the key strategies necessary for a successful research environment.


Role of soil organic carbon and colloids in sorption and transport of TNT, RDX and HMX in training range soils.
Contamination of soils and groundwater by munitions compounds (MCs) is of significant concern at many U.S. Department of Defense sites. Soils were collected from operational training ranges in Maryland (APG), Massachusetts (MMR-B and MMR-E) and Washington (JBLM) and sorption and transport studies were conducted to investigate the effects of soil organic carbon (OC) and textural clay content on fate of dissolved MCs (TNT, RDX, HMX). Sorption experiments showed higher distribution coefficients [TNT:42-68 L kg(-1), RDX:6.9-8.7 L kg(-1) and HMX:2.6-3.1 L kg(-1)] in OC rich soils (JBLM, MMR-E) compared to clay rich soils (MMR-B and APG) [TNT:19-21 L kg(-1), RDX:2.5-3.4 L kg(-1), HMX:0.9-1.2 L kg(-1)]. In column experiments, breakthrough of MCs was faster in MMR-B and APG compared to MMR-E and JBLM soils. Among TNT, RDX and HMX, breakthrough was fastest for RDX followed by HMX and TNT for all columns. Defining the colloidal fraction as the difference between unfiltered samples and samples filtered with a 3 kDa filter, ~36%, ~15% and ~9% of TNT, RDX and HMX were found in the colloidal fraction in the solutions from sorption experiments, and around 20% of TNT in the effluent from the transport experiments. Results demonstrate that OC rich soils may enhance sorption and delay transport of TNT, RDX and HMX compared to clay-rich soils. Further, transport of TNT may be associated with soil colloid mobilization.


The exposed carbohydrates of schistosomula of Schistosoma mansoni and their modification during maturation in vivo.
Lectins labeled with 125I or conjugated with fluorescein were employed to study the carbohydrates on the surface of different stages of schistosomula of Schistosoma mansoni. Newly transformed schistosomula were shown to bind concanavalin A; the 60 000 and 120 000 dalton agglutinins from Ricinus communis; the fucose-binding protein from Lotus tetragonolobus; wheat germ agglutinin and peanut agglutinin. Soybean agglutinin, Ulex europaeus agglutinin and Dolichos biflorus agglutinin, on the other hand, failed to bind to the schistosomulum surface. The binding of peanut and soybean agglutinin was unaffected by pretreatment of the parasites with neuraminidase. Binding of concanavalin A, the 120 000 dalton agglutinin from Ricinus communis, wheat germ agglutinin and peanut agglutinin to the surface of 5-day schistosomula, recovered from the lungs of mice, was also demonstrated. In each case, however, the level of binding was approximately 70% less than that observed with newly transformed schistosomula and the binding of the fucose-binding protein from L. tetragonolobus practically disappeared. In contrast with newly transformed schistosomula, lung stage schistosomula, pretreated with neuraminidase, displayed a significant increase in the binding of peanut and soybean agglutinin. The results indicate that a significant alteration in the surface carbohydrates of S. mansoni occurs during in vivo maturation of the parasite. This change may contribute to the organism's ability to survive in the vertebrate host.


Pd@PtRuNi core-shell nanowires as oxygen reduction electrocatalysts.
Fuel cells, as the alternative to fossil energy, have engaged widespread attention by reason of the high conversion efficiency from the chemical energy to the electric energy combined with low pollution emissions. The cathodic ORR catalysts with excellent performance and cost-effectiveness are the dominant point towards the massive development of fuel cells. Here, our group select the Pd NWs as the template and construct the Pd@PtRuNi core-shell bilayer nanostructure to expand platinum atom utilization. Pd@PtRuNi bilayer core-shell NWs unfold elevated mass activity of1.62Amgmetal-1at 0.9 V versus RHE in alkaline media, 2.03- and 6.23-fold of pristine Pd NWs and benchmark commercial Pt/C, respectively. Meanwhile, the cyclic stability tests reveal the excellent durability of Pd@PtRuNi NWs, whose mass activity is only 13.58% degradation after accelerated durability tests. The catalytic activity and durability towards ORR are better than the U.S. 2025 DOE target (0.44Amgpt-1and less than 40% activity attenuation at 0.9 V after 30 000 potential cycles). The elevated catalytic properties can be traceable to the synergism between the ligand effect of Ni and Ru and one-dimensional structure superiority, which optimizes the electronic structure of active sites, promotes the charge transfer and restrains the agglomeration and detachment.


Parental cancer in an unselected cohort of children with cancer referred to a single centre.
A study of parental cancer in 326 children referred to a single Paediatric Oncology Unit found a significant increase in breast cancer in mothers of children with solid tumours. The 5 tumours found were 8.9 times the expected number. This increase could not be accounted for by any of the known risk factors for breast cancer. The incidence of cancer in mothers of leukaemic children and in all groups of fathers was not significantly raised. Further prospective studies in the mothers of young children with soft tissue tumours are needed to clarify the groups at risk and to determine whether counselling and surveillance of these mothers is appropriate.


Evolution of the PEBP gene family in Juglandaceae and their regulation of flowering pathway under the synergistic effect of JrCO and JrNF-Y proteins.
Phosphatidyl ethanolamine-binding protein (PEBP) has a conserved PEBP domain and plays an important role in regulating the flowering time and growth of angiosperms. To understand the evolution of PEBP family genes in walnut family and the mechanism of regulating flowering in photoperiod pathway, 53 genes with PEBP domain were identified from 5 Juglandaceae plants. The PEBP gene family of Juglandaceae can be divided into four subgroups, FT-like, TFL-like, MFT-like and PEBP-like subgroups. These genes all show very high homology for motifs and gene structure in Juglandaceae. In addition, the results of gene replication and collinearity analysis showed that the evolution of PEBP genes was mainly purified and selected, and segmental repetition was the main driving force for the evolution of PEBP gene family in walnut family. We found that PEBP gene family played an important role in female flower bud differentiation, and most JrPEBP genes were highly expressed in leaf bud and female flower bud by qRT-PCR. In Arabidopsis, AtCO can not only directly bind to CORE2, but also interact with NF-Y complex to positively regulate the expression of AtFT gene. In this study, we proved that JrCO (the lineal homologue of AtCO) could not directly regulate the expression of JrFT gene, but could enhance the binding of JrNF-YB4/6 protein to the promoter of JrFT gene by forming a heteropolymer with NF-YB4/NF-YB6. We also confirmed that JrNF-YC1/3/7, JrNF-YB4/6 and JrCO can form a trimer structure similar to AtNF-YB-YC-CO of Arabidopsis, and then bind to the promoter of JrFT gene to promote the transcription of JrFT gene. In a word, through identification and analysis of PEBP gene family in Juglandaceae and study on the mechanism of photoperiod pathway regulating flowering in walnut, we have found that nuclear transcription factor NF-YB/YC plays a more important role in the trimer structure of NF-YB-YC-CO in walnut species. Our study has further perfected the flowering regulatory network of walnut species.


Thyroid histological changes in lambs from iodine-supplemented and untreated ewes.
To identify the histological changes in the thyroid associated with subclinical goitre. Thyroids were histologically examined from lambs that died within 24 hours of birth in a trial to investigate the effect of iodine supplementation to Merino ewes on perinatal mortality. Thyroids with follicles depleted of colloid, infolded and lined by columnar epithelium are indicative of hypothyroidism. These findings can occur in thyroids considered to be in the normal weight range of less than 1.3 g. Thyroid histological changes are a useful aid in diagnosing subclinical goitre.


Pleiotropic and diverse expression of ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the "Mowat-Wilson" syndrome.
ZFHX1B encodes Smad-interacting protein 1, a transcriptional corepressor involved in the transforming growth factors beta (TGFbeta) signaling pathway. ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects. We compared the distribution of ZFHX1B transcripts during mouse and human embryogenesis as well as in adult mice and humans. This showed that this gene is strongly transcribed at an early stage in the developing peripheral and central nervous systems of both mice and humans, in all neuronal regions of the brains of 25-week human fetuses and adult mice, and at varying levels in numerous nonneural tissues. Northern blot analysis suggested that ZFHX1B undergoes tissue-specific alternative splicing in both species. These results strongly suggest that ZFHX1B determines the transcriptional levels of target genes in various tissues through the combinatorial interactions of its isoforms with different Smad proteins. Thus, as well as causing neural defects, ZFHX1B mutations may also cause other malformations.


Target2 imbalances and poverty in the eurozone.
This paper aims to investigate the relationship between external imbalances and poverty in the Eurozone. The former are registered through the Target2 (T2) settlement mechanism and can be assimilated into changes in official reserves to cover the balance of payments disequilibrium in a fixed exchange rate regime. The presence of T2 discrepancies has led to differences in interest rates and increased distances in general living conditions inside the Eurozone. An empirical investigation implemented in 11 Eurozone countries reveals that T2 is negatively correlated with poverty, therefore allowing for an interpretation that approximates balance of payment crisis models. Results that appear to be robust to several control variables suggest that the policy framework of the Eurozone-in the absence of a compensatory mechanism-should be revised towards centralised fiscal instruments and anti-speculative monetary interventions.


Development of intestinal microbiota in infants and its impact on health.
Throughout the human lifetime, the intestinal microbiota performs vital functions, such as barrier function, metabolic reactions, trophic effects, and maturation of the host's innate and adaptive immune responses. Development of the intestinal microbiota in infants is characterized by rapid and large changes in microbial abundance, diversity, and composition. These changes are influenced by medical, cultural, and environmental factors such as mode of delivery, diet, familial environment, diseases, and therapies used. Thus, it is nearly impossible to define a universal standard for intestinal colonization and development of the intestinal microbiota. This review discusses recent data on the early colonization of the gut by microbial species, development of the intestinal microbiota, and its impact on health.


Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy.
To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy. Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (γ), arterial blood flow (BFA), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (vI), extraction fraction, mean intracellular water molecule lifetime (τC), and fractional intracellular volume (vC) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing. The WX-TK-model-derived γ (P = 0.022) and vI (P = 0.010), and WX-ETK-model-derived τC (P = 0.023) and vC (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BFA (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived vC (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS. The WX-ETK-model-derived vC was an effective prognostic biomarker for advanced HCC treated with sunitinib.


Platelet free cytosolic calcium concentration during ageing of type 2 diabetic patients.
The aim of this study was to examine the effects of biological ageing on concentration of free calcium ions ([Ca(2+)](i)) in platelets of type 2 diabetic patients, an issue not documented till now. Since diabetes platelets are surrounded by a hyperglycemic environment enriched in products of nonenzymatic glycation and oxidation of proteins (known as "advanced glycation end products" (AGEs)), we questioned on the individual effect of high glucose concentration, AGEs, and oxidative stress on platelet [Ca(2+)](i). To these purposes, we performed: (i) measurement of basal and thrombin-stimulated [Ca(2+)](i) in platelets isolated from type 2 diabetic patients and from normal subjects of young (27 +/- 7 years), mature (48 +/- 12 years) and older (>60 years) age, and (ii) quantitation of [Ca(2+)](i) when platelets of young healthy subjects were exposed to 25.5 mM glucose (vs. 11 mM glucose), 0.23-1.7 mM AGE-poly-L-lysine (vs. poly-L-lysine), 0.3-2.26 mM AGE-albumin (vs. albumin), and to 10 mM and 100 mM H(2)O(2). Reactions of nonenzymatic glycation were conducted in vitro to prepare AGE-poly-L-lysine and AGE-albumin, and spectrofluorimetry was used to measure platelet free [Ca(2+)](i) following Fura-2/AM cells loading. The results showed that: (i) in physiological conditions, [Ca(2+)](i) was approximately 10% increased in the platelets of the mature subjects, and approximately 33% enhanced at the older group (vs. young), sustaining that biological ageing is associated with accumulation of free [Ca(2+)](i) within the platelets cytoplasm; (ii) in type 2 diabetes, [Ca(2+)](i) was approximately 16% and approximately 27% higher in the platelets of mature and older patients, respectively (vs. age-matched normals), demonstrating that ageing of diabetics is accompanied by alterations in calcium balance (vs. physiological ageing); (iii) thrombin (1U/ml) induced approximately 39% increase of [Ca(2+)](i) in platelets of matures and approximately 29% at older normals, and approximately 34% increase at the mature diabetics, approximately 84% at the older diabetics (vs. no thrombin condition), indicating that under thrombin stimulation simultaneous insults of diabetes and advanced age produced a higher thrombin-evoked mobilization of Ca(2+) from intracellular stores; (iv) the components of the diabetic milieu had various effects on platelet free [Ca(2+)](i): high enhancement ( approximately 73%) in 25.5 mM glucose (vs. 11 mM glucose), a minor increase ( approximately 15%) in 100 mM H(2)O(2), and a decrease (by approximately 56% and approximately 132%) in 1.7 mM AGE- poly-L-lysine (vs. poly-L-lysine) and 2.26 mM AGE- albumin (vs. albumin), respectively. Thus, a complex of factors contribute to platelet free [Ca(2)(+)](i) during biological ageing of diabetics: age, hyperglycemia and oxidative stress release Ca(2)(+) from intracellular stores, while AGE products reduced the cytosolic free Ca(2+). Thus, platelets [Ca(2)(+)](i) level is the final result of the combined effects of ageing and of the components of the diabetic milieu.


Spectroscopic determination of the role of vanadyl oxygen in room temperature NH3 sensing by V2O5 nanoparticles.
In the present study, a multi-modal approach consisting of in-situ photoluminescence, Raman, and UV-Vis absorption spectroscopic studies is carried out along with chemiresistive sensing to unveil the mechanism of NH3 gas sensing by V2O5 nanoparticles in ambient air. V2O5 nanoparticles with an average size of 49 nm show a superior sensor response of 17 ± 1.5 % towards 1 ppm of NH3 gas with a response and recovery time of 96 s and 45 s, respectively. The photoluminescence and UV-Vis absorption studies in the presence of NH3 reveal electron doping to a new energy level at 1.84 eV, resulting in conduction band filling and increase in the optical band gap. The intensity of the photoluminescence spectrum shows an increase in the presence of NH3 gas as a result of this electron doping. The sensor response from the optical sensing carried out by in-situ photoluminescence study is 43 % for 40 ppm of NH3 gas. The vanadyl oxygen site is the most active in the sensing process, as evident by a selective enhancement in the intensity of V-O (vanadyl) bond vibration. This study gives an experimental evidence for the changes in optical and electronic properties of V2O5 on the adsorption of NH3 gas molecules.


Functional platelet-activating factor receptors in immature forms of leukemic blasts.
Platelet-activating factor (PAF) is a phospholipid mediator with potent immunoregulatory activities on mature leukocytes. PAF modulates leukocyte cytosolic Ca2+ concentration ([Ca2+]i) through a Gq mediated pathway. We highlight, for the first time, Gq transcripts, PAF receptor (PAF-R) transcripts and protein in blast cells of acute myeloid (AML) and lymphoid (ALL) leukemia patients. PAF stimulated [Ca2+]i in leukemic blast cells; PAF effects being prevented by a specific PAF-R antagonist. In conclusion, functional PAF-R are present in blast cells of patients with acute leukemia; a result that could be of physiologic importance regarding the important effect of PAF on leukocytes maturation and functions.


Where is bone science taking us?
Bone science has over the last decades unraveled many important pathways in bone and mineral metabolism and the interplay between genetic factors and the environment. Some of these discoveries have led to the development of pharmacological treatments of osteoporosis and rare bone diseases. Other scientific avenues have uncovered a role for the gut microbiome in regulating bone mass, which have led to investigations on the possible therapeutic role of probiotics in the prevention of osteoporosis. Huge advances have been made in identifying the genes that cause rare bone diseases, which in some cases have led to therapeutic interventions. Advances have also been made in understanding the genetic basis of the more common polygenic bone diseases, including osteoporosis and Paget's disease of bone (PDB). Polygenic profiles are used for establishing genetic risk scores aiming at early diagnosis and intervention, but also in Mendelian randomization (MR) studies to investigate both desired and undesired effects of targets for drug design.


Definition of the boundaries of the origin of DNA replication in simian virus 40.
We have determined by use of DNA sequencing techniques the exact location of the deletion in d1 892, a viable deletion mutant of Simian virus 40 (SV40) reported to map very near the unique replication origin or SV40. With the help of this localization we have narrowed down the boundaries of the replication origin to 85 nucleotides within the sequence of SV40.


Late onset of distinct neurologic syndromes in galactosemic siblings.
We discuss siblings with galactose-1-phosphate uridyl transferase deficiency who developed neurologic complications after the age of 30. One has partial complex seizures and the other has generalized seizures, progressive ataxia, and apraxia. As more galactosemic children survive into adulthood, more neurologic complications may become more prevalent.


Retracted: Intelligent Detection and Diagnosis of Power Failure Relying on BP Neural Network Algorithm.
[This retracts the article DOI: 10.1155/2022/3758660.].


Slow-acting antirheumatic drugs.
Rheumatoid arthritis can be controlled by the use of an increasing range of slow-acting drugs and treatments whose mode of action, currently unexplained or lacking a rational basis, may eventually provide a better understanding of the disease.


Extending Se substitution to the limit: from 5S to 5Se in high-efficiency non-fullerene acceptors.
Based on the newly synthesized seleno[3,2-b]selenophene unit, two near-infrared non-fullerene acceptors (NFAs) of 4Se and 5Se are constructed by replacing four or all sulfurs with selenium in high-efficiency Y-series NFAs. Consequently, binary devices based on 4Se and 5Se afford PCEs of 15.17% and 15.23%, respectively, with a photoelectric response approaching 1000 nm. More excitingly, the energy loss of the 5Se-based device was as low as 0.477 eV along with almost the smallest non-radiative loss of ∼0.15 eV thus far.


Six-microns-under acts upstream of Draper in the glial phagocytosis of apoptotic neurons.
The removal of apoptotic cells by phagocytic neighbors is essential for metazoan development but remains poorly characterized. Here we report the discovery of a Drosophila phagocytosis receptor, Six-microns-under (SIMU), which is expressed in highly phagocytic cell types during development and required for efficient apoptotic cell clearance by glia in the nervous system and by macrophages elsewhere. SIMU is part of a conserved family of proteins that includes CED-1 and Draper (DRPR). Phenotypic analysis reveals that simu acts upstream of drpr in the same pathway and affects the recognition and engulfment of apoptotic cells, while drpr affects their subsequent degradation. SIMU strongly binds to apoptotic cells, presumably through its EMILIN-like domain, but requires no membrane anchoring, suggesting that it can function as a bridging molecule. Our study introduces an important factor in tissue-resident apoptotic clearance and underscores the prominent role of glia as "semiprofessional" phagocytes in the nervous system.