Landfill leachate as an alternative moisture source for hydrothermal carbonization of municipal solid wastes to solid biofuels.
Hydrothermal carbonization (HTC) of yard waste (YW) and food waste (FW) was performed in landfill leachate (LL) to overcome the unnecessary exploitation of our limited natural resources. The physicochemical properties and combustion behavior of the resulting hydrochars were compared with those obtained using distilled water (DW) as reaction medium. Although performing HTC in LL led to lower hydrochar mass yields (43% YWH and 36% FWH) than DW (47.1% YWH and 41.5% FWH), it had minimal impact on the fuel characteristics of the hydrochars. Notably, the higher heating value of the hydrochars prepared in LL (22.8 MJ kg-1 for YWH and 30.2 MJ kg-1 for FWH) is comparable to that of conventional solid fuels, and may, therefore, be considered as inexpensive alternatives to fossil fuels. Overall, the results of this study conclusively suggest that the use of LL as an alternative moisture source can significantly improve the sustainability of HTC technology.


Epidemiological investigations of the associations between major mental disorders and crime: methodological limitations and validity of the conclusions.
Five epidemiological investigations of post-World War II birth cohorts have examined the relation between major mental disorders and criminality. This article critically reviews the objectives, methodology and findings of these investigations. The validity of the results is assessed as are the limitations which restrict their interpretation. It is concluded that persons who develop major mental disorders are at increased risk across the lifespan of committing both non-violent and violent crimes. However, this increased risk may be limited to generations of persons with major mental disorders born in the late 1940s, 1950s and 1960s. It is hypothesized that these generations of persons with major mental disorders have received inappropriate and inadequate mental health care and that they include a larger proportion of individuals than previous and perhaps subsequent generations, who display a pattern of stable antisocial behaviour from childhood through adulthood.


Mapping the Patient-Oriented Prostate Utility Scale From the Expanded Prostate Cancer Index Composite and the Short-Form Health Surveys.
This study aimed to develop mapping algorithms from the Expanded Prostate Cancer Index Composite (EPIC) and the Short-Form (SF) Health Surveys to the Patient-Oriented Prostate Utility Scale (PORPUS), an econometric instrument specifically developed for patients with prostate cancer. Data were drawn from 2 cohorts concurrently administering PORPUS, EPIC-50, and SF-36v2. The development cohort included patients who had received a diagnosis of localized or locally advanced prostate cancer from 2017 to 2019. The validation cohort included men who had received a diagnosis of localized prostate cancer from 2014 to 2016. Linear regression models were constructed with ln(1 - PORPUS utility) as the dependent variable and scores from the original and brief versions of the EPIC and SF as independent variables. The predictive capacity of mapping models constructed with all possible combinations of these 2 instruments was assessed through the proportion of variance explained (R2) and the agreement between predicted and observed values. Validation was based on the comparison between estimated and observed utility values in the validation cohort. Models constructed with EPIC-50 with and without SF yielded the highest predictive capacity (R2 = 0.884, 0.871, and 0.842) in comparison with models constructed with EPIC-26 (R2 = 0.844, 0.827, and 0.776). The intraclass correlation coefficient was excellent in the 4 models (>0.9) with EPIC and SF. In the validation cohort, predicted PORPUS utilities were slightly higher than those observed, but differences were not statistically significant. Mapping algorithms from both the original and the abbreviated versions of the EPIC and the SF Health Surveys allow estimating PORPUS utilities for economic evaluations with cost-utility analyses in patients with prostate cancer.


Percutaneous embolization of persistent urinary fistula after partial nephrectomy using N-butyl-2-cyanoacrylate.
Percutaneous closure of a calyceal fistula following partial nephrectomy for kidney cancer was achieved with fistula embolization with n-butyl-2-cyanoacrylate. Previous attempts at closure by conservative and endoscopic means were unsuccessful. Tissue adhesives are useful in the management of persistent urinary leakage after partial nephrectomy.


Ulcerative colitis and thrombocytosis: Case report and literature review.
Ulcerative colitis (UC) is an autoimmune disease of unknown etiology, sometimes associated with anemia and thrombocytosis. Platelets (PLTs) play a role in amplifying inflammatory and immune responses in chronic inflammation. This study discusses the diagnosis and treatment of a case of UC combined with secondary thrombocytosis and reviews the relevant literature. We report an interaction between thrombocytosis and UC to raise clinicians' awareness of this condition. In the current report, we discuss the case of a 30-year-old female patient who presented with frequent diarrhea and thrombocytosis. Severe UC combined with intestinal infection was diagnosed based on colonoscopy and intestinal biopsy. The patient had a PLT count >450 × 109/L and was diagnosed with reactive thrombocytosis. The patient was discharged from the hospital in remission after receiving vedolizumab and anticoagulant treatment. In patients with severe UC with thrombocytosis, clinicians should pay attention to PLTs promoting inflammatory progression, as well as screening for venous thromboembolism risk and prophylactic anti-venous thromboembolism therapy at the time of dosing to avoid adverse effects.


Effects of pulsed contaminant exposures on early life stages of the fathead minnow.
Water quality standards for protecting aquatic life are based primarily on laboratory tests that use constant exposure concentrations. Typical effluent and nonpoint source exposure concentrations fluctuate in frequency, magnitude, and duration, which may result in different toxicological impacts. Current information indicates that pulsed or fluctuating exposures are generally more toxic than continuous exposures, when averaged over the applicable time period. However, few studies have evaluated chronic or sublethal effects of pulsed exposures, particularly those applicable to wastewater discharge situations. To address this issue, several pulsed exposure toxicity tests were conducted using modified fathead minnow (Pimephales promelas) early life stage (7 d) tests and several chemicals representative of those commonly encountered in wastewater effluents including copper, nitric acid, cadmium, and sodium chloride. Results suggest that survival and/or growth effects depend on the combination of frequency, magnitude, and duration, as well as the type of chemical. Nitric acid and sodium chloride pulsed treatments did not exhibit growth effects independent of survival effects, but both metals did elicit only growth effects in some treatments. Growth effects were related to pulse frequency and duration for copper and pulse duration and magnitude for cadmium. A 12-h exposure of approximately five times the 7-d continuous exposure IC(25) concentration of either metal quickly elicited mortality responses. Prolonged (>24 h) lag effects on survival were not observed in any of the experiments, regardless of the contaminant tested. Our results suggest that current water quality criteria may be underprotective if based on an average concentration over a 2-4 d exposure. For these contaminants, a short-term increase in concentration may elicit effects even though the average concentration is within nontoxic ranges for the organism.


Genomic selection for wheat traits and trait stability.
Based on the estimates of accuracy, genomic selection would be useful for selecting for improved trait values and trait stability for agronomic and quality traits in wheat. Trait values and trait stability estimated by two methods were generally independent indicating a breeder could select for both simultaneously. Genomic selection (GS) is a new marker-assisted selection tool for breeders to achieve higher genetic gain faster and cheaper. Breeders face challenges posed by genotype by environment interaction (GEI) pattern and selecting for trait stability. Obtaining trait stability is costly, as it requires data from multiple environments. There are few studies that evaluate the efficacy of GS for predicting trait stability. A soft winter wheat population of 273 lines was genotyped with 90 K single nucleotide polymorphism markers and phenotyped for four agronomic and seven quality traits. Additive main effect and multiplicative interaction (AMMI) model and Eberhart and Russell regression (ERR) were used to estimate trait stability. Significant GEI variation was observed and stable lines were identified for all traits in this study. The accuracy of GS ranged from 0.33 to 0.67 for most traits and trait stability. Accuracy of trait stability was greater than trait itself for yield (0.44 using AMMI versus 0.33) and heading date (0.65 using ERR versus 0.56). The opposite trend was observed for the other traits. GS did not predict the stability of the quality traits except for flour protein, lactic acid and softness equivalent. Significant GS accuracy for some trait stability indicated that stability was under genetic control for these traits. The magnitude of GS accuracies for all the traits and most of the trait stability index suggests the possibility of rapid selection for these trait and trait stability in wheat breeding.


Heritability of irritable impulsiveness: a study of twins reared together and apart.
The heritability of self-reported personality traits related to impulsiveness, irritability, and the inhibition of assertive or aggressive behavior was examined in up to 500 healthy monozygotic and dizygotic twin pairs raised together or apart. Two factors related to "(lack of) assertiveness/aggression" (Factor I) and "impulsive irritability" (Factor II) were examined using traditional and model-fitting procedures. Results of model-fitting procedures were consistent with a genetic, but not a shared environmental, influence for both factors. Further analysis suggested a nonadditive genetic influence for Factor II and an additive influence for Factor I. Bivariate model-fitting analyses suggest that self-reported "irritable impulsiveness" and "(lack of) assertiveness/aggressiveness" show substantial, though different, genetic influences.


Putative association of mitochondria with a subpopulation of intermediate-sized filaments in cultured human skin fibroblasts.
Cultured cell Triton cytoskeletons enriched in intermediate filaments by extraction in high and low salt show, in addition to known intermediate-filament proteins and actin, a few other tenaciously bound polypeptides. An antibody raised against one of these polypeptides (IEF 24) is shown to react specifically with mitochondria of different cell types. With methanol-acetone fixation, required for the antibody reaction, the characteristically long mitochondria of human skin fibroblasts fragment into strings of beads, as identified by antibody staining in the light microscope and whole-mount electron microscopy. From the colinear organization of these beads, their codistribution with the intermediate-filament network and their retention in salt-extracted cytoskeletons, it is suggested that a subpopulation of the intermediate filaments can serve as an anchorage site for mitochondria.


Impairment in planning tasks of children and adolescents with anxiety disorders.
Anxiety disorders are associated with poor neuropsychological performance in attention and memory. However, little is known about the impact of these difficulties on other cognitive functions, such as planning. The ability to plan, including attention, working memory and set-shifting components, can be assessed by the Tower of Hanoi task (ToH). This study evaluated seventy-one participants, aged from 7-17 years. Thirty-seven subjects met DSM-IV diagnostic criteria for at least one anxiety disorder and 34 individuals comprised the controls. The neuropsychological tests used were: the ToH, a problem-solving task, involves planning ability and other executive functions (working memory, attentional control and cognitive flexibility); for the assessment of processing speed and problem-solving, the Vocabulary/Matrix Reasoning subtests of the Wechsler Abbreviated Scale of Intelligence was used to measure for estimated-IQ in both groups. The groups were compared with a generalized linear model controlling for age, IQ and ADHD comorbidity. Compared with controls, anxiety disorders subjects made more errors and required more time to complete the ToH. Children and adolescents with anxiety disorders have poorer planning ability compared to subjects without anxiety disorders, and the difficulty in planning is affected by interference from other cognitive functions, such as attention, working memory, cognitive flexibility and problems-solutions.


Vismodegib, itraconazole and sonidegib as hedgehog pathway inhibitors and their relative competencies in the treatment of basal cell carcinomas.
The advent of more sophisticated studies published has clarified the understating of the root cause of various skin cancers or basal cell carcinomas (BCCs). The remarkable role is played by the comprehensive work done on unraveling the mechanism controlling the function of hedgehog (Hh) pathway. The defective Hh pathway has been found as the major cause for BCCs as activated Hh signaling within primary cilia plays a key role in the pathogenesis of BCCs. The BCC accounts for up to 40% of all cancers in the US, with growing incidences in other countries as well. Thus, it is considered to be utmost important by the researchers all over the world developing drugs for the treatment of skin cancers targeting Hh pathway. Fewer drugs like vismodegib, itraconazole and sonidegib have shown promising results inhibiting the awry function of Hh pathway resulting in treatment of different forms of skin cancers. These drugs have shown positive results but failed to prove their potential as expected. Vismodegib and sonidegib are better but fail in case of resistant tumors. This review article describes the mechanism of actions of these Hh pathway inhibitors and provides the rationale for their effectiveness/non-effectiveness for the treatment of metastatic or locally advanced BCC.


Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a TH2-skewed immune response.
Dendritic cells (DCs) are important in allergic diseases such as asthma, although little is known regarding the mechanisms by which DCs induce T(H)2-polarized responses in atopic individuals. It has been suggested that intrinsic properties of allergens can directly stimulate T(H)2 polarizing functions of DCs, but little is known of the underlying mechanisms. To identify novel genes expressed by house dust mite (HDM) allergen-exposed DCs. We screened for allergen-induced gene expression by microarray, and validated differentially expressed genes at the mRNA and protein levels. Thrombomodulin (CD141, blood dendritic cell antigen 3) expression by microarray was higher on HDM-stimulated DCs from atopic (relative to nonatopic) individuals. These findings were confirmed at both the mRNA and protein levels in an independent group. Purified thrombomodulin(+) DCs induced a strongly T(H)2-polarized cytokine response by allergen-specific T cells compared with DCs lacking thrombomodulin. In vivo, thrombomodulin(+) circulating DCs were significantly more frequent in subjects with HDM allergy and asthma, compared with control subjects. Furthermore, thrombomodulin expression in blood leukocytes was higher in children with acute asthma than at convalescence 6 weeks later. Thrombomodulin expression on DCs may be involved in the pathogenesis of atopy and asthma.


Localization of concansvalin-A binding sites in Tetrahymena by scanning electron microscopy.
Binding sites of concanavalin-A were detected in Tetrahymena on the body ciliature, while the cell membrane itself and the oral ciliature failed to bind the lectine.


NIR-light-controlled G-quadruplex hydrogel for synergistically enhancing photodynamic therapy via sustained delivery of metformin and catalase-like activity in breast cancer.
Severely hypoxic condition of tumour represents a notable obstacle against the efficiency of photodynamic therapy (PDT). While mitochondria targeted therapy by metformin has been considered as a promising strategy for reducing oxygen consumption in tumours, its low treatment sensitivity, short half-life and narrow absorption window in vivo remain the intractable challenges. In this report, 5'-guanosine monophosphate (5'GMP), indocyanine green (ICG), hemin and metformin, were combined to construct a smart G-quadruplex (G4) hydrogel named HMI@GEL for breast cancer (BC) treatment. Benefiting from the photothermal (PTT) effect of ICG, HMI@GEL exhibited excellent characteristics of NIR-light-triggered and persistent drug delivery to maintain high intratumoral concentration of metformin. Furthermore, drug loading concentration of metformin reached an amazing 300 mg mL-1 in HMI@GEL. To our knowledge, it might be the highest loading efficiency in the reported literatures. With the combination of catalase-mimicking Hemin@mil88, metformin could inhibit tumour mitochondrial respiratory significantly, which sequentially permitted in situ efficient oxygen generation. Remarkable apoptosis and necrosis were achieved by the combination of PTT and synergistically enhanced PDT as well as the activated tumour immunotherapy. Collectively, the HMI@GEL in situ injectable platform showed a promising strategy for enhanced PDT by metformin, and opened new perspectives for treating BC versatilely.


SARS-CoV-2: analysis of the effects of mutations in non-structural proteins.
A worldwide pandemic that started in China in late 2019 was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded RNA virus belonging to the family Coronaviridae. Due to its structural variability and mutability, this virus continues to evolve and pose a major health threat around the world. Its characteristics, such as transmissibility, antigenicity, and resistance to drugs and vaccines, are continually altered through mutations. Examining mutational hotspots and their structural repercussions can thus aid in the development of more-effective vaccinations and treatment plans. In this study, we used full genome sequences of SARS-CoV-2 variants to predict structural changes in viral proteins. These sequences were obtained from the Global Initiative on Sharing Avian Influenza Data (GISAID), and a set of significant mutations were identified in each of the non-structural proteins (NSP1-16) and structural proteins, including the envelope, nucleocapsid, membrane, and spike proteins. The mutations were characterized as stabilizing or destabilizing based on their effect on protein dynamics and stability, and their impact on structure and function was evaluated. Among all of the proteins, NSP6 stands out as especially variable. The results of this study augment our understanding of how mutational events influence virus pathogenicity and evolution.


Paradoxical manifestations during tuberculous meningitis treatment among HIV-negative patients: a retrospective descriptive study and literature review.
Tuberculous meningitis (TBM) is the most frequent, severe, and disabling form of central nervous system (CNS) tuberculosis (TB). TBM paradoxical manifestations are characterized by clinical or paraclinical worsening after 1 month of effective anti-TB treatment in patients who initially responded to treatment despite the use of adjunctive corticosteroids. Retrospective descriptive study of consecutive HIV-negative adult patients (≥ 18 years) with definitive TBM who developed a paradoxical manifestation following anti-TB in a tertiary-care hospital in Mexico from 2009 to 2019; we also conducted a literature review of published cases/series of paradoxical manifestations in HIV-negative patients from 1980 to 2020. We detected 84 cases of definitive TBM; 55 (68.7%) HIV-negative patients and 29 (36.3%) HIV-infected patients. Among HIV-negative patients, four (7.3%), three female and one male (19-49 years old), developed a paradoxical manifestation within 4-14 weeks following treatment initiation despite receiving adequate corticosteroid doses; Mycobacterium bovis was isolated from the cerebrospinal fluid of three cases and Mycobacterium tuberculosis in one more. Two patients developed vasculopathy-related cerebral infarctions, one severe basilar meningitis, and hydrocephalus, one more a tuberculoma. Two were treated with intravenous cyclophosphamide, and two with steroids. One of the patients treated with steroids died; patients who received cyclophosphamide had a good clinical response. This case series illustrates the diverse clinical/radiologic paradoxical manifestations of TBM in HIV-negative patients. Cyclophosphamide may be safe and effective in treating TBM-associated paradoxical manifestations. Specific diagnostic and care protocols for these patients are needed.


Evaluation of peritraumatic distress at the point of care: A cross-sectional study.
COVID-19 related peritraumatic distress has been investigated in the general population with contrasting results probably due to the perceived risk of developing COVID-19. Our study aims to investigate this condition in individuals with ascertained or probable SARS-CoV-2 exposure. The Coronavirus Peritraumatic Distress Index (CPDI) was administered to people attending a COVID-19 point of care. The sample was stratified for perceived risk in SARS-CoV-2 positive cases, close contacts, case relatives, undergoing screening subjects, and symptomatic subjects. 1463 subjects participated, and with a mean CPDI Score of 28.2 (SD 16.9). CPDI Scores in SARS-CoV-2 positive cases were significantly higher than case relatives (p = 0.02). Multiple logistic regression revealed that having had work changes (p = 0.001), night sleep changes (p < 0.001), physical activity reduction (p = 0.002), alcohol consumption changes (p = 0.003), and at least one relative lost to COVID-19 (p < 0.001) independently predicted higher CPDI Scores. Male sex (p < 0.001), age ≥ 35 years (p < 0.001), higher educational level (p = 0.002), night sleep >7 hours (p = 0.002), and being physically active (p = 0.018) were identified as protective factors. Cross-sectional design and the regional recruitment area limit the generalizability of results. Mean CPDI values were above the threshold for medium grade peritraumatic distress, with greater CPDI Scores in subjects who tested positive for SARS-CoV-2, compared to family members or caregivers without a clear indication to undergo the swab. Specific demographics, physical and mental health events could help in identifying individuals at greater risk of COVID-19 related peritraumatic distress that may benefit from early treatment.


Contemporary Commercial Music Singing Students-Voice Quality and Vocal Function at the Beginning of Singing Training.
The purpose of this study was to assess the voice quality and the vocal tract function in popular singing students at the beginning of their singing training at the High School of Music. This is a retrospective cross-sectional study. The study consisted of 45 popular singing students (35 females and 10 males, mean age: 19.9 ± 2.8 years). They were assessed in the first 2 months of their 4-year singing training at the High School of Music, between 2013 and 2016. Voice quality and vocal tract function were evaluated using videolaryngostroboscopy, palpation of the vocal tract structures, the perceptual speaking and singing voice assessment, acoustic analysis, maximal phonation time, the Voice Handicap Index, and the Singing Voice Handicap Index (SVHI). Twenty-two percent of Contemporary Commercial Music singing students began their education in the High School, with vocal nodules. Palpation of the vocal tract structure showed in 50% correct motions and tension in speaking and in 39.3% in singing. Perceptual voice assessment showed in 80% proper speaking voice quality and in 82.4% proper singing voice quality. The mean vocal fundamental frequency while speaking in females was 214 Hz and in males was 116 Hz. Dysphonia Severity Index was at the level of 2, and maximum phonation time was 17.7 seconds. The Voice Handicap Index and the SVHI remained within the normal range: 7.5 and 19, respectively. Perceptual singing voice assessment correlated with the SVHI (P = 0.006). Twenty-two percent of the Contemporary Commercial Music singing students began their education in the High School, with organic vocal fold lesions.


EIF4A3-induced circular RNA ASAP1 promotes tumorigenesis and temozolomide resistance of glioblastoma via NRAS/MEK1/ERK1-2 signaling.
Acquired chemoresistance is a major challenge in the clinical treatment of glioblastoma (GBM). Circular RNAs have been verified to play a role in tumor chemoresistance. However, the underlying mechanisms remain unclear. The aim of this study was to elucidate the potential role and molecular mechanism of circular (circ)RNA ADP-ribosylation factor GTPase activating proteins with Src homology 3 domain, ankyrin repeat and Pleckstrin homology domain 1 (circASAP1) in temozolomide (TMZ) resistance of GBM. We analyzed circRNA alterations in recurrent GBM tissues relative to primary GBM through RNA sequencing. Real-time quantitative reverse transcription PCR verified the expression of circASAP1 in tissues and cells. Knockdown and overexpressed plasmids were used to evaluate the effect of circASAP1 on GBM cell proliferation and TMZ-induced apoptosis. Mechanistically, fluorescent in situ hybridization, dual-luciferase reporter, and RNA immunoprecipitation assays were performed to confirm the regulatory network of circASAP1/miR-502-5p/neuroblastoma Ras (NRAS). An intracranial tumor model was used to verify our findings in vivo. CircASAP1 expression was significantly upregulated in recurrent GBM tissues and TMZ-resistant cell lines. CircASAP1 overexpression enhanced GBM cell proliferation and TMZ resistance, which could be reduced by circASAP1 knockdown. Further experiments revealed that circASAP1 increased the expression of NRAS via sponging miR-502-5p. Moreover, circASAP1 depletion effectively restored the sensitivity of TMZ-resistant xenografts to TMZ treatment in vivo. Our data demonstrate that circASAP1 exerts regulatory functions in GBM and that competing endogenous (ce)RNA-mediated microRNA sequestration might be a potential therapeutic strategy for GBM treatment.


Longitudinal effects of growth restriction on the murine gut microbiome and metabolome.
Undernutrition-induced growth restriction in the early stages of life increases the risk of chronic disease in adulthood. Although metabolic impairments have been observed, few studies have characterized the gut microbiome and gut-liver metabolome profiles of growth-restricted animals during early-to-mid-life development. To induce growth restriction, mouse offspring were either born to gestational undernutrition (GUN) or suckled from postnatal undernutrition (PUN) dams fed a protein-restricted diet (8% protein) or control diet (CON; 20% protein) until weaning at postnatal age of 21 days (PN21). At PN21, all mice were fed the CON diet until adulthood (PN80). Livers were collected at PN21 and PN80, and fecal samples were collected weekly starting at PN21 (postweaning week 1) until PN80 (postweaning week 5) for gut microbiome and metabolome analyses. PUN mice exhibited the most alterations in gut microbiome and gut and liver metabolome compared with CON mice. These mice had altered fecal microbial β-diversity (P = 0.001) and exhibited higher proportions of Bifidobacteriales [linear mixed model (LMM) P = 7.1 × 10-6), Clostridiales (P = 1.459 × 10-5), Erysipelotrichales (P = 0.0003), and lower Bacteroidales (P = 4.1 × 10-5)]. PUN liver and fecal metabolome had a reduced total bile acid pool (P < 0.01), as well as lower abundance of riboflavin (P = 0.003), amino acids [i.e., methionine (P = 0.0018), phenylalanine (P = 0.0015), and tyrosine (P = 0.0041)], and higher excreted total peptides (LMM P = 0.0064) compared with CON. Overall, protein restriction during lactation permanently alters the gut microbiome into adulthood. Although the liver bile acids, amino acids, and acyl-carnitines recovered, the fecal peptides and microbiome remained permanently altered into adulthood, indicating that inadequate protein intake in a specific time frame in early life can have an irreversible impact on the microbiome and fecal metabolome.NEW & NOTEWORTHY Undernutrition-induced early-life growth restriction not only leads to increased disease risk but also permanently alters the gut microbiome and gut-liver metabolome during specific windows of early-life development.


Mycotoxins in house dust problems and analytical Approaches.
People in developed countries spend up to 90% of their time indoors. This led to an increased awareness for problems regarding indoor environment in the recent years. It is known that mycotoxins formed by moulds can be harmful to human health.The body burden of mycotoxins is caused primarily by the uptake of cereals and related products but sometimes also by animal products. However the health effects caused by indoor moulds are currently under investigation. Therefore the aim of an investigation program is to study mould-dependent health effects in a burdened population of the city of Leipzig, Germany. To estimate exposure situation house dust samples are collected from loaded apartments. To realise the measurements of selected mycotoxins in house dust the development of a suitable analytical method was necessary. Capillary electrophoresis in combination with a special clean up of the samples was found to be an useful tool for these investigations.


cis-Methyldioxolane specifically recognizes the m2 muscarinic receptor.
cis-Methyldioxolane (CD) is a muscarinic receptor agonist. [3H]CD has been used to label a subpopulation of muscarinic receptors described as exhibiting high agonist affinity. Pharmacological evidence suggests that the population of receptors labeled by [3H]CD consists of m2 and/or m4 subtypes; however, no studies have directly addressed the subtype selectivity of [3H]CD. The present study characterizes binding of this ligand to individual human receptor subtypes expressed in transfected Chinese hamster ovary cells. Results indicate that [3H]CD binds with high affinity only to Hm2 receptors but not to all Hm2 receptors. Twenty-eight percent of Hm2 receptors bound [3H]CD with a KD of 3.5 +/- 0.5 nM. Binding was eliminated in the presence of guanosine 5'-O-(3-thiotriphosphate), indicating that the Hm2 receptors labeled by [3H]CD are those that are associated with GDP-bound G protein. Binding of [3H]CD by only a subpopulation of Hm2 receptors is in agreement with data generated from studies of [3H]CD binding in mammalian brain. Because muscarinic receptors have been implicated to play a role in the pathogenesis of both Alzheimer's and Parkinson's disease, as well as the neurotoxicity of organophosphorus compounds, knowledge of the binding specificity of the muscarinic agonist [3H]CD should aid research in these areas.


Design of experiments and multivariate analysis approach to study dissolution stability of a modified-release drug product to support lean design strategies.
The purpose of this paper is to present the use of Design of Experiments and multivariate analysis for evaluation of a modified-release drug product stability to support post-approval lean stability approaches. The focus of the paper was to investigate potential root-causes for acceleration of dissolution upon stability. For statistical evaluation of stability data, multiple linear regression statistics was used. The design space of the stability study was modeled using MODDE 12.1 software. For experimental set-up, parameters such as Temperature, Time, Packaging, Batch, and Active Pharmaceutical Ingredient supplier were selected. With multiple linear regression modeling of the all generated stability data until six months, we were able to identify or confirm the Stability-related quality attributes and Shelf life limiting attributes. From the multiple linear regression correlation coefficients, we have evaluated that decrease of an antioxidant upon stability could cause potential shift in dissolution. However, main factors for accelerated dissolution can be attributed to other material and process variables. In the last part of the study, we have shown the usefulness of these methodologies for supporting lean stability approaches. With enhanced drug product knowledge, we designed two reduced long-term stability studies and showed that with 'One-half' reduced design, we would still be able to confirm 24-month shelf life. Implementing Quality by design approaches on stability studies could reduce the need for excessive analytical testing, help to evaluate meaningfulness of the data and set a risk-based stability testing strategy.


Smoothing and differentiation of displacement-time data: an application of splines and digital filtering.
The advent of the digital computer has allowed workers in the field of biomechanics to perform data smoothing and time differentiation numerically. The methods which are most commonly used are spline functions and digital filtering. This paper provides raw displacement-time data for an object falling in the earth's gravitational field and demonstrates the results obtained using splines and digital filtering to calculate acceleration. It is recommended that the quintic spline is a good method to use provided one has sufficient core available, and the digital filter, with some form of augmentation and/or velocity smoothing, can yield satisfactory results for the user who has a mini- or micro-computer. Listings of the digital filter and finite difference subroutines are provided.


2H NMR and X-ray diffraction studies of methyl rotation in crystals of ortho-methyldibenzocycloalkanones.
We have used (2)H NMR lineshape analyses and single crystal X-ray diffraction (XRD) to investigate the effects of molecular structure and crystalline environment on the rotational dynamics of methyl groups in four aromatic cycloalkanones. These include two methyl-substituted anthrones, one anthraquinone and one dibenzosuberone, which are known to undergo excited state H-atom tunneling from the ortho-methyl group to the carbonyl oxygen. With experiments conducted between 100 and 300K, samples 1,4-dimethylanthrone (DMAT) and 1,4-dimethylanthraquinone (DMAQ) were shown to enter the intermediate exchange regime (k(rot) approximately <10(7)s(-1)) at ca. 120K while samples of 1,4,10,10-tetramethylanthrone (TMAT) and 1,4-dimethyldibenzosuberone (DMDBS) remained in the fast exchange regime even at ca. 100K. Single crystal XRD analyses suggest that high intramolecular hindrance is avoided by molecular distortions, and that intermolecular contacts play an important role.


Immunochemical, molecular genetic, and transmission studies on a case of Gerstmann-Sträussler-Scheinker syndrome.
Using immunostaining with anti-prion protein (PrP) antiserum, we detected numerous kuru plaques in the brain of a 24-year-old man with Gerstmann-Sträussler-Scheinker syndrome. Immunoreactivity on Western blotting of the protease-resistant PrP fraction from the frozen brain was weak. PrP gene analysis showed substitution of alanine to valine in codon 117 but no substitution in codon 102. As the experimental transmission of the disease to mice was negative, a pathogen of a relatively low infectivity may cause the disease in predisposed family members.


Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Afterload independence and sensitivity to inotropic state.
Previous studies suggest that the relationship between end-diastolic volume and stroke work calculated as the area of the pressure-volume work loop is linear, afterload independent, and sensitive to the inotropic state. The correlation of myocardial oxygen consumption with this stroke work could provide an integrated measure of cardiac performance and metabolism to assess perturbations induced by ischemia or pathologic loading conditions. Fourteen canine hearts instrumented for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during progressive volume infusion on right heart bypass (1.5 to 3.5 L/min in 250 ml/min increments). Data acquisition both in the control state and during continuous infusion of calcium chloride (0.03 mEq/kg/min, n = 7) to increase contractility or phenylephrine (2 micrograms/kg/min, n = 7) to alter afterload facilitated the construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least-squares regression analysis. The cardiac mechanics assessment for this group of dogs confirmed a highly linear (mean r = 0.984) work versus preload relationship that was unaffected by changes in afterload but sensitive to increased contractility (71% increase in slope). The myocardial energetics correlation was also linear (mean r = 0.939) and demonstrated an increased oxygen utilization characteristic of the higher inotropic state produced by calcium chloride infusion (0.047 +/- 0.003 versus 0.070 +/- 0.008 ml oxygen/beat/100 gm left ventricular weight, p = 0.008). Although phenylephrine administration produced variable perturbations of myocardial oxygen consumption, the energetics relationship for this subgroup was not statistically altered by changes in afterload. The features of this cardiac energetics assessment suggest its value as a biological marker to evaluate the postischemic, hypertrophied, or failing heart.


Cell division cycle associated 5 promotes colorectal cancer progression by activating the ERK signaling pathway.
Cell division cycle associated 5 (CDCA5) is implicated in the development and progression of a variety of human cancers. Functional significance of CDCA5 in colorectal cancer (CRC), however, has not been investigated. Using a combination of on-line data mining, biochemistry, and molecular biology, we examined the potential oncogenic activity of CDCA5 and the underlying mechanisms. Experiments with human tissue sample showed increased CDCA5 expression in CRC vs. in noncancerous adjacent tissue, and association of CDCA5 upregulation in CRC tissues with shorter patient survival. Also, representative CRC cell-lines had higher CDCA5 expression vs. fetal colonic mucosal cells. CDCA5 knockdown using lentivirus-mediated shRNA inhibited the proliferation and induced apoptosis in cultured HCT116 and HT-29 cells, and suppressed the growth of xenograft in nude mice. CDCA5 knockdown decreased the expression of CDK1 and CyclinB1, increased caspase-3 activity, cleaved PARP and the Bax/Bcl-2 ratio. CDCA5 knockdown also significantly decreased phosphorylation of ERK1/2 and expression of c-jun. Taken together, these findings suggest a significant role in CRC progression of CRC, likely by activating the ERK signaling pathway.


Dynamic decision support graph--visualization of ANN-generated diagnostic indications of pathological conditions developing over time.
A common objection to using artificial neural networks in clinical decision support systems is that the reasoning behind diagnostic indications cannot be sufficiently well explained. This paper presents a method for visualizing diagnostic indications generated from an artificial neural network-based decision support algorithm (ANN-algorithm) in conditions developing over time. The main idea behind the method is first to calculate and graphically present the decision regions corresponding to the diagnostic indications given as output from the ANN-algorithm, in the space of two selected, clinically established 'display variables'. Secondly, the trajectory of time series measurement results of these, often biochemical markers, together with the respective 95% confidence intervals are superimposed on the decision regions. This will permit a nurse or clinician to grasp the diagnostic indication graphically at a glance. The indication is further presented in relation to clinical variables that the clinician is already familiar with, thus providing a sort of explanation. The predictive value of the indication is expressed by the proximity of the measurement result to the decision boundary, separating the decision regions, and by a numerically calculated individualized predictive value. The method is illustrated as applied to a previously published ANN-algorithm for the early ruling-in and ruling-out of acute myocardial infarction, using monitoring of measurement results of myoglobin and troponin-I in plasma. The method is appropriate when there is a limited number of clinically established variables, i.e. variables which the clinician is used to taking into account in clinical reasoning.


Multidrug resistance gene (MDR1) polymorphisms may not be directly associated with response to imatinib in chronic myeloid leukemia.
Our study aimed to investigate the association between multidrug resistance (MDR1) gene polymorphisms and the response to imatinib (IM) in chronic myeloid leukemia (CML). An electronic databases in PubMed, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and VIP were searched using combinations of keywords relating to MDR1 polymorphisms and the response to IM in CML. Studies retrieved from database searches were screened using stringent inclusion and exclusion criteria. The Comprehensive Meta-analysis 2.0 software was utilized for all statistical analyses. In total, 186 studies were initially retrieved, and 10 studies, involving 987 CML patients, were eventually included in this meta-analysis. Results of our study revealed no significant associations between MDR1 rs1045642, rs1128503, and rs2032582 polymorphisms and major molecular response and complete molecular response in CML patients. Significant differences were observed in the genotype frequencies of MDR1 rs1128503 under homozygous, heterozygous, and recessive models, between CML patients sensitive and resistant to IM. A significant difference in genotype frequencies of MDR1 rs2032582 was also observed under allele, homozygous, heterozygous, and recessive models between CML patients sensitive and resistant to IM. In conclusion, based on our meta-analysis, the MDR1 polymorphisms, rs1045642, rs1128503, and rs2032582, are not directly correlated with the curative effect of IM treatment of CML patients.


RNA extraction protocol from low-biomass bacterial Nitrosomonas europaea and Nitrobacter winogradskyi cultures for whole transcriptome studies.
RNA-sequencing for whole transcriptome analysis requires high-quality RNA in adequate amounts, which can be difficult to generate with low-biomass-producing bacteria where sample volume is limited. We present an RNA extraction protocol for low-biomass-producing autotrophic bacteria Nitrosomonas europaea and Nitrobacter winogradskyi cultures. We describe steps for sample collection, lysozyme-based enzymatic lysis, and a commercial silica-column-based RNA extraction. We then detail evaluation of RNA yield and quality for downstream applications such as RNA-Seq. For complete details on the use and execution of this protocol, please refer to Verbeelen et al.1.


Clinical and analytical performance of the PapilloCheck HPV-Screening assay using the VALGENT framework.
The benefit of HPV testing for cervical cancer screening and disease management has been shown in many recent studies and is part of several new evidence-based guidelines. Assessment of emerging HPV tests in this context is essential, using well-annotated samples, such as those generated via the Validation of Genotyping Tests-HPV (VALGENT) framework. Our aim was to assess the PapilloCheck HPV assay in terms of absolute and relative accuracy for primary cervical cancer screening, using a standard comparator test (GP5+/6+EIA)already validated in randomised trials. Type-specific HPV prevalence was stratified by age and cytology grade and compared with the luminex typing assay incorporating a GP5+6+ PCR (GP5+/6+ LMNX Assay). Clinical outcomes were compared with GP5+/6+EIA. Prevalence of hrHPV types (high-risk HPV) increased with severity of cytology. The concordance between PapilloCheck and the GP5+/6+ LMNX Assay was excellent when assessed at the qualitative hrHPV presence/absence level also at the type-specific level in the whole population and in women over 30 years of age. Absolute clinical sensitivity and specificity of the PapilloCheck was high and ranged between 95.5% and 98.2% for sensitivity and between 82.7% and 91.6% for specificity, depending on the outcome and population. The sensitivity and specificity of this assay for the outcomes of CIN2+ were similar to those of the standard comparator assay, GP5+/6+ EIA.


Multicenter clinical evaluation of three commercial reagent kits based on the interferon-gamma release assay for the rapid diagnosis of tuberculosis in China.
To evaluate the performance of three interferon-gamma release assay (IGRA) kits in detecting Mycobacterium tuberculosis infection in China. A multicenter clinical trial was used to compare the effectiveness and application of the three kits. A total of 1026 participants were enrolled at three hospitals, including 597 tuberculosis (TB) patients diagnosed clinically (517 patients with pulmonary TB and 80 patients with extrapulmonary TB) and 429 negative controls (244 patients with pulmonary disease but not TB, or with non-tuberculosis mycobacterial lung diseases, and 185 healthy people). Detection performance indicators including sensitivity, specificity, and the Youden index (YI) were used to evaluate performance. Through bacterial culture evaluation, 224 of the 517 pulmonary TB patients were positive and all 429 negative controls were negative. When the gold standard bacterial methods were used, the sensitivity, specificity, and YI were 89.7% (201/224), 91.1% (391/429), and 0.81 for T-SPOT.TB, 86.2% (193/224), 87.2% (374/429), and 0.73 for QB-SPOT, and 83.9% (188/224), 88.6% (380/429), and 0.73 for TB-IGRA, respectively. There were no significant differences in the sensitivity and specificity of the three kits. The results showed that the three kits had very high sensitivity and specificity and exhibited a good performance for the detection of M. tuberculosis infection.


Urethral mucosal sensitivity testing--a standardized contact medium.
A standardized contact medium for urethral mucosal sensitivity testing is described. The effects of temperature, pulse width and composition of the urethral contact medium on the electrical characteristics of the system and the effect of changing composition of the medium on its lubricant properties are discussed. It is recommended that a 50:50 volume for volume mixture of KY jelly and normal saline be adopted as a standard in order to facilitate the comparison of results between groups working in this field.


Development of an up-grading process to produce MLM structured lipids from sardine discards.
The aim of the work was to produce MLM structured lipids with caprylic acid (M) as medium chain fatty acid located at the external bonds of the glycerol backbone and concentrated polyunsaturated fatty acids (L) from sardine discards (Sardine pilchardus) in the central bond of the glycerol. To that end, the following steps were conducted: (i) fish oil extraction, (ii) Omega-3 free fatty acids (FFA) concentration (low temperature winterization), (iii) two-steps enzymatic esterification and (iv) triacylglycerols (TAG) purification (liquid column chromatography). The resultant purified triacylglycerols accomplished with the oxidative state (peroxide and anisidine value, PV and AV) required for refined oils. As enzymatic treatment, Omega-3 concentrate FFA (Omega-3>600mg Omega-3 per g oil) were esterified with dicaprylic glycerol employing Novozyme 435. This process presented high regioselectivity, with ∼80mol% of concentrated fatty acids esterified at the sn-2 position.


A Domino Effect? The Spread of Implantation of Penile Foreign Bodies in the Prison System.
Subcutaneous penile insertion of foreign bodies is a practice performed globally but has mostly been reported outside of the United States. An incarcerated 29-year-old Caucasian male in a midwestern prison whittled a domino into a dog bone shape and placed it into his ventral penile subcutaneous tissue. He presented to our facility with erosion of the corners of the foreign body through his skin without evidence of infection. Self-insertion of foreign bodies into penile subcutaneous tissue by incarcerated American men for sexual enhancement is more widespread than previously reported. Erosion is a novel presentation.


Role of Jasmonate in Modulation of Mycorrhizae-Induced Resistance Against Fungal Pathogens.
Symbiotic association of plants with arbuscular mycorrhizal (AM) fungi brings about changes in levels of the phytohormone jasmonate (JA) in root and shoot tissues of a plant. The enhanced JA levels not only play a role in controlling the extent of AM colonization but are also involved in the expression of mycorrhizal-induced resistance (MIR) against pathogens. We describe a method used to study the levels of a volatile jasmonate derivative, methyl jasmonate (MeJA), in tomato plants colonized by AM fungi and in response to subsequent attack by the foliar pathogen Alternaria alternata.


Changes in carbohydrate metabolism by triazole growth regulators in cassava (Manihot esculenta Crantz); effects on tuber production and quality.
We have evaluated the ability of two triazole growth regulators, viz. triadimefon (TDM) and hexaconazole (HEX), in the enhancement of tuber production and quality in cassava (Manihot esculenta Crantz) through their effects on carbohydrate metabolism. One litre of 20 mg(-1) TDM and 15 mg(-1) HEX solution per plant were used for the treatments and groundwater was given to control plants. Triazole treatments reduced plant height and leaf area, but increased fresh and dry weights. Plants treated with TDM showed an increased net assimilation rate, which is followed by HEX and control plants. Triazole compounds increased the relative growth rate of cassava after 200 DAP, i.e. in the phase of tuber enlargement. Triazole compounds increased the starch and other carbohydrate contents and carbohydrate metabolising enzyme activities. From the results of this study, it can be concluded that these triazoles can significantly enhance the tuber production and quality by affecting the starch metabolism, apart from their fungicidal properties.


Multi-block classification of Italian semolina based on Near Infrared Spectroscopy (NIR) analysis and alveographic indices.
Durum wheat (Triticum turgidum ssp. durum) is widely grown in the Mediterranean area. The semolina obtained by this grain is used to prepare pasta, couscous, and baked products all over the world. The growing area affects the characteristics of Durum wheat; consequently, it is relevant to trace this product. The present study aims at developing an analytical methodology which would allow tracing durum semolina harvested in 7 different Italian macro-areas. In order to achieve this goal, 597 samples of semolina have been analysed by Near Infrared Spectroscopy, and by measuring alveographic parameters. Eventually, the information collected have been handled by a multi-block classifier (SO-PLS-LDA) in order to predict the origin of samples. The proposed approach provided extremely satisfactory results (in external validation, on a test set of 140 objects), correctly classifying all samples according to their growing area, confirming it represents a suitable solution for tracing durum wheat semolina.


Lytic clavicular lesions in fibromatosis colli.
Two patients with fibromatosis colli (congenital torticollis) presented with lytic lesions in the clavicle at the insertion of the fibrosed clavicular head of the sternocleidomastoid muscle. Biopsy of one lesion showed intraosseous fibrosis. These lesions are probably not uncommon but radiographs are rarely performed in uncomplicated cases.


Non-targeted effects of ionising radiation and radiotherapy.
Modern radiobiology is undergoing rapid change due to new discoveries contradicting the target concept which is currently used to predict dose-response relationships. Thus relatively recently discovered radiation-induced bystander effects (RIBEs), that include additional death, mutation and radio-adaptation in non-irradiated cells, change our understanding of the target concept and broadens its boundaries. This can be significant from a radioprotection point of view and also has the potential to reassess radiation damage models currently used in radiotherapy. This article reviews briefly the general concepts of RIBEs such as the proposed underlying mechanisms of signal induction and propagation, experimental approaches and biological end points used to investigate these phenomena. It also summarises several mathematical models currently proposed in an attempt to quantify RIBE. The main emphasis of this article is to review and highlight the potential impact of the bystander phenomena in radiotherapy.


Cyclic loading history alters the joint compression tolerance and regional indentation responses in the cartilaginous endplate.
This study quantified the effect of subthreshold loading histories that differed by joint posture (neutral, flexed), peak loading variation (10%, 20%, 40%), and loading duration (1000, 3000, 5000 cycles) on the post-loading Ultimate Compressive Tolerance (UCT), yield force, and regional Cartilaginous End Plate (CEP) indentation responses (loading stiffness and creep displacement). One hundred and fourteen porcine spinal units were included. Following conditioning and cyclic compression exposures, spinal units were transected and one endplate from each vertebra underwent subsequent UCT or microindentation testing. UCT testing was conducted by compressing a single vertebra at a rate of 3 kN/s using an indenter fabricated to a representative intervertebral disc size and shape. Force and actuator position were sampled at 100 Hz. Non-destructive uniaxial CEP indentation was performed at five surface locations (central, anterior, posterior, right, left) using a Motoman robot and aluminum indenter (3 mm hemisphere). Force and end-effector position were sampled at 10 Hz. A significant three-way interaction was observed for UCT (p = 0.038). Compared to neutral, the UCT was, on average, 1.9 kN less following each flexed loading duration. No effect of variation was observed in flexion; however, 40% variation caused the UCT to decrease by an average of 2.13 kN and 2.06 kN following 3000 and 5000 cycles, respectively. The indentation stiffness in the central CEP mimicked the UCT response. These results demonstrate a profound effect of posture on post-loading UCT and CEP behaviour. Control of peak compression exposures became particularly relevant only when a neutral posture was maintained and beyond the midpoint of the predicated lifespan.


Medium-term Outcomes after Whole-gland High-intensity Focused Ultrasound for the Treatment of Nonmetastatic Prostate Cancer from a Multicentre Registry Cohort.
High-intensity focused ultrasound (HIFU) is a minimally-invasive treatment for nonmetastatic prostate cancer. To report medium-term outcomes in men receiving primary whole-gland HIFU from a national multi-centre registry cohort. Five-hundred and sixty-nine patients at eight hospitals were entered into an academic registry. Whole-gland HIFU (Sonablate 500) for primary nonmetastatic prostate cancer. Redo-HIFU was permitted as part of the intervention. Our primary failure-free survival outcome incorporated no transition to any of the following: (1) local salvage therapy (surgery or radiotherapy), (2) systemic therapy, (3) metastases, or (4) prostate cancer-specific mortality. Secondary outcomes included adverse events and genitourinary function. Mean age was 65 yr (47-87 yr). Median prostate-specific antigen was 7.0 ng/ml (interquartile range 4.4-10.2). National Comprehensive Cancer Network low-, intermediate-, and high-risk disease was 161 (28%), 321 (56%), and 81 (14%), respectively. One hundred and sixty three of 569 (29%) required a total of 185 redo-HIFU procedures. Median follow-up was 46 (interquartile range 23-61) mo. Failure-free survival at 5 yr after first HIFU was 70% (95% confidence interval [CI]: 64-74). This was 87% (95% CI: 78-93), 63% (95% CI: 56-70), and 58% (95% CI: 32-77) for National Comprehensive Cancer Network low-, intermediate-, and high-risk groups, respectively. Fifty eight of 754 (7.7%) had one urinary tract infection, 22/574 (2.9%) a recurrent urinary tract infection, 22/754 (3%) epididymo-orchitis, 227/754 (30%) endoscopic interventions, 1/754 (0.13%) recto-urethral fistula, and 1/754 (0.13%) osteitis pubis. Of 206 known to be pad-free pre-HIFU, 183/206 (88%) remained pad free, and of 236 with good baseline erectile function, 91/236 (39%) maintained good function. The main limitation is lack of long-term data. Whole-gland HIFU is a repeatable day-case treatment that confers low rates of urinary incontinence. Disease control at a median of just under 5 yr of follow-up demonstrates its potential as a treatment for nonmetastatic prostate cancer. Endoscopic interventions and erectile dysfunction rates are similar to other whole-gland treatments. In this report we looked at the 5-yr outcomes following whole-gland high-intensity focused ultrasound treatment for prostate cancer and found that cancer control was acceptable with a low risk of urine leakage. However, risk of erectile dysfunction and further operations was similar to other whole-gland treatments like surgery and radiotherapy.


Comparative study on the fractionation of cellulases on some hydrophobic interaction chromatography adsorbents.
In this work, a comparative study for the fractionation of Trichoderma reesei cellulases on five different hydrophobic interaction chromatography adsorbents (Butyl-Sepharose 4 FF, Phenyl-Sepharose 6 FF, Octyl-Sepharose 4 FF, Epoxy-Sepharose CL-6B and Polypropylene glycol-Sepharose CL-6B) is shown. The influence of the mobile phase composition on the chromatographic behaviour of T. reesei cellulases complex was evaluated using different concentrations of ammonium sulphate in the eluent buffer. A selective separation of beta-glucosidase with two-fold increase in specific activity and good recoveries of cellobiase activity were obtained with Butyl-Sepharose 4 FF and Phenyl-Sepharose 6 FF using 7% (w/v) ammonium sulphate in the eluent buffer. A beta-glucosidase fractionation was also obtained with Epoxy-Sepharose CL-6B, using 13% (w/v) of the salt in the mobile phase.


Patients' experiences of dental implant treatment: A literature review of key qualitative studies.
To identify and summarise the findings of previous qualitative studies relating to patients' experience of dental implant treatment (DIT) at various stages of their implant treatment, by means of textual narrative synthesis. Original articles reporting patients' experience with dental implant were included. A two-stage search of the literature, electronic and hand search identified relevant qualitative studies up to July 2014. An extensive electronic search was conducted of databases including PubMed, Embase, Scopus, Web of Knowledge, Cochrane Database and Google Scholar. Included primary studies (n=10) used qualitative research methods and qualitative analysis to investigate patients' experiences with dental implants treatment. While the growing interest in implant treatment for the replacement of missing dentition is evident, it is essential to investigate patients' perceptions of different aspects of implant treatment. This textual narrative synthesis conducted to review qualitative studies which provided insight into patients' experience of two types of implant prostheses namely ISOD (implant-supported overdenture) and FISP (fixed implant supported prostheses). Primary reviewed studies tended to include samples of older patients with more extensive tooth loss, and to focus on experiences prior to and post-treatment rather than on the treatment period itself. Findings across reviewed studies (n=10) suggested that patients with FISP thought of implant treatment as a process of 'normalisation'(1) and believed that such implant restorations could be similar to natural teeth, whereas patients with ISOD focused more on the functional and social advantages of their implant treatment. The growing interest in qualitative research is evident in several branches of clinical dentistry and dental implantology is not an exception. Qualitative studies concerning the patients account of their experience of dental implants is however limited. The aim of this review is to firstly identify recent work within this field and to subsequently categorise it more consistently by means of textural narrative synthesis, thus highlighting similarities and differences and enabling identification of gaps in research knowledge thereby setting the direction of further research.


N-terminal PPE domain plays an integral role in extracellular transportation and stability of the immunomodulatory Rv3539 protein of the Mycobacterium tuberculosis.
Multigene PE/PPE family is exclusively present in mycobacterium species. Only few selected genes of this family have been characterized till date. Rv3539 was annotated as PPE63 with conserved PPE domain at N-terminal and PE-PPE at C-terminal. An α/β hydrolase structural fold, characteristic of lipase/esterase, was present in the PE-PPE domain. To assign the biochemical function to Rv3539, the corresponding gene was cloned in pET-32a (+) as full-length, PPE, and PE-PPE domains individually, followed by expression in E. Coli C41 (DE3). All three proteins demonstrated esterase activity. However, the enzyme activity in the N-terminal PPE domain was very low. The enzyme activity of Rv3539 and PE-PPE proteins was approximately same with the pNP-C4 as optimum substrate at 40 °C and pH 8.0. The loss of enzyme activity after mutating the predicted catalytic triad (Ser296Ala, Asp369Ala, and His395Ala) found only in the PE-PPE domain, confirmed the candidature of the bioinformatically predicted active site residue. The optimal activity and thermostability of the Rv3539 protein was altered by removing the PPE domain. CD-spectroscopy analysis confirmed the role of PPE domain to the thermostability of Rv3539 by maintaining the structural integrity at higher temperatures. The presence of the N-terminal PPE domain directed the Rv3539 protein to the cell membrane/wall and the extracellular compartment. The Rv3539 protein could generate humoral response in TB patients. Therefore, results demonstrated that Rv3539 demonstrated esterase activity. PE-PPE domain of Rv3539 is functionally automated, however, N-terminus domain played a role in protein stabilization and its transportation. Both domains participated in immunomodulation.


Levels of plasma glycan-binding auto-IgG biomarkers improve the accuracy of prostate cancer diagnosis.
Strategies to improve the early diagnosis of prostate cancer will provide opportunities for earlier intervention. The blood-based prostate-specific antigen (PSA) assay is widely used for prostate cancer diagnosis but specificity of the assay is not satisfactory. An algorithm based on serum levels of PSA combined with other serum biomarkers may significantly improve prostate cancer diagnosis. Plasma glycan-binding IgG/IgM studies suggested that glycan patterns differ between normal and tumor cells. We hypothesize that in prostate cancer glycoproteins or glycolipids are secreted from tumor tissues into the blood and induce auto-immunoglobulin (Ig) production. A 24-glycan microarray and a 5-glycan subarray were developed using plasma samples obtained from 35 prostate cancer patients and 54 healthy subjects to identify glycan-binding auto-IgGs. Neu5Acα2-8Neu5Acα2-8Neu5Acα (G81)-binding auto-IgG was higher in prostate cancer samples and, when levels of G81-binding auto-IgG and growth differentiation factor-15 (GDF-15 or NAG-1) were combined with levels of PSA, the prediction rate of prostate cancer increased from 78.2% to 86.2% than with PSA levels alone. The G81 glycan-binding auto-IgG fraction was isolated from plasma samples using G81 glycan-affinity chromatography and identified by N-terminal sequencing of the 50 kDa heavy chain variable region of the IgG. G81 glycan-binding 25 kDa fibroblast growth factor-1 (FGF1) fragment was also identified by N-terminal sequencing. Our results demonstrated that a multiplex diagnostic combining G81 glycan-binding auto-IgG, GDF-15/NAG-1 and PSA (≥ 2.1 ng PSA/ml for cancer) increased the specificity of prostate cancer diagnosis by 8%. The multiplex assessment could improve the early diagnosis of prostate cancer thereby allowing the prompt delivery of prostate cancer treatment.


International differences and inaccuracies in the public advertising about calcaneal apophysitis: an audit of websites originating in Australia, UK and USA.
Calcaneal apophysitis is a common condition in childhood. Parents often seek online information for children's' health care concerns prior to seeking care. Therefore, we aimed to evaluate the credibility, readability, and accuracy of calcaneal apophysitis advertising on popular websites in three countries. We used content analysis of publicly accessible data. This involved identifying the top 50 websites in each country from their hit rates. We used elements of validated tools to audit and determine frequencies relevant to credibility (e.g. publisher), readability (e.g. literacy score) and accuracy (e.g. alignment with evidence). Data were analysed quantitatively and reported against each element. Websites were predominantly hosted by private health services (n = 118, 79%). The mean (SD) SMOG (readability) score was 9.3 (4.5). The majority of websites (n = 140, 93%) provided at least one treatment recommendation, and less than 10% (n = 11) of websites advertised treatments fully aligned with evidence. Use of treatment modalities without evidence and with high risk to children were also found including surgery, extracorporeal shock wave therapy and laser. Calcaneal apophysitis online advertising is mostly curated by clinicians. Clinicians should consider revising online advertising to increase understandability and accuracy to reduce health care wastage, risk, and low value care.


Removal mechanism of low-concentration Cr (VI) in a submerged membrane bioreactor activated sludge system.
Removal mechanism of low-concentration Cr (VI) (0.4 mg/L) was studied in a submerged membrane bioreactor (SMBR) activated sludge system. SMBR was operated with the synthetic wastewater containing 0.4 mg/L Cr (VI). Bio-removal and inactivation batch experiments were also carried out for studying the low-concentration Cr (VI) removal mechanism. SMBR activated sludge system recovered rapidly from the 0.4 mg/L Cr (VI) shock to achieve the excellent removal of chemical oxygen demand (COD) and NH4 (+)-N. Sulfuricurvum kujiense grew quickly in the bacterial community of activated sludge after Cr (VI) addition. Cr (VI) was mainly removed by the adsorption of extracellular polymeric substances, probably in the form as R2(SOH(+))2 (.)CrO4 (2-). Only few of Cr (VI) was transferred into Cr (III) under aerobic condition. All the results indicated that the sulfur was probably involved in 0.4 mg/L Cr (VI) removal process in SMBR.


The effect of changing technique, dose, and PTV margin on therapeutic ratio during prostate radiotherapy.
To quantify the dosimetric and radiobiological changes seen when using intensity-modulated radiation therapy (IMRT) or planning target volume (PTV) margin reduction with consistent planning parameters in a representative sample of localized prostate cancer patients. Twenty patients were randomly selected from a cohort that received 79.8 Gy using six-field conformal radiotherapy. Using the clinical contours, PTV margin, planning system, and dose constraints, five-field IMRT plans were generated for 79.8, 83.8, and 88.0 Gy. The 88.0-Gy IMRT plan was then reoptimized with a PTV margin reduced to 3 mm. These plans were then compared using various dosimetric and radiobiological endpoints calculated for various alpha/beta. Intensity-modulated RT resulted in greater conformity to the PTV (p < 0.001). No improvement in mean normal tissue complication probabilities in the rectal wall (NTCPrw) was seen, and the modified therapeutic ratio (TR(mod)) was largely unchanged between six-field conformal and IMRT for the majority of the patients. When IMRT was used to escalate dose, NTCPrw increased by 9% at each 5% prescription increase (p < 0.001). Reducing the posterior PTV margin from 7 mm to 3 mm for an IMRT plan reduced the mean NTCPrw by 12% (p < 0.001) and resulted in a trend toward increased TR(mod)(p = 0.005). Changes in TR(mod) between conformal and IMRT planning or PTV reduction showed large interpatient variability. Changing from conformal to IMRT, or from PTV(10-7) to PTV(3), did not produce a uniform interpatient increase in TR(mod)when the CTV contained the prostate alone. Radiobiological benefits of these two methods seem to be dependent on the particular anatomy of individual patients, supporting the use of patient-specific margin, planning, and dose prescription strategies.


Inflammation in cancer and depression: a starring role for the kynurenine pathway.
Depression is a common comorbidity in cancer cases, but this is not only due to the emotional distress of having a life-threatening disease. A common biological mechanism, involving a dysregulated immune system, seems to underpin this comorbidity. In particular, the activation of the kynurenine pathway of tryptophan degradation due to inflammation may play a key role in the development and persistence of both diseases. As a consequence, targeting enzymes involved in this pathway offers a unique opportunity to develop new strategies to treat cancer and depression at once. In this work, we provide a systematic review of the evidence up to date on the kynurenine pathway role in linking depression and cancer and on clinical implications of this evidence. In particular, complications due to chemotherapy are discussed, as well as the potential antidepressant efficacy of novel immunotherapies for cancer.


Systemic therapy of hepatocellular carcinoma: current and promising.
Treatment of advanced hepatocellular carcinoma (HCC) remains challenging, particularly with the limited systemic therapy options. Sorafenib remains the only approved, targeted molecule for the treatment of advanced HCC. Although a survival benefit was demonstrated with sorafenib, it remains only true in the population of patients with Child-Turcotte-Pugh class A disease. Sorafenib also has distinct side effects that require close monitoring. Newer tyrosine kinase inhibitors and angiogenic inhibitors have been evaluated with disappointing results, particularly in phase III trials. Herein we review the pertinent trials for targeted therapy in HCC to date.


Developmental validation of the ANDE™ rapid DNA system with FlexPlex™ assay for arrestee and reference buccal swab processing and database searching.
A developmental validation was performed to demonstrate reliability, reproducibility and robustness of the ANDE System with the FlexPlex assay, including an integrated Expert System, across a number of laboratories and buccal sample variations. Previously, the related DNAscan™/ANDE 4C Rapid DNA System using the PowerPlex®16 assay and integrated Expert System Software received NDIS approval in March 2016. The enhanced ANDE instrument, referred to as ANDE 6C, and the accompanying 6-dye, 27-locus STR assay, referred to as FlexPlex, have been developed to be compatible with all widely used global loci, including the expanded set of the CODIS core 20 loci. Six forensic and research laboratories participated in the FlexPlex Rapid DNA developmental validation experiments, testing a total of 2045 swabs, including those obtained from 1387 unique individuals. The goal of this extensive and comprehensive validation was to thoroughly evaluate and document the ANDE System and its internal Expert System to reliably genotype reference buccal swab samples in a manner compliant with the FBI's Quality Assurance Standards and the NDIS Operational Procedures. The ANDE System, including automated Expert System analysis, generated reproducible and concordant results for buccal swabs when testing various instruments at different laboratories by a number of different operators. When testing a number of non-human DNAs, including oral bacteria, the ANDE System and FlexPlex assay demonstrated limited cross-reactivity. Potential PCR inhibitors were evaluated as part of the validation and no inhibition was detected. Reproducible and concordant profiles were generated from buccal swab samples collected with a limit of detection appropriate for buccal swab collections from arrestees. The precision and resolution of the System met industry standards for detection of microvariants and single base resolution. The integrated Expert System appropriately demonstrated the ability to correctly pass or fail profiles for CODIS upload without human review. During this comprehensive developmental validation, the ANDE System successfully interpreted over 2000 samples tested with over 99.99% concordant alleles. The data package described herein led to the ANDE System with the FlexPlex assay receiving NDIS approval in June 2018.


Continuous light abolishes the maternal entrainment of the circadian activity rhythm of the pups in the field mouse.
12:12-h cycles of presence and absence of mother mouse act as a 'zeitgeber' and entrain the circadian rhythm of locomotor activity in the pups of Mus booduga under continuous darkness or continuous dim light. Continuous higher illumination of 15-25 lx abolishes this impressive maternal entrainment.


An enzyme inhibition assay for 2,4-diamino-5-(3'4'-dichlorophenyl)-6-methylpyrimidine (DDMP,NSC 19494).
An enzyme inhibiton method for the determination of serum levels of DDMP is described. This has proved to be a simple, practical, and reliable method for the clinical monitoring of patients.


The emerging role of noncoding RNAs in neuroinflammation: Implications in pathogenesis and therapeutic approaches.
Noncoding RNAs (ncRNAs) are important regulators of gene expression in different cell processes. Due to their ability in monitoring neural development genes, these transcripts confer neurons with the potential to exert broad control over the expression of genes for performing neurobiological functions. Although the change of ncRNA expression in different neurodegenerative diseases has been reviewed elsewhere, only recent evidence drove our attention to unravel the involvement of these molecules in neuroinflammation within these devastating disorders. Remarkably, the interactions between ncRNAs and inflammatory pathways are not fully recognized. Therefore, this review has focused on the interplay between diverse inflammatory pathways and the related ncRNAs, including microRNAs, long noncoding RNAs, and competing endogenous RNAs in Alzheimer's disease, Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy, multiple sclerosis, Huntington's disease, and prion diseases. Providing novel insights in the field of combining biomarkers is a critical step for using them as diagnostic tools and therapeutic targets in clinical settings.


Separation of basic drugs by high-performance liquid chromatography on a silica column using a methanol-ethylenediamine buffer.
The application of methanol-aqueous ethylenediamine-ammonium nitrate eluents has been investigated for the high-performance liquid chromatographic separation of basic drugs on silica stationary phases. These eluents were shown to be more reproducible than previously studied systems based on methanol-aqueous ammonia-ammonium nitrate eluents. The effects of different eluent pH and buffer concentrations have been examined.


Subcutaneous immunoglobulin in polymyositis and dermatomyositis: a novel application.
To describe the feasibility and safety of subcutaneous immunoglobulin (SCIg) in polymyositis (PM) and dermatomyositis (DM). Since 2009, we used SCIg to treat patients with severe idiopathic myositis (4 with DM, 3 with PM), diagnosed according to the Bohan and Peter's criteria. SCIg (Vivaglobin®; CSL Behring) was administered by a programmable pump at the patient's usual IVIg monthly dose fractioned into equal doses given subcutaneously at weekly intervals. A standardized protocol was used to evaluate patients and to assess disease activity, treatment response and quality of life. Seven female patients were studied. All were Caucasians, with a median age of 53 years and a median disease duration of 72 months. The median follow-up period was 14±4 months. During treatment period, no relapse of the disease occurred. All patients showed a favourable clinical response and reported a good tolerance to the treatment with an improved quality of life. CK serum levels decreased over time with a concomitant improvement in MRC and Rankin modified scores. Three patients were able to discontinue the immunosuppressant and all to reduce the daily maintenance prednisone dose. Our experience demonstrates the beneficial effect and the safety of SCIg administration in active and refractory inflammatory myopathies.


Growth Assessment of Pulmonary Adenocarcinomas Manifesting as Subsolid Nodules on CT: Comparison of Diameter-Based and Volume Measurements.
To analyze the performances of diameter-based measurements, either using diameters, or by calculating diameter-based volumes, as compared to volume measurements in assessing growth of pulmonary adenocarcinomas manifesting as subsolid nodules on CT. In this IRB-approved, retrospective study, 74 pulmonary adenocarcinomas presenting as subsolid nodules and resected in 69 patients (21 men, 48 women, mean age 70 ± 9 years) were included. Three CTs were available for each patient. Nodule size on each CT was assessed with diameter measurements, calculated volume based on diameter measurements, and measured volume. Nodule growth was defined as an increase of measured volume ≥25% between two sequential CTs. Sensitivity, specificity, accuracy, positive and negative predictive values of diameter-based measurements for growth assessment were calculated. Nodule characteristics were compared with nonparametric tests and analysis of variance. There were fewer growing nodules during CT1-CT2 interval (n = 22, 30%) than during CT2-CT3 interval (n = 33, 45%, p =.060). Specificity and negative predictive value of diameter-based measurements for growth assessment ranged respectively from 52 to 77% and 81 to 83% between CT1 and CT2, and from 66 to 76% and 79 to 90% between CT2 and CT3. Nongrowing nodules tended to be larger, regardless how size was measured, and some of these differences in size were statistically significant (p =.002 to .046). For pulmonary adenocarcinomas presenting as subsolid nodules on CT, diameter-based assessment of nodule volume is reasonably accurate at confirming a lack of nodule growth but may overestimate actual growth, as compared to growth assessment based on measured volume.


Comorbidity between lung cancer and COVID-19 pneumonia: role of immunoregulatory gene transcripts in high ACE2-expressing normal lung.
SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC). This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [n = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial (n = 32 metastatic NSCLC). We identified patient subgroups with high and low ACE2 expression (p = 1.55 × 10-19) in normal lung tissue, presumed to be at higher and lower risk, respectively, of developing severe COVID-19 should they become infected. ACE2 transcript expression in normal lung tissues (but not in tumor tissue) of patients with NSCLC was higher in individuals with more advanced disease. High-ACE2 expressors had significantly higher levels of CD8+ cytotoxic T lymphocytes and natural killer cells but with presumably impaired function by high Thymocyte Selection-Associated High Mobility Group Box Protein TOX (TOX) expression. In addition, immune checkpoint-related molecules - PD-L1, CTLA-4, PD-1, and TIGIT - are more highly expressed in normal (but not tumor) lung tissues; these molecules might dampen immune response to either viruses or cancer. Importantly, however, high inducible T-cell co-stimulator (ICOS), which can amplify immune and cytokine reactivity, significantly correlated with high ACE2 expression in univariable analysis of normal lung (but not lung tumor tissue). We report a normal lung immune-tolerant state that may explain a potential comorbidity risk between two diseases - NSCLC and susceptibility to COVID-19 pneumonia. Further, a NSCLC patient subgroup has normal lung tissue expressing high ACE2 and high ICOS transcripts, the latter potentially promoting a hyperimmune response, and possibly leading to severe COVID-19 pulmonary compromise.


Developmental and other factors affecting regeneration of crayfish CNS axons.
According to histological and ultrastructural criteria, nongiant CNS axons in newly hatched crayfish regenerate more rapidly and with greater frequency than do similar axons in adult crayfish. Regenerative ability is greater in one species (Procambarus clarkii) than in another species (Procambarus simulans), is greater at 20-25 degrees C than at 15-16 degrees C, and is greater in nongiant axons than in giant axons. In contrast to axonal regeneration, nerve cell bodies do not regenerate in newly hatched or adult crayfish of either species. While the ability to regenerate CNS axons differs between newly hatched and adult crayfish, the ultrastructural appearance of the CNS is very similar at any age it is examined.


Chemical signals might mediate interactions between females and juveniles of Latrodectus geometricus (Araneae: Theridiidae).
Studies related to communication on spiders show that, as in other invertebrates, the interactions between conspecifics are also made through chemical signals. Therefore, in order to assess whether the composition of cuticular compounds might be involved in interactions that occur during the days after the emergence of juveniles in Latrodectus geometricus, we conducted behavioral and cuticular chemical profiles analysis of females and juveniles of different ages. The results show that females, regardless of their reproductive state, tolerate juveniles of other females with up to 40 days post-emergence and attack juveniles of 80 days post-emergence. Cuticlar chemical analysis shows that while the profile of juveniles is similar to adult's profile, they can remain in the web without being confused with threat or prey. Also, cuticular chemical profiles vary between different populations probably due to genetic and environmental differences or similarities between them. Finally, females in incubation period are able to detect the presence of eggs within any egg sac, but cannot distinguish egg sacs produced by conspecifics from the ones they had produced.


Dual extraction based on solid phase extraction and solidified floating organic drop microextraction for speciation of arsenic and its distribution in tea leaves and tea infusion by electrothermal vaporization ICP-MS.
A dual extraction based on solid phase extraction (SPE) and solidified floating organic drop microextraction (SFODME) was developed for As species in tea leaves and tea infusion by electrothermal vaporization inductively coupled plasma mass spectrometry, including total, suspended, soluble, organic and inorganic As as well as As(III) and As(V). In SPE step, titanium dioxide nanotubes were used for preconcentration of analytes and removal of sample matrix. Elution solution from SPE was employed for further preconcentration and separation of analytes with SFODME. Under optimal conditions, detection limits of this method were 0.046 and 0.072pgmL(-1) with relative standard deviations of 6.3% and 5.8% for As(III) and As(V) (n=9, c=1.0ngmL(-1)), respectively. A preconcentration factor of 500-fold was achieved for As(III) and As(V). This method was successfully applied for analysis of speciation of arsenic and its distribution in tea leaves, tea infusion and certified reference material of tea leaves.


Mutations in the epidermal growth factor receptor gene are linked to smoking-independent, lung adenocarcinoma.
Epidermal growth factor receptor (EGFR) mutations are a potential predictor of the effectiveness of EGFR inhibitors for the treatment of lung cancer. Although EGFR mutations were reported to occur with high frequency in nonsmoking Japanese adenocarcinoma patients, the exact nature has not been fully elucidated. We examined EGFR gene mutations within exons 18-21 and their correlations to clinico-pathological factors and other genetic alterations in tumour specimens from 154 patients who underwent resection for lung cancer at Kyoto University Hospital. Epidermal growth factor receptor mutations were observed in 60 tumours (39.0%), all of which were adenocarcinoma. Among the patients with adenocarcinoma (n=108), EGFR mutations were more frequently observed in nonsmokers than former smokers or current smokers (83.0, 50.0, 15.2%, respectively), in women than men (76.3 vs 34.0%), in tumours with bronchio-alveolar component than those without bronchio-alveolar component (78.9 vs 42.9%), and in well or moderately differentiated tumours than poorly differentiated tumours (72.0, 64.4, 34.2%). No tumours with EGFR mutations had any K-ras codon 12 mutations, which were well-known smoking-related gene mutations. In conclusion, adenocarcinomas with EGFR mutation had a distinctive clinico-pathological feature unrelated to smoking. Epidermal growth factor receptor mutations may play a key role in the development of smoking-independent adenocarcinoma.


Association between circadian rhythm disruption and polycystic ovary syndrome.
To explore the association of circadian rhythm disruption with polycystic ovary syndrome (PCOS) and the potential underlying mechanism in ovarian granulosa cells (GCs). Multicenter questionnaire-based survey, in vivo and ex vivo studies. Twelve hospitals in China, animal research center, and research laboratory of a women's hospital. A total of 436 PCOS case subjects and 715 control subjects were recruited for the survey. In vivo and ex vivo studies were conducted in PCOS-model rats and on ovarian GCs collected from women with PCOS and control subjects. The PCOS rat model was established with the use of testosterone propionate. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA sequencing, rhythmicity analysis, functional enrichment analysis. There was a significant correlation between night shift work and PCOS. PCOS-model rats presented distinct differences in the circadian variation of corticotropin-releasing hormone, adrenocorticotropic hormone, prolactin, and a 4-h phase delay in thyrotropic hormone levels. The motif enrichment analysis of ATAC-seq revealed the absence of clock-related transcription factors in specific peaks of PCOS group, and RNA sequencing ex vivo at various time points over 24 hours demonstrated the differential rhythmic expression patterns of women with PCOS. Kyoto Encyclopedia of Genes and Genomes analysis further highlighted metabolic dysfunction, including both carbohydrate and amino acid metabolism and the tricarboxylic acid cycle. There is a significant association of night shift work with PCOS, and genome-wide chronodisruption exists in ovarian GCs.


Erratum: Corridengum to: Self-Rated Smell Ability Enables Highly Specific Predictors of COVID-19 Status: A Case-Control Study in Israel.
[This corrects the article DOI: 10.1093/ofid/ofaa589.].


Retrofitting of concrete for rigid pavement using bacterial: A meta-analysis.
Cracking in tension causes damage to regular concrete. When the surface of the concrete cracks, liquids can enter and damage the structure. Remediating concrete in rigid pavements is time-consuming, costly, and challenging. Concrete cracking can be reduced using sustainable solutions, such as concrete bacteria. Using concrete bacteria is an innovative method for continuously retrofitting concrete, improving its durability, and reducing maintenance costs. Several studies have explored the possibilities of a wide range of bacteria and demonstrated concrete retrofitting. However, in these extensive studies of sustainable solutions, the role of concrete bacteria in retrofitting concrete for rigid pavement has not been clarified. This meta-analysis aims to compare and contrast the performance of various microorganisms in concrete restoration, considering the bacteria concentration, total concrete components, and water/cement ratio. Data from 371 articles were entered into the initial database and 37 articles into the final database for meta-analysis. Low concentrations (10 CFU/mL) of Bacillus subtilis increased the compressive strength after 28 days at 46.8 MPa, and the optimum concentration of Bacillus subtilis was 105 CFU/mL, resulting in an optimum compressive strength of 58.2 MPa after 28 days, an optimum water/cement ratio of 0.3, and the optimum total ingredients (cement, fine and coarse aggregates) ranging from 2000 to 2400 kg/m3. This meta-analysis study supports a new approach to selecting concrete bacteria and developing sustainable advances in concrete technology.


Visual detection of tetracycline antibiotics with the turned on fluorescence induced by a metal-organic coordination polymer.
Here, a rapid, simple and sensitive method for visual detection of tetracycline antibiotics (TCs) was developed based on the turned on fluorescence induced by a metal-organic coordination polymer of Zn(bix) [bix=1,4-bis(imidazol-1-ylmethyl)benzene]. Tetracycline antibiotics, such as tetracycline hydrochloride (TC), doxycycline hyclate (DC), chlortetracycline hydrochloride (CTC) and oxytetracyline hydrochloride (OTC), showed very weak fluorescence in Tris-HCl buffer of pH 8.68-9.40. However, the fluorescence intensities of these TCs were greatly enhanced in the presence of Zn(bix) and were found to be proportional to the concentrations of TCs. Accordingly, TCs could be quantitatively determined with the detection limits of 12.0, 6.0, 19.0 and 19.0nM for TC, DC, CTC and OTC, respectively. Furthermore, this fluorimetric method was successfully applied to the determination of DC contents in doxycycline hyclate tablets from three factories with satisfactory results compared with the HPLC method. Also, the interaction mechanism between TCs and Zn(bix) was investigated by the absorption spectra, fluorescence spectra and circular dichroism spectra. The results showed that TCs could interact with Zn(bix) to form TCs-Zn(bix) ternary complexes and the turned on fluorescence was mainly ascribed to the restricted conformational rotation of TCs molecules through coordination with Zn(II) from the polymeric networks of Zn(bix).


Advances in and the Applicability of Machine Learning-Based Screening and Early Detection Approaches for Cancer: A Primer.
Despite the efforts of the past decades, cancer is still among the key drivers of global mortality. To increase the detection rates, screening programs and other efforts to improve early detection were initiated to cover the populations at a particular risk for developing a specific malignant condition. These diagnostic approaches have, so far, mostly relied on conventional diagnostic methods and have made little use of the vast amounts of clinical and diagnostic data that are routinely being collected along the diagnostic pathway. Practitioners have lacked the tools to handle this ever-increasing flood of data. Only recently, the clinical field has opened up more for the opportunities that come with the systematic utilisation of high-dimensional computational data analysis. We aim to introduce the reader to the theoretical background of machine learning (ML) and elaborate on the established and potential use cases of ML algorithms in screening and early detection. Furthermore, we assess and comment on the relevant challenges and misconceptions of the applicability of ML-based diagnostic approaches. Lastly, we emphasise the need for a clear regulatory framework to responsibly introduce ML-based diagnostics in clinical practice and routine care.


Metalign: efficient alignment-based metagenomic profiling via containment min hash.
Metagenomic profiling, predicting the presence and relative abundances of microbes in a sample, is a critical first step in microbiome analysis. Alignment-based approaches are often considered accurate yet computationally infeasible. Here, we present a novel method, Metalign, that performs efficient and accurate alignment-based metagenomic profiling. We use a novel containment min hash approach to pre-filter the reference database prior to alignment and then process both uniquely aligned and multi-aligned reads to produce accurate abundance estimates. In performance evaluations on both real and simulated datasets, Metalign is the only method evaluated that maintained high performance and competitive running time across all datasets.


Prevalence of periodontal disease among adults in India: A systematic review and meta-analysis.
We designed this systematic review of the available literature to measure the pooled prevalence of periodontal disease among Indian adults. An electronic search was conducted for studies assessing the prevalence of periodontal disease (gingivitis and periodontitis) in India. The search yielded forty studies, of which thirty eligible cross-sectional studies assessing the prevalence among those 18 years and above were included. The methodological quality of the included studies was assessed. Meta-analyses were conducted for periodontitis outcomes, stratified for different covariates like age groups, gender, geographic region, population group, type of index and study quality. Pooled prevalence was used to estimate overall effect, with 95% confidence intervals (CI). A total of 92,219 adults participated in 30 studies included for qualitative analysis. Studies utilizing convenience sampling were excluded from quantitative analysis. Pooled prevalence estimates of periodontitis and gingivitis were assessed on from 24 to 21 studies respectively. We found that overall prevalence of periodontal disease was 51% (CI: 41.9-60.1) and gingivitis was 46.6% (CI: 37.8-55.5). Prevalence of mild to moderate periodontitis was 26.2% (CI: 21.1-31.6), while for severe periodontitis it was 19% (CI: 14.3-24.2). Participants 65 years or above had highest proportion of severe periodontitis (32.7%, CI: 23.7-42.5). Urban population showed the highest prevalence of mild to moderate periodontitis 22.7% (CI: 17.3-28.5). Females had lower prevalence (34.4%) of the periodontitis than males (42.2%). The methodological heterogeneity of included studies was low. Half of Indian adults suffer from some form of periodontal disease. There is need to adopt uniform and accurate measurement tools for recording periodontal condition.


Functional genomics of the lactic acid bacterium Limosilactobacillus fermentum LAB-1: metabolic, probiotic and biotechnological perspectives.
A genome-based systematic analysis was conducted to characterize the metabolic, probiotic, fitness, and safety properties of Limosilactobacillus fermentum LAB-1, a lactic acid bacterium demonstrating strong antimicrobial effects against clinical pathogens. Gene functional characterization revealed a large number of genes for carbohydrate metabolism and a heterofermentative system for carbon dissimilation. Genes for intact pyruvate oxidation, pentose phosphate, and PRPP biosynthetic pathways were identified. Substantial carbohydrate-active enzymes and transporters were also predicted. Metabolic reconstruction revealed complete sets of enzymes for arginine, lysine, methionine, threonine, proline, and ornithine biosynthesis. The bacterium harbors a diverse range of peptidases, and a large variety of peptide and amino acid uptake systems. It encodes restriction-modification and CRISPR-Cas systems for protection against phage infections and carries a wide spectrum of stress proteins for adaptation in the gut and industrial conditions. Genes related to the biosynthesis of B-group and K vitamins were identified allowing its application for novel bio-enriched food production. Other beneficial traits of probiotic and industrial importance such as production of flavor compounds, exopolysaccharide, acetoin, and butanediol were identified. Three antimicrobial peptides were predicted which showed >98% sequence-identity to experimentally validated bacteriocins. Negative traits such as transmissible antibiotic resistance, pathogenicity or virulence appeared to be absent suggesting the strain to be considered safe. The genome analysis will allow precisely targeted laboratory research and full exploitation of the probiotic potentials towards functional-food, biotechnology and health-related applications.


Results of various operations for urinary stress incontinence.
Four hundred and eleven women with urinary incontinence were studied and treated over a 12-year period. The surgical procedures undertaken included 45 colporrahies with Kelly stitches, 12 interposition operations, 49 fascial slings, 49 Zoedler slings using Mersilene, 66 slings using dura, 136 retropubic colpourethrocystopexies, and 54 other operations. Retropubic operations, such as colpourethrocystopexy, should be considered the primary operation for stress incontinence, for if correctly executed, they give the best long-term cure rate (97%).