bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient reported outcome on endourethrotomy combined with Amplatz dilatation for treatment of incompletely obliterated posterior urethral stricture following pelvic trauma: Validation in the era of urethroplasty
Authors: Wishahi Mohamed , Mehena Ahmed 
Published: July 2021

ABSTRACTIntroductionDirect vision internal urethrotomy (DVIU) is gaining revival among urologists, the procedure having the advantages of being minimally invasive as well as keeping continence and sexual function unaffected. The recurrence rate at 12 months was diminished by combination of DVIU with a Amplatz dilatation at the time of the procedure. Objectives are of present work is to present the outcome of the procedure.Materials and methodsThis is an observational study with a cross-sectional approach. Patients underwent combined endo-urethrotomy and Amplatz dilation for posterior urethral strictures between February 2015 and January2020 were purposively recruited. We performed a retrospective review of the records of 48 patients who completed 12 months follow-up. Patient-reported outcome measures for urethral stricture surgery (USS-PROMs) and sexual function were assessed at 12 months follow-up. A questionnaire was used to assess quality of life, patients in the study filled a questionnaire. Correlation between status before and after treatment were analyzed using simple statistical analysis to evaluate the effect of treatment on quality of life. Clinician-driven outcome were uroflowmetry, retrograde urethrogram, and reporting of complications.ResultsMean length of stricture segment was 2 cm (range 1-2.5 cm). At 12 months follow up patients reported very satisfactory. Restenosis that was treated with redo was reported in 2%. Mild stenosis that was treated with Amplatz dilatation was in 3%. Patients reported very satisfactory or satisfactory for USS-PROSMs, sexual function in comparison to pre-trauma status.ConclusionsEndourethrotomy combined with Amplatz dilation is an effective treatment for short segment passable posterior urethral stricture and it has a place in the era of endourethrotomy.
Frontal lobe fALFF measured from resting-state fMRI at baseline predicts acute treatment response in first episode psychosis
Authors: Lencz Todd , Moyett Ashley , Argyelan Miklos , Barber Anita D. , Cholewa John , Birnbaum Michael L. , Gallego Juan A. , John Majnu , Szeszko Philip R. , Robinson Delbert G. , Malhotra Anil K. 
Published: July 2021

AbstractWhile antipsychotic medications have been utilized for decades, many patients experiencing psychosis do not demonstrate a satisfactory positive symptom response, even in the first episode of illness. Resting state functional magnetic resonance imaging (rs-fMRI) has increasingly been studied as a potential biomarker of antipsychotic treatment response, but studies to date remain limited in terms of sample size and brain regions examined. The present study examined fractional amplitude of low frequency fluctuations (fALFF) derived from rs-fMRI to search the whole brain, in a hypothesis-free manner, for regions that might predict response to 12 weeks of treatments with standard antipsychotic medications (risperidone or aripiprazole). To our knowledge, the present study represents the largest first episode psychosis treatment sample studied with rs-fMRI to date (N=126). At baseline, patients who would later meet strict criteria for clinical response demonstrated significantly greater baseline fALFF in bilateral orbitofrontal cortex compared to non-responders. In a subset of 62 patients who were scanned a second time at the end of treatment, responders and non-responders demonstrated significant increases in fALFF in differing brain regions. Specifically, responders demonstrated significant increases in fALFF, from baseline to follow-up, in bilateral dorsal prefrontal cortex; prefrontal changes were not observed in non-responders or in healthy individuals (n=45) scanned at two time points. Thus, spontaneous activity in orbitofrontal cortex may serve as a prognostic biomarker of antipsychotic treatment, while spontaneous activity in the dorsal prefrontal cortex may serve as a critical target of effective medication.
Modelling the effect of infection prevention and control measures on rate of Mycobacterium tuberculosis transmission to clinic attendees in primary health clinics in South Africa
Authors: McCreesh Nicky , Karat Aaron S , Baisley Kathy , Diaconu Karin , Bozzani Fiammetta , Govender Indira , Beckwith Peter , Yates Tom A , Deol Arminder K , Houben Rein MGJ , Kielmann Karina , White Richard G , Grant Alison D 
Published: July 2021

AbstractBackgroundElevated rates of tuberculosis in health care workers demonstrate the high rate of Mycobacterium tuberculosis (Mtb) transmission in health facilities in high burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on Mtb transmission to patients and other clinic attendees.MethodsAn individual-based model of patient movements through clinics, ventilation in waiting areas, and Mtb transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa. Seven interventions – co-developed with health professionals and policy-makers - were simulated: 1. queue management systems with outdoor waiting areas, 2. ultraviolet germicidal irradiation systems (UVGI), 3. appointment systems, 4. opening windows and doors, 5. surgical mask wearing by clinic attendees, 6. simple clinic retrofits, and 7. increased coverage of long antiretroviral therapy prescriptions and community medicine collection points through the CCMDD service.ResultsIn the model, 1. outdoor waiting areas reduced the transmission to clinic attendees by 83% (interquartile range [IQR] 76-88%), 2. UVGI by 77% (IQR 64-85%), 3. appointment systems by 62% (IQR 45-75%), 4. opening windows and doors by 55% (IQR 25-72%), 5. masks by 47% (IQR 42-50%), 6. clinic retrofits by 45% (IQR 16-64%), and 7. increasing the coverage of CCMDD by 22% (IQR 12-32%).ConclusionsThe majority of the interventions achieved median reductions in the rate of transmission to clinic attendees of at least 45%, meaning that a range of highly effective intervention options are available, that can be tailored to the local context. Measures that are not traditionally considered to be IPC interventions, such as appointment systems, may be as effective as more traditional IPC measures, such as mask wearing.
Association between COVID-19 infection rates by region and implementation of non-pharmaceutical interventions: A cross-sectional study in Japan
Authors: Anan Tomomi , Ishimaru Tomohiro , Hino Ayako , Nagata Tomohisa , Tateishi Seiichiro , Tsuji Mayumi , Ogami Akira , Matsuda Shinya , Fujino Yoshihisa ,   for the CORoNaWork project
Published: July 2021

AbstractBackgroundDuring a pandemic, non-pharmaceutical interventions (NPIs) play an important role in protecting oneself from infection and preventing the spread of infection to others. There are large regional differences in COVID-19 infection rates in Japan. We hypothesized that the local infection incidence may affect adherence to individual NPIs.MethodsThis cross-sectional study was conducted online among full-time workers in Japan in December 2020. Data from a total of 27,036 participants were analyzed. The questionnaire asked the respondents to identify their habits regarding seven well-known NPIs.ResultsCompared to the region with the lowest infection rate, the odds ratios for the region with the highest infection rate were 1.24 (p<0.001) for wearing a mask in public, 1.08 (p=0.157) for washing hands after using the bathroom, 1.17 (p=0.031) for disinfecting hands with alcohol sanitizers when entering indoors, 1.54 (p<0.001) for gargling when returning home, 1.45 (p<0.001) for ventilating the room, 1.33 (p<0.001) for disinfecting or washing hands after touching frequently touched surfaces, and 1.32 (p<0.001) for carrying alcohol sanitizers when outdoors. Five of the seven NPIs showed statistically significant trends across regional infection levels, the two exceptions being wearing a mask in public and washing hands after using the bathroom. Multivariate adjustment did not change these trends.ConclusionsThis study found that NPIs were more prevalent in regions with higher incidence rates of COVID-19 in Japanese workers. The findings suggest that the implementation of NPIs was influenced not only by personal attributes but also by contextual effects of the local infection level.
Higher polygenic scores for empathy increase posttraumatic stress severity in response to certain traumatic events
Authors: Wendt Frank R , Warrier Varun , Pathak Gita A , Koenen Karestan C , Stein Murray B , Krystal John H , Pietrzak Robert H , Gelernter Joel , Goldfarb Elizabeth V , Baron-Cohen Simon , Polimanti Renato 
Published: July 2021

ABSTRACTBackgroundPosttraumatic stress disorder (PTSD) is triggered by environmental stressors. Empathy may predispose an individual to respond to life events differently if high empathizers are emotionally more sensitive to trauma. For the first time, we test this hypothesis at the genetic level.MethodsWe applied polygenic scoring (PGS) to investigate the shared genetics linking empathy (measured using the Empathy Quotient (EQ), a self-report measure of empathy; N=46,861) and PTSD symptom severity (measured using the 6-item PTSD Checklist 6-item (PCL-6)) in the UK Biobank (N=126,219). Follow-up analyses were performed in the context of (1) experiencing any of 16 potential traumas, (2) the total number of traumas endorsed, and (3) the context of trauma. Autism, depression, generalized anxiety, and PCL-17 PGS were included as covariates to verify the specificity of the effect.ResultsEQPGSassociated with PCL-6 (R2=0.012%,P=9.35×10−5). This effect remained significant after accounting for autism, depression, PTSD, and anxiety PGS but was observed only in those who endorsed experiencing at least one traumatic event. EQPGSshowed the strongest effect on PCL-6 (β=2.32, s.e.=0.762,P=0.002) among those who endorsed childhood neglect/abuse (felt hated as a child). In the highest EQPGSdecile, feelinghated as a childwas associated with lower odds of healthy adulthood interpersonal relationships (OR=0.623, 95%CI 0.443-0.885) but this association was not seen in the lowest EQPGSdecile.ConclusionsA genetic predisposition to higher empathy, which may index greater emotional sensitivity, predisposes an individual to more severe PTSD symptoms, specifically in the presence of early negative life events.
Resting State Functional Connectivity Alterations in Individuals with Autism Spectrum Disorders: A Systematic Review
Authors: Kumar Varun , Garg Rahul 
Published: July 2021

AbstractMany studies investigate the alterations in resting state functional connectivity in autism. Most of these studies focus on different regions of the brain to find the connectivity differences between autism spectrum disorder and typically developing populations. The present review quantitatively extracts this data from all the seed based studies on autism spectrum disorder and uses it to build, for the first time, an Autism Altered Functional Connectome (AAFC) which summarizes the alterations in functional connectivity consistently reported in the literature. The data extracted from all the studies matching the inclusion criteria are presented at one place in human as well as a machine-readable format for further interpretation and analysis. Systematically reviewing 41 publications on 2818 subjects comprising 1459 typically developing and 1359 subjects with autism spectrum disorder, a total of 932 altered functional connectivity links were employed to construct an AAFC. The AAL atlas mapping of these links resulted in 71 replicated links of which 49 were consistent, and 574 unreplicated links that were reported just once. Out of 49, 38 were replicated across different non overlapping datasets. Majority of the studies analyzed the functional connectivity of the Default Mode Network (DMN) and its regions. Two important DMN regions, namely precuneus and posterior cingulate cortex were reported to exhibit different connectivity profiles with former majorly underconnected and later majorly overconnected consistently reported across multiple studies. After mapping the AAFLs to an atlas of brain networks, poor integration within DMN regions, and poor segregation of DMN regions with extra-DMN regions was observed.
Association of acute kidney injury with the risk of dementia: A meta-analysis protocol
Authors: Hussain Salman , Singh Ambrish , Antony Benny , Klugarová Jitka , Líčeník Radim , Klugar Miloslav 
Published: July 2021

AbstractAcute kidney injury (AKI) is a complex disorder characterized by an abrupt decline in kidney function over a short period of time. Published epidemiological studies linked AKI with the development of dementia. This meta-analysis aims to understand the pooled risk of dementia in AKI patients compared to non-AKI patients. MEDLINE and Embase databases, and the grey literature in five sources were searched to identify the studies assessing the association of AKI with dementia. The Newcastle-Ottawa scale (NOS) will be used to determine the quality of included studies. The primary outcome of this study will be the risk of dementia among AKI patients compared to non-AKI patients. Subgroup analysis and sensitivity analysis will also be performed. Review Manager version 5.4.1 will be used to perform the meta-analysis.
A Proteogenomic Signature of Age-related Macular Degeneration in Blood
Authors: Emilsson Valur , Gudmundsson Elias F. , Jonmundsson Thorarinn , Twarog Michael , Gudmundsdottir Valborg , Finkel Nancy , Poor Stephen , Liu Xin , Esterberg Robert , Zhang Yiyun , Jose Sandra , Huang Chia-Ling , Liao Sha-Mei , Loureiro Joseph , Zhang Qin , Grosskreutz Cynthia L , Nguyen Andrew A , Huang Qian , Leehy Barrett , Pitts Rebecca , Jonsson Brynjolfur G. , Aspelund Thor , Lamb John R. , Jonasson Fridbert , Launer Lenore J. , Cotch Mary Frances , Jennings Lori L. , Gudnason Vilmundur , Walshe Tony E. 
Published: July 2021

AbstractAge-related macular degeneration (AMD) is one of the most frequent causes of visual impairment in the elderly population. The overall etiology of AMD is complex and still poorly understood, though age, obesity, smoking, and high-density lipoprotein are known risk factors. In one of the first successful reported genome-wide association studies (GWAS), common genetic variants were strongly associated with AMD, including variants within the complement factor H (CFH) gene. To date, 34 genomic regions have been linked to AMD; however, the genes that mediate the risk remain largely unknown, indicating that novel approaches to identifying causal candidates are needed. Recent advances in proteomic technology have exposed the serum proteome’s depth and complexity. In the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), a broad population-based study of the elderly (N = 5764), levels of 4137 human serum proteins and associated networks were integrated with established genetic risk loci for AMD, revealing many predicted as well as novel proteins and pathways, linked to the disease. Serum proteins were also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study of five proteins associated with AMD found CFHR1, CFHR5, and FUT5 to be causally related to the disease, all of which were directionally consistent with the observational estimates. This study provides a robust and unique framework for elucidating the pathobiology of AMD.
Overlapping Time Scales Obscure Early Warning Signals of the Second COVID-19 Wave
Authors: Dablander Fabian , Heesterbeek Hans , Borsboom Denny , Drake John M. 
Published: July 2021

AbstractEarly warning indicators based on critical slowing down have been suggested as a model-independent and low-cost tool to anticipate the (re)emergence of infectious diseases. We studied whether such indicators could reliably have anticipated the second COVID-19 wave in European countries. Contrary to theoretical predictions, we found that characteristic early warning indicators generallydecreasedrather thanincreasedprior to the second wave. A model explains this unexpected finding as a result of transient dynamics and the multiple time scales of relaxation during a non-stationary epidemic. Particularly, if an epidemic that seems initially contained after a first wave does not fully settle to its new quasi-equilibrium prior to changing circumstances or conditions that force a second wave, then indicators will show a decreasing rather than an increasing trend as a result of the persistent transient trajectory of the first wave. Our simulations show that this lack of time scale separation was to be expected during the second European epidemic wave of COVID-19. Overall, our results emphasize that the theory of critical slowing down applies only when the external forcing of the system across a critical point is slow relative to the internal system dynamics.
Predictive modelling of highly multiplexed tumour tissue images by graph neural networks
Authors: Martin-Gonzalez Paula , Crispin-Ortuzar Mireia , Markowetz Florian 
Published: July 2021

AbstractThe progression and treatment response of cancer largely depends on the complex tissue structure that surrounds cancer cells in a tumour, known as the tumour microenvironment (TME). Recent technical advances have led to the development of highly multiplexed imaging techniques such as Imaging Mass Cytometry (IMC), which capture the complexity of the TME by producing spatial tissue maps of dozens of proteins. Combining these multidimensional cell phenotypes with their spatial organization to predict clinically relevant information is a challenging computational task and so far no method has addressed it directly. Here, we propose and evaluate MULTIPLAI, a novel framework to predict clinical biomarkers from IMC data. The method relies on attention-based graph neural networks (GNNs) that integrate both the phenotypic and spatial dimensions of IMC images. In this proof-of- concept study we used MULTIPLAI to predict oestrogen receptor (ER) status, a key clinical variable for breast cancer patients. We trained different architectures of our framework on 240 samples and benchmarked against graph learning via graph kernels. Propagation Attribute graph kernels achieved a class-balanced accuracy of 66.18% in the development set (N=104) while GNNs achieved a class-balanced accuracy of 90.00% on the same set when using the best combination of graph convolution and pooling layers. We further validated this architecture in internal (N=112) and external test sets from different institutions (N=281 and N=350), demonstrating the generalizability of the method. Our results suggest that MULTIPLAI captures important TME features with clinical importance. This is the first application of GNNs to this type of data and opens up new opportunities for predictive modelling of highly multiplexed images.
Clostridioides difficile SpoVAD and SpoVAE interact and are required for DPA packaging into spores
Authors: Baloh Marko , Sorg Joseph A. 
Published: July 2021

AbstractClostridioides difficile spores, like the spores from most endospore-forming organisms, are a metabolically dormant stage of development with a complex structure that conveys considerable resistance to environmental conditions, e.g., dry heat. This resistance is due to the large amount of dipicolinic acid (DPA) that is packaged into the spore core, thereby replacing the majority of water. DPA is synthesized by the mother cell and its packaging into the spore core is regulated by the spoVA operon that has a variable number of genes, depending on the organism. C. difficile encodes 3 spoVA orthologues, spoVAC, spoVAD, and spoVAE. Prior work has shown that C. difficile SpoVAC is a mechanosensing protein responsible for DPA release from the spore core upon the initiation of germination. However, the roles of SpoVAD and SpoVAE remain unclear in C. difficile. In this study we analyzed the roles of SpoVAD and SpoVAE and found that they are essential for DPA packaging into the spore, similar to SpoVAC. Using split luciferase protein interaction assays we found that these proteins interact, and we propose a model where SpoVAC / SpoVAD / SpoVAE proteins interact at or near the inner spore membrane, and each member of the complex is essential for DPA packaging into the spore core.ImportanceC. difficile spore heat resistance provides an avenue for it to survive the disinfection protocols in hospital and community settings. The spore heat resistance is mainly the consequence of the high DPA content within the spore core. By elucidating the mechanism by which DPA is packaged into the spore core, this study may provide insight in how to disrupt the spore heat resistance with the aim of making the current disinfection protocols more efficient at preventing the spread of C. difficile in the environment.
Genome-scale metabolic modelling of lifestyle changes in Rhizobium leguminosarum
Authors: Schulte Carolin C. M. , Ramachandran Vinoy K. , Papachristodoulou Antonis , Poole Philip S. 
Published: July 2021

AbstractBiological nitrogen fixation in rhizobium-legume symbioses is of major importance for sustainable agricultural practices. To establish a mutualistic relationship with their plant host, rhizobia transition from free-living bacteria in soil to growth down infection threads inside plant roots and finally differentiate into nitrogen-fixing bacteroids. We reconstructed a genome-scale metabolic model for Rhizobium leguminosarum and integrated the model with transcriptome, proteome, metabolome and gene essentiality data to investigate nutrient uptake and metabolic fluxes characteristic of these different lifestyles. Synthesis of leucine, polyphosphate and AICAR is predicted to be important in the rhizosphere, while myo-inositol catabolism is active in undifferentiated nodule bacteria in agreement with experimental evidence. The model indicates that bacteroids utilize xylose and glycolate in addition to dicarboxylates, which could explain previously described gene expression patterns. Histidine is predicted to be actively synthesized in bacteroids, consistent with transcriptome and proteome data for several rhizobial species. These results provide the basis for targeted experimental investigation of metabolic processes specific to the different stages of the rhizobium-legume symbioses.ImportanceRhizobia are soil bacteria that induce nodule formation on plant roots and differentiate into nitrogen-fixing bacteroids. A detailed understanding of this complex symbiosis is essential for advancing ongoing efforts to engineer novel symbioses with cereal crops for sustainable agriculture. Here, we reconstruct and validate a genome-scale metabolic model for Rhizobium leguminosarum bv. viciae 3841. By integrating the model with various experimental datasets specific to different stages of symbiosis formation, we elucidate the metabolic characteristics of rhizosphere bacteria, undifferentiated bacteria inside root nodules, and nitrogen-fixing bacteroids. Our model predicts metabolic flux patterns for these three distinct lifestyles, thus providing a framework for the interpretation of genome-scale experimental datasets and identifying targets for future experimental studies.