bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Impact of Prophylactic Eculizumab on Renal Graft Survival in Atypical Hemolytic Uremic Syndrome
Authors: Glover Emily K. , Smith-Jackson Kate , Brocklebank Vicky , Wilson Valerie , Walsh Patrick R. , Montgomery Emma K. , Wong Edwin K.S. , Johnson Sally , Malina Michal , Kavanagh David , Sheerin Neil S. ,   UK aHUS Transplant Consortium
Published: November 2022

Background
Atypical hemolytic uremic syndrome (aHUS) is a rare cause of end-stage kidney disease and associated with poor outcomes after kidney transplantation from early disease recurrence. Prophylactic eculizumab treatment at the time of transplantation is used in selected patients with aHUS. We report a retrospective case note review describing transplant outcomes in patients with aHUS transplanted between 1978 and 2017, including those patients treated with eculizumab.

Methods
The National Renal Complement Therapeutics Centre database identified 118 kidney transplants in 86 recipients who had a confirmed diagnosis of aHUS. Thirty-eight kidney transplants were performed in 38 recipients who received prophylactic eculizumab. The cohort not treated with eculizumab comprised 80 transplants in 60 recipients and was refined to produce a comparable cohort of 33 transplants in 32 medium and high-risk recipients implanted since 2002. Complement pathway genetic screening was performed. Graft survival was censored for graft function at last follow-up or patient death. Graft survival without eculizumab treatment is described by complement defect status and by Kidney Disease: Improving Global Outcomes risk stratification.

Results
Prophylactic eculizumab treatment improved renal allograft survival (P = 0.006) in medium and high-risk recipients with 1-y survival of 97% versus 64% in untreated patients. Our data supports the risk stratification advised by Kidney Disease: Improving Global Outcomes.

Conclusions.
Prophylactic eculizumab treatment dramatically improves graft survival making transplantation a viable therapeutic option in aHUS.
Feasibility and Potential of Transcriptomic Analysis Using the NanoString nCounter Technology to Aid the Classification of Rejection in Kidney Transplant Biopsies
Authors: Varol Hilal , Ernst Angela , Cristoferi Iacopo , Arns Wolfgang , Baan Carla C. , van Baardwijk Myrthe , van den Bosch Thierry , Eckhoff Jennifer , Harth Ana , Hesselink Dennis A. , van Kemenade Folkert J. , de Koning Willem , Kurschat Christine , Minnee Robert C. , Mustafa Dana A. , Reinders Marlies E.J. , Shahzad-Arshad Shazia P. , Snijders Malou L.H. , Stippel Dirk , Stubbs Andrew P. , von der Thüsen Jan , Wirths Katharina , Becker Jan U. , Clahsen-van Groningen Marian C. 
Published: November 2022

Background.
Transcriptome analysis could be an additional diagnostic parameter in diagnosing kidney transplant (KTx) rejection. Here, we assessed feasibility and potential of NanoString nCounter analysis of KTx biopsies to aid the classification of rejection in clinical practice using both the Banff-Human Organ Transplant (B-HOT) panel and a customized antibody-mediated rejection (AMR)–specific NanoString nCounter Elements (Elements) panel. Additionally, we explored the potential for the classification of KTx rejection building and testing a classifier within our dataset.

Methods.
Ninety-six formalin-fixed paraffin-embedded KTx biopsies were retrieved from the archives of the ErasmusMC Rotterdam and the University Hospital Cologne. Biopsies with AMR, borderline or T cell–mediated rejections (BLorTCMR), and no rejection were compared using the B-HOT and Elements panels.

Results.
High correlation between gene expression levels was found when comparing the 2 chemistries pairwise (r = 0.76–0.88). Differential gene expression (false discovery rate; P < 0.05) was identified in biopsies diagnosed with AMR (B-HOT: 294; Elements: 76) and BLorTCMR (B-HOT: 353; Elements: 57) compared with no rejection. Using the most predictive genes from the B-HOT analysis and the Element analysis, 2 least absolute shrinkage and selection operators–based regression models to classify biopsies as AMR versus no AMR (BLorTCMR or no rejection) were developed achieving an receiver-operating–characteristic curve of 0.994 and 0.894, sensitivity of 0.821 and 0.480, and specificity of 1.00 and 0.979, respectively, during cross-validation.

Conclusions.
Transcriptomic analysis is feasible on KTx biopsies previously used for diagnostic purposes. The B-HOT panel has the potential to differentiate AMR from BLorTCMR or no rejection and could prove valuable in aiding kidney transplant rejection classification.
Reports of deaths are an exaggeration: German (PCR-test-positive) fatality counts during the SARS-CoV-2 era in the context of all-cause mortality
Authors: Rockenfeller Robert , Günther Michael , Mörl Falk 
Published: November 2022

AbstractAs of March 2020, counts of SARS-CoV-2-related (‘CoViD-19’) deaths have been key numbers for justifying severe political, social, and economical measures put into action by authorities world-wide. A particular focus thereby was the concomitant excess mortality (EM), i.e. fatalities above the normally expected all-cause mortality (AM). Recent reports and studies, inter alia by the WHO, estimated the SARS-CoV-2-related EM in Germany between 2020 and 2021 as high as 200,000. In this study, we attempt to scrutinise these numbers by putting them into the context of German AM since the year 2000.To this end, we propose two straightforward, low-parametric models to estimate German AM, and thus EM, for the years 2020 and 2021 as well as the flu seasons 2020/21 and 2021/22. Additionally, we give a forecast of the AM expected in 2022. After having derived age-cohort-specific mortality rates out of historical data, weighted with their corresponding demographic proportion, EM is obtained by subtracting (model-)calculated AM counts from observed ones. For Germany, we find even an overall negative EM (‘under-mortality’) of about -18,500 for the year 2020, and a minor positive EM of about 7,000 for 2021, unveiling that officially communicated EM numbers are a great exaggeration. Further, putting CoViD-19 “cases” (defined by positive PCR test outcomes) and their related death counts into the context of AM, we are able to estimate how many Germans have dieddue torather thanwithCoViD-19; an analysis not provided by the appropriate authority, the RKI. Thereby, varying governmental PCR test strategies are shown to heavily obscure reliable estimations of SARS-CoV-2-related EM, particularly within the second year of the proclaimed pandemic.
Blink rate measuredin situdecreases while reading from printed text or digital devices, regardless of task duration, complexity or working distance
Authors: Chidi-Egboka Ngozi Charity , Jalbert Isabelle , Chen Jiaying , Briggs Nancy E. , Golebiowski Blanka 
Published: November 2022

AbstractPurposeTo compare blinking measuredin situduring various tasks and examine relationships with ocular surface symptoms. Day-to-day repeatability of blink rate and interblink interval was assessed.MethodsTwenty-four students (28.6±6.3 years; 8M:16F) completed six reading tasks (printed text, laptop, TV, smartphone, smartphone at 50% brightness, smartphone with complex text), and two non-reading tasks (conversation, walking) in a randomised cross-over study. Ocular surface symptoms and clinical signs were assessed. Blink rate and interblink interval were measured using a wearable eye tracking headset. Blink parameters were compared across tasks and time (linear mixed model and post hoc comparisons with Bonferroni correction). Associations between blinking, symptoms, ocular surface, and clinical signs were assessed (Spearman’s correlation). The smartphone reading task was completed twice to determine coefficient of repeatability.ResultsBlink rate was lower (mean 10.7±9.7 blinks/min) and interblink interval longer (mean 9.6±8.7s) during all reading tasks compared to conversation (mean 32.4±12.4 blinks/min; 1.5±0.6s) and walking (mean 31.3±15.5 blinks/min; 1.9±1.3s) (p<0.001). There were no significant differences in blink parameters between any of the reading tasks, nor between conversation and walking. Changes in blinking occurred within one minute of starting the task. No associations were evident between blink rate or interblink interval and ocular surface symptoms or signs. Coefficient of repeatability was ±12.4 blinks/min for blink rate and ±18.8s for interblink interval.ConclusionSpontaneous blinking can be reliably measuredin situ. Blink rate was reduced and interblink interval increased during reading compared to conversation and walking. Changes in blinking were immediate and sustained, and not associated with ocular surface symptoms or signs.
Behavioural Voluntary and Social Bioassays Enabling Identification of Complex and Sex-Dependent Pain- (-Related) Phenotypes in Rats with Bone Cancer
Authors: Segelcke Daniel , Linnemann Jan , Pradier Bruno , Kronenberg Daniel , Stange Richard , Richter Helene , Görlich Dennis , Baldini Nicola , Di Pompo Gemma , Verri Waldiceu A. , Avnet Sofia , Pogatzki-Zahn Esther 
Published: November 2022

AbstractCancer-induced bone pain (CIBP) is a common and devastating symptom with limited treatment options in patients, significantly affecting their quality of life. To uncover the mechanisms underlying CIBP, using rodent models is the most common approach; however, the translation of results to the clinic may be hindered because the assessment of pain-related behavior is often based exclusively on reflexive-based methods, which are only partially indicative relevant pain in patients. In order to improve the accuracy and strength of the preclinical experimental model of CIBP in rodents, we used a battery of multimodal behavioral tests that were also aimed at identifying rodent-specific behavioral components by using a homecage monitoring assay (HCM).Rats of all sexes received an injection with either heat-deactivated (sham-group) or potent mammary gland carcinoma Walker 256 cells into the tibia. By integrating multimodal datasets, we assessed pain-related behavioral trajectories of CIBP-phenotype, including evoked and non-evoked based assays and HCM.Using principal component analysis (PCA), we discovered sex-specific differences in establishing the CIBP-phenotype, which occurred earlier (and different) in males. In addition, HCM phenotyping revealed the occurrence of sensory-affective states manifested by mechanical hypersensitivity in sham when housed with a tumor-bearing cagemate (CIBP) of the same sex.This multimodal battery allows an in-depth characterization of the CIBP-phenotype under social aspects in rats. The detailed, sex-specific, and rat-specific social phenotyping of CIBP enabled by PCA provides the basis for mechanism-driven studies to ensure robustness and generalisability of results and provide information for targeted drug development in the future.
3D spheroid-microvasculature-on-a-chip for tumor-endothelium mechanobiology interplay
Authors: Zhang Yingqi , Jiang Fengtao , Zhao Yunduo Charles , Cho Ann-Na , Fang Guocheng , Cox Charles D. , Zreiqat Hala , Lu Zu Fu , Lu Hongxu , Ju Lining Arnold 
Published: November 2022

AbstractIn the final step of cancer metastasis, tumor cells become lodged in a distant capillary bed, where they can undergo extravasation and form a secondary tumor. While increasing evidence suggests blood/lymphatic flow and shear stress play a critical role in the tumor extravasation process, there is a lack of systematic and biomechanical approaches to recapitulate sophisticated 3D microtissue interactions within the controllable hydrodynamic microenvironment. Here, we report a simple-to-use 3D spheroid-microvasculature-on-a-chip (SMAC) model. Under static and controlled flow conditions, the SMAC recapitulates the biomechanical crosstalk between heterogeneous tumor spheroids and the endothelium in a high-throughput and quantitative manners. As anin vitrometastasis mechanobiology model, we discover 3D spheroid-induced endothelial compression and cell-cell junction degradation in the process of tumor migration and expansion. Lastly, we examine the shear stress effects on the endothelial orientation, polarization as well as the tumor spheroid expansion. Taken together, our SMAC model offers a miniaturized, cost-efficient and versatile platform for future investigation on metastasis mechanobiology, enhanced permeability and retention effect and even personalized therapeutic evaluation.
Computational investigations in inhibition of alcohol/aldehyde dehydrogenase in lignocellulosic hydrolysates
Authors: Kumar Karan , Siddiqa Azeeza , Pragati  , Chandane Priti , Yadav Saanya , Kori Mahima , Shivram A , Barbora Lepakshi , Moholkar Vijayanand S. 
Published: November 2022

AbstractSecond generation alcoholic biofuels synthesis from lignocellulosic biomass (LB) consists three steps viz., pre-treatment, detoxification, and fermentation. This dilute acid pre-treatment process generates several compounds like acids, aldehydes, ketones, oxides and their phenolic derivatives that are potential inhibitors of some of the crucial enzymes in the metabolic pathway of ABE fermentation. With application of hybrid quantum mechanics/ molecular mechanics (QM/MM) approach, our aim is to discern the molecular mechanism of inhibition of keyAADsacross solventogenic species. The objectives of present study are: (1) identification and homology modelling of keyAADs; (2) validation, quality assessment and physiochemical characterization of the modelled enzymes; (3) identification, construction and optimization of chemical structure of potent microbial inhibitors in LH; and (4) applications of hybrid QM/MM simulations to profile the molecular interactions between microbial inhibitors and keyAADs. Our computational investigation has revealed various important facets of inhibition of theAADenzymes, which could guide structural biologist in designing efficient and robust enzymes. Moreover, our methodology also provides a general framework which could applied for deciphering the molecular mechanism of inhibition behaviour of other enzymes.HighlightsHomology modelling of 7alcohol/aldehyde dehydrogenase(AAD) in solventogenicClostridiaIdentification and structural optimization of potent microbial inhibitors in lignocellulosic hydrolysatesQM/MM simulations to profile the molecular interactions between 10 inhibitors and 7AADsDiscernment of the molecular mechanism of inhibition of keyalcohol/aldehyde dehydrogenaseA methodological framework for deciphering the molecular mechanism of enzyme inhibition
Prolific non-research authors in high impact scientific journals: meta-research study
Authors: Ioannidis John P.A. 
Published: November 2022

ABSTRACTJournalistic papers published in high impact journals can be very influential, especially in hot fields. This meta-research analysis aimed to evaluate the publication profiles, impact, and disclosures of conflicts of interest of non-research authors who had published >200 Scopus-indexed papers in Nature, Science, PNAS, Cell, BMJ, Lancet, JAMA or New England Journal of Medicine. 154 prolific authors were identified, 148 of whom had published 67,825 papers in their main affiliated journal in a non-researcher capacity. Of 25 massively prolific authors with over 700 publications in one of these journals, only 3 had a PhD degree in any subject matter. Only 2 of the 25 disclosed potential conflicts with some specificity. The practice of assigning so much power to non-researchers in shaping scientific discourse should be further debated and disclosures of potential conflicts of interest should be emphasized.
High levels of detection of non-pneumococcal species ofStreptococcusin saliva from adults in the USA
Authors: Hislop Maikel S. , Allicock Orchid M. , Thammavongsa Darani A. , Mbodj Sidiya , Nelson Allison , Shaw Albert C. , Weinberger Daniel M. , Wyllie Anne L. 
Published: November 2022

ABSTRACTBackgroundWhile the sensitivity of detection of pneumococcal carriage can be improved by testing respiratory tract samples with qPCR, concerns have been raised regarding the specificity of this approach. We therefore investigated the reliability of the widely-usedlytAqPCR assay when applied to saliva samples from older adults in relation to a more specific qPCR assay (piaB).MethodsDuring the autumn/winter seasons of 2018/2019 and 2019/2020, saliva was collected at multiple timepoints from 103 healthy adults aged 21-40 (n=34) and ≥64 (n=69) years. Following culture-enrichment, extracted DNA was tested using qPCR forpiaBandlytA. By sequencing the variable region ofrpsB(S2-typing), we identified the species of bacteria isolated from samples testinglytA-positive only.ResultsWhile 30/344 (8.7%) saliva samples (16.5% individuals) tested qPCR-positive for bothpiaBandlytA, 52 (15.1%) samples testedlytA-positive only. No samples testedpiaB-positive only. Through extensive re-culture of the 32lytA-positive samples collected in 2018/2019, we isolated 23 strains (from 8 samples, from 5 individuals) that were also qPCR-positive for onlylytA. Sequencing determined thatStreptococcus mitisandStreptococcus infantiswere predominantly responsible for thislytA-positive qPCR signal.ConclusionsWe identified a comparatively large proportion of samples generating positive signals with the widely usedlytA-qPCR and identified non-pneumococcal streptococcal species responsible for this signal. This highlights the importance of testing for the presence of multiple gene targets in tandem for reliable and specific detection of pneumococcus in respiratory tract samples.
AN INTEGRATED APPROACH TO CARDIOVASCULAR DISEASE IN HOMELESS INDIVIDUALS: A QUALITATIVE STUDY
Authors: Bark Pippa , Ramasawmy Mel , Hayward Andrew , Luchenski Serena A , Aldridge Robert , Burridge Stan , Banerjee Amitava 
Published: November 2022

ABSTRACTBackgroundHomelessness is associated with an increased risk of cardiovascular disease (CVD), beyond impact of socioeconomic status. CVD is preventable and treatable, with barriers to both for homeless people. Those with lived experience of homelessness and health professionals with relevant expertise can help to understand and address these barriers.ObjectivesTo understand and make recommendations to improve CVD care in homeless populations through those with lived experience and professional expertise.MethodFour focus groups were conducted in March-July 2019. Three groups included people currently or previously homeless, each attended by a cardiologist (AB), a health services researcher (PB) and an “expert by experience” (SB) who coordinated participants. One group included multidisciplinary health and social care professionals in and around London to explore solutions.ParticipantsThe three homeless groups included 16 men and 9 women, aged 20- 60 years, of whom 24 were homeless and currently living in hostels and 1 rough sleeper. At least 14 discussed sleeping rough at some point.ResultsParticipants were aware of CVD risks and relevance of healthy habits but identified barriers to prevention and health access, starting with disorientation affecting planning and self-care, lack of facilities for food, hygiene, and exercise, and experiences of discrimination.ConclusionsCVD care for those experiencing homelessness should account for fundamental problems of the environment, be co-designed with service users and cover key principles: flexibility, public and staff education, integration of support, and advocacy for health service rights.
Performance comparison of reusable versus disposable colonoscopes:a non-inferiority Trial
Authors: Wei Mingtong , Liang Chenghai , Ruan Huaqiang , Liao Guolin , Peng Peng , Li Xin , Zou Jun , Liu Shiquan , Cao Ge , Qin Mengbin , Huang Jiean 
Published: November 2022

AbstractObjectiveWe herein compared the performance of reusable and disposable colonoscopes in patients scheduled to undergo colonoscopy with a view of preventing patient cross-infection, protecting the safety of clinical medical staff, reducing the risk of infection, and minimizing the decontamination process, particularly during the coronavirus disease 2019 pandemic.MethodsWe randomly divided patients meeting the enrollment criteria into reusable and disposable colonoscopy groups; the success rate of photographing customary anatomical sites with a non-inferiority margin of -8% was the primary endpoint. Secondary endpoints were the adenoma detection rate, operation time, endoscopic image quality score, endoscopic mucosal resection (EMR) success rate, and adverse events.ResultsWe recruited patients who were treated using reusable or disposable (n = 45, each) colonoscopes. Both groups had 100% success rate for capturing images of customary anatomical sites, with no between-group differences. The lower limit of 95% CI was - 7.8654%, which was greater than the non-inferiority threshold of -8%. The disposable group had a significantly lower average image quality score (26.09 ±1.33 vs. 27.44±0.59,P< 0.001) than the reusable group. The groups did not significantly differ in maneuverability, safety, or device failure/defect rate. Theen-blocEMR success rate was 100% in both groups. EMR took significantly longer in the disposable group (466.18 s±180.56 svs. 206.32 s±109.54 s,P< 0.001). The incidence of EMR-related bleeding and perforation did not significantly differ between the groups.ConclusionsDisposable colonoscope endoscopy is safe and feasible for endoscopy examinations and EMR.
Meta-analysis of public RNA sequencing data revealed potential key genes associated with reproductive division of labor in social Hymenoptera and termites
Authors: Toga Kouhei , Bono Hidemasa 
Published: November 2022

AbstractEusociality in insects has evolved independently many times. One of the most notable characteristics of eusociality is the reproductive division of labor. In social insects, the reproductive division of labor is accomplished by queens and workers. Transcriptome analyses of queens and workers have been conducted for various eusocial species. However, the genes that regulate the reproductive division of labor across all or multiple eusocial species have not yet been fully elucidated. Therefore, we conducted a meta-analysis using publicly available RNA-sequencing data from four major groups of social insects. In this meta-analysis, we collected 258 pairs (queen vs. worker) of RNA-sequencing data from 34 eusocial species. The meta-analysis identified a total of 20 genes that were differentially expressed in queens or workers. Out of these, 12 genes have not previously been reported to be involved in the reproductive division of labor. Functional annotation of these 20 genes in other organisms revealed that they could be regulators of behaviors and physiological states related to the reproductive division of labor. These 20 genes, revealed using massive datasets of numerous eusocial insects, may be key regulators of the reproductive division of labor.