bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe COVID‐19 represents an undiagnosed primary immunodeficiency in a high proportion of infected individuals
Authors: Gray Paul E , Bartlett Adam W , Tangye Stuart G 
Published: April 2022

AbstractSince the emergence of the COVID‐19 pandemic in early 2020, a key challenge has been to define risk factors, other than age and pre‐existing comorbidities, that predispose some people to severe disease, while many other SARS‐CoV‐2‐infected individuals experience mild, if any, consequences. One explanation for intra‐individual differences in susceptibility to severe COVID‐19 may be that a growing percentage of otherwise healthy people have a pre‐existing asymptomatic primary immunodeficiency (PID) that is unmasked by SARS‐CoV‐2 infection. Germline genetic defects have been identified in individuals with life‐threatening COVID‐19 that compromise local type I interferon (IFN)‐mediated innate immune responses to SARS‐CoV‐2. Remarkably, these variants – which impact responses initiated through TLR3 and TLR7, as well as the response to type I IFN cytokines – may account for between 3% and 5% of severe COVID‐19 in people under 70 years of age. Similarly, autoantibodies against type I IFN cytokines (IFN‐α, IFN‐ω) have been detected in patients' serum prior to infection with SARS‐CoV‐2 and were found to cause c. 20% of severe COVID‐19 in the above 70s and 20% of total COVID‐19 deaths. These autoantibodies, which are more common in the elderly, neutralise type I IFNs, thereby impeding innate antiviral immunity and phenocopying an inborn error of immunity. The discovery of PIDs underlying a significant percentage of severe COVID‐19 may go some way to explain disease susceptibility, may allow for the application of targeted therapies such as plasma exchange, IFN‐α or IFN‐β, and may facilitate better management of social distancing, vaccination and early post‐exposure prophylaxis.
NUTM1‐fusion positive malignant neoplasms of the genitourinary tract: A report of six cases highlighting involvement of unusual anatomic locations and histologic heterogeneity
Authors: Xu Bin , Chen Jie‐Fu , Sarungbam Judy , Tickoo Satish , Dickson Brendan C. , Reuter Victor E. , Antonescu Cristina R. 
Published: April 2022

AbstractTumors with NUTM1 fusions occur predominantly in the thoracic cavity and head and neck region. However, recent literature expanded the location of NUTM1‐translocated malignancy to soft tissue, brain, and visceral organs. In this study, we describe the first series of six NUTM1‐translocated carcinomas and sarcomas occurring in the genitourinary tract. The sites of origin were kidney (n = 2), bladder (n = 3), and penis (n = 1). All tumors occurred in adulthood (range: 30–78 years). The histologic features were heterogeneous, showing epithelial, spindle cell, or primitive small blue round cell morphology. Glandular architecture, keratinization, rhabdoid cells, or myxoid‐to‐edematous stromal component were also noted. In three cases, features were in keeping with a carcinoma (two from kidney and one from bladder), whereas the remaining three were classified as malignant undifferentiated neoplasm (MUN)/sarcoma. Fusion partners detected in four cases tested by either FISH and/or RNA sequencing were BRD4 in two kidney tumors, MXD1 in a bladder sarcoma, and MXD4 in a penile sarcoma. NUT immunostain showed diffuse spiculated positivity in five cases. Immunopositivity for various cytokeratins was noted in two tumors. The outcome of NUTM1‐rearranged genitourinary malignancy was dismal: four of five cases with follow‐up developed distant metastasis, and three suffered disease‐specific death. In conclusion, NUTM1‐rearranged carcinoma and sarcoma can affect the genitourinary tract, including kidney, bladder, and penis. Histologic features and keratin immunoexpression are highly variable. A NUTM1‐fusion positive malignancy may be included in the differential diagnosis of a MUN of the genitourinary tract given the dismal outcome and the existing BET‐targeted therapy for tumors with BRD3/4::NUTM1 fusion.
Prognostic impact of copy number alterations and tumor mutational burden in carcinoma of unknown primary
Authors: Bochtler Tilmann , Wohlfromm Timothy , Hielscher Thomas , Stichel Damian , Pouyiourou Maria , Kraft Bianca , Neumann Olaf , Endris Volker , von Deimling Andreas , Stenzinger Albrecht , Krämer Alwin 
Published: April 2022

AbstractIntroductionChromosomal aberrations are known to drive metastatic spread, but their profile is still elusive in carcinoma of unknown primary (CUP). Therefore, the aim of this study was to characterize the chromosomal aberration pattern in CUP depending on histological and clinical features and to assess its prognostic impact together with chromothripsis, tumor mutational burden (TMB), microsatellite instability (MSI), and mutational profiles as potential prognostic biomarkers.MethodsChromosomal aberrations and chromothripsis were detected by methylation‐based copy number variation (CNV) analysis, whereas TMB and MSI were calculated based on large next‐generation sequencing (NGS) panels. Putative primaries were assigned by consensus between two independent oncologists.ResultsCNV losses varied depending on putative primaries and were more abundant in patients harboring TP53 mutations and/or deletions 17p. CNV loss was prognostically adverse in localized CUP treated with surgery and/or radiotherapy, but not in disseminated poor‐risk CUP treated with palliative chemotherapy. CNV loss also worsened the prognosis in squamous cell CUP. Chromothripsis was detected in 18/59 (30.5%) patients without prognostic effect. TMB was highest in cases with MSI, squamous cell histology, and with lung, anal or cervical putative primaries.ConclusionOverall, CNV, chromothripsis, TMB, and MSI profiles in CUP are reminiscent of biological characteristics known from other cancer entities without a unifying CUP‐specific signature. Markedly, high‐level CNV loss is an adverse predictive biomarker in localized but not disseminated chemotherapy‐treated CUP. This implies that chromosomal losses drive CUP progression, but also increase susceptibility to chemotherapy, with both effects apparently leveling out in disseminated CUP.
Tight association between microbial eukaryote and giant virus communities in the Arctic Ocean
Authors: Xia Jun , Kameyama Sohiko , Prodinger Florian , Yoshida Takashi , Cho Kyoung‐Ho , Jung Jinyoung , Kang Sung‐Ho , Yang Eun‐Jin , Ogata Hiroyuki , Endo Hisashi 
Published: April 2022

AbstractViruses are important regulatory factors of the marine microbial community including microeukaryotes. However, little is known about their role in the northern Chukchi Sea in the Arctic basin, which has oligotrophic conditions in summer. To clarify the link between microbial eukaryotic communities and viruses as well as environmental conditions, we investigated the community structures of microeukaryotes (from 3 to144 μm and from 0.23 μm size bio‐particles collected from seawater) and Imitervirales (from 0.23 μm size bio‐particles collected from seawater), a dominant group of viruses infecting marine microeukaryotes. To the best of our knowledge, no study has investigated both Imitervirales and eukaryotic communities in the Arctic Ocean. Surface water samples were collected at 21 ocean stations located in the northeastern Chukchi Sea and an adjacent area outside the Beaufort Gyre (Adjacent Sea), and at two melt ponds on sea ice in the summer of 2018. At the ocean stations, nutrient concentrations were low in most of the locations, except the shelf in the adjacent sea. The community variations were significantly correlated between eukaryotes and Imitervirales, even within the northeastern Chukchi Sea characterized by relatively homogeneous environmental conditions. The association of the eukaryotic community with the viral community was stronger than that with geographical and physicochemical environmental factors. These results suggest that Imitervirales actively infect their hosts even in the cold and oligotrophic seawater in the Arctic Ocean.
SARS-CoV-2 and neurodegenerative diseases: what we know and what we don’t
Authors: Lingor Paul , Demleitner Antonia F. , Wolff Andreas W. , Feneberg Emily 
Published: April 2022

AbstractInfection of the CNS with the SARS-CoV-2 can occur via different routes and results in para- or post-infectious manifestations with a variety of neurological symptoms. In patients with neurodegenerative diseases, SARS-CoV-2 is often associated with a higher fatality rate, which is a relevant problem in increasingly older populations. Apart from the direct consequences of an infection in patients with neurodegenerative diseases, indirect consequences of the pandemic such as limited access to care facilities and treatment have negative effects on the course of these chronic disorders. The occurrence of long-lasting neurological symptoms after infection with SARS-CoV-2 indicates a prolonged impact on the CNS. However, while it is known that SARS-CoV-2 affects neuronal populations that are relevant in the pathogenesis of neurodegenerative diseases, it is yet unclear whether an infection with SARS-CoV-2 is sufficient to trigger neurodegeneration. Reflecting on the impact of SARS-CoV-2 on neurodegeneration, we provide a concise overview on the current knowledge of SARS-CoV-2-induced pathology in the CNS and discuss yet open questions in the field.
Enhancing the performance of smart electrical grids using data mining and fuzzy inference engine
Authors: El-Balka Rana Mohamed , Saleh Ahmed I. , Abdullah Ahmed A. , Sakr Noha 
Published: April 2022

AbstractThis paper is about enhancing the smart grid by proposing a new hybrid feature-selection method called feature selection-based ranking (FSBR). In general, feature selection is to exclude non-promising features out from the collected data at Fog. This could be achieved using filter methods, wrapper methods, or a hybrid. Our proposed method consists of two phases: filter and wrapper phases. In the filter phase, the whole data go through different ranking techniques (i.e., relative weight ranking, effectiveness ranking, and information gain ranking) The results of these ranks are sent to a fuzzy inference engine to generate the final ranks. In the wrapper phase, data is being selected based on the final ranks and passed on three different classifiers (i.e., Naive Bayes, Support Vector Machine, and neural network) to select the best set of the features based on the performance of the classifiers. This process can enhance the smart grid by reducing the amount of data being sent to the cloud, decreasing computation time, and decreasing data complexity. Thus, the FSBR methodology enables the user load forecasting (ULF) to take a fast decision, the fast reaction in short-term load forecasting, and to provide a high prediction accuracy. The authors explain the suggested approach via numerical examples. Two datasets are used in the applied experiments. The first dataset reported that the proposed method was compared with six other methods, and the proposed method was represented the best accuracy of 91%. The second data set, the generalization data set, reported 90% accuracy of the proposed method compared to fourteen different methods.
Ideas, hopes, and fears: what young adults think about genome editing, nature, and society
Authors: Ebeling Smillo , Gebhard Ulrich 
Published: April 2022

AbstractGene technologies are developing at a high speed. Yet, the understandings and ethical conceptions about these developments are not sufficiently scrutinized and reflected. Our qualitative analysis examines everyday myths of younger generations about genome editing; these contribute to a complex fabric of rationally and intuitively justified opinions on genome editing. We argue that current thought patterns and social ways of thinking co-constitute the everyday myths. On the basis of group discussions with teenagers and students about genome editing, we reconstruct their topical views of humanity, the world, science and technology, value orientations, fears, hopes, and desires that are connected to genome editing. Our focus is on everyday myths about health and nature (particularly the nature–culture dichotomy) as well as their implications for social developments in the times of genome editing. Among these developments feared by the young generations are first and foremost conceptions regarding population density, environmental destruction, family relationships, normalization processes, and nature as a fundamental normative authority. The juveniles and students also reflect abstract ideals, e.g., perfection and health, within their contexts, and demystify these ideals.
Decomposing the effects of digitalization on workers’ job satisfaction
Authors: Bolli Thomas , Pusterla Filippo 
Published: April 2022

AbstractThis paper provides novel results on the relative importance of multiple channels through which digitalization affects job satisfaction. Using part-time students and graduates of professional education and training colleges in Switzerland as a case study, we investigate the relative strength of ten different channels. We find that the association between digitalization and job satisfaction is positive on average. This relationship is mainly due to the increase in productivity and more interesting work. Heterogeneity analyses on subsets of workers suggest that the effect through increasing productivity is more beneficial for women, for older workers, for workers without an executive position, and for workers who did not study in technology-related fields. The effect through the interestingness of work is larger for males and for older workers. Our results further suggest that among the channels that decrease job satisfaction, increase of time pressure and worsening of work-life balance are much more important than the threat of losing one’s job. Both channels are more relevant for men, for older workers, and for workers whose field of study is technology-related.
Adaptive personalized routing for vulnerable road users
Authors: Darko Justice , Folsom Larkin , Pugh Nigel , Park Hyoshin , Shirzad Khadijeh , Owens Justin , Miller Andrew 
Published: April 2022

AbstractThis research presents an adaptive and personalized routing model that enables individuals with mobility impairments to save their route preferences to a mobility assistant platform. The proactive approach based on anticipated user need accommodates vulnerable road users' personalized optimum dynamic routing rather than a reactive approach passively awaiting input. Most currently available trip planners target the general public's use of simpler route options prioritized based on static road characteristics. These static normative approaches are only satisfactory when conditions of intermediate intersections in the network are consistent, a constant rate of change occurs per each change of the segment condition, and the same fixed routes are valid every day regardless of the user preference. In this study, the vulnerable road user mobility problem is modeled by accommodating personalized preferences changing by time, sidewalk segment traversability, and the interaction between sidewalk factors and weather conditions for each segment contributing to a path choice. The developed reinforcement learning solution presents a lower average cost of personalized, accessible, and optimal path choices in various trip scenarios and superior to traditional shortest path algorithms (e.g., Dijkstra) with static and dynamic extensions.
Blockade of Microglial Activation in Hypothalamic Paraventricular Nucleus Improves High Salt-Induced Hypertension
Authors: Yu Xiao-Jing , Liu Xiao-Jing , Guo Jing , Su Yu-Kun , Zhang Nianping , Qi Jie , Li Ying , Fu Li-Yan , Liu Kai-Li , Li Yanjun , Kang Yu-Ming 
Published: April 2022

Abstract

BACKGROUND
It has been shown that activated microglia in brain releasing proinflammatory cytokines (PICs) contribute to the progression of cardiovascular diseases. In this study, we tested the hypothesis that microglial activation in hypothalamic paraventricular nucleus (PVN), induced by high-salt diet, increases the oxidative stress via releasing PICs and promotes sympathoexcitation and development of hypertension.

METHODS
High-salt diet was given to male Dahl salt-sensitive rats to induce hypertension. Those rats were bilaterally implanted with cannula for PVN infusion of minocycline, a selective microglial activation blocker, or artificial cerebrospinal fluid for 4 weeks.

RESULTS
High-salt diet elevated mean arterial pressure of Dahl salt-sensitive rats. Meanwhile, elevations of renal sympathetic nerve activity and central prostaglandin E2, as well as increase of plasma norepinephrine, were observed in those hypertensive rats. Tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 increased in the PVN of those rats, associated with a significant activation of microglia and prominent disruption of redox balance, which was demonstrated by higher superoxide and NAD(P)H oxidase 2 (NOX-2) and NAD(P)H oxidase 4 (NOX-4), and lower Cu/Zn superoxide dismutase in PVN. PVN infusion of minocycline attenuated all hypertension-related alterations described above.

CONCLUSION
This study indicates that high salt leads to microglial activation within PVN of hypertensive rats, and those activated PVN microglia release PICs and trigger the production of reactive oxygen species, which contributes to sympathoexcitation and development of hypertension. Blockade of PVN microglial activation inhibits inflammation and oxidative stress, therefore attenuating the development of hypertension induced by high-salt diet.
Tamponade dressing versus no dressing after haemorrhoidectomy: multicentre, randomized clinical trial
Authors: Langenbach Mike Ralf , Florescu Razvan-Valentin , Köhler Andreas , Barkus Jörg , Ritz Jörg-Peter , Quemalli Eduart , Siegel Robert , Zirngibl Hubert , Lefering Rolf , Bönicke Lars 
Published: April 2022

Abstract

Background
Symptomatic haemorrhoids are a common anorectal disorder. The aim of the study was to investigate whether the omission of tamponade dressings after haemorrhoidectomy reduces postoperative pain without increasing the risk of severe bleeding.

Method
This was an open-label, randomized clinical trial conducted at 14 German hospitals. All patients with third- or fourth-degree haemorrhoids undergoing haemorrhoidectomy were considered eligible for selection in the intervention (no dressing) or control group (tamponade applied). Two co-primary outcomes were analysed by testing hierarchically ordered hypotheses. First, maximum pain intensity within 48 h after surgery was compared between the groups (superiority). This was followed by an analysis of severe bleeding complications, defined as any bleeding requiring surgical re-intervention within 7 days (non-inferiority). Secondary outcomes included health-related quality of life, patient satisfaction, haemoglobin levels, and adverse events.

Results
Out of 950 patients screened, 754 were randomized and 725 received intervention (366 patients in the intervention and 359 patients in the control group). In the group with tamponade dressings, median pain intensity on the 0 to 10 scale was 6 (interquartile range (i.q.r.) 4–7). Patients without tamponade dressings reported significantly less pain (median 5 (i.q.r. 3–7), P &lt; 0.001). In each group, five patients (1.4 per cent) experienced severe bleeding. The absolute difference for the severe bleeding rate was −0.03 per cent with the 90 per cent confidence interval ranging from −1.47 per cent to +1.41 per cent, in line with the non-inferiority aim. No significant between-group difference was found for secondary outcomes.

Conclusions
The practice of inserting tamponade dressings after haemorrhoidectomy correlates with increased postoperative pain and does not provide benefits in terms of reduced postoperative bleeding.

Registration number
DRKS00011590
Structured Understanding of Assessment and Plans in Clinical Documentation
Authors: Stupp Doron , Barequet Ronnie , Lee I-Ching , Oren Eyal , Feder Amir , Benjamini Ayelet , Hassidim Avinatan , Matias Yossi , Ofek Eran , Rajkomar Alvin 
Published: April 2022

AbstractPhysicians record their detailed thought-processes about diagnoses and treatments as unstructured text in a section of a clinical note called the assessment and plan. This information is more clinically rich than structured billing codes assigned for an encounter but harder to reliably extract given the complexity of clinical language and documentation habits. We describe and release a dataset containing annotations of 579 admission and progress notes from the publicly available and de-identified MIMIC-III ICU dataset with over 30,000 labels identifying active problems, their assessment, and the category of associated action items (e.g. medication, lab test). We also propose deep-learning based models that approach human performance, with a F1 score of 0.88. We found that by employing weak supervision and domain specific data-augmentation, we could improve generalization across departments and reduce the number of human labeled notes without sacrificing performance.
Whole Genome DNA and RNA Sequencing of Whole Blood Elucidates the Genetic Architecture of Gene Expression Underlying a Wide Range of Diseases
Authors: Liu Chunyu , Joehanes Roby , Ma Jiantao , Wang Yuxuan , Sun Xianbang , Keshawarz Amena , Sooda Meera , Huan Tianxiao , Hwang Shih-Jen , Bui Helena , Tejada Brandon , Munson Peter J. , Cumhur Demirkale , Heard-Costa Nancy L. , Pitsillides Achilleas N , Peloso Gina M. , Feolo Michael , Sharopova Nataliya , Vasan Ramachandran S. , Levy Daniel 
Published: April 2022

ABSTRACTTo create a scientific resource of expression quantitative trail loci (eQTL), we conducted a genome-wide association study (GWAS) using genotypes obtained from whole genome sequencing (WGS) of DNA and gene expression levels from RNA sequencing (RNA-seq) of whole blood in 2622 participants in Framingham Heart Study. We identified 6,778,286 cis-eQTL variant-gene transcript (eGene) pairs at p<5×10−8 (2,855,111 unique cis-eQTL variants and 15,982 unique eGenes) and 1,469,754 trans-eQTL variant-eGene pairs at p<1e-12 (526,056 unique trans-eQTL variants and 7,233 unique eGenes). In addition, 442,379 cis-eQTL variants were associated with expression of 1518 long non-protein coding RNAs (lncRNAs). Gene Ontology (GO) analyses revealed that the top GO terms for cis-eGenes are enriched for immune functions (FDR <0.05). The cis-eQTL variants are enriched for SNPs reported to be associated with 815 traits in prior GWAS, including cardiovascular disease risk factors. As proof of concept, we used this eQTL resource in conjunction with genetic variants from public GWAS databases in causal inference testing (e.g., COVID-19 severity). After Bonferroni correction, Mendelian randomization analyses identified putative causal associations of 60 eGenes with systolic blood pressure, 13 genes with coronary artery disease, and seven genes with COVID-19 severity. This study created a comprehensive eQTL resource via BioData Catalyst that will be made available to the scientific community. This will advance understanding of the genetic architecture of gene expression underlying a wide range of diseases.