bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 contact tracing during first delta wave, Lebanon, 2021
Authors: Baakliny Maryo , Naim Julia , Hage Aya , Tohmeh Tatiana , Malak Reem Abdel , Bassila Joelle , Sweidan Hawraa , Zein Mohamad , Wehbeh Darine , Chaalan Kassem , Chaito Lina , Ghosn Nada 
Published: February 2022

AbstractBackgroundOn the 11th March, the WHO has declared COVID-19 pandemic. Officially, the virus was introduced in Lebanon on the 21st February 2020. Since then, the national curve has drawn several waves. From July to September 2021, Lebanon has experienced the first delta wave. As part of the investigation, contact tracing was enhanced to limit virus transmission. The objective is to describe close tracing approach and profile of close contacts identified during the first delta wave.MethodsCOVID-19 surveillance is integrated within the national communicable diseases surveillance. The case definitions are adopted from WHO guides. Laboratories report positive cases on daily basis to the Ministry of Public Health, on DHIS2 platform directly or indirectly via excel files importation. Once reported, case investigation is initiated. It includes contact tracing with: 1) identification of close contacts, 2) advice on quarantine and self-monitoring, 3) contact testing. Referral to field testing is made available free of charge for close contacts. Collected data is updated on DHIS2 platform. Later, data is cleaned and analyzed to generate the daily report including description of close contacts. The report is shared with decision makers, professionals, media and public.ResultsFrom week 2021W27 to week 2021W40, 85490 cases were reported. Case investigation rate reached 78.8% of the cases were investigated within 24 hours. 66.5% of investigated cases shared lists of contacts, with 3.6 as average number of contacts per case.We identified a total of 161805 close contacts, 95% were from family members, 71% were not vaccinated and 10 % had prior COVID-19 infection.As for contact testing, 65% had RT-PCR test upon investigation, with 32% positive result. Furthermore, 19205 were referred and tested via field testing, with 25% positivity rate. Of all identified contacts, the reported positive tests reached 56,904 representing 35.2% of all contacts.ConclusionDuring community transmission and mitigation strategy, contact tracing contributes to increase awareness to the contacts and importance to abide to quarantine measures and thus to slow down the virus circulation.Current close contacts are characterized with new profile of prior infection, vaccination history and testing behavior. There is need to adapt the quarantine measures to close contacts based on their profile, and to ensure easy access to free testing.
Emergency department utilization and hospitalizations for ambulatory care sensitive conditions among unattached people actively seeking a primary care provider during the COVID-19 pandemic: a retrospective cohort study
Authors: Marshall Emily Gard , Stock David , Buote Richard , Andrew Melissa K. , Breton Mylaine , Cossette Benoit , Green Michael E. , Isenor Jennifer E. , Mathews Maria , Lenskjold Anders , MacKenzie Adrian , Martin-Misener Ruth , McDougall Beth , Mooney Melanie , Moritz Lauren R. 
Published: February 2022

ABSTRACTBackgroundPrimary care (PC) attachment improves healthcare access and prevention and management of chronic conditions. Yet, growing proportions of Canadians are unattached, signing-up on provincial waitlists. Understanding variations in healthcare utilization during COVID-19, and among potentially vulnerable unattached patients, is needed. This study compares emergency department (ED) utilization and hospitalization among those on and off a provincial PC waitlist, during the first two waves of COVID-19.MethodsWaitlist and administrative health data were linked to describe persons ever/never on the waitlist between January 1, 2017, and December 24, 2020. ED utilization and ambulatory care sensitive conditions (ACSC) hospitalization rates by current waitlist status were quantified from physician claims and hospitalization data. Relative differences during COVID-19 first and second waves were compared with the previous year.ResultsDuring the study period, 100,867 Nova Scotians (10.1%) were on the waitlist. Those on the waitlist had higher ED utilization and ACSC hospitalizations. ED utilization was higher overall for individuals ≥65 years and females; lowest during first two COVID-19 waves; and differed more by waitlist status for those <65 years. ED contacts and ACSC hospitalizations decreased during COVID-19 relative to the previous year, and for ED utilization this difference was more pronounced for those on the waitlist.InterpretationNova Scotians seeking PC attachment utilize hospital-based services more frequently than those not on the waitlist. Both groups had lower utilization during the COVID-19 pandemic than the year before. The degree to which forgone services produces downstream health burden remains to be seen.
Pediatric Nemaline Myopathy: A systematic review using individual patient data
Authors: Christophers Briana , Lopez Michael A. , Gupta Vandana A. , Baylies Mary 
Published: February 2022

AbstractContextNemaline myopathy (NM) is a skeletal muscle disease that affects 1 in 50,000 live births.ObjectiveDevelop a narrative synthesis of the findings of a systematic review of the latest case descriptions of patients with nemaline myopathy.Data SourcesA systematic search of MEDLINE, Embase, CINAHL, Web of Science, and Scopus was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the keywords pediatric, child, nemaline myopathy, nemaline rod, rod myopathy.Study SelectionCase studies focused on pediatric NM and published in English between January 1, 2010 and December 31, 2020 in order to represent the most recent findings.Data ExtractionInformation was collected about the age of first signs, earliest presenting neuromuscular signs and symptoms, systems affected, progression, death, pathological description, and genetic changes.ResultsOf a total of 385 records, 55 case reports or series were reviewed, covering 101 pediatric patients from 23 countries. We review varying presentations in children ranging in severity despite being caused by the same mutation, in addition to current and future clinical considerations relevant to the care of patients with nemaline myopathy.LimitationsThe results are limited by findings shared in the literature, which varied in their detail and sometimes lacked histological or genetic results. Trends and correlations may be altered by information available.ConclusionsThis review synthesizes genetic, histopathologic, and disease presentation findings from pediatric nemaline myopathy case reports. These data strengthen our understanding of the wide spectrum of disease seen in nemaline myopathy. Future studies are needed to identify the underlying molecular mechanism of pathology, to improve diagnostics, and to develop better methods to improve quality of life for these patients.
High-Throughput Clinical Trial Emulation with Real World Data and Machine Learning: A Case Study of Drug Repurposing for Alzheimer’s Disease
Authors: Zang Chengxi , Zhang Hao , Xu Jie , Zhang Hansi , Fouladvand Sajjad , Havaldar Shreyas , Cheng Feixiong , Chen Kun , Chen Yong , Glicksberg Benjamin S. , Chen Jin , Bian Jiang , Wang Fei 
Published: February 2022

ABSTRACTClinical trial emulation, which is the process of mimicking targeted randomized controlled trials (RCT) with real-world data (RWD), has attracted growing attention and interest in recent years from the pharmaceutical industry. Different from RCTs which have stringent eligibility criteria for recruiting participants, RWD are more representative of real-world patients to whom the drugs will be prescribed. One technical challenge for trial emulation is how to conduct effective confounding control with complex RWD so that the treatment effects can be objectively derived. Recently many approaches, including deep learning algorithms, have been proposed for this goal, but there is still no systematic evaluation and practical guidance on them. In this paper, we emulate 430, 000 trials from two large-scale RWD warehouses, covering both electronic health records (EHR) and general claims, over 170 million patients spanning more than 10 years, aiming to identify new indications of approved drugs for Alzheimer’s disease (AD). We have investigated the behaviors of multiple different approaches including logistic regression and deep learning models, and propose a new model selection strategy that can significantly improve the performance of confounding balance of the participants in different arms of emulated trials. We demonstrate that regularized logistic regression-based propensity score (PS) model outperforms the deep learning-based PS model and others, which contradicts with our intuitions to a certain extent. Finally, we identified 8 drugs whose original indications are not AD (pantoprazole, gabapentin, acetaminophen, atorvastatin, albuterol, fluticasone, amoxicillin, and omeprazole), hold great potential of being beneficial to AD patients.
The benefits and harms of adjuvant chemotherapy for non-small cell lung cancer in patients with major comorbidities: A simulation study
Authors: Leiter Amanda , Kong Chung Yin , Gould Michael K. , Kale Minal S. , Veluswamy Rajwanth R. , Smith Cardinale B. , Mhango Grace , Huang Brian Z. , Wisnivesky Juan P. , Sigel Keith 
Published: February 2022

AbstractBackgroundRandomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of stage IB-IIIA non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however.MethodsWe used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in stage IB-IIIA NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases.ResultsAdjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with stage IB cancers. For patients with CHF and stage IB disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for stages II-IIIA for younger patients with CHF. In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts.ConclusionsOlder, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients.
Blood transcriptomes of SARS-CoV-2 infected kidney transplant recipients demonstrate immune insufficiency
Authors: Sun Zeguo , Zhang Zhongyang , Banu Khadija , Azzi Yorg Al , Reghuvaran Anand , Fredericks Samuel , Planoutene Marina , Hartzell Susan , Pell John , Tietjen Gregory , Asch William , Kulkarni Sanjay , Formica Richard , Rana Meenakshi , Zhang Weijia , Akalin Enver , Cravedi Paolo , Heeger Peter S. , Menon Madhav C. 
Published: February 2022

AbstractBackgroundKidney transplant recipients (KTRs) with COVID-19 have poor outcomes compared to non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.□MethodsClinical data were collected by chart review. PAXgene blood RNA was poly-A selected and RNA sequencing was performed to evaluate transcriptome changes.ResultsA total of 64 cases of COVID-19 in KTRs were enrolled, including 31 acute cases (< 4 weeks from diagnosis) and 33 post-acute cases (>4 weeks). In the blood transcriptome of acute cases, we identified differentially expressed genes (DEGs) in positive or negative association COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways, but downregulation of T-cell and adaptive immune-activation pathways proportional to severity score. This finding was independent of lymphocyte count and despite reduction in immunosuppression (IS) in most KTRs. Comparison with post-acute cases showed “normalization” of these enriched pathways after >4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of IS. The latter analysis was adjusted for COVID-19 severity score and lymphocyte count. DEGs associated with worsening disease severity in a non-KTR cohort with COVID-19 (GSE152418) showed significant overlap with KTRs in these identified enriched pathways.ConclusionBlood transcriptome of KTRs affected by COVID-19 shows decrease in T-cell and adaptive immune activation pathways during acute disease that associate with severity despite IS reduction and show recovery after acute illness.Significance statementKidney transplant recipients (KTRs) are reported to have worse outcomes with COVID-19, and empiric reduction of maintenance immunosuppression is pursued. Surprisingly, reported rates of acute rejection have been low despite reduced immunosuppression. We evaluated the peripheral blood transcriptome of 64 KTRs either during or after acute COVID-19. We identified transcriptomic signatures consistent with suppression of adaptive T-cell responses which significantly associated with disease severity and showed evidence of recovery after acute disease, even after adjustment for lymphocyte number. Our transcriptomic findings of immune-insufficiency during acute COVID-19 provide an explanation for the low rates of acute rejection in KTRs despite reduced immunosuppression. Our data support the approach of temporarily reducing T –cell-directed immunosuppression in KTRs with acute COVID-19.
Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes
Authors: Messing Melina , Sekhon Mypinder S. , Hughes Michael R. , Stukas Sophie , Hoiland Ryan L. , Cooper Jennifer , Ahmed Nyra , Hamer Mark , Li Yicong , Shin Samuel B. , Tung Lin Wei , Wellington Cheryl , Sin Don D. , Leslie Kevin B. , McNagny Kelly M. 
Published: February 2022

AbstractThe COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum levels of four cytokines (IL-1β, IL-6, IL-10 and TNFα) as well as standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies. All measurements and patient samples were taken at time of ICU admission and retrospectively linked to patient clinical outcomes through statistical approaches. These analyses resulted in the definition of a new measure of patient clinical outcome: patients who will recover after short ICU stays (< 6 days) and those who will subsequently die or recover after long ICU stays (> 6 days). Based on these clinical outcome categories, we identified blood prognostic biomarkers that, at time of ICU admission, prospectively distinguish, with 91% sensitivity and 91% specificity (positive likelihood ratio 10.1), patients in the two clinical outcome groups. This is achieved through a tiered evaluation of serum IL-10 and targeted immunophenotyping of monocyte subsets, specifically, CD11clow classical monocytes. Immunophenotyping revealed clear predictors of clinical outcome in COVID-19 providing a highly sensitive and specific prognostic test that could prove useful in guiding clinical resource allocation.Graphical Abstract
Three decades of hospital evacuations in the Netherlands: a scoping review
Authors: Barten Dennis G. , Fijten Marjolein H.M. , Gaakeer Menno I. , Klokman Vincent W. , Mortelmans Luc J. , van Osch Frits , Peters Nathalie A.L.R. , Wijnands Jaap J.J. , Tan Edward C.T.H. , Boin Arjen 
Published: February 2022

AbstractBackgroundHospitals are expected to provide their essential services under all circumstances, including disasters and crisis situations. However, crises and disasters may disrupt essential hospital functions, and necessitate evacuation of the facility. Data on the prevalence and causes of hospital evacuations is limited, whilst realistic evacuation planning will make hospitals more resilient during future crises and disasters. The aim of this study was to develop a systematic understanding of hospital evacuation frequency, causes and characteristics in the Netherlands.MethodsA systematic scoping review of news articles retrieved from the LexisNexis database, Google, Google News, PubMed and EMBASE between 1990 and 2020. All articles mentioning a hospital evacuation in the Netherlands were analyzed.ResultsA total of 67 hospital evacuations were identified in a 30-year time period. The most common primary incidents were internal fire (33%), technological failure (21%) and hazardous materials (12%). Cascading events transpired in 37% of all events. As a result, internal fire (34%), internal power failure (19%) and hazardous materials (16%) were the most important reasons to evacuate a medical facility. The number of evacuees ranged from 1 to 339 patients (median 10.5, interquartile range 36), and there were 13 (19%) complete hospital evacuations. The frequency of hospital evacuations increased over time, with a more diverse etiology during later years.ConclusionsHospital evacuations do occur, and hospitals are vulnerable to both internal and external hazards. Internal fire, internal power failure, hazardous materials and flooding incidents were the most important reasons to (partly) evacuate a hospital. Our findings suggest that facility-specific evacuation guidelines are necessary, and that evacuation preparedness will benefit if the most relevant evacuation scenarios are planned and practiced.
Syllable-PBWT for space-efficient haplotype long-match query
Authors: Wang Victor , Naseri Ardalan , Zhang Shaojie , Zhi Degui 
Published: February 2022

AbstractThe positional Burrows-Wheeler transform (PBWT) has led to tremendous strides in haplotype matching on biobank-scale data. For genetic genealogical search, PBWT-based methods have optimized the asymptotic runtime of finding long matches between a query haplotype and a predefined panel of haplotypes. However, to enable fast query searches, the full-sized panel and PBWT data structures must be kept in memory, preventing existing algorithms from scaling up to modern biobank panels consisting of millions of haplotypes. In this work, we propose a space-efficient variation of PBWT named Syllable-PBWT, which divides every haplotype into syllables, builds the PBWT positional prefix arrays on the compressed syllabic panel, and leverages the polynomial rolling hash function for positional substring comparison. With the Syllable-PBWT data structures, we then present a long match query algorithm named Syllable-Query. Compared to Algorithm 3 of Sanaullah et al. (2021), the most time- and space-efficient previously published solution to the long match query problem, Syllable-Query reduced the memory use by a factor of over 100 on both the UK Biobank genotype data and the 1000 Genomes Project sequence data. Surprisingly, the smaller size of our syllabic data structures allows for more efficient iteration and CPU cache usage, granting Syllable-Query even faster runtime than existing solutions. The implementation of our algorithm is available athttps://github.com/ZhiGroup/Syllable-PBWT.
Selective inhibitors of JAK1 targeting a subtype-restricted allosteric cysteine
Authors: Kavanagh Madeline E. , Horning Benjamin D. , Khattri Roli , Roy Nilotpal , Lu Justine P. , Whitby Landon R. , Brannon Jaclyn C. , Parker Albert , Chick Joel M. , Eissler Christie L. , Wong Ashley , Rodriguez Joe L. , Rodiles Socorro , Masuda Kim , Teijaro John R. , Simon Gabriel M. , Patricelli Matthew P. , Cravatt Benjamin F. 
Published: February 2022

AbstractThe JAK family of non-receptor tyrosine kinases includes four subtypes (JAK1, JAK2, JAK3, and TYK2) and is responsible for signal transduction downstream of diverse cytokine receptors. JAK inhibitors have emerged as important therapies for immuno(onc)ological disorders, but their use is limited by undesirable side effects presumed to arise from poor subtype selectivity, a common challenge for inhibitors targeting the ATP-binding pocket of kinases. Here, we describe the chemical proteomic discovery of a druggable allosteric cysteine present in the non-catalytic pseudokinase domain of JAK1 (C817) and TYK2 (C838), but absent from JAK2 or JAK3. Electrophilic compounds selectively engaging this site block JAK1-dependent transphosphorylation and cytokine signaling, while appearing to act largely as “silent” ligands for TYK2. Importantly, the allosteric JAK1 inhibitors do not impair JAK2-dependent cytokine signaling and are inactive in cells expressing a C817A JAK1 mutant. Our findings thus reveal an allosteric approach for inhibiting JAK1 with unprecedented subtype selectivity.
Cellular genome wide association study identifies common genetic variation influencing lithium induced neural progenitor proliferation
Authors: Wolter Justin M. , Le Brandon D. , Matoba Nana , Lafferty Michael J. , Aygün Nil , Liang Dan , Courtney Kenan , Piven Joseph , Zylka Mark J. , Stein Jason L. 
Published: February 2022

AbstractLithium is used in the treatment of bipolar disorder (BD) and is known to increase neural progenitor cell (NPC) proliferation. Though the mechanism of lithium’s therapeutic effect is not understood, evidence suggests that genetic variation influences response to treatment. Here, we used a library of genetically diverse human NPCs to identify common genetic variants that modulate lithium induced proliferation. We identified a locus on chr3p21.1 associated with lithium induced proliferation that colocalizes with BD risk. One lithium responsive gene, GNL3, was detected within the locus. The allele associated with increased baseline and lithium-induced GNL3 expression was also associated with increased lithium-induced NPC proliferation. Experimental manipulation of GNL3 expression using CRISPRa/i in NPCs showed that GNL3 was necessary for lithium’s full proliferative effects, and sufficient to induce proliferation without lithium treatment. In all, our data suggest that GNL3 expression sensitizes NPCs for a stronger proliferative response to lithium.