bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends and Challenges of Telehealth in an Academic Institution: The Unforeseen Benefits of the COVID-19 Global Pandemic
Authors: Wamsley Christine E , Kramer Alan , Kenkel Jeffrey M , Amirlak Bardia 
Published: July 2020

Abstract
The COVID-19 pandemic has necessitated a reorganization of healthcare delivery, shedding light on the many unrealized advantages telehealth has to offer. In addition to facilitating social distancing, minimizing the risk of pathogen exposure, and preserving healthcare resources, there are many benefits of utilizing this platform that can extend beyond the current pandemic, which will change the way healthcare is delivered for generations to come. With the rapid expansion of telehealth, we present data from our high-volume academic institution’s telehealth efforts, with a more focused analysis of plastic surgery. Although state legislation regarding telehealth varies greatly, we discuss challenges such as legal issues, logistical constraints, privacy concerns, and billing. We also discuss various advantages and the future direction of telehealth not only for plastic surgery but also its general utilization for the future of medicine in the United States.
Proteome-scale analysis of phase-separated proteins in immunofluorescence images
Authors: Yu Chunyu , Shen Boyan , You Kaiqiang , Huang Qi , Shi Minglei , Wu Congying , Chen Yang , Zhang Chaolin , Li Tingting 
Published: July 2020

Abstract
Phase separation is an important mechanism that mediates the spatial distribution of proteins in different cellular compartments. While phase-separated proteins share certain sequence characteristics, including intrinsically disordered regions (IDRs) and prion-like domains, such characteristics are insufficient for making accurate predictions; thus, a proteome-wide understanding of phase separation is currently lacking. Here, we define phase-separated proteomes based on the systematic analysis of immunofluorescence images of 12 073 proteins in the Human Protein Atlas. The analysis of these proteins reveals that phase-separated candidate proteins exhibit higher IDR contents, higher mean net charge and lower hydropathy and prefer to bind to RNA. Kinases and transcription factors are also enriched among these candidate proteins. Strikingly, both phase-separated kinases and phase-separated transcription factors display significantly reduced substrate specificity. Our work provides the first global view of the phase-separated proteome and suggests that the spatial proximity resulting from phase separation reduces the requirement for motif specificity and expands the repertoire of substrates. The source code and data are available at https://github.com/cheneyyu/deepphase.
The Russian Drug Reaction Corpus and neural models for drug reactions and effectiveness detection in user reviews
Authors: Tutubalina Elena , Alimova Ilseyar , Miftahutdinov Zulfat , Sakhovskiy Andrey , Malykh Valentin , Nikolenko Sergey 
Published: July 2020

Abstract

Motivation
Drugs and diseases play a central role in many areas of biomedical research and healthcare. Aggregating knowledge about these entities across a broader range of domains and languages is critical for information extraction (IE) applications. To facilitate text mining methods for analysis and comparison of patient’s health conditions and adverse drug reactions reported on the Internet with traditional sources such as drug labels, we present a new corpus of Russian language health reviews.

Results
The Russian Drug Reaction Corpus (RuDReC) is a new partially annotated corpus of consumer reviews in Russian about pharmaceutical products for the detection of health-related named entities and the effectiveness of pharmaceutical products. The corpus itself consists of two parts, the raw one and the labeled one. The raw part includes 1.4 million health-related user-generated texts collected from various Internet sources, including social media. The labeled part contains 500 consumer reviews about drug therapy with drug- and disease-related information. Labels for sentences include health-related issues or their absence. The sentences with one are additionally labeled at the expression level for identification of fine-grained subtypes such as drug classes and drug forms, drug indications and drug reactions. Further, we present a baseline model for named entity recognition (NER) and multilabel sentence classification tasks on this corpus. The macro F1 score of 74.85% in the NER task was achieved by our RuDR-BERT model. For the sentence classification task, our model achieves the macro F1 score of 68.82% gaining 7.47% over the score of BERT model trained on Russian data.

Availability and implementation
We make the RuDReC corpus and pretrained weights of domain-specific BERT models freely available at https://github.com/cimm-kzn/RuDReC.

Supplementary information
Supplementary data are available at Bioinformatics online.
Deuteros 2.0: peptide-level significance testing of data from hydrogen deuterium exchange mass spectrometry
Authors: Lau Andy M , Claesen Jürgen , Hansen Kjetil , Politis Argyris 
Published: July 2020

AbstractSummaryHydrogen deuterium exchange mass spectrometry (HDX-MS) is becoming increasing routine for monitoring changes in the structural dynamics of proteins. Differential HDX-MS allows comparison of protein states, such as in the absence or presence of a ligand. This can be used to attribute changes in conformation to binding events, allowing the mapping of entire conformational networks. As such, the number of necessary cross-state comparisons quickly increases as additional states are introduced to the system of study. There are currently very few software packages available that offer quick and informative comparison of HDX-MS datasets and even fewer which offer statistical analysis and advanced visualization. Following the feedback from our original software Deuteros, we present Deuteros 2.0 which has been redesigned from the ground up to fulfill a greater role in the HDX-MS analysis pipeline. Deuteros 2.0 features a repertoire of facilities for back exchange correction, data summarization, peptide-level statistical analysis and advanced data plotting features.Availability and implementationDeuteros 2.0 can be downloaded for both Windows and MacOS from https://github.com/andymlau/Deuteros_2.0 under the Apache 2.0 license.
lncMat2B regulated by severe hypoxia induces cisplatin resistance by increasing DNA damage repair and tumor-initiating population in breast cancer cells
Authors: García-Venzor Alfredo , Mandujano-Tinoco Edna Ayerim , Ruiz-Silvestre Araceli , Sánchez José Manuel , Lizarraga Floria , Zampedri Cecilia , Melendez-Zajgla Jorge , Maldonado Vilma 
Published: July 2020

AbstractMulticellular tumor spheroids (MCTSs) constitute a three-dimensional culture system that recapitulates the in vivo tumor microenvironment. Tumor cells cultured as MCTSs present antineoplastic resistance due to the effect of microenvironmental signals acting upon them. In this work, we evaluated the biological function of a new microenvironment-regulated long non-coding RNA, lncMat2B, in breast cancer. In MCTSs, the expression of lncMat2B presented an increase and a zonal heterogeneity, as it was expressed principally in quiescent cells of hypoxic regions of the MCTSs. As expected, functional assays supported the role of severe hypoxia in the regulation of lncMat2B. Moreover, gain- and loss-of-function assays using a transcriptional silencing CRISPR/Cas9 system and gBlock revealed that lncMAT2B regulates the tumor-initiating phenotype. Interestingly, lncMat2B is overexpressed in a cisplatin-resistant MCF-7 cell line, and its ectopic expression in wild type MCF-7 cells increased survival to cisplatin exposure by reducing DNA damage and reactive oxygen species accumulation. lncMAT2B is a possible link between severe hypoxia, tumor-initiating phenotype and drug resistance in breast cancer cells.
Deaths Attributable to Cancer in the US Human Immunodeficiency Virus Population During 2001–2015
Authors: Horner Marie-Josèphe , Shiels Meredith S , Pfeiffer Ruth M , Engels Eric A 
Published: July 2020

AbstractBackgroundAntiretroviral therapy (ART) has reduced mortality among people living with human immunodeficiency virus (HIV), but cancer remains an important cause of death. We characterized cancer-attributable mortality in the HIV population during 2001–2015.MethodsWe used data from population-based HIV and cancer registries in the United States (US). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) associating cancer diagnoses with overall mortality. Population-attributable fractions (PAFs) were calculated using these HRs and the proportion of deaths preceded by cancer. Cancer-specific PAFs and cancer-attributable mortality rates were calculated for demographic subgroups, AIDS-defining cancers (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL], cervical cancer), and non–AIDS-defining cancers.ResultsCancer-attributable mortality was 386.9 per 100 000 person-years, with 9.2% and 5.0% of deaths attributed to non–AIDS-defining and AIDS-defining cancers, respectively. Leading cancer-attributable deaths were from NHL (3.5%), lung cancer (2.4%), KS (1.3%), liver cancer (1.1%), and anal cancer (0.6%). Overall, cancer-attributable mortality declined from 484.0 per 100 000 person-years during 2001–2005 to 313.6 per 100 000 person-years during 2011–2015, while the PAF increased from 12.6% to 17.1%; the PAF for non–AIDS-defining cancers increased from 7.2% to 11.8% during 2011–2015. Cancer-attributable mortality was highest among those aged ≥60 years (952.2 per 100 000 person-years), with 19.0% of deaths attributed to non–AIDS-defining cancers.ConclusionsAlthough cancer-attributable mortality has declined over time, it remains high and represents a growing fraction of deaths in the US HIV population. Mortality from non–AIDS-defining cancers may rise as the HIV population ages. ART access, early cancer detection, and improved cancer treatment are priorities for reducing cancer-attributable mortality.
Vancomycin Area Under the Curve to Predict Timely Clinical Response in the Treatment of Methicillin-resistantStaphylococcus aureusComplicated Skin and Soft Tissue Infections
Authors: Alosaimy Sara , Murray Kyle P , Zasowski Evan J , Morrisette Taylor , Lagnf Abdalhamid M , Lodise Thomas P , Rybak Michael J 
Published: July 2020

AbstractIntroductionAlthough recent guidelines have recommended monitoring vancomycin (VAN) area under the curve (AUC)/minimum inhibitory concentration (MIC) to ensure clinical efficacy and minimize toxicity in methicillin-resistant Staphylococcus aureus (MRSA) for various infections, there are no recommendations regarding complicated skin and soft tissue infections (cSSTIs). We aimed to evaluate the association between VAN AUC and clinical outcomes in MRSA cSSTIs.MethodsThis was a retrospective cohort study of adult patients treated with ≥72 hours of VAN for MRSA cSSTI from 2008 to 2013 at Detroit Medical Center. The primary outcome was timely clinical success (TCS) defined as (1) resolution of signs and symptoms of infection within 72 hours, (2) stabilization and/or reduction in lesion size, (3) alternative agents not required due to VAN failure or toxicity as elected by the prescribing clinician. Classification and regression tree (CART) analysis was performed to determine the AUC associated with TCS in the cohort. Multivariable logistic regression was used to evaluate the association between VAN-AUC and the primary outcome.ResultsA total of 154 patients were included in this analysis. CART identifed an AUC ≥435 mg*hr/L for TCS. Overall, 60.9% of patients experienced TCS; 69.7% in the target-AUC group versus 52.5% in the below-target AUC group, (P = .013). Target-AUC attainment was independently associated with increased odds of TCS (adjusted odds ratio [aOR], 2.208; 95% confidence interval [CI], 1.047–4.659).ConclusionsIn adults treated with VAN for MRSA cSSTI, target-AUC attainment was independently associated with improved clinical outcomes and maybe most warranted for patients at high risk of VAN failure or VAN-associated toxicity.
Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care
Authors: Olender Susan A , Perez Katherine K , Go Alan S , Balani Bindu , Price-Haywood Eboni G , Shah Nirav S , Wang Su , Walunas Theresa L , Swaminathan Shobha , Slim Jihad , Chin BumSik , De Wit Stéphane , Ali Shamim M , Soriano Viladomiu Alex , Robinson Philip , Gottlieb Robert L , Tsang Tak Yin Owen , Lee I-Heng , Hu Hao , Haubrich Richard H , Chokkalingam Anand P , Lin Lanjia , Zhong Lijie , Bekele B Nebiyou , Mera-Giler Robertino , Phulpin Chloé , Edgar Holly , Gallant Joel , Diaz-Cuervo Helena , Smith Lindsey E , Osinusi Anu O , Brainard Diana M , Bernardino Jose I ,   GS-US-540–5773 and GS-US-540–5807 Investigators
Published: July 2020

Abstract

Background
We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care.

Methods
GS-US-540–5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540–5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality.

Results
After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34–3.08, P &lt; .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22–.68, P = .001).

Conclusions
In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19.

Clinical Trials Registration
NCT04292899 and EUPAS34303.
Bacillus Calmette-Guérin (BCG) Infections at High Frequency in Both AR-CGD and X-CGD Patients Following BCG Vaccination
Authors: Ishikawa Takashi , Okai Masashi , Mochizuki Emi , Uchiyama Toru , Onodera Masafumi , Kawai Toshinao 
Published: July 2020

Abstract

Background
Patients with chronic granulomatous disease (CGD) develop severe infections, including Bacillus Calmette-Guérin (BCG). Although the autosomal recessive CGD (AR-CGD) patients should hypothetically develop relatively fewer infections compared to the X-linked CGD (X-CGD) patients due to more residual reactive oxygen intermediates, the impacts of BCG vaccination on AR-CGD and X-CGD patients are unclear. Herein, we demonstrated the clinical features of BCG infections, treatments, and genetic factors in CGD patients after BCG vaccination under the Japanese immunization program.

Methods
We collected data retrospectively from 43 patients with CGD and assessed their history of initial infection, age at diagnosis of CGD, BCG vaccination history, clinical course, treatment for BCG infections, and genetic mutations associated with CGD.

Results
Fourteen CGD patients avoided BCG vaccination because of other preceding infections and family history. Of 29 patients with CGD who received BCG vaccination, 20 patients developed BCG infections. Although the age at onset of initial infection in X-CGD patients was significantly younger than that in AR-CGD patients (P &lt; .01), the onset and frequency of BCG infections were similar in X-CGD and AR-CGD patients. In X-CGD patients, BCG infections equally developed in the patients carrying missense, insertion, deletion, nonsense, and splice mutations of CYBB. All CGD patients with BCG infections were successfully treated with anti-tuberculous drugs.

Conclusions
Although X-CGD patients develop severe infections at a younger age than AR-CGD patients, our data suggested that BCG infections develop at high frequency in both AR-CGD and X-CGD patients, regardless of genotype and mutant forms.
Cost-effectiveness of Preemptive Therapy Versus Prophylaxis in a Randomized Clinical Trial for the Prevention of Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors
Authors: Singh Nina , Winston Drew J , Razonable Raymund R , Lyon G Marshall , Silveira Fernanda P , Wagener Marilyn M , Limaye Ajit P 
Published: July 2020

AbstractBackgroundThe relative costs of preemptive therapy (PET) or prophylaxis for the prevention of cytomegalovirus (CMV) disease in high-risk donor CMV-seropositive/recipient-seronegative (D+/R−) liver transplant recipients have not been assessed in the context of a randomized trial.MethodsA decision tree model was constructed based on the probability of outcomes in a randomized controlled trial that compared valganciclovir as PET or prophylaxis for 100 days in 205 D+/R− liver transplant recipients. Itemized costs for each site were obtained from a federal cost transparency database. Total costs included costs of implementation of the strategy and CMV disease treatment-related costs. Net cost per patient was estimated from the decision tree for each strategy.ResultsPET was associated with a 10% lower absolute rate of CMV disease (9% vs 19%). The cost of treating a case of CMV disease in our patients was $88 190. Considering cost of implementation of strategy and treatment-related cost for CMV disease, the net cost-savings per patient associated with PET was $8707 compared to prophylaxis. PET remained cost-effective across a range of assumptions (varying costs of monitoring and treatment, and rates of disease).ConclusionsPET is the dominant CMV prevention strategy in that it was associated with lower rates of CMV disease and lower overall costs compared to prophylaxis in D+/R− liver transplant recipients. Costs were driven primarily by more hospitalizations and higher CMV disease–associated costs due to delayed onset postprophylaxis disease in the prophylaxis group.
Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study
Authors: Jeong Han Eol , Lee Hyesung , Shin Hyun Joon , Choe Young June , Filion Kristian B , Shin Ju-Young 
Published: July 2020

Abstract

Background
Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells.

Methods
We conducted a cohort study using South Korea’s nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding.

Results
Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13–2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96–2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49–4.14).

Conclusions
While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.
Navigating Clinical Utilization of Direct-from-Specimen Metagenomic Pathogen Detection: Clinical Applications, Limitations, and Testing Recommendations
Authors: Filkins Laura M , Bryson Alexandra L , Miller Steve A , Mitchell Stephanie L 
Published: July 2020

AbstractBackgroundMetagenomic next generation sequencing (mNGS) is becoming increasingly available for pathogen detection directly from clinical specimens. These tests use target-independent, shotgun sequencing to detect potentially unlimited organisms. The promise of this methodology to aid infection diagnosis is demonstrated through early case reports and clinical studies. However, the optimal role of mNGS in clinical microbiology remains uncertain.ContentWe reviewed studies reporting clinical use of mNGS for pathogen detection from various specimen types, including cerebrospinal fluid, plasma, lower respiratory specimens, and others. Published clinical study data were critically evaluated and summarized to identify promising clinical indications for mNGS-based testing, to assess the clinical impact of mNGS for each indication, and to recognize test limitations. Based on these clinical studies, early testing recommendations are made to guide clinical utilization of mNGS for pathogen detection. Finally, current barriers to routine clinical laboratory implementation of mNGS tests are highlighted.SummaryThe promise of direct-from-specimen mNGS to enable challenging infection diagnoses has been demonstrated through early clinical studies of patients with meningitis or encephalitis, invasive fungal infections, community acquired pneumonia, and other clinical indications. However, the proportion of patient cases with positive clinical impact due to mNGS testing is low in published studies and the cost of testing is high, emphasizing the importance of improving our understanding of ‘when to test’ and for which patients mNGS testing is appropriate.
Long-Term Clinical Effectiveness of Ustekinumab in Patients With Crohn’s Disease: A Retrospective Cohort Study
Authors: Ito Takahiro , Maemoto Atsuo , Katsurada Takehiko , Tanaka Hiroki , Motoya Satoshi , Ueno Nobuhiro , Fujiya Mikihiro , Ashida Toshifumi , Hirayama Daisuke , Nakase Hiroshi 
Published: July 2020

Abstract

Background
This study clarifies the long-term effectiveness of ustekinumab based on real-life data from Japanese Crohn’s disease (CD) patients.

Methods
A total of 137 patients were included, and 124 patients (90.5%) were exposed to anti-tumor necrosis factor-α agents.

Results
The clinical remission rate at week 52 was 32.4% in moderate to severely active CD patients. The achievement of clinical remission for 8 weeks after ustekinumab therapy induction was associated with clinical remission at week 52. Ustekinumab persistence rate at week 104 was 81.4%.

Conclusion
Ustekinumab is effective and persistent in CD patients with the previous treatment history of several biologics.