bluuebunny/crossref_metadata_2025_split huggingface dataset:
DrDimont: explainable drug response prediction from differential analysis of multi-omics networks
Authors: Hiort Pauline , Hugo Julian , Zeinert Justus , Müller Nataniel , Kashyap Spoorthi , Rajapakse Jagath C , Azuaje Francisco , Renard Bernhard Y , Baum Katharina 
Published: September 2022

AbstractMotivationWhile it has been well established that drugs affect and help patients differently, personalized drug response predictions remain challenging. Solutions based on single omics measurements have been proposed, and networks provide means to incorporate molecular interactions into reasoning. However, how to integrate the wealth of information contained in multiple omics layers still poses a complex problem.ResultsWe present DrDimont, Drug response prediction from Differential analysis of multi-omics networks. It allows for comparative conclusions between two conditions and translates them into differential drug response predictions. DrDimont focuses on molecular interactions. It establishes condition-specific networks from correlation within an omics layer that are then reduced and combined into heterogeneous, multi-omics molecular networks. A novel semi-local, path-based integration step ensures integrative conclusions. Differential predictions are derived from comparing the condition-specific integrated networks. DrDimont’s predictions are explainable, i.e. molecular differences that are the source of high differential drug scores can be retrieved. We predict differential drug response in breast cancer using transcriptomics, proteomics, phosphosite and metabolomics measurements and contrast estrogen receptor positive and receptor negative patients. DrDimont performs better than drug prediction based on differential protein expression or PageRank when evaluating it on ground truth data from cancer cell lines. We find proteomic and phosphosite layers to carry most information for distinguishing drug response.Availability and implementationDrDimont is available on CRAN: https://cran.r-project.org/package=DrDimont.Supplementary informationSupplementary data are available at Bioinformatics online.
SimBu: bias-aware simulation of bulk RNA-seq data with variable cell-type composition
Authors: Dietrich Alexander , Sturm Gregor , Merotto Lorenzo , Marini Federico , Finotello Francesca , List Markus 
Published: September 2022

AbstractMotivationAs complex tissues are typically composed of various cell types, deconvolution tools have been developed to computationally infer their cellular composition from bulk RNA sequencing (RNA-seq) data. To comprehensively assess deconvolution performance, gold-standard datasets are indispensable. Gold-standard, experimental techniques like flow cytometry or immunohistochemistry are resource-intensive and cannot be systematically applied to the numerous cell types and tissues profiled with high-throughput transcriptomics. The simulation of ‘pseudo-bulk’ data, generated by aggregating single-cell RNA-seq expression profiles in pre-defined proportions, offers a scalable and cost-effective alternative. This makes it feasible to create in silico gold standards that allow fine-grained control of cell-type fractions not conceivable in an experimental setup. However, at present, no simulation software for generating pseudo-bulk RNA-seq data exists.ResultsWe developed SimBu, an R package capable of simulating pseudo-bulk samples based on various simulation scenarios, designed to test specific features of deconvolution methods. A unique feature of SimBu is the modeling of cell-type-specific mRNA bias using experimentally derived or data-driven scaling factors. Here, we show that SimBu can generate realistic pseudo-bulk data, recapitulating the biological and statistical features of real RNA-seq data. Finally, we illustrate the impact of mRNA bias on the evaluation of deconvolution tools and provide recommendations for the selection of suitable methods for estimating mRNA content. SimBu is a user-friendly and flexible tool for simulating realistic pseudo-bulk RNA-seq datasets serving as in silico gold-standard for assessing cell-type deconvolution methods.Availability and implementationSimBu is freely available at https://github.com/omnideconv/SimBu as an R package under the GPL-3 license.Supplementary informationSupplementary data are available at Bioinformatics online.
Increasing confidence in proteomic spectral deconvolution through mass defect
Authors: Clasen Milan A , Kurt Louise U , Santos Marlon D M , Lima Diogo B , Liu Fan , Gozzo Fabio C , Barbosa Valmir C , Carvalho Paulo C 
Published: September 2022

Abstract

Motivation
Confident deconvolution of proteomic spectra is critical for several applications such as de novo sequencing, cross-linking mass spectrometry and handling chimeric mass spectra.

Results
In general, all deconvolution algorithms may eventually report mass peaks that are not compatible with the chemical formula of any peptide. We show how to remove these artifacts by considering their mass defects. We introduce Y.A.D.A. 3.0, a fast deconvolution algorithm that can remove peaks with unacceptable mass defects. Our approach is effective for polypeptides with less than 10 kDa, and its essence can be easily incorporated into any deconvolution algorithm.

Availability and implementation
Y.A.D.A. 3.0 is freely available for academic use at http://patternlabforproteomics.org/yada3.

Supplementary information
Supplementary information is available at Bioinformatics online.
Diaphragmatic pacing for the prevention of sudden unexpected death in epilepsy
Authors: Purnell Benton S , Braun Alexander , Fedele Denise , Murugan Madhuvika , Boison Detlev 
Published: September 2022

AbstractSudden unexpected death in epilepsy is the leading cause of epilepsy related death. Currently, there are no reliable methods for preventing sudden unexpected death in epilepsy. The precise pathophysiology of sudden unexpected death in epilepsy is unclear; however, convergent lines of evidence suggest that seizure-induced respiratory arrest plays a central role. It is generally agreed that sudden unexpected death in epilepsy could be averted if the patient could be rapidly ventilated following the seizure. The diaphragm is a muscle in the chest which contracts to draw air into the lungs. Diaphragmatic pacing is a surgical intervention which facilitates normal ventilation in situations, such as spinal cord injury and sleep apnoea, in which endogenous respiration would be inadequate or non-existent. In diaphragmatic pacing, electrodes are implanted directly onto diaphragm or adjacent to the phrenic nerves which innervate the diaphragm. These electrodes are then rhythmically stimulated, thereby eliciting contractions of the diaphragm which emulate endogenous breathing. The goal of this study was to test the hypothesis that seizure-induced respiratory arrest and death can be prevented with diaphragmatic pacing. Our approach was to induce respiratory arrest using maximal electroshock seizures in adult, male, C57BL6 mice outfitted with EEG and diaphragmatic electrodes (n = 8 mice). In the experimental group, the diaphragm was stimulated to exogenously induce breathing. In the control group, no stimulation was applied. Breathing and cortical electrographic activity were monitored using whole body plethysmography and EEG, respectively. A majority of the animals that did not receive the diaphragmatic pacing intervention died of seizure-induced respiratory arrest. Conversely, none of the animals that received the diaphragmatic pacing intervention died. Diaphragmatic pacing improved postictal respiratory outcomes (two-way ANOVA, P &lt; 0.001) and reduced the likelyhood of seizure-induced death (Fisher’s exact test, P = 0.026). Unexpectedly, diaphragmatic pacing did not instantly restore breathing during the postictal period, potentially indicating peripheral airway occlusion by laryngospasm. All diaphragmatically paced animals breathed at some point during the pacing stimulation. Two animals took their first breath prior to the onset of pacing and some animals had significant apnoeas after the pacing stimulation. Sudden unexpected death in epilepsy results in more years of potential life lost than any other neurological condition with the exception of stroke. By demonstrating that seizure-induced respiratory arrest can be prevented by transient diaphragmatic pacing in animal models we hope to inform the development of closed-loop systems capable of detecting and preventing sudden unexpected death in epilepsy.
Delta-band neural tracking primarily reflects rule-based chunking instead of semantic relatedness between words
Authors: Lu Yuhan , Jin Peiqing , Ding Nai , Tian Xing 
Published: September 2022

AbstractIt is debated whether cortical responses matching the time scales of phrases and sentences mediate the mental construction of the syntactic chunks or are simply caused by the semantic properties of words. Here, we investigate to what extent delta-band neural responses to speech can be explained by semantic relatedness between words. To dissociate the contribution of semantic relatedness from sentential structures, participants listened to sentence sequences and paired-word sequences in which semantically related words repeated at 1 Hz. Semantic relatedness in the 2 types of sequences was quantified using a word2vec model that captured the semantic relation between words without considering sentential structure. The word2vec model predicted comparable 1-Hz responses with paired-word sequences and sentence sequences. However, empirical neural activity, recorded using magnetoencephalography, showed a weaker 1-Hz response to paired-word sequences than sentence sequences in a word-level task that did not require sentential processing. Furthermore, when listeners applied a task-related rule to parse paired-word sequences into multi-word chunks, 1-Hz response was stronger than that in word-level task on the same sequences. Our results suggest that cortical activity tracks multi-word chunks constructed by either syntactic rules or task-related rules, whereas the semantic relatedness between words contributes only in a minor way.
Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination and Booster on Coronavirus Disease 2019 (COVID-19) Symptom Severity Over Time in the COVID-OUT Trial
Authors: Boulware David R , Murray Thomas A , Proper Jennifer L , Tignanelli Christopher J , Buse John B , Liebovitz David M , Nicklas Jacinda M , Cohen Kenneth , Puskarich Michael A , Belani Hrishikesh K , Siegel Lianne K , Klatt Nichole R , Odde David J , Karger Amy B , Ingraham Nicholas E , Hartman Katrina M , Rao Via , Hagen Aubrey A , Patel Barkha , Fenno Sarah L , Avula Nandini , Reddy Neha V , Erickson Spencer M , Lindberg Sarah , Fricton Regina , Lee Samuel , Zaman Adnin , Saveraid Hanna G , Tordsen Walker J , Pullen Matthew F , Sherwood Nancy E , Huling Jared D , Bramante Carolyn T ,   for the COVID-OUT study team
Published: September 2022

Abstract

Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has decreasing protection from acquiring any infection with emergence of new variants; however, vaccination continues to protect against progression to severe coronavirus disease 2019 (COVID-19). The impact of vaccination status on symptoms over time is less clear.

Methods
Within a randomized trial on early outpatient COVID-19 therapy testing metformin, ivermectin, and/or fluvoxamine, participants recorded symptoms daily for 14 days. Participants were given a paper symptom diary allowing them to circle the severity of 14 symptoms as none (0), mild (1), moderate (2), or severe (3). This is a secondary analysis of clinical trial data on symptom severity over time using generalized estimating equations comparing those unvaccinated, SARS-CoV-2 vaccinated with primary vaccine series only, or vaccine-boosted.

Results
The parent clinical trial prospectively enrolled 1323 participants, of whom 1062 (80%) prospectively recorded some daily symptom data. Of these, 480 (45%) were unvaccinated, 530 (50%) were vaccinated with primary series only, and 52 (5%) vaccine-boosted. Overall symptom severity was least for the vaccine-boosted group and most severe for unvaccinated at baseline and over the 14 days (P &lt; .001). Individual symptoms were least severe in the vaccine-boosted group including cough, chills, fever, nausea, fatigue, myalgia, headache, and diarrhea, as well as smell and taste abnormalities. Results were consistent over Delta and Omicron variant time periods.

Conclusions
SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19, which abated the quickest over time.
Clinical Trial Registration. NCT04510194.
Effectiveness of Ultraviolet-C Disinfection on Hospital-Onset Gram-Negative Rod Bloodstream Infection: A Nationwide Stepped-Wedge Time-Series Analysis
Authors: Goto Michihiko , Hasegawa Shinya , Balkenende Erin C , Clore Gosia S , Safdar Nasia , Perencevich Eli N ,   VA-CDC Practice-Based Research Network, Bradley Suzanne F , Morgan Daniel , Gupta Kalpana , Hostler Christopher , Evans Charlesnika , Goetz Matthew , Reisinger Heather , Safdar Nasia , Lira Gio J Baracco , DeVries Aaron , Harris Bryan , Bittner Marvin , Pfeiffer Christopher , Rubin Michael , Cadena-Zuluaga Jose , Suda Katie 
Published: September 2022

Abstract

Background
The effectiveness of enhanced terminal room cleaning with ultraviolet C (UV-C) disinfection in reducing gram-negative rod (GNR) infections has not been well evaluated. We assessed the association of implementation of UV-C disinfection systems with incidence rates of hospital-onset (HO) GNR bloodstream infection (BSI).

Methods
We obtained information regarding UV-C use and the timing of implementation through a survey of all Veterans Health Administration (VHA) hospitals providing inpatient acute care. Episodes of HO-GNR BSI were identified between January 2010 and December 2018. Bed days of care (BDOC) was used as the denominator. Over-dispersed Poisson regression models were fitted with hospital-specific random intercept, UV-C disinfection use for each month, baseline trend, and seasonality as explanatory variables. Hospitals without UV-C use were also included to the analysis as a nonequivalent concurrent control group.

Results
Among 128 VHA hospitals, 120 provided complete survey responses with 40 reporting implementations of UV-C systems. We identified 13 383 episodes of HO-GNR BSI and 24 141 378 BDOC. UV-C use was associated with a lower incidence rate of HO-GNR BSI (incidence rate ratio: 0.813; 95% confidence interval: .656–.969; P = .009). There was wide variability in the effect size of UV-C disinfection use among hospitals.

Conclusions
In this large quasi-experimental analysis within the VHA System, enhanced terminal room cleaning with UV-C disinfection was associated with an approximately 19% lower incidence of HO-GNR BSI, with wide variability in effectiveness among hospitals. Further studies are needed to identify the optimal implementation strategy to maximize the effectiveness of UV-C disinfection technology.
Impact of Enterococcus faecalis Endocarditis Treatment on Risk of Relapse
Authors: Danneels Pierre , Hamel Jean-François , Picard Léa , Rezig Schéhérazade , Martinet Pauline , Lorleac’h Aurélien , Talarmin Jean-Philippe , Buzelé Rodolphe , Guimard Thomas , Le Moal Gwenaël , Brochard-Libois Julia , Beaudron Aurélie , Letheulle Julien , Codde Cyrielle , Chenouard Rachel , Boutoille David , Lemaignen Adrien , Bernard Louis , Cattoir Vincent , Dubée Vincent ,   the EFEMER study group, Danneels Pierre , Dubee Vincent , HAMEL Jean-François , Kempf Marie , Chenouard Rachel , Rihet Camille , Vannier Clémence , Beaudron Aurélie , Perez Lucia , Boutoille David , Leroy Anne-Gaëlle , Bernard Louis , Lemaignen Adrien , Lartigue Marie Frédérique , Brun Cécile Le , Cattoir Vincent , Revest Matthieu , Picard Léa , Poussier Léa , Moaligou Camile , Nogues Sophie , Sassi Asma Zouari , Guérin François , Moal Gwenaël Le , Plouzeau-Jayle Chloé , Talarmin Jean-Philippe , Fangous Marie-Sarah , Codde Cyrielle , Faucher Jean-François , Brochard-Libois Julia , Guimard Thomas , Pelerin Hélène , Berthome Hélène , Buzele Rodolphe , Lorleac'h Aurélien , Rezig Scheherazade , Martinet Pauline , Jan Didier , Letheulle Julien , Turnier Paul Le 
Published: September 2022

Abstract

Background
Enterococcus faecalis infective endocarditis (EFIE) is characterized by a higher frequency of relapses than other infective endocarditis. The role of the treatment on its occurrence remains poorly understood. The aim of this study was to investigate whether the antibiotic regimen could impact the risk of relapse in EFIE.

Materials
This was a multicenter retrospective study of patients diagnosed with definite EFIE between 2015 and 2019 in 14 French hospitals. The primary endpoint was the occurrence of relapses within the year following endocarditis diagnosis. As death was a competing risk for relapse, Fine and Gray models were used for studying risk factors and impact of treatment.

Results
Of the 279 patients included, 83 (29.7%) received the amoxicillin-gentamicin (A-G) combination, 114 (40.9%) amoxicillin-ceftriaxone (A-C), 63 (22.6%) A-G and A-C (A-G/A-C) sequentially, 9 (3.2%) amoxicillin (A), and 10 received other treatments. One-year-relapse rate was 9.3% (26 patients). Relapse occurred after a median delay of 107 days from EFIE diagnosis; 6 occurred after 6 months, and 6 were diagnosed by blood cultures in asymptomatic patients. In multivariate analysis, surgery during treatment was a protective factor against one-year relapse and death.
The cumulative incidence of relapse 1 year after endocarditis was 46.2% for patients treated with amoxicillin, 13.4% with A-G, 14.7% with A-C, and 4.3% with A-G/A-C (P≥.05 in multivariate analysis).

Conclusions
Relapses after treatment of EFIE are frequent, frequently asymptomatic, and may occur more than 6 months after the initial episode.
Tofacitinib for the Treatment of Ulcerative Colitis: An Integrated Summary of up to 7.8 Years of Safety Data from the Global Clinical Programme
Authors: Sandborn William J , D’Haens Geert R , Sands Bruce E , Panaccione Remo , Ng Siew C , Lawendy Nervin , Kulisek Nicole , Modesto Irene , Guo Xiang , Mundayat Rajiv , Su Chinyu , Vranic Ivana , Panés Julian 
Published: September 2022

AbstractBackground and AimsTofacitinib is an oral small molecule Janus kinase [JAK] inhibitor for the treatment of ulcerative colitis. We report an integrated summary of tofacitinib safety [exposure: ≤7.8 years] from the global clinical programme.MethodsPatients receiving tofacitinib 5 or 10 mg twice daily [BID] from completed phase [P]2/3 placebo-controlled studies, an open-label, long-term extension study [final data cut-off: August 24, 2020], and interim analysis of a P3b/4 study (interim data cut-off: February 20, 2020; Overall plus P3b/4 [2020] Cohort) were included. Proportions with adverse events [AEs] and serious AEs, and incidence rates [IRs; unique patients with events/100 patient-years] for deaths and AEs of special interest [AESI] were evaluated. Opportunistic infections, malignancies, major adverse cardiovascular events [MACE] and gastrointestinal perforations were adjudicated.ResultsIn total, 1157 patients received one or more dose of tofacitinib (mean duration: 946.9 days); 955/1157 [83%] received a predominant dose of 10 mg BID; 412/1157 [35.6%] received tofacitinib for &gt;4 years; 992/1157 [85.7%] had AEs, 244/1157 [21.1%] had serious AEs and 134/1157 (11.6%) discontinued use due to AEs. IRs [95% confidence intervals] for all tofacitinib doses were: deaths, 0.23 [0.09–0.46]; serious infections, 1.69 [1.26–2.21]; herpes zoster [non-serious and serious], 3.30 [2.67–4.04]; opportunistic infections, 1.03 [0.70–1.46]; malignancies (excluding non-melanoma skin cancer [NMSC]), 0.84 [0.55–1.24]; NMSC, 0.73 [0.45–1.10]; MACE, 0.29 [0.13–0.55]; deep vein thrombosis, 0.03 [0.00–0.18]; pulmonary embolism, 0.19 [0.07–0.42]; gastrointestinal perforations, 0.10 [0.02–0.28].ConclusionsAESI IRs were stable to 7.8 years and generally &lt;2.0 in the Overall plus P3b/4 [2020] Cohort, with the exception of herpes zoster [a known risk of tofacitinib treatment]. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304JCC Topic/keyword selection: 3. Clinical trials
Case report of a patient with congenital long QT syndrome Type 2 presenting with electrical storm: do not judge a book by its cover!
Authors: Lawin Dennis , Poudel Madan Raj , Lawrenz Thorsten , Stellbrink Christoph 
Published: September 2022

Abstract

Background
Patients with congenital long QT syndrome (LQTS) are at high risk for sudden cardiac death (SCD). Although several triggers can provoke ventricular fibrillation (VF) in patients suffering from LQTS acquired heart disease in addition to LQTS should not be overlooked.

Case summary
We present a case of a 47-year-old female patient who was diagnosed with congenital LQTS Type 2 at the age of 23 after surviving SCD. At that time, she underwent implantable cardioverter-defibrillator (ICD) implantation and was free of events for 24 years. Recently, the patient was referred to our institution after suffering from an ICD shock during sleep. Upon arrival she developed electrical storm and received overall six ICD shocks. The initial electrocardiogram (ECG) showed atrially triggered ventricular pacing. However, distinct ST segment elevations in the inferior leads could be observed. Thus, coronary angiography was immediately performed and showed subtotal occlusion of the right coronary artery, which was treated by drug-eluting stent implantation. Atrioventricular conduction immediately resumed after revascularization and the following non-paced ECG revealed a prolonged QT interval. Laboratory measurements confirmed acute myocardial infarction with elevated cardiac enzymes. The patient was put on betablockers, dual antiplatelet therapy, and statins and discharged in good condition.

Discussion
This case report highlights that diagnostic work-up in patients with LQTS presenting with VF should always include the search for additional acquired heart disease such as myocardial infarction, as a potential trigger for electrical storm. Moreover, signs of ischaemia can be discerned even in a paced ECG which should lead to immediate cardiac catheterization.