bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward Open and Reproducible Epidemiology
Authors: Mathur Maya B , Fox Matthew P 
Published: January 2023

AbstractStarting in the 2010s, researchers in the experimental social sciences rapidly began to adopt increasingly open and reproducible scientific practices. These practices include publicly sharing deidentified data when possible, sharing analytical code, and preregistering study protocols. Empirical evidence from the social sciences suggests such practices are feasible, can improve analytical reproducibility, and can reduce selective reporting. In academic epidemiology, adoption of open-science practices has been slower than in the social sciences (with some notable exceptions, such as registering clinical trials). Epidemiologic studies are often large, complex, conceived after data have already been collected, and difficult to replicate directly by collecting new data. These characteristics make it especially important to ensure their integrity and analytical reproducibility. Open-science practices can also pay immediate dividends to researchers’ own work by clarifying scientific reasoning and encouraging well-documented, organized workflows. We consider how established epidemiologists and early-career researchers alike can help midwife a culture of open science in epidemiology through their research practices, mentorship, and editorial activities.
ABSP: an automated R tool to efficiently analyze region-specific CpG methylation from bisulfite sequencing PCR
Authors: Denoulet Marie , Brulé Mathilde , Anquez François , Vincent Audrey , Schnipper Julie , Adriaenssens Eric , Toillon Robert-Alain , Le Bourhis Xuefen , Lagadec Chann 
Published: January 2023

Abstract

Motivation
Nowadays, epigenetic gene regulations are studied in each part of the biology, from embryonic development to diseases such as cancers and neurodegenerative disorders. Currently, to quantify and compare CpG methylation levels of a specific region of interest, the most accessible technique is the bisulfite sequencing PCR (BSP). However, no existing user-friendly tool is able to analyze data from all approaches of BSP. Therefore, the most convenient way to process results from the direct sequencing of PCR products (direct-BSP) is to manually analyze the chromatogram traces, which is a repetitive and prone to error task.

Results
Here, we implement a new R-based tool, called ABSP for analysis of bisulfite sequencing PCR, providing a complete analytic process of both direct-BSP and cloning-BSP data. It uses the raw sequencing trace files (.ab1) as input to compute and compare CpG methylation percentages. It is fully automated and includes a user-friendly interface as a built-in R shiny app, quality control steps and generates publication-ready graphics.

Availability and implementation
The ABSP tool and associated data are available on GitHub at https://github.com/ABSP-methylation-tool/ABSP.

Supplementary information
Supplementary data are available at Bioinformatics online.
EWF: simulating exact paths of the Wright–Fisher diffusion
Authors: Sant Jaromir , Jenkins Paul A , Koskela Jere , Spanò Dario 
Published: January 2023

Abstract

Motivation
The Wright–Fisher diffusion is important in population genetics in modelling the evolution of allele frequencies over time subject to the influence of biological phenomena such as selection, mutation and genetic drift. Simulating the paths of the process is challenging due to the form of the transition density. We present EWF, a robust and efficient sampler which returns exact draws for the diffusion and diffusion bridge processes, accounting for general models of selection including those with frequency dependence.

Results
Given a configuration of selection, mutation and endpoints, EWF returns draws at the requested sampling times from the law of the corresponding Wright–Fisher process. Output was validated by comparison to approximations of the transition density via the Kolmogorov–Smirnov test and QQ plots.

Availability and implementation
All softwares are available at https://github.com/JaroSant/EWF.

Supplementary information
Supplementary data are available at Bioinformatics online.
Dealing with dimensionality: the application of machine learning to multi-omics data
Authors: Feldner-Busztin Dylan , Firbas Nisantzis Panos , Edmunds Shelley Jane , Boza Gergely , Racimo Fernando , Gopalakrishnan Shyam , Limborg Morten Tønsberg , Lahti Leo , de Polavieja Gonzalo G 
Published: January 2023

AbstractMotivationMachine learning (ML) methods are motivated by the need to automate information extraction from large datasets in order to support human users in data-driven tasks. This is an attractive approach for integrative joint analysis of vast amounts of omics data produced in next generation sequencing and other -omics assays. A systematic assessment of the current literature can help to identify key trends and potential gaps in methodology and applications. We surveyed the literature on ML multi-omic data integration and quantitatively explored the goals, techniques and data involved in this field. We were particularly interested in examining how researchers use ML to deal with the volume and complexity of these datasets.ResultsOur main finding is that the methods used are those that address the challenges of datasets with few samples and many features. Dimensionality reduction methods are used to reduce the feature count alongside models that can also appropriately handle relatively few samples. Popular techniques include autoencoders, random forests and support vector machines. We also found that the field is heavily influenced by the use of The Cancer Genome Atlas dataset, which is accessible and contains many diverse experiments.Availability and implementationAll data and processing scripts are available at this GitLab repository: https://gitlab.com/polavieja_lab/ml_multi-omics_review/ or in Zenodo: https://doi.org/10.5281/zenodo.7361807.Supplementary informationSupplementary data are available at Bioinformatics online.
PANACEA: network-based methods for pharmacotherapy prioritization in personalized oncology
Authors: Ulgen Ege , Ozisik Ozan , Sezerman Osman Ugur 
Published: January 2023

Abstract

Motivation
Identifying appropriate pharmacotherapy options from genomics results is a significant challenge in personalized oncology. However, computational methods for prioritizing drugs are underdeveloped. With the hypothesis that network-based approaches can improve the performance by extending the use of potential drug targets beyond direct interactions, we devised two network-based methods for personalized pharmacotherapy prioritization in cancer.

Results
We developed novel personalized drug prioritization approaches, PANACEA: PersonAlized Network-based Anti-Cancer therapy EvaluAtion. In PANACEA, initially, the protein interaction network is extended with drugs, and a driverness score is assigned to each altered gene. For scoring drugs, either (i) the ‘distance-based’ method, incorporating the shortest distance between drugs and altered genes, and driverness scores, or (ii) the ‘propagation’ method involving the propagation of driverness scores via a random walk with restart framework is performed. We evaluated PANACEA using multiple datasets, and demonstrated that (i) the top-ranking drugs are relevant for cancer pharmacotherapy using TCGA data; (ii) drugs that cancer cell lines are sensitive to are identified using GDSC data; and (iii) PANACEA can perform adequately in the clinical setting using cases with known drug responses. We also illustrate that the proposed methods outperform iCAGES and PanDrugs, two previous personalized drug prioritization approaches.

Availability and implementation
The corresponding R package is available on GitHub. (https://github.com/egeulgen/PANACEA.git).

Supplementary information
Supplementary data are available at Bioinformatics online.
Reconstructive techniques following low anterior resection for carcinoma of the rectum: meta-analysis
Authors: Mathew Anvin , Ramachandra Deepti , Goyal Anuj , Nariampalli Karthyarth Mithun , Joseph Princy , Raj Rakesh Nirjhar , Kaushal Gourav , Agrawal Abhishek , Singh Bhadoria Ajeet , Dhar Puneet 
Published: January 2023

Abstract

Background
Multiple trials have compared reconstruction techniques used following the resection of distal rectal cancers, including straight colorectal anastomosis (SCA), colonic J pouch (CJP), side-to-end anastomosis (SEA), and transverse coloplasty (TCP). The latest meta-analysis on the subject concluded that all the reservoir techniques produce equally good surgical and functional outcomes compared with SCA. Numerous trials have been published in this regard subsequently. Hence, a network analysis (NMA) was performed to rank these techniques.

Methods
A literature search of MEDLINE, Embase, and the Cochrane Library from their inception until April 2021 was conducted to identify randomized trials. Functional and surgical outcome data were pooled. ORs and standardized mean differences (MDs) were used as pooled effect size measures. A frequentist NMA model was used.

Results
Thirty-two trials met the eligibility criteria comprising 3072 patients. CJP showed better functional outcomes, such as low stool frequency and better incontinence score, both in the short term (stool frequency, MD −2.06, P &lt; 0.001; incontinence, MD −1.17, P = 0.007) and intermediate term (stool frequency, MD −0.81, P = 0.021; incontinence MD −0.56, P = 0.083). Patients with an SEA (long-term OR 4.37; P = 0.030) or TCP (long-term OR 5.79; P &lt; 0.001) used more antidiarrheal medications constantly. The urgency and sensation of incomplete evacuation favoured CJP in the short term. TCP was associated with a higher risk of anastomotic leakage (OR 12.85; P &lt; 0.001) and stricture (OR 3.21; P = 0.012).

Conclusion
Because of its better functional outcomes, CJP should be the reconstruction technique of choice. TCP showed increased anastomotic leak and stricture rates, warranting judicious use.
Hotspots within a hotspot: evolutionary measures unveil interesting biogeographic patterns in threatened coastal forests in Chile
Authors: Mardones Daniela , Scherson Rosa A 
Published: January 2023

Abstract
Given the continuous loss of biodiversity, there is an urgent need to study its patterns to generate conservation measures. Complementing traditional biodiversity measures with indices that incorporate evolutionary aspects such as phylogenetic diversity or phylogenetic endemism (PD or PE) allows us to infer possible historical processes that could explain the conformation of current biodiversity. In this study, patterns of richness and endemism were determined and contrasted with the evolutionary indices PD, PE, PDres (residual PD), RPD (relative PD) and RPE (relative PE) for the woody flora in a latitudinal gradient (30°S to 40°S) in the Chilean coastal range. A phylogenetic tree was constructed using three DNA regions to calculate evolutionary indices (PD and PE) and compare them at different taxonomic levels. The results of PD and PE were spatially consistent with those of richness and endemism, but evolutionarily important sites were discovered. PD-derived indices indicate three evolutionary hotspots: a cradle-type site with a predominance of neoendemics (generating recent diversity) at 33°S, three museum-type sites with a predominance of palaeoendemics (maintaining relict diversity) at 30°S, 38°S and 40°S and one with high PD and PE at 37°S. We found evolutionary hotspots within the hotspot of Central Chile with different characteristics. Incorporating measures that consider the evolutionary aspect has important implications for the conservation of highly diverse and endemic areas.
Plasma biomarker profiles in autosomal dominant Alzheimer’s disease
Authors: Johansson Charlotte , Thordardottir Steinunn , Laffita-Mesa José , Rodriguez-Vieitez Elena , Zetterberg Henrik , Blennow Kaj , Graff Caroline 
Published: January 2023

AbstractEmerging plasma biomarkers of Alzheimer's disease might be non-invasive tools to trace early Alzheimer's disease-related abnormalities such as the accumulation of amyloid-beta peptides, neurofibrillary tau tangles, glial activation and neurodegeneration. It is, however, unclear which pathological processes in the CNS can be adequately detected by peripheral measurements and whether plasma biomarkers are equally applicable in both clinical and preclinical phases. Here we aimed to explore the timing and performance of plasma biomarkers in mutation carriers compared to non-carriers in autosomal dominant Alzheimer's disease.Samples (n = 164) from mutation carriers (n = 33) and non-carriers (n = 42) in a Swedish cohort of autosomal dominant Alzheimer's disease (APP p.KM670/671NL, APP p.E693G and PSEN1 p.H163Y) were included in explorative longitudinal analyses. Plasma phosphorylated tau (P-tau181), total tau (T-tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) concentrations were measured with a single-molecule array method as previously described. Plasma biomarkers were additionally correlated to Alzheimer's disease core biomarkers in the CSF.Results from the longitudinal analyses confirmed that plasma P-tau181, NfL and GFAP concentrations were higher in mutation carriers compared to non-carriers. This change was observed in the presymptomatic phase and detectable first as an increase in GFAP approximately 10 years before estimated symptom onset, followed by increased levels of P-tau181 and NfL closer to expected onset. Plasma P-tau181 levels were correlated to levels of P-tau181 and T-tau in the CSF.Altogether, plasma P-tau181, GFAP and NfL seem to be feasible biomarkers to detect different Alzheimer's disease-related pathologies already in presymptomatic individuals. Interestingly, changes in plasma GFAP concentrations were detected prior to P-tau181 and NfL. Our results suggest that plasma GFAP might reflect Alzheimer's disease pathology upstream to accumulation of tangles and neurodegeneration. The implications of these findings need additional validation, in particular because of the limited sample size.
Safety and Effectiveness of Ustekinumab for Crohn’s Disease in Japanese Post-marketing Surveillance in Biologic-Naive and -Experienced Conriemed
Authors: Nagano Katsumasa , Hata Erina , Asano Teita , Tsuchiya Hiroaki , Takagishi Masayuki , Yamazaki Hiroshi , Tominaga Sonoko , Matsumoto Takayuki 
Published: January 2023

AbstractBackgroundTo present the real-world evidence on the safety and effectiveness of ustekinumab (UST) through 52-week treatment for Crohn’s disease (CD) under an analysis of post-market surveillance data in Japan.MethodsThis prospective, post-marketing surveillance study was conducted in 341 patients from 91 medical facilities in Japan. Patients received UST 90 mg injected subcutaneously once every 12 weeks (or every 8 weeks if patients show weak effectiveness) after an induction dose given intravenously. Clinical response (100-point decrease in Crohn’s Disease Activity Index [CDAI] score), clinical remission (CDAI score of &lt;150), steroid-free clinical remission, C-reactive protein, endoscopy, physician global assessment, and adverse drug reactions (ADRs) were evaluated through 52 weeks.ResultsThe overall rate of clinical remission was 49.2% at week 8 and 56.0% at week 52. The rate of clinical remission in biologic-naive patients was 75.9% and 66.7% at weeks 8 and 52, respectively, whereas the rate in biologic-experienced patients was 41.4% and 52.6% at weeks 8 and 52, respectively. For 52 weeks, the overall incidence of ADRs and serious adverse drug reactions (SADRs) was 11.7% and 6.7%, respectively. The most frequently reported SADRs was worsening of CD (1.8%). In multivariate analysis, ADRs incidence was significantly lower in patients with ileal involvement of CD (odds ratio = 0.25, 95% CI 0.07–0.85, P = .026), although disease location has no association with effectiveness of UST.ConclusionsThe present study identified no new safety concerns and effectiveness for CD in Japanese patients treated with UST.
Retrograde venography to navigate an occluded subclavian vein to achieve cardiac resynchronization therapy upgrade via His bundle pacing: a case report
Authors: Pavitt Christopher , Luther Vishal , Lefroy David , Tanner Mark 
Published: January 2023

AbstractBackgroundGuidelines support upgrade to cardiac resynchronization therapy (CRT) through His-bundle pacing (HBP) in pacing-induced cardiomyopathy and moderate left ventricular systolic dysfunction (LVSD). Lead-related venous occlusion can represent an obstacle to upgrade procedures. We describe a technique to overcome venous occlusion through direct puncture of a collateral vein facilitating upgrade to HBP.Case summaryAn 84-year-old man with a right ventricular (RV) pacemaker was referred with New York Heart Association (NYHA) Class III breathlessness secondary to moderate LVSD (left ventricular ejection fraction [LVEF] 45%). Device interrogation revealed 100% RV pacing and AV-dyssynchrony. To optimize atrioventricular (AV) and interventricular (VV) synchrony a CRT upgrade with HBP was planned. Venography revealed an occluded left subclavian vein which was probed in a retrograde manner using a 6F MPA catheter from right femoral venous access. We were able to direct the catheter distal to the left brachio-cephalic vein and define the occlusion using contrast. A collateral branch was identified, a J-wire was left in this branch and venous access was secured at this medial subclavian site using the Seldinger technique. A right atrial lead was deployed and 69 cm ISI-1 His lead was deployed via a C315 sheath at the His-bundle. The resulted in non-selective HBP (Stim-QRS end 146 ms). There were no procedural complications. Two months later both symptoms and LV function (LVEF 55%) improved.DiscussionLead-related venous occlusion occurs frequently and can be probed in a retrograde manner from femoral venous access using contrast, facilitating direct percutaneous puncture of collateral venous branches to allow upgrade to CRT via HBP.
Cardiac sarcoidosis presenting with complex conduction abnormalities as the first manifestation of widespread systemic sarcoidosis: a case report
Authors: Müller Maximilian L , Poller Wolfgang , Skurk Carsten , Poddubnyy Denis , Siegmund Britta , Schneider Thomas , Landmesser Ulf , Heidecker Bettina 
Published: January 2023

Abstract

Background
Sarcoidosis is a granulomatous multi-organ disease of unknown aetiology. Despite being relatively rare, cardiac sarcoidosis constitutes a very important manifestation of sarcoidosis, as its symptoms regularly precede or occur in isolation of more prevalent ones, and as it is the main driver of mortality in systemic sarcoidosis.

Case summary
We present the case of a 37-year-old woman, in which clinically isolated cardiac sarcoidosis revealed widespread systemic sarcoidosis. Apart from constitutional symptoms and strong recurrent dizziness (i.e. near-syncopes), which persisted for multiple years already, our patient initially presented with complex conduction abnormalities, including a right bundle branch block, left anterior hemi-block, and atrioventricular block °1. Following inconclusive endomyocardial biopsies, performed due to detection of focal septal scarring on cardiac magnetic resonance imaging, an 18F-FDG-PET-CT, performed upon admission to our clinic, showed distinct hypermetabolic lesions indicative of active inflammation in various organs and raised suspicion of systemic sarcoidosis. Eventually, histopathological evidence of non-caseating granulomas in affected lymph nodes, extracted by bronchoscopy, confirmed the diagnosis of systemic sarcoidosis after reasonable exclusion of other granulomatous diseases. Immediate initiation of long-term immunosuppressive therapy led to almost complete remission, as monitored by consequential 18F-FDG-PET-CT scans.

Discussion
Unexplained complex conduction abnormalities in young patients may be a sign of sarcoidosis, even in isolation of more prevalent symptoms. Correct interpretation and prompt initiation of a structured interdisciplinary diagnostic workup, including 18F-FDG-PET-CT as the imaging modality of choice, are essential to initiate specific treatment and obviate the major risk of mortality resulting from cardiac sarcoidosis.
Switch to a bicarbonate-based Impella CP™ purge solution in a patient with haemothorax: a case report
Authors: Van Edom Charlotte , Van Puyvelde Tim , Jacobs Steven , Vandenbriele Christophe 
Published: January 2023

Abstract

Background
Percutaneous mechanical circulatory support (pMCS) by an Impella™ device implies the initiation of systemic anticoagulation to prevent systemic thrombotic complications and a purge fluid to prevent device blockage. Traditionally, unfractionated heparin (UFH) was used for both. In April 2022, the use of bicarbonate-based purge solution (BBPS) as an alternative to UFH in dextrose solution was approved by the Food and Drug Administration in case of contraindications for UFH.

Case summary
We present the case of a 73-year-old female that was admitted to the cardiac intensive care unit with cardiogenic shock, requiring upgrade with pMCS by an axillary Impella CP™. When she developed a severe haemothorax, all UFH was stopped and the purge was switched to BBPS-dextrose solution without increase in purge pressures nor development of haemolysis. The bleeding stagnated and the patient could be weaned from the Impella™ after 2 days.

Discussion
Here, we present the first case report of the switch to BBPS in an Impella CP™ supported patient with major bleeding since the FDA approval in April 2022. The switch to BBSP in addition with the administration of platelets and protamine resulted in cessation of the bleeding in this case.