bluuebunny/crossref_metadata_2025_split huggingface dataset:
A deep-learning-based RNA-seq germline variant caller
Authors: Cook Daniel E , Venkat Aarti , Yelizarov Dennis , Pouliot Yannick , Chang Pi-Chuan , Carroll Andrew , De La Vega Francisco M 
Published: June 2023

Abstract

Summary
RNA sequencing (RNA-seq) can be applied to diverse tasks including quantifying gene expression, discovering quantitative trait loci and identifying gene fusion events. Although RNA-seq can detect germline variants, the complexities of variable transcript abundance, target capture and amplification introduce challenging sources of error. Here, we extend DeepVariant, a deep-learning-based variant caller, to learn and account for the unique challenges presented by RNA-seq data. Our DeepVariant RNA-seq model produces highly accurate variant calls from RNA-sequencing data, and outperforms existing approaches such as Platypus and GATK. We examine factors that influence accuracy, how our model addresses RNA editing events and how additional thresholding can be used to facilitate our models’ use in a production pipeline.

Supplementary information
Supplementary data are available at Bioinformatics Advances online.
Markers of limbic system damage following SARS-CoV-2 infection
Authors: Thomasson Marine , Voruz Philippe , Cionca Alexandre , Jacot de Alcântara Isabele , Nuber-Champier Anthony , Allali Gilles , Benzakour Lamyae , Lalive Patrice H , Lövblad Karl-Olof , Braillard Olivia , Nehme Mayssam , Coen Matteo , Serratrice Jacques , Reny Jean-Luc , Pugin Jérôme , Guessous Idris , Landis Basile N , Griffa Alessandra , Van De Ville Dimitri , Assal Frederic , Péron Julie A 
Published: June 2023

Abstract
Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system–related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG Cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (P = 0.03 corrected), as did severe patients for disgust (P = 0.04 corrected) and irritation (P &lt; 0.01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or post-traumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.
Catheter-directed mechanical aspiration thrombectomy in a real-world pulmonary embolism population: a multicenter registry
Authors: Sławek-Szmyt Sylwia , Stępniewski Jakub , Kurzyna Marcin , Kuliczkowski Wiktor , Jankiewicz Stanisław , Kopeć Grzegorz , Darocha Szymon , Mroczek Ewa , Pietrasik Arkadiusz , Grygier Marek , Lesiak Maciej , Araszkiewicz Aleksander 
Published: June 2023

Abstract

Aims
High- (HR) and intermediate-high risk (IHR) pulmonary embolisms (PEs) are related to high early mortality and long-term sequelae. We aimed to describe clinical outcomes and adverse events in IHR and HR pulmonary embolism (PE) treated with catheter-directed mechanical thrombectomy (CDMT) in a real-world population.

Methods and Results
This study is a multicenter, prospective registry enrolling 110 PE patients treated with CDMT between 2019 and 2022. The CDMT was performed using the 8F Indigo (Penumbra, Alameda, CA, USA) system bilaterally in pulmonary arteries (PAs). The primary safety endpoints included device or PE-related death during the 48-h after CDMT, procedure-related major bleeding, or other major adverse events. Secondary safety outcomes were all-cause mortality during hospitalization or the follow-up. The primary efficacy outcomes were the reduction of PA pressures and change in the right-to-left ventricular (RV/L) ratio assessed in the imaging 24–48 h after the CDMT.
71.8% of patients had IHR PE and 28.2% HR PE. 11.8% of patients had a failure and 34.5% had contraindications to thrombolysis, and 2.7% had polytrauma. There was 0.9% intraprocedural death related to RV failure and 5.5% deaths within the first 48 h. CDMT was complicated by major bleeding in 1.8%, pulmonary artery injury in 1.8%, and ischaemic stroke in 0.9%. Immediate haemodynamic improvements included a 10.4 ± 7.8 mmHg (19.7%) drop in systolic PAP (P &lt; 0.0001), a 6.1 ± 4.2 mmHg (18.8%) drop in mean PAP, and 0.48 ± 0.4 (36%) drop in RV/LV ratio (P &lt; 0.0001).

Conclusion
These observational findings suggest that CDMT may improve hemodynamics with an acceptable safety profile in patients with IHR and HR PE.
Three-dimensional echocardiographic left ventricular strain analysis in Fabry disease: correlation with heart failure severity, myocardial scar, and impact on long-term prognosis
Authors: Marek Josef , Chocholová Barbora , Rob Daniel , Paleček Tomáš , Mašek Martin , Dostálová Gabriela , Linhart Aleš 
Published: June 2023

Abstract

Aims
Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis.

Methods and results
3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = −0.49, P &lt; 0.0001) than with 3D LV global circumferential strain (GCS, r = −0.38, P &lt; 0.001) or 3D LVEF (r = −0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75–0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324).

Conclusion
3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD.
Coronary angiography-derived index of microcirculatory resistance and evolution of infarct pathology after ST-segment-elevation myocardial infarction
Authors: Wang Xiao , Guo Qian , Guo Ruifeng , Guo Yingying , Yan Yan , Gong Wei , Zheng Wen , Wang Hui , Ai Hui , Que Bin , Xu Lei , Huo Yunlong , Fearon William F , Nie Shaoping 
Published: June 2023

Abstract

Aims
This study sought to evaluate the association of coronary angiography-derived index of microcirculatory resistance (angio-IMR) measured after primary percutaneous coronary intervention (PPCI) with the evolution of infarct pathology during 3-month follow-up after ST-segment-elevation myocardial infarction (STEMI).

Methods and Results
Patients with STEMI undergoing PPCI were prospectively enrolled between October 2019 and August 2021. Angio-IMR was calculated using computational flow and pressure simulation immediately after PPCI. Cardiac magnetic resonance (CMR) imaging was performed at a median of 3.6 days and 3 months. A total of 286 STEMI patients (mean age 57.8 years, 84.3% men) with both angio-IMR and CMR at baseline were included. High angio-IMR (&gt;40 U) occurred in 84 patients (29.4%) patients. Patients with angio-IMR &gt;40 U had a higher prevalence and extent of MVO. An angio-IMR &gt;40 U was a multivariable predictor of infarct size with a three-fold higher risk of final infarct size &gt;25% (adjusted OR 3.00, 95% CI 1.23–7.32, P = 0.016). Post-procedure angio-IMR &gt;40 U significantly predicted presence (adjusted OR 5.52, 95% CI 1.65–18.51, P = 0.006) and extent (beta coefficient 0.27, 95% CI 0.01–0.53, P = 0.041) of myocardial iron at follow-up. Compared with patients with angio-IMR ≤40 U, those with angio-IMR &gt;40 U had less regression of infarct size and less resolution of myocardial iron at follow-up.

Conclusions
Angio-IMR immediately post-PPCI showed a significant association with the extent and evolution of infarct pathology. An angio-IMR &gt;40 U indicated extensive microvascular damage with less regression of infarct size and more persistent iron at follow-up.
Progression from different blood glucose states to cardiovascular diseases: a prospective study based on multi-state model
Authors: Chen Yarong , Xu Lulu , Cheng Zhiyuan , Zhang Desheng , Yang Jingli , Yin Chun , Li Siyu , Li Jing , Hu Yujia , Wang Yufeng , Liu Yanyan , Wang Zhongge , Zhang Lizhen , Chen Ruirui , Dou Qian , Bai Yana 
Published: June 2023

Abstract

Aims
To quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cardiovascular death, and the effects of risk factors on the rates of transition.

Methods and results
We used data from the Jinchang Cohort of 42 585 adults aged 20–88 free of coronary heart disease (CHD) and stroke at baseline. A multistate model was applied for analysing the progression of CVD and its relation to various risk factors. During a median follow-up of 7 years, 7498 participants developed pre-diabetes, 2307 developed T2DM, 2499 developed CVD, and 324 died from CVD. Among 15 postulated transitions, transition from comorbid CHD and stroke to cardiovascular death had the highest rate (157.21/1000 person-years), followed by transition from stroke alone to cardiovascular death (69.31/1000 person-years) and transition from pre-diabetes to normoglycaemia (46.51/1000 person-years). Pre-diabetes had a sojourn time of 6.77 years, and controlling weight, blood lipids, blood pressure, and uric acid within normal limits may promote reversion to normoglycaemia. Among transitions to CHD alone and stroke alone, transition from T2DM had the highest rate (12.21/1000 and 12.16/1000 person-years), followed by transition from pre-diabetes (6.81/1000 and 4.93/1000 person-years) and normoglycaemia (3.28/1000 and 2.39/1000 person-years). Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions.

Conclusion
Pre-diabetes was the optimal intervention stage in the disease trajectory. The derived transition rates, sojourn time, and influence factors could provide scientific support for the primary prevention of both T2DM and CVD.
Single-Cell Heterogeneity in Snake Venom Expression Is Hardwired by Co-Option of Regulators from Progressively Activated Pathways
Authors: Westfall Aundrea K , Gopalan Siddharth S , Perry Blair W , Adams Richard H , Saviola Anthony J , Mackessy Stephen P , Castoe Todd A 
Published: June 2023

Abstract
The ubiquitous cellular heterogeneity underlying many organism-level phenotypes raises questions about what factors drive this heterogeneity and how these complex heterogeneous systems evolve. Here, we use single-cell expression data from a Prairie rattlesnake (Crotalus viridis) venom gland to evaluate hypotheses for signaling networks underlying snake venom regulation and the degree to which different venom gene families have evolutionarily recruited distinct regulatory architectures. Our findings suggest that snake venom regulatory systems have evolutionarily co-opted trans-regulatory factors from extracellular signal-regulated kinase and unfolded protein response pathways that specifically coordinate expression of distinct venom toxins in a phased sequence across a single population of secretory cells. This pattern of co-option results in extensive cell-to-cell variation in venom gene expression, even between tandemly duplicated paralogs, suggesting this regulatory architecture has evolved to circumvent cellular constraints. While the exact nature of such constraints remains an open question, we propose that such regulatory heterogeneity may circumvent steric constraints on chromatin, cellular physiological constraints (e.g., endoplasmic reticulum stress or negative protein–protein interactions), or a combination of these. Regardless of the precise nature of these constraints, this example suggests that, in some cases, dynamic cellular constraints may impose previously unappreciated secondary constraints on the evolution of gene regulatory networks that favors heterogeneous expression.
ricu: R’s interface to intensive care data
Authors: Bennett Nicolas , Plečko Drago , Ukor Ida-Fong , Meinshausen Nicolai , Bühlmann Peter 
Published: June 2023

Abstract

Objective
To develop a unified framework for analyzing data from 5 large publicly available intensive care unit (ICU) datasets.

Findings
Using 3 American (Medical Information Mart for Intensive Care III, Medical Information Mart for Intensive Care IV, electronic ICU) and 2 European (Amsterdam University Medical Center Database, High Time Resolution ICU Dataset) databases, we constructed a mapping for each database to a set of clinically relevant concepts, which are grounded in the Observational Medical Outcomes Partnership Vocabulary wherever possible. Furthermore, we performed synchronization in the units of measurement and data type representation. On top of this, we built functionality, which allows the user to download, set up, and load data from all of the 5 databases, through a unified Application Programming Interface. The resulting ricu R-package represents the computational infrastructure for handling publicly available ICU datasets, and its latest release allows the user to load 119 existing clinical concepts from the 5 data sources.

Conclusion
The ricu R-package (available on GitHub and CRAN) is the first tool that enables users to analyze publicly available ICU datasets simultaneously (datasets are available upon request from respective owners). Such an interface saves researchers time when analyzing ICU data and helps reproducibility. We hope that ricu can become a community-wide effort, so that data harmonization is not repeated by each research group separately. One current limitation is that concepts were added on a case-to-case basis, and therefore the resulting dictionary of concepts is not comprehensive. Further work is needed to make the dictionary comprehensive.
Hormones and carbohydrates synergistically regulate the formation of swollen roots in a Chinese cabbage translocation line
Authors: Ren Xiaojing , Ma Wei , Xuan Shuxin , Li Dandan , Wang Yanhua , Xu Yuanchao , Feng Daling , Zhao Jianjun , Chen Xueping , Luo Shuangxia , Shen Shuxing , Gu Aixia 
Published: June 2023

Abstract
The genus Brassica contains a rich diversity of species and morphological types, including leaf, root, and oil crops, all of which show substantial phenotypic variation. Both Chinese cabbage and cabbage are typical leaf-type crops with normal roots. We created translocation lines based on interspecific crosses between Chinese cabbage and cabbage and identified qdh225, which exhibited a swollen-root phenotype. The swollen root of qdh225 contained a large number of granular substances, and the formation of its irregular morphological tissue was caused by a thickening of the phloem. Transcriptomic and metabolomic data suggested that differential expression of genes encoding nine types of enzymes involved in starch and sucrose metabolism caused changes in starch synthesis and degradation in the swollen root. These genes jointly regulated sucrose and starch levels, leading to significant enrichment of starch and soluble proteins in the swollen root and a reduction in the content of soluble sugars such as d-glucose and trehalose 6-phosphate. A significant increase in auxin (IAA) and abscisic acid (ABA) contents and a decrease in gibberellin (GA) content in the swollen root likely promoted the differential expression of genes associated with hormone signal transduction, thereby regulating the development of the swollen root. Taken together, our data suggest that accumulation of IAA and ABA and reduction in GA promote swollen root formation by regulating hormone-mediated signaling, leading to a thickening of phloem, root enlargement, and substantial accumulation of starch and soluble proteins. The latter provide materials, energy, and nutrient sources for the development of swollen roots.
The modified capsular arthroplasty for young patients with developmental dislocation of the hip
Authors: Zhang Zhendong , Luo Dianzhong , Cheng Hui , Zhang Hong , Zhang Jianli , Ren Ningtao , Li Yong , Ganz Reinhold 
Published: June 2023

ABSTRACT
The present study aimed to investigate the clinical results of the modified Codivilla–Hey Groves–Colonna capsular arthroplasty in the treatment of young patients with developmental dislocation of the hip. We retrospectively evaluated 90 patients (92 hips) who underwent the modified capsular arthroplasty from June 2012 to June 2021. Hips were evaluated using the modified hip Harris score (mHHS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and the 12-item International Hip Outcome Tool (iHOT-12). The Tönnis osteoarthritis grade and the Severin classification system were used to assess the radiographic outcomes. The average age was 15.7 years (range: 8–26 years). The mean pre-operative mHHS, the WOMAC score and the iHOT-12 score were 83.03, 14.05 and 52.79, respectively. The patients were followed for a mean of 41.1 months (range: 12.1–120.9 months). The patients had a mean mHHS of 83.61 (range: 31.2–97), a WOMAC score of 16.41 (range: 0–51) and an iHOT-12 score of 64.81 (range: 12.9–98.2) at the final follow-up. Capsular thickness had a positive predication on the final functional outcomes. The excellent/good rate of radiological reduction was 79.3%. More than 60% of patients had no/slight osteoarthritis. A total of 54 hips (58.7%) had superior radiographic outcomes. The risk factors for inferior radiographic outcomes were capsular quality (odds ratio [OR]: 0.358, 95% confidence interval [CI]: 0.113–0.931) and capsular thickness (OR: 0.265, 95% CI: 0.134–0.525). Joint stiffness was the most common complication (14.1%). We confirmed the efficacy of this procedure in the treatment of developmental hip dislocation. Patients with poor capsular quality are not suitable for this procedure. With suitable selection according to indications, this procedure can restore the hip rotation center with a low incidence of femoral head necrosis or severe osteoarthritis.
On the request for an advisory opinion on climate change under UNCLOS before the International Tribunal for the Law of the Sea
Authors: Feria-Tinta Monica 
Published: June 2023

Abstract
Sinking Islands form part of the dystopian reality faced by a world increasingly affected by climate breakdown today. As reported, around the world, ‘many islands are slowly but surely being submerged’. This article enquires into the potential role that the International Tribunal for the Law of the Sea (ITLOS) may have, in its advisory capacity, in tackling the effects of climate change. In particular, this article deals with two broad issues: (i) it identifies the potential benefits and risks of an ITLOS Advisory Opinion on the issue of climate change under the United Nations Convention on the Law of the Sea (UNCLOS) and (ii) it examines the questions that COSIS recently posed to the tribunal, a number of sub-questions and relevant provisions under UNCLOS are further identified, and whether the Commission on Small Island States on Climate Change and International Law has complied with the procedural rules of ITLOS to trigger its advisory functions.
Post hoc analysis of patients with rheumatoid arthritis under clinical remission in two Japanese Phase 3 trials of peficitinib treatment (RAJ3 and RAJ4)
Authors: Tanaka Yoshiya , Takeuchi Tsutomu , Morita Yoshiaki , Kato Daisuke , Kaneko Yuichiro , Terada Wataru 
Published: June 2023

ABSTRACT

Objective
We evaluated remission rates and their relationship with baseline characteristics in patients with rheumatoid arthritis treated with the oral Janus kinase inhibitor peficitinib.

Methods
This post hoc analysis of data from two Phase 3 studies (RAJ3 and RAJ4) of peficitinib (100 and 150 mg/day) in Asian rheumatoid arthritis patients investigated clinical disease activity index (CDAI) remission and low disease activity rates from baseline to Week 52. CDAI, Health Assessment Questionnaire-Disability Index, and van der Heijde–modified total Sharp score remission/low disease activity rates at Week 52 were evaluated among patients achieving CDAI remission at Weeks 12/28. Logistic regression analyses explored the relationship between baseline characteristics and CDAI remission/low disease activity rates.

Results
CDAI remission rates increased over time in a dose-dependent manner in both peficitinib-treated groups. Most patients achieving CDAI remission at Weeks 12/28 also achieved remission at Week 52. Following the multivariate analysis of demographic and baseline characteristics, factors associated with the achievement of CDAI remission at Week 28 included male sex, low baseline prednisone dose (RAJ3 only), and low baseline Disease Activity Score 28-C-reactive protein (RAJ4 only).

Conclusions
Peficitinib demonstrated persistent efficacy in clinical remission to Week 52. Baseline characteristics associated with CDAI remission were mostly consistent with previous studies using other disease-modifying antirheumatic drugs.