bluuebunny/crossref_metadata_2025_split huggingface dataset:
scDFC: A deep fusion clustering method for single-cell RNA-seq data
Authors: Hu Dayu , Liang Ke , Zhou Sihang , Tu Wenxuan , Liu Meng , Liu Xinwang 
Published: June 2023

Abstract
Clustering methods have been widely used in single-cell RNA-seq data for investigating tumor heterogeneity. Since traditional clustering methods fail to capture the high-dimension methods, deep clustering methods have drawn increasing attention these years due to their promising strengths on the task. However, existing methods consider either the attribute information of each cell or the structure information between different cells. In other words, they cannot sufficiently make use of all of this information simultaneously. To this end, we propose a novel single-cell deep fusion clustering model, which contains two modules, i.e. an attributed feature clustering module and a structure-attention feature clustering module. More concretely, two elegantly designed autoencoders are built to handle both features regardless of their data types. Experiments have demonstrated the validity of the proposed approach, showing that it is efficient to fuse attributes, structure, and attention information on single-cell RNA-seq data. This work will be further beneficial for investigating cell subpopulations and tumor microenvironment. The Python implementation of our work is now freely available at https://github.com/DayuHuu/scDFC.
DeepITEH: a deep learning framework for identifying tissue-specific eRNAs from the human genome
Authors: Zhang Tianjiao , Li Liangyu , Sun Hailong , Wang Guohua 
Published: June 2023

Abstract

Motivation
Enhancers are vital cis-regulatory elements that regulate gene expression. Enhancer RNAs (eRNAs), a type of long noncoding RNAs, are transcribed from enhancer regions in the genome. The tissue-specific expression of eRNAs is crucial in the regulation of gene expression and cancer development. The methods that identify eRNAs based solely on genomic sequence data have high error rates because they do not account for tissue specificity. Specific histone modifications associated with eRNAs offer valuable information for their identification. However, identification of eRNAs using histone modification data requires the use of both RNA-seq and histone modification data. Unfortunately, many public datasets contain only one of these components, which impedes the accurate identification of eRNAs.

Results
We introduce DeepITEH, a deep learning framework that leverages RNA-seq data and histone modification data from multiple samples of the same tissue to enhance the accuracy of identifying eRNAs. Specifically, deepITEH initially categorizes eRNAs into two classes, namely, regularly expressed eRNAs and accidental eRNAs, using histone modification data from multiple samples of the same tissue. Thereafter, it integrates both sequence and histone modification features to identify eRNAs in specific tissues. To evaluate the performance of DeepITEH, we compared it with four existing state-of-the-art enhancer prediction methods, SeqPose, iEnhancer-RD, LSTMAtt, and FRL, on four normal tissues and four cancer tissues. Remarkably, seven of these tissues demonstrated a substantially improved specific eRNA prediction performance with DeepITEH, when compared with other methods. Our findings suggest that DeepITEH can effectively predict potential eRNAs on the human genome, providing insights for studying the eRNA function in cancer.

Availability and implementation
The source code and dataset of DeepITEH have been uploaded to https://github.com/lyli1013/DeepITEH.
Integrating computational skills in undergraduate Microbiology curricula in developing countries
Authors: Adenaike Omolara , Olabanjo Olufemi Emmanuel , Adedeji Ayansewa Adeleke 
Published: June 2023

Abstract
The employability of young graduates has gained increasing significance in the labour market of the 21st century. Universities turn out millions of graduates annually, but at the same time, employers highlight their lack of the requisite skills for sustainable employment. We live today in a world of data, and therefore courses that feature numerical and computational tools to gather and analyse data are to be sourced for and integrated into life sciences’ curricula as they provide a number of benefits for both the students and faculty members that are engaged in teaching the courses. The lack of this teaching in undergraduate Microbiology curricula is devastating and leaves a knowledge gap in the graduates that are turned out. This results in an inability of the emerging graduates to compete favourably with their counterparts from other parts of the world. There is a necessity on the part of life science educators to adapt their teaching strategies to best support students’ curricula that prepare them for careers in science. Bioinformatics, Statistics and Programming are key computational skills to embrace by life scientists and the need for training beginning at undergraduate level cannot be overemphasized. This article reviews the need to integrate computational skills in undergraduate Microbiology curricula in developing countries with emphasis on Nigeria.
Once-daily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase IIb study
Authors: Kircik Leon H , Alonso-Llamazares Javier , Bhatia Neal , Bukhalo Michael , Devani Alim R , Draelos Zoe D , DuBois Janet , Gooderham Melinda J , Kempers Steven E , Lain Edward  , Lee Mark , Moore Angela , Murrell Dedee F , Papp Kim A , Pariser David M , Sinclair Rodney  , Zirwas Matthew , Burnett Patrick , Higham Robert C , Krupa David , Berk David R 
Published: June 2023

Abstract

Background
Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat.

Objectives
To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis.

Methods
In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of ‘clear’ or ‘almost clear’ plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated.

Results
Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P &lt; 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P &lt; 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included.

Conclusions
The results support the further development of roflumilast foam for treating scalp and body psoriasis.
Safety and efficacy of lirentelimab in patients with refractory indolent systemic mastocytosis: a first-in-human clinical trial
Authors: Siebenhaar Frank , Altrichter Sabine , Bonnekoh Hanna , Hawro Tomasz , Hawro Marlena , Michaelis Edward G , Kantor Andrea M , Chang Alan T , Youngblood Bradford A , Singh Bhupinder , Rasmussen Henrik S , Maurer Marcus 
Published: June 2023

Abstract

Background
Indolent systemic mastocytosis (ISM) is characterized by excessive mast cell (MC) accumulation and MC-driven signs and symptoms. Currently used therapies are not approved and have limited efficacy. Lirentelimab (AK002) is a monoclonal antibody against sialic acid-binding immunoglobulin-like lectin (Siglec)-8 that inhibits MC activation.

Objectives
To determine the safety, tolerability and efficacy of lirentelimab in reducing the symptoms of ISM.

Methods
At a specialty centre for mastocytosis in Germany, we conducted a phase I first-in-human single-ascending and multidose clinical trial of lirentelimab in patients with ISM. Eligible adults had World Health Organization-confirmed ISM and an unsatisfactory response to available treatment. In part A, patients received a single dose of lirentelimab 0.0003, 0.001, 0.003, 0.01 or 0.03 mg kg–1; in part B, patients received one lirentelimab dose of 0.3 mg kg–1 or 1.0 mg kg–1; and in part C, patients received either 1.0 mg kg–1 lirentelimab every 4 weeks for 6 months or ascending doses of lirentelimab (one dose of 1 mg kg–1 followed by five doses of 3–10 mg kg–1 every 4 weeks). The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in Mastocytosis Symptom Questionnaire (MSQ), Mastocytosis Activity Score (MAS) and Mastocytosis Quality of Life Questionnaire (MC-QoL) scores at 2 weeks after the final dose.

Results
In 25 patients with ISM (13 in parts A + B and 12 in part C; median age 51 years, 76% female, median 4.6 years from diagnosis), the most common treatment-related adverse events (AEs) were feeling hot (76%) and experiencing a headache (48%). No serious AEs occurred. Median MSQ and MAS symptom severity scores in part C improved (vs. baseline) across all symptoms [MSQ: skin (38–56%), gastrointestinal (49–60%), neurological (47–59%), musculoskeletal (26–27%); MAS: skin (53–59%), gastrointestinal (72–85%), neurological (20–57%), musculoskeletal (25%)]. Median MC-QoL scores improved across all domains: symptoms (39%), social life/functioning (42%), emotions (57%) and skin (44%).

Conclusions
Lirentelimab was generally well tolerated and improved symptoms and quality of life in patients with ISM. The therapeutic potential of lirentelimab should be considered for ISM.
The Impact of Age in the Treatment of Patients with Localized Rectal Cancer - Survival Outcomes from the National Cancer Database
Authors: Erdem-Sanchez S , Warschkow R , Kuemmerli C , Schmied B M , von Strauss Und Torney M , Blazer D , Nussbaum D , Worni M , Studer P 
Published: June 2023

Abstract

Background
Multimodal therapy for localized rectal cancer (RC), including (neo-)adjuvant systemic therapy and surgery, has improved survival outcomes significantly. However, these results cannot be extrapolated to elderly patients.

Aims
The aim of this study was to evaluate whether patients aged &gt;/=75 years receive substandard oncological treatment compared to their younger counterparts and if this affects survival.

Methods
This is a retrospective study from the National Cancer Data Base (NCDB) for histologically confirmed localized RC from 2002–2014. Non-comorbid patients (i.e., Charlson-Deyo comorbidity index 0) between &gt;/=50 - &lt;/=85 years were included and assigned to a younger (&lt;75 years) and an older (&gt;/=75 years) group.Treatment modalities and their impact on relative survival (RS) were analyzed using loess regression models. Mediation analysis was performed to measure the independent relative effect of age on RS.

Results
59,769 patients were identified of which 48,389 (81.0%) were assigned to the younger group (&lt;75 years). Oncologic resection was performed in 79.6% of the younger compared to 67.2% of the older patients (p&lt;0.001). Chemo- (74.3% vs. 56.1%) and radiotherapy (72.0% vs. 58.1%) were provided more often to younger patients (p&lt;0.001). Increasing age was associated with higher 90-day (2.0% vs. 1.1%) mortality in the elderly group (p&lt;0.001) and worse RS rates (multivariable adjusted HR: 1.93 (95%CI:1.87-2.00), p&lt;0.001). Guideline adherent oncological therapy resulted in a significant increase of 5-year RS in both groups (multivariable adjusted HR: 0.80 (95%CI:0.74-0.86), p&lt;0.001). Mediation analysis revealed that RS was mainly affected by age itself (84%) rather than the choice of therapy.

Conclusions
The likelihood to receive substandard oncological therapy increases in the older population and negatively affects RS. Since age itself has a major impact on RS, it is important to identify patients potentially eligible for standard oncological care regardless of their age to improve survival outcomes for this age group.
Five-Year Outcomes of Gastric Bypass in Young versus Older Diabetic Adults
Authors: Giudicelli G , Krause N , Toso C , Hagen M E , Dupuis A , Gastaldi G , Jung M K 
Published: June 2023

Abstract

Background
Timely metabolic surgery improves glycemic control and reduces cardiovascular risk for patients with type 2 diabetes. Young age is a known predictor of metabolic success but RYGB is often delayed due to the reported vulnerability of young adults.

Aims
To compare diabetes remission, metabolic outcomes and surgical adverse events in young (18-35 years) and older (&gt;35 years) adults in the first five years following Roux-en-Y gastric bypass (RYGB).

Methods
We analysed prospective registry data from a single center on young (29.4 years, [standard deviation (SD)=5]) and older (47.7 years, [SD=6.7]) non-insulin-dependent diabetic adults undergoing RYGB. Younger adults were matched one to two to their older counterparts for sex, body mass index, duration of preoperative diabetes and American Society of Anaesthesiologist score. The rate of diabetes remission and adverse events in both groups were compared.

Results
A total of 78.2% (43/55) of the young and 75.4% (86/114) of the older adults attended the five-year follow-up. Diabetes remission occurred significantly earlier in the young adults group with a hazard ratio of 0.57 [95% confidence interval (CI) 0.23-0.87] and a median time to remission of 12 months [95% CI 3.2-20.8] compared to 24 months [95% CI 10.5-37.4, p=0.031] for older adults. There were no significant differences in loss to follow-up, percent weight change, and all-cause adverse events.

Conclusions
Diabetes remission occurred earlier and more frequently in young adults within the first 5 years after RYGB. The risk of surgical complications, nutritional deficiency or failure to achieve successful weight loss did not increase in the investigated young adult group.
Interim Analysis of an Ongoing Study Evaluating Preventive Aortic Stent Graft Implantation Prior to Major Thoracic Tumor Resection and a Review of the Literature
Authors: Theisen-Lauk O T , Opitz I , Schneiter D , Zimmermann A , Reutersberg B 
Published: June 2023

Abstract

Introduction
There is limited data in the literature on the use of thoracic aortic stent graft implantation (TEVAR) to facilitate en-bloc resection of tumors that have invaded the aortic wall. After TEVAR, extended resections can be performed, avoiding aortic wall replacement or catastrophic situations such as life-threatening bleeding from aortic injury.

Aims
The aim of this interim analysis was to demonstrate the feasibility of TEVAR without increased risk of perioperative morbidity and mortality.

Methods
A retro- and prospective data analysis was performed including all consecutive patients with suspicious aortic wall infiltration on preoperative imaging, who received a TEVAR implantation prior to resection of thoracic malignancy between 1/2008 and 12/2022. In addition, a literature review was conducted.

Results
Thirteen patients (median age 67 years, range 23-75, 62% female) have been treated at our institution so far. Nine patients received neoadjuvant therapy. In all patients it was possible to implant the stent graft with sufficient overlap at the level of the tumor mass. In 69% the proximal landing zone was located in aortic zone 3 to 4. No postoperative endograft related morbidity, especially no spinal cord ischemia, no stroke, no postoperative bleeding or access site complications, as well as no dissection or aortic rupture was observed.
In nine patients, aortic wall infiltration was confirmed intraoperatively, and a partial non-circumferential resection of the aortic wall was necessary.
The 30-day mortality rate was 15% (one case) due to respiratory failure and ARDS as well as postoperative empyema. Eight patients died during a median follow up of 11 month (0.7-94).

Conclusions
In this, to the best of our knowledge, largest analysis to date, the results of previous smaller series were confirmed. Aortic stent grafting prior to thoracic tumor resection allows extensive resections while maintaining low morbidity and a low 30-day mortality risk.
Decoding the molecular landscape of keloids: new insights from single-cell transcriptomics
Authors: Xia Yijun , Wang Youbin , Shan Mengjie , Hao Yan , Liang Zhengyun 
Published: June 2023

AbstractKeloids are a fibrotic disease caused by an excessive accumulation of extracellular matrix in the dermis; they have neoplasia-like properties of aggressive growth and high posttreatment recurrence rates. Therefore, it is imperative to gain additional insight into the pathobiology of keloid formation. Single-cell RNA sequencing (scRNA-seq) technology has brought data-driven innovation to understanding the pathogenesis of keloids by breaking the limitations of traditional sequencing technologies to resolve cell composition and to distinguish functional cell subtypes at an unprecedented resolution. The present review aims to cover the application of scRNA-seq technology in keloids and its exploratory findings, including the depiction of the cellular landscape of keloids, fibroblast heterogeneity, the lineage development of Schwann cells and the mesenchymal-activation phenomenon of endothelial cells. Furthermore, scRNA-seq records the transcriptional profiles of fibroblasts and immune cells in a more refined manner, and this gene expression information provides excellent material for inferring intercellular communication networks and lays an important theoretical foundation for future studies.
Shared identity endorsement narratives: a framework for studying celebrity endorsements of minority political candidates in the US
Authors: Reddi Madhavi 
Published: June 2023

Abstract
This article introduces the concept of shared identity endorsement narratives (SIENs), or celebrity endorsements of political candidates that intentionally highlight shared social identities between the endorser and the endorsed. Scholars of celebrity endorsements in political contexts have primarily focused on the efficacy rather than the rhetorical content of these endorsements and what latent social structures make them effective. Through close readings of two SIENs of Vice President Kamala Harris by American celebrities of Indian descent, I draw upon social identity theory to elucidate the ways in which these endorsements create valuable networks of support for Indian Americans, but simultaneously create homogenizing articulations of Indian American identity that exploit caste, ethnolinguistic, and racial differences. Analyzing how Indian Americans and other minority groups present themselves/connect with their community provides insights into what it takes to succeed in America’s diversifying political and media landscape.
Classic costimulatory interactions in MAIT cell responses: from gene expression to immune regulation
Authors: Wang Nicole I , Ninkov Marina , Haeryfar S M Mansour 
Published: June 2023

Summary
Mucosa-associated invariant T (MAIT) cells are evolutionarily conserved, innate-like T lymphocytes with enormous immunomodulatory potentials. Due to their strategic localization, their invariant T cell receptor (iTCR) specificity for major histocompatibility complex-related protein 1 (MR1) ligands of commensal and pathogenic bacterial origin, and their sensitivity to infection-elicited cytokines, MAIT cells are best known for their antimicrobial characteristics. However, they are thought to also play important parts in the contexts of cancer, autoimmunity, vaccine-induced immunity, and tissue repair. While cognate MR1 ligands and cytokine cues govern MAIT cell maturation, polarization, and peripheral activation, other signal transduction pathways, including those mediated by costimulatory interactions, regulate MAIT cell responses. Activated MAIT cells exhibit cytolytic activities and secrete potent inflammatory cytokines of their own, thus transregulating the biological behaviors of several other cell types, including dendritic cells, macrophages, natural killer cells, conventional T cells, and B cells, with significant implications in health and disease. Therefore, an in-depth understanding of how costimulatory pathways control MAIT cell responses may introduce new targets for optimized MR1/MAIT cell-based interventions. Herein, we compare and contrast MAIT cells and mainstream T cells for their expression of classic costimulatory molecules belonging to the immunoglobulin superfamily and the tumor necrosis factor (TNF)/TNF receptor superfamily, based not only on the available literature but also on our transcriptomic analyses. We discuss how these molecules participate in MAIT cells’ development and activities. Finally, we introduce several pressing questions vis-à-vis MAIT cell costimulation and offer new directions for future research in this area.
Plasma pentraxin 3 in idiopathic inflammatory myopathies: a possible new biomarker of disease activity
Authors: Fornaro M , Girolamo F , Cacciapaglia F , Carabellese G , Bizzoca R , Scioscia C , Coladonato L , Lopalco G , Ruggieri M , Mastrapasqua M , Fari G , D’Abbicco D , Iannone F 
Published: June 2023

Abstract
Pentraxin-3 (PTX3) is a component of humoral innate immunity with essential functions both in promotion and resolution of inflammation. We aimed to study the PTX3 in the plasma and in the muscle of patients with idiopathic inflammatory myopathies (IIM) and whether PTX3 may correlate with disease activity. Plasma PTX3 levels were assessed in 20 patients with IIMs, 10 dermatomyositis (DM), and 10 polymyositis (PM), compared to 10 patients with rheumatoid arthritis (RA) and 10 healthy donors (HDs) aged, sex, and body mass index matched. Disease activity in IIMs was assessed by Myositis Disease Activity Assessment Visual Analog Scale (MYOACT), while disease activity score on 28 joints (DAS28) was used for RA patients. Muscle histopathology and immunohistochemical (IHC) analyses were also performed. Mean plasma PTX3 levels were significantly higher in IIM patients than HDs (518 ± 260 pg/ml vs. 275 ± 114 pg/ml, P = 0.009). Linear regression analysis adjusted for age, sex, and disease duration showed a direct correlation between PTX3 and CPK levels (β: 0.590), MYOACT (β: 0.759), and physician global assessment of disease activity (β: 0.832) in IIMs. No association between PTX3 levels and DAS28 was found in RA. Global PTX3 pixel fraction was higher in IIM than HDs muscle, but a lower PTX3 expression was found in perifascicular areas of DM and in myofibers with sarcolemmal staining for membrane attack complement. PTX3 plasma levels were increased in IIMs and correlated with disease activity suggesting a possible role as biomarker of disease activity. PTX3 showed a different distribution in DM or PM muscle.