bluuebunny/crossref_metadata_2025 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

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

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

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

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 < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 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

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

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 >/=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 >/=50 - </=85 years were included and assigned to a younger (<75 years) and an older (>/=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 (<75 years). Oncologic resection was performed in 79.6% of the younger compared to 67.2% of the older patients (p<0.001). Chemo- (74.3% vs. 56.1%) and radiotherapy (72.0% vs. 58.1%) were provided more often to younger patients (p<0.001). Increasing age was associated with higher 90-day (2.0% vs. 1.1%) mortality in the elderly group (p<0.001) and worse RS rates (multivariable adjusted HR: 1.93 (95%CI:1.87-2.00), p<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<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

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 (>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

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

Keloids 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

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.
Adalimumab does not cause weight gain in patients with psoriasis in the first year of treatment
Authors: Schwarz Christopher W , Loft Nikolai , Kaur-Knudsen Diljit , Zachariae Claus , Skov Lone
Published: June 2023

Treatment of psoriasis with adalimumab has been associated with weight gain; however, data are sparse. We conducted a cohort study in Danish patients with psoriasis treated with adalimumab, secukinumab and ustekinumab. After 1 year of treatment, we found no significant weight gain and the three treatments were comparable with regards to change in bodyweight. Therefore, our study does not support that adalimumab results in weight gain.
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

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

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.
Tocilizumab suppresses NF-kappa B activation via toll-like receptor 9 signaling by reducing cell-free DNA in rheumatoid arthritis
Authors: Hashimoto Teppei , Yoshida Kohsuke , Yokoyama Yuichi , Hashimoto Naonori , Kaneshiro Kenta , Yoshikawa Takahiro , Tateishi Koji , Terashima Yasuhiro , Matsui Kiyoshi , Hashiramoto Akira
Published: June 2023

Endogenous DNA is released into the bloodstream as cell-free DNA (cfDNA) following cell death and is associated with various pathological conditions. However, their association with therapeutic drugs against rheumatoid arthritis (RA) remains unknown. Therefore, we investigated the significance of cfDNA in RA treated with tocilizumab and tumour necrosis factor inhibitor (TNF-I). Biological DMARDs (bDMARDs), including tocilizumab and TNF-I, were administered to 77 and 59 RA patients, respectively. Plasma cfDNA levels were measured at weeks 0, 4, and 12 by quantitative polymerase chain reaction. Disease activity was evaluated at the same time point using DAS28ESR. cfDNA levels from RA synovial cells treated with tocilizumab or etanercept for 24 h were measured. Human toll-like receptor 9 (hTLR9)-expressing HEK293 cells, which release secreted embryonic alkaline phosphatase (SEAP) upon NF-κB activation, were stimulated by cfDNA from RA patients, and subsequently, SEAP levels were determined. NF-κB translocation was evaluated by immunofluorescence staining with or without tocilizumab. The DAS28ESR significantly improved in both bDMARD groups at week 12. However, plasma cfDNA levels significantly decreased in the tocilizumab group at week 12 compared to that in week 0. cfDNA levels correlated with DAS28ESR in biological treatment-naïve patients administered tocilizumab. cfDNA levels in synovial cells were significantly suppressed by tocilizumab treatment and unaltered with etanercept. HEK293 cells released SEAP upon cfDNA stimulation, and the observed NF-κB nuclear translocation was suppressed by tocilizumab. Tocilizumab suppressed inflammation via the TLR9 pathway by decreasing cfDNA levels. Regulation of cfDNA may be a therapeutic target for RA.
One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019: A Randomized Controlled Phase 2 Trial
Authors: Jilg Nikolaus , Chew Kara W , Giganti Mark J , Daar Eric S , Wohl David A , Javan Arzhang Cyrus , Kantor Amy , Moser Carlee , Coombs Robert W , Neytman Gene , Hoover Keila , Jana Atasi , Hart Phil A , Greninger Alexander L , Szurgot Bob , Eron Joseph J , Currier Judith S , Hughes Michael D , Smith Davey M , Li Jonathan Z ,   for the ACTIV-2/A5401 Study Team, Chew Kara , Smith David , Daar Eric , Wohl David , Currier Judith , Eron Joseph , Javan Arzhang Cyrus , Hughes Michael , Moser Carlee , Giganti Mark , Ritz Justin , Hosey Lara , Roa Jhoanna , Patel Nilam , Colsh Kelly , Rwakazina Irene , Beck Justine , Sieg Scott , Li Jonathan , Fletcher Courtney , Fischer William , Evering Teresa , Coombs Robert , Ignacio Rachel Bender , Cardoso Sandra , Corado Katya , Jagannathan Prasanna , Jilg Nikolaus , Perelson Alan , Pillay Sandy , Riviere Cynthia , Singh Upinder , Taiwo Babafemi , Gottesman Joan , Newell Matthew , Pedersen Susan , Dragavon Joan , Jennings Cheryl , Greenfelder Brian , Murtaugh William , Kosmyna Jan , Gapara Morgan , Shahkolahi Akbar , Szurgot Bob
Published: June 2023

Background

Camostat inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. We studied the safety and efficacy of camostat in ACTIV-2/A5401, a phase 2/3 platform trial of therapeutics for COVID-19 in nonhospitalized adults.

Methods

We conducted a phase 2 study in adults with mild-to-moderate COVID-19 randomized to oral camostat for 7 days or a pooled placebo arm. Primary outcomes were time to improvement in COVID-19 symptoms through day 28, proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal swabs through day 14, and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28.

Results

Of 216 participants (109 randomized to camostat, 107 to placebo) who initiated study intervention, 45% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Median age was 37 years. Median time to symptom improvement was 9 days in both arms (P = .99). There were no significant differences in the proportion of participants with SARS-CoV-2 RNA <LLoQ on days 3, 7, and 14. Through day 28, 6 (5.6%) participants in the camostat arm and 5 (4.7%) in the placebo arm were hospitalized; 1 participant in the camostat arm subsequently died. Grade ≥3 TEAEs occurred in 10.1% of camostat versus 6.5% of placebo participants (P = .35).

Conclusions

In a phase 2 study of nonhospitalized adults with mild-to-moderate COVID-19, oral camostat did not accelerate viral clearance or time to symptom improvement, or reduce hospitalizations or deaths.

Clinical Trials Registration. ClinicalTrials.gov identifier: NCT 04518410.
Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States
Authors: Lewnard Joseph A , Hong Vennis , Bruxvoort Katia J , Grant Lindsay R , Jódar Luis , Cané Alejandro , Arguedas Adriano , Pomichowski Magdalena E , Gessner Bradford D , Tartof Sara Y
Published: June 2023

Background

Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults.

Methods

We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status.

Results

Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3–131.8) and 108.6 (50.4–159.1) medically attended LRTI cases; 21.9 (10.1–32.0) and 26.6 (12.4–38.7) hospitalized LRTI cases; and 7.1 (3.3–10.5) and 8.7 (4.0–12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6–131.5) and 102.7 (47.8–156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4–8.6) and 6.2 (2.8–10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4–1.4) and 1.1 (0.5–1.7) excess LRTI-associated deaths per 10 000 person-years.

Conclusions

Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.
Stealth Address Schemes With Fast Retrievability Based On Subgroup Membership Assumptions Related To Factoring
Authors: Wang Xin , Lin Li , Wang Yao
Published: June 2023

Stealth address is a known technique to ensure the privacy (anonymity) of a recipient participating in a certain transaction in a distributed blockchain scenario. However, most existing stealth address schemes require linear judge time and search time $\mathcal{O}(n)$, where $n$ is the number of transactions of a certain block, so the only way to claim transactions for a recipient is to traverse the transaction list to find out whether an ever-arrived transaction belongs to him. To overcome this drawback, we proposed the notion of Fast Stealth Address (FSA), a novel approach that simultaneously preserves privacy and improves search efficiency of recipients. We give a generic construction of FSA scheme under subgroup membership assumption related to factoring and instantiate concrete schemes based on specific number-theoretic assumptions. Our framework mainly improves on two aspects: (i) allowing constant recognize time $\mathcal{O}(1)$ to judge whether a certain block contains recipient’s transactions and (ii) allowing logarithmic search time $\mathcal{O}(\log{n})$ to find out the precise transactions intended for a recipient. We formalize the security model of an FSA scheme and provide provable security analysis to ensure the security of our constructions. Besides, we implement our schemes to measure their real-world performance on several metrics and give comparison results to stealth address scheme utilized by Monero.
A Genetic Algorithm Based Scheduling Method With Carrier Aggregation In 5G Networks
Authors: Hsu Ching-Kuo
Published: June 2023

Recently, 5G has become an important mechanism to serve a growing amount of users in the network, which provides enhanced mobile broadband (eMBB) and ultra-reliable low latency communications (URLLC) services. Meanwhile, Carrier Aggregation (CA) is a promising 5G technology which lets users aggregate fragmented carrier components (CCs) to enhance transmission efficiency. This paper addresses 5G scheduling problem in the CA-enabled eMBB–URLLC coexistence network using genetic algorithm (GA). The key idea is first treating the serving time slot of each user equipment (UE) as a gene and combining all genes to form a chromosome, then generating a set of chromosomes as the initial population and letting the population evolve to iteratively select the fittest one as the resource scheduling decision. Up to now, this is the first work using GA for solving the scheduling problem in the CA-enabled 5G network. Simulation results show that our proposed method can serve the most UEs ($4\%$) with the highest throughput ($7.1\%$) and lower delay.
Hybrid Optimal Ensemble SVM Forest Classifier for Task Offloading in Mobile Cloud Computing
Authors: Subramaniam Erana Veerappa Dinesh , Krishnasamy Valarmathi
Published: June 2023

Mobile devices (MDs) are becoming more prevalent and their battery life is optimised by offloading tasks to cloud servers. However, communication costs must be considered when offloading tasks. To make task offloading worthwhile, it is important to measure the energy consumed during communication activities. Thus, a heterogeneous framework is developed to enhance the energy efficiency of smartphones by analysing parameters such as task and non-task offloading, local cloudlets, radio access networks and remote cloud servers. This paper proposes a task offloading framework that uses a novel algorithm, the Hybrid Red Fox Flow Direction-based Ensemble SVM Forest Classifier, to enhance the system parameters and schedule tasks in offloading cloud computing conditions. The multi-objective function aims to improve user satisfaction by maximising resource utilisation and minimising function. The framework was tested in the Cloudsim simulation tool and compared with different techniques, with the results demonstrating its superiority in terms of energy efficiency and system performance. The proposed framework can optimise the energy efficiency of MDs and improve battery life.
“Overworked and Stretched Thin”: Burnout and Systemic Failure in School Social Work
Authors: Carnes Stephanie L
Published: June 2023

The effects of burnout on client service provision, organizational health, and individual well-being are increasingly a focus of social work research, particularly against the societal backdrop of the post-COVID-19 era. Children and their families rely on school social workers (SSWs) to meet increasingly pressing and common mental health needs. However, burnout may jeopardize not only SSWs’ well-being, but also their collective ability to serve this vulnerable population. The current study captures SSW perspectives on burnout related to the following themes: SSW–administrator dynamics; role conflict and lack of role definition; presence of trauma in caseload; systemic challenges (including the subthemes of unrealistic workload, the desire for more interprofessional collaboration and social work–specific supervision, and limited resources); and the effects of the COVID-19 pandemic. Using these perspectives as a guide, policy recommendations are made to enhance interprofessional collaboration, clarify roles and responsibilities, and safeguard SSWs as “first responders” for children’s mental health.
Efficacy and safety of modified endoscopic submucosal tunnel dissection for superficial esophageal circumferential lesions
Authors: Tian Ye , Xue Chengjun , Li Xiaomin , Bai Jianan , Xiao Zequan , He Qibin , Kan Jingbao , Zhu Guoqin , Tang Qiyun
Published: June 2023

To evaluate the efficacy and safety of intra-tunnel dissection using hemostatic forceps and needle-type device for patients with esophageal circumferential lesions (ECLs). Patients with ECLs were enrolled in the study and underwent endoscopic submucosal tunnel dissection (ESTD) or hemostatic forceps-based ESTD (ESFTD). All patients were divided into three subgroups according to longitudinal length of the lesions (LLLs): >8 cm, 4–8 cm and < 4 cm. The clinical data such as gender, age, length of lesions and operating time were collected. A total of 152 patients were included in this study and comprised 80 cases of ESFTD and 72 cases of ESTD. The procedure time was markedly shorter in the ESFTD group than in the ESTD group (P < 0.001). Moreover, ESFTD significantly increased the rate of complete resection and reduced specimen injury in LLLs >8 cm and 4–8 cm subgroup compared with ESTD (P < 0.001), but not in <4 cm subgroup (P > 0.05). The perforation and infection rate were similar in ESFTD and ESTD group (P > 0.05). However, ESFTD effectively decreased the muscular injury rate’ the duration of chest pain and the time from endoscopic surgery to first occurrence of esophageal stenosis compared with ESTD group (P < 0.01). ESFTD has better efficacy and safety than ESTD in the treatment of ECLs, especially for large lesions. ESFTD could be recommended for patients with ECLs.
Systematic review of quality of life after esophagectomy and total gastrectomy in patients with gastro-esophageal junction cancer
Authors: Walmsley James , Ariyarathenam Arun , Berrisford Richard , Humphreys Lee , Sanders Grant , Tham Ji Chung , Wheatley Tim , Chan David S Y
Published: June 2023

The optimal management of cancer of the gastro-esophageal junction (GEJ) is an area of contention. GEJ tumors are typically resected via total gastrectomy or esophagectomy. Despite many studies aiming to determine the superiority of either procedure based on surgical or oncological outcomes, the evidence is equivocal. Data focusing specifically on quality of life (QoL), however, is limited. This systematic review was performed to determine if there is any difference in patient’s QoL after total gastrectomy or esophagectomy. A systematic search of PubMed, Medline and Cochrane libraries was conducted for literature published between 1986 and 2023. Studies that used the internationally validated questionnaires EORTC QLQ-C30 and EORTC-QLQ-OG25, to compare QoL after esophagectomy to gastrectomy for the management of GEJ cancer were included. Five studies involving 575 patients undergoing either esophagectomy (n = 365) or total gastrectomy (n = 210) for GEJ tumors were included. QoL was predominantly assessed at 6, 12 and 24 months postoperatively. Although individual studies demonstrated significant differences in certain domains, these differences were not consistently demonstrated in more than one study. There is no evidence to suggest any significant differences in QoL after total gastrectomy compared to esophagectomy for management of gastro-esophageal junction cancer.
Phenotyping heart failure by genetics and associated conditions
Authors: Wong Joshua , Peters Stacey , Marwick Thomas H
Published: June 2023

Heart failure is a highly heterogeneous disease, and genetic testing may allow phenotypic distinctions that are incremental to those obtainable from imaging. Advances in genetic testing have allowed for the identification of deleterious variants in patients with specific heart failure phenotypes (dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and hypertrophic cardiomyopathy), and many of these have specific treatment implications. The diagnostic yield of genetic testing in heart failure is modest, and many rare variants are associated with incomplete penetrance and variable expressivity. Environmental factors and co-morbidities have a large role in the heterogeneity of the heart failure phenotype. Future endeavours should concentrate on the cumulative impact of genetic polymorphisms in the development of heart failure.
Foreign Investors of the World, Unite! The International Association for the Promotion and Protection of Private Foreign Investments (APPI) 1958–1968
Authors: Batselé Filip
Published: June 2023

This article studies lobbying efforts by the actors that investment treaties protect – namely, foreign investors. It uses a legal-historical approach to analyse the activities of the International Association for the Promotion and Protection of Private Foreign Investments (Association internationale pour la promotion et la protection des investissements privés en territoires étrangers or APPI), a transnational business interest association that lobbied for better protection of private foreign investment under international law. The article considers the role of this group in lobbying for three multilateral investment treaties (an investment code, investor-state arbitration and investment insurance) during the 1950s and 1960s, using unexplored archival sources. The article makes three substantive contributions to the literature. First, it shows that the key actors involved in APPI were a transnational advocacy network of businessmen and lawyers at multinational companies, mainly in the oil and banking sector. Second, it shows how these two types of actors (businessmen and lawyers) acted symbiotically. The businessmen provided access to policy-makers and introduced company lawyers into the policy-making cycle. The company lawyers provided expertise and specific legal texts with which civil servants could work. Third, it argues that, despite the group members’ common goal to improve foreign investment security, competing individual initiatives and institutional competition, next to state preferences, often impeded more effective lobbying.
The Future in the Past? The Replication of Existing Treaty Language in the Making of the ILC’s Draft Articles on Crimes against Humanity
Authors: Biazatti Bruno
Published: June 2023

Treaty-making often occurs through the reuse of existing legal solutions. Instead of creating new language, drafters often replicate past treaty wording in the instrument under negotiation. The Draft Articles on Prevention and Punishment of Crimes against Humanity (DACaH), formulated by the International Law Commission (ILC or the Commission), were an example. This article evaluates the ILC’s reliance on past treaty language to produce the DACaH. In addition to assessing some contextual reasons why, and the manner in which, the Commission used such a drafting approach, this article notes that, given its mandate as an expert body subsidiary to the United Nations General Assembly, the ILC may face specific challenges while using this technique. Taking the DACaH as a case study, the article also explores some pragmatic and normative considerations that may motivate or impact the replication of past treaty language in international law-making. In conclusion, the ILC’s reliance on existing treaty wording to craft the DACaH was deeply consequential as it was part of the Commission’s broader goal of placating states via the adoption of an effective, but minimalist and conformist, set of draft articles with greater chances of becoming a widely adhered to treaty.
Wars of Recovery
Authors: Lieblich Eliav
Published: June 2023

Aggressor state A occupies territory belonging to victim state V. After decades, V decides to go to war to recover its territory, although hostilities have long subsided. Are such ‘wars of recovery’ lawful under international law? Should they be? Recent conflicts have generated a heated scholarly debate on this question, which has ended in stark disagreement. A permissive approach argues that wars of recovery are lawful instances of self-defence, while a restrictive view claims that situations of prolonged occupation are territorial disputes that should be settled peacefully. This article uncovers the theoretical premises that underlie both approaches. As it shows, the dilemma reflects a larger tension within the contemporary international law on the use of force – mainly, between its traditional focus on state rights such as territory and sovereignty and a competing view that seeks to place individual rights at the core of the legal regime. As the article shows, deciding on the question of wars of recovery requires making commitments in four normative spheres: instrumentally, it requires considering questions of international stability, and, non-instrumentally, it requires considering questions of justice as well as possible justifications for killing and sacrifice. These considerations, however, result in instability owing, among other factors, to the fluctuating effects of the passage of time, which follow our normative assumptions about the legal order. Ultimately, the article suggests that those engaging in debate on wars of recovery make explicit their normative assumptions on the ends of jus ad bellum and that, in any case, even if wars of recovery would be deemed legal, they would still remain heavily contestable owing to strong competing reasons against them.
Towards an extended resource theory of marital power: parental education and household decision-making in rural China
Authors: Cheng Cheng , Xie Yu
Published: June 2023

Existing literature on the resource theory of marital power has focused on the relative resources of spouses and overlooked the resource contributions of spouses’ extended families. We propose an extended resource theory that considers how the comparative resources of a couple’s natal families are directly associated with marital power, net of the comparative resources of the couple. Using data from the China Panel Family Studies, we examine how the relative education of a couple’s respective parents affects the wife’s decision-making power, net of the relative education of the couple. Results suggest that the higher the wife’s parental education relative to her husband’s parental education, the more likely she is to have the final say over household financial decisions. Our study underscores the importance of situating the study of marital power in the extended family context and highlights the significance of social origins and intergenerational exchanges for marital power.