bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chief medical officers in the United Kingdom: maintaining ‘independence’ inside government
Authors: Smith Katherine E , Macintyre Anna , MacAulay Margaret , Fafard Patrick 
Published: October 2024

Abstract

Background
The Chief Medical Officer (CMO), one of the UK’s most senior public health leadership roles, was crucial in supporting policymakers in responding to COVID-19. Yet, there exist only a handful of (largely historical) accounts of the role in England. This article is the first to empirically examine how the scope, focus and boundaries of the CMO role vary over time across the four UK nations, including during public health emergencies.

Methods
We undertook semi-structured interviews with 10 current and former CMOs/Deputy CMOs in the four UK nations and analysed relevant documents.

Findings
The CMO role is not clearly defined in contemporary UK legislation and is instead shaped by iterative policies, incumbent preferences, and organizational needs, leading to variation over time and between nations. Nonetheless, most participants framed the role as primarily providing ‘independent’ advice to government despite being senior civil servants who, in communicating with the public, sometimes speak ‘on behalf’ of government.

Conclusions
The flexibility of UK CMO roles allows for responsive adaption but poses risks for how well these roles are understood. A potential tension between providing ‘independent’ policy advice and a need to publicly communicate government policies and guidelines may be exacerbated in emergency contexts.
Not Just They/Them: Exploring Diversity and Meaning in Pronoun Use among Non-Binary Individuals
Authors: Moeder Jessica , Scarborough William J , Risman Barbara 
Published: October 2024

ABSTRACT
Gender-neutral pronouns, such as they/them, have been studied as a site of identity affirmation and, at other times, contestation for non-binary individuals. In this study, we draw from interviews with 123 non-binary individuals to better understand the role of pronouns in these individuals’ lives. We find that pronoun practices are ontoformative—they actively (re)construct the meanings attached to gender and gender identities. Yet, not all non-binary individuals use similar pronoun practices, resulting in diverse ontologies of non-binary identity. Half of our respondents consistently used non-binary pronouns, such as they/them, and felt they were a stable and direct reflection of identity—an approach we refer to as a fixed expression. These individuals define non-binary gender as independent from the woman/man binary. The other half of our sample held flexible pronoun expressions—they used multiple pronouns and anticipated future changes. Some of these individuals rejected the idea that pronouns expressed their identity, offering a definition of non-binary that eschewed categorical distinctions. Others embrace pronouns as identity expressing and forming, but felt that multiplicity best reflected their identity, offering a definition of non-binary as category-spanning. Our findings highlight the central and diverse role of pronouns in the social construction of non-binary ontology.
Uterine carcinosarcoma: Unraveling the role of epithelial‐to‐mesenchymal transition in progression and therapeutic potential
Authors: Gopinatha Pillai Mohan Shankar , Shaw Pallab , Dey Bhowmik Arpan , Bhattacharya Resham , Rao Geeta , Dhar Dwivedi Shailendra Kumar 
Published: October 2024

AbstractUterine carcinosarcoma (UCS) is a rare and highly aggressive gynecological malignancy characterized by poor prognosis. Due to its rarity, UCS remains relatively unexplored, and specific treatment guidelines are scarce. Despite standard treatments, including surgery, adjuvant chemotherapy, and radiotherapy, UCS has a high recurrence rate and poor overall prognosis. The aggressive nature of UCS is attributed to the metaplastic transformation of carcinomatous elements into sarcoma. This “biphasic” neoplasm features a mixture of epithelial and mesenchymal/tumor components, which partially share molecular signatures and exhibit a typical epithelial‐to‐mesenchymal transition (EMT) gene expression profile. Recent scientific advancements have highlighted the pivotal role of EMT in UCS progression and mortality. This review covers the epidemiology of UCS, theories regarding its origin, and the current state of clinical trials with more emphasis on the role of EMT drivers in UCS progression and scope of targeting these molecules. By shedding light on the molecular mechanisms supporting UCS, particularly emphasizing the importance of EMT, we aim to provide a more comprehensive understanding of the disease to support the development of more effective therapeutic strategies.
Efficacy and safety of tegoprazan (LXI-15028) vs. esomeprazole in patients with erosive esophagitis: A multicenter, randomized, double-blind, non-inferiority phase Ⅲ trial
Authors: Zhu Huiyun , Xue Qian , Song Yingxiao , Zhang Zhenyu , Li Xing , Lyu Shengxiang , Zhan Qiang , Liu Fei , Lu Lungen , Zhong Liang , Chen Weixing , Shao Dong , Ding Yanbing , Liu Deliang , Yang Xiaozhong , Huang Zhiming , Li Zhaoshen , Du Yiqi 
Published: October 2024

Abstract

Background:
An evidence gap still exists regarding the efficacy and safety of tegoprazan in Chinese patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China.

Methods:
This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement.

Results:
A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: −1.7, 95% confidence interval [CI]: −8.5, 5.0, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients’ diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively.

Conclusion:
Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Trial Registration:

ClinicalTrials.gov, NCT03615677.
Safety and Efficacy of Neoadjuvant Docetaxel and Radiotherapy in Localized High-Risk Prostate Cancer
Authors: Ohaegbulam Kim C. , Post Carl M. , Farris Paige E. , Garzotto Mark , Beer Tomasz M. , Hung Arthur , Williamson Casey W. 
Published: October 2024

Objectives:
Approximately 15% of patients with localized prostate cancer are at high risk for disease recurrence. Many clinical trials have evaluated the impact of neoadjuvant therapy before radical prostatectomy with mixed results (NCT00321698).

Methods:
This phase I/II clinical trial evaluated the tolerability and preliminary efficacy of neoadjuvant radiation therapy and docetaxel before prostatectomy in 25 men with high-risk prostate cancer. The treatment regimen included 45 Gy radiotherapy in 25 fractions to the prostate and seminal vesicles over 5 weeks, along with weekly dose-escalated docetaxel up to 30 mg/m², followed by prostatectomy and bilateral lymph node dissection. The primary endpoint was the rate of pathologic complete response (pCR). Secondary endpoints included adverse events, symptom and quality of life measures, and prostate-specific antigen metrics.

Results:
All 25 patients completed the planned treatment. The primary endpoint of pCR was not achieved. Lymphopenia was the most common grade 3 or higher toxicity, with no grade 3 or higher genitourinary or gastrointestinal toxicities observed. With a median follow-up of 11.6 years, the 10-year biochemical recurrence-free survival was 60%, and distant metastasis-free survival was 80%. Prostate cancer-specific survival and overall survival at 10 years were 84% and 60%, respectively.

Conclusions:
Although pCR was not met, the treatment demonstrated a modest toxicity profile and reasonable long-term outcomes, suggesting feasibility and safety. Further studies are needed to optimize endpoints and assess the efficacy of neoadjuvant treatments compared with standard approaches in high-risk prostate cancer patients.
Observation of Two Novel mcr-10.1–Carrying Plasmids in Clinical Escherichia coli Strains
Authors: Liu Zhaopeng , Zheng Xinrou , Nan Congcong , Xu Jihua , Zhu Jiaming , Li Ling , Wang Mingyu , Wang Wenjia , Shen Wenlong 
Published: October 2024

Abstract
Polymyxins are a class of last-resort antibiotics used to treat infections caused by multidrug-resistant bacteria. Mobile resistance determinants for polymyxins, including mcr-1 to mcr-10 genes, have previously been reported. Among them, mcr-10 has commonly been observed in Enterobacter and Klebsiella species. However, the presence of mcr-10 in Escherichia coli, an important opportunistic pathogen, has rarely been reported. This work describes the observation of mcr-10.1 in two clinical E. coli strains, with mcr-10.1 hosted on two novel plasmids, one of which carries transconjugation genes. These strains were isolated from anal fistula–suffering patients, suggesting their close relation to human bacterial infection. The genetic context of mcr-10.1 was also found to differ from those previously identified in E. coli strains. This work is the first observation of mcr-10.1–carrying E. coli in clinical settings, expanding our knowledge of this important antibiotic resistance gene.
New Insights Into the Molecular Characteristics of Binary Toxin-Producing Clostridioides difficile Strains in China: A Comparative Genomics Study
Authors: Wu Tao , Bi Xiajing , Zhao Yuhong , Lv Tao , Zhou Yizheng , Zheng Lisi , Shen Ping , Zhu Danhua , Chen Yunbo 
Published: October 2024

Abstract
Binary toxin (CDT)-producing Clostridioides difficile is associated with severe clinical symptoms and high mortality rates. However, the fundamental genomic factors that underpin the differentiated prevalence of CDT-producing C. difficile strains in China remain to be elucidated. To provide a comprehensive view of the genetic characteristics, this study comprehensively analyzed whole-genome sequences of CDT-producing C. difficile strains from China. The number of unique accessory genes in sequence type (ST)-5 strains, which are predominant in China, increased steadily with the increasing number of genomes sampled, while the accumulation curve for ST-1 strains was shallower. This suggests that ST-5 may have an open pangenome, whereas ST-1 may have a relatively conservative and stable pangenome. The pathogenicity locus (PaLoc) variants of Clades 1, 2 and 5 were found to share a common genetic organization, with the CDT locus (CdtLoc) showing lower variability than PaLoc. PaLoc in Clade 3 exhibits an insertion of transposon Tn6218, which is clade-specific. The flexibility of the C. difficile accessory genome has facilitated the development of divergent lineages characterized by the presence of evolutionarily advantageous genetic traits. This genetic diversification has led to enhanced antimicrobial resistance, increased virulence and improved metabolic capacities, which collectively augment the ability of C. difficile to survive and proliferate.
Can Benzimidazole Resistance Undermine the Philippines’ Success in Controlling and Eliminating Soil-Transmitted Helminth Infections? A Mini-Review
Authors: Tenorio Jan Clyden B. , Belizario Vicente Y. , Furtado Luis Fernando Viana , Suttiprapa Sutas 
Published: October 2024

Abstract
Soil-transmitted helminth (STH) infections remain a significant global health burden, affecting over 1.5 billion people worldwide. In the Philippines, STH infections continue to be prevalent, despite ongoing control efforts. The Integrated Helminth Control Program, whose cornerstone is the mass drug administration with benzimidazole drugs, has shown some success in reducing STH prevalence in the country. However, the persistence of infection prevalence being above the national and global targets and the potential for benzimidazole resistance have raised concerns about the long-term sustainability of current control strategies. This review examines the development of benzimidazole resistance in STH, focusing on the role of single nucleotide polymorphisms in the β-tubulin isotype that alter the protein’s amino acid composition, thereby negatively affecting benzimidazole binding efficiency. This review discusses the epidemiology of STH infections in the Philippines, the implementation of the Integrated Helminth Control Program and the potential challenges posed by benzimidazole resistance. This review highlights the need for further research to assess the occurrence of benzimidazole resistance in Philippine STH populations and to explore alternative control strategies. Understanding the mechanisms of benzimidazole resistance and developing effective countermeasures is crucial for achieving sustainable STH control and elimination in the Philippines.
UK Government COVID-19 Response Employees’ Perceptions of Working From Home
Authors: Hall Charlotte E. , Brooks Samantha K. , Greenberg Neil , Weston Dale 
Published: October 2024

Objective
This study investigates perceptions of homeworking in UK Government response-focused employees that contributed to the COVID-19 pandemic response.

Method
A cross-sectional online survey with open-ended questions was conducted. Free-text responses detailing participants’ perceptions of barriers, facilitators, advantages, and disadvantages were analyzed using content analysis.

Results
A total of 1943 free-text responses (from 150 participants) were analyzed. There were many conflicting advantages and disadvantages provided by participants, but crudely more positive statements were provided than negative. Flexibility associated with working from home was the most common positive factor, and the isolation and impact on working relationships was the most reported negative factor of working from home.

Conclusions
We suggest a ‘one size fits all’ approach to supporting staff working from home is not fit for purpose due to individual circumstances and contextual factors.
Trust and Organizational Commitment in a Postpandemic Environment
Authors: Porter Marlene T. , Williams Kate , Boaze Alicia , Rennert Melissa , Brunson Amy 
Published: October 2024

OBJECTIVE
This study aimed to evaluate nurses' trust in their leader and organizational commitment, examining the relationship between these factors postpandemic and investigating if age, tenure, and specialty area predicted trust and commitment.

BACKGROUND
The nursing shortage was intensified by COVID-19. Nonnursing studies have explored the relationship of employee trust with organizational commitment, illustrating sparsity in nursing literature.

METHODS
This study used a cross-sectional, descriptive, correlational design. An electronic survey was sent to more than 1000 nurses, with a final sample size of 135 over 6 weeks.

RESULTS
Results demonstrated high levels of both trust and commitment. The correlation coefficients of all study variables were significant (P < 0.001). Organizational tenure predicted employee trust.

CONCLUSIONS
Developing leadership skills in building trust with the nursing team contributes to increased organizational commitment. Interventions such as leader development in establishing trust and building relationships with their team members may improve nurse retention and organizational commitment.
Expedited Partner Therapy Review
Authors: Jackson Kendra J. , Pickett Michelle L. 
Published: October 2024

Abstract
Sexually transmitted infection rates continue to rise in adolescents and young adults. Treatment of patients and their partners is vitally important to prevent reinfection and morbidity. Expedited partner therapy (EPT) is a legally available option for clinicians. EPT is endorsed by the Centers for Disease Control and Prevention and allows clinicians to prescribe medication for certain STIs for their patients' partner(s) without an evaluation of the partner(s). However, EPT is underutilized, and multisystem-level barriers exist to successful EPT exist. This article reviews the indications of EPT, common barriers to EPT and solutions to overcome these barriers, and practical considerations when prescribing EPT.
Exploring genetic signatures of zoonotic influenza A virus at the swine-human interface with phylogenetic and ancestral sequence reconstruction
Authors: Anker K.M. , Ciucani M.M. , Nissen J.N. , Anderson T.K. , Pedersen A.G. , Trebbien R. 
Published: October 2024

AbstractInfluenza A viruses (IAVs) in swine have zoonotic potential and pose a continuous threat of causing human pandemics, as demonstrated by the H1N1 pandemic in 2009. Despite increased genomic surveillance, we have limited knowledge of the IAV evolutionary dynamics leading to such zoonotic events and no clear understanding of genetic markers associated with interspecies transmission of IAV between humans and swine. To explore this, we analyzed a comprehensive publicly available whole genome dataset of human and swine IAV sequences. We conducted phylogenetic analyses and inference of ancestral host and sequence states for each IAV segment and mapped inferred mutations that were associated with transmission within and between swine and human hosts. We developed a custom python library to combine information from host and ancestral sequence annotated trees and applied statistical models to identify genetic markers associated with intra- or interspecies transmissions between swine and humans. This included analyzing mutation rates and the selective pressures acting on the viral proteins following intra- and interspecies transmissions and using a scalable, gradient-boosted decision tree machine learning approach to predict key amino acid positions critical for different transmission types. Our analyses indicated complex mutational patterns within and across viral proteins, but also suggested that specific protein regions and amino acid positions of especially several of the internal gene segments were more important for interspecies transmission. Our findings identify potential genetic signatures across the IAV proteins associated with host adaptation and zoonotic potential, offering valuable markers for early-warning genomic surveillance systems to enhance animal health and minimize the potential for zoonotic transmission of IAV.
Shared Genetic and Regulatory Mechanisms in Acute Myeloid Leukaemia and Blast Crisis Chronic Myeloid Leukaemia
Authors: Basu Sulagna , Pandey Rakesh 
Published: October 2024

ABSTRACTAcute Myeloid Leukemia (AML) and Blast Crisis Chronic Myeloid Leukemia (BC CML) share several clinical characteristics, including the accumulation of immature myeloid cells and disrupted hematopoiesis. Despite the similarities, the two diseases exhibit different genetic profiles, contributing to distinct disease progressions and therapeutic outcomes. In this study, we perform a comparative analysis using bioinformatics and systems biology approaches to explore shared and unique mutational signatures, transcriptional networks, and molecular regulators in AML and BC CML. Our analysis identifies 29 genes common to both diseases, which are involved in key biological processes such as cell proliferation, cell death regulation, and transcriptional control. A subsequent pathway enrichment highlights common pathways, including the PI3K-AKT signaling and cytokine-mediated signaling, that may contribute to disease progression and resistance to therapy. Additionally, we construct a protein-protein interaction network and a transcription factor-miRNA coregulatory network, revealing key hub genes such as TP53, RUNX1, and BCL2. These genes could be potential shared therapeutic targets for treating AML and BC CML. Therefore, our analysis offers insights into the molecular underpinnings of these aggressive hematological malignancies.
Label-Free Optical Biopsy Reveals Biomolecular and Morphological Features of Diabetic Kidney Tissue in 2D and 3D
Authors: Fung Anthony A. , Li Zhi , Boote Craig , Markov Petar , Jain Sanjay , Shi Lingyan 
Published: October 2024

AbstractKidney disease, the ninth leading cause of death in the United States, has one of the poorest diagnostic efficiencies of only 10%1. Conventional diagnostic methods often rely on light microscopy analysis of 2D fixed tissue sections with limited molecular insight compared to omics studies. Targeting multiple features in a biopsy using molecular or chemical reagents can enhance molecular phenotyping but are limited by overlap of their spatial and chromatic properties, variations in quality of the products, limited multimodal nature and need additional tissue processing. To overcome these limitations and increase the breadth of molecular information available from tissue without an impact on routine diagnostic workup, we implemented label-free imaging modalities including stimulated Raman scattering (SRS) microscopy, second harmonic generation (SHG), and two photon fluorescence (TPF) into a single microscopy setup. We visualized and identified morphological, structural, lipidomic, and metabolic biomarkers of control and diabetic human kidney biopsy samples in 2D and 3D at a subcellular resolution. The label-free biomarkers, including collagen fiber morphology, mesangial-glomerular fractional volume, lipid saturation, redox status, and relative lipid and protein concentrations in the form of Stimulated Raman Histology (SRH), illustrate distinct features in kidney disease tissues not previously appreciated. The same tissue section can be used for routine diagnostic work up thus enhancing the power of cliniopathological insights obtainable without compromising already limited tissue. The additional multimodal biomarkers and metrics are broadly applicable and deepen our understanding of the progression of kidney diseases by integrating lipidomic, fibrotic, and metabolic data.Abstract FigureGraphical AbstractLabel-free indicators of diabetic nephropathies.