bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chinese herbal medicine combined with cognitive–behavioural therapy for avoidant paruresis: a controlled trial
Authors: Liang Shijie , Zhou Ying , Yu Chao , Gao Xiang , Ji Fangbin , Fang Qianyuan , Zhang Zhihang , Yang Libin , Zhao Youkang , Zhao Yuhui , Yin Renwu , Chen Kaimin , Lu Zheng 
Published: October 2023

BackgroundAvoidant paruresis is a common clinical condition in urology and psychosomatic medicine. However, it has limited treatment options that are safe and effective with few side effects.AimsOur study aimed to investigate the effectiveness and safety of the Chinese herbal Yangxin Tongquan decoction combined with cognitive–behavioural therapy (CBT) for avoidant paruresis.MethodsSixty-eight patients with avoidant paruresis were divided into a treatment group (33 patients) and a control group (35 patients). The control group was assigned 10 weeks of CBT and systematic desensitisation. In addition to CBT and systematic desensitisation, the treatment group was given the Chinese herbal Yangxin Tongquan decoction during the 10-week study. The Shy Bladder Syndrome Scale (SBS) and the Self-rating Anxiety Scale (SAS) were administered before and after treatment to measure any change.ResultsThe overall efficacy in the treatment group (n=30) was 80.0% vs 62.5% in the control group (n=33). Comparing pretreatment and post-treatment measures, both groups showed improvement in SBS scores and SAS scores (treatment group: t(SBS)=8.397, p(SBS)<0.001, t(SAS)=8.216, p(SAS)<0.001; control group: t(SBS)=6.802, p(SBS)<0.001, t(SAS)=5.171, p(SAS)<0.001). Moreover, both groups’ SBS and SAS scores changed significantly over time (SBS scores: Ftime=118.299, p<0.001; SAS scores: Ftime=92.114, p<0.001). However, the treatment group performed better than the control group (SBS scores: Ftime*group=5.709, p=0.020; SAS scores: Ftime*group=7.235, p=0.009).ConclusionsThe Chinese herbal Yangxin Tongquan decoction combined with cognitive–behavioural psychotherapy positively affects the treatment of avoidant paruresis without significant adverse effects.
Pathophysiological insights into machine learning-based subphenotypes of acute heart failure with preserved ejection fraction
Authors: Sotomi Yohei , Tamaki Shunsuke , Hikoso Shungo , Nakatani Daisaku , Okada Katsuki , Dohi Tomoharu , Sunaga Akihiro , Kida Hirota , Sato Taiki , Matsuoka Yuki , Sakamoto Daisuke , Kitamura Tetsuhisa , Komukai Sho , Seo Masahiro , Yano Masamichi , Hayashi Takaharu , Nakagawa Akito , Nakagawa Yusuke , Ohtani Tomohito , Yasumura Yoshio , Yamada Takahisa , Sakata Yasushi 
Published: October 2023

ObjectiveThe heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology.MethodsThis study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated.ResultsPhenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15.ConclusionsDistinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy.Trial registration numberUMIN-CTR ID: UMIN000021831.
UK trainees’ perceptions of leadership and leadership development
Authors: Snelling Iain , Brown Hilary , Hardy Louise , Somerset Lara , Bosence Samantha , Thurlow Jane 
Published: October 2023

PurposeThis paper reports on trainees’ perceptions of leadership and leadership development, to inform the support that may be provided to them. It draws on a formative evaluation of the new role of clinical leadership mentor (CLM), introduced by Health Education England South-West in 2018. CLMs are responsible for ‘overseeing the process and progress of leadership development among the trainees within their Trust/Local Education Provider’.MethodsThe evaluation was a formative evaluation, based on interviews with CLMs, trainees and trainers and a survey of trainees and trainers. Recruitment was through 8 of the 19 CLMs in the South West. A report for each participating CLM was available to support the development of their individual role. In exploring trainees’ perceptions of leadership and leadership development, this paper draws on data from trainees: 112 survey returns which included over 7000 words of free text data and 13 interviews.FindingsOur findings suggest a more nuanced understanding of leadership in medical trainees than was previously reported in the literature, and a wider acceptance of their leadership role. We highlight the problem of considering postgraduate doctors as a homogeneous group, particularly with reference to specialty. We also highlight that the organisational context for leadership development can be supportive or non-supportive. Leadership learning through genuine leadership experience with appropriate support from trainers and the wider Trust offers opportunities for both trainees and Trusts.Practical implicationsTrainees are accepting of their roles as leaders. The value of leadership learning through genuine leadership experience was highlighted. Improving the environment for leadership development offers Trusts and trainees opportunities for genuine service improvement.
Mission possible: open innovation in nursing and patient care services at Massachusetts General Hospital
Authors: Nadel Hiyam M , Al-Sultan Nour , Berger Alex , McCree Paula , Banister Gaurdia , Jung Olivia 
Published: October 2023

ObjectivesAlthough front-line nurses and staff are uniquely positioned to identify the inefficiencies and gaps in care delivery, formal processes are not always in place to hear from those very employees.DesignWe established a scalable process that embodies open innovation principles, to broaden and distribute the innovation locus.SettingMassachusetts General Hospital, Boston, MA.ParticpitantsWe invited 8800+ nurses and other direct caregivers to participate in organisational problem solving.InterventionsWe solicited employees to (1) identify pain points and develop solutions and (2) crowd vote to indicate which ideas they want to see implemented.Results177 employees submitted 225 ideas, and 928 cast a vote. The 40 participants who submitted top-voted ideas were invited to develop a detailed implementation plan; of those, 27 submitted one. Four ideas emerged as winners.ConclusionsFormulating a clear call for ideas, securing leadership buy-in and generating excitement about the process were essential to our efforts. Challenges associated with opening the innovation process involved managing a large volume of participants and submissions, and providing on-the-go training to nurses and staff who were not used to being asked to participate in organisational problem solving.
Mental health concerns precede quits: shifts in the work discourse during the Covid-19 pandemic and great resignation
Authors: del Rio-Chanona R. Maria , Hermida-Carrillo Alejandro , Sepahpour-Fard Melody , Sun Luning , Topinkova Renata , Nedelkoska Ljubica 
Published: October 2023

AbstractTo study the causes of the 2021 Great Resignation, we use text analysis and investigate the changes in work- and quit-related posts between 2018 and 2021 on Reddit. We find that the Reddit discourse evolution resembles the dynamics of the U.S. quit and layoff rates. Furthermore, when the COVID-19 pandemic started, conversations related to working from home, switching jobs, work-related distress, and mental health increased, while discussions on commuting or moving for a job decreased. We distinguish between general work-related and specific quit-related discourse changes using a difference-in-differences method. Our main finding is that mental health and work-related distress topics disproportionally increased among quit-related posts since the onset of the pandemic, likely contributing to the quits of the Great Resignation. Along with better labor market conditions, some relief came beginning-to-mid-2021 when these concerns decreased. Our study underscores the importance of having access to data from online forums, such as Reddit, to study emerging economic phenomena in real time, providing a valuable supplement to traditional labor market surveys and administrative data.
Genetic Polymorphisms of UDP-Glucuronosyltransferases and Susceptibility to Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis
Authors: Chen Xinyu , Hao Zhuolu , Wang Nannan , Zhu Jia , Yi Honggang , Tang Shaowen 
Published: October 2023

Background and Aim. UDP-glucuronosyltransferases (UGTs) play an important role in drug metabolism and detoxification by catalyzing the glucuronidation reaction, which is associated with the occurrence of antituberculosis drug-induced liver injury (AT-DILI). The relationship between UGTs polymorphisms and AT-DILI risk has been reported but with inconsistent results. We conducted a systematic review and meta-analysis to summarize the previous study results and evaluate the precise relationships. Methods. The PRISMA statement was strictly followed, and the protocol was registered in PROSPERO (CRD42022339317). The PICOS framework was used: patients received antituberculosis treatment, UGTs polymorphisms (mutants), UGTs polymorphisms (wild), AT-DILI, and case-control studies. Eligible studies were searched through nine databases up to April 27, 2022. The study’s qualities were assessed by the revised Little’s recommendations. Meta-analysis was conducted with a random-effects model using odds ratios (ORs) with 95% confidence intervals (95% CIs) as the effect size. Results. Twelve case-control studies with 2128 cases and 4338 controls were included, and 32 single nucleotide polymorphisms (SNPs) in the seven UGT genes have been reported in Chinese and Korean. All studies were judged as high quality. The pooled results indicated that UGT1A1 rs3755319 (AC vs. AA, OR = 1.454, 95% CI: 1.100–1.921,

P

= 0.009), UGT2B7 rs7662029 (G vs. A, OR = 1.547, 95% CI: 1.249–1.917,

P

< 0.0001; GG + AG vs. AA, OR = 2.371, 95% CI: 1.779–3.160,

P

< 0.0001; AG vs. AA, OR = 2.686, 95% CI: 1.988–3.627,

P

< 0.0001), and UGT2B7 rs7439366 (C vs. T, OR = 0.585, 95% CI: 0.477–0.717,

P

< 0.0001; CC + TC vs. TT, OR = 0.347, 95% CI: 0.238–0.506,

P

< 0.0001; CC vs. TC + TT, OR = 0.675, 95% CI: 0.507–0.898,

P

= 0.007) might be associated with the risk of AT-DILI. Conclusions. The polymorphisms of UGT1A1 rs3755319, UGT2B7 rs7662029, and UGT2B7 rs7439366 were significantly associated with AT-DILI susceptibility. However, this conclusion should be interpreted with caution due to the low number of studies and the relatively small sample size.
Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti–PD-1 Monotherapy: A Report from the International RRD Consortium
Authors: Das Anirban , Fernandez Nicholas R. , Levine Adrian , Bianchi Vanessa , Stengs Lucie K. , Chung Jiil , Negm Logine , Dimayacyac Jose Rafael , Chang Yuan , Nobre Liana , Ercan Ayse B. , Sanchez-Ramirez Santiago , Sudhaman Sumedha , Edwards Melissa , Larouche Valerie , Samuel David , Van Damme An , Gass David , Ziegler David S. , Bielack Stefan S. , Koschmann Carl , Zelcer Shayna , Yalon-Oren Michal , Campino Gadi Abede , Sarosiek Tomasz , Nichols Kim E. , Loret De Mola Rebecca , Bielamowicz Kevin , Sabel Magnus , Frojd Charlotta A. , Wood Matthew D. , Glover Jason M. , Lee Yi-Yen , Vanan Magimairajan , Adamski Jenny K. , Perreault Sebastien , Chamdine Omar , Hjort Magnus Aasved , Zapotocky Michal , Carceller Fernando , Wright Erin , Fedorakova Ivana , Lossos Alexander , Tanaka Ryuma , Osborn Michael , Blumenthal Deborah T. , Aronson Melyssa , Bartels Ute , Huang Annie , Ramaswamy Vijay , Malkin David , Shlien Adam , Villani Anita , Dirks Peter B. , Pugh Trevor J. , Getz Gad , Maruvka Yosef E. , Tsang Derek S. , Ertl-Wagner Birgit , Hawkins Cynthia , Bouffet Eric , Morgenstern Daniel A. , Tabori Uri 
Published: October 2023

Abstract

Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti–PD-1; 20 are progression free (median follow-up, 3.7 years). After second progression/recurrence (n = 55), continuing ICI-based salvage prolonged survival to 11.6 months (n = 38; P &lt; 0.001), particularly for those with extreme mutation burden (P = 0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and the immune microenvironment. Response to reirradiation was explained by an absence of deleterious postradiation indel signatures (ID8). CTLA4 expression increased over time, and subsequent CTLA4 inhibition resulted in response/stable disease in 75%. RAS–MAPK-pathway inhibition led to the reinvigoration of peripheral immune and radiologic responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency &gt; Lynch syndrome). We provide a mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology.

Significance:
Hypermutant RRD-HGG are susceptible to checkpoint inhibitors beyond initial progression, leading to improved survival when reirradiation and synergistic immune/targeted agents are added. This is driven by their unique biological and immune properties, which evolve over time. Future research should focus on combinatorial regimens that increase patient survival while limiting immune toxicity.
This article is featured in Selected Articles from This Issue, p. 201
Potent Personalized Venetoclax Partners for Acute Myeloid Leukemia Identified by Ex Vivo Drug Screening
Authors: Becker Pamela S. 
Published: October 2023

Summary:
High-throughput screens (HTS) have been utilized to assess the efficacy of single drugs against patient tumor samples with the purpose of optimizing precision therapy, but testing the synergy of drug combinations can identify the ideal second drug to add. With novel sophisticated HTS, effective venetoclax combinations can be revealed that provide the cell state, phenotype, and molecular features of the susceptible and resistant cell populations.
See related article by Eide, Kurtz et al., p. 452 (14) .
Concurrent Targeting of HDAC and PI3K to Overcome Phenotypic Heterogeneity of Castration-resistant and Neuroendocrine Prostate Cancers
Authors: Zhang Ailin , Lau Nathan A. , Wong Alicia , Brown Lisha G. , Coleman Ilsa M. , De Sarkar Navonil , Li Dapei , DeLucia Diana C. , Labrecque Mark P. , Nguyen Holly M. , Conner Jennifer L. , Dumpit Ruth F. , True Lawrence D. , Lin Daniel W. , Corey Eva , Alumkal Joshi J. , Nelson Peter S. , Morrissey Colm , Lee John K. 
Published: October 2023

Abstract

Castration-resistant prostate cancer (CRPC) consists of multiple phenotypic subtypes including androgen receptor (AR)-active prostate cancer (ARPC) and neuroendocrine prostate cancer (NEPC). Tumor cells with these phenotypes can coexist between metastases within a patient and within an individual tumor. Treatments that are effective across CRPC subtypes are currently lacking. Histone deacetylation is crucial for the regulation of chromatin structure and maintenance of cancer cell state and activation of the PI3K/AKT/mTOR signaling cascade is a tumor growth–promoting pathway. We therefore investigated combined targeting of histone deacetylase (HDAC) and PI3K using a rationally designed dual inhibitor, fimepinostat, in CRPC subtypes in vitro and in vivo. Dual HDAC1/2 and PI3K/AKT pathway inhibition by fimepinostat led to robust tumor growth inhibition in both ARPC and NEPC models including cell line– and patient-derived xenografts. HDAC1/2 inhibition combined with PI3K/AKT inhibition was more effective than targeting each pathway alone, producing growth inhibitory effects through cell-cycle inhibition and apoptosis. Molecular profiling revealed on-target effects of combined HDAC1/2 and PI3K/AKT inhibition independent of tumor phenotype. Fimepinostat therapy was also associated with the suppression of lineage transcription factors including AR in ARPC and Achaete-scute homolog 1 (ASCL1) in NEPC. Together, these results indicate that fimepinostat represents a novel therapeutic that may be effective against both ARPC and NEPC through CRPC subtype-dependent and -independent mechanisms.

Significance:
CRPC is a heterogeneous disease constituting multiple phenotypic subtypes that often co-occur within tumors or across metastases in patients. Existing targeted therapies for CRPC do not take this into account. Here we show that fimepinostat, a dual HDAC1/2 and PI3K/AKT inhibitor investigated clinically in other cancer types but not prostate cancer, may overcome this heterogeneity by effectively inhibiting both ARPC and NEPC subtypes of CRPC.
Chronic Total Occlusion is Not a Risk Factor for Mortality in Patients With Successful Percutaneous Coronary Intervention: A Cohort Study
Authors: Holck Emil N. , Winther Naja S. , Mogensen Lone Juul‐Hune , Christiansen Evald Høj 
Published: October 2023

Background
Fifteen percent of patients with coronary artery disease undergoing angiography have a chronic total occlusion (CTO). The current study aimed to investigate the long‐term prognosis after successful and unsuccessful CTO percutaneous coronary intervention (PCI) compared with PCI for non‐CTO lesions.

Methods and Results

The current study was designed as an observational, region‐wide, register‐based cohort study enrolling all patients undergoing PCI in the Central Region of Denmark in 2009 to 2019. Patients were stratified into non‐CTO, successful CTO, and unsuccessful CTO revascularization. Patients were followed until an event or January 1, 2022. The primary end point was all‐cause mortality. In 21 141 patients enrolled, 2108 underwent CTO PCI. Clinical presentation was acute coronary syndrome in 11 879 patients and chronic coronary syndrome in 7887 patients. After a median of 5.7 years (interquartile range, 3.3–8.8), long‐term all‐cause mortality was higher after CTO PCI compared with non‐CTO PCI, but the difference was statistically insignificant when adjusting for clinical factors (unadjusted hazard ratio [HR], 1.19 [95% CI, 1.09–1.29], adjusted HR, 1.08 [95% CI, 0.97–1.20];
P
=0.165). After successful CTO PCI, no difference compared with non‐CTO PCI was observed (unadjusted HR, 0.99 [95% CI, 0.90–1.10], adjusted HR, 0.99 [95% CI, 0.87–1.12];
P
=0.873). After unsuccessful CTO PCI, long‐term all‐cause mortality was higher than non‐CTO PCI (unadjusted HR, 1.82 [95% CI, 1.59–2.08], adjusted HR, 1.35 [95% CI, 1.13–1.63];
P
<0.001).

Conclusions
Patients undergoing PCI for CTO have elevated long‐term mortality compared with patients without CTO. Successful opening of the CTO(s) is associated with equal mortality compared with non‐CTO PCI. In contrast, failed CTO PCI is associated with worse long‐term mortality. These findings suggest the need for CTO programs with high success rates and low complication rates.
Abstract P1007: Graph Neural Network Analysis Of Dynamic Temporal Relationships Between Chromatin Accessibility And RNA Expression In The Developing Mouse Heart
Authors: Xu Sidra Y , Galdos Francisco X , Lee Carissa , Wu Sean M 
Published: October 2023

Mammalian development is a dynamic process that transforms the epigenetic and transcriptomic landscapes of cells as they differentiate into various cell types and tissues. In vertebrates, the heart is the first functioning organ of the embryo, but its development has yet to be fully understood. Using simultaneous scRNA-seq and scATAQ-seq data from three major timepoints (E8.5, E10.5, E16.5) of murine development, we develop a novel approach to analyze the temporal relationship between chromatin accessibility and gene expression across development using RNA velocity and interpretable graph neural network (GNN) models.
RNA velocity is a powerful splicing kinetics tool for uncovering directed transcriptional dynamics in complex biological systems, and it infers the direction and rate of change of gene expression in single cells over time by comparing the ratio of unspliced to spliced mRNA reads between adjacent cells. We represent the vectors identified through RNA velocity as a directed graph, thereby transforming the single-cell data with the additional simultaneous ATAC-seq information into an input for a GNN. The GNN then learns the temporal epigenetic and transcriptomic dynamics from the node feature information, ie. scATAC-seq, with the graph structure, ie. RNA velocity vectors, to predict the developmental trajectories of cells. After training of the GNN model, we implement an additional GNN explainer model to analyze it and identify subgraphs, ie. networks of DNA regions, that maximize the mutual information associated with its trajectory predictions.
By interpreting the contributions of ATAC peaks in the GNN model, we identify novel regulatory dynamics and trends involved in the separation of distinct cardiac lineages in the developing mouse heart. Ultimately, we provide new insight for future investigation into the temporal relationship between chromatin accessibility and gene expression levels..