bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental health workers’ perspectives on the implementation of a peer support intervention in five countries: qualitative findings from the UPSIDES study
Authors: Haun Maria Hildegard , Girit Selina , Goldfarb Yael , Kalha Jasmine , Korde Palak , Kwebiiha Eric , Moran Galia , Mtei Rachel , Niwemuhwezi Jackline , Nixdorf Rebecca , Nugent Lena , Puschner Bernd , Ramesh Mary , Ryan Grace Kathryn , Slade Mike , Charles Ashleigh , Krumm Silvia 
Published: May 2024

ObjectiveThe introduction of peer support in mental health teams creates opportunities and challenges for both peer and non-peer staff. However, the majority of research on mental health workers’ (MHWs) experiences with peer support comes from high-income countries. Using Peer Support In Developing Empowering Mental Health Services (UPSIDES) is an international multicentre study, which aims at scaling up peer support for people with severe mental illness in Europe, Asia and Africa. This study investigates MHWs experiences with UPSIDES peer support.DesignSix focus groups with MHWs were conducted approximately 18 months after the implementation of the UPSIDES peer support intervention. Transcripts were analysed with a descriptive approach using thematic content analysis.SettingQualitative data were collected in Ulm and Hamburg (Germany), Butabika (Uganda), Dar es Salaam (Tanzania), Be’er Sheva (Israel) and Pune (India).Participants25 MHWs (19 females and 6 males) from UPSIDES study sites in the UPSIDES Trial (ISRCTN26008944) participated.FindingsFive overarching themes were identified in MHWs’ discussions: MHWs valued peer support workers (PSWs) for sharing their lived experiences with service users (theme 1), gained trust in peer support over time (theme 2) and provided support to them (theme 3). Participants from lower-resource study sites reported additional benefits, including reduced workload. PSWs extending their roles beyond what MHWs perceived as appropriate was described as a challenge (theme 4). Perceptions about PSWs varied based on previous peer support experience, ranging from considering PSWs as equal team members to viewing them as service users (theme 5).ConclusionsConsidering local context is essential in order to understand MHWs’ views on the cooperation with PSWs. Especially in settings with less prior experience of peer support, implementers should make extra effort to promote interaction between MHWs and PSWs. In order to better understand the determinants of successful implementation of peer support in diverse settings, further research should investigate the impact of contextual factors (eg, resource availability and cultural values).Trial registration numberISRCTN26008944.
Adult bacterial conjunctivitis: resistance patterns over 12 years in patients attending a large primary eye care centre in the UK
Authors: Silvester Alexander , Neal Timothy , Czanner Gabriela , Briggs Michael , Harding Simon , Kaye Stephen 
Published: May 2024

PurposeTo determine whether there was a change in the resistance pattern of bacteria isolated from cases of conjunctivitis following the introduction of over-the-counter availability of chloramphenicol in 2005.Design and settingRetrospective review of laboratory records for adult patients with suspected bacterial conjunctivitis between 2001 and 2012 attending the Royal Liverpool University Hospital.ParticipantsPatients with suspected bacterial conjunctivitis. Organisms were identified by standard laboratory methods. Scanty growth and normal flora were considered as a negative result. For positive results, susceptibility testing was undertaken as per British Society for Antimicrobial Chemotherapy guidelines.Main outcome measuresPrevalence of groups of bacteria associated with acute conjunctivitis and their resistance to chloramphenicol, ciprofloxacin, gentamicin, and methicillin.ResultsA total of 8209 conjunctival swabs were reviewed; 1300 (15.8%) were considered positive, of which 977 (75.2%) and 323 (24.8%) bacteria were identified as Gram positive and Gram negative, respectively.Staphylococcus aureuswas the most prevalent organism identified. Resistance of all bacterial isolates to chloramphenicol was 8.4% varying from 3.0% to 16.4% while that for ciprofloxacin and gentamicin was 16.4% and 14.0%, respectively. Methicillin resistance amongS. aureuswas 8.3%.ConclusionResistance to chloramphenicol has remained stable since being made available over the counter. Among Gram-positive bacteria, the most prevalent causative agent of bacterial conjunctivitis, chloramphenicol sensitivity remains high.
Pancreatic neuroendocrine tumours: a comparison of cytological classification systems
Authors: Ackroyd Lauren , Hanks Matthew , Bancu Andrei , Khan Marium , Sajid Saira , Lobo Dileep N , Zaitoun Abed M 
Published: May 2024

AimsCytological classification systems provide a standardised interpretation framework for reporting cytological specimens. Three well-known classification systems can be applied when reporting pancreatic cytology. This study aimed to compare the accuracy of these classification systems (C1–C5 system, the Papanicolaou system and the WHO classification) for the assessment of pancreatic neuroendocrine lesions.MethodsWe analysed 73 pancreatic neuroendocrine tumour resections, 49 of which had corroborative cytology available, reported over a 12-year period, at a single UK tertiary referral centre. Each cytology case was classified using the aforementioned systems. The final tumour grade allocated at resection was used to assess and compare the accuracy of each cytological classification system.ResultsCytological assessment accurately reported 77.6% of neuroendocrine lesions as category IVB (neoplastic - other) on Papanicolaou grading, 77.6% as C5 (malignant) lesions and 85.7% as VII (malignant) on WHO grading. 74.3% of resected tumours were grade 1, 17.1% grade 2 and 8.6% grade 3. Complete resection was achieved in 80.8% of cases.ConclusionsThe results demonstrated that the WHO classification appeared to provide reduced ambiguity when compared with both ‘C’ and Papanicolaou classification systems; with a lower proportion of cases being classified as suspicious of malignancy as opposed to malignant. The Papanicolaou system was able to supersede the other two systems through its ability to distinguish neuroendocrine tumours from more aggressive entities such as pancreatic adenocarcinoma, thus, offering flexibility in management while still retaining a similar level of accuracy to the WHO classification system in distinguishing benign from malignant lesions.
Development and interpretation of a pathomics-driven ensemble model for predicting the response to immunotherapy in gastric cancer
Authors: Han Zhen , Zhang Zhicheng , Yang Xianqi , Li Zhe , Sang Shengtian , Islam Md Tauhidul , Guo Alyssa A , Li Zihan , Wang Xiaoyan , Wang Jing , Zhang Taojun , Sun Zepang , Yu Lequan , Wang Wei , Xiong Wenjun , Li Guoxin , Jiang Yuming 
Published: May 2024

BackgroundOnly a subset of patients with gastric cancer experience long-term benefits from immune checkpoint inhibitors (ICIs). Currently, there is a deficiency in precise predictive biomarkers for ICI efficacy. The aim of this study was to develop and validate a pathomics-driven ensemble model for predicting the response to ICIs in gastric cancer, using H&E-stained whole slide images (WSI).MethodsThis multicenter study retrospectively collected and analyzed H&E-stained WSIs and clinical data from 584 patients with gastric cancer. An ensemble model, integrating four classifiers: least absolute shrinkage and selection operator, k-nearest neighbors, decision trees, and random forests, was developed and validated using pathomics features, with the objective of predicting the therapeutic efficacy of immune checkpoint inhibition. Model performance was evaluated using metrics including the area under the curve (AUC), sensitivity, and specificity. Additionally, SHAP (SHapley Additive exPlanations) analysis was used to explain the model’s predicted values as the sum of the attribution values for each input feature. Pathogenomics analysis was employed to explain the molecular mechanisms underlying the model’s predictions.ResultsOur pathomics-driven ensemble model effectively stratified the response to ICIs in training cohort (AUC 0.985 (95% CI 0.971 to 0.999)), which was further validated in internal validation cohort (AUC 0.921 (95% CI 0.839 to 0.999)), as well as in external validation cohort 1 (AUC 0.914 (95% CI 0.837 to 0.990)), and external validation cohort 2 (0.927 (95% CI 0.802 to 0.999)). The univariate Cox regression analysis revealed that the prediction signature of pathomics-driven ensemble model was a prognostic factor for progression-free survival in patients with gastric cancer who underwent immunotherapy (p<0.001, HR 0.35 (95% CI 0.24 to 0.50)), and remained an independent predictor after multivariable Cox regression adjusted for clinicopathological variables, (including sex, age, carcinoembryonic antigen, carbohydrate antigen 19-9, therapy regime, line of therapy, differentiation, location and programmed death ligand 1 (PD-L1) expression in all patients (p<0.001, HR 0.34 (95% CI 0.24 to 0.50)). Pathogenomics analysis suggested that the ensemble model is driven by molecular-level immune, cancer, metabolism-related pathways, and was correlated with the immune-related characteristics, including immune score, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data score, and tumor purity.ConclusionsOur pathomics-driven ensemble model exhibited high accuracy and robustness in predicting the response to ICIs using WSIs. Therefore, it could serve as a novel and valuable tool to facilitate precision immunotherapy.
Cosmological implications of the Weyl geometric gravity theory
Authors: Harko Tiberiu , Shahidi Shahab 
Published: May 2024

AbstractWe consider the cosmological implications of the Weyl geometric gravity theory. The basic action of the model is obtained from the simplest conformally invariant gravitational action, constructed, in Weyl geometry, from the square of the Weyl scalar, the strength of the Weyl vector, and a matter term, respectively. The total action is linearized in the Weyl scalar by introducing an auxiliary scalar field. To maintain the conformal invariance of the action the trace condition is imposed on the matter energy–momentum tensor, thus making the matter sector of the action conformally invariant. The field equations are derived by varying the action with respect to the metric tensor, the Weyl vector field, and the scalar field, respectively. We investigate the cosmological implications of the theory, and we obtain first the cosmological evolution equations for a flat, homogeneous and isotropic geometry, described by Friedmann–Lemaitre–Robertson–Walker metric, which generalize the Friedmann equations of standard general relativity. In this context we consider two cosmological models, corresponding to the vacuum state, and to the presence of matter described by a linear barotropic equation of state. In both cases we perform a detailed comparison of the predictions of the theory with the cosmological observational data, and with the standard $$\Lambda $$
Λ
CDM model. By assuming that the presence of the Weyl geometric effects induce small perturbations in the homogeneous and isotropic cosmological background, and that the anisotropy parameter is small, the equations of the cosmological perturbations due to the presence of the Weyl geometric effects are derived. The time evolution of the metric and matter perturbations are explicitly obtained. Therefore, if Weyl geometric effects are present, the Universe would acquire some anisotropic characteristics, and its geometry will deviate from the standard FLRW one.
Prospects of buffer layer optimization for electrodeposited CZTS-based thin-film solar cell using SCAPS-1D
Authors: Alee Soheil , Soltanmohammadi Mina , Abrari Masoud , Ghanaatshoar Majid 
Published: May 2024

Kesterite Cu2ZnSnS4 (CZTS) has recently attracted the intensive attention of researchers as a significant photovoltaic material for the scalable production of thin film solar cells. We have particularly focused on replacing the conventional CdS buffer layer with non-toxic and earth-abundant materials of zinc stannate (Zn2SnO[Formula: see text] in environmentally friendly thin-film solar cells based on CZTS. Zinc stannate (ZTO) with a wide bandgap energy of about 3.33[Formula: see text]eV can be a promising material to reduce photon absorption loss and improve the photovoltaic performance of the device. Thus, the absorber and buffer layers were practically prepared to determine the bandgaps of layers for citation in SCAPS-1D simulation program. We employed chemical methods to deposit the CdS and CZTS layers and succeeded to obtain a high-quality kesterite phase of CZTS. The common configuration of FTO/CZTS/buffer/ZnO/AZO was the basis of the simulations in which, the thicknesses of the absorber and buffer layers were optimized by using the SCAPS-1D. According to the outcome of the simulations, the ZTO buffer layer has a better performance than CdS.
From Classification to Clinical Insights
Authors: Englhardt Zachary , Ma Chengqian , Morris Margaret E. , Chang Chun-Cheng , Xu Xuhai "Orson" , Qin Lianhui , McDuff Daniel , Liu Xin , Patel Shwetak , Iyer Vikram 
Published: May 2024

Passively collected behavioral health data from ubiquitous sensors could provide mental health professionals valuable insights into patient's daily lives, but such efforts are impeded by disparate metrics, lack of interoperability, and unclear correlations between the measured signals and an individual's mental health. To address these challenges, we pioneer the exploration of large language models (LLMs) to synthesize clinically relevant insights from multi-sensor data. We develop chain-of-thought prompting methods to generate LLM reasoning on how data pertaining to activity, sleep and social interaction relate to conditions such as depression and anxiety. We then prompt the LLM to perform binary classification, achieving accuracies of 61.1%, exceeding the state of the art. We find models like GPT-4 correctly reference numerical data 75% of the time.
While we began our investigation by developing methods to use LLMs to output binary classifications for conditions like depression, we find instead that their greatest potential value to clinicians lies not in diagnostic classification, but rather in rigorous analysis of diverse self-tracking data to generate natural language summaries that synthesize multiple data streams and identify potential concerns. Clinicians envisioned using these insights in a variety of ways, principally for fostering collaborative investigation with patients to strengthen the therapeutic alliance and guide treatment. We describe this collaborative engagement, additional envisioned uses, and associated concerns that must be addressed before adoption in real-world contexts.
Striking the Balance with a PD-L1×4–1BB Bispecific Antibody
Authors: Ha JongHoon , Grippin Adam J. , Kim Betty Y.S. , Jiang Wen 
Published: May 2024

AbstractAntibody-based immune checkpoint blockade therapy has revolutionized the field of cancer immunotherapy, yet its efficacy remains limited in immunologically cold tumors. Combining checkpoint inhibitors with costimulatory agonists improves tumoricidal activity of T cells but also can lead to off-target hepatotoxicity. Although bispecific antibodies confer tumor selectivity to alleviate undesirable adverse effects, toxicity concerns persist with increased dosing. In this issue of Cancer Research, Yuwen and colleagues introduce ATG-101, a tetravalent PD-L1×4–1BB bispecific antibody with high programmed death ligand 1 (PD-L1) affinity and low 4–1BB affinity, aiming to mitigate hepatotoxicity. ATG-101 demonstrates PD-L1–dependent 4–1BB activation, leading to selective T-cell activation within the tumor microenvironment. ATG-101 exhibits potent antitumor activity, even in large, immunologically cold, and monotherapy-resistant tumor models. Single-cell RNA sequencing reveals significant shifts of immune cell populations in the tumor microenvironment from protumor to antitumor phenotypes following ATG-101 treatment. In cynomolgus monkeys, no serious cytokine storm and hepatotoxicity are observed after ATG-101 treatment, indicating a broad therapeutic window for ATG-101 in cancer treatment. This study highlights the potential of tetravalent bispecific antibodies in cancer immunotherapy, with implications for various antibody-based treatment modalities across different fields.See related article by Yuwen et al., p. 1680
Genotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells
Authors: Rozenbaum Meir , Fluss Reut , Marcu-Malina Victoria , Sarouk Ifat , Meir Amilia , Elitzur Sarah , Zinger Tal , Jacob-Hirsch Jasmine , Saar Efrat G. , Rechavi Gideon , Jacoby Elad 
Published: May 2024

Abstract
Somatic variants in DNA damage response genes such as ATM are widespread in hematologic malignancies. ATM protein is essential for double-strand DNA break repair. Germline ATM deficiencies underlie ataxia–telangiectasia (A–T), a disease manifested by radiosensitivity, immunodeficiency, and predisposition to lymphoid malignancies. Patients with A–T diagnosed with malignancies have poor tolerance to chemotherapy or radiation. In this study, we investigated chimeric antigen receptor (CAR) T cells using primary T cells from patients with A–T (ATM−/−), heterozygote donors (ATM+/−), and healthy donors. ATM−/− T cells proliferate and can be successfully transduced with CARs, though functional impairment of ATM−/− CAR T-cells was observed. Retroviral transduction of the CAR in ATM−/− T cells resulted in high rates of chromosomal lesions at CAR insertion sites, as confirmed by next-generation long-read sequencing. This work suggests that ATM is essential to preserve genome integrity of CAR T-cells during retroviral manufacturing, and its lack poses a risk of chromosomal translocations and potential leukemogenicity.
Significance: CAR T-cells are clinically approved genetically modified cells, but the control of genome integrity remains largely uncharacterized. This study demonstrates that ATM deficiency marginally impairs CAR T-cell function and results in high rates of chromosomal aberrations after retroviral transduction, which may be of concern in patients with DNA repair deficiencies.
A Novel Macrophage Subpopulation Conveys Increased Genetic Risk of Coronary Artery Disease
Authors: Jiang Jiahao , Hiron Thomas K. , Agbaedeng Thomas A. , Malhotra Yashaswat , Drydale Edward , Bancroft James , Ng Esther , Reschen Michael E. , Davison Lucy J. , O’Callaghan Chris A. 
Published: May 2024

BACKGROUND:
Coronary artery disease (CAD), the leading cause of death worldwide, is influenced by both environmental and genetic factors. Although over 250 genetic risk loci have been identified through genome-wide association studies, the specific causal variants and their regulatory mechanisms are still largely unknown, particularly in disease-relevant cell types such as macrophages.

METHODS:
We utilized single-cell RNA-seq and single-cell multiomics approaches in primary human monocyte–derived macrophages to explore the transcriptional regulatory network involved in a critical pathogenic event of coronary atherosclerosis—the formation of lipid-laden foam cells. The relative genetic contribution to CAD was assessed by partitioning disease heritability across different macrophage subpopulations. Meta-analysis of single-cell RNA-seq data sets from 38 human atherosclerotic samples was conducted to provide high-resolution cross-referencing to macrophage subpopulations in vivo.

RESULTS:

We identified 18 782 cis-regulatory elements by jointly profiling the gene expression and chromatin accessibility of >5000 macrophages. Integration with CAD genome-wide association study data prioritized 121 CAD-related genetic variants and 56 candidate causal genes. We showed that CAD heritability was not uniformly distributed and was particularly enriched in the gene programs of a novel CD52-hi lipid-handling macrophage subpopulation. These CD52-hi macrophages displayed significantly less lipoprotein accumulation and were also found in human atherosclerotic plaques. We investigated the cis-regulatory effect of a risk variant rs10488763 on
FDX1
, implicating the recruitment of AP-1 and C/EBP-β in the causal mechanisms at this locus.

CONCLUSIONS:
Our results provide genetic evidence of the divergent roles of macrophage subsets in atherogenesis and highlight lipid-handling macrophages as a key subpopulation through which genetic variants operate to influence disease. These findings provide an unbiased framework for functional fine-mapping of genome-wide association study results using single-cell multiomics and offer new insights into the genotype-environment interactions underlying atherosclerotic disease.
Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study
Authors: Li Weili , Wang Sifei , Liu Lan , Chen Jiahao , Lan Jing , Ding Jiayue , Chen Zhiying , Yuan Shuhua , Qi Zhifeng , Wei Ming , Ji Xunming 
Published: May 2024

BACKGROUND:
Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment.

METHODS:
This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate.

RESULTS:

Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (
P
=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted
P
values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (
P
<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events.

CONCLUSIONS:
The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05404373.