bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of ChatGPT on Stage 1 of the Taiwanese medical licensing exam
Authors: Huang Chao-Hsiung , Hsiao Han-Jung , Yeh Pei-Chun , Wu Kuo-Chen , Kao Chia-Hung
Published: February 2024

Introduction

Since its release by OpenAI in November 2022, numerous studies have subjected ChatGPT to various tests to evaluate its performance in medical exams. The objective of this study is to evaluate ChatGPT's accuracy and logical reasoning across all 10 subjects featured in Stage 1 of Senior Professional and Technical Examinations for Medical Doctors (SPTEMD) in Taiwan, with questions that encompass both Chinese and English.

Methods

In this study, we tested ChatGPT-4 to complete SPTEMD Stage 1. The model was presented with multiple-choice questions extracted from three separate tests conducted in February 2022, July 2022, and February 2023. These questions encompass 10 subjects, namely biochemistry and molecular biology, anatomy, embryology and developmental biology, histology, physiology, microbiology and immunology, parasitology, pharmacology, pathology, and public health. Subsequently, we analyzed the model's accuracy for each subject.

Result

In all three tests, ChatGPT achieved scores surpassing the 60% passing threshold, resulting in an overall average score of 87.8%. Notably, its best performance was in biochemistry, where it garnered an average score of 93.8%. Conversely, the performance of the generative pre-trained transformer (GPT)-4 assistant on anatomy, parasitology, and embryology was not as good. In addition, its scores were highly variable in embryology and parasitology.

Conclusion

ChatGPT has the potential to facilitate not only exam preparation but also improve the accessibility of medical education and support continuous education for medical professionals. In conclusion, this study has demonstrated ChatGPT's potential competence across various subjects within the SPTEMD Stage 1 and suggests that it could be a helpful tool for learning and exam preparation for medical students and professionals.
Developing a second language listening and speaking assessment instrument for Use in student-led seminars in a chinese middle school english language acquisition class
Authors: Clark John Stewart , Terrett Matthew
Published: February 2024

L2 speaking and listening practice typically involves inauthentic highly scripted learning experiences that are not reflected in real-world contexts. Seminars represent an unscripted authentic learning experience preparing students for future college courses and public discourse. Using an action research design, we developed a listening and speaking assessment instrument for L2 students to be implemented in student-led seminar discussions. The assessment instrument also served as a method of feedforward. Our results indicate an increase in student engagement across the seminar sessions. This was demonstrated by corresponding increases in the number of contributions, number of times students initiated dialogue, and positive listening indicators. Limitations in our assessment instrument were identified but the positive outcomes in increasing student participation and engagement justify further development of this instrument.
Relationships Between Speech, Spatial and Qualities of Hearing Short Form SSQ12 Item Scores and their Use in Guiding Rehabilitation for Cochlear Implant Recipients
Authors: Mecklenburg Dianne J. , Graham Petra L. , James Chris J.
Published: February 2024

Cochlear implantation successfully improves hearing in most adult recipients. However, in rare cases, post-implant rehabilitation is required to maximize benefit. The primary aim of this investigation was to test if self-reports by cochlear implant users indicate the need for post-implant rehabilitation. Listening performance was assessed with the Speech, Spatial and Qualities short-form SSQ12, which was self-administered via a web-based survey. Subjects included over 2000 adult bilateral or unilateral cochlear implant users with at least one year of experience. A novel application of regression tree analysis identified core SSQ12 items that serve as first steps in establishing a plan for further rehabilitation: items 1, 8, and 11 dealing with single-talker situations, loudness perception, and clarity, respectively. Further regression and classification tree analyses revealed that SSQ12 item scores were weakly related to age, degree of tinnitus, and use of bilateral versus unilateral implants. Conversely, SSQ12 scores were strongly associated with self-rated satisfaction and confidence in using their cochlear implant. The SSQ12 total scores did not vary significantly over 1–9 or more years’ experience. These findings suggest that the SSQ12 may be a useful tool to guide rehabilitation at any time after cochlear implantation. Identification of poor performance may have implications for timely management to improve the outcomes, through various techniques such as device fitting adjustments, counseling, active sound exposure, and training spatial hearing.
The Incidental Diagnosis of Adenomatoid Tumour on Fallopian Tubes Submitted for Tubal Ligation at a Tertiary Laboratory in Northern Pretoria, South Africa
Authors: Thobakgale Nosipho Maria , Khaba Moshawa Calvin
Published: February 2024

Introduction:

Adenomatoid tumours are the most common benign mesothelial neoplasms of the fallopian tube. They are usually diagnosed incidentally in specimens submitted for bilateral tubal ligation and can be mistake for vascular or epithelial lesions.

Materials and methods:

A retrospective analysis of cases with adenomatoid tumour of the fallopian submitted for tubal ligation from 2012 to 2020. The clinicopathological characteristic data was retrieved from the laboratory information system.

Results:

A total of 11 cases with adenomatoid tumour of the fallopian tubes submitted for tubal ligation were identified in women with average age of 30.9 years. In all the cases, only 1 fallopian tube was affected. Grossly, the fallopian tubes did not show any discernible tumour. Immunohistochemical stains confirmed the diagnosis of adenomatoid tumours in all the cases.

Conclusion:

Adenomatoid tumours in fallopian tubes are infrequent, and pathologists shouldn’t overlook them especially in unsuspicious instances. As frequent as adenomatoid tumour of the fallopian tubes are uncommon, pathologists show be aware of as their misdiagnosis could lead mismanagement of patient with far reaching complication.
Comparison of common multiple imputation approaches: An application of logistic regression with an interaction
Authors: Smith Matthew J , Quartagno Matteo , Belot Aurelien , Rachet Bernard , Njeru Njagi Edmund
Published: February 2024

Background

Multiple imputation is often used to reduce bias and gain efficiency when there is missing data. The most appropriate imputation method depends on the model the analyst is interested in fitting. We consolidate and compare the performance and ease of use for several commonly implemented imputation approaches.

Methods

Using 1000 simulations, each with 10,000 observations, under six data-generating mechanisms (DGM), we investigate the performance of four methods: (i) ’passive imputation’, (ii) ’just another variable’ (JAV), (iii) ’stratify-impute-append’ (SIA), and (iv) ’substantive model compatible fully conditional specification’ (SMCFCS). The application of each method is shown in an empirical example using England-based cancer registry data.

Results

SMCFCS and SIA showed the least biased estimate of the coefficients for the fully, and partially, observed variable and the interaction term. SMCFCS and SIA showed good coverage and low relative error for all DGMs. SMCFCS had a large bias when there was a low prevalence of the fully observed variable in the interaction. SIA performed poorly when the fully observed variable in the interaction had a continuous underlying form.

Conclusion

SMCFCS and SIA give consistent estimation and either can be used in most analyses. SMCFCS performed better than SIA when the fully observed variable in the interaction had an underlying continuous form. Researchers should be cautious when using SMCFCS when there is a low prevalence of the fully observed variable in the interaction.
Be a man: A theory of climate change, masculinities and violence
Authors: Francis Ben
Published: February 2024

Experts increasingly agree that the impacts of climate change are likely to create new violent conflict risks and exacerbate existing ones. However, the extent of this link and the specific causal pathways are much less clear, and the role of gender in this process is under-examined. This paper theorizes that gendered norms, especially the expectations of how men perform their masculinities, are an intervening variable that might explain some of this relationship. In doing so, it engages with the emerging debate around the extent to which climate change influences the evolution of violent conflict, theorizing with an illustrative observation of the events of the Arab Spring in Tunisia and Syria. I find that there are plausible explanations for climate–conflict links involving gendered expectations of men’s behaviour serving as an intervening variable between climate change and violent conflict and discuss the implications of this for moving away from securitized approaches, future study and peacebuilding work.
Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission
Authors: Othman Jad , Potter Nicola , Ivey Adam , Jovanovic Jelena , Runglall Manohursingh , Freeman Sylvie D. , Gilkes Amanda , Thomas Ian , Johnson Sean , Canham Joanna , Cavenagh Jamie , Kottaridis Panagiotis , Arnold Claire , Ommen Hans Beier , Overgaard Ulrik Malthe , Dennis Mike , Burnett Alan , Wilhelm-Benartzi Charlotte , Dillon Richard , Russell Nigel H.
Published: February 2024

Selection of patients with NPM1-mutated acute myeloid leukemia (AML) for allogeneic transplant in first complete remission (CR1-allo) remains controversial because of a lack of robust data. Consequently, some centers consider baseline FLT3–internal tandem duplication (ITD) an indication for transplant, and others rely on measurable residual disease (MRD) status. Using prospective data from the United Kingdom National Cancer Research Institute AML17 and AML19 studies, we examined the impact of CR1-allo according to peripheral blood NPM1 MRD status measured by quantitative reverse transcription polymerase chain reaction after 2 courses of induction chemotherapy. Of 737 patients achieving remission, MRD was positive in 19%. CR1-allo was performed in 46% of MRD+ and 17% of MRD− patients. We observed significant heterogeneity of overall survival (OS) benefit from CR1-allo according to MRD status, with substantial OS advantage for MRD+ patients (3-year OS with CR1-allo vs without: 61% vs 24%; hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.64; P < .001) but no benefit for MRD− patients (3-year OS with CR1-allo vs without: 79% vs 82%; HR, 0.82; 95% CI, 0.50-1.33; P = .4). Restricting analysis to patients with coexisting FLT3-ITD, again CR1-allo only improved OS for MRD+ patients (3-year OS, 45% vs 18%; compared with 83% vs 76% if MRD-); no interaction with FLT3 allelic ratio was observed. Postinduction molecular MRD reliably identifies those patients who benefit from allogeneic transplant in first remission. The AML17 and AML19 trials were registered at www.isrctn.com as #ISRCTN55675535 and #ISRCTN78449203, respectively.
let-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching
Authors: Huang Peng , Peslak Scott A. , Shehu Vanessa , Keller Cheryl A. , Giardine Belinda , Shi Junwei , Hardison Ross C. , Blobel Gerd A. , Khandros Eugene
Published: February 2024

The switch from fetal hemoglobin (γ-globin, HBG) to adult hemoglobin (β-globin, HBB) gene transcription in erythroid cells serves as a paradigm for a complex and clinically relevant developmental gene regulatory program. We previously identified HIC2 as a regulator of the switch by inhibiting the transcription of BCL11A, a key repressor of HBG production. HIC2 is highly expressed in fetal cells, but the mechanism of its regulation is unclear. Here we report that HIC2 developmental expression is controlled by microRNAs (miRNAs), as loss of global miRNA biogenesis through DICER1 depletion leads to upregulation of HIC2 and HBG messenger RNA. We identified the adult-expressed let-7 miRNA family as a direct posttranscriptional regulator of HIC2. Ectopic expression of let-7 in fetal cells lowered HIC2 levels, whereas inhibition of let-7 in adult erythroblasts increased HIC2 production, culminating in decommissioning of a BCL11A erythroid enhancer and reduced BCL11A transcription. HIC2 depletion in let-7-inhibited cells restored BCL11A–mediated repression of HBG. Together, these data establish that fetal hemoglobin silencing in adult erythroid cells is under the control of a miRNA–mediated inhibitory pathway (let-7 ⊣ HIC2 ⊣ BCL11A ⊣ HBG).
Glyphosate- and aminomethylphosphonic acid (AMPA)-induced mortality and residues in juvenile brown trout (Salmo trutta f. fario) exposed at different temperatures
Authors: Drechsel Victoria , Krais Stefanie , Peschke Katharina , Ziegler Michael , Köhler Heinz-R. , Triebskorn Rita
Published: February 2024

Background

Glyphosate is a broad-spectrum, non-selective systemic herbicide with a commonly assumed low potential for accumulation in biota. Nevertheless, glyphosate has been shown to bioaccumulate in the tissues of several organisms. To understand the bioconcentration dynamics of glyphosate in fish, brown trout (Salmo trutta forma fario) of different age were exposed to different concentrations of glyphosate, the formulation Roundup® LB Plus, and the major transformation product aminomethylphosphonic acid (AMPA) for two, three, or four weeks at different temperatures in the laboratory. Mortality rates were determined, and tissue samples were collected at the end of the experiment to ascertain concentrations of glyphosate and AMPA residues by liquid chromatography coupled to mass spectrometry (LC–MS/MS).

Results

Brown trout mortality during exposure to glyphosate or AMPA was considerably higher at 15 °C than at 7 °C. Also, a significant increase in glyphosate concentrations in samples containing muscle, head, backbone, and caudal fin tissue with increasing exposure concentrations and temperatures was observed. Six-month-old fish contained more glyphosate per kg wet weight after exposure than ten-month-old fish. The bioconcentration factors (BCFs) for glyphosate and AMPA were much higher at 15 °C than at 7 °C, but in both cases decreased with higher glyphosate concentrations. The BCF for glyphosate formulated in Roundup® was higher than the one for the parent compound. Approximately 30–42% of the organ-absorbed glyphosate and AMPA remained in the tissues even when the fish were kept in clean water lacking the test substances for three weeks after termination of exposure.

Conclusion

Our study demonstrated that there is an interaction between glyphosate and ambient temperature in terms of toxicity. Further it was shown that increasing concentrations of glyphosate and AMPA in the surrounding media lead to significantly increased concentrations of these substances in brown trout tissues, although neither bioconcentration nor bioaccumulation of glyphosate in animal tissues is expected due to the high water solubility of this chemical. As a consequence, the uptake of glyphosate by humans through the consumption of contaminated edible fish is very likely.
Upregulation of CALD1 predicted a poor prognosis for platinum-treated ovarian cancer and revealed it as a potential therapeutic resistance target
Authors: Li Wei , Huang Limei , Qi Nana , Zhang Qinle , Qin Zailong
Published: February 2024

Background

Ovarian cancer (OC) has the worst prognosis among gynecological malignancies, most of which are found to be in advanced stage. Cell reduction surgery based on platinum-based chemotherapy is the current standard of treatment for OC, but patients are prone to relapse and develop drug resistance. The objective of this study was to identify a specific molecular target responsible for platinum chemotherapy resistance in OC.

Results

We screened the protein-coding gene Caldesmon (CALD1), expressed in cisplatin-resistant OC cells in vitro. The prognostic value of CALD1 was evaluated using survival curve analysis in OC patients treated with platinum therapy. The diagnostic value of CALD1 was verified by drawing a Receiver Operating Characteristic (ROC) curve using clinical samples from OC patients. This study analyzed data from various databases including Gene Expression Omnibus (GEO), Human Protein Atlas (HPA), The Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), GEPIA 2, UALCAN, Kaplan–Meier (KM) plotter, LinkedOmics database, and String. Different expression genes (DEGs) between cisplatin-sensitive and cisplatin-resistant cells were acquired respectively from 5 different datasets of GEO. CALD1 was selected as a common gene from 5 groups DEGs. Online data analysis of HPA and CCLE showed that CALD1 was highly expressed in both normal ovarian tissue and OC. In TCGA database, high expression of CALD1 was associated with disease stage and venous invasion in OC. Patients with high CALD1 expression levels had a worse prognosis under platinum drug intervention, according to Kaplan–Meier (KM) plotter analysis. Analysis of clinical sample data from GEO showed that CALD1 had superior diagnostic value in distinguishing patients with platinum "resistant" and platinum "sensitive" (AUC = 0.816), as well as patients with worse progression-free survival (AUC = 0.741), and those with primary and omental metastases (AUC = 0.811) in ovarian tumor. At last, CYR61 was identified as a potential predictive molecule that may play an important role alongside CALD1 in the development of platinum resistance in OC.

Conclusions

CALD1, as a member of cytoskeletal protein, was associated with poor prognosis of platinum resistance in OC, and could be used as a target protein for mechanism study of platinum resistance in OC.
Identifying quality indicators to measure workplace violence in healthcare settings: a rapid review
Authors: Lyver Brendan , Gorla Jaswanth , Schulz-Quach Christian , Anderson Melanie , Singh Brendan , Hanagan Trevor , Haines Jennifer , Sethi Rickinder
Published: February 2024

Structured summary

Background

Workplace violence (WPV) in healthcare is a growing challenge posing significant risks to patient care and employee well-being. Existing metrics to measure WPV in healthcare settings often fail to provide decision-makers with an adequate reflection of WPV due to the complexity of the issue. This increases the difficulty for decision-makers to evaluate WPV in healthcare settings and implement interventions that can produce sustained improvements.

Objective

This study aims to identify and compile a list of quality indicators that have previously been utilized to measure WPV in healthcare settings. The identified quality indicators serve as tools, providing leadership with the necessary information on the state of WPV within their organization or the impact of WPV prevention interventions. This information provides leadership with a foundation for planning and decision making related to addressing WPV.

Methods

Ovid databases were used to identify articles relevant to violence in healthcare settings, from which 43 publications were included for data extraction. Data extraction produced a total of 229 quality indicators that were sorted into three indicator categories using the Donabedian model: structure, process, and outcome.

Results

A majority of the articles (93%) contained at least 1 quality indicator that possessed the potential to be operationalized at an organizational level. In addition, several articles (40%) contained valuable questionnaires or survey instruments for measuring WPV. In total, the rapid review process identified 84 structural quality indicators, 121 process quality indicators, 24 outcome quality indicators, 57 survey-type questions and 17 survey instruments.

Conclusions

This study provides a foundation for healthcare organizations to address WPV through systematic approaches informed by quality indicators. The utilization of indicators showed promise for characterizing WPV and measuring the efficacy of interventions. Caution must be exercised to ensure indicators are not discriminatory and are suited to specific organizational needs. While the findings of this review are promising, further investigation is needed to rigorously evaluate existing literature to expand the list of quality indicators for WPV.
Stability and consistency of symptom clusters in younger versus older patients receiving chemotherapy
Authors: Morse Lisa , Cooper Bruce A. , Ritchie Christine S. , Wong Melisa L. , Kober Kord M. , Harris Carolyn , Shin Joosun , Oppegaard Kate , Hammer Marilyn J. , Schimmel Alejandra Calvo , Paul Steven M. , Conley Yvette P. , Levine Jon D. , Miaskowski Christine
Published: February 2024

Background

By 2035, the number of newly diagnosed cancer cases will double and over 50% will be in older adults. Given this rapidly growing demographic, a need exists to understand how age influences oncology patients’ symptom burden. The study purposes were to evaluate for differences in the occurrence, severity, and distress of 38 symptoms in younger (< 60 years) versus older (≥ 60 years) oncology patients undergoing chemotherapy and to evaluate for differences in the stability and consistency of symptom clusters across the two age groups.

Methods

A total of 1329 patients were dichotomized into the younger and older groups. Patients completed demographic and clinical questionnaires prior to the initiation of their second or third cycle of chemotherapy. A modified version of Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, and distress of 38 common symptoms associated with cancer and its treatment. Differences between the two age groups in demographic and clinical characteristics and ratings of occurrence, severity, and distress for the 38 symptoms were evaluated using parametric and nonparametric tests. Exploratory factor analyses were done within each age group to identify symptom clusters using symptom occurrence rates.

Results

Compared to the younger group (14.8 (± 7.0)), older adults reported a lower mean number of symptoms (12.9 (± 7.2)). Older patients experienced lower occurrence rates for almost 50% of the symptoms. Regarding symptom clusters, an eight-factor solution was selected for both age groups. Across the two age groups, the eight symptom clusters (i.e., physical and cognitive fatigue, respiratory, psychological, hormonal, chemotherapy-related toxicity, weight gain, gastrointestinal, epithelial) were stable. However, symptoms within the physical and cognitive, chemotherapy-related toxicity, and gastrointestinal clusters were not consistent across the age groups.

Conclusions

To be able to provide tailored and effective symptom management interventions to older oncology patients, routine assessments of the core symptoms unique to the symptom clusters identified for this group warrants consideration. The underlying mechanism(s) for these inconsistencies in symptom burden is an important focus for future studies.
The prevalence of hepatitis B in Chinese general population from 2018 to 2022: a systematic review and meta-analysis
Authors: Bai Shuwen , Dang Wen , Hong Wenying , Liao Wenyu , Smith Robert David
Published: February 2024

Background

Within China, Hepatitis B virus (HBV) infection remains widely prevalent and one of the major public health problems. There have been only two previous estimates of its prevalence at the population level in China, with the latest survey conducted in 2006. A meta-analysis estimated the prevalence of HBV within China between 2013 and 2017 as 7%. This review provides an updated estimate of HBV prevalence in China from 2018 to 2022.

Methods

Systematic searches of literature from January 1, 2018 to December 25, 2022 were conducted in four international databases (Medline, Web of Science, Embase, Cochrane Database of Systematic Reviews) and three Chinese databases (CNKI, CBM, and WanFang data). Random-effects meta-analyses were conducted to calculate the pooled HBV prevalence with 95% confidence intervals in the overall population and subgroups. Publication bias, heterogeneity between studies, and study quality were assessed.

Results

Twenty-five articles were included in the meta-analysis. The pooled prevalence of HBV infection in the Chinese general population from 2018 to 2022 was 3% (95%CI: 2–4%). The prevalence of HBV infection was similar between males and females (both 3%), while rural areas had a higher prevalence than urban areas (3% vs 2%). The highest prevalence of HBV was reported in the eastern provinces (4, 95%CI: 2–6%). The HBV prevalence of people aged ≥18 years old (6, 95%CI: 4–8%) was higher than people aged < 18 years old (0, 95%CI: 0–1%).

Conclusion

Compared to the previous meta-analysis prevalence in 2013–2017, the updated meta-analysis estimated prevalence of HBV infection (3%) from 2018 to 2020 showed a decreasing trend, suggesting China had moved into a lower intermediate epidemic area (2–5%). However, the prevalence of HBV in rural areas and eastern regions was still higher than the national average. People aged ≥18 years old showed a higher HBV prevalence. HBV prevention should be prioritized in the highest-prevalence areas and high-risk populations. Due to heterogeneity in data collection methods among studies, there remains a need for systematic surveillance of nationwide HBV prevalence.
Fetal hemodynamic changes and mitochondrial dysfunction in myocardium and brain tissues in response to anemia: a lesson from hemoglobin Bart’s disease
Authors: Luewan Suchaya , Apaijai Nattayaporn , Chattipakorn Nipon , Chattipakorn Siriporn C. , Tongsong Theera
Published: February 2024

Objective

Whether or not the effects of anemia in the early phase, while the fetuses attempts to increase cardiac output to meet oxygen requirement in peripheral organs, is detrimental to the fetal developing vital organs is little-known. The objective of this is to compare prenatal cardiovascular changes and post-abortal cellular damages in the myocardium as a pumping organ and the brain as a perfused organ between anemic fetuses (using fetal Hb Bart’s disease as a study model) in pre-hydropic phase and non-anemic fetuses.

Methods

Fetuses affected by Hb Bart’s disease and non-anemic fetuses at 16–22 weeks were recruited to undergo comprehensive fetal echocardiography. Cord blood analysis was used to confirm the definite diagnosis of fetal Hb Bart’s disease and normal fetuses. Fetal cardiac and brain tissues were collected shortly after pregnancy termination for the determination of oxidative stress and mitochondrial function, including mitochondrial ROS production and mitochondrial membrane changes.

Results

A total of 18 fetuses affected by Hb Bart’s disease and 13 non-anemic fetuses were recruited. The clinical characteristics of both groups were comparable. The affected fetuses showed a significant increase in cardiac dimensions, cardiac function, cardiac output and brain circulation without deteriorating cardiac contractility and preload. However, in the affected fetuses, mitochondrial dysfunction was clearly demonstrated in brain tissues and in the myocardium, as indicated by a significant increase in the membrane potential change (p-value < 0.001), and a significant increase in ROS production in brain tissues, with a trend to increase in myocardium. The findings indicated cellular damage in spite of good clinical compensation.

Conclusion

The new insight is that, in response to fetal anemia, fetal heart increases in size (dilatation) and function to increase cardiac output and blood flow velocity to provide adequate tissue perfusion, especially brain circulation. However, the myocardium and brain showed a significant increase in mitochondrial dysfunction, suggesting cellular damage secondary to anemic hypoxia. The compensatory increase in circulation could not completely prevent subtle brain and heart damage.
MZ1, a BRD4 inhibitor, exerted its anti-cancer effects by suppressing SDC1 in glioblastoma
Authors: Li Gen , Ma Liya , Feng Chenxi , Yin Hongli , Bao Jianping , Wu Di , Zhang Zimu , Li Xiaolu , Li Zhiheng , Yang Chun , Wang Hairong , Fang Fang , Hu Xiaohan , Li Mei , Xu Lixiao , Xu Yunyun , Liang Hansi , Yang Tianquan , Wang Jianwei , Pan Jian
Published: February 2024

Background

Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM.

Methods

The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses.

Results

In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM.

Conclusion

In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.
The association of HBV infection and head and neck cancer: a systematic review and meta-analysis
Authors: Tan Rukeng , Zhu Xinyu , Sun Yutong , Yang Shihao , Peng Chao , Feng Xinkai , Chen Zengyu , Yimamu Yiliyaer , Liao Guiqing , Yang Le
Published: February 2024

Background

Hepatitis B virus (HBV) infections is an important public health problem worldwide and closely affect extrahepatic cancer. Several recent studies have investigated the relationship between HBV infection and head and neck cancer (HNC), but their findings were inconsistent.In order to address the limitations of small sample sizes, we conducted a meta-analysis to assess the association between HBV and HNC.

Methods

We systematically searched PubMed, Web of Science, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure from inception to August 2023. Original articles published as a case-control or cohort study were included. HBV infection was identified by HBsAg, HBV DNA or ICD codes. Review articles, meeting abstracts, case reports, communications, editorials and letters were excluded, as were studies in a language other than English or Chinese. According to the MOOSE guidelines, frequencies reported for all dichotomous variables were extracted by two reviewers independently. Similarly, the outcomes of OR, RR or HR, and 95% CIs after adjusting for age and gender were collected.

Results

Thirteen relevant studies and 58,006 patients with HNC were included. Our analysis revealed a positive correlation between HBV and HNC (OR = 1.50; 95% CI: 1.28–1.77). After adjusting for age and gender, the similar result (OR = 1.30; 95% CI: 1.10–1.54) was obtained. Subgroup analysis further demonstrated a significant association between HBV infection and oral cancer (OR = 1.24; 95% CI: 1.05–1.47), as well as nasopharyngeal carcinoma (OR = 1.41; 95% CI: 1.26–1.58). However, due to the limited number of studies included, the statistical significance was not reached for cancer of the oropharynx (OR = 1.82; 95% CI: 0.66–5.05), hypopharynx (OR = 1.33; 95% CI: 0.88-2.00), and larynx (OR = 1.25; 95% CI: 0.69–2.24) after adjusting for age and gender. When excluding the interference of HIV/HCV, smoking and alcohol use, the final outcome (OR = 1.17; 95% CI: 1.01–1.35) got the same conclusion.

Conclusions

Our study confirmed a positive relationship between HNC, specifically oral cancer and nasopharyngeal carcinoma, and HBV infection. However, further investigation is required at the molecular level to gather additional evidence in HNC.
Physical and psychological correlates of somatic symptom in patients with functional constipation: a cross-sectional study
Authors: Zhao Zhifeng , Bai Bin , Wang Shiqi , Zhou Yin , Yu Pengfei , Zhao Qingchuan , Yang Bin
Published: February 2024

Background

The symptoms of functional constipation (FC) were obviously affected by mental symptoms, which was consistent with somatic symptoms. However, the characteristics of FC patients with somatic symptom remains unexplored.

Methods

Clinical characteristics including somatic symptom (SOM, PHQ-15), depression (PHQ-9), anxiety (GAD-7), quality of life (PAC-QOL), constipation (KESS), demographic variables, anatomical abnormalities and symptoms were investigated. Subsequent analyses encompassed the comparison of clinical parameters between patients with SOM + group (PHQ-15 ≥ 10) and SOM- group (PHQ-15 < 10), subgroup analysis, correlation analysis, and logistic regression. Lastly, we evaluated the somatic symptom severity (SSS) among FC patients subjected to various stressors.

Results

Notable disparities were observed between SOM + and SOM- groups in variety of physiological and psychological variables, including gender, stressful events, sleep disorders, reduced interest, GAD-7, PHQ-15, PHQ-9, PAC-QOL, anterior rectocele, KESS, and internal anal sphincter achalasia (IASA) (P < 0.05). Subgroup analysis affirmed consistent findings across mental symptoms. Correlation analyses revealed significant associations between SSS and KESS, anterior rectocele, GAD-7, PHQ-9, and PAC-QOL (P < 0.05). Logistic regression identified PHQ-9 (OR = 7.02, CI: 2.06–27.7, P = 0.003), GAD-7 (OR = 7.18, CI: 2.00–30.7, P = 0.004), and KESS (OR = 16.8, CI: 3.09–113, P = 0.002) as independent predictors of SSS. Elevated SSS scores were significantly associated with couple, parental, and work-related stressors (P < 0.05).

Conclusion

A marked heterogeneity was observed between SOM + and SOM- patients of FC, with SOM + accompanied by more severe constipation, anxiety and depression symptoms. This finding underscores the importance of considering somatic symptoms in diagnosis and treatment of FC.
Particulate matter 2.5 causally increased genetic risk of autism spectrum disorder
Authors: Jin Tianyu , Pang Qiongyi , Huang Wei , Xing Dalin , He Zitian , Cao Zheng , Zhang Tong
Published: February 2024

Background

Growing evidence suggested that particulate matter (PM) exhibit an increased risk of autism spectrum disorder (ASD). However, the causal association between PM and ASD risk remains unclear.

Methods

We performed two-sample Mendelian randomization (MR) analyses, using instrumental variables (IVs) sourced from the largest genome-wide association studies (GWAS) databases. We employed three MR methods: inverse-variance weighted (IVW), weighted median (WM), and MR-Egger, with IVW method serving as our primary MR method. Sensitivity analyses were performed to ensure the stability of these findings.

Results

The MR results suggested that PM2.5 increased the genetic risk of ASD (β = 2.41, OR = 11.13, 95% CI: 2.54–48.76, P < 0.01), and similar result was found for PM2.5 absorbance (β = 1.54, OR = 4.67, 95% CI: 1.21–18.01, P = 0.03). However, no such association was found in PM10 (β = 0.27, OR = 1.30, 95% CI: 0.72–2.36, P = 0.38). After adjusting for the false discovery rate (FDR) correction, our MR results remain consistent. Sensitivity analyses did not find significant heterogeneity or horizontal pleiotropy.

Conclusions

Our findings indicate that PM2.5 is a potential risk factor for ASD. Effective strategies to mitigate air pollutants might lead to a reduced incidence of ASD.
Mobile phone problem use and depressive symptoms: the mediating role of social support and attitude to aging among Chinese older adults
Authors: Ding Linlin , Li Zhihan , Jiang Hao , Zhang Xiaona , Xiong Zhenfang , Zhu Xinhong
Published: February 2024

Background

Little is known about mobile phone problem use (MPPU) among older adults. This study investigated critical factors affecting MPPU and filled the gap between MPPU and depressive symptoms in older people.

Methods

A cross-sectional study was conducted in community (n = 376) with questionnaires of Multidimensional Scale of Perceived Social Support (MSPSS), Geriatric Depression Scale (GDS-15), Attitudes to Aging Questionnaire (AAQ) and Mobile Phone Problem Use Scale (MPPUS).

Results

80.9% of older people used smartphones and spend less than three hours on mobile phone per day. The average MPPU score of Chinese elderly is greater than the cut off to 41. Female (β = -0.11, P = 0.037), living with spouse (β = -0.17, P = 0.03), and late marriage age (β = -0.16, P = 0.007) are less likely to develop MPPU. The relationship between MPPU and depressive symptoms was partially mediated by social support and attitude to aging.

Conclusion

Elderly people generally have higher MPPU scores. MPPU was associated with depressive symptoms, through social support and attitude to aging.
Impact of depressive symptoms on medication adherence in older adults with chronic neurological diseases
Authors: Schönenberg Aline , Heimrich Konstantin G. , Prell Tino
Published: February 2024

Background

Nonadherence to medication contributes substantially to worse health outcomes. Especially among older adults with chronic illness, multimorbidity leads to complex medication regimes and high nonadherence rates. In previous research, depressive symptomology has been identified as a major contributor to nonadherence, and some authors hypothesize a link via motivational deficits and low self-efficacy. However, the exact mechanisms linking depressive symptomology and nonadherence are not yet understood. This is in part because the often-employed sum scores cannot do justice to the complexity of depressive symptomology; instead, it is recommended to assess the influence of individual symptoms.

Methods

Following this symptom-based approach, we performed correlation, network and regression analysis using depressive symptoms as depicted by the items of the revised Beck Depression Inventory II (BDI) to assess their influence with nonadherence in N = 731 older adults with chronic neurological diseases. Nonadherence was measured with the self-report Stendal Adherence to Medication Score (SAMS).

Results

Even when controlling for sociodemographic and health-related covariates, the BDI remained the most influential contributor to nonadherence. Across different methods, Loss of Interest and Difficulty with Concentration were identified as particularly influential for nonadherence, linking nonadherence with other affective or somatic BDI items, respectively. Additionally, Fatigue, Problems with Decision Making, Suicidal Thoughts, and Worthlessness contribute to nonadherence.

Conclusion

Using a symptom-driven approach, we aimed to understand which depressive symptoms contribute to higher levels of nonadherence. Our results refine previous hypotheses about motivation and control beliefs by suggesting that it is not merely a lack of beliefs in the efficacy of medication that connects depressive symptoms and nonadherence, but rather an overall lack of interest in improving one’s health due to feelings of worthlessness and suicidal tendencies. This lack of interest is further substantiated by already sparse resources caused by changes in concentration and fatigue. In order to improve health outcomes and reduce nonadherence, these associations between depressive symptoms must be further understood and targeted in tailored interventions.
Heterogeneity in COVID-19 vaccine uptake within low-income minority communities: evidence from the watts neighborhood health study
Authors: Wong Elizabeth , Liu Ying , Shier Victoria , Datar Ashlesha
Published: February 2024

Background

The literature on disparities in COVID-19 vaccine uptake focuses primarily on the differences between White versus non-White individuals or differences by socioeconomic status. Much less is known about disparities in vaccine uptake within low-income, minority communities and its correlates.

Methods

This study investigates disparities in COVID-19 vaccination uptake within racial and ethnic minoritized communities with similar socioeconomic backgrounds and built environments, specifically focusing on Black-Hispanic disparities and disparities within the Hispanic community by country of origin. Data are analyzed from the fourth wave (June 2021- May 2022) of the Watts Neighborhood Health Study, a cohort study of public housing residents in south Los Angeles, CA. Linear probability models estimated the association between vaccine uptake and participants’ race/ethnicity, sequentially adding controls for sociodemographic characteristics, health care access and insurance, prior infection, and attitudes towards COVID-19 vaccines. Differences in reasons for vaccination status by race/ethnicity were also tested.

Results

Mexican Hispanic and non-Mexican Hispanic participants were 31% points (95% CI: 0.21, 0.41, p < 0.001) and 44% points (95% CI: 0.32, 0.56, p < 0.001) more likely to be vaccinated than non-Hispanic Black participants, respectively. The disparity between Black and Hispanic participants was reduced by about 40% after controlling for attitudes towards COVID-19 vaccines. Among Hispanic participants, non-Mexican participants were 13% points (95% CI: 0.03, 0.24, p = 0.01) more likely to be vaccinated than Mexican participants, however, these differences were no longer significant after controlling for individual and household characteristics (β = 0.04, 95% CI: -0.07, 0.15, p = 0.44).

Conclusion

There are sizeable racial and ethnic COVID-19 vaccination disparities even within low-income and minoritized communities. Accounting for this heterogeneity and its correlates can be critically important for public health efforts to ensure vaccine equity.
Impact of indoor Air Pollution on the Linear growth of children in Jimma, Ethiopia
Authors: Mulat Elias , Tamiru Dessalegn , Abate Kalkidan Hassen
Published: February 2024

Background

Stunting in children is the term for reduced linear growth and development, which is frequently brought on by a persistently inadequate diet, recurrent infections and chronic diseases or poor health conditions. Apart from the classic covariates of stunting, which include diet and illness, the relative contribution of household air pollution to chronic nutrition conditions is least studied. Hence, this study is conducted to investigate the impact of household air pollution on the linear growth of under-five children in Jimma town, Ethiopia.

Methods

A prospective cohort study was employed to collect data from 280 under-five children who lived in households using solid fuel (exposed group, n = 140) and clean fuel (unexposed group, n = 140). Height-for-age Z scores were compared in both groups over a 12-month follow-up period. The difference in differences estimators were used for comparison of changes in the height-for-age Z scores from baseline to end line in exposed and non-exposed groups. The independent effect of the use of solid fuels on height-for-age Z scores was analyzed through a multivariable linear regression model. Statistical Significances were declared at P < 0.05 and 95% CI level.

Results

In an unadjusted model (Model 1), compared with the clean fuel type, the mean difference in the height-for-age Z score of children in households using solid fuel was lower by 0.54 (-0.54, 95% CI -0.97, -0.12, P = 0.011). The beta coefficient remained negative after adjusting for age and sex (Model 2 -0.543, 95% CI -1.373, -0.563) and sociodemographic variables (Model 3: -0.543, 95% CI -1.362, -0.575). In the final model (Model 4), which adjusted for wealth quantile, dietary practice, water, sanitation and hygiene status and household food insecurity access scale, the beta coefficient held the same and significant (beta: -0.543, 95% CI -1.357, -0.579, P < 0.001). Higher HAZ scores were observed among female child (β: = 0.48, 95%CI: 0.28, 0.69), Child with father attended higher education (β: = 0.304 95%CI: 0.304, 95% CI 0.19, 0.41) as compared to male gender and those who did not attend a formal education, respectively. In contrast, child living in households with poor hygiene practices had lower HAZ score (β: -0.226, 95% CI: -0.449, -0.003), P < 0.001.

Conclusions

Exposure to indoor air pollution was inversely related to linear growth. Furthermore, sex, educational status and hygiene were found relevant predictors of linear growth. In such a setting, there is a need to step up efforts to design and implement public education campaigns regarding the health risks associated with exposure to household air pollution. Promoting improvements to kitchen ventilation and the use of improved cooking stoves, which will help to mitigate the detrimental effects of indoor air pollution on child growth impairment and its long-term effects.
Associations of habitual sedentary time with executive functioning and short-term memory in 7th and 8th grade adolescents
Authors: Van Oeckel Veerle , Poppe Louise , Deforche Benedicte , Brondeel Ruben , Miatton Marijke , Verloigne Maïté
Published: February 2024

Background

While there is increasing evidence for negative physical health consequences of high volumes of sedentary time and prolonged sedentary time in adolescents, the association with cognition is less clear. This study investigated the association of volumes of habitual sedentary time and prolonged sedentary time with executive functions and short-term memory in adolescents.

Methods

This study has a cross-sectional observational study design. Volumes of sedentary time and prolonged sedentary time (accumulated sedentary time spent in bouts of  ≥ 30 min) were measured using the Axivity AX3 accelerometer. Six cognitive functions (spatial and verbal short-term memory; and working memory, visuospatial working memory, response inhibition and planning as executive functions) were measured using six validated cognitive assessments. Data were analysed using generalised linear models.

Results

Data of 119 adolescents were analysed (49% boys, 13.4 ± 0.6 year). No evidence for an association of volumes of sedentary time and prolonged sedentary time with spatial and verbal short-term memory, working memory, and visuospatial working memory was found. Volumes of sedentary time and prolonged sedentary time were significantly related to planning. One hour more sedentary time or prolonged sedentary time per day was associated with respectively on average 17.7% (95% C.I.: 3.5–29.7%) and 12.1% (95% C.I.: 3.9–19.6%) lower scores on the planning task.

Conclusions

No evidence was found for an association of volumes of habitual sedentary time and prolonged sedentary time with short-term memory and executive functions, except for planning. Furthermore, the context of sedentary activities could be an important confounder in the association of sedentary time and prolonged sedentary time with cognition among adolescents. Future research should therefore collect data on the context of sedentary activities.

Trial registration

This study was registered at ClinicalTrials.gov in January 2020 (NCT04327414; released on March 11, 2020).