bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal pathways in lymphoid leukemia: the gut microbiota, immune cells, and serum metabolites
Authors: Zhuang Xin , Yin Qingning , Yang Rong , Man Xiaoying , Wang Ruochen , Geng Hui , Shi Yifen 
Published: September 2024

BackgroundWe employed Mendelian randomization (MR) to investigate the causal relationship between the gut microbiota and lymphoid leukemia, further exploring the causal relationships among immune cells, lymphoid leukemia, and potential metabolic mediators.MethodsWe utilized data from the largest genome-wide association studies to date, encompassing 418 species of gut microbiota, 713 types of immune cells, and 1,400 serum metabolites as exposures. Summary statistics for lymphoid leukemia, acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL) were obtained from the FinnGen database. We performed bidirectional Mendelian analyses to explore the causal relationships among the gut microbiota, immune cells, serum metabolites, and lymphoid leukemia. Additionally, we conducted a two-step mediation analysis to identify potential intermediary metabolites between immune cells and lymphoid leukemia.ResultsSeveral gut microbiota were found to have causal relationships with lymphoid leukemia, ALL, and CLL, particularly within the Firmicutes and Bacteroidetes phyla. In the two-step MR analysis, various steroid hormone metabolites (such as DHEAS, pregnenolone sulfateprogestogen derivatives, and androstenediol-related compounds) were identified as potential intermediary metabolites between lymphoid leukemia and immune cells. In ALL, the causal relationship between 1-palmitoyl-2-docosahexaenoyl-GPE (16:0/22:6) and ALL was mediated by CD62L-plasmacytoid DC%DC (mediated proportion=-2.84%, P=0.020). In CLL, the causal relationship between N6,n6,n6-trimethyllysine and CLL was mediated by HLA DR+ CD8br AC (mediated proportion=4.07%, P=0.021).ConclusionThis MR study provides evidence supporting specific causal relationships between the gut microbiota and lymphoid leukemia, as well as between certain immune cells and lymphoid leukemia with potential intermediary metabolites.
Characteristic of clinical trials related to traumatic brain injury registered on ClinicalTrials.gov over the past two decades (2004–2023)
Authors: Guo Ruili , Yang Qingya , Zhou Xuan , Li Shining , Liu Yao 
Published: September 2024

ObjectiveThe aim of this report is to provide a comprehensive overview of clinical trials and protocols related to traumatic brain injury over the past two decades.MethodsWe collected information on clinical trials related to traumatic brain injury (TBI) from the ClinicalTrials.gov database, identified key categorical variables, and assessed their characteristics.ResultsA total of 367 TBI-related trials were identified for analysis. All identified trials were interventional clinical trials. Most trials were small-scale, with 75.2% enrolling 1–100 participants, and only about 20% were funded by industry or the National Institutes of Health (NIH). In most trials, participants were gender-neutral (96.5%), and the primary age group was adults and older adults (56.9%). Of all identified TBI trials, 78.2% were randomized, and 69.4% were blinded. Additionally, the primary purpose of 297 trials (80.9%) was treatment, with drug therapy as the most common intervention. A total of 153 trials (41.7%) were completed; however, only 58 trials submitted results to the registry. Furthermore, 81 trials (22.1%) were discontinued early, primarily due to recruitment problems. Clinical trials started between 2004 and 2013 reported a higher proportion of results compared with those started between 2014 and 2023 (35.1% vs. 11.1%, p &lt; 0.001). In addition, between 2014 and 2023, there was an increase in trials for diagnostic purposes (2.4% vs. 6.5%, p &lt; 0.001).ConclusionBased on the data collected from the ClinicalTrials.gov, our study reveals that most clinical trials related to TBI focus on drug-related treatments, underreporting remains a significant concern, and greater emphasis should be placed on improving the publication and dissemination of clinical trial results.
Network pharmacology and molecular docking approach to elucidate the mechanisms of safflower, phellodendron, scutellaria baicalensis, coptis, and gardenia in hand–foot syndrome
Authors: Li Pengxing , Chen Lizhu , Liu Jianhui 
Published: September 2024

BackgroundSafflower, phellodendron, scutellaria baicalensis, coptis, and gardenia (SPSCG) are medicinal plants with a wide range of anti-inflammatory and antioxidant effects. However, the related mechanism of SPSCG against hand-foot syndrome (HFS) has yet to be revealed.ObjectiveTo investigate the mechanisms of SPSCG in the treatment of HFS using the Network Pharmacology.MethodsActive ingredients and targets of SPSCG for HFS were screened by the Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction databases. Potential therapeutic targets were collected from the GeneCards and OMIM databases. Subsequently, protein–protein interactions (PPI), Gene Ontology (GO) annotations, and pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to investigate the potential mechanism of the SPSCG in HFS. Then, molecular docking and molecular dynamics simulations were performed to predict the binding interactions between the active compound and the core target. Finally, vitro experiments were used to verify the repair effect of key ingredients of SPSCG on cell damage caused by 5-Fluorouracil.ResultsQuercetin, kaempferol, β-sitosterol, and stigmasterol were identified as the major active components of SPSCG. GO analysis showed a total of 1,127 biological processes, 42 terms cellular components, and 57 molecular functions. KEGG analysis showed that the MAPK, TNF, and IL-17 signaling pathways were significantly enriched. The PPI analysis discovered that EGFR, CASP3, AKT1, CCND1, and CTNNB1 shared the highest centrality among all target genes. The experimental results confirmed that these SPSCG active ingredients could treat HFS by reducing inflammation reaction and promoting cell damage repair.ConclusionSPSCG may alleviate HFS by exerting antioxidative effects and suppressing inflammatory responses.
Circadian gene signatures in the progression of obesity based on machine learning and Mendelian randomization analysis
Authors: Cheng Zhi’ang , Liu Binghong , Liu Xiaoyong 
Published: September 2024

ObjectiveObesity, a global health concern, is associated with a spectrum of chronic diseases and cancers. Our research sheds light on the regulatory role of circadian genes in obesity progression, providing insight into the immune landscape of obese patients, and introducing new avenues for therapeutic interventions.MethodsExpression files of multiple datasets were retrieved from the GEO database. By 80 machine-learning algorithm combinations and Mendelian randomization analysis, we discovered the key circadian genes contributing to and protecting against obesity. Subsequently, an immune infiltration analysis was conducted to examine the alterations in immune cell types and their abundance in the body and to investigate the relationships between circadian genes and immune cells. Furthermore, we delved into the molecular mechanisms of key genes implicated in obesity.ResultsOur study identified three key circadian genes (BHLHE40, PPP1CB, and CSNK1E) associated with obesity. BHLHE40 was found to promote obesity through various pathways, while PPP1CB and CSNK1E counteracted lipid metabolism disorders, and modulated cytokines, immune receptors, T cells, and monocytes.ConclusionIn conclusion, the key circadian genes (BHLHE40, CSNK1E, and PPP1CB) may serve as novel biomarkers for understanding obesity pathogenesis and have significant correlations with infiltrating immune cells, thus providing potential new targets for obese prevention and treatment.
Survival outcomes in patients with de novo metastatic Merkel cell carcinoma according to site of metastases
Authors: Khaddour Karam , Liu Mofei , Kim Emily Y. , Bahar Furkan , Lôbo Matheus M. , Giobbie-Hurder Anita , Silk Ann W. , Thakuria Manisha 
Published: September 2024

IntroductionMerkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin with a predilection for metastases. This study investigates the clinical outcomes in patients presenting with de novo Stage IV MCC according to the metastatic site(s) at presentation.Materials and methodsPatients who presented with one or more sites of distant metastatic MCC at initial diagnosis between 2009 and 2023 were identified. The presence or absence of one or more metastases in each organ was categorized for each patient at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Competing risk analysis was used to estimate the cumulative occurrence risk of MCC-specific death. Fisher’s exact test was used for response rate analysis. Results were considered statically significant if p &lt; 0.05.ResultsThirty-four patients presented with de novo distant metastatic MCC. There was no association between the number of metastatic sites at diagnosis and OS (p= 0.58), PFS (p=0.79), or response rates (p=0.53). However, the presence of bone metastases was associated with significantly shorter OS (8.2 versus 25.2 months, HR: 2.4, 95% CI 1.01-5.7, p= 0.04). MCC-specific death in patients with lymph node metastases was significantly lower than in patients without (HR: 0.28, 95% CI: 0.09-0.87, p= 0.013). The presence of bone metastases tended to associate with an increased risk of MCC-specific death, although not statistically significant. The location of metastases was not associated with the response rate to first-line treatment. There was no significant association between site of metastases and PFS.ConclusionIn this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of organs involved, was associated with significantly worse OS. The presence of lymph node metastases was associated with lower MCC-specific death. Further research is warranted in larger cohorts to investigate the impact of the location of metastases on clinical outcomes.
Clinical efficacy of Fufang Yinhua Jiedu (FFYH) granules in mild COVID-19 and its anti-SARS-CoV-2 mechanism by blocking autophagy through inhibiting the AKT/mTOR signaling pathway
Authors: Wang Wenlei , Zheng Zhihui , Qi Xiaoyuan , Wei Hailin , Mao Xuhua , Su Qin , Chen Xiang , Feng Yan , Qiao Guohong , Ma Tieliang , Tang Zhian , Zhou Guangming , Zhuang Jinqiang , Zhang Pinghu 
Published: September 2024

BackgroundFufang Yinhua Jiedu (FFYH) granules are recommended for treating coronavirus pneumonia (COVID-19) in China. However, its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity and clinical efficacy against COVID-19 remain to be confirmed.AimsOur study aimed to investigate the anti-SARS-CoV-2 effect and potential mechanism of FFYH.Materials and MethodsThe activity of FFYH against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated via cell pathogenic effects, immunoblotting, immunofluorescence staining, and qRT-PCR. The potential mechanism of FFYH against SARS-CoV-2 was investigated by immunoblotting. One head-to-head randomized controlled trial was designed to evaluate the clinical efficacy of FFYH in mild COVID-19. Two hundred patients were randomly recruited to receive either FFYH or LHQW (Lianhua Qingwen) granules.ResultsThe in vitro results indicated that FFYH effectively inhibited SARS-CoV-2 replication by suppressing CPE and decreasing viral RNA and protein expression. A time-of-drug-addition assay confirmed that FFYH mainly targeted the binding and replication stages of the SARS-CoV-2 life cycle. Mechanistic studies revealed that blocking SARS-CoV-2-triggered autophagy may be the primary mechanism by which FFYH protects against SARS-CoV-2 infection by regulating the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Clinical results confirmed that FFYH effectively shortened the recovery time of clinical symptoms and viral nucleic acid negativity, improved abnormal hematology parameters, and controlled excessive cytokine responses in mild COVID-19 patients. Subgroup analysis revealed that FFYH improved the recovery time of clinical symptoms, improved hematological parameters, and controlled excessive cytokine storms to a greater extent in the mild COVID-19 male subgroup, abnormal hematology subgroup, and 32–42-year-old subgroup than in the corresponding LHQW subgroup (P &lt; 0.05). No patients progressed to severe or critical cases.ConclusionOur results indicate that FFYH not only has good anti-viral activity against SARS-CoV-2 but also has significant efficacy against COVID-19, indicating that FFYH may be a novel complementary option for treating COVID-19.
Identifying precondition configurations of mathematics anxiety among middle school students in China: using NCA and QCA approaches
Authors: Zhang Kai , Zhou Jinhua 
Published: September 2024

IntroductionAddressing mathematics anxiety is important to ensure that students achieve good academic performance and maintain their mental health during the critical middle school period. However, previous studies have focused on the separate effects of the preconditions for mathematics anxiety, ignoring the interaction of factors. Therefore, this study aims to identify the determinants of mathematics anxiety from the perspective of complex systems via necessary condition analysis (NCA) and qualitative comparative analysis (QCA). To the best of our knowledge, this is the first study to identify configurations of preconditions of mathematics anxiety among middle school students.MethodsA total of 183 middle school students aged 16 to 19 years (Mage = 17.47, SD = 0.89) in China participated in this cross-sectional study. The outcome variable of the study is mathematics anxiety, and the condition variables include mathematics grade, parental support, learning motivation, learning planning, and learning interest.ResultsThe necessity condition analysis shows that not all the condition variables constitute the necessity condition of mathematics anxiety alone. Four paths for the influence of multiple condition variables on mathematics anxiety are identified via the configuration analysis. Notably, even students with high mathematics scores and learning interest still experience mathematics anxiety due to a lack of practical parental support and learning motivation. High levels of parental support can exacerbate the mathematics anxiety of students under two conditions: 1) a lack of learning motivation and learning plans, and 2) interest in learning but low mathematics scores and unclear learning plans.DiscussionThis study highlights the need to consider the comprehensive impact of mathematics anxiety, and the findings will help educators and researchers identify the different characteristics of mathematics anxiety in student populations.
Social media addiction and personality dimensions among Tunisian medical students
Authors: Guermazi Fatma , Abid Wissal , Baati Imen , Cherif Farah , Mziou Emna , Mnif Dorra , Feki Ines , Masmoudi Rim , Masmoudi Jawaher 
Published: September 2024

PurposeSocial media (SM) has become a common activity for today’s young people. It is sometimes overused and potentially results in SM addiction. This study aims to assess SM addiction and its associated factors in medical students and to examine its relationship with dimensions of personality global self-esteem, and social self-esteem.Materials and methodsWe carried out a cross-sectional study among a sample of medical students in the region of Sfax in Tunisia. Social Media Addiction Scale-Student Form (SMAS-SF), Big Five Inventory, Rosenberg Self-Esteem Scale, and Social Self-Esteem Inventory were used to collect data.ResultsOverall, 116 medical students were included in the survey. The median age of the participants was 26 years, and 91 students (78.4%) were female. Almost half of them (55.20%) were enrolled in the third cycle. The most widely used SM was Facebook (98.3%). Students with the highest SMAS-SF scores had a significantly younger age of first use (p=0.011, r=-0.235), spent more time on their favorite SM (p=0.005, r=0.260), and performed more activities on SM, namely: making comments (p=0.005), browsing SM profiles (p=0.018), and posting videos (p=0.007) or pictures (p=0.002). The need to establish an identity was significantly associated with higher SMAS-SF scores (p=0.011). We also found that neuroticism and a low level of conscientiousness were linked to high SMAS-SF scores (p=0.006, r=0.252 and p=0.050, r=-0.183, respectively). Moreover, high SMAS-SF scores were significantly related to lower global and social self-esteem scores (p=0.015, r=-0.226 and p=0.032, r=-0.199, respectively).ConclusionOur results highlight the critical need to take into consideration the evaluation and intervention of self-esteem and personality dimensional issues to target interventions for SM addiction among medical students.
Revisiting the hospital-issued gown in hospitalizations from a locus of control and patient-centered care perspectives: a call for design thinking
Authors: Gabay Gillie , Ornoy Hana 
Published: September 2024

IntroductionPatient-centered care (PCC) is the preferred health policy approach that emphasizes responding to individual patient preferences, wishes, and needs. PCC requires active patient engagement. While there has been extensive research on physicians' robes, there is limited research on hospital-issued patient gowns during hospitalizations. How does the gown affect the cognitive–emotional experience of hospitalized patients? How is the gown associated with PCC?MethodsThe sample of this cross-sectional study consisted of 965 patients who were hospitalized at least once during the past year in a tertiary hospital. Measures were previously published.ResultsThe gown was strongly associated with lack of control and increased distress, and was negatively associated with patient proactiveness, engagement, and taking responsibility for self-management of chronic illness. Compared to male patients, female patients wearing the gown had stronger negative emotions and cognitively strong associations with the external locus of control, which inhibited engagement.DiscussionThe hospital gown is an unacknowledged barrier to achieving PCC, inhibits patient engagement, and reflects the paradoxes of inadvertently excluding patients' needs from hospital practice. The hospital gown must be modified to protect the patient's voice and enhance engagement. Policymakers are called to apply design thinking to facilitate patient participation in decision-making to accord hospital clothing to PCC and improve healthcare delivery.
Generation Rx: evaluation of medication misuse prevention education for older adults
Authors: Emptage Ruth E. , Lovatt Brittany S. , Sloan Cynthia D. , Li Junan , Downing Molly N. , Summers Katherine E. 
Published: September 2024

ObjectiveIncreased medication misuse over the last two decades has prompted extensive discussion about the lack of evidence-based and evidence-informed prevention education programs targeting the topic. As older adults are high utilizers of medications, this is an important population to reach with such educational programming. This study was designed to assess the change in knowledge and behavioral intentions of older adult participants after attending an educational session focused on safe medication use utilizing the Generation Rx Older Adult Toolkit (GROAT) resources.MethodsThe Generation Rx team at The Ohio State University College of Pharmacy (OSU COP) partnered with The Ohio State University Extension offices (OSU Extension) across the state of Ohio to provide GROAT educational programming in their communities. OSU Extension Educators were trained via the standardized virtual training program, Generation Rx Ambassadors. Program participants were surveyed immediately before and after the educational events. Pre- and post-survey data was then analyzed to assess knowledge gain and behavioral intentions about safe medication practices, as well as program perception and program satisfaction.ResultsProgramming occurred between May 2022 and September 2022. In total, OSU Extension Educators collectively engaged 843 individuals in a prevention education program utilizing the GROAT materials. After excluding participants under 50 years of age, there were 297 pre surveys and 245 post surveys included in the data analysis. Knowledge gains from pre- to post-survey showed a significant increase in correct responses in seven of the eight questions asked regarding safe medication practices. All five questions evaluating behavioral intentions demonstrated positive results after the programming (p &lt; 0.001). Participants’ perceptions and program satisfaction were also favorable.ConclusionThis study found through pre- and post-survey results that the Generation Rx Older Adult Toolkit programming delivered by Generation Rx trained OSU Extension Educators significantly increased older adult participants’ knowledge and favorably impacted behavioral intentions around safe medication use practices.
Development and validation of the Upstream Social Interaction Risk Scale (U-SIRS-13): a scale to assess threats to social connectedness among older adults
Authors: Smith Matthew Lee , Barrett Matthew E. 
Published: September 2024

BackgroundSocial interactions are essential to social connectedness among older adults. While many scales have been developed to measure various aspects of social connectedness, most are narrow in scope, which may not be optimally encompassing, practical, or relevant for use with older adults across clinical and community settings. Efforts are needed to create more sensitive scales that can identify “upstream risk,” which may facilitate timey referral and/or intervention.ObjectiveThe purposes of this study were to: (1) develop and validate a brief scale to measure threats to social connectedness among older adults in the context of their social interactions; and (2) offer practical scoring and implementation recommendations for utilization in research and practice contexts.MethodsA sequential process was used to develop the initial instrument used in this study, which was then methodologically reduced to create a brief 13-item scale. Relevant, existing scales and measures were identified and compiled, which were then critically assessed by a combination of research and practice experts to optimize the pool of relevant items that assess threats to social connectedness while reducing potential redundancies. Then, a national sample of 4,082 older adults ages 60 years and older completed a web-based questionnaire containing the initial 36 items about social connection. Several data analysis methods were applied to assess the underlying dimensionality of the data and construct measures of different factors related to risk, including item response theory (IRT) modeling, clustering techniques, and structural equation modeling (SEM).ResultsIRT modeling reduced the initial 36 items to create the 13-item Upstream Social Interaction Risk Scale (U-SIRS-13) with strong model fit. The dimensionality assessment using different clustering algorithms supported a 2-factor solution to classify risk. The SEM predicting highest risk items fit exceptionally well (RMSEA = 0.048; CFI = 0.954). For the 13-item scale, theta scores generated from IRT were strongly correlated with the summed count of items binarily identifying risk (r = 0.896, p &lt; 0.001), thus supporting the use of practical scoring techniques for research and practice (Cronbach’s alpha = 0.80).ConclusionThe U-SIRS-13 is a multidimensional scale with strong face, content, and construct validity. Findings support its practical utility to identify threats to social connectedness among older adults posed by limited physical opportunities for social interactions and lacking emotional fulfillment from social interactions.