bluuebunny/crossref_metadata_2025_split huggingface dataset:
SGK1-HDAC4-HMGB1 signaling pathway in the spinal cord dorsal horn participates in diabetic neuropathic pain
Authors: Zhang Mao-Biao , Chen Jia-Li , Lu Jia-Hui , Jia Gai-Li , Cao Hong , Li Jun 
Published: February 2025

Purpose: This study aimed to determine whether serum-and glucocorticoid-inducible kinase1 (SGK1) activation-dependent histone deacetylase 4 (HDAC4) phosphorylation, nucleocytoplasmic trafficking, and subsequent regulation of high-mobility group protein box 1 (HMGB1) expression are involved in type 2 diabetic neuropathic pain (DNP). Methods: The type 2 diabetic neuropathic pain model was established in rats by feeding them with a high-fat and high-sugar diet for 8 weeks and then fasting them for 12 h, followed by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). SGK1 was inhibited in the spinal cord by intrathecal administration of the SGK1 inhibitor GSK-650394. Results: The present study revealed that pSGK1/tSGK1 was persistently upregulated in the spinal cord of rats with type-2 DNP. The downregulation of pSGK1/tSGK1 through the intrathecal injection of the SGK1 inhibitor GSK-650394 significantly ameliorated the pain hypersensitivity, relieved the abnormal expression of pHDAC4/tHDAC4 and HMGB1, and affected HDAC4 nucleocytoplasmic trafficking in DNP rats. Conclusion: Our data suggest that SGK1 in the spinal cord modulates type-2 DNP by regulating the HDAC4/HMGB1 pathway.
Clinical thumb ulnar collateral ligament injury owing to a pathological fracture through an enchondroma of the proximal phalanx
Authors: van de Lucht Veronique , van Heijl Mark , Schep Niels 
Published: February 2025

A young woman presented with an acute ulnar collateral ligament injury of the thumb, owing to a pathological fracture through an enchondroma. Treatment included bone graft and fracture fixation, with successful healing and functional recovery. Level of evidence: V
Comparative analysis of alectinib and brigatinib in real-world treatment of advanced NSCLC with ALK rearrangements
Authors: Kim Kyuhwan , Kim Kyu Yean , Kang Hye Seon , Shin Ah Young , Kim Sung Kyoung , Park Chan Kwon , Lee Sang Haak , Kim Seung Joon , Lim Jeong Uk , Yeo Chang Dong 
Published: February 2025

Background and objectives: This study aimed to compare the efficacy of the second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) alectinib and brigatinib in the treatment of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements based on real-world data. Design and methods: We conducted a multicenter retrospective study using the Clinical Data Warehouse from seven university hospitals affiliated with the Catholic Medical Center. Patients diagnosed with ALK-positive advanced NSCLC and treated with alectinib or brigatinib were included. Key outcomes such as time to discontinuation (TTD), duration of response (DOR), overall survival (OS), and objective response rate (ORR) were analyzed. Results: A total of 143 patients were included (107 treated with alectinib, 36 with brigatinib). Alectinib was more frequently used as a first-line treatment (71% vs 44.4% for brigatinib, p = 0.008). Prior crizotinib treatment was more frequent in the brigatinib group (52.8% vs 22.4% for alectinib, p < 0.001). The best ORR was similar between the groups (84.1% for alectinib vs 83.3% for brigatinib, p = 0.518). The median TTD was 57.8 months (95% confidence interval (CI): 29.0–86.7) for alectinib and 39.6 months (95% CI: 21.7–57.4) for brigatinib ( p = 0.462). No significant differences were observed in intracranial TTD, intracranial DOR, or OS between the groups. Prior crizotinib treatment significantly shortened TTD for second-generation TKIs ( p = 0.025), but the overall TKI treatment duration did not show a significant difference between patients who received frontline second-generation ALK TKIs and those who received second-generation ALK TKIs sequentially after crizotinib. Conclusion: Alectinib and brigatinib demonstrated comparable efficacy in ALK-positive advanced NSCLC. Undergoing crizotinib followed by a second-generation TKI was not significantly different from initiating a second-generation TKI without prior crizotinib in terms of outcomes.
A bidirectional Mendelian randomization study integrating genome-wide association studies, expression quantitative trait locus, and methylation quantitative trait locus data revealed causal relationship between heavy cigarette dependence and Barrett’s esophagus
Authors: An Zhou , Zeng Meichun , Wang Xianhua 
Published: February 2025

Background: The association between smoking dependence and the risk of developing Barrett’s esophagus remains unclear. This study aimed to investigate whether a causal relationship exists between smoking dependence and Barrett’s esophagus, using Mendelian randomization analysis. Methods: Two-sample Mendelian randomization analysis was conducted to evaluate the impact of smoking and Barrett’s esophagus. Additionally, we applied summary data-based Mendelian randomization techniques to combine information from genome-wide association studies (GWAS) with expression quantitative trait locus and methylation quantitative trait locus. Results: Multivariable Mendelian randomization showed an association between smoking per day (odds ratio = 1.2, 95% confidence interval: 1.038–1.38, p = 0.014) or current smoking (odds ratio = 2.41, 95% confidence interval: 1.06–5.5, p = 0.037) and Barrett’s esophagus. Inverse variance-weighted methods of bidirectional Mendelian randomization also revealed that smoking per day was significantly associated with elevated risks of Barrett’s esophagus (odds ratio = 1.34, 95% confidence interval: 1.092–1.649, p = 0.005), while Barrett’s esophagus was also a susceptibility factor for smoking per day (odds ratio = 1.05, 95% confidence interval: 1.017–1.087, p = 0.003). By incorporating consistent summary data-based Mendelian randomization associations between DNA methylation and smoke/Barrett’s esophagus, gene expression and smoke/Barrett’s esophagus, and DNA methylation and gene expression, we identified that the genetic variant-cg00935895-RBM43 (ENSG00000184898)-smoke/Barrett’s esophagus axis exerted an effect on smoke/Barrett’s esophagus by altering the DNA methylation level, which regulated the expression level of RBM43. Conclusions: Our study provides evidence of a bidirectional causal association between smoking and Barrett’s esophagus from a genetic perspective, which sheds new light on the potential role of RBM43 as a mediator in facilitating the impact of smoking and Barrett’s esophagus.
Factors associated with in-hospital mortality in octogenarians managed by geriatric service in a referral hospital in Colombia
Authors: Cortes Bahamon Carlos Mario , Rodríguez Ángel Jenny , Ballesteros Tapias Jennifer Katherine , Chavarro-Carvajal Diego Andrés , Muñoz Oscar Mauricio 
Published: February 2025

Introduction: The demographic transition has significantly increased the number of hospitalizations in octogenarian patients. Previous studies have documented the importance of clinical, functional, and cognitive variables for in-hospital mortality risk, but their frequency and importance in Latin American populations is yet to be described. It is important because Colombia has multiple ethnic races, with different types of longevity, and we have a history of social violence that affects our life expectancy. The aim of this study is to define which risk factors are associated with in-hospital mortality in octogenarians, and how frequent they are and quantify the weight of each of these factors in the outcomes. Methodology: We present an analytical observational retrospective cohort study in adult patients over 80 years of age hospitalized and followed by the geriatrics service at Hospital Universitario San Ignacio (Bogotá, Colombia). The association between in-hospital mortality and multiple clinical, functional, and cognitive variables was evaluated by means of univariate and multivariate logistic regression analysis. Results: A total of 1235 hospitalizations were analyzed (age 85.5 ± 4.4 years, 58.62% women). Malnutrition was documented in 22.4%, dependency for basic activities (Barthel ⩽ 95) in 75.9%, and positive screening for frailty (FRAIL ⩾ 3) in 55.3%. Mortality was 5.67%. Factors independently associated with mortality were history of cancer (Odds ratio (OR): 2.31; 95% Confidence interval (CI): 1.34–3.98, p < 0.003), delirium (OR: 2.48; 95% CI: 1.44–4.28, p < 0.001), malnutrition (OR: 2.50; 95% CI: 1.46–4.28; p = 0.001), frailty (OR: 2.25; 95% CI: 1.13–4.45, p = 0.019), tachypnea on admission (OR: 1.09; 95% CI: 1.03–1.14, p = 0.002), and creatinine elevation (OR: 2.47; 95% CI: 1.47–4.15, p = 0.001). Conclusion: Factors easily identifiable at hospital admission and amenable to intervention could predict an increased risk of mortality in octogenarian patients, such as the presence of malnutrition, frailty, and delirium. These findings facilitate the estimation of mortality risk and serve as a starting point to investigate the potential benefit of early interventions in this population.
Targeted therapy and immunotherapy for gastric cancer: rational strategies, novel advancements, challenges, and future perspectives
Authors: Luo Dong , Liu Yunmei , Lu Zhengmao , Huang Lei 
Published: February 2025

Abstract
Gastric cancer (GC) is one of the most common malignant tumors worldwide, and its treatment has been a focus of medical research. Herein we systematically review the current status of and advancements in targeted therapy and immunotherapy for GC, which have emerged as important treatment strategies in recent years with great potential, and summarize the efficacy and safety of such treatments. Targeted therapies against key targets in GC, including epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR), have shown remarkable therapeutic efficacies by inhibiting tumor progression and/or blood supply. In particular, markable breakthroughs have been made in HER2-targeting drugs for HER2-positive GC patients. To address intrinsic and acquired resistances to HER2-targeting drugs, novel therapeutic agents including bispecific antibodies and antibody–drug conjugates (ADC) targeting HER2 have been developed. Immunotherapy enhances the recognition and elimination of cancer cells by activating body anticancer immune system. Programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) antibodies are the most commonly used immunotherapeutic agents and have been used with some success in GC treatment. Innovative immunotherapy modalities, including adoptive immune cell therapy, tumor vaccines, and non-specific immunomodulators therapy, and oncolytic viruses have shown promise in early-stage clinical trials for GC. Clinical trials have supported that targeted therapy and immunotherapy can significantly improve the survival and quality of life of GC patients. However, the effects of such therapies need to be further improved and more personalized, with advancement in researches on tumor immune microenvironment. Further studies remain needed to address the issues of drug resistance and adverse events pertaining to such therapies for GC. The combined application of such therapies and individualized treatment strategies should be further explored with novel drugs developed, to provide more effective treatments for GC patients.
Analysis and Experimental Study on the Internal Flow Performance of Deep-Sea Biological Pumping Sampler
Authors: Liu Guangping , Jin Yongping , Peng Youduo , Liu Deshun , Wan Buyan 
Published: February 2025

Abstract
To accurately acquire deep-sea live biological samples, a hydraulic suction macro-biological pressure-retaining sampler (HSMPS) was designed to achieve active capture of seafloor biological by a suction pump. The complex flow fields of deep-sea biologicals at three different locations were simulated. The deep-sea biologicals cause the flow field pressure and velocity to rise at different locations of the sampler, and the magnitude of the rise varies at different locations. The internal flow properties of the sampler were analyzed for different pumping flow rates the sampler. When the flow rate of the sampler pump was greater than 14 m3/h, the velocity of the inlet of the inflow area was greater than the limiting velocity of the deep-sea biologicals. The pumping test of deep-sea biologicals pumping sampler was carried out in the laboratory, and the test results were basically consistent with the simulation analysis. In order to balance the deep-sea biologicals damage and escape rate, the pumping flow of the sampler should be controlled between 14 and 16 m3/h. The test results provide a theoretical basis for the design of deep-sea biologicals sampling equipment.
Using problem formulation for an efficient, fit-for-purpose risk assessment of microbial plant protection products
Authors: Steenbergh Anne K. , Arts Gertie , Bakker Peter A. H. M. , de Boer Wietse , Glandorf Debora C. M. , ter Horst Mechteld M. S. , de Jonge Rob , de Kogel Willem Jan , Köhl Jürgen 
Published: February 2025

Abstract
The safety of the use of microbial plant protection products (PPP) is assessed before the products can be placed on the market. Due to large differences amongst microbial PPP a case-by-case approach is needed for this assessment. We propose to use the problem formulation approach based on pathways to harm to tailor the assessment to individual microbial PPP and to harmonise this approach when possible. The steps in problem formulation are described and examples are given of how the approach can be used for case-by-case assessments of microbial PPP. We also describe which other elements are needed to fully optimise the risk assessment of microbial PPP and how our approach fits in with the current EU regulatory framework and ongoing activities.
A generative model for evaluating missing data methods in large epidemiological cohorts
Authors: Radosavljević Lav , Smith Stephen M. , Nichols Thomas E. 
Published: February 2025

Abstract

Background
The potential value of large scale datasets is constrained by the ubiquitous problem of missing data, arising in either a structured or unstructured fashion. When imputation methods are proposed for large scale data, one limitation is the simplicity of existing evaluation methods. Specifically, most evaluations create synthetic data with only a simple, unstructured missing data mechanism which does not resemble the missing data patterns found in real data. For example, in the UK Biobank missing data tends to appear in blocks, because non-participation in one of the sub-studies leads to missingness for all sub-study variables.

Methods
We propose a tool for generating mixed type missing data mimicking key properties of a given real large scale epidemiological data set with both structured and unstructured missingness while accounting for informative missingness. The process involves identifying sub-studies using hierarchical clustering of missingness patterns and modelling the dependence of inter-variable correlation and co-missingness patterns.

Results
On the UK Biobank brain imaging cohort, we identify several large blocks of missing data. We demonstrate the use of our tool for evaluating several imputation methods, showing modest accuracy of imputation overall, with iterative imputation having the best performance. We compare our evaluations based on synthetic data to an exemplar study which includes variable selection on a single real imputed dataset, finding only small differences between the imputation methods though with iterative imputation leading to the most informative selection of variables.

Conclusions
We have created a framework for simulating large scale data with that captures the complexities of the inter-variable dependence as well as structured and unstructured informative missingness. Evaluations using this framework highlight the immense challenge of data imputation in this setting and the need for improved missing data methods.
Association between a publicly funded universal drug program and antipsychotic and antidepressant medication dispensing to children
Authors: Kitchen Sophie A. , Gomes Tara , Tadrous Mina , Pajer Kathleen , Gardner William , Lunsky Yona , Penner Melanie , Juurlink David , Mamdani Muhammad , Antoniou Tony 
Published: February 2025

Abstract

Background
The prescribing of antidepressants and antipsychotics to children has increased worldwide, but little is known about how changes in drug funding policy influence the practice. In 2018, Ontario introduced a universal pharmacare program (OHIP+) for children and youth, amending it in April 2019 to cover only those without private insurance. We examined the association of these policy changes with antipsychotic and antidepressant medication prescribing.

Methods
We conducted a population-based study of antidepressant and antipsychotic medication dispensing to children ≤ 18 years old between September 1, 2014, and February 29, 2020. We obtained dispensing data from the IQVIA Geographic Prescription Monitor database, and used interventional autoregressive integrated moving average models to examine whether the implementation of OHIP + and its subsequent revision were associated with changes in dispensing.

Results
The implementation of OHIP + was not associated with changes in the rate of antidepressants (-19.3 units per 1,000 population; 95% confidence interval [CI]: -41.7 to 3.1) or antipsychotics (+ 1.0 unit per 1,000 population; 95% CI: -5.4 to 7.5) dispensed. Similarly, subsequent changes to the program restricting coverage to children without private insurance were not associated with antidepressant (0.3 units per 1,000; 95% CI: -7.4 to 7.9) or antipsychotic (1.0 units per 1,000; 95% CI: -0.9 to 2.9) dispensing trends.

Conclusion
Implementation of a publicly-funded pharmacare program did not influence trends in antidepressant or antipsychotic medication dispensing among children.
COVID-19 in the years 2020 to 2022 in Germany: effects of comorbidities and co-medications based on a large-scale database analysis
Authors: Linder Roland , Peltner Jonas , Astvatsatourov Anatoli , Gomm Willy , Haenisch Britta 
Published: February 2025

Abstract

Background
The SARS-CoV-2 pandemic was a challenge for health care systems worldwide. People with pre-existing chronic diseases have been identified as vulnerable patient groups. Furthermore, some of the drugs used for these chronic diseases such as antihypertensive drugs have been discussed as possible influencing factors on the progression of COVID-19. This study examines the effect of medication- and morbidity-associated risk factors suspected to moderate the disease course and progression of COVID-19.

Methods
The study is based on claims data of the Techniker Krankenkasse, Germany’s largest statutory health insurance. The data cover the years 2020 to 2022 and include insured persons with COVID-19 diagnosis from both the outpatient and inpatient sectors and a control of insured persons without COVID-19 diagnosis. We conducted a matched case-control study and matched each patient with an inpatient diagnosis of COVID-19 to (a) 10 control patients and (b) one patient with an outpatient diagnosis of COVID-19 to form two study cohorts. We performed a descriptive analysis to describe the proportion of patients in the two cohorts who were diagnosed with comorbidities or medication use known to influence the risk of COVID-19 progression. Multiple logistic regression models were used to identify risk factors for disease progression.

Results
In the first study period the first study cohort comprised a total of 150,018 patients (13,638 cases hospitalised with COVID-19 and 136,380 control patients without a COVID-19 infection). Study cohort 2 included 27,238 patients (13,619 patients hospitalised with COVID-19 and 13,619 control patients with an outpatient COVID-19 diagnosis). Immunodeficiencies and use of immunosuppressives were strongest risk modifying factors for hospitalization in both study populations. Other comorbidities associated with hospitalization were diabetes, hypertension, and depression.

Conclusion
We have shown that hospitalisation with COVID-19 is associated with past medical history and medication use. Furthermore, we have demonstrated the ability of claims data as a timely available data source to identify risk factors for COVID-19 severity based on large numbers of patients. Given our results, claims data have the potential to be useful as part of a surveillance protocol allowing early-stage access to epidemiological data in future pandemics.
The mediating effect of air pollution on the association between meteorological factors and influenza-like illness in China
Authors: Yan Qinling , Cheke Robert A. , Tang Sanyi 
Published: February 2025

Abstract

Purpose
Although numerous studies have explored the complex relationship between air pollution, meteorological factors and respiratory infections, evidence for a mediating effect of air pollutants being involved in the association between meteorological factors and Influenza-like illness (ILI) is limited.

Methods
Correlations among ILI cases, air pollutants and meteorological factors were examined with Pearson correlation analyses. Further, we formulated six candidate mediation models to explore the mediating effect of air pollutant on the association between meteorological factors and ILI infections.

Results
The meteorological factors minimum temperature/maximum humidity moderated by maximum humidity/minimum temperature and pressure directly affect ILI infections, and that some of meteorological factors can also indirectly affect them through air pollutants. Increases in maximum humidity and minimum temperature can directly reduce the numbers of ILI cases, or indirectly reduce them by reducing the concentration of air pollutants.

Conclusion
When the haze with low temperature, low humidity is forecasted by the meteorological agency, the environmental protection departments can take effective control measures to reduce the concentration of air pollutants, and public health departments should advocate human behavioral changes in order to mitigate and control ILI prevalence.