bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infectious outcomes of a standardized subcutaneous immunoglobulin dose reduction strategy in primary immune deficiencies amid global shortage
Authors: Moral Moral Pedro , Cabanero-Navalon Marta Dafne , López-León Paula Teresa , Balastegui-Martín Héctor , Martínez Mercader Sandra , Mir Amparo , Garcia-Bustos Victor 
Published: January 2025

IntroductionImmunoglobulin replacement therapy (IgRT), either intravenous (IVIg) or subcutaneous (SCIg), is crucial for managing primary immune deficiencies (PIDs) with hypogammaglobulinemia by reducing infection rates and mortality. During the COVID-19 pandemic, a global shortage of SCIg prompted our unit to reduce SCIg doses or maintain the same dose intravenously. This study evaluates the impact of a standardized SCIg dose reduction on infection rates and clinical outcomes in patients with humoral PID and with a low burden of infections.MethodsAdult PID patients on SCIg for at least 6 months, with IgG trough levels ≥ 700 mg/dL (or ≥ 900 mg/dL under specific conditions), and no significant infections in the past 6 months were eligible. A dose reduction of 15 mg/kg/week (60 mg/kg/month) for every 150 mg/dL above 700 mg/dL (or 900 mg/dL) was proposed. Clinical and laboratory data, and infectious events at 6- and 12-month follow-ups, were analyzed.ResultsThirty-one patients with PID were included: common variable immunodeficiency (54.83%), IgG subclass deficiency (9.67%), and other PIDs (35.48%). The average SCIg dose was initially reduced from 7.82 g/week to 5.72 g/week and adjusted to 6.94 g/week at 12 months. There was no significant change in severe or mild infections before and at 6- and 12-months post-dose adjustment. The dose reduction saved an average of 5,550 euros per patient annually, totaling 172,050 euros annually for our cohort.DiscussionOptimizing SCIg doses in selected well-controlled humoral PIDs is feasible without increasing infection rates, conserving this plasma-derived product during shortages. Larger prospective studies are needed to confirm this strategy's utility and its application to other Ig formulations.
The role of isoniazid dosage and NAT2 gene polymorphism in the treatment of tuberculous meningitis
Authors: Jian Yi , Bao Yuhang , Yang Fashuang , Zhu Mei 
Published: January 2025

BackgroundTuberculous meningitis (TBM) is a non-purulent inflammatory condition affecting the meninges and spinal membranes, caused by Mycobacterium tuberculosis (MTB) infection. This study seeks to explore the impact of varying INH dosages and NAT2 gene polymorphisms on TBM treatment, contributing new insights to improve clinical management and patient prognosis.MethodsPatients with TBM hospitalized between July 2020 and December 2022 were categorized into two groups based on INH dosage: the standard-dose group (300 mg/day) and the high-dose group (600 mg/day). General and baseline data were collected, and NAT2 genotypes were identified using real-time fluorescent PCR with melting curve analysis. The clinical characteristics and outcomes of patients with TBM under varying INH dosages were analyzed.ResultsThis study enrolled 119 patients with TBM, including 32 (26.9%) in the standard-dose group and 87 (73.1%) in the high-dose group. The NAT2 genotypes were distributed as follows: 34 (28.6%) fast acetylators (FA), 73 (61.3%) intermediate acetylators (IA), and 12 (10.1%) slow acetylators (SA). By month 12, 25 patients (21.0%) experienced disability or death, with 22 cases (18.5%) occurring by the end of the 3rd month. Disability and mortality rates differed significantly between the standard-dose and high-dose groups for IA-type TBM patients (P = 0.014). Univariate analysis showed significant differences between groups in baseline focal neurological impairment and disability or mortality by the 3rd and 12th months. Multivariate logistic regression identified INH dosage, cranial nerve palsy, age, and headache as key prognostic factors for TBM.ConclusionHigh-dose INH treatment was associated with a reduced incidence of disability or death compared to the standard-dose regimen, indicating better efficacy and prognosis. In patients with IA-type TBM, the high-dose group showed a significantly lower rate of disability or mortality, suggesting that higher INH dosages may reduce the risk of adverse outcomes.
Association between albumin changes and prognosis in older patients with acute myocardial infarction
Authors: Yang Zhi-cheng , Zhang Lei , Xi Ying-bin , Jiang Gui-hua , Lin He , Pan Hui , Wang Zhi-hao 
Published: January 2025

Background and aimsAcute myocardial infarction (AMI) is the leading cause of death in the world. Therefore, early identification of the prognosis of older patients with AMI are particularly urgent, and better to improve treatment. This study aimed to explore the association between albumin changes and prognosis in older patients with AMI.MethodsOutcomes included all-cause death during hospitalization, cardiac death, gastrointestinal hemorrhage, nonfatal myocardial infarction, acute heart failure, and severe arrhythmia. Multivariable-adjusted Cox regression analysis and curve fitting were used to assess the relationship between albumin changes and prognosis in patients with AMI.ResultsOur study included 288 older patients with AMI. A S-shaped association between the albumin changes and mortality of patients with AMI was found. For all-cause death, we found two inflection points were − 3.27 and 0.92 g/L. On the left side of −3.27 g/L, the OR was 0.41 (OR: 0.41, 95%CI: 0.32–0.64, p &lt; 0.05). On the right side of 0.92 g/L, the OR was 0.58 (OR: 0.58, 95%CI: 0.34–0.86, p &lt; 0.05). The OR was 2.12 between −3.27 and 0.92 g/L (OR: 2.12, 95%CI: 1.16–6.24, p &lt; 0.05). For cardiac death, two inflection points were − 3.19 and 1.17 g/L. On the left side of −3.19 g/L, the OR was 0.45 (OR: 0.45, 95%CI: 0.28–0.79, p &lt; 0.05). On the right side of 1.17 g/L, the OR was 0.63 (OR: 0.63, 95%CI: 0.38–0.86, p &lt; 0.05). The OR was 4.53 between −3.19 and 1.17 g/L (OR: 4.53, 95%CI: 0.90–12.52, p &gt; 0.05). After adjusting for all potential covariates, albumin changes were negatively associated with gastrointestinal hemorrhage (OR: 0.87; 95%CI: 0.81–0.94, p &lt; 0.001). After adjusting for all potential covariates, albumin changes were negatively associated with acute heart failure (OR: 0.86; 95%CI: 0.75–0.99, p = 0.046).ConclusionOut findings showed that a S-shaped association between the albumin changes and mortality of older AMI patients, with the inflection of roughly −3.27 g/L and 0.92/L. And changes in albumin levels are negatively correlated with gastrointestinal bleeding and acute heart failure. These findings were helpful for the clinical treatment.
Chinese medicine for headaches in emergency department: a retrospective analysis of real-world electronic medical records
Authors: Mao Zhenhui , Wu Shirong , Fan Yuzhen , Sun Jingbo , Lyu Shaohua , Su Qiaozhen 
Published: January 2025

BackgroundHeadaches are common complaints in the emergency department (ED) and have raised concern about acute medication overuse. Chinese medicine is a major complementary and alternative medicine in China and effective for headaches. This study aims to summarize characteristics of headache patients at EDs and the utilization of Chinese medicine for headache managements in EDs.MethodsThe study conducted a retrospective analysis based on existing electronic medical records at EDs from four branches of Guangdong Provincial Hospital of Chinese Medicine. Only complete medical records with a first diagnosis of headache within the specified timeframe were included. Data was extracted, screened and standardized using a structured approach. Descriptive analyses and Apriori algorithm-based association rules were employed for the study.ResultsA total of 3,355 medical records were analyzed, with over 86% of headaches classified as non-urgent. Approximately 97% of the patients received a general diagnosis of headaches without further classification. Hypertension was the most prevalent concomitant diagnosis, affecting 27.42% of the patients. Western medicine was prescribed to 66% of the patients for headaches and co-existing conditions, while each type of acute medication was prescribed to fewer than 10% of the patients. Conversely, over one-third of the patients utilized headache-specific patented Chinese herbal medicine products. Additionally, oral and topical Chinese herbal medicine treatments were also administered for headaches in the emergency departments.ConclusionThe majority of headaches consulting in the EDs were non-urgent and treated with various forms of Chinese medicine, alone or in conjunction of western medicine. Chinese herbal medicine may be promoted as alternatives to Western acute medications for treating benign headaches.
Relationship between sleep quality and dietary nutrients in rural elderly individuals: a latent class analysis
Authors: Zhao Xinlei , Xie Xinyan , Zhou Han , Zhong Feng , Liu Cuiping 
Published: January 2025

BackgroundThis study sought to identify sleep patterns in older adults residing in rural regions, as well as investigate the potential influence of dietary nutrient intake on these patterns.MethodsData were collected from a cross-sectional sample of Qingdao Town, Shandong Province, China. The study investigated 1,167 elderly participants using a general questionnaire, the Pittsburgh Sleep Quality Index, the simplified Food Frequency Questionnaire, and 24-h dietary recall methods. Latent profile analysis and binary logistic regression were applied for data analysis.ResultsTwo sleep categories were identified as “Quick falling asleep, long time, high efficiency group,” Class 1(89.1%) and “Difficult falling asleep, short time, low efficiency group,” Class 2(10.9%). In comparison to Class 1, individuals in Class 2 exhibited a higher likelihood of experiencing difficulties in falling asleep quickly and having poor sleep efficiency when consuming less than 50 g/d of potatoes (OR = 1.863, p = 0.034). Conversely, a daily protein intake of 60 g or more (OR = 0.367, p = 0.007), a daily intake of retinol of 700 equivalents or more (OR = 0.212, p = 0.002), and a daily milk intake of 300 g or more (OR = 0.295, p = 0.035) were associated with a greater probability of falling asleep quickly, having longer sleep duration, and experiencing higher sleep efficiency.ConclusionOur analysis identified two distinct sleep quality patterns among elderly individuals in rural areas. The sleep quality of rural elderly individuals is influenced by their dietary habits. The findings demonstrated a positive association between enhanced sleep quality and higher intake of dairy products, potatoes, and foods containing retinol and protein. Therefore, we propose increased consumption of these nutritional sources for the elderly population.
Hippocampus-sparing volume-modulated arc therapy in patients with World Health Organization grade II glioma: a feasibility study
Authors: Xie Renxian , Huang Hongxin , Cai Qingxin , Lu Jiayang , Chen Tong , Xie Keyan , Chen Jianzhou , Chen Chuangzhen 
Published: January 2025

BackgroundRadiotherapy can improve the survival rates of patients with glioma; meanwhile, impaired cognitive functions have been brought to the forefront with the offending organ, the radiosensitive hippocampus. This study aimed to assess the feasibility of hippocampus-sparing volumetric-modulated arc therapy (HS VMAT) in patients with World Health Organization (WHO) grade II glioma.MethodsHS VMAT plans and non-hippocampus-sparing volumetric-modulated arc therapy (NHS VMAT) plans were generated using a computed tomography (CT) dataset of 10 patients who underwent postoperative radiotherapy. The dose volume histogram (DVH), homogeneity index (HI), conformity index (CI), and irradiated dose of the hippocampus and other organs at risk (OARs) were analyzed.ResultsNo significant differences were observed in HI and CI between the two plans. Regarding the protection of OARs, HS VMAT plans were equally capable and even lowered the radiation dosages to the brainstem (35.56 vs. 41.74 Gy, p = 0.017) and spinal cord (1.34 vs. 1.43 Gy, p = 0.006). Notably, HS VMAT plans markedly decreased doses to the ipsilateral hippocampus and the contralateral hippocampus, demonstrating its efficacy in hippocampal dose reduction.ConclusionThe HS VMAT plan can be used to efficiently lower the dosage delivered to the hippocampus and may, to some extent, help lessen the risk of cognitive damage. The encouraging results of our study need to be further validated by clinical trials to confirm the benefits of the HS VMAT plans in preserving cognitive functions in patients with glioma.
Cyanoacrylate glue in breast surgery: the GLUBREAST Trial
Authors: Esposito Emanuela , Siani Claudio , Donzelli Ivana , Crispo Anna , Coluccia Sergio , Di Gennaro Piergiacomo , Luongo Assunta , Avino Franca , Fucito Alfredo , Marone Ugo , Melucci Maria Teresa , Saponara Ruggero , di Giacomo Raimondo 
Published: January 2025

IntroductionIn 2018, the National Cancer Institute of Naples has launched the GLUBREAST Trial to verify the efficacy of cyanoacrylate sealing glue to prevent or reduce seroma after axillary dissection in breast surgery. The glue is a synthetic sealant (N-Butyl-2-CyanoAcrylate+Metacryloxisulfolane) biocompatible, CE approved for internal human uses and surgical procedures. The assumed mechanism of action in breast surgery is that the glue would create a seal coating in the operative field to occlude lymphatic leaks and limit seroma formation.Materials and methodsThe trial included 180 patients scheduled for breast-conserving surgery or for radical modified mastectomy without reconstruction. Out of 180 patients, 91 were randomized to receive suction drain and sealant glue after axillary dissection (Experimental Arm), whereas 89 patients (Control Arm) received suction drain without glue.StatisticsA multivariable mixed effect model on presence of liquid drained and volume drained was calculated. Stratified models by visits were performed.ResultsThe trial ended in June 2022. Older age was associated with a higher volume of seroma drained per day (β 0.30; 95% CI: 0.00–0.60). A 5-U increase in body mass index was associated with higher daily drained seroma volume in patients who underwent breast-conserving surgery (β 5.0; 95% CI: 0.62–9.4), but not in patients who underwent mastectomy (β 2.5; 95% CI: −3.6–8.6). We did not find statistically significant differences in presence of liquid drained and volume drained among the study groups. An advantage for the Experimental Arm was observed from third and fourth to fifth outpatient visits without reaching a statistical significance (p=0.069 and p=0.072, respectively); so far, 5% of patients in the Experimental Group had clinical benefit from the glue.ConclusionsThe vast majority of data in the literature come from case series, and surgeons need a higher level of evidence to drive surgical decision-making and choose proper devices to increase patient quality of life. The GLUBREAST randomized trial tested the efficacy of cyanoacrylate sealing glue to prevent postoperative seroma in breast surgery. Although only a small number of patients benefited from sealant application, we regret to say this trial has some limitation, i.e., the prolonged presence of suction drain. Further research is warranted to better clarify the benefit of cyanoacrylate glue in breast surgery.
Burden of esophageal cancer in global, regional and national regions from 1990 to 2021 and its projection until 2050: results from the GBD study 2021
Authors: Zhang Chengcheng , Chen Linzhi , Xiu Yuqi , Zhang Hongling , Zhang Yuejuan , Ying Wenjuan 
Published: January 2025

BackgroundEsophageal cancer (EC) is a major global health issue characterized by high morbidity and mortality rates, with a notably low five-year survival rate. Comprehensive analyses of the global burden of EC remain limited and outdated, despite its global significance. This study aimed to systematically assess the global burden and trends of esophageal cancer across diverse populations.MethodsData on the burden of EC were collected from the Global Burden of Disease (GBD) 2021 study, including estimates of incidence, mortality, and disability-adjusted life years (DALYs), as well as risk factors, spanning 204 countries and territories. Age-standardized rates (ASRs) were calculated to allow comparisons across populations. The study further explored the relationship between EC burden and socioeconomic development by utilizing the Socio-demographic Index (SDI), aggregating data by regions. The Bayesian age-period-cohort model was applied to project future trends until 2050.ResultsIn 2021, there were 576,529 new esophageal cancer cases, with an age-standardized incidence rate (ASIR) of 6.65 per 100,000, reflecting a 24.87% decrease since 1990. The global number of deaths reached 538,602, with an age-standardized death rate (ASDR) of 6.25 per 100,000, representing a 30.67% decline. DALYs totaled 12,999,264, corresponding to an estimated annual percentage change (EAPC) of a 1.73% decrease in the age-standardized DALYs rate. East Asia accounted for nearly two-thirds of global EC cases and deaths, while Central Sub-Saharan Africa recorded the highest ASIR and ASDR. Central Asia experienced the largest reductions, whereas Western Sub-Saharan Africa showed increasing trends. Middle-SDI countries, such as Malawi and Lesotho, had disproportionately high burdens, while high-SDI countries, including Tunisia and Kuwait, had lower burdens. Males had higher incidence and mortality rates across all age groups. By 2050, the ASIR is projected to decrease to 6.17 per 100,000, and the ASDR to 5.23 per 100,000, though the absolute number of cases and deaths is expected to rise.ConclusionsThe global burden of EC remains significant, with ongoing challenges in regions such as Africa and East Asia. These findings highlight the need for sustained and targeted prevention efforts, particularly in high-risk populations, to address the increasing absolute number of cases and deaths.
α-methyltryptophan-mediated protection against diabetic nephropathy in db/db mice as studied with a metabolomics approach
Authors: Cai Aimin , Shen Dingchao , Xiong Qiushuang , Ding Jie , Ding Yang , Lin Xinlu , Chen Lijia , Yao Qing , Lin Guangyong , Chen Ruijie , Ganapathy Vadivel , Kou Longfa 
Published: January 2025

IntroductionDiabetic nephropathy (DN), a major complication of diabetes, presents with poor clinical outcomes and affects patients throughout their lifetime. α-Methyltryptophan (α-MT) is a blocker of the amino acid transporter. SLC6A14 and also an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1).MethodsIn this study, we employed a nuclear magnetic resonance-based metabolomic approach to investigate the therapeutic effects of α-MT in a db/db mouse model of DN and explore the underlying molecular mechanisms.ResultsThe results of the study demonstrated that α-MT significantly reduced the urinary excretion of albumin and creatinine, improved kidney function, and decreased renal fibrosis in db/db mice. Metabolomic analyses of kidney tissues and urine samples indicated that db/db mice displayed increased activity of the enzyme IDO1, and alongside pronounced metabolic disturbances. These disturbances are chiefly characterized by alterations in amino acid metabolism, energy production pathways, membrane biochemical features, and nicotinamide metabolism, all of which have been implicated in mTOR signaling and apoptotic pathways.DiscussionAdministration of α-MT to db/db mice showed evidence of IDO1 inhibition and rectification of metabolic dysfunctions with concurrent suppression of mTOR signaling and apoptosis. These findings highlight the potential of α-MT as a promising therapeutic agent for diabetic nephropathy.
4,6-Disubstituted pyrimidine-based microtubule affinity-regulating kinase 4 (MARK4) inhibitors: synthesis, characterization, in-vitro activity and in-silico studies
Authors: Haque Ashanul , Alenezi Khalaf M. , Rasheed Mohd. Saeed Maulana Abdul , Rahman Md. Ataur , Anwar Saleha , Ahamad Shahzaib , Gupta Dinesh 
Published: January 2025

IntroductionAlzheimer’s disease (AD) is a neurodegenerative disorder that significantly impacts the cognitive function and memory of a person. Despite the significant research efforts, the ability to completely prevent or effectively treat AD and its related dementias remains limited. Protein kinases are integral to AD pathology and represent promising targets for therapeutic intervention.MethodsA series of pyrimidine-based compounds 4-(4-(arylsulfonyl)piperazin-1-yl)-6-(thiophen-3-yl)pyrimidine derivatives (8-14) were synthesized and characterised. ATPase inhibition was carried out against the MARK4 enzyme. Molecular docking and molecular dynamics (MD) simulation at 500 ns was carried out against MARK4 (PDB: 5ES1). The drug-likeness feature and toxicity of the molecules were evaluated using QikProp and other tools.ResultsCompounds were synthesized following a multi-step approach and characterized using multi-nuclear magnetic resonance (1H/13C-NMR) and mass spectrometry. ATPase inhibition assay of the compounds against MARK4 showed an IC50 value in the micromolar (μM) range. The results of the docking studies were consistent with the in-vitro experiments and identified (9) and (14) as the candidates with the highest affinity towards MARK4. MD simulation further supported these results, showing that the binding of ligands stabilises the target protein.ConclusionUsing experimental and theoretical approaches, we demonstrated that the reported class of pyrimidine derivatives are an excellent starting point for developing the next-generation anti-AD drugs.
Efficacy and safety of tenofovir and entecavir in patients with chronic hepatitis B-related cirrhosis: a systematic review and meta-analysis
Authors: Cao Lu , Li Li , Yang Lixing , Zhou Nan , Zhang Yu 
Published: January 2025

ObjectivesTo systematically evaluate the efficacy and safety of tenofovir and entecavir in chronic hepatitis B-related cirrhosis.MethodsA comprehensive search was conducted in databases including PubMed, Web of Science, Embase and Cochrane Library from the inception until June 2024. Studies on the use of tenofovir and entecavir for chronic hepatitis B-related cirrhosis were collected.ResultsA total of 14 studies involving 14,208 patients were included. The meta-analysis revealed that tenofovir significantly reduced the cumulative incidence of hepatocellular carcinoma and cumulative mortality compared to entecavir in East Asian popupation, while in non East Asian populations, the two groups are roughly equivalent. After 48 weeks, the hepatitis B virus-deoxyribonucleic acid clearance rate in the tenofovir group were comparable to the entecavir group. Both tenofovir and entecavir showed similar effect in reducing the incidence of hepatic encephalopathy. Compared with the entecavir group, patients in the tenofovir group, including tenofovir disoproxil fumarate and tenofovir alafenamide fumarate showed a significant increase in estimated glomerular filtration rate after 48 weeks of treatment.ConclusionCompared to entecavir, tenofovir significantly reduced the cumulative incidence of hepatocellular carcinoma and cumulative mortality in chronic hepatitis B-related cirrhosis in East Asian population. However, both drugs were comparable in terms of hepatitis B virus-deoxyribonucleic acid clearance and hepatic encephalopathy. Tenofovir did not significantly cause renal dysfunction, but instead improved estimated glomerular filtration rate levels compared with entecavir. Randomized controlled trials with larger sample size are still needed for validation.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024588432.