bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationship between T2DM microvascular complications and gut microbiota: a Mendelian randomization study
Authors: Zhang Junping , Yu Zilu , Li Shanshan , Zhang Qingfang , Chen Wen , Wang Jingying , He Shasha , Liu Ying , Chen Shen , Xu Jixiong 
Published: June 2024

BackgroundGowing number of studies have demonstrated the association between gut microbiome and T2DM microvascular complications, however the causal relationship remains unclear. Therefore, we using the Mendelian randomization (MR) approach to investigate this causal relation.MethodsUsing gut microbiome data from the International MiBioGen Consortium genome-wide association study (GWAS) and T2DM microvascular complications data from the FinnGen Consortium GWAS to perform MR analyses. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), the inverse variance weighting (IVW) method was used as the primary analysis method, and the results were tested for heterogeneity and horizontal pleiotropy.ResultsOur research identified that there are 5 known microbial species and 2 unknown microbial species in the gut microbiome that were causally related to T2DM retinopathy. Besides, three and seven known microbial species causal relationships between the gut microbiome and T2DM neuropathy and T2DM nephropathy, respectively.ConclusionsUsing MR methods, we demonstrated the causal relationship between gut microbiome and microvascular complications in T2DM, providing a new strategy for the prevention and treatment of it.
Mediation effect of cognitive impairment for the relationship of type 2 diabetes mellitus with mortality among elderly individuals
Authors: Wei Boyang , He Jun 
Published: June 2024

ObjectivesTo investigate the potential mediating role of cognitive impairment on the link between type 2 diabetes mellitus (T2DM) and mortality among elderly individuals using data from the National Health and Nutrition Examination Survey (NHANES) database.MethodsTotally, 1,891 individuals from the NHANES database were included in this cohort study. All-cause mortality was considered study endpoint. Cognitive impairment was assessed by digit symbol substitution test (DSST). Adopted weighted logistic regression analyses to explore the relationship of T2DM with cognitive impairment. Constructed weighted Cox proportional hazard models to investigate the relationship of T2DM with all-cause mortality. We employed distribution-of-the-product method to investigate the mediating effect. RMediation software package was used to calculate the 95% confidence interval (CI) of the distribution-of-the-product. If CI does not contain 0, it suggests a significant mediation effect.ResultsThe findings from the weighted logistic regression revealed that individuals with T2DM had a significantly higher likelihood of experiencing cognitive impairment [odds ratio =1.86, 95% CI: 1.39–2.49]. The result showed that T2DM was related to an increased all-cause mortality (hazard ratio=1.37, 95%CI: 1.01–1.87). Importantly, the mediation effect of cognitive impairment on the relationship of T2DM with all-cause mortality is significant (95%CI: 0.06–0.59). The percentage of mediation effect was calculated as 16.2%.ConclusionOur study suggested that the presence of cognitive impairment plays a significant role in explaining the link between T2DM and all-cause mortality in older individuals.
Association between life’s essential 8 and testosterone deficiency in men: NHANES 2011–2016
Authors: Cai Min , Chen Jinzao 
Published: June 2024

BackgroundSerum testosterone is intrinsically associated to cardiovascular disease. Our aim is to explore the relationship between the recently updated cardiovascular health measurement, known as Life’s Essential 8 (LE8), and the prevalence of testosterone deficiency (TD) in adult males in the United States.MethodsStudy data was obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. A weighted multivariate logistic regression model was applied to evaluate the correlation between LE8 and testosterone deficiency. Restricted Cubic Spline (RCS) was employed to explore its non-linear relationship. In addition, a stratified analysis was conducted.ResultsThe final analysis included 2332 participants from NHANES from 2011 to 2016. After adjusting for confounding factors, the odds ratios (ORs) and 95% confidence intervals (CIs) for testosterone deficiency in participants with moderate and higher LE8 scores compared to the lowest LE8 scores were 0.59 (0.38–0.92) and 0.38 (0.19–0.76), respectively. The results of subgroup analysis showed that LE8 score was significantly associated with TD among young and middle-aged participants.ConclusionA lower LE8 score is related to a higher incidence of testosterone deficiency, especially in young and middle-aged men. Further research is necessary to explore the potential mechanisms between them.
18F-AlF-NOTA-octreotide PET/CT in the localization of tumor-induced osteomalacia: case series and literature review
Authors: Li Jing 
Published: June 2024

IntroductionThis study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT).MethodsWe analyzed TIO patients who underwent 18F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed.Results6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent 18F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm3).ConclusionThe implementation of whole-body 18F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of 18F-OC PET/CT in managing TIO.
Predicting Kawasaki disease shock syndrome in children
Authors: Zhao Zhihui , Yuan Yue , Gao Lu , Li Qirui , Wang Ying , Zhao Shunying 
Published: June 2024

BackgroundKawasaki disease shock syndrome (KDSS) is a critical manifestation of Kawasaki disease (KD). In recent years, a logistic regression prediction model has been widely used to predict the occurrence probability of various diseases. This study aimed to investigate the clinical characteristics of children with KD and develop and validate an individualized logistic regression model for predicting KDSS among children with KD.MethodsThe clinical data of children diagnosed with KDSS and hospitalized between January 2021 and December 2023 were retrospectively analyzed. The best predictors were selected by logistic regression and lasso regression analyses. A logistic regression model was built of the training set (n = 162) to predict the occurrence of KDSS. The model prediction was further performed by logistic regression. A receiver operating characteristic curve was used to evaluate the performance of the logistic regression model. We built a nomogram model by visualizing the calibration curve using a 1000 bootstrap resampling program. The model was validated using an independent validation set (n = 68).ResultsIn the univariate analysis, among the 24 variables that differed significantly between the KDSS and KD groups, further logistic and Lasso regression analyses found that five variables were independently related to KDSS: rash, brain natriuretic peptide, serum Na, serum P, and aspartate aminotransferase. A logistic regression model was established of the training set (area under the receiver operating characteristic curve, 0.979; sensitivity=96.2%; specificity=97.2%). The calibration curve showed good consistency between the predicted values of the logistic regression model and the actual observed values in the training and validation sets.ConclusionHere we established a feasible and highly accurate logistic regression model to predict the occurrence of KDSS, which will enable its early identification.
Preparation of kartogenin-loaded PLGA microspheres and a study of their drug release profiles
Authors: Chang Hyun-Kyung , Koh Yong-Gon , Hong Hyoung-Taek , Kang Kyoung-Tak 
Published: June 2024

Introduction: Kartogenin, a potent inducer of chondrogenic differentiation in mesenchymal stem cells and a key agent in cartilage regeneration, presents a viable therapeutic strategy for osteoarthritis management. Despite the abundance of literature on therapeutic potential of kartogenin, there is a paucity of studies characterizing the formulation specifics in microsphere fabrication. This exploration is pivotal to advances in regenerative medicine, particularly in the domain of cartilage regeneration, to assure clinical efficacy and safety.Methods: In this work, we fabricated kartogenin-loaded PLGA microspheres with diverse formulations and their particle size, size distribution, encapsulation efficiency, drug loading and release profiles were characterized. Ratio of polymer, drug, and solvent and the use of surfactant was used as variables, and in particular, the effect of surfactant on particles was investigated.Results: The average diameter of the spheres was 16.0–31.7 μm. Morphological variations from solid to porous surface structures depending on surfactant incorporation during the emulsification process was observed. Cumulative kartogenin release from microspheres ranged from 53.8% to 80.9% on day 28, and release profiles conform predominantly to the Korsmeyer-Peppas kinetics model.Discussion: This study provides a foundational framework for modulating kartogenin release dynamics, a critical consideration for optimizing therapeutic efficacy and minimizing adverse effects in cartilage tissue engineering applications.
Enterovirus genotype diversity with emergence of coxsackievirus A2 circulating in pediatric patients with acute gastroenteritis in Thailand, 2019–2022
Authors: Xie Zhenfeng , Khamrin Pattara , Jampanil Nutthawadee , Yodmeeklin Arpaporn , Ukarapol Nuthapong , Maneekarn Niwat , Kumthip Kattareeya 
Published: June 2024

IntroductionEnteroviruses (EVs) are recognized as potential causative agents of acute gastroenteritis (AGE) in children worldwide. This study aimed to investigate the epidemiology and molecular characteristics of EV infection in children admitted to hospitals with AGE in Chiang Mai, Thailand from 2019 to 2022.MethodsA total of 1,148 fecal samples collected from patients with AGE were screened for the presence of EV using RT-PCR. The prevalence, co-infection with common diarrheal viruses, and seasonal pattern of EV were examined. The genotypes of EV were identified based on the VP1 sequence and phylogenetic analysis.ResultsThe overall prevalence of EV in AGE patients was 8.8% (101/1,148). After the COVID-19 outbreak in 2019, a significant decrease in the EV infection rate and genotype diversity was observed (p &lt; 0.05). EV infection alone was observed in 68.3% (69/101) of cases while co-infection with other enteric viruses was 31.7% (32/101). The seasonal pattern of EV infection showed a peak prevalence during the rainy season. EV species A was the most prevalent (37.5%), followed by species B (32.3%), species C (29.2%), and species D (1.0%). Twenty-five genotypes of EV were identified with the most predominant of the coxsackievirus A2 (CV-A2) (13.5%), CV-B2 (7.3%) and CV-A24 (5.2%).ConclusionOur data demonstrate a significant decrease in the prevalence and diversity of EV circulating in AGE patients during the COVID-19 pandemic and highlight the emergence of CV-A2 during this study period. These findings contribute to a better understanding of the molecular epidemiology and diversity of EV in patients with AGE and provide useful information for further investigation into the potential association between specific EV genotypes and AGE in future studies.
The effect of feedback timing on category learning and feedback processing in younger and older adults
Authors: Nunn Kristen , Creighton Robert , Tilton-Bolowsky Victoria , Arbel Yael , Vallila-Rohter Sofia 
Published: June 2024

IntroductionCorrective feedback can be received immediately after an action or with a temporal delay. Neuroimaging studies suggest that immediate and delayed feedback are processed by the striatum and medial temporal lobes (MTL), respectively. Age-related changes in the striatum and MTL may influence the efficiency of feedback-based learning in older adults. The current study leverages event-related potentials (ERPs) to evaluate age-related differences in immediate and delayed feedback processing and consequences for learning. The feedback-related negativity (FRN) captures activity in the frontostriatal circuit while the N170 is hypothesized to reflect MTL activation.Methods18 younger (Myears = 24.4) and 20 older (Myears = 65.5) adults completed learning tasks with immediate and delayed feedback. For each group, learning outcomes and ERP magnitudes were evaluated across timing conditions.ResultsYounger adults learned better than older adults in the immediate timing condition. This performance difference was associated with a typical FRN signature in younger but not older adults. For older adults, impaired processing of immediate feedback in the striatum may have negatively impacted learning. Conversely, learning was comparable across groups when feedback was delayed. For both groups, delayed feedback was associated with a larger magnitude N170 relative to immediate feedback, suggesting greater MTL activation.Discussion and conclusionDelaying feedback may increase MTL involvement and, for older adults, improve category learning. Age-related neural changes may differentially affect MTL- and striatal-dependent learning. Future research can evaluate the locus of age-related learning differences and how feedback can be manipulated to optimize learning across the lifespan.
The randomized study of enteral nutrition with rapid versus conventional administration in acute stroke patients; the protocol of rapid EN trial
Authors: Suzuki Kentaro , Onodera Hidetaka , Sugiyama Rie , Okubo Seiji , Kimura Naoto , Kaku Shogo , Seki Rieko , Fujita Satoshi , Nomura Koichi , Takagiwa Taiki , Katafuchi Izumi , Nakamura Homare , Kanamaru Takuya , Oda Momoyo , Kimura Shohei , Sonoda Shota , Kakita Hiroto , Otsuka Toshiaki , Kimura Kazumi 
Published: June 2024

RationaleEnteral nutrition is beneficial for stroke patients with oral intake difficulties. However, it is time consuming and may interfere with routine medical care. Therefore, there is a clinical benefit if enteral nutrition can be safely administered in a short time. Although our retrospective study showed the safety of rapid administration, it remains unclear whether rapid administration of enteral nutrition is as safe as conventional administration.AimThe randomized study of Enteral Nutrition with Rapid versus conventional administration in acute stroke patients (Rapid EN trial) aims to clarify the safety of rapid feeding of enteral nutrition compared with conventional feeding.Methods and designThis is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded end-point clinical trial. Eligible criteria include acute stroke patients who have difficulty with oral intake defined as severe altered consciousness (Japan Coma Scale 10–300) or modified water swallowing test &lt;4. The target enrollment is 700 patients, with 350 patients receiving rapid enteral nutrition at a rate of 100 mL in 5 min (Rapid EN group) and 350 patients receiving conventional enteral nutrition at a rate of 100 mL in 30 min (Conventional EN group).Study outcomeThe primary outcome is the incidence of one or more complications of vomiting or diarrhea or pneumonia within 7 days would be non-inferior in the rapid EN group compared to the conventional EN group. Secondary outcomes were total time spent on enteral nutrition within 7 days from enteral nutrition, the incidence of vomiting, diarrhea and pneumonia within 3 or 7 days, and the rate of favorable clinical outcome.DiscussionSince no previous reports have focused on the speed of administration, we felt it was necessary to prove the safety of rapid administration. If this study shows positive results, it will not only benefit patients, but also reduce the burden of medical care. We believe this study is novel and will be useful in clinical practice.Clinical trial registrationhttps://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000046610 Identifier UMIN000046610.
PD-L1 expression as a potential predictor of immune checkpoint inhibitor efficacy and survival in patients with recurrent or metastatic nasopharyngeal cancer: a systematic review and meta-analysis of prospective trials
Authors: Xu Ruyu , Wong Charlene H.L. , Chan Kenneth S.K. , Chiang Chi Leung 
Published: June 2024

BackgroundThe predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains controversial. This study aimed to evaluate the optimal threshold of PD-L1 expression in predicting the efficacy of ICIs in patients with recurrent or metastatic (R/M) NPC.MethodsA meta-analysis was performed by retrieving relevant literature from PubMed, EMBASE, and Cochrane Library databases. Data on the pooled risk ratio (RR), mean overall survival (OS), progression-free survival (PFS), overall response rate (ORR) with 95% confidence interval, and 1%, 10%, and 25% PD-L1 expression cutoff points were obtained to examine the role of PD-L1 as a biomarker in R/M NPC patients receiving immunotherapy.ResultsIn total, 1,312 patients from 14 studies were included. An improvement in PFS was observed in both patients with PD-L1 ≥ 1% (RR = 0.76, 95% CI 0.62–0.92, P = 0.005) and those with PD-L1 &lt; 1% (RR = 0.68, 95% CI: 0.35–1.32, P = 0.26) who received first-line treatment with immunotherapy, with no significant difference between these subgroups. The pooled ORR was significantly higher in patients with PD-L1 ≥ 1% (ORR = 0.37) than in those with PD-L1 &lt; 1% (ORR = 0.22) (P &lt; 0.01) undergoing subsequent-line treatment. However, when we used the PD-L1 cutoff values of 10% and 25%, there was no significant difference between the positive (PD-L1 expression ≥ the cutoff value) and negative (PD-L1 expression &lt; the cutoff value) subgroups. PD-L1 ≥ 1% also tended to be associated with better PFS and OS.ConclusionsOur meta-analysis suggested that first-line immunotherapy could significantly improve PFS in R/M NPC patients, regardless of the PD-L1 expression levels. Positive PD-L1 expression (≥ 1%) might be a potential predictive biomarker for a better overall response to immunotherapy in R/M NPC patients in subsequent-line setting.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024495841 PROSPERO, identifier CRD42024495841.
Predictive model based on multiple immunofluorescence quantitative analysis for pathological complete response to neoadjuvant immunochemotherapy in lung squamous cell carcinoma
Authors: Xiao Meng , Tu Lili , Zhou Ting , He Ye , Li Xiaohui , Zuo Qiunan 
Published: June 2024

ObjectiveThis study aims to establish a prediction model for neoadjuvant immunochemotherapy (NICT) in lung squamous cell carcinoma to guide clinical treatment.MethodsThis retrospective study included 50 patients diagnosed with lung squamous cell carcinoma who received NICT. The patients were divided into the pathological complete response (PCR) group and the non-PCR group. HE staining and multiple immunofluorescence (mIF) techniques were utilized to analyze the differences in the immune microenvironment between these groups. LASSO regression and optimal subset regression were employed to identify the most significant variables and construct a prediction model.ResultsThe PCR group showed higher densities of lymphocyte nuclei and karyorrhexis based on HE staining. Furthermore, based on mIF analysis, the PCR group showed higher cell densities of CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region, while showing lower cell densities of CD3+Foxp3+, Foxp3+, and CD163+. Logistic univariate analysis revealed CD8+PD-L1+, PD-L1+, CD8+, CD4+LAG-3+, lymphocyte nuclei, and karyorrhexis as significant factors influencing PCR. By using diverse screening methods, the three most relevant variables (CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region) were selected to establish the prediction model. The model exhibited excellent performance in both the training set (AUC=0.965) and the validation set (AUC=0.786). In the validation set, In comparison to the conventional TPS scoring criteria, the model attained superior accuracy (0.85), specificity(0.67), and sensitivity (0.92).ConclusionNICT treatment might induce anti-tumor effects by enriching immune cells and reactivating exhausted T cells. CD8+, PD-L1+, and CD8+PD-L1+ cell abundances within the tumor region have been closely associated with therapeutic efficacy. Incorporating these three variables into a predictive model allows accurate forecasting of treatment outcomes and provides a reliable basis for selecting NICT treatment strategies.
Avelumab first-line maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma: real-world results from a Korean expanded access program
Authors: Park Se Hoon , Shin Sang Joon , Rha Sun Young , Beom Seung-Hoon , Seo Ho Kyung , Keam Bhumsuk , Kim Miso , Hong Yoon-Hee , Yoon Shinkyo , Lee Jae-Lyun 
Published: June 2024

BackgroundThe JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP).MethodsThis open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice.ResultsOverall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received &gt;12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died.ConclusionResults from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies.