bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryo transfer impact: a comprehensive national cohort analysis comparing maternal and neonatal outcomes across varied embryo stages in fresh and frozen transfers
Authors: Chang Chih-Ting , Weng Shih-Feng , Chuang Hui-Yu , Hsu I-Le , Hsu Chia-Yi , Tsai Eing-Mei 
Published: June 2024

IntroductionThe utilization of frozen embryo transfer not only enhances reproductive outcomes by elevating the likelihood of live birth and clinical pregnancy but also improves safety by mitigating the risks associated with ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. There has been an increasing debate in recent years regarding the advisability of making elective frozen embryo transfer the standard practice. Our study aims to determine the optimal choice between fresh and frozen embryo transfer, as well as whether the transfer should occur at the cleavage or blastocyst stage.MethodIn this retrospective cohort study conducted in Taiwan, data from the national assisted reproductive technology (ART) database spanning from January 1st, 2013, to December 31st, 2017, were analyzed. The study included 51,762 eligible female participants who underwent ART and embryo transfer. Pregnancy outcomes, maternal complications, and singleton neonatal outcomes were evaluated using the National Health Insurance Database from January 1st, 2013, to December 31st, 2018. Cases were categorized into groups based on whether they underwent fresh or frozen embryo transfers, with further subdivision into cleavage stage and blastocyst stage transfers. Exposure variables encompassed clinical pregnancy rate, live birth rate, OHSS, pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, preterm premature rupture of membranes (PPROM), gestational age, newborn body weight, and route of delivery.ResultsFrozen blastocyst transfers showed higher rates of clinical pregnancy (CPR) and live births (LBR) compared to fresh blastocyst transfers. Conversely, frozen cleavage stage transfers demonstrated lower rates of clinical pregnancy and live birth compared to fresh cleavage stage transfers. Frozen embryo transfers were associated with reduced risks of OHSS but were linked to a higher risk of pregnancy-induced hypertension compared to fresh embryo transfers. Additionally, frozen embryo transfers were associated with a higher incidence of large for gestational age infants and a lower incidence of small for gestational age infants.ConclusionThe freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, FET is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option.
Association between remote resistance exercises programs delivered by a smartphone application and skeletal muscle mass among elderly patients with type 2 diabetes– a retrospective real-world study
Authors: Yang Jing , Tan Hongyu , Yu Haoyan , Li Jingshuo , Cui Yang , Lu Yuanjian , Liu Xin , Chen Qimin , Zhou Daan 
Published: June 2024

ObjectiveWe aimed to explore the relationship between remote resistance exercise programs delivered via a smartphone application and skeletal muscle mass among elderly patients with type 2 diabetes, utilizing real-world data.MethodsThe resistance exercises were provided through Joymotion®, a web-based telerehabilitation smartphone application (Shanghai Medmotion Medical Management Co., Ltd). The primary outcome was the changes in skeletal muscle index (SMI) before and after the remote resistance exercises programs. The secondary outcomes were changes in skeletal muscle cross-sectional area (SMA), skeletal muscle radiodensity (SMD) and intermuscular adipose tissue (IMAT).ResultsA total of 101 elderly patients with type 2 diabetes were analyzed. The participants had an average age of 72.9 ± 6.11 years for males and 74.4 ± 4.39 years for females. The pre- and post-intervention SMI mean (± SE) was 31.64 ± 4.14 vs. 33.25 ± 4.22 cm2/m2 in male, and 22.72 ± 3.24 vs. 24.28 ± 3.60 cm2/m2 in female respectively (all P &lt; 0.001). Similarly, a statistically significant improvement in SMA, IMAT, and SMD for both male and female groups were also observed respectively (P &lt; 0.001). Multiple linear regression models showed potential confounding factors of baseline hemoglobin A1c and duration of diabetes with changes in SMI in male, while hemoglobin A1c and high density lipoprotein cholesterol with changes in SMI in female.ConclusionRemote resistance exercises programs delivered by a smartphone application were feasible and effective in helping elderly patients with type 2 diabetes to improve their skeletal muscle mass.
Identification and validation of immune-related gene signature models for predicting prognosis and immunotherapy response in hepatocellular carcinoma
Authors: Liu Zhiqiang , Yang Lingge , Liu Chun , Wang Zicheng , Xu Wendi , Lu Jueliang , Wang Chunmeng , Xu Xundi 
Published: June 2024

BackgroundThis study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize the assessment of immunotherapy response.MethodsA training set comprising 305 HCC cases was obtained from The Cancer Genome Atlas (TCGA) database. Initially, a screening process was undertaken to identify prognostically significant immune-related genes (IRGs), followed by the application of logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods for gene modeling. Subsequently, the final model was constructed using support vector machines-recursive feature elimination (SVM-RFE). Following model evaluation, quantitative polymerase chain reaction (qPCR) was employed to examine the gene expression profiles in tissue samples obtained from our cohort of 54 patients with HCC and an independent cohort of 231 patients, and the prognostic relevance of the model was substantiated. Thereafter, the association of the model with the immune responses was examined, and its predictive value regarding the efficacy of immunotherapy was corroborated through studies involving three cohorts undergoing immunotherapy. Finally, the study uncovered the potential mechanism by which the model contributed to prognosticating HCC outcomes and assessing immunotherapy effectiveness.ResultsSVM-RFE modeling was applied to develop an OS prognostic model based on six IRGs (CMTM7, HDAC1, HRAS, PSMD1, RAET1E, and TXLNA). The performance of the model was assessed by AUC values on the ROC curves, resulting in values of 0.83, 0.73, and 0.75 for the predictions at 1, 3, and 5 years, respectively. A marked difference in OS outcomes was noted when comparing the high-risk group (HRG) with the low-risk group (LRG), as demonstrated in both the initial training set (P &lt;0.0001) and the subsequent validation cohort (P &lt;0.0001). Additionally, the SVMRS in the HRG demonstrated a notable positive correlation with key immune checkpoint genes (CTLA-4, PD-1, and PD-L1). The results obtained from the examination of three cohorts undergoing immunotherapy affirmed the potential capability of this model in predicting immunotherapy effectiveness.ConclusionsThe HCC predictive model developed in this study, comprising six genes, demonstrates a robust capability to predict the OS of patients with HCC and immunotherapy effectiveness in tumor management.
Activation of the aryl hydrocarbon receptor improves allergen-specific immunotherapy of murine allergic airway inflammation: a novel adjuvant option?
Authors: Heine Sonja , Alessandrini Francesca , Grosch Johannes , Graß Carina , Heldner Alexander , Schnautz Benjamin , Grosch Johanna , Buters Jeroen , Slusarenko Benjamin O. , Krappmann Daniel , Fallarino Francesca , Ohnmacht Caspar , Schmidt-Weber Carsten B. , Blank Simon 
Published: June 2024

BackgroundAllergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed.MethodsA murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome.ResultsAlthough AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels.ConclusionThis study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.
Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis
Authors: Georgieva Tanya , Diddens Jolien , Friedrich Verena , Lepennetier Gildas , Brand Rosa Margareta , Lehmann-Horn Klaus 
Published: June 2024

Background and objectivesB cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in vivo in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE.MethodsApplying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model.ResultsThe immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4+ T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed.DiscussionOur results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies.
Machine learning models predicts risk of proliferative lupus nephritis
Authors: Yang Panyu , Liu Zhongyu , Lu Fenjian , Sha Yulin , Li Penghao , Zheng Qu , Wang Kefen , Zhou Xin , Zeng Xiaoxi , Wu Yongkang 
Published: June 2024

ObjectiveThis study aims to develop and validate machine learning models to predict proliferative lupus nephritis (PLN) occurrence, offering a reliable diagnostic alternative when renal biopsy is not feasible or safe.MethodsThis study retrospectively analyzed clinical and laboratory data from patients diagnosed with SLE and renal involvement who underwent renal biopsy at West China Hospital of Sichuan University between 2011 and 2021. We randomly assigned 70% of the patients to a training cohort and the remaining 30% to a test cohort. Various machine learning models were constructed on the training cohort, including generalized linear models (e.g., logistic regression, least absolute shrinkage and selection operator, ridge regression, and elastic net), support vector machines (linear and radial basis kernel functions), and decision tree models (e.g., classical decision tree, conditional inference tree, and random forest). Diagnostic performance was evaluated using ROC curves, calibration curves, and DCA for both cohorts. Furthermore, different machine learning models were compared to identify key and shared features, aiming to screen for potential PLN diagnostic markers.ResultsInvolving 1312 LN patients, with 780 PLN/NPLN cases analyzed. They were randomly divided into a training group (547 cases) and a testing group (233 cases). we developed nine machine learning models in the training group. Seven models demonstrated excellent discriminatory abilities in the testing cohort, random forest model showed the highest discriminatory ability (AUC: 0.880, 95% confidence interval(CI): 0.835–0.926). Logistic regression had the best calibration, while random forest exhibited the greatest clinical net benefit. By comparing features across various models, we confirmed the efficacy of traditional indicators like anti-dsDNA antibodies, complement levels, serum creatinine, and urinary red and white blood cells in predicting and distinguishing PLN. Additionally, we uncovered the potential value of previously controversial or underutilized indicators such as serum chloride, neutrophil percentage, serum cystatin C, hematocrit, urinary pH, blood routine red blood cells, and immunoglobulin M in predicting PLN.ConclusionThis study provides a comprehensive perspective on incorporating a broader range of biomarkers for diagnosing and predicting PLN. Additionally, it offers an ideal non-invasive diagnostic tool for SLE patients unable to undergo renal biopsy.
Correlation between diameter of esophageal varices and early rebleeding following endoscopic variceal ligation: a multicenter retrospective study based on artificial intelligence-based endoscopic virtual rule
Authors: Cao Chuankun , Jin Jing , Cai Rui , Chu Yuan , Wu Kai , Wang Zuo , Xiao Ting , Zhang Heng , Huang Hongfei , Liu Heng , Zhang Qianqian , Mei Xuecan , Kong Derun 
Published: June 2024

Background and objectiveBleeding following endoscopic variceal ligation (EVL) may occur as a result of numerous factors, including a diameter of esophageal varices (EV) that is too large to be completely ligated. The present study aimed to develop an artificial intelligence-based endoscopic virtual ruler (EVR) to measure the diameter of EV with a view to finding more suitable cases for EVL.MethodsThe present study was a multicenter retrospective study that included a total of 1,062 EVLs in 727 patients with liver cirrhosis with EV, who underwent EVL from April 2016 to March 2023. Patients were divided into early rebleeding (n = 80) and non-rebleeding groups (n = 982) according to whether postoperative bleeding occurred at 6 weeks. The characteristics of patient baseline data, the status of rebleeding at 6 weeks after surgery and the survival status at 6 weeks after rebleeding were analyzed.ResultsThe early rebleeding rate following 1,062 EVL procedures was 7.5%, and the mortality rate at 6 weeks after bleeding was 16.5%. Results of the one-way binary logistic regression analysis demonstrated that the risk factors for early rebleeding following EVL included: high TB (P = 0.009), low Alb (P = 0.001), high PT (P = 0.004), PVT (P = 0.026), HCC (P = 0.018), high Child-Pugh score (P &lt; 0.001), Child-Pugh grade C(P &lt; 0.001), high MELD score(P = 0.004), Japanese variceal grade F3 (P &lt; 0.001), diameter of EV (P &lt; 0.001), and number of ligature rings (P = 0.029). Results of the multifactorial binary logistic regression analysis demonstrated that Child-Pugh grade C (P = 0.007), Japanese variceal grade F3 (P = 0.009), and diameter of EV (P &lt; 0.001) may exhibit potential in predicting early rebleeding following EVL. ROC analysis demonstrated that the area under curve (AUC) for EV diameter was 0.848, and the AUC for Japanese variceal grade was 0.635, which was statistically significant (P &lt; 0.001). Thus, results of the present study demonstrated that EV diameter was more optimal in predicting early rebleeding following EVL than Japanese variceal grade criteria. The cut-off value of EV diameter was calculated to be 1.35 cm (sensitivity, 70.0%; specificity, 89.2%).ConclusionIf the diameter of EV is ≥1.4 cm, there may be a high risk of early rebleeding following EVL surgery; thus, we recommend caution with EVL.
Active and machine learning-enhanced discovery of new FGFR3 inhibitor, Rhapontin, through virtual screening of receptor structures and anti-cancer activity assessment
Authors: Zeng Qingxin , Hu Haichuan , Huang Zhengwei , Guo Aotian , Lu Sheng , Tong Wenbin , Zhang Zhongheng , Shen Tao 
Published: June 2024

Introduction: This study bridges traditional remedies and modern pharmacology by exploring the synergy between natural compounds and Ceritinib in treating Non-Small Cell Lung Cancer (NSCLC), aiming to enhance efficacy and reduce toxicities.Methods: Using a combined approach of computational analysis, machine learning, and experimental procedures, we identified and analyzed PD173074, Isoquercitrin, and Rhapontin as potential inhibitors of fibroblast growth factor receptor 3 (FGFR3). Machine learning algorithms guided the initial selection, followed by Quantitative Structure-Activity Relationship (QSAR) modeling and molecular dynamics simulations to evaluate the interaction dynamics and stability of Rhapontin. Physicochemical assessments further verified its drug-like properties and specificity.Results: Our experiments demonstrate that Rhapontin, when combined with Ceritinib, significantly suppresses tumor activity in NSCLC while sparing healthy cells. The molecular simulations and physicochemical evaluations confirm Rhapontin’s stability and favorable interaction with FGFR3, highlighting its potential as an effective adjunct in NSCLC therapy.Discussion: The integration of natural compounds with established cancer therapies offers a promising avenue for enhancing treatment outcomes in NSCLC. By combining the ancient wisdom of natural remedies with the precision of modern science, this study contributes to evolving cancer treatment paradigms, potentially mitigating the side effects associated with current therapies.
Physical activity patterns and cognitive function in elderly women: a cross-sectional study from NHANES 2011–2014
Authors: Wu Junyu , Qiu Peng , Liu Meihan , Yu Weiqiang , Li Min , Li Youqiang 
Published: June 2024

BackgroundAmid the backdrop of global aging, the increasing prevalence of cognitive decline among the elderly, particularly within the female demographic, represents a considerable public health concern. Physical activity (PA) is recognized as an effective non-pharmacological intervention for mitigating cognitive decline in older adults. However, the relationship between different PA patterns and cognitive function (CF) in elderly women remains unclear.MethodsThis study utilized data from National Health and Nutrition Examination Survey (NHANES) 2011–2014 to investigate the relationships between PA, PA patterns [inactive, Weekend Warrior (WW), and Regular Exercise (RE)], and PA intensity with CF in elderly women. Multivariate regression analysis served as the primary analytical method.ResultsThere was a significant positive correlation between PA and CF among elderly women (β-PA: 0.003, 95% CI: 0.000–0.006, P = 0.03143). Additionally, WW and RE activity patterns were associated with markedly better cognitive performance compared to the inactive group (β-WW: 0.451, 95% CI: 0.216–0.685, P = 0.00017; β-RE: 0.153, 95% CI: 0.085–0.221, P = 0.00001). Furthermore, our results indicate a progressive increase in CF with increasing PA intensity (β-MPA- dominated: 0.16, 95% CI: 0.02–0.09, P = 0.0208; β-VPA-dominated: 0.21, 95% CI: 0.09–0.34, P = 0.0011; β-Total VPA: 0.31, 95% CI: −0.01–0.63, P = 0.0566).ConclusionOur study confirms a positive association between PA and CF in elderly women, with even intermittent but intensive PA models like WW being correlated with improved CF. These findings underscore the significant role that varying intensities and patterns of PA play in promoting cognitive health among older age groups, highlighting the need for adaptable PA strategies in public health initiatives targeting this population.
Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task
Authors: Dubbelman Mark A. , Diez Ibai , Gonzalez Christopher , Amariglio Rebecca E. , Becker J. Alex , Chhatwal Jasmeer P. , Gatchel Jennifer R. , Johnson Keith A. , Locascio Joseph J. , Udeogu Onyinye J. , Wang Sharon , Papp Kathryn V. , Properzi Michael J. , Rentz Dorene M. , Schultz Aaron P. , Sperling Reisa A. , Vannini Patrizia , Marshall Gad A. 
Published: June 2024

BackgroundChanges in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults.MethodsSeventy-six cognitively unimpaired participants (72 ± 6 years old, 61% female) completed multiple Harvard Automated Phone Task (APT) assessments over 2.0 ± 0.9 years. The Harvard APT consists of three tasks, performed through an automated phone system, in which participants refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and transfer money to pay a bill (APT-Bank). Participants underwent Pittsburgh compound-B and flortaucipir positron emission tomography scans at baseline. We computed distribution volume ratios for a cortical amyloid aggregate and standardized uptake volume ratios for medial temporal and neocortical tau regions. In separate linear mixed models, baseline amyloid by time and tau by time interactions were used to predict longitudinal changes in performance on the Harvard APT tasks. Three-way amyloid by tau by time interactions were also investigated. Lastly, we examined associations between tau and change in Harvard APT scores in exploratory voxel-wise whole-brain analyses. All models were adjusted for age, sex, and education.ResultsAmyloid [unstandardized partial regression coefficient estimate (β) = −0.007, 95% confidence interval (95% CI) = (−0.013, −0.001)], and medial temporal tau [β = −0.013, 95% CI = (−0.022, −0.004)] were associated with change over time in years on APT-PCP only, i.e., higher baseline amyloid and higher baseline tau were associated with steeper rate of decline of APT-PCP. Voxel-wise analyses showed widespread associations between tau and change in APT-PCP scores over time.ConclusionEven among cognitively unimpaired older adults, changes over time in the performance of cognitively complex everyday activities relate to cortical amyloid and widespread cerebral tau burden at baseline. These findings support the link between Alzheimer's disease pathology and function and highlight the importance of measuring everyday functioning in preclinical disease stages.