bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of bone fracture by using dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: a network meta-analysis of population-based cohort studies
Authors: Mostafa Mohamed E. A. , Alrasheed Tariq 
Published: October 2024

BackgroundType 2 diabetes mellitus (T2DM) is linked to a heightened likelihood of experiencing fractures. It is crucial to ascertain whether medications used to lower blood sugar levels can elevate the risk of fractures. We aimed to investigate and compare the effects of glucagon-like peptide 1 receptor agonists (GLP-1RA), Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) on the fracture risk in patients with T2D in the real world.MethodsA network meta-analysis conducted an inclusive literature search in PubMed, Scopus, Web of Science, and Cochrane Library to select appropriate population-based cohort studies that investigated the risk of bone fractures of (GLP-1RA), (DPP-4i) or (SGLT-2i) in the real world. A network meta-analysis (NMA) was performed using R software to investigate the risk of total fractures as a primary outcome among patients who used (GLP-1RAs), (SGLT-2i) or (DPP-4i) versus each other or other glucose-lowering medications (GLMs). The odds ratio (OR) and 95% confidence interval (CI) were summarized overall network and for each pairwise direct and indirect comparison. The surface under the cumulative ranking curve (SUCRA) with the P-scores was calculated for each treatment in the network meta-analysis to detect their cumulative ranking probabilities in lowering the risk of total fractures.ResultsIn our NMA, we identified a set of 13 population-based cohort studies comprising a total of 1,064,952 patients. The risk of fracture was identified with the follow-up duration for each class. We found a significant decrease in the fracture risk by about 87% associated with patients who used SGLT2 inhibitors in combination with other glucose-lowering medications, followed by SGLT2 inhibitors alone by about 67%, then GLP-1 receptor agonists by about 60%, and at last DPP-4 inhibitors by about 55%.ConclusionOur study’s collective findings suggest a significant association of the low risk of fracture with the use of SGLT2i with other GLMs combination, SGLT2i alone, GLP-1RA, and DPP-4i, respectively. This population-based analysis offers the best available evidence and might be helpful for clinicians in the decision of the most suitable T2DM treatment strategies, especially for elderly type 2 diabetic patients, as they may be safe in terms of fracture.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023448720.
DNA polymorphisms in inflammatory and endocrine signals linked to frailty are also associated with obesity: data from the FRASNET cohort
Authors: Damanti Sarah , Citterio Lorena , Zagato Laura , Brioni Elena , Magnaghi Cristiano , Simonini Marco , De Lorenzo Rebecca , Ruggiero Mariapia , Santoro Simona , Senini Eleonora , Messina Marco , Vitali Giordano , Manunta Paolo , Manfredi Angelo Andrea , Lanzani Chiara , Rovere Querini Patrizia 
Published: October 2024

BackgroundObesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity.MethodsWe aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures.ResultsSNPs related to frailty and linked to the renin–angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21–23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults.ConclusionsFrailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies.
Serum iron status is associated with all-cause mortality in metabolic dysfunction-associated steatotic liver disease: a prospective, observational study
Authors: Xia Ting , Ni Jie , Ni Yuqin , Wu Xinhui , Du Kangming , Wan Xuemei , You Xuli 
Published: October 2024

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic liver disease worldwide. Emerging evidence suggests a close crosstalk between iron status and metabolic syndrome. Therefore, this cohort study aimed to investigate the relationship between serum iron status and all-cause mortality in individuals with MASLD.MethodsA total of 3393 subjects with MASLD identified by ultrasound from the Third National Health and Nutrition Examination Survey (NHANES III) were included in the analysis. Iron status indicators included serum iron, ferritin, transferrin saturation, total iron binding capacity, hemoglobin concentration, mean corpuscular hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Cox proportional hazards models and restricted cubic spline models with adjustment for multiple confounders were applied. Stratified analyses were performed by sex and age.ResultsDuring a median of 26.08 years of follow-up, high serum iron and transferrin saturation were significantly associated with reduced all-cause mortality in a linear pattern (Poverall&lt;0.001). Compared with the lowest quartile, individuals with serum iron and transferrin saturation in the third or fourth quartile intervals had a 20-40% reduction in long-term mortality. However, there was no independent association of serum ferritin, total iron binding capacity, and red blood cell indices with all-cause mortality in MASLD.ConclusionThis study suggests that serum iron and transferrin saturation have the potential to serve as independent biomarkers of all-cause mortality in patients with MASLD and implies the therapeutic potential of modifying iron status.
Can agricultural water rights trading promote intensive and economical utilization of water resources in China based on the difference-in-differences model?
Authors: Rong Lili , Cheng Xin 
Published: October 2024

IntroductionImproving the level of intensive and economical utilization of water resources is an important step towards water and food security.MethodsBased on China’s provincial panel data from 2015 to 2021, this study uses a difference-in-differences (DID) model to examine the effect of agricultural water rights trading on intensive and economical utilization of water resources.ResultsThe results show that agricultural water rights trading can significantly promote an intensive and economical utilization of water resources at the 1% level, and the results remain valid even after a series of robustness tests. Further analysis indicates that agricultural water rights trading can promote better utilization of water resources by significantly reducing agricultural water consumption at the 1% level and reducing the proportion of agricultural water consumption at the 5% level to optimize water use structure. Moreover, in regions with scarce water resources, strong water resource constraints, more farmland water conservancy projects, and greater economic development, the promoting effect of agricultural water rights trading on the intensive and economical use of water resources is more significant.DiscussionThis study provides evidence of the impact of China’s agricultural water rights trading policy and offers new ideas and experiences to improve China’s water resource utilization efficiency. The contributions of this work are mainly threefold. First, this paper clearly distinguishes the intensive conservation of water resources, presents an evaluation index system, and complements the existing literature on measuring the intensive and economical utilization of water resources. Second, the path of agricultural water rights trading is analyzed to improve the level of intensive and economical utilization of water resources, thus enriching related research on transmission mechanisms. Third, the heterogeneity of the influence of different regional conditions on the level of intensive and economical utilization of water resources is discussed to improve relevant policies.
Brucellosis outbreak in a remote village in northwestern Tajikistan in 2023: a matched case-control study
Authors: Qurbonov Emomali , Silemonshoeva Jamila , Horth Roberta , Tilloeva Zulfiya , Yusufi Salomudin , Nabirova Dilyara 
Published: October 2024

BackgroundA sharp increase in reported brucellosis incidence was observed in northwestern Tajikistan (from 1.0/100,000 people in January–May 2022 to 32.7/100,000 in January–May 2023). Most (82%) cases were from the same remote mountainous village (population = 10,712). The aim of this study was to identify risk factors for brucellosis infection and mitigate disease risk.MethodsUsing a case-control design, we conducted face-to-face interviews and collected blood samples during May-June 2023. Fifty-seven cases and 114 controls were recruited. Cases were the first person in a household diagnosed with brucellosis during February–June 2023 with positive serum agglutination test and antibody titers ≥1/160 from blood samples. Two controls were selected for each case (neighbors from different households matched by age and sex). Controls testing positive were excluded and replaced. We conducted conditional multivariable logistic regression to calculate adjusted odds ratio (AOR) and 95% confidence intervals (CI).ResultsAmong the 87 brucellosis patients reported, 57 (66%) agreed to participate and didn't have secondary cases in the household. Of the 57 cases, 68% were 15–44 years old, and 44% were male. Cases peaked in May 2023. Common symptoms were joint pain (95%), fever (84%), weakness (72%), and night sweats (65%). Of selected controls, 13% tested positive and were excluded. All cases and 94% of controls owned livestock (mostly cattle, sheep, or goats); no animals had not been vaccinated in the past 5 years. Brucellosis was associated with consumption of both homemade kaymak (clotted cream) and home-raised meat compared with neither (AOR: 59 [95%CI: 4.3–798], p &lt; 0.01), home-raised meat but not kaymak compared with neither (AOR: 54 [4.0–731], p &lt; 0.01), and involvement in animal slaughter compared with no involvement (AOR: 36 [2.8–461], p &lt; 0.01).ConclusionContact with unvaccinated livestock or consumption of their products was a key contributor to this outbreak in a remote village of Tajikistan. With 13% of controls testing positive, true incidence was likely greater than reported. Following our investigation, a brucellosis awareness education campaign and animal vaccination campaigns were carried out in the region and only one case was reported in September 2023.
PD-L1 blockade immunotherapy rewires cancer-induced emergency myelopoiesis
Authors: Boumpas Athina , Papaioannou Antonis S. , Bousounis Pavlos , Grigoriou Maria , Bergo Veronica , Papafragkos Iosif , Tasis Athanasios , Iskas Michael , Boon Louis , Makridakis Manousos , Vlachou Antonia , Gavriilaki Eleni , Hatzioannou Aikaterini , Mitroulis Ioannis , Trompouki Eirini , Verginis Panayotis 
Published: October 2024

IntroductionImmune checkpoint blockade (ICB) immunotherapy has revolutionized cancer treatment, demonstrating exceptional clinical responses in a wide range of cancers. Despite the success, a significant proportion of patients still fail to respond, highlighting the existence of unappreciated mechanisms of immunotherapy resistance. Delineating such mechanisms is paramount to minimize immunotherapy failures and optimize the clinical benefit.MethodsIn this study, we treated tumour-bearing mice with PD-L1 blockage antibody (aPD-L1) immunotherapy, to investigate its effects on cancer-induced emergency myelopoiesis, focusing on bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). We examined the impact of aPD-L1 treatment on HSPC quiescence, proliferation, transcriptomic profile, and functionality.ResultsHerein, we reveal that aPD-L1 in tumour-bearing mice targets the HSPCs in the BM, mediating their exit from quiescence and promoting their proliferation. Notably, disruption of the PDL1/PD1 axis induces transcriptomic reprogramming in HSPCs, observed in both individuals with Hodgkin lymphoma (HL) and tumour-bearing mice, shifting towards an inflammatory state. Furthermore, HSPCs from aPDL1-treated mice demonstrated resistance to cancer-induced emergency myelopoiesis, evidenced by a lower generation of MDSCs compared to control-treated mice.DiscussionOur findings shed light on unrecognized mechanisms of action of ICB immunotherapy in cancer, which involves targeting of BM-driven HSPCs and reprogramming of cancer-induced emergency myelopoiesis.
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape
Authors: Xiao Shuo-meng , Xu Rui , Yang Ying-xin , Zhao Rui , Xie Yuan , Lei Xu-dan , Wu Xiao-ting 
Published: October 2024

PurposeThe infiltration of immune cells and their roles of the infiltrating-immune cells in gastrointestinal stromal tumor (GIST) is still unclear. We aimed to discover the infiltration cell types and the relationship between the infiltrating-immune cells and the progression of GIST.Experimental designSingle-cell RNA sequencing were performed to discover types of the infiltrating-immune cells and to analyze CellChat between cells. Immunohistochemistry of 80 GIST samples were used to clarify the relation between macrophages and recurrence risk. In vitro, flow cytometry and Real-time PCR were performed to uncover a potential mechanism of tumor cell regulation of macrophages.ResultsTumor cells, macrophages, and T-cells were the predominant cell types. The MIF/CXCR4 axis was the most common ligand–receptor interaction between macrophages and tumor cells. As the risk increased, expression levels of CD68, CD206, MIF, and CXCR4 gradually increased. In vitro, we found that GIST882 was able to secrete MIF and GIST882 cell supernatant upregulated M2 polarization. Real-time PCR showed that expression levels of IL-10 mRNA and Arginase-1 mRNA were also the highest in the GIST882 cell supernatant group.ConclusionsThese findings identify that macrophages are the most abundant infiltrating cells in GIST. The MIF/CXCR4 axis is the most common ligand–receptor interaction between macrophages and tumor cells. GIST cells can regulate macrophage M2 polarization through the MIF/CXCR4 axis.
Efferocytosis dysfunction in CXCL4-induced M4 macrophages: phenotypic insights in systemic sclerosis in vitro and in vivo
Authors: Le Tallec Erwan , Bellamri Nessrine , Lelong Marie , Morzadec Claudie , Frenger Quentin , Ballerie Alice , Cazalets Claire , Lescoat Alain , Gros Frédéric , Lecureur Valérie 
Published: October 2024

IntroductionSystemic sclerosis (SSc) is an autoimmune disease characterized by antinuclear antibody production, which has been linked to an excess of apoptotic cells, normally eliminated by macrophages through efferocytosis. Additionally, circulating levels of CXCL4, a novel SSc biomarker, correlate with more severe fibrotic manifestations of the disease. Considering the defective efferocytosis of macrophages in SSc and the CXCL4-related M4 macrophage phenotype, we hypothesized that CXCL4 could be involved in the alteration of phagocytic functions of macrophages in SSc, including LC3-associated phagocytosis (LAP), another phagocytic process requiring autophagy proteins and contributing to immune silencing.MethodsIn this study, CXCL4 levels were measured by ELISA in vitro in the serum of SSc patients, and also in vivo in the serum and lungs of C57BL/6J SSc mice induced by intradermal injections of hypochloric acid (HOCl) or Bleomycin (BLM), with evaluation of M4 markers. Circulating monocytes from healthy donors were also differentiated in vitro into M4 monocytes-derived macrophages (MDMs) in the presence of recombinant CXCL4. In M4-MDMs, phagocytosis of fluorescent beads and expression level of efferocytic receptors were evaluated by flow cytometry in vitro, while efferocytosis of pHrodo-stained apoptotic Jurkat cells was evaluated by real-time fluorescence microscopy. LAP quantification was made by fluorescence microscopy in M4-MDMs exposed to IgG-coated beads as well as apoptotic Jurkat cells.ResultsOur results demonstrated that efferocytosis was significantly reduced in M0-MDMs from healthy donors exposed to the CXCL4-rich plasma of SSc patients. In vivo, CXCL4 expression was increased in the lungs of both SSc-mouse models, along with elevated M4 markers, while efferocytosis of BLM-mice alveolar macrophages was decreased. In vitro, M4-MDMs exhibited reduced efferocytosis compared to M0-MDMs, notably attributable to lower CD36 receptor expression and impaired phagocytosis capacities, despite enhanced LAP. Autophagic gene expression was increased both in vitro in SSc MDMs and in vivo in BLM mice, thus acting as a potential compensatory mechanism.DiscussionAltogether, our results support the role of CXCL4 on the impaired efferocytosis capacities of human macrophages from SSc patients and in SSc mice.
An integrative predictive model for orthokeratology lens decentration based on diverse metrics
Authors: Xiao Kunhong , Lu Wenrui , Zhang Xuemei , Lin Shenghua , Wei Jingting , Lin Xiangjie , Cai Qingyuan , Ye Yunxi , Yao Yuan , Lin Jiawen , Li Li 
Published: October 2024

PurposeTo develop a predictive model for orthokeratology (Ortho-K) lens decentration 1 month after wear.MethodsThis study included myopic children who were fitted with Ortho-K lenses at Fujian Provincial Hospital between December 2022 and May 2024. Corneal topography parameters and other relevant metrics were collected pre- and post-treatment. Feature selection was conducted using univariate logistic regression and Lasso regression analysis. A machine learning approach was used to develop multiple predictive models, including Decision Tree, Logistic Regression, Multilayer Perceptron, Random Forest, and Support Vector Machine. Model performance was evaluated using accuracy, sensitivity, specificity, ROC curves, DCA curves, and calibration curves. SHAP values were employed to interpret the models.ResultsThe Logistic Regression model demonstrated the best predictive performance, with an AUC of 0.82 (95% CI: 0.69–0.95), accuracy of 77.59%, sensitivity of 85%, and specificity of 61.11%. The most significant predictors identified were age, 8 mm sag height difference, 5 mm Kx1, and 7 mm Kx2. SHAP analysis confirmed the importance of these features, particularly the 8 mm sag height difference.ConclusionsThe Logistic Regression model successfully predicted the risk of Ortho-K lens decentration using key corneal morphological metrics and age. This model provides valuable support for clinicians in optimizing Ortho-K lens fitting strategies, potentially reducing the risk of adverse outcomes and improving the quality of vision for patients. Further validation in clinical settings is recommended.
Diffusion and functional MRI reveal microstructural and network connectivity impairment in adult-onset neuronal intranuclear inclusion disease
Authors: Zhu Rui , Qu Junyu , Wu Yongsheng , Xu Guihua , Wang Dawei 
Published: October 2024

ObjectivesNeuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable neuroimaging biomarkers. This study aimed to evaluate microstructural and functional connectivity alterations using diffusion kurtosis imaging (DKI) and resting-state fMRI (rs-fMRI), and to investigate their diagnostic potential as biomarkers.MethodsTwenty-three patients with NIID and 40 matched healthy controls (HCs) were recruited. Firstly, gray matter (GM) and white matter (WM) changes were assessed by voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Then we explored modifications in brain functional networks connectivity by independent component analysis. And the relationship between the altered DKI parameters and neuropsychological evaluation was analyzed. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different gray matter and white matter parameters.ResultsCompared with the HCs, NIID patients showed reduced mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), and kurtosis fractional anisotropy (KFA) values in deep gray matter regions. Significantly decreased MK, RK, AK, KFA and fractional anisotropy (FA), and increased mean diffusivity (MD) values were observed in extensive white matter fiber tracts. Notable alterations in functional connectivity were also detected. Among all DKI parameters, the diagnostic efficiency of AK in GM and FA in WM regions was the highest.ConclusionAdult-onset NIID patients exhibited altered microstructure and functional network connectivity. Our findings suggest that DKI parameters may serve as potential imaging biomarkers for diagnosing adult-onset NIID.
Robot-mediated impairment-oriented and task-specific training on upper limb post stroke: feasibility and preliminary effects on physical function and quality of life
Authors: Tay San San , Zhang Fuquan , Visperas Christine Alejandro , Koh Xuan Han , Lau Borisut , Neo Jin Rui Edmund 
Published: October 2024

ObjectiveTo assess the feasibility and safety of conducting robot-mediated impairment training (RMIT) and robot-mediated task-specific training (RMTT). The device deployed is the Optimo Regen (OR®), capable of delivering both impairment-oriented training and task-specific training.MethodsThis was a single-centre, randomized, single-blinded, two-arm, parallel group, controlled trial. Patients fulfilling criteria were randomized into either the RMIT or RMIT + RMTT group and provided with 20 h of robotic therapy on top of standard care.ResultsA total of 4 patients were recruited, with 2 patients receiving treatment in each arm. The study was feasible, with a 66.7% enrolment rate, 75% completion rate, and 100% attendance for each intervention session. We achieved a 90% satisfaction rate with no serious adverse effects. All patients had improvement of motor power, Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Functional Independence Measure (FIM), Hospital Anxiety and Depression Scale (HADS), and quality of life scores at 1 month. FIM continued to improve at 3 months post-commencement of intervention. There was relative ease of use of the device.ConclusionThis trial is feasible. A full-scale study is warranted, to compare RMIT against RMTT, which is a novel application.