bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of periprocedural myocardial injury after transcatheter aortic valve implantation on long-term mortality: a meta-analysis of Kaplan-Meier derived individual patient data
Authors: de Sá Marchi Mauricio Felippi , Calomeni Pedro , Gauza Mateus de Miranda , Kanhouche Gabriel , Ravani Lis Victória , Rodrigues Caio Vinicius Fernandes , Tarasoutchi Flávio , de Brito Fábio Sandoli , Rodés-Cabau Josep , Van Mieghem Nicolas M. , Abizaid Alexandre , Ribeiro Henrique Barbosa 
Published: November 2023

BackgroundPeriprocedural myocardial injury (PPMI) frequently occurs after transcatheter aortic valve implantation (TAVI), although its impact on long-term mortality is uncertain.MethodsWe performed a pooled analysis of Kaplan-Meier-derived individual patient data to compare survival in patients with and without PPMI after TAVI. Flexible parametric models with B-splines and landmark analyses were used to determine PPMI prognostic value. Subgroup analyses for VARC-2, troponin, and creatine kinase-MB (CK-MB)-defined PPMI were also performed.ResultsEighteen observational studies comprising 10,094 subjects were included. PPMI was associated with lower overall survival (OS) after two years (HR = 1.46, 95% CI 1.30–1.65, p &lt; 0.01). This was also observed when restricting the analysis to overall VARC-2-defined PPMI (HR = 1.23, 95% CI 1.07–1.40, p &lt; 0.01). For VARC-2 PPMI criteria and VARC-2 troponin-only, higher mortality was restricted to the first 2 months after TAVI (HR = 1.64, 95% CI 1.31–2.07, p &lt; 0.01; and HR = 1.32, 95% CI 1.05–1.67, p = 0.02, respectively), while for VARC-2 defined CK-MB-only the increase in mortality was confined to the first 30 days (HR = 7.44, 95% CI 4.76–11.66, p &lt; 0.01).ConclusionPPMI following TAVI was associated with lower overall survival compared with patients without PPMI. PPMI prognostic impact is restricted to the initial months after the procedure. The analyses were consistent for VARC-2 criteria and for both biomarkers, yet CK-MB was a stronger prognostic marker of mortality than troponin.
Case Report: A leadless and endovascular pacemaker teamwork
Authors: Zeriouh Sarah , Sousonis Vasileios , Menè Roberto , Boveda Serge , Voglimacci-Stephanopoli Quentin , Combes Stéphane 
Published: November 2023

BackgroundCardiac Implantable Electronic Device infections increase short- and long-term mortality, along with healthcare costs. Leadless pacemakers (PM) were developed to overcome pocket- and minimize lead-related complications in selected high-risk patients. Recent advancements enable leadless devices to mechanically detect atrial activity, facilitating atrioventricular (AV) synchronous stimulation.Case summaryA 90-year-old woman, implanted with a dual-chamber pacemaker eight years ago due to sinus node dysfunction, presented with syncope. A diagnosis of complete AV block, in the setting of ventricular lead dysfunction was made. Due to a high risk of infection, the patient was implanted with a leadless PM capable of maintaining AV synchrony in VDD mode (MICRA™ model MC1AVR1). The transvenous PM was programmed to AAI-R mode to drive the atria, which, in turn, triggered the leadless PM to stimulate the ventricles. At six month follow-up, the AV synchrony rate was 85%.ConclusionThe combination of classic atrial pacing with leadless ventricular stimulation can be used in high-risk patients to reduce the risk of complications, in the setting of ventricular lead dysfunction. In this manner, AV synchrony can be maintained, improving hemodynamic parameters and quality of life. Low sinus rate variability at rest is essential to achieve a high AV synchrony rate in such cases.
Comparative safety of different recommended doses of sodium–glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials
Authors: Chen Lu , Xue Qingxia , Yan Chunyan , Tang Bingying , Wang Lu , Zhang Bei , Zhao Quan 
Published: November 2023

ObjectiveThe safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.MethodsPubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.ResultsTwenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.ConclusionCurrent evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.
Effects of different volumes of ovariectomy on fertility and offspring development of rats
Authors: Yang Yu , Ruan Xiangyan , Cheng Jiaojiao , Xu Xin , Mueck Alfred O. 
Published: November 2023

ObjectiveThe purpose of this study was to explore the effect of removal of different volumes of ovarian tissue on fertility and offspring development of SD rats.MethodsSD rats were randomly divided into 6 groups according to different volumes of ovariectomy: Sham group (n=6), non-ovariectomized; 25%-OVX group (n=6), with half of the left ovary excised; 50%-OVX group (n=5), with the left ovary excised; 75%-OVX group (n=5), with the left ovary and half of the right ovary excised; 87.5%-OVX group (n=6), with the left ovary and three quarters of the right ovary excised; 100%-OVX group (n=6), with bilateral ovaries excised. These female rats (F0) were mated with healthy male rats one and four months after the surgery, and the offspring of F0 rats were named F11mon and F14mon, respectively. The number of days from mating to delivery and number of live cubs were recorded. At postnatal day 21 (P21), the body weight, length and anogenital distance (AGD) of the cubs were measured.ResultsThere were no differences in the number of live cubs between 25%-OVX, 50%-OVX and sham groups. Rats in the 87.5%-OVX group did not give birth at 1 month and 4 months after the operation. When compared with the sham group, the body weight and length of F11mon at P21 were increased in 25%-OVX group and 50%-OVX group. However, after the second delivery, we controlled each mother’s lactation to no more than eight pups. As a result, there were no differences in the body weight, length and AGD of F14mon compared with sham group.ConclusionRemoval of less than 50% of the ovaries did not affect the fertility of rats and offspring development of rats.
Association between serum Klotho concentration and hyperlipidemia in adults: a cross-sectional study from NHANES 2007–2016
Authors: Yan Shaohua , Luo Wei , Lei Li , Zhang Qiuxia , Xiu Jiancheng 
Published: November 2023

ObjectiveThe Klotho protein is a well-documented anti-aging protein known for its diverse biological functions. Hyperlipidemia is an established independent risk factor for various chronic diseases. However, there is limited understanding of the connection between Klotho and hyperlipidemia. The aim was to assess the association between serum Klotho levels and hyperlipidemia among adults.MethodsThe study included 11,618 individuals from the NHANES database from 2006 to 2017. Hyperlipidemia was diagnosed following the National Cholesterol Education Program guidelines. Serum Klotho concentration was measured by an enzyme-linked immunosorbent assay kit, and the association between Klotho and hyperlipidemia was assessed by a multivariable logistic regression model. Fitted smoothing curves and threshold-effect analysis were employed to describe nonlinear relationships.ResultsIn our multiple logistic regression models, serum Klotho concentration was significantly associated with hyperlipidemia after adjusting for comprehensive confounders (per SD increment odds ratio (OR): 0.91; 95% confidence interval (CI): 0.86–0.97). Compared to individuals in the lowest Klotho quartile, those in the highest quartile exhibited a substantially decreased prevalence of hyperlipidemia (OR: 0.72; 95% CI: 0.58–0.90). Using a two-segment logistic regression model, we identified a U-shaped relationship between serum Klotho concentration and hyperlipidemia, with an inflection point at 1,365.5 pg/mL. Subgroup analysis did not reveal any potential moderating effects.ConclusionThis study revealed an inverse relationship between Klotho levels and hyperlipidemia. Further investigation is warranted to explore the underlying mechanism between serum Klotho and hyperlipidemia.
Causal association between lipid-lowering drugs and female reproductive endocrine diseases: a drug-targeted Mendelian randomization study
Authors: Zhao Jing , Wang Runfang , Song Liyun , Han Hua , Wang Pei , Zhao Yuan , Zhang Yunxia , Zhang Hongzhen 
Published: November 2023

PurposeThe relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs.MethodsIn this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann–Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility.ResultsPCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p&lt;0.05). In contrast, HMGCR inhibitors significantly reduced the risk of menorrhagia in female patients (OR [95%CI] = 0.85 [0.75, 0.97], p&lt;0.05), but had no statistical impact on patients with oligomenorrhea.ConclusionThe findings suggest that PCSK9 inhibitors may significantly increase the risk of infertility in patients. On the other hand, HMGCR inhibitors could potentially offer protection against menorrhagia in women. However, no effects of lipid-lowering drugs have been observed on other reproductive endocrine disorders, such as PCOS, POF, PMS and oligomenorrhea.
The green GDP accounting system based on the BP neural network: an environmental pollution perspective
Authors: Zhu Yinglun , Xu Yingying , Luo Yuhui 
Published: November 2023

Introduction: The green GDP accounting system has become the focus of sustainable development, but a comprehensive accounting of environmental pollution cost and resource depletion cost has not yet been formed.Methods: This study measures environmental pollution cost and resource loss cost, and establishes the green GDP accounting system based on the SEEA-2012. To analyze the environmental effects brought by the adoption of green GDP accounting system, a BP neural network model including green GDP, traditional GDP and global climate indicators is constructed to predict the global climate changes.Results: The empirical results show that after the adoption of the green GDP accounting system, the global climate extreme weather can be reduced, the sea level will be lowered, and the climate problem is thus alleviated.
Competing risks modeling of length of hospital stay enhances risk-stratification of patient care: application to under-five children hospitalized in Malawi
Authors: Stanley Christopher C. , Zulu Madalitso , Msuku Harrison , Phiri Vincent S. , Kazembe Lawrence N. , Chinkhumba Jobiba , Mvalo Tisungane , Mathanga Don P. 
Published: November 2023

IntroductionLength of hospital stay (LOS), defined as the time from inpatient admission to discharge, death, referral, or abscondment, is one of the key indicators of quality in patient care. Reduced LOS lowers health care expenditure and minimizes the chance of in-hospital acquired infections. Conventional methods for estimating LOS such as the Kaplan-Meier survival curve and the Cox proportional hazards regression for time to discharge cannot account for competing risks such as death, referral, and abscondment. This study applied competing risk methods to investigate factors important for risk-stratifying patients based on LOS in order to enhance patient care.MethodsThis study analyzed data from ongoing safety surveillance of the malaria vaccine implementation program in Malawi's four district hospitals of Balaka, Machinga, Mchinji, and Ntchisi. Children aged 1–59 months who were hospitalized (spending at least one night in hospital) with a medical illness were consecutively enrolled between 1 November 2019 and 31 July 2021. Sub-distribution-hazard (SDH) ratios for the cumulative incidence of discharge were estimated using the Fine-Gray competing risk model.ResultsAmong the 15,463 children hospitalized, 8,607 (55.7%) were male and 6,856 (44.3%) were female. The median age was 22 months [interquartile range (IQR): 12–33 months]. The cumulative incidence of discharge was 40% lower among HIV-positive children compared to HIV-negative (sub-distribution-hazard ratio [SDHR]: 0.60; [95% CI: 0.46–0.76]; P &lt; 0.001); lower among children with severe and cerebral malaria [SDHR: 0.94; (95% CI: 0.86–0.97); P = 0.04], sepsis or septicemia [SDHR: 0.90; (95% CI: 0.82–0.98); P = 0.027], severe anemia related to malaria [SDHR: 0.54; (95% CI: 0.48–0.61); P &lt; 0.001], and meningitis [SDHR: 0.18; (95% CI: 0.09–0.37); P &lt; 0.001] when compared to non-severe malaria; and also 39% lower among malnourished children compared to those that were well-nourished [SDHR: 0.61; (95% CI: 0.55–0.68); P &lt; 0.001].ConclusionsThis study applied the Fine-Gray competing risk approach to more accurately model LOS as the time to discharge when there were significant rates of in-hospital mortality, referrals, and abscondment. Patient care can be enhanced by risk-stratifying by LOS based on children's age, HIV status, diagnosis, and nutritional status.
Decoding the internesting movements of marine turtles using a fine-scale behavioral state approach
Authors: Santos Armando J. B. , Cullen Joshua , Vieira Daniel H. G. , Lima Eduardo H. S. M. , Quennessen Victoria , Santos Erik A. P. dos , Bellini Claudio , Ramos Renata , Fuentes Mariana M. P. B. 
Published: November 2023

IntroductionAn understanding of animal behavior is critical to determine their ecological role and to inform conservation efforts. However, observing hidden behaviors can be challenging, especially for animals that spend most of their time underwater. Animal-borne devices are valuable tools to estimate hidden behavioral states.MethodsWe investigated the fine-scale behavior of internesting hawksbill turtles using the mixed-membership method for movement (M4) which integrated dive variables with spatial components and estimated latent behavioral states.ResultsFive latent behavioral states were identified: 1) pre-nesting, 2) transit, 3) quiescence, and 4) area restricted search within and 5) near the residence of turtles. The last three states associated with a residency period, showed lower activity levels. Notably, when compared to other behaviors the pre-nesting exhibited shallower and remarkably long dives of up to 292 minutes. We noted high fidelity to residence core areas and nesting beaches, within and between nesting seasons, with residence areas decreasing within a season.DiscussionThe latent behaviors identified provide the most detailed breakdown of turtle movement behaviors during the internesting period to date, providing valuable insights into their ecology and behavior. This information can inform marine turtle conservation and management efforts since utilization distributions of individual behavioral states can be used to determine spatially-explicit susceptibility of turtles to various threats based on their behavior. The analyses of utilization distribution revealed a minimal overlap with existing marine protected areas (0.4%), and we show how a new proposal would expand protection to 30%. In short, this study provides valuable guidance for conservation and management of internesting marine turtles at a fine spatiotemporal resolution and can be used to enhance national action plans for endangered species, including the expansion of existing Marine Protected Areas. By flexibly incorporating biologically informative parameters, this approach can be used to study behavior outside of the hawksbill breeding season or even beyond this species.
Artificial intelligence for the detection of sacroiliitis on magnetic resonance imaging in patients with axial spondyloarthritis
Authors: Lee Seulkee , Jeon Uju , Lee Ji Hyun , Kang Seonyoung , Kim Hyungjin , Lee Jaejoon , Chung Myung Jin , Cha Hoon-Suk 
Published: November 2023

BackgroundMagnetic resonance imaging (MRI) is important for the early detection of axial spondyloarthritis (axSpA). We developed an artificial intelligence (AI) model for detecting sacroiliitis in patients with axSpA using MRI.MethodsThis study included MRI examinations of patients who underwent semi-coronal MRI scans of the sacroiliac joints owing to chronic back pain with short tau inversion recovery (STIR) sequences between January 2010 and December 2021. Sacroiliitis was defined as a positive MRI finding according to the ASAS classification criteria for axSpA. We developed a two-stage framework. First, the Faster R-CNN network extracted regions of interest (ROIs) to localize the sacroiliac joints. Maximum intensity projection (MIP) of three consecutive slices was used to mimic the reading of two adjacent slices. Second, the VGG-19 network determined the presence of sacroiliitis in localized ROIs. We augmented the positive dataset six-fold. The sacroiliitis classification performance was measured using the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). The prediction models were evaluated using three-round three-fold cross-validation.ResultsA total of 296 participants with 4,746 MRI slices were included in the study. Sacroiliitis was identified in 864 MRI slices of 119 participants. The mean sensitivity, specificity, and AUROC for the detection of sacroiliitis were 0.725 (95% CI, 0.705–0.745), 0.936 (95% CI, 0.924–0.947), and 0.830 (95%CI, 0.792–0.868), respectively, at the image level and 0.947 (95% CI, 0.912–0.982), 0.691 (95% CI, 0.603–0.779), and 0.816 (95% CI, 0.776–0.856), respectively, at the patient level. In the original model, without using MIP and dataset augmentation, the mean sensitivity, specificity, and AUROC were 0.517 (95% CI, 0.493–0.780), 0.944 (95% CI, 0.933–0.955), and 0.731 (95% CI, 0.681–0.780), respectively, at the image level and 0.806 (95% CI, 0.729–0.883), 0.617 (95% CI, 0.523–0.711), and 0.711 (95% CI, 0.660–0.763), respectively, at the patient level. The performance was improved by MIP techniques and data augmentation.ConclusionAn AI model was developed for the detection of sacroiliitis using MRI, compatible with the ASAS criteria for axSpA, with the potential to aid MRI application in a wider clinical setting.
Development of a semi-automated MHC-associated peptide proteomics (MAPPs) method using streptavidin bead-based immunoaffinity capture and nano LC-MS/MS to support immunogenicity risk assessment in drug development
Authors: Lee M. Violet , Saad Ola M. , Wong Sylvia , LaMar Jason , Kamen Lynn , Ordonia Ben , Melendez Rachel , Hassanzadeh Azadeh , Chung Shan , Kaur Surinder 
Published: November 2023

Major histocompatibility complex (MHC)-Associated Peptide Proteomics (MAPPs) is an ex vivo method used to assess the immunogenicity risk of biotherapeutics. MAPPs can identify potential T-cell epitopes within the biotherapeutic molecule. Using adalimumab treated human monocyte derived dendritic cells (DCs) and a pan anti-HLA-DR antibody (Ab), we systematically automated and optimized biotin/streptavidin (SA)-capture antibody coupling, lysate incubation with capture antibody, as well as the washing and elution steps of a MAPPs method using functionalized magnetic beads and a KingFisher Magnetic Particle processor. Automation of these steps, combined with capturing using biotinylated-Ab/SA magnetic beads rather than covalently bound antibody, improved reproducibility as measured by minimal inter-and intra-day variability, as well as minimal analyst-to-analyst variability. The semi-automated MAPPs workflow improved sensitivity, allowing for a lower number of cells per analysis. The method was assessed using five different biotherapeutics with varying immunogenicity rates ranging from 0.1 to 48% ADA incidence in the clinic. Biotherapeutics with ≥10%immunogenicity incidence consistently presented more peptides (1.8-28 fold) and clusters (10-21 fold) compared to those with &lt;10% immunogenicity incidence. Our semi-automated MAPPs method provided two main advantages over a manual workflow- the robustness and reproducibility affords confidence in the epitopes identified from as few as 5 to 10 donors and the method workflow can be readily adapted to incorporate different capture Abs in addition to anti-HLA-DR. The incorporation of semi-automated MAPPs with biotinylated-Ab/SA bead-based capture in immunogenicity screening strategies allows the generation of more consistent and reliable data, helping to improve immunogenicity prediction capabilities in drug development.MHC associated peptide proteomics (MAPPs), Immunogenicity risk assessment, in vitro/ex vivo, biotherapeutics, Major Histocompatibility Complex Class II (MHC II), LC-MS, Immunoaffinity Capture, streptavidin magnetic beads