bluuebunny/crossref_metadata_2025_split huggingface dataset:
The morphokinetic signature of human blastocysts with mosaicism and the clinical outcomes following transfer of embryos with low-level mosaicism
Authors: Zou Yaoyu , Sui Yilun , Fu Jing , Ge Naidong , Sun Xiaoxi , Sun Yijuan 
Published: January 2024

Abstract
Background
Genetic mosaicism is commonly observed in human blastocysts. Embryos’ morphokinetic feature observed from time-lapse monitoring (TLM) is helpful to predict the embryos’ ploidy status in a non-invasive way. However, morphokinetic research on mosaic embryos is extremely limited. Moreover, transfer of mosaic embryos is a new attempt in reproductive medicine, while studies regarding the clinical and neonatal outcomes following transfer of embryos with different levels and types of mosaicism are needed. This study aimed to investigate the morphokinetic characteristics of mosaic blastocysts, uncover clinical outcomes of mosaic embryos, and evaluate the effect of level and type of mosaicism on transfer outcomes.

Results
A total of 923 blastocysts from 229 preimplantation genetic testing cycles were cultured in TLM incubators in a single fertilization center between July 2016 and July 2021. Multivariate logistic regression models showed mosaic embryos had significantly shorter time to reach morula when compared with euploid (P = 0.002), mosaic with aneuploid (P = 0.005), and aneuploid (P = 0.005) embryos after adjusting the potential confounders. KIDScore is an artificial intelligence scoring program from time lapse incubation system to predict embryo implantation potential. Mosaic with aneuploid embryos had significantly lower KIDScore than euploid (P = 6.47e−4), mosaic (P = 0.005), and aneuploid (P = 0.004) embryos after adjustment. Meanwhile, we compared the clinical outcomes following transfer of low-level (< 50%) mosaic embryos (N = 60) with euploid embryos (N = 1301) matched using propensity scoring collected from September 2020 to January 2023. Mosaic embryos had significantly lower clinical pregnancy rate (41.67% vs. 57.65%, P = 0.015) and live birth rate (38.33% vs. 51.35%, P = 0.048) than the euploid embryos. Subgroup analyses showed the whole, segmental, and complex chromosome mosaic embryos had the similar clinical outcomes.

Conclusions
The shortened time to reach morula in mosaic embryos and the low KIDScore in mosaic with aneuploid embryos revealed innovative clues to embryo selection with the non-invasive TLM and provided new insights into biological mechanism of chromosomal abnormality. The analyses of overall and subgroups of mosaic embryo transfer outcomes helped to optimize embryo transfer scheme for in-vitro fertilization procedures. Multi-center prospective studies with large sample sizes are warranted to validate our results in the future.
InterVFast—effectiveness and acceptance of intermittent fasting in cardiac rehabilitation patients: study protocol of a randomized controlled trial
Authors: Pieper Claudia , Kaistha Florian Tim Hitesh , Schroeer Sarah , Borgert Maria , Michalsen Andreas , Mayer-Berger Wolfgang 
Published: January 2024

Abstract
Background
Research on intermittent fasting has shown that it can improve a variety of health outcomes, including blood sugar control, blood lipid levels and blood pressure. Only few studies document longer periods of fasting, especially in rehabilitation participants. Cardiac inpatient rehabilitation follows a multidisciplinary approach including change of health behaviour to reduce patients’ risk of future cardiovascular events. To date, evidence suggests that intermittent fasting can be an effective way to improve health and well-being, but more research is needed to fully understand its long-term effects and factors that promote the implementation. Therefore, the aim of the ongoing InterVFast trial is to investigate the effectiveness of intermittent fasting amongst cardiac rehabilitation patients after 4-week inpatient rehabilitation as well as 3 and 12 months subsequently including patients’ perspective.

Methods
This single-centre randomized controlled trial evaluates the effectiveness of the InterVFast intervention in weight loss (primary outcome). We also examine patients’ acceptance and the effect on relevant outcomes as blood glucose and triglyceride levels, cholesterol and high-sensitivity C-reactive protein. Weight, blood samples and clinical data are collected as part of the initial and final examination during inpatient rehabilitation. During inpatient rehabilitation, participants daily note fasting intervals and meals eaten as well as practicability in a fasting diary. In addition, interviews about perceived advantages and disadvantages and acceptance are carried out with the participants in the IG. A standardized follow-up examination (weight, blood samples) will be carried out by the family doctor after 3 and 12 months (t2 and t3).

Discussion
Compared to other weight-loss intervention studies, our study addresses patients with coronary heart disease and includes patients’ acceptance as well as long-term maintenance. It is hypothesized that participation in the InterVfast intervention will improve relevant health outcomes in a sample of cardiac rehabilitation patients and thus constitute a behavioural prevention strategy to reduce the risk of future cardiac events and improve overall health and quality of life.

Trial registration
ClinicalTrials.gov DRKS00023983. Registered on February 17, 2022.
Determining the effects of targeted high-definition transcranial direct current stimulation on reducing post-stroke upper limb motor impairments—a randomized cross-over study
Authors: Peng Rita Huan-Ting , He Dorothy , James Shirley A. , Williamson Jordan N. , Skadden Carly , Jain Sanjiv , Hassaneen Wael , Miranpuri Amrendra , Kaur Amandeep , Sarol Jesus N. , Yang Yuan 
Published: January 2024

Abstract
Background
Stroke is one of the leading causes of death in the USA and is a major cause of serious disability for adults. This randomized crossover study examines the effect of targeted high-definition transcranial direct current transcranial brain stimulation (tDCS) on upper extremity motor recovery in patients in the post-acute phase of stroke recovery.

Methods
This randomized double-blinded cross-over study includes four intervention arms: anodal, cathodal, and bilateral brain stimulation, as well as a placebo stimulation. Participants receive each intervention in a randomized order, with a 2-week washout period between each intervention. The primary outcome measure is change in Motor Evoked Potential. Secondary outcome measures include the Fugl-Meyer Upper Extremity (FM-UE) score, a subset of FM-UE (A), related to the muscle synergies, and the Modified Ashworth Scale.

Discussion
We hypothesize that anodal stimulation to the ipsilesional primary motor cortex will increase the excitability of the damaged cortico-spinal tract, reducing the UE flexion synergy and enhancing UE motor function. We further hypothesize that targeted cathodal stimulation to the contralesional premotor cortex will decrease activation of the cortico-reticulospinal tract (CRST) and the expression of the upper extremity (UE) flexion synergy and spasticity. Finally, we hypothesize bilateral stimulation will achieve both results simultaneously. Results from this study could improve understanding of the mechanism behind motor impairment and recovery in stroke and perfect the targeting of tDCS as a potential stroke intervention. With the use of appropriate screening, we anticipate no ethical or safety concerns. We plan to disseminate these research results to journals related to stroke recovery, engineering, and medicine.

Trial registration
ClinicalTrials.gov NCT05479006. Registered on 26 July 2022.
Transcriptional signals of transformation in human cancer
Authors: Kildisiute Gerda , Kalyva Maria , Elmentaite Rasa , van Dongen Stijn , Thevanesan Christine , Piapi Alice , Ambridge Kirsty , Prigmore Elena , Haniffa Muzlifah , Teichmann Sarah A. , Straathof Karin , Cortés-Ciriano Isidro , Behjati Sam , Young Matthew D. 
Published: January 2024

Abstract
Background
As normal cells transform into cancers, their cell state changes, which may drive cancer cells into a stem-like or more primordial, foetal, or embryonic cell state. The transcriptomic profile of this final state may encode information about cancer’s origin and how cancers relate to their normal cell counterparts.

Methods
Here, we used single-cell atlases to study cancer transformation in transcriptional terms. We utilised bulk transcriptomes across a wide spectrum of adult and childhood cancers, using a previously established method to interrogate their relationship to normal cell states. We extend and validate these findings using single-cell cancer transcriptomes and organ-specific atlases of colorectal and liver cancer.

Results
Our bulk transcriptomic data reveals that adult cancers rarely return to an embryonic state, but that a foetal state is a near-universal feature of childhood cancers. This finding was confirmed with single-cell cancer transcriptomes.

Conclusions
Our findings provide a nuanced picture of transformation in human cancer, indicating cancer-specific rather than universal patterns of transformation pervade adult epithelial cancers.
The association between plasma free amino acids and type 2 diabetes mellitus complicated with infection in Chinese patients
Authors: Zhang Jing-Xi , Luo Wei-Ming , Wang Bo-Wen , Li Ru-Tao , Zhang Qian , Zhang Xiang-Yu , Fang Zhong-Ze , Zhang Zhi-Peng 
Published: January 2024

Abstract
Background
Type 2 diabetes mellitus (T2DM), one of the most common public diseases threatening human health, is always accompanied by infection. Though there are still a variety of flaws in the treatment of some infectious diseases, metabolomics provides a fresh perspective to explore the relationship between T2DM and infection. Our research aimed to investigate the association between plasma free amino acids (PFAAs) and T2DM complicated with infection in Chinese patients.

Methods
A cross-sectional study was conducted from May 2015 to August 2016. We retrieved the medical records of 1032 inpatients with T2DM from Liaoning Medical University First Affiliated Hospital and we used mass spectrometry to quantify 23 PFAAs. Infections contained 15 individual categories that could be retrieved from the database. Principal component analysis was used to extract factors of PFAAs. Multi-variable binary logistic regression was used to obtain odds ratios (OR) and their 95% confidence intervals (CI).

Results
Among 1032 inpatients,109 (10.6%) had infectious diseases. Six factors, accounting for 68.6% of the total variance, were extracted. Factor 4 consisted of Glu, Asp and Orn. Factor 5 consisted of Hcy and Pip. After adjusting for potential confounders, factor 4 was positively correlated with T2DM complicated with infection in Chinese T2DM patients (OR: 1.27, 95%CI: 1.06–1.52). Individual Hcy in factor 5 was positively associated with T2DM complicated with infection (OR: 1.33, 95%CI: 1.08–1.64). Furthermore, factor 4 (OR: 1.44, 95%CI: 1.11–1.87), Orn (OR: 1.01, 95%CI: 1.00-1.02) and Hcy (OR: 1.56, 95%CI: 1.14–3.14) were positively associated with bacterial infection in Chinese T2DM patients, while factor 5 (OR: 0.71, 95%CI: 0.50-1.00) was negatively associated with bacterial infection.

Conclusions
Urea cycle-related metabolites (Orn, Asp, Glu) and Hcy were positively associated with T2DM complicated with infection in China. Orn and Hcy were positively associated with bacterial infection in T2DM patients in China.
Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study
Authors: Zhao Jiaxi , Chen Rong , Luo Mengqi , Gong Hongping , Li Kaixin , Zhao Qian 
Published: January 2024

Abstract
Background
Inflammatory bowel disease (IBD) has been associated with lipid-lowering drugs in observational studies. Drug-target Mendelian randomization (MR) was utilized in this study to examine the causal relationship between lipid-lowering drugs and incidence of IBD, aiming to identify new preventive uses for the drugs.

Methods
We identified instrumental variables for three classes of lipid-lowering drugs: HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors, using data from the Global Lipids Genetics Consortium. Summary statistics of IBD were obtained from UK Inflammatory Bowel Disease Genetics. The summary-data-based MR (SMR) and the inverse-variance weighted (IVW) MR were used for analysis. Sensitivity analyses were performed by conventional MR methods.

Results
The SMR analysis showed no significant genetic association between increased gene expression of HMGCR, PCSK9, and NPC1L1 and IBD, Crohn’s disease (CD) and ulcerative colitis (UC). According to IVW-MR analysis, increased HMGCR expression is associated with a reduced risk of IBD (OR = 0.73, 95% confidence interval (CI) 0.59–0.90, P = 0.003) and CD (OR = 0.75, 95% CI 0.57–0.97, P = 0.03), but not with UC. Additionally, increased NPC1L1 gene expression was associated with elevated risk of IBD (OR = 1.60, 95% CI 1.07–2.40, P = 0.023), but not with CD and UC. However, no significant causal relationships were found between PCSK9 gene expression and IBD, CD, and UC. The sensitivity analysis demonstrated no evidence of heterogeneity or pleiotropy among the reported results.

Conclusions
The heightened expression of genetic variations in HMGCR inhibitor targets could potentially reduce the risk of IBD and CD, while genetic variation in the expression of NPC1L1 targets was positively associated with IBD.
Transformed Salmonella typhimurium SL7207/pcDNA-CCOL2A1 as an orally administered DNA vaccine
Authors: Long Juan , Zeng Yang , Liang Fei , Liu Nan , Xi Yongzhi , Sun Yuying , Zhao Xiao 
Published: January 2024

AbstractThe use of attenuated bacteria for oral delivery of DNA vaccines is a recent innovation. We designed and constructed the naked plasmid DNA vaccine pcDNA-CCOL2A1, which effectively prevented and treated a rheumatoid arthritis model by inducing immunotolerance. We aimed to ensure a reliable, controllable dosage of this oral DNA vaccine preparation and establish its stability. We transformed pcDNA-CCOL2A1 via electroporation into attenuated Salmonella typhimurium SL7207. A resistant plate assay confirmed the successful construction of the transformed strain of the SL7207/pcDNA-CCOL2A1 oral DNA vaccine. We verified its identification and stability in vitro and in vivo. Significant differences were observed in the characteristics of the transformed and blank SL7207 strains. No electrophoretic restriction patterns or direct sequencing signals were observed in the original extract of the transformed strain. However, target gene bands and sequence signals were successfully detected after PCR amplification. CCOL2A1 expression was detected in the ilea of BALB/c mice that were orally administered SL7207/pcDNA-CCOL2A1. The pcDNA-CCOL2A1 plasmid of the transformed strain was retained under the resistant condition, and the transformed strain remained stable at 4 °C for 100 days. The concentration of the strain harboring the pcDNA-CCOL2A1 plasmid was stable at 109 CFU/mL after 6–8 h of incubation. The results demonstrated that the transformed strain SL7207/pcDNA-CCOL2A1 can be expressed in vivo, has good stability, and may be used to prepare the oral DNA vaccine pcDNA-CCOL2A1 with a stable, controllable dosage and the capacity to provide oral immunization. This vehicle can effectively combine both oral immunotolerance and DNA vaccination.
The association of medical, social, and normative factors with the implementation of end-of-life care practices
Authors: Ziv Arnona , Shaulov Adir , Rubin Carmit , Oberman Bernice , Tawil Yoel , Kaplan Giora , Velan Baruch , Bodas Moran 
Published: January 2024

Abstract
Background
End-of-life (EoL) care practices (EoLCP) are procedures carried out at the EoL and bear directly on this stage in the patient’s life. Public support of these practices in Israel is far from uniform. Previous studies show that while ∼30% of participants support artificial respiration or feeding of terminally ill patients, 66% support analgesic treatment, even at the risk of shortening life. This study aimed to create a typology of six end-of-life care practices in Israel and assess the association of medical, social, and normative factors with the implementation of those practices. These practices included mechanical ventilation, artificial feeding, deep sedation, providing information to the patient and family caregivers, including family caregivers in EoL decision-making, and opting for death at home.

Methods
This cross-sectional study was performed as an online survey of 605 adults aged 50 or more in Israel, of which ~ 50% (n = 297) reported supporting a dying terminally ill relative in the last 3 years. Participants were requested to provide their account of the EoL process of their relative dying from a terminal illness in several aspects, as well as the EoL care practices utilized by them.

Results
The accounts of the 297 interviewees who supported a dying relative reveal a varied EoL typology. The utilization of end-of-life care practices was associated with the socio-normative beliefs of family caregivers but not with their socioeconomic status. Strong correlations were found between family caregiver support for three key practices (mechanical ventilation, artificial feeding, and family involvement in EoL) and the actual utilization of these practices in the care of dying patients.

Conclusions
The findings portray an important image of equity in the utilization of EoLCP in Israel, as the use of these practices was not associated with socioeconomic status. At the same time, the study found substantial diversity in family caregivers’ preferences regarding EoL care practices use not related to socioeconomic status. We believe that differences in preferences that do not lead to problems with equity or other important societal values should be respected. Accordingly, policymakers and health system leaders should resist calls for legislation that would impose uniform EoL practices for all Israelis. Instead, they should take concrete steps to preserve and enhance the widespread current practice of practitioners to adapt EoL care to the varied needs and preferences of Israeli families and cultural, social, and religious subgroups. These steps should include providing frameworks and tools for family caregivers to support their loved ones close to their deaths, such as educational programs, seminars, supportive care before and during the end of life of their loved ones, etc.
Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature
Authors: Zhao Shangkun , Qiao Zhi , Pfeifer Roman , Pape Hans-Christoph , Mao Keya , Tang Hai , Meng Bin , Chen Songfeng , Liu Hongjian 
Published: January 2024

AbstractThe senescence-associated secretory phenotype (SASP) is a generic term for the secretion of cytokines, such as pro-inflammatory factors and proteases. It is a crucial feature of senescent cells. SASP factors induce tissue remodeling and immune cell recruitment. Previous studies have focused on the beneficial role of SASP during embryonic development, wound healing, tissue healing in general, immunoregulation properties, and cancer. However, some recent studies have identified several negative effects of SASP on fracture healing. Senolytics is a drug that selectively eliminates senescent cells. Senolytics can inhibit the function of senescent cells and SASP, which has been found to have positive effects on a variety of aging-related diseases. At the same time, recent data suggest that removing senescent cells may promote fracture healing. Here, we reviewed the latest research progress about SASP and illustrated the inflammatory response and the influence of SASP on fracture healing. This review aims to understand the role of SASP in fracture healing, aiming to provide an important clinical prevention and treatment strategy for fracture. Clinical trials of some senolytics agents are underway and are expected to clarify the effectiveness of their targeted therapy in the clinic in the future. Meanwhile, the adverse effects of this treatment method still need further study.
Quantifying the climate change impacts on the magnitude and timing of hydrological extremes in the Baro River Basin, Ethiopia
Authors: Kassaye Shimelash Molla , Tadesse Tsegaye , Tegegne Getachew , Hordofa Aster Tesfaye 
Published: January 2024

AbstractExtreme hydrological events, like floods and droughts, exert considerable effects on both human and natural systems. The frequency, intensity, and duration of these events are expected to change due to climate change, posing challenges for water resource management and adaptation. In this study, the Soil and Water Assessment Tool plus (SWAT +) model was calibrated and validated to simulate flow under future shared socioeconomic pathway (SSP2-4.5 and SSP5-8.5) scenarios in the Baro River Basin with R2 values of 0.88 and 0.83, NSE of 0.83 and 0.74, and PBIAS of 0.39 and 8.87 during calibration and validation. Six bias-corrected CMIP6 Global Climate Models (GCM) were selected and utilized to investigate the effects of climate change on the magnitude and timing of hydrological extremes. All climate model simulation results suggest a general increase in streamflow magnitude for both emission scenarios (SSP2-4.5 and SSP5-8.5). The multi-model ensemble projections show yearly flow increases of 4.8% and 12.4% during the mid-term (MT) (2041–2070) and long-term (LT) (2071–2100) periods under SSP2-4.5, and 15.7% and 35.6% under SSP5-8.5, respectively. Additionally, the analysis revealed significant shifts in the projected annual 1 day, 3 day, 7 day, and 30 day maximum flows, whereas the annual 3 day and 7 day minimum flow fluctuations do not present a distinct trend in the future scenario compared to the baseline (1985–2014). The study also evaluated the timing of hydrological extremes, focusing on low and peak flow events, utilizing the annual 7 day maximum and minimum flow for this analysis. An earlier occurrence was noted for both peak and low flow in the SSP2-4.5 scenario, while a later occurrence was observed in the SSP5-8.5 scenario compared to the baseline. In conclusion, this study showed the significant effect of climate change on river hydrology and extreme flow events, highlighting their importance for informed water management and sustainable planning.