bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)
Authors: O’Hearn Katie , Menon Kusum , Weiler Hope A. , Amrein Karin , Fergusson Dean , Gunz Anna , Bustos Raul , Campos Roberto , Catalan Valentina , Roedl Siegfried , Tsampalieros Anne , Barrowman Nick , Geier Pavel , Henderson Matthew , Khamessan Ali , Lawson Margaret L. , McIntyre Lauralyn , Redpath Stephanie , Jones Glenville , Kaufmann Martin , McNally Dayre 
Published: April 2023

Abstract
Background: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU.
Methods: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D >75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial.
Results: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration >75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean (SD) 25(OH)D concentration in the treatment arm was 125.9 nmol/L (63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%).
Conclusions: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up.
Trial Registration: Clinicaltrials.gov NCT02452762Registered 25/05/2015, https://clinicaltrials.gov/ct2/show/NCT02452762?term=NCT02452762&draw=2&rank=1
The role of health behaviours, genetic factors, and early life environment in the association of family-related events and sustainable working life
Authors: Wang Mo , Svedberg Pia , Silventoinen Karri , Böckerman Petri , Narusyte Jurgita , Ropponen Annina 
Published: April 2023

Abstract
Background Studies are limited for family-related events in relation to sustainable working life (i.e., not having long-term periods of unemployment, sickness absence and disability pension). We aimed to investigate the associations between stability and change in family life and sustainable working life and whether these associations were explained by health behaviours, genetic factors, and early life environment.Methods Register data and surveys for family-related events, sustainable working life and health behaviours of 49 611 Swedish twins were used. Cox proportional hazards regressions were applied to estimate the associations between family-related events and sustainable working life, while conditional Cox models for twin pairs accounted for confounding of genetic factors and early life environment. Further, the analyses were stratified by health behaviours.Results Change from being single living without children to married living with children was associated with sustainable working life. Moreover, individuals who experienced divorce and single individuals who changed status of living with children were less likely to experience a sustainable working life. Genetic factors and early life environment played a role in some associations. Also, those with healthy behaviours were more likely to have sustainable working life even though they had changes in family life compared to those with unhealthy behaviours.Conclusions Family formation is associated with sustainable working life whereas divorce seems to decrease the possibility of sustainable working life. Health behaviours as well as genetic factors and early life environment also need to be considered in relation to changes in family life for supporting sustainable working life.
Exploring a new mechanism between lactate and VSMC calcification: PARP1/POLG/UCP2 signaling pathway and imbalance of mitochondrial homeostasis
Authors: Zhu Yi , Zhang Jia-li , Yan Xue-jiao , Ji Yuan , Wang Fang-fang 
Published: April 2023

Abstract
Lactate leads to the imbalance of mitochondria homeostasis, which then promotes vascular calcification. PARP1 can upregulate osteogenic genes and accelerate vascular calcification. However, the relationship among lactate, PARP1, and mitochondrial homeostasis is unclear. The present study aimed to explore the new molecular mechanism of lactate to promote VSMC calcification by evaluating PARP1 as a breakthrough molecule. A coculture model of VECs and VSMCs was established, and the model revealed that the glycolysis ability and lactate production of VECs were significantly enhanced after incubation in DOM. Osteogenic marker expression, calcium deposition, and apoptosis in VSMCs were decreased after lactate dehydrogenase A knockdown in VECs. Mechanistically, exogenous lactate increased the overall level of PARP and PARylation in VSMCs. PARP1 knockdown inhibited Drp1-mediated mitochondrial fission and partially restored PINK1/Parkin-mediated mitophagy, thereby reducing mitochondrial oxidative stress. Moreover, lactate induced the translocation of PARP1 from the nucleus to the mitochondria, which then combined with POLG and inhibited POLG-mediated mitochondrial DNA synthesis. This process led to the downregulation of mitochondria-encoded genes, disturbance of mitochondrial respiration, and inhibition of oxidative phosphorylation. The knockdown of PARP1 could partially reverse the damage of mitochondrial gene expression and function caused by lactate. Furthermore, UCP2 was upregulated by the PARP1/POLG signal, and UCP2 knockdown inhibited Drp1-mediated mitochondrial fission and partially recovered PINK1/Parkin-mediated mitophagy. Finally, UCP2 knockdown in VSMCs alleviated DOM-caused VSMC calcification in the coculture model. The study results thus suggest that upregulated PARP1 is involved in the mechanism through which lactate accelerates VSMC calcification partly via POLG/UCP2-caused unbalanced mitochondrial homeostasis.
Preparation of ZnGa2O4 Nanoflowers and Their Full-color Luminescence Properties
Authors: Liu Yan , Wan Xinhuan , Zheng Tingting , Zhang Xiuyun , Chen Chen 
Published: April 2023

Abstract
Gallate material, a luminescent matrix with excellent performance is normally prepared by vapor deposition or solid phase sintering method at high temperature, however, it has not been solved to prepare gallate-based fluorescent materials with full-color luminescent properties at low temperature. In this paper, ZnGa2O4 undoped or doped with Cr or Mn nanoflowers composed of nanosheet-level structure were prepared by hydrothermal method at low temperature. Under ultraviolet light irradiation, ZnGa2O4, ZnGa2O4:Mn2+ and ZnGa2O4:Cr3+ display three primary colors of blue, green and red luminescence through self-excitation, Mn2+ and Cr3+ excitation respectively. The solid fluorescence yields of blue, green, and red colors are 32.3, 36.5, and 40.7%, respectively. It is highly expected to be applied to color display, biological imaging, white light devices.
Sch C Ameliorates Pulmonary Fibrosis by Inhibiting the Level of LOX
Authors: Xu Mingchen , Zhao Chenghe , Song Haiming , Wang Chunmei , Li He , Qiu Xudong , Jing He , Zhuang Wenyue 
Published: April 2023

Abstract
Pulmonary fibrosis (PF) is a serious progressive fibrotic disease that is characterized by excessive accumulation of extracellular matrix (ECM), thus resulting in stiff lung tissues. Lysyl oxidase (LOX) is an enzyme involved in fibrosis by catalyzing collagen cross-linking. Studies found that the ingredients in schisandra ameliorated bleomycin (BLM)-induced PF, but it is unknown whether the anti-PF of schisandra is related to LOX. In this study, we established models of PF including a mouse model stimulated by BLM and a HFL1 cell model induced by transforming growth factor (TGF)-β1 to evaluate the inhibition effects of Schisandrin C (Sch C) on PF. We observed that Sch C treatment decreased pulmonary indexes compared to control group. Treatment of Sch C showed a significant reduction in the accumulation of ECM as evidenced by decreased expressions of alpha-smooth muscle actin (α-SMA)、fibronectin (FN)、matrix metalloproteinases-2 (MMP2)、MMP9、tissue inhibitor of matrix metalloproteinases (TIMP1) and collagen proteins such as collagen 1A1 (Col 1A1), and Col 3A1. In addition, the expression of LOX in the lung tissue of mice after Sch C treatment was effectively decreased compared with the MOD group. The inhibition effects in vitro were consistent with those in vivo. Mechanistic studies revealed that Sch C significantly inhibited TGF-β1/Smad2/3 and TNF-α/JNK signaling pathways. In conclusion, our data demonstrated that Sch C significantly ameliorated PF in vivo and vitro, which may play an important role by reducing ECM deposition and inhibiting the production of LOX.
Value of global longitudinal peak systolic strain derived by 2-D speckle tracking in detection of obstructive coronary artery disease
Authors: Areed Mohamed Fayez , Yossof Mahmoud Abdo , Wadie Moheb 
Published: April 2023

Abstract
Background:
Early detection of obstructive coronary artery disease (CAD) using Peak Systolic global longitudinal strain derived by 2-D Speckle Tracking in patients with chronic stable angina.
75 patients with chronic stable angina were enrolled in this cross sectional study, (Mean age was 56.69 ± 6.96 y, 35 were males), 42.7 % were diabetic and all patients were assessed by thorough history taking, clinical examination,12 lead surface ECG, conventional, speckle Echocardiography and coronary angiography in Mansoura specialized medical hospital from march 2017 to October 2017
Results:
Statistically significant decrease was found in GLS-Avg values in patients with obstructive CAD when compared to patients with normal coronary angiography (p<0001) and in patients with 3 or more risk factors when compared to patients with one or two risk factors (p=0.014), And when syntax score was increasing among patients with obstructive CAD a significant decrease in median GLS-Avg values was noted (p<0.001), but when regional systolic strain values were compared to affected coronary arteries no significant difference was found (p=0.844) i.e almost identical correlation between affected segments by speckle tracking and obstructed arteries by coronary angiography.
Multivariate logistic regression analysis showed that GLS-Avg was found as a predictor for CAD disease in patients with chronic stable angina (p=0.028 with odds ratio 31.4 and 95% CI (1.85-535))
ROC curves were established and cutoff value was determined for GLS-Avg as -16 with 89.8% sensitivity and 100% specificity
Conclusion:
longitudinal strain derived by speckle tracking can be used as non-invasive simple test for evaluation of patients with chronic stable angina and as a predictor for presence or absence of obstructive CAD
Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition
Authors: Silva Clovis Artur Almeida da , Kupa Leonard de Vinci Kanda , Medeiros-Ribeiro Ana Cristina , Pasoto Sandra Gofinet , Saad Carla Gonçalves Schahin , Yuki Emily Figueiredo Neves , Landim Joaquim Ivo Vasques Dantas , Léda Victor Hugo Ferreira e , Correia Luisa Sacchi de Camargo , Sartori Artur Fonseca , Martins Carolina Campagnoli Machado Freire , Ribeiro Carolina Torres , Waridel Filipe , Martins Victor Adriano de Oliveira , Shinjo Samuel Katsuyuki , Andrade Danieli Castro Oliveira , Barros Percival Degrava Sampaio , Neto Eduardo Ferreira Borba , Aikawa Nadia Emi , Bonfá Eloísa 
Published: April 2023

Abstract
Background: Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria.
Methods: Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥4 weeks and >12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria.
Results: ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of > 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p=0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p=0.5419). Regarding > 4 weeks post-acute COVID-19, frequencies of ≥3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p=0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p=0.1322). Further analysis of the risk factors for > 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p>0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p>0.05), with fatigue and memory loss being the most frequent manifestations.
Conclusion: We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).
WITHDRAWN: Analysis of heterogeneity in subpopulations of breast cancer using single-cell RNA sequencing
Authors: li guifa 
Published: April 2023

Abstract
Breast cancer is a complex disease with high levels of intra-tumor heterogeneity. Single-cell RNA sequencing (scRNA-seq) can identify the gene expression profile of different cell subpopulations, revealing key subpopulations that drive tumor progression and therapeutic resistance. We analyzed single-cell RNA-seq data from 26 primary tumors from three major clinical breast cancer subtypes. We inferred copy number variation (CNV) and identified 8 clusters of malignant epithelial cells, with Cluster 1 being the most widely present in breast cancer. We identified 28 subpopulations based on gene-expression profiles, with five subpopulations shared by multiple patients. We identified specific ligand-receptor interactions between different subpopulations and identified key pathway-associated prognostic markers, including EPHA3, JAML, LCK, and SEMA3B, which could serve as potential biomarkers. The tumor microenvironment plays a significant role in tumor growth and metastasis. Targeting proteins involved in the interaction between cancer cells and the microenvironment, including ALCAM, CD6, and Adgre5, has shown promise in preclinical cancer models. This study could provide valuable information to identify biomarkers for individualized cancer therapy, which is challenging due to high levels of intra-tumor heterogeneity.
Research on the spatial correlation and formation mechanism between traditional villages and rural tourism
Authors: Li ZiYang , Yang MeiYu , Zhou XianLan , Li ZhiGang , Li HaiDong , Zhai FeiFei , Zhang Yan , Zhang Yunxing 
Published: April 2023

Abstract
In recent years, the survival and development of traditional villages in China have been serious challenges. Rural tourism is regarded as an important way to solve rural problems, and the combination of rural culture and tourism has become a new power point for rural development. Therefore, it is necessary to explore the spatial distribution structure between traditional villages and rural tourism. In this paper, rural tourism was represented by the rural tourism characteristic village (RTCV), and Henan Province, China, was taken as a study area to analyze the distribution pattern and spatial correlation of rural tourism and traditional village (TV) and discuss the relationship between the spatial correlation and regional natural environment and socioeconomic factors. The results show that the coupling of the spatial correlation between RTCVs and TVs in Henan was clear. They could be divided into 5 regions based on geographical factors. In addition, the research summarized 4 typical spatial structures between TVs and RTCVs in Henan based on the regional symbiosis theory, and the spatial pattern formation mechanism of TVs and RTCVs was discussed based on three driving mechanisms. The spatial structure of the two can provide reference value for other developing countries and regions to achieve sustainable rural development.
Why do Older Adults Decline Participation in Research? Results from Two Deprescribing Clinical Trials
Authors: Strayer Thomas , Hollingsworth Emily , Shah Avantika , Vasilevskis Eduard , Simmons Sandra , Mixon Amanda 
Published: April 2023

Abstract
Background Heterogenous older adult populations are underrepresented in clinical trials, and their participation is necessary for interventions that directly target them. The purpose of this study was to evaluate reasons why hospitalized older adults declined participation in two deprescribing clinical trials.Methods We report enrollment data from two deprescribing trials, Shed-MEDS (non-Veterans) and VA DROP (Veterans). For both trials, inclusion criteria required participants to be hospitalized, age 50 or older, English-speaking, and taking five or more home medications. Eligible patients were approached for enrollment while hospitalized. When an eligible patient or surrogate declined participation, the reason(s) were recorded and subsequently analyzed inductively to develop themes, and a Chi-square test was used for comparison.Results Across both trials, 1226 patients (545 non-Veterans and 681 Veterans) declined enrollment and provided reasons, which were condensed into three themes: (1) feeling overwhelmed by their current health status, (2) lack of interest or mistrust of research, and (3) hesitancy to participate in a deprescribing study. A greater proportion of Veterans expressed a lack of interest or mistrust in research (42% vs 26%, chi-square value = 36.72, p < .001); whereas a greater proportion of non-Veterans expressed feeling overwhelmed by their current health status (54% vs 35%, chi-square value = 42.8 p < 0.001). Across both trials, similar proportion of patients expressed hesitancy to participate in a deprescribing study, with no significant difference between Veterans and non-Veterans (23% and 21%).Conclusions The inclusion of older adults in clinical trial research broadens its impact. Understanding the reasons older adults decline participation can inform future strategies to engage this multimorbid population.
A Data-driven Approach to Revamp the ACO Risk Adjustment Model
Authors: Park Yubin , Buchan Kevin , Piconne Jason , Sim Brandon 
Published: April 2023

Abstract
Accountable Care Organizations (ACOs) involve groups of healthcare providers
who voluntarily come together to deliver coordinated, high-quality care to aligned
beneficiaries. Many ACOs, such as the Medicare Shared Savings Program and the
ACO REACH program, can participate in alternative payment models that differ
from the prevalent Fee-for-Service model. In these alternative payment models,
providers and payers share financial risk to align the ACOs’ financial incentives
with the dual aims of reducing the total cost of care and improving the quality
of care. In other words, ACOs could profit by keeping their patients healthy and
preventing unnecessary hospitalization. However, to make this financial structure
work as intended, there needs to be a Risk Adjustment (RA) model to change
reimbursement proportional to a beneficiary’s risk; otherwise, ACOs may enroll
only healthy patients, i.e., adverse selection. While most ACOs adopt RA models
for this reason, the original RA methodology has mostly stayed the same over
the last several decades. As a result, some ACO participants have found ways to
“game” the system: to receive disproportional payments for the risk they bear.
To mitigate the waste, the federal government has added various post-adjustment
mechanisms, such as mixing the risk-adjusted benchmark with historical spending,
adjusting by a coding intensity factor, capping risk score growth rate, and
incorporating health equity incentives. Unfortunately, those mechanisms build
on top of each other in nonlinear and discontinuous ways, causing their actual
effects - and efficacy - to be difficult to disentangle and evaluate. In this paper,
we will summarize our lessons from operating one of the most successful ACOs in
the nation to help rebuild the RA model based on a data-driven approach. Next,
we outline the characteristics of an ideal RA model. Then, we propose a new one
that addresses such requirements, eliminating the need for a multi-step process
involving nonlinear and discontinuous staging. Finally, we provide experimental
results by applying this model to our ACO data and comparing them with the
current RA implementation.
Application of Hadoop Cloud Platform Based on Soft Computing in Financial Accounting Budget Control
Authors: Shuxiang Zhang 
Published: April 2023

Abstract
This article designs a Hadoop cloud platform system based on soft computing, and makes optimization research on its budget control application in financial accounting, stabilizing its solid position in financial accounting budget control. Based on this, the article improves the scheduling algorithm of the data migration module in the system, thereby optimizing the basic performance of the data migration module. By integrating the Hadoop cloud platform with the soft computing system, and using the Hadoop cloud platform to process big data, the system's query efficiency is fully demonstrated. This article also introduces the definition and theory of financial accounting budget control, combined with relevant budget control policies, and comprehensively summarizes the development status of a company's main business. Based on the era background of big data information technology innovation, we proposes an optimization strategy for comprehensive business budget management of an enterprise. The optimization plan addresses various issues mentioned above. By focusing on various aspects of enterprise budget management and strengthening the implementation of budget control processes, a comprehensive evaluation system for balanced budget management has been established, effectively resolving the above issues.