bluuebunny/crossref_metadata_2025_split huggingface dataset:
Children’s moderate-to-vigorous physical activity on weekdays versus weekend days: a multi-country analysis
Authors:   on behalf of the International Children’s Accelerometry Database (ICAD) Collaborators, Brazendale Keith , Beets Michael W. , Armstrong Bridget , Weaver R. Glenn , Hunt Ethan T. , Pate Russell R. , Brusseau Timothy A. , Bohnert Amy M. , Olds Timothy , Tassitano Rafael M. , Tenorio Maria Cecilia M. , Garcia Jeanette , Andersen Lars B. , Davey Rachel , Hallal Pedro C. , Jago Russell , Kolle Elin , Kriemler Susi , Kristensen Peter L. , Kwon Soyang , Puder Jardena J. , Salmon Jo , Sardinha Luis B. , van Sluijs Esther M. F. 
Published: February 2021

Abstract
Purpose
The Structured Days Hypothesis (SDH) posits that children’s behaviors associated with obesity – such as physical activity – are more favorable on days that contain more ‘structure’ (i.e., a pre-planned, segmented, and adult-supervised environment) such as school weekdays, compared to days with less structure, such as weekend days. The purpose of this study was to compare children’s moderate-to-vigorous physical activity (MVPA) levels on weekdays versus weekend days using a large, multi-country, accelerometer-measured physical activity dataset.

Methods
Data were received from the International Children’s Accelerometer Database (ICAD) July 2019. The ICAD inclusion criteria for a valid day of wear, only non-intervention data (e.g., baseline intervention data), children with at least 1 weekday and 1 weekend day, and ICAD studies with data collected exclusively during school months, were included for analyses. Mixed effects models accounting for the nested nature of the data (i.e., days within children) assessed MVPA minutes per day (min/day MVPA) differences between weekdays and weekend days by region/country, adjusted for age, sex, and total wear time. Separate meta-analytical models explored differences by age and country/region for sex and child weight-status.

Results/findings
Valid data from 15 studies representing 5794 children (61% female, 10.7 ± 2.1 yrs., 24% with overweight/obesity) and 35,263 days of valid accelerometer data from 5 distinct countries/regions were used. Boys and girls accumulated 12.6 min/day (95% CI: 9.0, 16.2) and 9.4 min/day (95% CI: 7.2, 11.6) more MVPA on weekdays versus weekend days, respectively. Children from mainland Europe had the largest differences (17.1 min/day more MVPA on weekdays versus weekend days, 95% CI: 15.3, 19.0) compared to the other countries/regions. Children who were classified as overweight/obese or normal weight/underweight accumulated 9.5 min/day (95% CI: 6.9, 12.2) and 10.9 min/day (95% CI: 8.3, 13.5) of additional MVPA on weekdays versus weekend days, respectively.

Conclusions
Children from multiple countries/regions accumulated significantly more MVPA on weekdays versus weekend days during school months. This finding aligns with the SDH and warrants future intervention studies to prioritize less-structured days, such as weekend days, and to consider providing opportunities for all children to access additional opportunities to be active.
Pneumonia scoring systems for severe COVID-19: which one is better
Authors: Cheng PengFei , Wu Hao , Yang JunZhe , Song XiaoYang , Xu MengDa , Li BiXi , Zhang JunJun , Qin MingZhe , Zhou Cheng , Zhou Xiang 
Published: February 2021

Abstract
Purpose
To investigate the predictive significance of different pneumonia scoring systems in clinical severity and mortality risk of patients with severe novel coronavirus pneumonia.

Materials and methods
A total of 53 cases of severe novel coronavirus pneumonia were confirmed. The APACHE II, MuLBSTA and CURB-65 scores of different treatment methods were calculated, and the predictive power of each score on clinical respiratory support treatment and mortality risk was compared.

Results
The APACHE II score showed the largest area under ROC curve in both noninvasive and invasive respiratory support treatment assessments, which is significantly different from that of CURB-65. Further, the MuLBSTA score had the largest area under ROC curve in terms of death risk assessment, which is also significantly different from that of CURB-65; however, no difference was noted with the APACHE II score.

Conclusion
For patients with COVID, the APACHE II score is an effective predictor of the disease severity and mortality risk. Further, the MuLBSTA score is a good predictor only in terms of mortality risk.
Association of serum calcium levels with renal impairment and all-cause death in Chinese patients with newly diagnosed multiple myeloma: a cross-sectional, longitudinal study
Authors: Cheng Jun , Zhang Wen , Zhao Yi , Li Xiayu , Lv Rong , Li Heng , Chen Jianghua 
Published: February 2021

Abstract
Background
More studies have shown that serum calcium has a crucial role in many types of cancers. However, few studies have determined the association between serum calcium levels and renal impairment (RI) and all-cause death in Chinese patients with multiple myeloma (MM).

Methods
A total of 246 of 565 participants who were followed for > 6 months from a MM cohort at our institution were eligible for the retrospective study. A generalized additive model and smooth curve fitting were performed to investigate the cross-sectional relationship between the serum calcium level and RI at baseline. Multivariate-adjusted Cox regression models were fitted to assess the associations between baseline serum calcium levels and the onset of end-stage renal disease (ESRD) or death in patients with MM.

Results
A total of 172 of 565 patients (30.4%) with newly diagnosed MM presented with RI. The mean duration of follow-up was 26.64 months. Twenty-one patients (8.54%) died and 28 patients (11.52%) had ESRD. In patients with a serum calcium level > 2.30 mmol/L, the serum calcium level was independently associated with the occurrence of MM-related RI. Cox regression analysis showed that baseline serum calcium levels were consistently associated with a higher risk of all-cause death in the fully adjusted model, but were not associated with the occurrence of ESRD. When patients were categorized into two groups according to baseline mean serum calcium level, deaths occurred in 13 patients (15.1%) with a mean serum calcium level > 2.44 mmol/L compared to eight patients (5.0%) with a mean serum calcium level < 2.44 mmol/L (p < 0.05); Eighteen patients (11.46%) with a mean serum calcium level < 2.44 mmol/L progressed to ESRD compared to 13 patients (11.6%) with a serum calcium level > 2.44 mmol/L (p > 0.05).

Conclusions
This observational study showed that there was a nonlinear relationship between the serum calcium level and the presence of RI in patients with MM. An elevated baseline calcium level predicted all-cause death, but did not predict the occurrence of ESRD in patients with MM followed for > 6 months.
Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles
Authors: Mehrnia Somayeh Sadat , Hashemi Bijan , Mowla Seyed Javad , Nikkhah Maryam , Arbabi Azim 
Published: February 2021

Abstract
Background
Gold nanoparticles (GNPs) have been used to sensitize cancer cells and enhance the absorbed dose delivered to such cells. Active targeting can provide specific effect and higher uptake of the GNPs in the tumor cells, while having small effect on healthy cells. The aim of this study was to assess the possible radiosensitiazation effect of GNPs conjugated with AS1411 aptamer (AS1411/GNPs) on cancer cells treated with 4 MeV electron beams.

Materials and methods
Cytotoxicity studies of the GNPs and AS1411/GNPs were carried out with MTT and MTS assay in different cancer cell lines of MCF-7, MDA-MB-231 and mammospheres of MCF-7 cells. Atomic absorption spectroscopy confirmed the cellular uptake of the gold particles. Radiosensitizing effect of the GNPs and AS1411/GNPs on the cancer cells was assessed by clonogenic assay.

Result
AS1411 aptamer increased the Au uptake in MCF-7 and MDA-MB-231 cells. Clonogenic survival data revealed that AS1411/GNPs at 12.5 mg/L could result in radiosensitization of the breast cancer cells and lead to a sensitizer enhancement ratio of 1.35 and 1.66 and 1.91 for MCf-7, MDA-MB-231 and mammosphere cells.

Conclusion
Gold nanoparticles delivery to the cancer cells was enhanced by AS1411 aptamer and led to enhanced radiation induced cancer cells death. The combination of our clonogenic assay and Au cell uptake results suggested that AS1411 aptamer has enhanced the radiation-induced cell death by increasing Au uptake. This enhanced sensitization contributed to cancer stem cell-like cells to 4 MeV electron beams. This is particularly important for future preclinical testing to open a new insight for the treatment of cancers.
Comparative transcriptomic analysis revealed novel potential therapeutic targets of traditional Chinese medicine (Pinggan-Qianyang decoction) on vascular remodeling in spontaneously hypertensive rats
Authors: Yao Jiamei , Zhang Cui , Yang Yushu , Fang Xia , Chen Qiong , Zhong Guangwei 
Published: February 2021

Abstract
Background
Both experimental and clinical studies have revealed satisfactory effects with the traditional Chinese formula Pinggan Qianyang decoction (PGQYD) for improving vascular remodeling caused by essential hypertension. The present study explored various therapeutic targets of PGQYD using mRNA transcriptomics.

Methods
In this study, rats were randomly divided into three groups: Wistar-Kyoto (WKY; normal control), spontaneously hypertensive (SHR), and PGQYD-treated rat groups. After 12 weeks of PGQYD treatment, behavioral tests were employed and the morphology of thoracic aortas were examined with hematoxylin–eosin (HE) and Masson staining and electron microscopy. The mRNA expression profiles were identified with RNA-Seq and quantitative real-time PCR to validate changes in gene expression observed with microarray analysis. The gene ontology and pathway enrichment analyses were carried out to predict gene function and gene co-expressions. Pathway networks were constructed to identify the hub biomarkers, which were further validated by western blotting and immunofluorescence analysis.

Results
After PGQYD treatment, the behavioral tests and histological and morphological findings of vascular remodeling were obviously meliorated compared with the SHR group. In the rat thoracic aorta tissues, 626 mRNAs with an exact match were identified. A total of 129 of mRNAs (fold change > 1.3 and P-value < 0.05) were significantly changed in the SHR group compared to the WKY group. Among them, 16 mRNAs were markedly regulated by PGQYD treatment and validated with quantitative real-time PCR. Additionally, target prediction and bioinformatics analyses revealed that these mRNAs could play therapeutic roles through biological processes for regulating cell metabolic processes (such as glycation biology), biological adhesions, rhythmic processes, and cell autophagy. The cellular signaling pathways involved in autophagy may be AGE–RAGE/PI3K/Akt/mTOR signaling pathway.

Conclusion
The present study provides novel insights for future investigations to explore the mechanisms by which PGQYD may effectively inhibit vascular remodeling by activating the AGE–RAGE/PI3K/Akt/mTOR signal pathway in cell autophagy biology.
Validation of diagnostic codes and epidemiologic trends of Huntington disease: a population-based study in Navarre, Spain
Authors: Vicente Esther , Ruiz de Sabando Ainara , García Fermín , Gastón Itziar , Ardanaz Eva , Ramos-Arroyo María A. 
Published: February 2021

Abstract
Background
There is great heterogeneity on geographic and temporary Huntington disease (HD) epidemiological estimates. Most research studies of rare diseases, including HD, use health information systems (HIS) as data sources. This study investigates the validity and accuracy of national and international diagnostic codes for HD in multiple HIS and analyses the epidemiologic trends of HD in the Autonomous Community of Navarre (Spain).

Methods
HD cases were ascertained by the Rare Diseases Registry and the reference Medical Genetics Centre of Navarre. Positive predictive values (PPV) and sensitivity with 95% confidence intervals (95% CI) were estimated. Overall and 9-year periods (1991–2017) HD prevalence, incidence and mortality rates were calculated, and trends were assessed by Joinpoint regression.

Results
Overall PPV and sensitivity of combined HIS were 71.8% (95% CI: 59.7, 81.6) and 82.2% (95% CI: 70.1, 90.4), respectively. Primary care data was a more valuable resource for HD ascertainment than hospital discharge records, with 66% versus 50% sensitivity, respectively. It also had the highest number of “unique to source” cases. Thirty-five per cent of HD patients were identified by a single database and only 4% by all explored sources. Point prevalence was 4.94 (95% CI: 3.23, 6.65) per 100,000 in December 2017, and showed an annual 6.1% increase from 1991 to 1999. Incidence and mortality trends remained stable since 1995–96, with mean annual rates per 100,000 of 0.36 (95% CI: 0.27, 0.47) and 0.23 (95% CI: 0.16, 0.32), respectively. Late-onset HD patients (23.1%), mean age at onset (49.6 years), age at death (66.6 years) and duration of disease (16.7 years) were slightly higher than previously reported.

Conclusion
HD did not experience true temporary variations in prevalence, incidence or mortality over 23 years of post-molecular testing in our population. Ascertainment bias may largely explain the worldwide heterogeneity in results of HD epidemiological estimates. Population-based rare diseases registries are valuable instruments for epidemiological studies on low prevalence genetic diseases, like HD, as long as they include validated data from multiple HIS and genetic/family information.
FGFR-TKI resistance in cancer: current status and perspectives
Authors: Yue Sitong , Li Yukun , Chen Xiaojuan , Wang Juan , Li Meixiang , Chen Yongheng , Wu Daichao 
Published: February 2021

AbstractFibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concern. Here, we review the mechanisms of FGFR-TKI resistance in cancer, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. In addition, we summarize strategies to overcome resistance, including developing covalent inhibitors, developing dual-target inhibitors, adopting combination therapy, and targeting lysosomes, which will facilitate the transition to precision medicine and individualized treatment.
ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma
Authors: Zhang Mengzhao , Wang Lu , Yue Yangyang , Zhang Lu , Liu Tianjie , Jing Minxuan , Liang Xiao , Ma Minghai , Xu Shan , Wang Ke , Wang Xinyang , Fan Jinhai 
Published: February 2021

Abstract
Background
Bladder carcinoma is one of the most common urological cancers. ITPR3, as a ubiquitous endoplasmic reticulum calcium channel protein, was reported to be involved in the development and progression of various types of cancer. However, the potential roles and molecular mechanism of ITPR3 in bladder cancer are still unclear. Herein, we elucidated a novel role of ITPR3 in regulating the proliferation, metastasis, and stemness of bladder cancer cells.

Methods
The expression of ITPR3 in bladder cancer was analyzed using public databases and bladder cancer tissue microarrays. To demonstrate the role of ITPR3 in regulating the NF-ĸB/CD44 pathway and the progression of bladder cancer, a series of molecular biology and biochemistry methods was performed on clinical tissues, along with in vivo and in vitro experiments. The methods used included western blot assay, quantitative RT-PCR assay, immunofluorescence assay, immunohistochemistry (IHC) assays, wound healing assay, Transwell assay, colony formation assay, tumorsphere formation assay, cell flow cytometry analysis, EdU assay, MTT assay, cell transfection, bisulfite sequencing PCR (BSP), a xenograft tumor model and a tail vein cancer metastasis model.

Results
Higher ITPR3 expression was found in bladder cancer tissues and bladder cancer cells compared with the corresponding normal peritumor tissues and SV-HUC-1 cells, which was attributed to demethylation in the ITPR3 promoter region. ITPR3 promoted the proliferation of bladder cancer by accelerating cell cycle transformation and promoted local invasion and distant metastasis by inducing epithelial-to-mesenchymal transition (EMT). Meanwhile, ITPR3 maintained the cancer stemness phenotype by regulating CD44 expression. NF-κB, which is upstream of CD44, also played a critical role in this process.

Conclusions
Our study clarifies that ITPR3 serves as an oncogene in bladder cancer cells and represents a novel candidate for bladder cancer diagnosis and treatment.
Effects of training podiatrists to use imagery‐based motivational interviewing when treating people with diabetes‐related foot disease: a mixed‐methods pilot study
Authors: Kaczmarek Tracey , Van Netten Jaap J. , Lazzarini Peter A. , Kavanagh David 
Published: February 2021

AbstractBackgroundSelf‐care in diabetes related foot disease (DFD) is challenging and contributes to poor outcomes. Motivational Interviewing (MI) can engage people in self‐care and modifying it by integrating imagery may further improve its outcomes. No previous studies have trained podiatrists in using MI to address DFD self‐care. This was the first study on training podiatrists to conduct imagery‐based motivational interviewing (MI) when treating people with DFD, and to examine impacts on MI related skills, job satisfaction and subjective experiences in a mixed‐methods pilot study.MethodsEleven recruited podiatrists (median age: 35 years, 9 female and 2 male) received two 4‐h training sessions, and three received subsequent mentoring. MI and imagery skills were rated using validated tools during two clinical sessions per participant at baseline, and 2‐ and 12‐weeks post‐training. Job satisfaction was assessed at baseline and 12 weeks. Semi‐structured interviews at 12 weeks were analysed using the framework approach.ResultsSignificant improvements over time (p = .006–.044) with substantial effect sizes (η2 = .50–.67) were found in three of four global MI related communication skills and two of four MI behaviours. However, effects on these indices were not sustained to 12 weeks, and imagery was rarely used. Job satisfaction was high at baseline and unchanged at follow‐up (p = 0.34, η2 = .100). In qualitative interviews, MI training and skills were valued, but significant challenges in using MI when treating people with DFD were reported.ConclusionTraining podiatrists in MI may have potential but more training, observation and mentoring appear needed to obtain sustained communication changes in practice.
Successful outcome of disseminated Candida tropicalis osteomyelitis on remission induction for childhood Philadelphia chromosome–positive acute lymphoblastic leukaemia-case report
Authors: Xie Lichun , Long Qingling , Zhou Guichi , Liu Sixi , Wen Fei-Qiu 
Published: February 2021

AbstractBackgroundInvasive fungal infection (IFI) is one of the most challenging complications in children undergoing acute lymphoblastic leukaemia (ALL) treatment, but acute fungal osteomyelitis (OM) is rarely encountered.Case presentationHere, we describe a case ofCandida tropicalisosteomyelitis in a 10-year-old patient with Philadelphia chromosome (Ph)-positive ALL. He was on remission induction therapy at the time of neutropenia, and an abscess developed in his right arm. The blood and bone cultures were positive forC. tropicalis. Antibiotics and antifungals were administered. Magnetic resonance imaging of the arm revealed an intraosseous abscess, suggestive of OM. Surgical irrigation and debridement of the bone were performed immediately. The patient was effectively treated with antifungal therapy and ALL treatment. He has fully recovered into complete clinical remission but with visible sequelae on magnetic resonance imaging (MRI). He took oral posaconazole for consolidation until disappearance of the lesion shadows on MRI and received subsequent cycles of chemotherapy in parallel.ConclusionsIn the successful management of Ph-positive ALL, dasatinib, a second-generation Abl-tyrosine kinase inhibitor, is crucial. The recommended treatment forCandidaosteomyelitis in Ph-positive ALL patients is a fungicidal agent combined with surgery and modification chemotherapy with dasatinib. The use of combined modalities of treatment seems to be crucial in the successful management of Ph-positive ALL.
High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure
Authors:   for the COVID-19 Spanish ICU Network, Mellado-Artigas Ricard , Ferreyro Bruno L. , Angriman Federico , Hernández-Sanz María , Arruti Egoitz , Torres Antoni , Villar Jesús , Brochard Laurent , Ferrando Carlos 
Published: February 2021

Abstract
Purpose
Whether the use of high-flow nasal oxygen in adult patients with COVID-19 associated acute respiratory failure improves clinically relevant outcomes remains unclear. We thus sought to assess the effect of high-flow nasal oxygen on ventilator-free days, compared to early initiation of invasive mechanical ventilation, on adult patients with COVID-19.

Methods
We conducted a multicentre cohort study using a prospectively collected database of patients with COVID-19 associated acute respiratory failure admitted to 36 Spanish and Andorran intensive care units (ICUs). Main exposure was the use of high-flow nasal oxygen (conservative group), while early invasive mechanical ventilation (within the first day of ICU admission; early intubation group) served as the comparator. The primary outcome was ventilator-free days at 28 days. ICU length of stay and all-cause in-hospital mortality served as secondary outcomes. We used propensity score matching to adjust for measured confounding.

Results
Out of 468 eligible patients, a total of 122 matched patients were included in the present analysis (61 for each group). When compared to early intubation, the use of high-flow nasal oxygen was associated with an increase in ventilator-free days (mean difference: 8.0 days; 95% confidence interval (CI): 4.4 to 11.7 days) and a reduction in ICU length of stay (mean difference: − 8.2 days; 95% CI − 12.7 to − 3.6 days). No difference was observed in all-cause in-hospital mortality between groups (odds ratio: 0.64; 95% CI: 0.25 to 1.64).

Conclusions
The use of high-flow nasal oxygen upon ICU admission in adult patients with COVID-19 related acute hypoxemic respiratory failure may lead to an increase in ventilator-free days and a reduction in ICU length of stay, when compared to early initiation of invasive mechanical ventilation. Future studies should confirm our findings.
Distribution of virulence genes and SCCmec types among methicillin-resistant Staphylococcus aureus of clinical and environmental origin: a study from community of Assam, India
Authors: Bhowmik Deepshikha , Chetri Shiela , Das Bhaskar Jyoti , Dhar Chanda Debadatta , Bhattacharjee Amitabha 
Published: February 2021

Abstract
Objective
This study was designed to discover the dissemination of virulence genes in Methicillin-resistant Staphylococcus aureus from clinical, community and environmental settings.

Results
This study includes 1165 isolates collected from hospital, community and environmental settings. Among them sixty three were confirmed as MRSA with varied SCCmec types viz; type I, type II, type III, type IV, type V, type VI, type VII, type VIII and type XII. The virulence gene such as sea (n = 54), seb (n = 21), eta (n = 27), etb (n = 2), cna (n = 24), ica (n = 2) and tst (n = 30) was also revealed from this study. The study underscores coexistence of resistance cassette and virulence genes among clinical and environment isolates which is first of its kind from this part of the world.