bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study
Authors: Xia Juan , Guo Chunyue , Liu Kuo , Xie Yunyi , Cao Han , Peng Wenjuan , Sun Yanyan , Liu Xiaohui , Li Bingxiao , Zhang Ling 
Published: June 2021

Abstract
Background
There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity.

Methods
Two-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies.

Results
Thirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901–0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941–0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949–1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950–0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950–1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981–1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960–1.009; P = 0.214).

Conclusions
This study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.
The targetable nanoparticle BAF312@cRGD-CaP-NP represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer
Authors: Gong Ke , Jiao Juyang , Xu Chaoqun , Dong Yang , Li Dongxiao , He Di , Zhao De , Yu Jian , Sun Ying , Zhang Wei , Bai Min , Duan Yourong 
Published: May 2021

Abstract
Background
Overexpressed vascular endothelial growth factor A (VEGFA) and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) cause unrestricted tumor growth and angiogenesis of breast cancer (BRCA), especially triple-negative breast cancer (TNBC). Hence, novel treatment strategy is urgently needed.

Results
We found sphingosine 1 phosphate receptor 1 (S1PR1) can regulate P-STAT3/VEGFA. Database showed S1PR1 is highly expressed in BRCA and causes the poor prognosis of patients. Interrupting the expression of S1PR1 could inhibit the growth of human breast cancer cells (MCF-7 and MDA-MB-231) and suppress the angiogenesis of human umbilical vein endothelial cells (HUVECs) via affecting S1PR1/P-STAT3/VEGFA axis. Siponimod (BAF312) is a selective antagonist of S1PR1, which inhibits tumor growth and angiogenesis in vitro by downregulating the S1PR1/P-STAT3/VEGFA axis. We prepared pH-sensitive and tumor-targeted shell-core structure nanoparticles, in which hydrophilic PEG2000 modified with the cyclic Arg-Gly-Asp (cRGD) formed the shell, hydrophobic DSPE formed the core, and CaP (calcium and phosphate ions) was adsorbed onto the shell; the nanoparticles were used to deliver BAF312 (BAF312@cRGD-CaP-NPs). The size and potential of the nanoparticles were 109.9 ± 1.002 nm and − 10.6 ± 0.056 mV. The incorporation efficacy for BAF312 was 81.4%. Results confirmed BAF312@cRGD-CaP-NP could dramatically inhibit tumor growth and angiogenesis in vitro and in MDA-MB-231 tumor-bearing mice via downregulating the S1PR1/P-STAT3/VEGFA axis.

Conclusions
Our data suggest a potent role for BAF312@cRGD-CaP-NPs in treating BRCA, especially TNBC by downregulating the S1PR1/P-STAT3/VEGFA axis.

Graphic abstract
Urinary vitamin D-binding protein as a marker of ovarian reserve
Authors: Li Sanglin , Hu Lina , Zhang Chanyu 
Published: June 2021

Abstract
Background
Ovarian reserve reflects the quality and quantity of available oocytes and has become an indispensable measure for the better understanding of reproductive potential. Proteomic approaches are especially helpful in discerning differential protein expression patterns associated with normal and diseased states and, thus, proteomic analyses are increasingly used to identify clinically useful biomarkers. The aim of this study was to investigate proteins secreted in the urine of patients with different ovarian reserve by proteomic techniques to identify potential markers for assessing ovarian reserve.

Methods
Urine samples were obtained from patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), and from normal control (NC)participants. We used isobaric tags for relative and absolute quantification (iTRAQ) technology combined with mass spectrometry analysis to identify candidate urinary proteins in the three groups. The selected proteins were confirmed using western blot analysis and enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic analysis.

Results
When Compared with NC samples, 285 differentially expressed proteins (DEPs) were identified in the DOR samples and 372 in the PCOS samples. By analyzing the intersection of the two groups of DEPs, we found 26 proteins with different expression trends in the DOR and PCOS groups. Vitamin D-binding protein (VDBP) was the key protein for the protein-protein interaction network. ELISA quantification of urinary VDBP revealed the highest levels in the PCOS group, followed by the NC group and the lowest levels in the DOR group (115.90 ± 26.02, 81.86 ± 23.92 and 52.84 ± 21.37 ng/ml, respectively; P < 0.05). As a diagnostic marker, VDBP had a sensitivity of 67.4% and a specificity of 91.8% for DOR, and a sensitivity of 93.8% and a specificity of 77.6% for PCOS.

Conclusions
Urinary VDBP is closely associated with ovarian reserve and can be considered as a novel noninvasive biomarker of ovarian reserve. However, studies including large sample sizes are needed to validate these results.
Coagulopathy and its associated factors among patients with a bleeding diathesis at the University of Gondar Specialized Referral Hospital, Northwest Ethiopia
Authors: Aynalem Melak , Shiferaw Elias , Gelaw Yemataw , Enawgaw Bamlaku 
Published: June 2021

AbstractBackgroundCoagulopathy is the major cause of mortality and morbidity throughout the world. Globally, about 26–45% of healthy people have a history of bleeding symptoms, which may be a result of thrombocytopenia, factor deficiency, or pathological inhibitory.ObjectiveTo assess coagulopathy and its associated factors among patients with bleeding diathesis at the University of Gondar Specialized Referral Hospital from January to May 2020.MethodA cross-sectional study was conducted on 384 study participants with bleeding diathesis recruited by using a convenient sampling technique. Socio-demographic and clinical characteristics were collected by using questioners. Then 6 ml venous blood was collected with a needle and syringe method. About 3 ml blood was transferred to EDTA test tube for platelet count and 2.7 ml blood was transferred to a test tube containing 0.3 ml of 3.2% sodium citrated anticoagulant for coagulation test. For those study participants with prolonged coagulation tests, a mixing test was done. Blood film and stool examination were also done for malaria and intestinal parasite identification, respectively. The data were entered into EPI-Info version 3.5.3 and then transferred to SPSS version-20 for analysis. Descriptive statistics were summarized as percentages, means, and standard deviations. Bivariate and multivariate logistic regression was used to identify the associated factors, and aP-value less than 0.05 was considered statistically significant.ResultsIn this study, the prevalence of coagulopathy was 253/384 (65.9%; 95% CI: 61.16, 70.64). From them, 21.3% (54/253), 51.4% (130/253), and 27.3% (69/253) had only thrombocytopenia, only prolonged coagulation test, and mixed abnormality, respectively. Among participants with prolonged coagulation time, the prevalence of factor deficiency was 21.1% (42/199). Cardiac disease (AOR = 4.80; 95% CI: 2.65, 23.1), and other chronic diseases (AOR = 8.1; 95% CI: 1.84, 35.58) were significantly associated with coagulopathy.ConclusionIn this study, coagulopathy due to inhibitory was a public health problem. The participants with cardiac and other chronic diseases were at high risk for coagulopathy. Therefore, mixing tests could be done for all prolonged coagulation tests and it could be considered as a routine laboratory test.
Measuring attentiveness toward oral care needs: a comparative study of Indonesian care workers in Japan and Indonesia
Authors: Hirano Yuko O. , Nugraha Susiana , Shiozu Hiroyasu , Higashijima Misako , Rahardjo Tri Budi W. 
Published: June 2021

Abstract
Background
Japan has opened its labor market to care workers from Indonesia under the Japan–Indonesia Economic Partnership Agreement (EPA). However, few studies have examined the types of care skills transferred between countries. We therefore analyzed Indonesian care workers employed in Japan and Indonesia to identify discrepancies in their attentiveness toward oral care in older adults.

Methods
A checklist comprising 42 items of universal oral care assessment was developed prior to the study and distributed via the Internet to 418 Indonesian EPA care workers in Japan and via a paper survey to 213 Indonesian care workers in Indonesia. The Mann–Whitney U test was used to compare the distribution of scores for each checklist item for each group.

Results
The respondents were 110 Japan-based EPA care workers (response rate: 26.3%) and 213 Indonesia-based care workers (response rate: 99.1%). Japan-based care workers were significantly more likely to perform environmental observations of their older adult patients (p < 0.001) and to check items on the oral care checklist during feeding (p < 0.001) and post-meal (p = 0.001), while Indonesia-based care workers were more likely to check the overall condition of patients before meals (p = 0.021).

Conclusions
Discrepancies in checking oral care between the two groups were attributed to the differences in laws and regulations governing the care environments. Indonesian care workers employed in Japan have the advantage of learning to employ a more systematic approach in caring for older adults, in accordance with Japan’s Long-Term Care Act. This approach could contribute toward lowering the risk of aspiration pneumonia in Indonesia. A training program designed for returning migrant workers to transfer newly developed oral care skills will thus be essential for Indonesia to diminish the negative impacts of its aging population.
PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through the inhibition of TM4 (UBAC2) degradation
Authors: Chen Lili , Ye Kuanping , Feng Xiaocheng , Li Lianxi , Li Qin , Huang Ying , Wang Xuanchun , Li Rumei , Hu Cheng , Yang Zhen , Lu Bin , Yang Yehong , Wen Jie , Zhang Zhaoyun , He Min , Wang Qinghua , Zhou Wenbai , Li Yintao , Liu Naijia , Huang Jinya , Shen Qiwei , Yao Qiyuan , Hu Renming 
Published: June 2021

Abstract
Background
The TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin–proteasome inhibitor PS-341 could regulate the function of TM4.

Methods
The metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro.

Results
TM4 KO mice developed obesity, hepatosteatosis, hypertension, and glucose intolerance under a high-fat diet. TM4 counterregulated Nur77, IKKβ, and NF-kB both in vivo and in vitro. The TM4 SNP rs147851454 is significantly associated with obesity after adjusting for age and sex (OR 1.606, 95% CI 1.065–2.422 P = 0.023) in 3394 non-diabetic and 1862 type 2 diabetic adults of Han Chinese. TM4 was significantly downregulated in the visceral fat of obese patients. PS-341 induced TM4 expression through inhibition of TM4 degradation in vitro. In db/db mice, PS-341 administration led to downregulation of Nur77/IKKβ/NF-κB expression in visceral fat and liver, and alleviation of hyperglycaemia, hypertension, and glucose intolerance. The hyperinsulinaemic-euglycaemic clamp demonstrated that PS-341 improved the glucose infusion rate and alleviated insulin resistance in db/db mice.

Conclusions
PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through inhibition of TM4 degradation.
The energy-spectrum of bicompatible sequences
Authors: Huang Fenix W. , Barrett Christopher L. , Reidys Christian M. 
Published: June 2021

AbstractBackgroundGenotype-phenotype maps provide a meaningful filtration of sequence space and RNA secondary structures are particular such phenotypes. Compatible sequences, which satisfy the base-pairing constraints of a given RNA structure, play an important role in the context of neutral evolution. Sequences that are simultaneously compatible with two given structures (bicompatible sequences), are beacons in phenotypic transitions, induced by erroneously replicating populations of RNA sequences. RNA riboswitches, which are capable of expressing two distinct secondary structures without changing the underlying sequence, are one example of bicompatible sequences in living organisms.ResultsWe present a full loop energy model Boltzmann sampler of bicompatible sequences for pairs of structures. The sequence sampler employs a dynamic programming routine whose time complexity is polynomial when assuming the maximum number of exposed vertices,$$\kappa $$κ, is a constant. The parameter$$\kappa $$κdepends on the two structures and can be very large. We introduce a novel topological framework encapsulating the relations between loops that sheds light on the understanding of$$\kappa $$κ. Based on this framework, we give an algorithm to sample sequences with minimum$$\kappa $$κon a particular topologically classified case as well as giving hints to the solution in the other cases. As a result, we utilize our sequence sampler to study some established riboswitches.ConclusionOur analysis of riboswitch sequences shows that a pair of structures needs to satisfy key properties in order to facilitate phenotypic transitions and that pairs of random structures are unlikely to do so. Our analysis observes a distinct signature of riboswitch sequences, suggesting a new criterion for identifying native sequences and sequences subjected to evolutionary pressure. Our free software is available at:https://github.com/FenixHuang667/Bifold.
Differences in health care experiences between rare cancer and common cancer patients: results from a national cross-sectional survey
Authors: de Heus Eline , Engelen Vivian , Dingemans Irene , Richel Carol , Schrieks Marga , van der Zwan Jan Maarten , Besselink Marc G. , van Berge Henegouwen Mark I. , van Herpen Carla M. L. , Duijts Saskia F. A. 
Published: June 2021

Abstract
Background
Patients with rare cancers face challenges in the diagnostic and treatment phase, and in access to clinical expertise. Since studies on health care experiences of these patients in comparison to patients with more common cancers are scarce, we aimed to explore these differences.

Methods
Data were cross-sectionally collected among (former) adult cancer patients through a national online survey in the Netherlands (October 2019). Descriptive statistics were reported and subgroups (rare vs. common patients) were compared.

Results
In total, 7343 patients (i.e., 1856 rare and 5487 common cancer patients) participated. Rare cancer patients were more often diagnosed and treated in different hospitals compared to common cancer patients (67% vs. 59%, p < 0.001). Rare cancer patients received treatment more often in a single hospital (60% vs. 57%, p = 0.014), but reported more negative experiences when treated in multiple hospitals than common cancer patients (14% vs. 9%, p < 0.001). They also more often received advise from their physician about the hospital to go to for a second opinion (50% vs. 36%, p < 0.001), were more likely to choose a hospital specialized in their cancer type (33% vs. 22%, p < 0.001), and were more willing to travel as long as necessary to receive specialized care than common cancer patients (55% vs. 47%, p < 0.001).

Conclusions
Rare and common cancer patients differ in their health care experiences. Health care for rare cancer patients can be further improved by proper referral to centers of expertise and building a clinical network specifically for rare cancers.
Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials
Authors: Vaschetto Rosanna , Pecere Alessandro , Perkins Gavin D. , Mistry Dipesh , Cammarota Gianmaria , Longhini Federico , Ferrer Miguel , Pletsch-Assunção Renata , Carron Michele , Moretto Francesca , Qiu Haibo , Della Corte Francesco , Barone-Adesi Francesco , Navalesi Paolo 
Published: June 2021

Abstract
Background
Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning.

Methods
In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation.

Results
We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, − 3.43; 95% CI − 5.17 to − 1.69 days, p < 0.001), a shorter duration of total days spent on mechanical ventilation (mean difference, − 2.04; 95% CI − 3.82 to − 0.27 days, p = 0.024), a reduced risk of ventilatory associated pneumonia (odds ratio, 0.24; 95% CI 0.08 to 0.71, p = 0.014), a reduction of time spent in ICU (time ratio, 0.81; 95% CI 0.68 to 0.96, p = 0.015) and in-hospital (time ratio, 0.81; 95% CI 0.69 to 0.95, p = 0.010), with no difference in ICU mortality.

Conclusions
Although primary studies are limited, using an individual patient data metanalysis approach, NIV after early extubation appears useful in reducing total days spent on invasive mechanical ventilation.

Trial registration

The protocol was registered to PROSPERO database on 12/06/2019 and available at PROSPERO website inserting the study code i.e., CRD42019133837.
Advancing precision public health using human genomics: examples from the field and future research opportunities
Authors: Roberts Megan C. , Fohner Alison E. , Landry Latrice , Olstad Dana Lee , Smit Amelia K. , Turbitt Erin , Allen Caitlin G. 
Published: June 2021

AbstractPrecision public health is a relatively new field that integrates components of precision medicine, such as human genomics research, with public health concepts to help improve population health. Despite interest in advancing precision public health initiatives using human genomics research, current and future opportunities in this emerging field remain largely undescribed. To that end, we provide examples of promising opportunities and current applications of genomics research within precision public health and outline future directions within five major domains of public health: biostatistics, environmental health, epidemiology, health policy and health services, and social and behavioral science. To further extend applications of genomics within precision public health research, three key cross-cutting challenges will need to be addressed: developing policies that implement precision public health initiatives at multiple levels, improving data integration and developing more rigorous methodologies, and incorporating initiatives that address health equity. Realizing the potential to better integrate human genomics within precision public health will require transdisciplinary efforts that leverage the strengths of both precision medicine and public health.