bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-27a-3p promotes the osteogenic differentiation by activating CRY2/ERK1/2 axis
Authors: Ren Li-Rong , Yao Ru-Bin , Wang Shi-Yong , Gong Xiang-Dong , Xu Ji-Tao , Yang Kai-Shun 
Published: April 2021

Abstract
Background
Osteoporosis seriously disturbs the life of people. Meanwhile, inhibition or weakening of osteogenic differentiation is one of the important factors in the pathogenesis of osteoporosis. It was reported that miR-27a-3p reduced the symptoms of osteoporosis. However, the mechanism by which miR-27a-3p in osteogenic differentiation remains largely unknown.

Methods
To induce the osteogenic differentiation in MC3T3-E1 cells, cells were treated with osteogenic induction medium (OIM). RT-qPCR was used to evaluate the mRNA expression of miR-27a-3p and CRY2 in cells. The protein levels of CRY2, Runt-related transcription factor 2 (Runx2), osteopontin (OPN), osteocalcin (OCN) and the phosphorylation level of extracellular regulated protein kinases (ERK) 1/2 in MC3T3-E1 cells were evaluated by western blotting. Meanwhile, calcium nodules and ALP activity were tested by alizarin red staining and ALP kit, respectively. Luciferase reporter gene assay was used to analyze the correlation between CRY2 and miR-27a-3p.

Results
The expression of miR-27a-3p and the phosphorylation level of ERK1/2 were increased by OIM in MC3T3-E1 cells, while CRY2 expression was decreased. In addition, OIM-induced increase of calcified nodules, ALP content and osteogenesis-related protein expression was significantly reversed by downregulation of miR-27a-3p and overexpression of CRY2. In addition, miR-27a-3p directly targeted CRY2 and negatively regulated CRY2. Meanwhile, the inhibitory effect of miR-27a-3p inhibitor on osteogenic differentiation was reversed by knockdown of CRY2 or using honokiol (ERK1/2 signal activator). Furthermore, miR-27a-3p significantly inhibited the apoptosis of MC3T3-E1 cells treated by OIM. Taken together, miR-27a-3p/CRY2/ERK axis plays an important role in osteoblast differentiation.

Conclusions
MiR-27a-3p promoted osteoblast differentiation via mediation of CRY2/ERK1/2 axis. Thereby, miR-27a-3p might serve as a new target for the treatment of osteoporosis.
Accelerated global sensitivity analysis of genome-wide constraint-based metabolic models
Authors: Nobile Marco S. , Coelho Vasco , Pescini Dario , Damiani Chiara 
Published: April 2021

Abstract
Background
Genome-wide reconstructions of metabolism opened the way to thorough investigations of cell metabolism for health care and industrial purposes. However, the predictions offered by Flux Balance Analysis (FBA) can be strongly affected by the choice of flux boundaries, with particular regard to the flux of reactions that sink nutrients into the system. To mitigate possible errors introduced by a poor selection of such boundaries, a rational approach suggests to focus the modeling efforts on the pivotal ones.

Methods
In this work, we present a methodology for the automatic identification of the key fluxes in genome-wide constraint-based models, by means of variance-based sensitivity analysis. The goal is to identify the parameters for which a small perturbation entails a large variation of the model outcomes, also referred to as sensitive parameters. Due to the high number of FBA simulations that are necessary to assess sensitivity coefficients on genome-wide models, our method exploits a master-slave methodology that distributes the computation on massively multi-core architectures. We performed the following steps: (1) we determined the putative parameterizations of the genome-wide metabolic constraint-based model, using Saltelli’s method; (2) we applied FBA to each parameterized model, distributing the massive amount of calculations over multiple nodes by means of MPI; (3) we then recollected and exploited the results of all FBA runs to assess a global sensitivity analysis.

Results
We show a proof-of-concept of our approach on latest genome-wide reconstructions of human metabolism Recon2.2 and Recon3D. We report that most sensitive parameters are mainly associated with the intake of essential amino acids in Recon2.2, whereas in Recon 3D they are associated largely with phospholipids. We also illustrate that in most cases there is a significant contribution of higher order effects.

Conclusion
Our results indicate that interaction effects between different model parameters exist, which should be taken into account especially at the stage of calibration of genome-wide models, supporting the importance of a global strategy of sensitivity analysis.
Positive natural selection in primate genes of the type I interferon response
Authors: Judd Elena N. , Gilchrist Alison R. , Meyerson Nicholas R. , Sawyer Sara L. 
Published: April 2021

Abstract
Background
The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one.

Results
We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid.

Conclusion
Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.
Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response
Authors: Schlamp Florencia , Delbare Sofie Y. N. , Early Angela M. , Wells Martin T. , Basu Sumanta , Clark Andrew G. 
Published: April 2021

AbstractBackgroundImmune responses need to be initiated rapidly, and maintained as needed, to prevent establishment and growth of infections. At the same time, resources need to be balanced with other physiological processes. On the level of transcription, studies have shown that this balancing act is reflected in tight control of the initiation kinetics and shutdown dynamics of specific immune genes.ResultsTo investigate genome-wide expression dynamics and trade-offs after infection at a high temporal resolution, we performed an RNA-seq time course onD. melanogasterwith 20 time points post Imd stimulation. A combination of methods, including spline fitting, cluster analysis, and Granger causality inference, allowed detailed dissection of expression profiles, lead-lag interactions, and functional annotation of genes through guilt-by-association. We identified Imd-responsive genes and co-expressed, less well characterized genes, with an immediate-early response and sustained up-regulation up to 5 days after stimulation. In contrast, stress response and Toll-responsive genes, among which were Bomanins, demonstrated early and transient responses. We further observed a strong trade-off with metabolic genes, which strikingly recovered to pre-infection levels before the immune response was fully resolved.ConclusionsThis high-dimensional dataset enabled the comprehensive study of immune response dynamics through the parallel application of multiple temporal data analysis methods. The well annotated data set should also serve as a useful resource for further investigation of theD. melanogasterinnate immune response, and for the development of methods for analysis of a post-stress transcriptional response time-series at whole-genome scale.
Long-term outcome of percutaneous transluminal renal angioplasty (PTRA) versus PTRA with stenting (PTRAS) in transplant renal artery stenosis
Authors: Wongpraparut Nattawut , Chaipruckmalakarn Thunyarat , Tongdee Thongtum , Jaspttananon Archan , Vongwiwatana Attapong , Premasathian Nalinee , Anusonadisai Kawin , Pongakasira Rungtiwa 
Published: April 2021

Abstract
Background
Endovascular treatment is standard of care for transplant renal artery stenosis (TRAS). No study has evaluated long-term outcomes compared between percutaneous transluminal renal angioplasty (PTRA) and PTRA with stenting (PTRAS). Accordingly, this study aimed to investigate the 1-year clinical success, and short- and long-term event-free survival between PTRA and PTRAS in patients diagnosed with TRAS at Thailand’s largest national tertiary referral center.

Methods
This single-center retrospective study included kidney transplant patients treated for TRAS during January 2001 to June 2019. Clinical success was defined as (1) increase in estimated glomerular filtration rate (eGFR) > 15%, or (2) reduction in mean arterial pressure (MAP) > 15% with no decrease in antihypertensive medication, or no reduction in MAP or reduction in MAP < 15% with decrease in antihypertensive medication. Incidence of kidney transplant graft failure and transplant renal artery stenosis were also collected.

Results
Sixty-five cases of TRAS were identified from 1072 patients who underwent kidney transplantation. The majority (98.5%) had end-to-side anastomosis technique. Thirty-four patients had PTRA, while 31 patients had PTRAS. One-year clinical success according to renal outcome and BP reduction was 78.5% and 49.2%, respectively. Both renal outcome (79.4% vs. 77.4%, p = 0.845) and BP reduction (40.6% vs. 58.1%, p = 0.166) at 1 year were similar between the PTRA and PTRAS groups. Compared between PTRA and PTRAS, event-free survival for composite of kidney transplant graft failure or transplant renal artery restenosis was significantly higher for PTRAS at 1 year (82.4% vs. 100%, p = 0.025), but not significantly different at 10 years (73.5% vs. 71%, p = 0.818).

Conclusions
We demonstrated the 1-year clinical success, and short- and long-term event-free survival between PTRA and PTRAS in TRAS patients. One-year clinical success was found to be similar between groups. Event-free survival for composite of kidney transplant graft failure or transplant renal artery restenosis was significantly higher in PTRAS at 1 year, but similar between groups at 10 years.
Trial registration Thai Clinical Trials Registry, TCTR20200626002. Registered 26 June 2020—Retrospectively registered, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trial search&smenu = fulltext&task = search&task2 = view1&id = 6441
Sex- and age-specific normative values for handgrip strength and components of the Senior Fitness Test in community-dwelling older adults aged 65–75 years in Germany: results from the OUTDOOR ACTIVE study
Authors: Albrecht Birte Marie , Stalling Imke , Bammann Karin 
Published: April 2021

Abstract
Background
Physical fitness is a key component of independent living and healthy ageing. For the measurement of physical fitness in older adults, the Senior Fitness Test is a commonly used tool. The objective of this study is to calculate sex- and age-specific normative values for handgrip strength and components of the Senior Fitness Test for older adults (65–75 years) in Germany.

Methods
Cross-sectional data of 1657 community-dwelling older adults residing in Bremen, Germany (53% female) were included in this study. Physical fitness was assessed using the following measurements of the Senior Fitness Test battery: 30s-chair stand test, 2 min-step test, sit-and-reach test, and back scratch test. In addition, handgrip strength was measured using a Saehan DHD-3 digital hand dynamometer SH1003. Sex- and age specific normative values were calculated for the 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th, and 99th percentile using the GAMLSS method.

Results
The normative values show differences dependent on sex and age. For handgrip strength, the 30s-chair stand test and the 2 min-step test, normative values were higher for men, while women reached higher values in the sit-and-reach test and the back scratch test. For both, men and women, normative values declined with age.

Conclusions
This study provides sex- and age-specific normative values for handgrip strength and components of the Senior Fitness Test for older adults in Germany. They might be useful for future research and for the application in practice.
Cardiovascular disease and cumulative incidence of cognitive impairment in the Health and Retirement Study
Authors: Covello Allyson L. , Horwitz Leora I. , Singhal Shreya , Blaum Caroline S. , Li Yi , Dodson John A. 
Published: April 2021

Abstract
Background
We sought to examine whether people with a diagnosis of cardiovascular disease (CVD) experienced a greater incidence of subsequent cognitive impairment (CI) compared to people without CVD, as suggested by prior studies, using a large longitudinal cohort.

Methods
We employed Health and Retirement Study (HRS) data collected biennially from 1998 to 2014 in 1305 U.S. adults age ≥ 65 newly diagnosed with CVD vs. 2610 age- and gender-matched controls. Diagnosis of CVD was adjudicated with an established HRS methodology and included self-reported coronary heart disease, angina, heart failure, myocardial infarction, or other heart conditions. CI was defined as a score < 11 on the 27-point modified Telephone Interview for Cognitive Status. We examined incidence of CI over an 8-year period using a cumulative incidence function accounting for the competing risk of death.

Results
Mean age at study entry was 73 years, 55% were female, and 13% were non-white. Cognitive impairment developed in 1029 participants over 8 years. The probability of death over the study period was greater in the CVD group (19.8% vs. 13.8%, absolute difference 6.0, 95% confidence interval 2.2 to 9.7%). The cumulative incidence analysis, which adjusted for the competing risk of death, showed no significant difference in likelihood of cognitive impairment between the CVD and control groups (29.7% vs. 30.6%, absolute difference − 0.9, 95% confidence interval − 5.6 to 3.7%). This finding did not change after adjusting for relevant demographic and clinical characteristics using a proportional subdistribution hazard regression model.

Conclusions
Overall, we found no increased risk of subsequent CI among participants with CVD (compared with no CVD), despite previous studies indicating that incident CVD accelerates cognitive decline.
Chronic diseases in the geriatric population: morbidity and use of primary care services according to risk level
Authors: Barrio-Cortes Jaime , Castaño-Reguillo Almudena , Beca-Martínez María Teresa , Bandeira-de Oliveira Mariana , López-Rodríguez Carmen , Jaime-Sisó María Ángeles 
Published: April 2021

Abstract
Background
Geriatric patients have significant morbidity and greater needs for care and assistance. The objective of this study was to describe the characteristics, morbidity, and use of services in primary care (PC) of patients with chronic diseases older than 65 years according to their risk level assigned by the adjusted morbidity groups (AMG) and to analyse the factors associated with the use of PC services.

Methods
This was a cross-sectional descriptive observational study. Patients older than 65 years from a healthcare service area, classified as chronically ill by the AMG classification system of the PC electronic medical record of the Community of Madrid, were included. Sociodemographic, clinical-care, and PC service utilization variables were collected. Univariate, bivariate and multivariate analyses were done.

Results
A total of 3292 chronic patients older than 65 years were identified, of whom 1628 (49.5%) were low risk, 1293 (39.3%) were medium risk and 371 (11.3%) were high risk. Their mean age was 78.1 (SD = 8.1) years and 2167 (65.8%) were women. Their mean number of chronic diseases was 3.8 (SD = 2), 89.4% had multimorbidity and 1550 (47.1%) were polymedicated. The mean number of contacts/year with PC was 19.5 (SD = 18.2) [men: 19.4 (SD = 19.8); women: 19.5 (SD = 17.4)]. The mean number of contacts/year in people over 85 years was 25.2 (SD = 19.6); in people 76–85 years old, it was 22.1 (SD = 20.3); and in people 66–75 years old, it was 14.5 (SD = 13.9). The factors associated with greater use of services were age (B coefficient [BC] = 0.3; 95%CI = 0.2–0.4), high risk level (BC = 1.9; 95%CI =0.4–3.2), weight of complexity (BC = 0.7; 95%CI = 0.5–0.8), and ≥ 4 chronic diseases (BC = 0.7; 95%CI = 0.3–1.1).

Conclusions
In the geriatric population, we found a high number of patients with chronic diseases and there were three levels of risk by AMG with differences in characteristics, morbidity, and use of PC services. The greatest use of services was by patients with older age, high risk level, greater weight of complexity and ≥ 4 chronic diseases. Further research is needed to develop an intervention model more adapted to the reality of the geriatric population based on risk levels by AMG.
Asymptomatic urinary tract infections and associated risk factors in Pakistani Muslim type 2 diabetic patients
Authors: Aamir Azizul Hasan , Raja Umar Yousuf , Asghar Ali , Mahar Saeed Ahmed , Ghaffar Tahir , Ahmed Ibrar , Qureshi Faisal Masood , Zafar Jamal , Hasan Mohammad Imtiaz , Riaz Amna , Raza Syed Abbas , Khosa Irshad Ahmed , Khan Jahanzeb , Raza Mahwish , Baqar Jaffer Bin 
Published: April 2021

Abstract
Background
One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic.

Methods
This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients.

Results
A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40–59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin.

Conclusion
Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.
Association between different peritoneal dialysis catheter placement methods and short‐term postoperative complications
Authors: Ma Yibo , Liu Shuiqing , Yang Min , Zou Yun , Xue Dong , Liu Yanping , Wang Yufeng , Xie Xiao , Chen Hui 
Published: April 2021

AbstractBackgroundConsidering that current peritoneal dialysis has its own shortcomings, In this study, the Seldinger technique was modified to explore the relationship between different catheter placement methods of peritoneal dialysis and short-term postoperative complications.MethodsWe retrospectively analyzed the data of 157 patients who received peritoneal dialysis in the Department of Nephrology of our hospital from January 2017 to December 2019. According to different catheter placement methods, the patients were divided into three groups: 111 cases of open surgery technique, 23 cases of Seldinger technique, and 23 cases of modified Seldinger technique (ultrasound-guided Veress needle puncture). The general data, laboratory indexes, and abdominal infection and catheter-related complications within one month postoperatively were collected.ResultsThere were 48 (31.0 %) cases of complications in 157 patients within one month postoperatively, which were mainly catheter-related complications (45 cases, 29.0 %). The incidence of catheter tip peritoneal drift (catheter migration) in the three groups was 27.3 %, 39.1 %, and 9.1 %, respectively, with no significant difference between groups (P = 0.069). Univariate logistic regression analysis showed that the systolic blood pressure, history of abdominal and pelvic surgery, creatinine, and modified Seldinger technique were possible impact factors of catheter migration (P < 0.10). After fully adjusting for confounding factors, Compared with the open surgery group, the modified Seldinger method group significantly reduced the risk of catheter migration with an OR of 0.161 (95 % confidence interval: 0.027–0.961,P = 0.045); However, the difference between the Seldinger method group and the open surgery group was not significant, with an OR of 1.061 (95 % confidence interval: 0.308–3.649,P = 0.926). Curve fitting showed that the average incidence of catheter migration in the three groups was 27.3 % (95% CI: 15.9-42.7 %), 28.5 % (95% CI: 10.7-56.9 %), and 5.7 % (95% CI: 1.0-27.0 %); the modified Seldinger method has the lowest average incidence of catheter migration.ConclusionsModified Seldinger technique can significantly reduce catheter-related short-term complications after peritoneal dialysis, and it is especially effective in reducing the incidence of catheter migration. Modified Seldinger technique is a safe and feasible method for the placement of a peritoneal dialysis catheter.