bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-431-5p regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis by targeting XIAP
Authors: Wang Yuejiao , Zhang Kailin , Yuan Xiaowei , Xu Neili , Zhao Shuai , Hou Linxin , Yang Lili , Zhang Ning 
Published: October 2020

Abstract
Background
miR-431-5p is dysregulated in various cancers and plays an important function in the development of cancer. However, its role in fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) remains to be understood.

Methods
Quantitative real-time polymerase chain reaction was used to detect the relative expression of miR-431-5p in synovial tissues and FLSs. Cell proliferation assays helped examine RA FLS proliferation. Flow cytometry was performed to determine apoptosis and cell cycle progression in RA FLSs. We used dual-luciferase assays to determine the correlation between miR-431-5p and its putative target, X-linked inhibitor of apoptosis (XIAP). Quantitative real-time PCR and western blotting were used to measure XIAP levels in synovial tissues and transfected RA FLSs.

Results
miR-431-5p was downregulated in synovial tissues and FLSs of patients with RA. Upregulation of miR-431-5p prohibited cell proliferation and the G0/G1-to-S phase transition but promoted apoptosis in RA FLSs, while miR-431-5p inhibition showed the opposite results. miR-431-5p directly targeted XIAP in RA FLSs and reversely correlated with XIAP levels in synovial tissues. Notably, XIAP silencing partially restored the effects of miR-431-5p inhibition in RA FLSs.

Conclusion
miR-431-5p regulates cell proliferation, apoptosis, and cell cycle of RA FLSs by targeting XIAP, suggesting its potential in the treatment of RA.
Unidentified dengue serotypes in DENV positive samples and detection of other pathogens responsible for an acute febrile illness outbreak 2016 in Cajamarca, Peru
Authors: del Valle-Mendoza Juana , Vasquez-Achaya Fernando , Aguilar-Luis Miguel Angel , Martins-Luna Johanna , Bazán-Mayra Jorge , Zavaleta-Gavidia Victor , Silva-Caso Wilmer , Carrillo-Ng Hugo , Tarazona-Castro Yordi , Aquino-Ortega Ronald , del Valle Luis J. 
Published: October 2020

Abstract
Objective
To describe the prevalence of dengue virus serotypes, as well as other viral and bacterial pathogens that cause acute febrile illness during an outbreak in Cajamarca in 2016.

Results
Dengue virus (DENV) was the most frequent etiologic agent detected in 25.8% of samples (32/124), followed by Rickettsia spp. in 8.1% (10/124), Zika virus in 4.8% (6/124), Chikungunya virus 2.4% (3/124) and Bartonella bacilliformis 1.6% (2/124) cases. No positive cases were detected of Oropouche virus and Leptospira spp. DENV serotypes identification was only achieved in 23% of the total positive for DENV, two samples for DENV-2 and four samples for DENV-4.
During the 2016 outbreak in Cajamarca—Peru, it was observed that in a large percentage of positive samples for DENV, the infecting serotype could not be determined by conventional detection assays. This represents a problem for the national surveillance system and for public health due to its epidemiological and clinical implications. Other viral and bacterial pathogens responsible for acute febrile syndrome were less frequently identified.
Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life
Authors: Jiménez Jessica A. , Ptacek Travis S. , Tuttle Alex H. , Schmid Ralf S. , Moy Sheryl S. , Simon Jeremy M. , Zylka Mark J. 
Published: October 2020

Abstract
Background
Chromodomain helicase DNA-binding protein 8 (Chd8) is a high-confidence risk gene for autism spectrum disorder (ASD). However, how Chd8 haploinsufficiency impairs gene expression in the brain and impacts behavior at different stages of life is unknown.

Methods
We generated a mutant mouse line with an ASD-linked loss-of-function mutation in Chd8 (V986*; stop codon mutation). We examined the behavior of Chd8 mutant mice along with transcriptional changes in the cerebral cortex as a function of age, with a focus on one embryonic (E14.5) and three postnatal ages (1, 6, and 12 months).

Results
Chd8V986*/+ mutant mice displayed macrocephaly, reduced rearing responses and reduced center time in the open field, and enhanced social novelty preference. Behavioral phenotypes were more evident in Chd8V986*/+ mutant mice at 1 year of age. Pup survival was reduced in wild-type x Chd8V986*/+ crosses when the mutant parent was female. Transcriptomic analyses indicated that pathways associated with synaptic and neuronal projections and sodium channel activity were reduced in the cortex of embryonic Chd8V986*/+ mice and then equalized relative to wild-type mice in the postnatal period. At 12 months of age, expression of genes associated with endoplasmic reticulum (ER) stress, chaperone-mediated protein folding, and the unfolded protein response (UPR) were reduced in Chd8V986*/+ mice, whereas genes associated with the c-MET signaling pathway were increased in expression.

Limitations
It is unclear whether the transcriptional changes observed with age in Chd8V986*/+ mice reflect a direct effect of CHD8-regulated gene expression, or if CHD8 indirectly affects the expression of UPR/ER stress genes in adult mice as a consequence of neurodevelopmental abnormalities.

Conclusions
Collectively, these data suggest that UPR/ER stress pathways are reduced in the cerebral cortex of aged Chd8V986*/+ mice. Our study uncovers neurodevelopmental and age-related phenotypes in Chd8V986*/+ mice and highlights the importance of controlling for age when studying Chd8 haploinsufficient mice.
A community-based study of demographics, medical and psychiatric conditions, and gender dysphoria/incongruence treatment in transgender/gender diverse individuals
Authors: James Haleigh A. , Chang Alice Y. , Imhof Reese L. , Sahoo Aradhana , Montenegro Monique M. , Imhof Nicole R. , Gonzalez Cesar A. , Lteif Aida N. , Nippoldt Todd B. , Davidge-Pitts Caroline J. 
Published: October 2020

Abstract
Background
Current understanding about health care in the gender diverse population is limited by the lack of community-based, longitudinal data, especially in the USA. We sought to characterize a community-based cohort of transgender individuals including demographics, gender identities, social characteristics, psychiatric and medical conditions, and medical therapy for gender dysphoria/incongruence.

Patients and methods
We performed a retrospective chart review of gender diverse residents of Olmsted County, Minnesota, who sought gender-specific healthcare from January 1, 1974, through December 31, 2015, using an infrastructure that links medical records of Olmsted County residents from multiple institutions.

Results
The number of patients seeking gender-specific healthcare increased from 1 to 2 per 5-year interval during the 1970s–1990s to 41 from 2011 to 2015 (n = 82). Forty-nine (59.8%) were assigned male sex at birth (AMAB), 31 (37.8%) were assigned female (AFAB), and 2 (2.4%) were intersex. Gender identities evolved over time in 16.3% and 16.1% of patients AMAB and AFAB, respectively, and at most recent follow-up, 8.2% and 12.9% of patients AMAB and AFAB, respectively, were non-binary. Depression affected 78%, followed by anxiety (62.2%), personality disorder (22%), and post-traumatic stress disorder (14.6%). 58.5% experienced suicidal ideation, 22% attempted suicide, and 36.6% were victims of abuse. The most prevalent medical conditions and cardiovascular (CV) risk factors included obesity (42.7%), tobacco use (40.2%), fracture [34.1% (86.2% traumatic)], hypertension (25.6%), hyperlipidemia (25.6%), and hypertriglyceridemia (15.9%). 67.3% of patients AMAB used feminizing and 48.4% of patients AFAB used masculinizing hormone therapy. When compared to US CDC National Health Statistics, there was a significantly greater prevalence of depression and anxiety but no difference in the prevalence of obesity, hypertension, hypercholesterolemia, type 2 diabetes, or stroke.

Conclusion
Transgender and gender diverse individuals represent a population who express various gender identities and are seeking gender-specific healthcare at increasing rates. Psychiatric illness is highly prevalent compared to the US population but there is no difference in the prevalence of CV risk factors including obesity, type 2 diabetes, hypertension, and dyslipidemia.
Association between autoimmune diseases and COVID-19 as assessed in both a test-negative case–control and population case–control design
Authors: Murtas Rossella , Andreano Anita , Gervasi Federico , Guido Davide , Consolazio David , Tunesi Sara , Andreoni Laura , Greco Maria Teresa , Gattoni Maria Elena , Sandrini Monica , Riussi Antonio , Russo Antonio Giampiero 
Published: October 2020

Abstract
Background
COVID-19 epidemic has paralleled with the so called infodemic, where countless pieces of information have been disseminated on putative risk factors for COVID-19. Among those, emerged the notion that people suffering from autoimmune diseases (AIDs) have a higher risk of SARS-CoV-2 infection.

Methods
The cohort included all COVID-19 cases residents in the Agency for Health Protection (AHP) of Milan that, from the beginning of the outbreak, developed a web-based platform that traced positive and negative cases as well as related contacts. AIDs subjects were defined ad having one the following autoimmune disease: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren disease, ankylosing spondylitis, myasthenia gravis, Hashimoto’s disease, acquired autoimmune hemolytic anemia, and psoriatic arthritis. To investigate whether AID subjects are at increased risk of SARS-CoV-2 infection, and whether they have worse prognosis than AIDs-free subjects once infected, we performed a combined analysis of a test-negative design case–control study, a case–control with test-positive as cases, and one with test-negative as cases (CC-NEG).

Results
During the outbreak, the Milan AHP endured, up to April 27th 2020, 20,364 test-positive and 34,697 test-negative subjects. We found no association between AIDs and being positive to COVID-19, but a statistically significant association between AIDs and being negative to COVID-19 in the CC-NEG. If, as likely, test-negative subjects underwent testing because of respiratory infection symptoms, these results imply that autoimmune diseases may be a risk factor for respiratory infections in general (including COVID-19), but they are not a specific risk factor for COVID-19. Furthermore, when infected by SARS-CoV-2, AIDs subjects did not have a worse prognosis compared to non-AIDs subjects. Results highlighted a potential unbalance in the testing campaign, which may be correlated to the characteristics of the tested person, leading specific frail population to be particularly tested.

Conclusions
Lack of availability of sound scientific knowledge inevitably lead unreliable news to spread over the population, preventing people to disentangle them form reliable information. Even if additional studies are needed to replicate and strengthen our results, these findings represent initial evidence to derive recommendations based on actual data for subjects with autoimmune diseases.
$${\text {FE}}^r$$ method with surrogate localization model for hyperelastic composite materials
Authors: Hatano Ryo , Matsubara Seishiro , Moriguchi Shuji , Terada Kenjiro , Yvonnet Julien 
Published: October 2020

AbstractThis study presents a method for constructing a surrogate localization model for a periodic microstructure, or equivalently, a unit cell, to efficiently perform micro-macro coupled analyses of hyperelastic composite materials. The offline process in this approach is to make a response data matrix that stores the microscopic stress distributions in response to various patterns of macroscopic deformation gradients, which is followed by the proper orthogonal decomposition (POD) of the matrix to construct a reduced order model (ROM) of the microscopic analysis (localization) with properly extracted POD bases. Then, response surfaces of the POD coefficients are constructed so that the ROM can be continuous with respect to the input datum, namely, the macroscopic deformation gradient. The novel contributions of this study are the application of the L2 regularization to the interpolation approximations of the POD coefficients by use of radial basis functions (RBFs) to make the response surfaces continuous and the combined use of the cross-validation and the Bayesian optimization to search for the optimal set of parameters in both the RBFs and L2regularization formula. The resulting model can be an alternative to microscopic finite element (FE) analyses in the conventional$${\text {FE}}^2$$FE2method and realizes$${\text {FE}}^r$$FErwith$$1<r<<2$$1<r<<2accordingly. Representative numerical examples of micro-macro coupled analysis with the$${\text {FE}}^r$$FErare presented to demonstrate the capability and promise of the surrogate localization model constructed with the proposed approach in comparison with the results with high-fidelity direct$${\text {FE}}^2$$FE2.
Using movement to inform conservation corridor design for Mojave desert tortoise
Authors: Hromada Steven J. , Esque Todd C. , Vandergast Amy G. , Dutcher Kirsten E. , Mitchell Corey I. , Gray Miranda E. , Chang Tony , Dickson Brett G. , Nussear Kenneth E. 
Published: October 2020

Abstract
Background
Preserving corridors for movement and gene flow among populations can assist in the recovery of threatened and endangered species. As human activity continues to fragment habitats, characterizing natural corridors is important in establishing and maintaining connectivity corridors within the anthropogenic development matrix. The Mojave desert tortoise (Gopherus agassizii) is a threatened species occupying a variety of habitats in the Mojave and Colorado Deserts. Desert tortoises have been referred to as corridor-dwellers, and understanding how they move within suitable habitat can be crucial to defining corridors that will sustain sufficient gene flow to maintain connections among populations amidst the increases in human development.

Methods
To elucidate how tortoises traverse available habitat and interact with potentially inhospitable terrain and human infrastructure, we used GPS dataloggers to document fine-scale movement of individuals and estimate home ranges at ten study sites along the California/Nevada border. Our sites encompass a variety of habitats, including mountain passes that serve as important natural corridors connecting neighboring valleys, and are impacted by a variety of linear anthropogenic features. We used path selection functions to quantify tortoise movements and develop resistance surfaces based on landscape characteristics including natural features, anthropogenic alterations, and estimated home ranges with autocorrelated kernel density methods. Using the best supported path selection models and estimated home ranges, we determined characteristics of known natural corridors and compared them to mitigation corridors (remnant habitat patches) that have been integrated into land management decisions in the Ivanpah Valley.

Results
Tortoises avoided areas of high slope and low perennial vegetation cover, avoided moving near low-density roads, and traveled along linear barriers (fences and flood control berms).

Conclusions
We found that mitigation corridors designated between solar facilities should be wide enough to retain home ranges and maintain function. Differences in home range size and movement resistance between our two natural mountain pass corridors align with differences in genetic connectivity, suggesting that not all natural corridors provide the same functionality. Furthermore, creation of mitigation corridors with fences may have unintended consequences and may function differently than natural corridors. Understanding characteristics of corridors with different functionality will help future managers ensure that connectivity is maintained among Mojave desert tortoise populations.
Usefulness of 18F-FDOPA PET for the management of primary brain tumors: a systematic review of the literature
Authors: Somme François , Bender Laura , Namer Izzie Jacques , Noël Georges , Bund Caroline 
Published: October 2020

AbstractContrast-enhanced magnetic resonance imaging is currently the standard of care in the management of primary brain tumors, although certain limitations remain. Metabolic imaging has proven useful for an increasing number of indications in oncology over the past few years, most particularly18F-FDG PET/CT. In neuro-oncology,18F-FDG was insufficient to clearly evaluate brain tumors. Amino-acid radiotracers such as18F-FDOPA were then evaluated in the management of brain diseases, notably tumoral diseases. Even though European guidelines on the use of amino-acid PET in gliomas have been published, it is crucial that future studies standardize acquisition and interpretation parameters. The aim of this article was to systematically review the potential effect of this metabolic imaging technique in numerous steps of the disease: primary and recurrence diagnosis, grading, local and systemic treatment assessment, and prognosis. A total of 41 articles were included and analyzed in this review. It appears that18F-FDOPA PET holds promise as an effective additional tool in the management of gliomas. More consistent prospective studies are still needed.
Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study
Authors: Sadiq Mohammad Ali , Hassan Muhammad , Afridi Rubbia , Halim Muhammad Sohail , Do Diana V. , Sepah Yasir J. , Nguyen Quan Dong ,   for the STOP-UVEITIS Investigators
Published: October 2020

Abstract
Background
Although fluorescein angiography (FA) is a frequently used imaging modality in patients with non-infectious uveitis (NIU), it has not been reliably used for objective assessment of posterior segment inflammatory outcomes in these patients. In this index study we report the posterior segment inflammatory outcomes of two different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with NIU using a semi-quantitative FA scoring system.

Methods
STOP-Uveitis is a randomized, multi-center clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with NIU. Thirty-seven (37) patients with NIU were randomized into one of two treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Posterior segment inflammatory outcomes were assessed by evaluating FA at baseline and month 6 by graders at a central reading center. A previously reported, semi-quantitative, scoring system for FA was used to assess signs that represent ongoing inflammatory processes in the posterior segment. These signs included optic disc hyperfluorescence, macular edema, retinal vascular staining and/or leakage, capillary leakage, retinal capillary nonperfusion, neovascularization of the optic disc, neovascularization elsewhere, pinpoint leaks, and retinal staining and/or subretinal pooling. Statistical significance was set at p < 0.05. Main outcome measures included change in posterior segment inflammation as assessed using FA at month 6.

Results
37 eyes (37 patients) were randomized in the STOP-Uveitis study. 30 eyes were found to be eligible for this sub-study based on study criteria. Seven eyes had ungradable images at either baseline or month 6 and were therefore excluded from the analysis. The reduction in FA inflammatory scores at month 6 were statistically significant in both groups (p < 0.05). The difference between the two groups was not significant (p = 0.351).

Conclusions
IV infusions of tocilizumab (both 4 and 8 mg/kg) are effective in improving posterior segment inflammation in eyes with NIU. A semi-quantitative FA scoring system may be used as a reliable outcome measure for assessment of posterior segment inflammation.
ClinicalTrials.gov Identifier: NCT01717170
Long-term exposure to pemetrexed induces chronic renal dysfunction in patients with advanced and recurrent non-squamous cell lung cancer: a retrospective study
Authors: Umehara Kengo , Yama Kaori , Koike Nozomi , Takayama Shintarou , Wakamoto Azusa , Hatuyama Tae , Kobayashi Michiya , Sato Hideki 
Published: October 2020

Abstract
Background
Pemetrexed (PEM) is administered over a long term to patients with non-squamous cell lung cancer as a maintenance therapy after platinum combination induction chemotherapy. Although decreased renal function owing to long-term PEM exposure has been reported, changes in the renal function of individual patients have not been reported. This study aimed to evaluate serum creatinine (Scr) in individual patients over time and determine whether long-term PEM exposure contributed to increased Scr.

Methods
A retrospective study was performed using 90 non-squamous cell lung cancer patients, who had received maintenance therapy with PEM ± bevacizumab (BEV) after carboplatin + PEM ± BEV therapy at the Sapporo Minami-Sanjo Hospital from February 2012 to February 2019. Using Scr at the start of induction chemotherapy as the baseline, we calculated the correlation coefficient (r) of the rate of Scr change in an individual patient and the number of treatment courses to divide patients into two groups for comparison: patients with + 0.4 < r ≦ + 1.0 and an observed positive correlation (the r+0.4< group), and patients with − 1.0 ≦ r ≦ + 0.4 and no observed positive correlation (the r+0.4≧ group).

Results
Statistically significant differences between the r+0.4< group and the r+0.4≧ group were observed for the following parameters: the median cumulative dose of PEM (interquartile range) [9100 (6365, 12,260) mg/body vs. 5600 (4140, 7440) mg/body, P < 0.01]; the number of patients taking nonsteroidal anti-inflammatory drugs at the start of treatment [15 patients (31%) vs. 3 patients (7%), P < 0.01]; and the median number of treatment courses starting from induction chemotherapy [11 (8, 14) courses vs. 8 (6, 11) courses, P < 0.01]. Next, the results of univariate and multivariate analyses demonstrated that the cumulative dose of PEM (≧ 7000 mg/body vs < 7000 mg/body, OR 2.40; 95% CI, 1.22–4.75, P = 0.01) was an independent explanatory variable of the r+0.4< group.

Conclusions
Long-term PEM exposure may induce chronic renal dysfunction. Hence, maintaining kidney function during PEM treatment by reducing the use of combination drugs and the risk of other renal dysfunctions, such as dehydration, may help patients continue therapy and contribute to their long-term survival.
Impact of using learning analytics in asynchronous online discussions in higher education
Authors: Cerro Martínez Juan Pedro , Guitert Catasús Montse , Romeu Fontanillas Teresa 
Published: October 2020

AbstractFollowing asynchronous online discussion activities as a complex communication process is a demanding task for teachers. In this paper, the authors have explored the potential in supporting such activity through learning analytics. From the beginning, the authors acknowledged the limitations of technology to support the complexities of a pedagogical activity. Therefore, the methodology used was participatory design-based research (DBR) divided into two main stages. The first design phase dealt with the engagement of teachers and pedagogical experts in defining the data and metrics to be used to support the pedagogical concepts. The second consisted of an implementation phase including pilots with students and with crucial engagement of teachers in commenting their understanding over students’ learning processes and the feedback the teachers could offer to them. Overall, the students shown improvements in their performance as monitored through the learning analytics group in contrast with control groups. The discussion over the design and its results could be potentially extrapolated to other educational contexts.