bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical applications of allogeneic adipose-derived mesenchymal stem cells ameliorate the canine keratoconjunctivitis sicca
Authors: Wei Li-Ning , Wu Ching-Ho , Lin Chung-Tien , Liu I-Hsuan 
Published: June 2022

Abstract
Background
Canine keratoconjunctivitis sicca (KCS) is predominantly an immune-mediated disease. Current therapy of canine KCS is mainly by immunosuppressant, but the effectiveness was limited in some patients. In the past few years, some studies showed the results of the use of mesenchymal stem cells in treating canine KCS via periocular injections. However, the periocular injection procedure requires sedation or general anesthesia, and may lead to iatrogenic or incidental injury during the injection process. The aim of this study was to investigate the efficacy of topical allogenic canine adipose-derived mesenchymal stem cells (cAD-MSCs) in clinical patients of canine KCS.

Results
The cAD-MSCs used in this study were characterized for their capability of tri-lineage differentiation and immunomodulatory properties. In addition, preparation methods for eye drops of cAD-MSCs was developed and its optimal preservation was tested. The canine KCS patients were recruited for clinical trial and divided into two groups based on their history of previous treatment. All patients received topical cAD-MSCs treatment once per week for 6 consecutive weeks and complete ophthalmic examinations were performed 1 week before treatment (week 0) and at 3rd, 6th, 9th weeks, respectively. The results showed that the quantity and quality of tears have improved significantly following topical cAD-MSCs treatment based on Schirmers tear test-1 and tear break-up time. More than half of all patients were found improved in the tear quantity. In particular, 56.5% of the patients that were unresponsive to prior immunosuppressant therapy had an effective increase in tear volume. The severity of clinical signs was also ameliorated according to the numeric rating scale score from both patient owners and the clinician.

Conclusion
To sum up, topical cAD-MSCs may be beneficial especially in KCS patients with poor owner compliance for frequent daily use of eye drops or those who are unresponsive to immunosuppressant therapy.
Antibacterial treatment for exotic species, backyard ruminants and small flocks: a narrative review highlighting barriers to effective and appropriate antimicrobial treatment
Authors: Jelinski Dana C. , Orsel Karin , Weese J. Scott , Conly John M. , Julien Danielle A. 
Published: June 2022

AbstractAntimicrobial resistance is a complex One Health issue that exists in both human and veterinary medicine. To mitigate this ever-growing problem, efforts have been made to develop guidelines for appropriate antimicrobial use (AMU) across sectors. In veterinary medicine, there are notable literature gaps for proper AMU in minor species. We conducted a structured narrative review covering the years of July 2006 – July 2021 to find antimicrobial treatments for common bacterial infections in exotic (birds, rodents, reptiles, and others), small flock (chickens, turkeys, and other fowl), and backyard small ruminant (sheep and goats) species. We retrieved a total of 4728 articles, of which 21 articles met the criteria for our review. Studies were grouped according to species, syndrome, and body system affected. Other data extracted included the bacterial pathogen(s), treatment (active ingredient), and geographical origin. Body systems reported included: intra-oral (n = 4), gastrointestinal (n = 1), respiratory (n = 2), reproductive (n = 1), skin (n = 3), aural (n = 1), ocular (n = 4), and other/multisystem (n = 5). By species, our search resulted in: rabbit (n = 5), rat (n = 2), guinea pig (n = 1), chinchilla (n = 1), guinea pig and chinchilla (n = 1), avian species (n = 1), psittacine birds (n = 2), loris and lorikeets (n = 1), turtles (n = 2), lizards (n = 1), goats (n = 2) and sheep (n = 2). The results of our findings identified a distinct gap in consistent antimicrobial treatment information for commonly encountered bacterial conditions within these species. There is a persisting need for clinical trials that focus on antibacterial treatment to strengthen the evidence base for AMU within exotic, small flock, and backyard small ruminant species.
Triglyceride-glucose index variability and incident cardiovascular disease: a prospective cohort study
Authors: Li Haibin , Zuo Yingting , Qian Frank , Chen Shuohua , Tian Xue , Wang Penglian , Li Xia , Guo Xiuhua , Wu Shouling , Wang Anxin 
Published: June 2022

Abstract
Background
Recent studies have suggested that triglyceride-glucose (TyG) index is an independent predictor of cardiovascular disease (CVD). However, the impact of long-term visit-to-visit variability in TyG index on the risk of CVD is not known. We aimed to investigate the longitudinal association between baseline and mean TyG index as well as TyG index variability and incident CVD in a Chinese population.

Methods
We included 49,579 participants without previous history of CVD in the Kailuan study who underwent three health examinations (2006, 2008, and 2010) and were followed up for clinical events until 2019. TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. We measured TyG index variability as the SD of the residuals obtained from a linear regression on the three TyG index measurements for each individual. Multivariate-adjusted Cox models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) with incident CVD.

Results
During a median follow-up time of 9.0 years, 2404 developed CVD. The highest tertile (T3) of baseline and mean TyG index were each associated with higher CVD incidence as compared with the lowest tertile (T1): aHR, 1.25; 95% CI 1.11–1.42; and aHR 1.40; 95% CI 1.24–1.58, respectively. Tertile 3 of TyG index variability was associated with increased CVD incidence compared to T1 group (aHR, 1.12; 95% CI 1.01–1.24). Similar findings were observed in a series of sensitivity analyses.

Conclusion
Higher TyG index level and greater TyGindex variability were each independently associated with a higher incidence of CVD.
KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma
Authors: Cui Yankang , Shen Tianyi , Xu Feng , Zhang Jing , Wang Yuhao , Wu Jiajin , Bu Hengtao , Fu Dian , Fang Bo , Lv Huichen , Wang Suchun , Shi Changjie , Liu Bianjiang , He Haowei , Tang Hao , Ge Jingping 
Published: June 2022

Abstract
Background
Studies over the past decade have shown that competitive endogenous RNA (ceRNA) plays an essential role in the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). Meanwhile, immune checkpoint blocker is gradually moving towards the first-line treatment of ccRCC. Hence, it’s urgent to develop a new prediction model for the efficiency of immunotherapy. At present, there is no study to reveal the effect of ceRNA network on the efficiency of immunotherapy for ccRCC.

Methods
To systematically analyze the effect of ceRNA hub genes in ccRCCon immune response, we constructed prognosis models based on ceRNAs and immune cells, respectively. We constructed ceRNA network using hypergeometric distribution test and correlation analysis with R script based on The Cancer Genome Atlas (TCGA) database. We then applied the Cibersort algorithm to simulate the infiltration overview of immune cells in kidney renal clear carcinoma (KIRC) samples. Prognosis-related immune cells were screened and a predictive model of these cells was constructed. Prognosis-related immune cells and ceRNA hub genes were performed with co-expression analysis. Finally, qRT-PCR and immunofluorescence assays were performed to validate the results.

Results
The construction of ceRNA related prognosis model contained 8 hub genes, including RELT, MYO9B, KCNN4, SIX1, OTOGL, MALAT1, hsa-miR-130b-3p, and hsa-miR-21-5p. The area under the receiver operating characteristic curve (AUC) was 0.77 at 5 years. For the construction of immune cells prognosis model, 3 immune cells (T cells regulatory, Macrophages, Mast cells resting) were adopted, and the AUC was 0.65 at 5 years. We then merged the two models by correlation analysis and co-expression analysis. Finally, we found that KCNN4 positively correlates with T cells regulatory (Tregs) and negatively correlates with mast cells resting significantly. Furthermore, higher expression of KCNN4 may lead to a higher potential for immune evasion and lower efficiency for immune checkpoint inhibitors (ICIs).

Conclusions
Generally, this is the first study to assess the prognostic value of immune related ceRNA hub genes in ccRCC, and KCNN4 was finally demonstrated to be a key regulatory factor with strong correlation with Tregs and mast cells resting.
Cattle-related risk factors for malaria in southwest Ethiopia: a cross-sectional study
Authors: Chan Kallista , Cano Jorge , Massebo Fekadu , Messenger Louisa A. 
Published: June 2022

Abstract
Background
Despite the low to moderate intensity of malaria transmission present in Ethiopia, malaria is still a leading public health problem. Current vector control interventions, principally long-lasting insecticidal nets and indoor residual spraying, when deployed alone or in combination, are insufficient to control the dominant vector species due to their exophagic and exophilic tendencies. Zooprophylaxis presents a potential supplementary vector control method for malaria; however, supporting evidence for its efficacy has been mixed.

Methods
To identify risk factors of malaria and to estimate the association between cattle and Anopheles vector abundance as well as malaria risk, a cross-sectional study was conducted in a village near Arba Minch, Ethiopia. Epidemiological surveys (households = 95, individuals = 463), mosquito collections using CDC light traps and a census of cattle and human populations were conducted. To capture environmental conditions, land cover and water bodies were mapped using satellite imagery. Risk factor analyses were performed through logistic, Poisson, negative binomial, and spatial weighted regression models.

Results
The only risk factor associated with self-reported malaria illness at an individual level was being a child aged 5 or under, where they had three times higher odds than adults. At the household level, variables associated with malaria vector abundance, especially those indoors, included socioeconomic status, the proportion of children in a household and cattle population density.

Conclusions
Study results are limited by the low abundance of malaria vectors found and use of self-reported malaria incidence. Environmental factors together with a household’s socioeconomic status and host availability played important roles in the risk of malaria infection in southwest Ethiopia. Cattle abundance in the form of higher cattle to human ratios may act as a protective factor against mosquito infestation and malaria risk. Humans should remain indoors to maximize potential protection against vectors and cattle kept outside of homes.
Application of the deep learning algorithm in nutrition research – using serum pyridoxal 5′-phosphate as an example
Authors: Ma Chaoran , Chen Qipin , Mitchell Diane C. , Na Muzi , Tucker Katherine L. , Gao Xiang 
Published: June 2022

AbstractBackgroundMultivariable linear regression (MLR) models were previously used to predict serum pyridoxal 5′-phosphate (PLP) concentration, the active coenzyme form of vitamin B6, but with low predictability. We developed a deep learning algorithm (DLA) to predict serum PLP based on dietary intake, dietary supplements, and other potential predictors.MethodsThis cross-sectional analysis included 3778 participants aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) 2007-2010, with completed information on studied variables. Dietary intake and supplement use were assessed with two 24-hour dietary recalls. We included potential predictors for serum PLP concentration in the models, including dietary intake and supplement use, sociodemographic variables (age, sex, race-ethnicity, income, and education), lifestyle variables (smoking status and physical activity level), body mass index, medication use, blood pressure, blood lipids, glucose, and C-reactive protein. We used a 4-hidden-layer deep neural network to predict PLP concentration, with 3401 (90%) participants for training and 377 (10%) participants for test using random sampling. We obtained outputs after sending the features of the training set and conducting forward propagation. We then constructed a loss function based on the distances between outputs and labels and optimized it to find good parameters to fit the training set. We also developed a prediction model using MLR.ResultsAfter training for 105steps with the Adam optimization method, the highestR2was 0.47 for the DLA and 0.18 for the MLR model in the test dataset. Similar results were observed in the sensitivity analyses after we excluded supplement-users or included only variables identified by stepwise regression models.ConclusionsDLA achieved superior performance in predicting serum PLP concentration, relative to the traditional MLR model, using a nationally representative sample. As preliminary data analyses, the current study shed light on the use of DLA to understand a modifiable lifestyle factor.
Activating cGAS–STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis
Authors: Ding Rui , Li Haiyan , Liu Yaqi , Ou Weiyang , Zhang Xifang , Chai Huihui , Huang Xiaofei , Yang Weijie , Wang Qiujing 
Published: June 2022

AbstractBackgroundNeuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase–stimulator of interferon gene (cGAS–STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS–STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear.MethodsA CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2′3′-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry.ResultscGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS–STING axis. RU.521 decreased the levels of 2′3′-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1β, and cleaved IL-1β/pro-IL-1β. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2′3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA.ConclusionsOur data demonstrate that repression of the cGAS–STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.
Regulation of brain iron uptake by apo- and holo-transferrin is dependent on sex and delivery protein
Authors: Baringer Stephanie L. , Neely Elizabeth B. , Palsa Kondaiah , Simpson Ian A. , Connor James R. 
Published: June 2022

Abstract
Background
The brain requires iron for a number of processes, including energy production. Inadequate or excessive amounts of iron can be detrimental and lead to a number of neurological disorders. As such, regulation of brain iron uptake is required for proper functioning. Understanding both the movement of iron into the brain and how this process is regulated is crucial to both address dysfunctions with brain iron uptake in disease and successfully use the transferrin receptor uptake system for drug delivery.

Methods
Using in vivo steady state infusions of apo- and holo-transferrin into the lateral ventricle, we demonstrate the regulatory effects of brain apo- and holo-transferrin ratios on the delivery of radioactive 55Fe bound to transferrin or H-ferritin in male and female mice. In discovering sex differences in the response to apo- and holo-transferrin infusions, ovariectomies were performed on female mice to interrogate the influence of circulating estrogen on regulation of iron uptake.

Results
Our model reveals that apo- and holo-transferrin significantly regulate iron uptake into the microvasculature and subsequent release into the brain parenchyma and their ability to regulate iron uptake is significantly influenced by both sex and type of iron delivery protein. Furthermore, we show that cells of the microvasculature act as reservoirs of iron and release the iron in response to cues from the interstitial fluid of the brain.

Conclusions
These findings extend our previous work to demonstrate that the regulation of brain iron uptake is influenced by both the mode in which iron is delivered and sex. These findings further emphasize the role of the microvasculature in regulating brain iron uptake and the importance of cues regarding iron status in the extracellular fluid.
Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis
Authors: Yuan Aidong , Wu Penghuan , Zhong Zhinian , He Zhengyan , Li Wenhu 
Published: June 2022

Abstract
Objective
This study was conducted to investigate the effect of long non-coding RNA (lncRNA) Gm37494 on osteoarthritis (OA) and its related molecular mechanism.

Methods
The cartilage tissues were obtained from OA patients, and an OA mouse model was induced by the destabilization of the medial meniscus, followed by measurement of Gm37494, microRNA (miR)-181a-5p, GABRA1 mRNA, and the encoded GABAARα1 protein expression. Thereafter, a cellular model was induced by interleukin-1β (IL-1β) treatment in chondrocytes, followed by ectopic and silencing experiments. Chondrocyte proliferation was detected by CCK-8 and EdU assays, chondrocyte apoptosis by flow cytometry and western blot, and the levels of inflammatory factors by ELISA. The binding of Gm37494 to miR-181a-5p was evaluated by dual-luciferase reporter gene and RIP assays, and that of GABRA1 to miR-181a-5p by dual-luciferase reporter gene and RNA pull-down assays.

Results
OA patients and mice had decreased GABRA1 mRNA and GABAARα1 protein levels and elevated miR-181a-5p expression in cartilage tissues. Additionally, Gm37494 was poorly expressed in OA mice. Mechanistically, Gm37494 directly bound to and inversely modulated miR-181a-5p that negatively targeted GABRA1. In IL-1β-induced chondrocytes, Gm37494 overexpression enhanced cell proliferation and suppressed cell apoptosis and inflammation, whereas further miR-181a-5p up-regulation or GABRA1 silencing abolished these trends.

Conclusions
Conclusively, Gm37494 elevated GABRA1 expression by binding to miR-181a-5p, thus ameliorating OA-induced chondrocyte damage.
Adolescents’ mental health and maladaptive behaviors before the Covid-19 pandemic and 1-year after: analysis of trajectories over time and associated factors
Authors: Pedrini Laura , Meloni Serena , Lanfredi Mariangela , Ferrari Clarissa , Geviti Andrea , Cattaneo Annamaria , Rossi Roberta 
Published: June 2022

AbstractBackgroundAdolescents have been deeply exposed to negative consequences of social distancing imposed by Covid-19. There is a lack of longitudinal studies regarding the impact on adolescents of this unfavorable condition, and their results are controversial. The aim of the present prospective study is to assess psychopathological symptoms in adolescent students over time and to evaluate what type of impact the Covid-19 pandemic had on adolescents. Moreover, the association between mental health indexes, potential risk and resilience factors is explored.MethodsPsychopathological symptoms (i.e., anxiety, depression, stress, emotional dysregulation, maladaptive behaviours), and potential risk and resilience factors (i.e., childhood trauma, emotional regulation skills, family function, personality traits) were assessed among a sample of 153 students (72% female; mean age 16.1 ± 0.49), living in a medium-size city in the north of Italy, at two time points: before the outbreak of the Covid-19 pandemic (November 2019–January 2020) and 1 year later (April–May 2021).ResultsAfter 1 year, we found an increase in mean scores on anxiety, stress for future uncertainty, and higher frequency of maladaptive behaviours. By contrast, the level of stress related to social domains (i.e., school attendance, romantic relationships, peer pressure) decreased. Dysfunctional emotional regulation skills, childhood trauma, low family functioning, and specific personality traits were associated to higher psychopathological symptoms. Cluster analysis detected three groups of youths based on their change over time in psychopathological symptoms: those who worsened (N = 23; 15%), improved (N = 55; 34%), or remained stable (N = 75; 46%). After controlling for baseline mental health status, those adolescents reporting increase in self-harm (OR = 2.61; p < 0.001), binge-drinking (OR = 3.0; p = 0.007), aggressiveness (OR 1.92; p = 0.004), and binge-eating (OR 2.55; p = 0.003) were more likely to present a worsened mental health condition.ConclusionThe present results suggest that the Covid-19 pandemic seems to have had a different impact on subgroups of students. Indeed, we found a global worsening of psychological well-being only in a subgroup of adolescents, otherwise other students remained stable or improved. Increased frequency of maladaptive behaviors was found as a predictor of worsened mental health, therefore interventions to strengthen emotional regulation strategies are warranted. Finally, the decrease of stress in social domains could be due to reduction of potential triggering situations, thus indicating only a temporary beneficial effect that requires careful monitoring.