bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Nucleotide Polymorphisms in HOTAIR Are Related to Breast Cancer Risk and Prognosis in the Northeastern Chinese Population
Authors: Lv Zheng , Kou Changgui , Chen Naifei , Jia Lin , Sun Xu , Gao Yangyang , Bai Rilan , Yang Ming , Cui Jiuwei 
Published: July 2021

BackgroundThe long noncoding RNA HOX transcript antisense RNA (HOTAIR) is highly expressed in breast cancer (BC) tissues and is associated with the recurrence and metastasis of BC. Until now, the results of studies on associations between several functional single nucleotide polymorphisms(SNPs) (rs920778, rs1899663, and rs4759314) in HOTAIR with BC susceptibility carried out in different regions of China are still inconsistent. There is no study on correlation between HOTAIR SNPs and prognosis of Chinese population. Therefore, we investigated the relationship between HOTAIR SNPs and susceptibility to and prognosis of BC.MethodWe conducted a population-based case-control study involving 828 BC cases and 905 healthy controls. Peripheral blood DNA was used for genotyping. The association between HOTAIR genotypes and BC risk were estimated by odds ratios (ORs) computed using the binary logistic regression model. The relationships between HOTAIR SNPs and clinicopathological features were tested by Pearson’s chi-square test or Fisher’s exact test. Survival was analyzed using the Kaplan-Meier method.ResultsThe functional rs920778 genetic variant increased BC risk in the codominant model. Individuals with the rs920778 GG genotype had an OR of 2.426 (95% confidence interval [CI] = 1.491–3.947, P &lt; 0.001) for developing BC compared to individuals with the AA genotype. Individuals with the AG genotype had an OR of 1.296 (95% CI = 1.040–1.614, P = 0.021) for developing BC compared to individuals with the AA genotype. Individuals with the rs4759314 GA genotype had a lower BC risk than individuals with the rs4759314 AA/GG genotype (OR = 0.566, 95% CI = 0.398–0.803, P = 0.001). The rs1899663 genotype had no correlation with BC susceptibility. Haplotypes composed of rs920778–rs1899663 and rs920778–rs1899663–rs4759314 could increase BC risk (all P &lt; 0.001). There were no statistically significant associations between HOTAIR SNPs and clinicopathological characteristics. The rs920778 GG/AG genotypes were associated with worse disease-free survival (DFS) (p = 0.012), and the rs4759314 GA genotype was associated with worse DFS and overall survival (OS) (p = 0.011).ConclusionHOTAIR SNPs(rs920778 and rs4759314) are significantly related to BC susceptibility and prognosis in the northeastern Chinese population, indicating the significance in the occurrence and development of BC.
Differential Use of Pediatric Video Visits by a Diverse Population During the COVID-19 Pandemic: A Mixed-Methods Study
Authors: Rosenthal Jennifer L. , O'Neal Christina , Sanders April , Fernandez y Garcia Erik 
Published: July 2021

Objective: To describe and explore pediatric ambulatory video visit use by patient characteristics during the coronavirus disease 2019 (COVID-19) pandemic.Methods: We conducted an explanatory sequential mixed methods study with integration at the design and methods level. Phase 1 was a cross-sectional analysis of general and specialty pediatric ambulatory encounters to profile the use of video visits by patient characteristics. We performed descriptive analyses for each variable of interest and estimated a multivariable logistic regression model to analyze factors associated with the odds of having a video visit. Phase 2 was a qualitative exploration using semi-structured interviews with healthcare team members to understand the contextual factors influencing video visit usage. We used an interview guide to solicit information related to general perceptions about ambulatory video visits, reactions to the quantitative phase data, and strategies for optimizing equitable reach of video visits. Data were analyzed using a combination of deductive and inductive analysis.Results: Among the 5,464 pediatric ambulatory encounters completed between March 11 and June 30, 2020, 2,127 were video visits. Patient factors associated with lower odds of having a video visit rather than an in-person visit included being Spanish-speaking (aOR 0.27, 95% CI 0.20–0.37) and other non-English-speaking (aOR 0.50, 95% CI 0.34–0.75) in comparison to English-speaking. Patients with public insurance also had a lower odds of having a video visit in comparison to privately insured patients (aOR 0.77, 95% CI 0.67–0.88). Qualitative interviews identified five solution-based themes: (1) Promoting video visits in a way that reaches all patient families; (2) Offering video visits to all patient families; (3) Mitigating digital literacy barriers; (4) Expanding health system resources to support families' specific needs; and (5) Engaging and empowering health system personnel to expand video visit access.Conclusion: We identified differences in pediatric ambulatory video visit use by patient characteristics, with lower odds of video visit use among non-English-speaking and publicly insured patients. The mixed-methods approach allowed for the perspectives of our interview participants to contextualize the finding and lead to suggestions for improvement. Both our findings and the approach can be used by other health systems to ensure that all patients and families receive equal video visit access.
Ginkgo biloba L. Prevents Hypobaric Hypoxia–Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling
Authors: Kushwah Neetu , Jain Vishal , Kadam Manisha , Kumar Rahul , Dheer Aastha , Prasad Dipti , Kumar Bhuvnesh , Khan Nilofar 
Published: July 2021

Hypobaric hypoxia (HH) is a stressful condition, which is more common at high altitudes and can impair cognitive functions.Ginkgo bilobaL. leaf extract (GBE) is widely used as herbal medicine against different disorders. Its ability to improve cognitive functions, reduce oxidative stress, and promote cell survival makes it a putative therapeutic candidate against HH. The present study has been designed to explore the effect of GBE on HH-induced neurodegeneration and memory impairment as well as possible signaling mechanisms involved. 220–250 gm (approximately 6- to 8-week-old) Sprague Dawley rats were randomly divided into different groups. GBE was orally administered to respective groups at a dose of 100 mg/kg/day throughout the HH exposure, i.e., 14 days. Memory testing was performed followed by hippocampus isolation for further processing of different molecular and morphological parameters related to cognition. The results indicated that GBE ameliorates HH-induced memory impairment and oxidative damage and reduces apoptosis. Moreover, GBE modulates the activity of the small conductance calcium-activated potassium channels, which further reduces glutamate excitotoxicity and apoptosis. The exploration of the downstream signaling pathway demonstrated that GBE administration prevents HH-induced small conductance calcium-activated potassium channel activation, and that initiates pro-survival machinery by activating extracellular signal–regulated kinase (ERK)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP response element–binding protein (CREB) signaling pathway. In summary, the current study demonstrates the beneficial effect of GBE on conditions like HH and provides various therapeutic targets involved in the mechanism of action of GBE-mediated neuroprotection.
Cyclotides Isolated From Violet Plants of Cameroon Are Inhibitors of Human Prolyl Oligopeptidase
Authors: Gattringer Jasmin , Ndogo Olivier Eteme , Retzl Bernhard , Ebermann Carina , Gruber Christian W. , Hellinger Roland 
Published: July 2021

Traditional medicine and the use of herbal remedies are well established in the African health care system. For instance, Violaceae plants are used for antimicrobial or anti-inflammatory applications in folk medicine. This study describes the phytochemical analysis and bioactivity screening of four species of the violettribeAllexis found in Cameroon.Allexis cauliflora,Allexis obanensis,Allexis batangaeandAllexis zygomorphawere evaluated for the expression of circular peptides (cyclotides) by mass spectrometry. The unique cyclic cystine-rich motif was identified in several peptides of all four species. Knowing that members of this peptide family are protease inhibitors, the plant extracts were evaluated for the inhibition of human prolyl oligopeptidase (POP). Since all four species inhibited POP activity, a bioactivity-guided fractionation approach was performed to isolate peptide inhibitors. These novel cyclotides, alca 1 and alca 2 exhibited IC50values of 8.5 and 4.4 µM, respectively. To obtain their amino acid sequence information, combinatorial enzymatic proteolysis was performed. The proteolytic fragments were evaluated in MS/MS fragmentation experiments and the full-length amino acid sequences were obtained byde novoannotation of fragment ions. In summary, this study identified inhibitors of the human protease POP, which is a drug target for inflammatory or neurodegenerative disorders.
Methadone, Buprenorphine, and Clonidine Attenuate Mitragynine Withdrawal in Rats
Authors: Hassan Rahimah , Sreenivasan Sasidharan , Müller Christian P. , Hassan Zurina 
Published: July 2021

Background:Kratom orMitragyna speciosaKorth has been widely used to relieve the severity of opioid withdrawal in natural settings. However, several studies have reported that kratom may by itself cause dependence following chronic consumption. Yet, there is currently no formal treatment for kratom dependence. Mitragynine, is the major psychoactive alkaloid in kratom. Chronic mitragynine treatment can cause addiction-like symptoms in rodent models including withdrawal behaviour. In this study we assessed whether the prescription drugs, methadone, buprenorphine and clonidine, could mitigate mitragynine withdrawal effects. In order to assess treatment safety, we also evaluated hematological, biochemical and histopathological treatment effects.Methods:We induced mitragynine withdrawal behaviour in a chronic treatment paradigm in rats. Methadone (1.0 mg/kg), buprenorphine (0.8 mg/kg) and clonidine (0.1 mg/kg) were i.p. administered over four days during mitragynine withdrawal. These treatments were stopped and withdrawal sign assessment continued. Thereafter, toxicological profiles of the treatments were evaluated in the blood and in organs.Results:Chronic mitragynine treatment caused significant withdrawal behaviour lasting at least 5 days. Methadone, buprenorphine, as well as clonidine treatments significantly attenuated these withdrawal signs. No major effects on blood or organ toxicity were observed.Conclusion:These data suggest that the already available prescription medications methadone, buprenorphine, and clonidine are capable to alleviate mitragynine withdrawal signs rats. This may suggest them as treatment options also for problematic mitragynine/kratom use in humans.
Species-Specific Effects of Cation Channel TRPM4 Small-Molecule Inhibitors
Authors: Arullampalam Prakash , Preti Barbara , Ross-Kaschitza Daniela , Lochner Martin , Rougier Jean-Sébastien , Abriel Hugues 
Published: July 2021

Background: The Transient Receptor Potential Melastatin member 4 (TRPM4) gene encodes a calcium-activated non-selective cation channel expressed in several tissues. Mutations in TRPM4 have been reported in patients with different types of cardiac conduction defects. It is also linked to immune response and cancers, but the associated molecular mechanisms are still unclear. Thus far, 9-phenanthrol is the most common pharmacological compound used to investigate TRPM4 function. We recently identified two promising aryloxyacyl-anthranilic acid compounds (abbreviated CBA and NBA) inhibiting TRPM4. However, all aforementioned compounds were screened using assays expressing human TRPM4, whereas the efficacy of mouse TRPM4 has not been assessed. Mouse models are essential to investigate ion channel physiology and chemical compound efficacy.Aim: In this study, we performed comparative electrophysiology experiments to assess the effect of these TRPM4 inhibitors on human and mouse TRPM4 channels heterologously expressed in TsA-201 cells.Methods and Results: We identified striking species-dependent differences in TRPM4 responses. NBA inhibited both human and mouse TRPM4 currents when applied intracellularly and extracellularly using excised membrane patches. CBA inhibited human TRPM4, both intracellularly and extracellularly. Unexpectedly, the application of CBA had no inhibiting effect on mouse TRPM4 current when perfused on the extracellular side. Instead, its increased mouse TRPM4 current at negative holding potentials. In addition, CBA on the intracellular side altered the outward rectification component of the mouse TRPM4 current. Application of 9-phenanthrol, both intracellularly and extracellularly, inhibited human TRPM4. For mouse TRPM4, 9-phenanthrol perfusion led to opposite effects depending on the site of application. With intracellular 9-phenanthrol, we observed a tendency towards potentiation of mouse TRPM4 outward current at positive holding potentials.Conclusion: Altogether, these results suggest that pharmacological compounds screened using “humanised assays” should be extensively characterised before application in vivo mouse models.
Sex Differences in Exercise-Training-Related Functional and Morphological Adaptation of Rat Gracilis Muscle Arterioles
Authors: Merkely Petra , Bakos Marcell , Bányai Bálint , Monori-Kiss Anna , Horváth Eszter M. , Bognár Judit , Benkő Rita , Oláh Attila , Radovits Tamás , Merkely Béla , Ács Nándor , Nádasy György L. , Török Marianna , Várbíró Szabolcs 
Published: July 2021

BackgroundThe cardiovascular effects of training have been widely investigated; however, few studies have addressed sex differences in arteriolar adaptation. In the current study, we examined the adaptation of the gracilis arterioles of male and female rats in response to intensive training.MethodsWistar rats were divided into four groups: male exercise (ME) and female exercise (FE) animals that underwent a 12-week intensive swim-training program (5 days/week, 200 min/day); and male control (MC) and female control (FC) animals that were placed in water for 5 min daily. Exercise-induced cardiac hypertrophy was confirmed by echocardiography. Following the training, the gracilis muscle arterioles were prepared, and their biomechanical properties and functional reactivity were tested, using pressure arteriography. Collagen and smooth muscle remodeling were observed in the histological sections.ResultsLeft ventricular mass was elevated in both sexes in response to chronic training. In the gracilis arterioles, the inner radius and wall tension increased in female animals, and the wall thickness and elastic modulus were reduced in males. Myogenic tone was reduced in the ME group, whereas norepinephrine-induced vasoconstriction was elevated in the FE group. More pronounced collagen staining was observed in the ME group than in the MC group. Relative hypertrophy and tangential stress of the gracilis arterioles were higher in females than in males. The direct vasoconstriction induced by testosterone was lower in females and was reduced as an effect of exercise in males.ConclusionThe gracilis muscle arteriole was remodeled as a result of swim training, and this adaptation was sex dependent.
Cecal Ligation and Puncture-Induced Sepsis Promotes Brown Adipose Tissue Inflammation Without Any Impact on Expression of Thermogenic-Related Genes
Authors: Moreno-Navarrete José María , Comas Ferran , de Jager Vincent , Fernández-Real José Manuel , Bouma Hjalmar R. 
Published: July 2021

Background and Aims: The negative effects of chronic low-level inflammation on adipose tissue physiology have been extensively demonstrated, whereas the effects of acute inflammation are less studied. Here, we aimed to investigate the effects of sepsis-induced acute inflammation on gene expression markers of brown and white adipose tissue functionality.Methods: Brown adipose tissue (BAT) and perirenal white adipose tissue (prWAT) gene expression markers were analyzed in cecal ligation and puncture (CLP)-induced sepsis mice model.Results: CLP-induced sepsis attenuated expression of adipogenesis-related genes, in parallel to increased Tnf, Il6, and Ltf gene expression in prWAT. In contrast, CLP-induced sepsis resulted in increased expression of pro-inflammatory genes (Il6, Ltf, and Lbp) in BAT, without affecting expression of genes encoding for thermogenic activity.Conclusion: Sepsis promotes both prWAT and BAT inflammation, associated with reduced adipogenesis-related gene expression in prWAT, without significant effects on BAT thermogenic genes.
What Type of Body Shape Moves Children? An Experimental Exploration of the Impact of Narrative Cartoon Character Body Shape on Children’s Narrative Engagement, Wishful Identification, and Exercise Motivation
Authors: Alon Dar , Sousa Caio Victor , Lu Amy Shirong 
Published: July 2021

BackgroundThe incorporation of narratives helps to enhance children’s engagement in active video games (AVGs), thus increasing moderate-to-vigorous physical activity (MVPA). Specific narrative elements, such as the visual representation of the characters’ body shape, have been rarely manipulated to explore their role in modulating children’s narrative engagement (NE) and exercise motivation.ObjectiveTo investigate the effects of character body shape manipulation (overweight/obese, average, or athletic slim) on children’s narrative immersion (NI), NE, wishful identification (WI), as well as their mediating effect on AVG and PA motivation.MethodsChildren ages 8–12 years old (N = 87) were randomly assigned to watch a 15-min animated video (designed for an existing AVG) in which the main characters had an overweight/obese, or average∗, or athletic slim body shape (all other elements were identical). Children’s NI, NE, WI, and AVG and physical activity (PA) motivation were then assessed.ResultsControlling for social desirability, the analysis indicated that participants with a BMI of greater than the 75th percentile had a significantly higher NI, NE, WI, and PA motivation when video characters were set to the overweight/obese condition, than they did for video characters set to the average or athletic slim conditions. On the other hand, children of equal or less than the 75th percentile exposed to the average character body condition had a greater NE, WI, and PA motivation than overweight/obese or athletic slim conditions. A mediation analysis with structural equation modeling indicated that NE mediated the effect between character body shape and AVG and PA motivation.ConclusionNarrative cartoon characters that mirror the target participant’s body shape can increase NE, which in turn mediates AVG and PA motivation. Content producers should identify optimal strategies in character body shape design to encourage children of different weight status to participate in PA with engaging stories to maximize health narratives’ persuasive potentials.∗The term average in this sense is not in reference to the national average body weight, but rather an average of the body weights represented in conditions A and C.
Seasonal Patterns in Incidence and Antimicrobial Resistance of Common Bacterial Pathogens in Nursing Home Patients and Their Rooms
Authors: Cassone Marco , Mantey Julia , Gontjes Kyle J. , Lansing Bonnie J. , Gibson Kristen E. , Wang Joyce , Mody Lona 
Published: July 2021

Background: Colonization is the main precursor to infection, which may lead to adverse clinical outcomes among older adults in nursing homes (NHs). Understanding seasonal changes in the local burden of common bacterial pathogens is key to implementing appropriate and cost-effective infection prevention measures in this resource-constrained healthcare environment. It is thus surprising that seasonal trends in patient and environmental colonization with major bacterial pathogens are presently unknown in the expanding NH setting.Methods: We examined the seasonal incidence of four major pathogens among 640 nursing home patients and high-touch surfaces within their rooms over 2 years. In cases where a significant number of antimicrobial-resistant strains was found, incidence in antimicrobial-susceptible and antimicrobial-resistant isolates was compared, along with antibiotic use trends.Results: We observed spring peaks in the incidence of vancomycin-resistant enterococci (1.70 peak to trough ratio for both patient and environmental isolates) and methicillin-resistant Staphylococcus aureus (1.95 peak to trough ratio for patient isolates, 1.50 for environmental isolates). We also observed summer peaks in Klebsiella pneumoniae (1.83 and 1.82 peak to trough ratio for patient and environmental isolates, respectively), and ciprofloxacin-resistant Escherichia coli. Susceptible S. aureus and E. coli did not follow seasonal patterns.Conclusions: A meaningful seasonal pattern may be present in the NH setting for several significant pathogens, and especially antimicrobial-resistant ones. Whether such patterns are consistent across geographic areas and over longer periods of time should be a key focus of investigation, in order to better inform timing of surveillance and infection prevention efforts in this setting.
A New Strategy to Quantitatively Identify Hot-Spot Areas in Growth of New HIV Infections for Targeted Interventions
Authors: Zhu Qiyu , JiKe Chunnong , Xu Chengdong , Liang Shu , Yu Gang , Wang Ju , Xiao Lin , Liu Ping , Chen Meibin , Guan Peng , Liu Zhongfu , Jin Cong 
Published: July 2021

Background: Previous geographic studies of HIV infection have usually used prevalence data, which cannot indicate the hot-spot areas of current transmission. To develop quantitative analytic measures for accurately identifying hot-spot areas in growth of new HIV infection, we investigated the geographic distribution features of recent HIV infection and long-term HIV infection using data from a whole-population physical examination in four key counties in Liangshan prefecture, which are most severely affected by HIV in China.Methods: Through a whole-population physical examination during November 2017- June 2018 in the four key counties, a total of 5,555 HIV cases were diagnosed and 246 cases were classified as recently infected by laboratory HIV recency tests. The geospatial patterns of recent and long-term HIV infected cases were compared using ordinary least squares regression and Geodetector. Further, geospatial-heterogeneity was quantified and indicated using a residual map to visualize hot-spot areas where new infection is increasing.Results: The geographic location of HIV cases showed an uneven distribution along major roads and clustered at road intersections. The geographic mapping showed that several areas were clustered with more recently infected HIV cases than long-term infected cases. The quantitative analyses showed that the geospatial asymmetry between recent and long-term HIV infection was 0.30 and 0.31 in ordinary least squares regression and Geodetector analysis, respectively. The quantitative analyses found twenty-three townships showing an increase in the number of recent infections.Conclusions: Quantitative analysis of geospatial-heterogeneous areas by comparing between recent and long-term HIV infections allows accurate identification of hot-spot areas where new infections are expanding, which can be used as a potent methodological tool to guide targeted interventions and curb the spread of the epidemic.