bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of a novel, liver-targeted thyroid hormone receptor-β agonist, CS271011, in the treatment of lipid metabolism disorders
Authors: Lin Suwen , Huang Shengjian , Deng Zhou , Zhang Yu , Huang Lin , Wu Yanyi , Lv Shuyan , Wang Zhiyi , Huang Ning , Wang Lan , Chen Ziqi , Yu Guangyin , Yin Weihua , Zhou You , Fang Zhengyu 
Published: January 2023

IntroductionThyroid hormone receptor β (THR-β) plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, in this study, we discovered CS271011, a novel THR-β agonist, and assessed the safety and efficiency of CS271011 compared to MGL-3196 in vitro and in vivo. MethodsWe conducted luciferase reporter gene assays to assess the activation of THR-β and α in vitro. C57BL/6J mice were fed a high-fat diet for 12 weeks, CS271011 was administered by gavage at the dose of 1 mg/kg and 3 mg/kg, and MGL-3196 was administered at the dose of 3 mg/kg for 10 weeks. Body weight, food intake, serum and hepatic parameters, histological analysis, pharmacokinetic studies, RNA sequencing of the liver and heart, and expression of hepatic lipid-metabolic genes were determined to evaluate the safety and efficiency of CS271011. ResultsCompared with MGL-3196, CS271011 showed higher THR-β activation in vitro. In the diet-induced obesity mice model, CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. ConclusionsCS271011 is a potent and liver-targeted THR-β agonist for treating lipid metabolism disorders.
Finerenone in type 2 diabetes and renal outcomes: A random-effects model meta-analysis
Authors: Ghosal Samit , Sinha Binayak 
Published: January 2023

BackgroundThe nonsteroidal mineralocorticoid antagonist finerenone is a new addition to the list of agents (angiotensin converting enzyme inhibitors and sodium glucose cotransporter 2 inhibitors) conferring renal protection to patients with diabetic kidney disease. Two recent meta-analyses using the fixed effect model in patients with chronic kidney disease (both diabetic and nondiabetic populations) came to a conflicting conclusion on the effect of finerenone on eGFR decline. This meta-analysis was undertaken exclusively in the type 2 diabetes (T2D) population to explore the robustness and heterogeneity of the effect size by conducting a random effects model meta-analysis along with draft plots and prediction intervals.Materials and methodsA database search was conducted using the Cochrane library, PubMed, and Embase to identify relevant citations. Analysis was conducted on the 14th of September 2022, using RevMan 5.4.1 and RStudio (2022.07.1, Build 554). The hazard ratio was used as the effect size for the renal composite, while the standardized mean difference (SMD) was used to estimate the effect size of eGFR decline and reduction in the urine albumin creatinine ratio (UACR). The Cochrane risk-of-bias was used to assess the quality of the studies. The primary outcome assessed was the renal composite defined as kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes.ResultsA pooled population of 13,943 patients from four citations was included for analysis. The Cochrane risk of bias was used to assess the quality of the studies. There was a significant 16% reduction in the renal composite (kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes) [HR: 0.84, 95% CI 0.77-0.92, 2: 0, I2: 0%). Finerenone was also associated with reduction in UACR (SMD: -0.49, 95% CI -0.53 to -0.46, τ2: &lt; 0.0001, I2: 0%, prediction interval: -0.57 to -0.41) and prevention of decline in eGFR (SMD: -0.32, 95% CI -0.37 to -0.27, τ2: &lt; 0.0001, I2: 0%, prediction interval: -0.43 to -0.21) without any evidence for significant heterogeneity. Except for an increase in hyperkalaemia (RR: 2.22, 95% CI 1.93-2.24), adverse events were observed with fineronone compared to placebo (RR: 1.00, 95% CI 0.98-1.01).ConclusionThere are significant benefits in renal outcomes associated with finerenone treatment in T2D patients with established chronic kidney disease with a side effect profile comparable to placebo.
Determining factors in shaping the sustainable behavior of the generation Z consumer
Authors: Dragolea Larisa-Loredana , Butnaru Gina Ionela , Kot Sebastian , Zamfir Cristina Gabriela , Nuţă Alina-Cristina , Nuţă Florian-Marcel , Cristea Dragoş Sebastian , Ştefănică Mirela 
Published: January 2023

Introduction: Organizations currently emphasize green marketing strategies by implementing marketing practices, aiming to design, produce, promote and sell green products. Thus, both consumers and producers have turned their attention to the category of environmental friendly products, taking into account that the concept of green marketing is now being given greater importance. Responsible organizations have begun to adapt their strategies in production, promotion and interaction activities with consumers or potential consumers of organic products in the context we are going through, when environmental protection becomes an imperative. Analysis of the sustainable behavior of Generation Z is a determining factor from the perspective of the task that this generation will naturally take on, in terms of environmental responsibility.Methods: The research aims to determine the profile of the Generation Z consumer, in order to adapt the strategic actions of the government or organizations to direct and educate as objectively and efficiently as possible towards adopting the principles of ecological, sustainable and responsible consumption. Based on the data collected through a survey, we analyzed the sustainable behavior of Generation Z consumers studying at Romanian universities where there are specializations in this field. The research is quantitative, using structural equation modelling with partial least squares (PLSSEM) to test the hypotheses regarding the relationship between the determining factors and the sustainable behavior of Generation Z consumers.Results and Discussion: The results show that there is a positive relationship between both the sustainable behavior of Generation Z consumers and the satisfaction it conveys to them, as well as their environmental protection activities. However, there is no relationship between the sustainable behavior of Generation Z consumers and the green marketing practices of the organizations, environmental issues and their identification with the environmentally responsible consumer.
Assessment of the longitudinal humoral response in non-hospitalized SARS-CoV-2-positive individuals at decentralized sites: Outcomes and concordance
Authors: Djaïleb Abdelhadi , Lavallée Étienne , Parker Megan-Faye , Cayer Marie-Pierre , Desautels Florence , de Grandmont Marie Joëlle , Stuible Matthew , Gervais Christian , Durocher Yves , Trottier Sylvie , Boudreau Denis , Masson Jean-Francois , Brouard Danny , Pelletier Joelle N. 
Published: January 2023

IntroductionEarly in the COVID-19 pandemic, reagent availability was not uniform, and infrastructure had to be urgently adapted to undertake COVID-19 surveillance.MethodsBefore the validation of centralized testing, two enzyme-linked immunosorbent assays (ELISA) were established independently at two decentralized sites using different reagents and instrumentation. We compared the results of these assays to assess the longitudinal humoral response of SARS-CoV-2-positive (i.e., PCR-confirmed), non-hospitalized individuals with mild to moderate symptoms, who had contracted SARSCoV-2 prior to the appearance of variants of concern in Québec, Canada.ResultsThe two assays exhibited a high degree of concordance to identify seropositive individuals, thus validating the robustness of the methods. The results also confirmed that serum immunoglobulins persist ≥ 6 months post-infection among non-hospitalized adults and that the antibodies elicited by infection cross-reacted with the antigens from P.1 (Gamma) and B.1.617.2 (Delta) variants of concern.DiscussionTogether, these results demonstrate that immune surveillance assays can be rapidly and reliably established when centralized testing is not available or not yet validated, allowing for robust immune surveillance.
Acute and long-term immune responses to SARS-CoV-2 infection in unvaccinated children and young adults with inborn errors of immunity
Authors: García-García Ana , Fortuny Claudia , Fumadó Victoria , Jordan Iolanda , Ruiz-López Laura , González-Navarro Europa Azucena , Egri Natalia , Esteve-Solé Ana , Luo Yiyi , Vlagea Alexandru , Cabedo Manel Monsonís , Launes Cristian , Soler Aleix , Codina Anna , Juan Manel , Pascal Mariona , Deyà-Martínez Angela , Alsina Laia 
Published: January 2023

PurposeTo describe SARS-CoV-2 infection outcome in unvaccinated children and young adults with inborn errors of immunity (IEI) and to compare their specific acute and long-term immune responses with a sex-, age-, and severity-matched healthy population (HC).MethodsUnvaccinated IEI patients up to 22 years old infected with SARS-CoV-2 were recruited along with a cohort of HC. SARS-CoV-2 serology and ELISpot were performed in the acute phase of infection (up to 6 weeks) and at 3, 6, 9, and 12 months.ResultsTwenty-five IEI patients (median age 14.3 years, min.-max. range 4.5-22.8; 15/25 males; syndromic combined immunodeficiencies: 48.0%, antibody deficiencies: 16.0%) and 17 HC (median age 15.3 years, min.-max. range 5.4-20.0; 6/17 males, 35.3%) were included. Pneumonia occurred in 4/25 IEI patients. In the acute phase SARS-CoV-2 specific immunoglobulins were positive in all HC but in only half of IEI in whom it could be measured (n=17/25): IgG+ 58.8% (10/17) (p=0.009); IgM+ 41.2% (7/17)(p&lt;0.001); IgA+ 52.9% (9/17)(p=0.003). Quantitative response (index) was also lower compared with HC: IgG IEI (3.1 ± 4.4) vs. HC (3.5 ± 1.5)(p=0.06); IgM IEI (1.9 ± 2.4) vs. HC (3.9 ± 2.4)(p=0.007); IgA IEI (3.3 ± 4.7) vs. HC (4.6 ± 2.5)(p=0.04). ELISpots positivity was qualitatively lower in IEI vs. HC (S-ELISpot IEI: 3/11, 27.3% vs. HC: 10/11, 90.9%; p=0.008; N-ELISpot IEI: 3/9, 33.3% vs. HC: 11/11, 100%; p=0.002) and also quantitatively lower (S-ELISpot IEI: mean index 3.2 ± 5.0 vs. HC 21.2 ± 17.0; p=0.001; N-ELISpot IEI: mean index 9.3 ± 16.6 vs. HC: 39.1 ± 23.7; p=0.004). As for long term response, SARS-CoV-2-IgM+ at 6 months was qualitatively lower in IEI(3/8, 37.5% vs. 9/10 HC: 90.0%; p=0.043), and quantitatively lower in all serologies IgG, M, and A (IEI n=9, 1.1 ± 0.9 vs. HC n=10, 2.1 ± 0.9, p=0.03; IEI n=9, 1.3 ± 1.5 vs. HC n=10, 2.9 ± 2.8, p=0.02; and IEI n=9, 0.6 ± 0.5 vs. HC n=10, 1.7 ± 0.8, p=0.002 –respectively) but there were no differences at remaining time points.ConclusionsOur IEI pediatric cohort had a higher COVID-19 pneumonia rate than the general age-range population, with lower humoral and cellular responses in the acute phase (even lower compared to the reported IEI serological response after SARS-CoV-2 vaccination), and weaker humoral responses at 6 months after infection compared with HC.
The incidence of vasovagal reactions during earlobe piercing
Authors: Xie Zi-ao , Zhang Kai-li , Han Fang , Tang Meng-yao , Chen Jue-wei , Liu Guang-peng 
Published: January 2023

BackgroundVasovagal reactions are common amongst patients with a fear of needles receiving injections or during venipuncture, but they are rarely studied in healthy people undergoing earlobe piercing. The purpose of this prospective study was to evaluate the incidence and the features of vasovagal reactions observed during earlobe piercing.MethodsThousand eight hundred and sixty six participants aged older than 13 years had their earlobes pierced in our department from January 2020 to January 2022. When vasovagal reactions occurred during the procedure (e.g., dizziness, pallor, diaphoresis, and faintness, etc.), they were recorded and more detailed demographic information was collected.ResultsA total of 196 cases of vasovagal reactions were reported in females amongst 1,866 participants, including 58 who actually lost consciousness during earlobe piercing. The incidence of vasovagal reactions and vasovagal syncope was 10.5 and 3.11% respectively. All syncopal reactions occurred in persons younger than 30 years.ConclusionVasovagal syncope is often very sudden and occurs without warning. Practitioners need to be familiar with these reactions, and prevent people from an unpredictable fall and subsequent injury during ear piercing.
A transcriptional activator from Rhizophagus irregularis regulates phosphate uptake and homeostasis in AM symbiosis during phosphorous starvation
Authors: Zhang Shuyuan , Nie Yuying , Fan Xiaoning , Wei Wei , Chen Hui , Xie Xianan , Tang Ming 
Published: January 2023

IntroductionPhosphorus (P) is one of the most important nutrient elements for plant growth and development. Under P starvation, arbuscular mycorrhizal (AM) fungi can promote phosphate (Pi) uptake and homeostasis within host plants. However, the underlying mechanisms by which AM fungal symbiont regulates the AM symbiotic Pi acquisition from soil under P starvation are largely unknown. Here, we identify a HLH domain containing transcription factor RiPho4 from Rhizophagus irregularis.MethodsTo investigate the biological functions of the RiPho4, we combined the subcellular localization and Yeast One-Hybrid (Y1H) experiments in yeasts with gene expression and virus-induced gene silencing approach during AM symbiosis.ResultsThe approach during AM symbiosis. The results indicated that RiPho4 encodes a conserved transcription factor among different fungi and is induced during the in planta phase. The transcription of RiPho4 is significantly up-regulated by P starvation. The subcellular localization analysis revealed that RiPho4 is located in the nuclei of yeast cells during P starvation. Moreover, knock-down of RiPho4 inhibits the arbuscule development and mycorrhizal Pi uptake under low Pi conditions. Importantly, RiPho4 can positively regulate the downstream components of the phosphate (PHO) pathway in R. irregularis.DiscussionIn summary, these new findings reveal that RiPho4 acts as a transcriptional activator in AM fungus to maintain arbuscule development and regulate Pi uptake and homeostasis in the AM symbiosis during Pi starvation.
Endometrial microbiota in women with and without adenomyosis: A pilot study
Authors: Lin Qi , Duan Hua , Wang Sha , Guo Zhengchen , Wang Sirui , Chang Yanan , Chen Chao , Shen Minghong , Shou Hejun , Zhou Chang 
Published: January 2023

IntroductionThe endometrial microbiota plays an essential role in the health of the female reproductive system. However, the interactions between the microbes in the endometrium and their effects on adenomyosis remain obscure.Materials and methodsWe profile endometrial samples from 38 women with (n=21) or without (n=17) adenomyosis to characterize the composition of the microbial community and its potential function in adenomyosis using 5R 16S rRNA gene sequencing.ResultsThe microbiota profiles of patients with adenomyosis were different from the control group without adenomyosis. Furthermore, analysis identified Lactobacillus zeae, Burkholderia cepacia, Weissella confusa, Prevotella copri, and Citrobacter freundii as potential biomarkers for adenomyosis. In addition, Citrobacter freundii, Prevotella copri, and Burkholderia cepacia had the most significant diagnostic value for adenomyosis. PICRUSt results identified 30 differentially regulated pathways between the two groups of patients. In particular, we found that protein export, glycolysis/gluconeogenesis, alanine, aspartate, and glutamate metabolism were upregulated in adenomyosis. Our results clarify the relationship between the endometrial microbiota and adenomyosis.DiscussionThe endometrial microbiota of adenomyosis exhibits a unique structure and Citrobacter freundii, Prevotella copri, and Burkholderia cepacia were identified as potential pathogenic microorganisms associated with adenomyosis. Our findings suggest that changes in the endometrial microbiota of patients with adenomyosis are of potential value for determining the occurrence, progression, early of diagnosis, and treatment oadenomyosis.
Lipid profiles in the cerebrospinal fluid of rats with 6-hydroxydopamine-induced lesions as a model of Parkinson’s disease
Authors: Qiu Jiewen , Peng Guoyou , Tang Yuting , Li Shiyin , Liu Zengfu , Zheng Jiayun , Wang Yunxin , Liu Hanqun , Wei Lijian , Su Yilin , Lin Yuwan , Dai Wei , Zhang Zhiling , Chen Xiang , Ding Liuyan , Guo Wenyuan , Zhu Xiaoqin , Xu Pingyi , Mo Mingshu 
Published: January 2023

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disease with characteristic pathological abnormalities, including the loss of dopaminergic (DA) neurons, a dopamine-depleted striatum, and microglial activation. Lipid accumulation exhibits a close relationship with these pathologies in PD.MethodsHere, 6-hydroxydopamine (6-OHDA) was used to construct a rat model of PD, and the lipid profile in cerebrospinal fluid (CSF) obtained from model rats was analyzed using lipidomic approaches.ResultsEstablishment of this PD model was confirmed by apomorphine-induced rotation behaviors, loss of DA neurons, depletion of dopamine in the striatum, and microglial activation after 6-OHDA-induced lesion generation. Unsupervised and supervised methods were employed for lipid analysis. A total of 172 lipid species were identified in CSF and subsequently classified into 18 lipid families. Lipid families, including eicosanoids, triglyceride (TG), cholesterol ester (CE), and free fatty acid (FFA), and 11 lipid species exhibited significantly altered profiles 2 weeks after 6-OHDA administration, and significant changes in eicosanoids, TG, CE, CAR, and three lipid species were noted 5 weeks after 6-OHDA administration. During the period of 6-OHDA-induced lesion formation, the lipid families and species showed concentration fluctuations related to the recovery of behavior and nigrostriatal abnormalities. Correlation analysis showed that the levels of eicosanoids, CE, TG families, and TG (16:0_20:0_18:1) exhibited positive relationships with apomorphine-induced rotation behaviors and negative relationships with tyrosine hydroxylase (TH) expression in the midbrain.ConclusionThese results revealed that non-progressive nigrostriatal degeneration induced by 6-OHDA promotes the expression of an impairment-related lipidomic signature in CSF, and the level of eicosanoids, CE, TG families, and TG (16:0_20:0_18:1) in CSF may reveal pathological changes in the midbrain after 6-OHDA insult.
A retrospective evaluation of the Brain and Body Fitness Studio service on functional capacity and quality of life in people with neurological disorders
Authors: Ramos Joyce S. , Chakraborty Ranjay , Dalleck Lance C. , Sarunic Kristina , Khadka Jyoti , Haslam Tayla , Nassaris Olivia 
Published: January 2023

BackgroundPeople with neurological disorders (ND) are less physically active than the general population due to physical, sensory, and/or cognitive impairments. These individuals often feel intimidated to join mainstream health and wellness centers due to lack of specialized support for people with ND. The Brain and Body Fitness Studio (BBFS) is one of the first Accredited Exercise Physiologist-led interprofessional services in Adelaide South Australia to provide individualized evidence-based multimodal exercise prescription and social support for this population. This comprehensive retrospective study evaluated the impact of BBFS on functional capacity (FC) determined as the 6-min walk distance (6 MWD) achieved during a 6-min walk test (6 MWT), of its members with ND.MethodsSixty-two BBFS members (age, 66 ± 10 years; 60% male) with ND (85% Parkinson's Disease; average time since diagnosis, 4 years [IQR, 2 to 12 years]) and complete pre- and post-6-month clinical assessment of the primary outcome of the study, the 6 MWD, were included in this retrospective analysis. A series of sub-analyses were also performed to investigate the effects of adherence to the recommended prescription of at least twice a week in the program (≥80 vs. &lt; 80% adherence), and disease stage (time since diagnosis; ≥6 vs. &lt; 6 years) on FC.ResultsAlthough there was no statistically significant change in 6 MWD from pre- to post-6-month BBFS program (+15 ± 90 m,p= 0.19), a clinically meaningful improvement of &gt;14 m was evident. Improvement in 6 MWD was significantly greater in members who attended at least 80% of the recommended visits (≥80% visits, +37 ± 58 m; ≤ 80% visits,−1 ± 105 m,p= 0.046). We also found a 6 MWD improvement from pre- to post-6 months in those in the early years of their ND (&lt; 6 years since diagnosis, +39 ± 76 m), but not in those in the later years of their ND (≥6 years since diagnosis, −36 ± 123 m, between group difference,p= 0.029).ConclusionA clinically meaningful 6 MWD improvement may be elicited by services provided by BBFS in people with ND. Overall, the benefits appear to be more evident in members who attended the BBFS for at least 80% of the recommended visits and those who were in the early stage of their ND diagnosis.
Association of BDNF gene missense polymorphism rs6265 (Val66Met) with three quantitative traits, namely, intelligence quotient, body mass index, and blood pressure: A genetic association analysis from North India
Authors: Fatma Rafat , Chauhan Waseem , Shahi Mehdi Hayat , Afzal Mohammad 
Published: January 2023

BackgroundBrain-derived neurotrophic factor (BDNF), a neurotransmitter modulator, plays a significant role in neuronal survival and growth and participates in neuronal plasticity, thus being essential for learning, memory, and the development of cognition. Additionally, it is crucial for appetite, weight, and metabolic control and plays a pivotal role in the cardiovascular system. The Val66Met polymorphism (rs6265) of the BDNF gene causes a decrease in BDNF secretion and plays a role in impairments in cognition, energy homeostasis, and cardiovascular events. The present study aimed to evaluate the association of polymorphism (rs6265) of the BDNF gene with three quantitative traits simultaneously, namely, intelligence quotient (IQ), body mass index (BMI), and blood pressure (BP).MethodsPsychometric, morphometric, and physiometric data of the total participants (N = 246) were collected. WASI-IIINDIA was used to measure cognitive ability. Genotyping was carried out using allele-specific PCR for the rs6265 polymorphism (C196T), and genotypes were determined. Statistical analyses were performed at p &lt; 0.05 significance level using MS-Excel and SigmaPlot. The odds ratio models with a 95% confidence interval were used to test the associations. The used models are co-dominant, recessive, dominant, over–dominant, and additive.ResultsThe allelic frequencies of alleles C and T were 72 and 28%, respectively. Under the dominant genetic model, a significant susceptible association of minor allele T was observed with a lower average verbal comprehensive index (OR = 2.216, p = 0.003, CI (95%) =1.33–3.69), a lower average performance reasoning index (OR = 2.634, p &lt; 0.001, CI (95%) = 1.573–4.41), and a lower average full-scale IQ-4 (OR = 3.159, p &lt; 0.001, CI (95%) = 1.873–5.328). Carriers of Met-alleles were found to have an increased body mass index (OR = 2.538, p &lt; 0.001, CI (95%) = 1.507–4.275), decreased systolic blood pressure (OR = 2.051, p = 0.012, CI (95%) = 1.202–3.502), and decreased diastolic blood pressure (OR = 2.162, p = 0.006, CI (95%) = 1.278–3.657). Under the recessive genetic model, several folds decrease in IQ and BP and an increase in BMI with the presence of the T allele was also detected.ConclusionThis novel study may improve our understanding of genetic alterations to the traits and hence be helpful for clinicians and researchers to investigate the diagnostic and prognostic value of this neurotrophic factor.