bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-99a-5p up-regulates LDLR and functionally enhances LDL-C uptake via suppressing PCSK9 expression in human hepatocytes
Authors: Chen Xuemei , Liu Ying , Zhou Qiujing , Zhang Chenxi , Wang Wei , Xu Menglong , Zhao Yaqiang , Zhao Wenfeng , Gu Dian , Tan Shuhua 
Published: November 2024

BackgroundMicroRNAs (miRs/miRNAs) play pivotal roles in modulating cholesterol homeostasis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR) at the surface of hepatocytes and accelerates its degradation in lysosomes, thereby impairing the clearance of circulating low-density lipoprotein cholesterol (LDL-C) from plasma. Thus, suppressing PCSK9 expression level has become an effective approach for treating hypercholesterolemia. Here, we sought to identify novel miRNAs that inhibit PCSK9 expression.MethodsBy in silico analyses, miR-99a-5p was predicted to bind to human PCSK9 mRNA. Following transfection of miR-99a-5p or anti-miR-99a-5p in human and mouse hepatocytes, qRT-PCR, Western blot, immunofluorescence, ELISA, flow cytometry, LDL-C uptake, and cellular cholesterol measurement were performed.ResultsmiR-99a-5p overexpression potently inhibited PCSK9 expression, thereby up-regulating LDLR, functionally enhancing LDL-C uptake and increasing intracellular cholesterol levels in human, but not in mouse, cells. Conversely, anti-miR-99a-5p upregulates PCSK9, leading to a reduction in LDLR, attenuation of LDL-C uptake, and a decrease in the intracellular cholesterol levels of human hepatocytes. Furthermore, miR-99a-5p was shown to bind to the predicted target site “UACGGGU” in the 3′-UTR of human PCSK9 mRNA via a luciferase reporter assay in combination with site-directed mutagenesis.ConclusionMiR-99a-5p potently downregulates the expression of PCSK9 by directly interacting with a target site in the human PCSK9 3′-UTR, thereby up-regulating LDLR and functionally enhancing LDL-C uptake in human hepatocytes. MiR-99a-5p could serve as an inhibitor of PCSK9 for treating hypercholesterolemia to inhibit atherosclerosis.
Stimulation of microneedles alleviates pathology of Parkinson’s disease in mice by regulating the CD4+/CD8+ cells from the periphery to the brain
Authors: Kim Jin Hee , Choi Yujin , Kim Jin Se , Lee Hanbyeol , Ju In Gyoung , Yoo Na Young , La Sookie , Jeong Do Hyeon , Na Changsu , Park Hi-Joon , Oh Myung Sook 
Published: November 2024

IntroductionImmune dysfunction is a major cause of neuroinflammation and accelerates the progression of Parkinson’s disease (PD). Numerous studies have shown that stimulation of specific acupuncture points (acupoints) can ameliorate PD symptoms. The purpose of this study was to investigate whether attaching microneedles to acupoints would improve PD pathology by recovering immune dysfunction.MethodsThe PD mouse model was induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA), and microneedle patches (MPs) or sham patches (SPs) were attached to GB20 and GB34, representative acupoints for treating PD for 14 days.ResultsFirst, the behavioral experiment showed that motor disorders induced by 6-OHDA were significantly improved by MP. Simultaneously, 6-OHDA-induced dopaminergic neuronal death and brain neuroinflammation decreased. Conversely, SP had no effect on behavioral disorders, neuronal death, or neuroinflammation. Measurement results from flow cytometry of immune cells in the brain and blood revealed a disruption in the CD4+/CD8+ ratio in the 6-OHDA group, which was significantly restored in the MP group. The brain mRNA expression of cytokines was significantly increased in the 6-OHDA group, which was significantly decreased by MP.DiscussionOverall, our results suggest that the attachment of MPs to GB20 and GB34 is a new method to effectively improve the pathology of PD by restoring peripheral and brain immune function.
Effect of fit-for-purpose biochars on rumen fermentation, microbial communities, and methane production in cattle
Authors: Martinez-Fernandez Gonzalo , Kinley Robert D. , Smith Wendy J. M. , Simington Jessica , Joseph Stephen , Tahery Sara , Durmic Zoey , Vercoe Phil 
Published: November 2024

IntroductionBiochar has gained significant attention as a possible anti-methanogenic supplement for ruminants due to its potential to reduce methane (CH₄) emissions from enteric fermentation. However, its effects on rumen methanogenesis have been inconsistent and, in some cases, contradictory. These variations are likely influenced by factors such as the type of biochar used, its source material, and how it is administered, including the form in which it is provided and the dosage needed to achieve desired outcomes. This study aimed to examine the effects of two fit-for-purpose biochars on rumen fermentation, CH4 emissions, and the rumen microbiome of cattle-fed roughage-based diets. Two experiments were conducted to assess the potential of biochar in mitigating CH4 emissions.Experiment 1This was a controlled pen trial conducted over 56 days, involving 12 steers that were fed Rhodes grass hay ad libitum. The animals were assigned to one of four treatment groups: control (no biochar, only molasses), low dose (50 g biochar/animal/day), mid dose (100 g biochar/animal/day), or high dose (200 g biochar/animal/day). Two types of biochar, Biochar 1 and Biochar 2, were administered with molasses (200 mL per animal/day). Methane emissions were measured using open-circuit respiration chambers, and rumen fluid samples were collected for analysis of the rumen microbial community and fermentation metabolite.Experiment 2In this trial, 45 heifers were selected and grazed together in a single paddock for 60 days to assess the effects of biochar on productivity and CH4 emissions under grazing conditions. The animals were allocated to one of three treatment groups (15 animals per group): control (no biochar, only molasses), Biochar 1, or Biochar 2. Each group was administered biochar at an estimated single dose of 100 g per animal/day mixed with molasses. Methane emissions were measured using GreenFeed systems in the field to monitor CH₄ production from individual animals.ResultsIn the controlled pen trial (Experiment 1), biochar supplementation resulted in a reduction of CH₄ emissions by 8.8–12.9% without any negative effects on rumen fermentation or dry matter intake (DMI). Minor changes were observed in the rumen bacterial community, particularly in the Christensenellaceae and Prevotellaceae families. However, in the grazing trial (Experiment 2), no significant differences in CH₄ emissions or productivity were detected with biochar supplementation.ConclusionWhile the results from controlled feeding conditions suggest that biochar has the potential to reduce enteric CH₄ emissions, the lack of significant findings under grazing conditions highlights the need for further research. Future studies should focus on identifying biochar types, doses, and delivery methods that are effective in reducing CH₄ emissions in grazing systems without compromising cattle productivity.
Genomic tools for post-elimination measles molecular epidemiology using Canadian surveillance data from 2018–2020
Authors: Hiebert Joanne , Zubach Vanessa , Schulz Helene , Severini Alberto 
Published: November 2024

IntroductionMeasles is caused by the highly infectious measles virus, MeV, for which there is an effective vaccine. Monitoring of progress of measles elimination requires enhanced surveillance and tracking of MeV strains, including documenting the absence of an endemically circulating strain. Due to a reduction in the number of circulating genotypes, additional sequence information, beyond the standardized 450 nucleotide window of the nucleoprotein (N450), is required to corroborate the information from epidemiological investigations and, ideally, fill in gaps in the surveillance data.MethodsThis study applies MeV sequencing tools, namely the N450, the non-coding region between the matrix and fusion genes (MF-NCR), and the complete coding sequence of the genome (WGS-t), to clinical specimens obtained from cases occurring over a three-year time period in Canada. This data was systematically analyzed, including with Bayesian evolutionary analysis by sampling trees (BEAST) of the WGS-t.Results and discussionOf the 143 reported cases, N450, MF-NCR, and WGS-t sequences were obtained from 101, 81, and 75 cases, respectively. The BEAST analysis confirmed that the two most frequently detected lineages (B3 named strain MVi/Marikina City.PHL/10.18 and D8 named strain MVs/Gir Somnath.IND/42.16) were the result of repeated importations. Of the 16 outbreaks occurring during the study period, the analysis conclusively corroborated the epidemiological information for 13. BEAST analysis of the WGS-t convincingly demonstrated the expansion of two outbreaks by the inclusion of additional contemporary cases for which the epidemiological investigation had been unable to identify links. Furthermore, the analysis revealed the existence of three additional unrecognized outbreaks among the cases categorized as unknown source. One outbreak was without WGS-t and could not be resolved.ConclusionMeasles WGS-t data corroborated and expanded upon the outbreak analysis from traditional epidemiological investigations of measles outbreaks. However, both are needed for fulsome investigations in elimination settings.
Learning-based object's stiffness and shape estimation with confidence level in multi-fingered hand grasping
Authors: Kutsuzawa Kyo , Matsumoto Minami , Owaki Dai , Hayashibe Mitsuhiro 
Published: November 2024

IntroductionWhen humans grasp an object, they are capable of recognizing its characteristics, such as its stiffness and shape, through the sensation of their hands. They can also determine their level of confidence in the estimated object properties. In this study, we developed a method for multi-fingered hands to estimate both physical and geometric properties, such as the stiffness and shape of an object. Their confidence levels were measured using proprioceptive signals, such as joint angles and velocity.MethodWe have developed a learning framework based on probabilistic inference that does not necessitate hyperparameters to maintain equilibrium between the estimation of diverse types of properties. Using this framework, we have implemented recurrent neural networks that estimate the stiffness and shape of grasped objects with their uncertainty in real time.ResultsWe demonstrated that the trained neural networks are capable of representing the confidence level of estimation that includes the degree of uncertainty and task difficulty in the form of variance and entropy.DiscussionWe believe that this approach will contribute to reliable state estimation. Our approach would also be able to combine with flexible object manipulation and probabilistic inference-based decision making.
The H-reflex study of the flexor carpi radialis muscle in healthy individuals
Authors: Mercan Metin , Kuruoğlu Reha 
Published: November 2024

ObjectiveThis study aimed to investigate the physiological and anatomical factors influencing the flexor carpi radialis (FCR) H-reflex and to establish reference values for FCR H-reflex parameters in relation to these factors.MethodsThe FCR H-reflexes, elicited by median nerve stimulation, were assessed in 80 healthy individuals both at rest and during isometric voluntary contraction (IVC). Multiple linear regression analyses were performed with H-reflex parameters as the dependent variables, while age, gender, height, arm length, and weight were included as independent variables.ResultsThe FCR H-reflex was recorded bilaterally in nearly all healthy individuals (76 out of 80) during IVC, while it could be obtained in only 35% (28 out of 80) of these individuals at rest. During IVC, the maximum H-reflex amplitude (Hmax) and its ratio to the maximum M-response amplitude (Hmax/Mmax ratio) were significantly increased (p &lt; 0.001). However, there were no changes in H-reflex latency, latency difference, conduction velocity (HRCV), or amplitude ratio (p &gt; 0.05). In both conditions, age and arm length were the most important factors affecting H-reflex latency (p &lt; 0.001), while HRCV was influenced only by age (p &lt; 0.01). Women exhibited shorter H-reflex latencies (p &lt; 0.01), and both Hmax amplitude and Hmax/Mmax ratio were higher in women during IVC (p &lt; 0.05). The H-reflex amplitude ratio during IVC showed a tendency to decrease with age (p &lt; 0.05).ConclusionThese findings suggest that FCR H-reflexes are more reliably elicited during IVC, and that both physiological and anatomical factors should be considered when assessing H-reflex abnormalities.
SMART-PET: a Self-SiMilARiTy-aware generative adversarial framework for reconstructing low-count [18F]-FDG-PET brain imaging
Authors: Raymond Confidence , Zhang Dong , Cabello Jorge , Liu Linshan , Moyaert Paulien , Burneo Jorge G. , Dada Michael O. , Hicks Justin W. , Finger Elizabeth , Soddu Andrea , Andrade Andrea , Jurkiewicz Michael T. , Anazodo Udunna C. 
Published: November 2024

IntroductionIn Positron Emission Tomography (PET) imaging, the use of tracers increases radioactive exposure for longitudinal evaluations and in radiosensitive populations such as pediatrics. However, reducing injected PET activity potentially leads to an unfavorable compromise between radiation exposure and image quality, causing lower signal-to-noise ratios and degraded images. Deep learning-based denoising approaches can be employed to recover low count PET image signals: nonetheless, most of these methods rely on structural or anatomic guidance from magnetic resonance imaging (MRI) and fails to effectively preserve global spatial features in denoised PET images, without impacting signal-to-noise ratios.MethodsIn this study, we developed a novel PET only deep learning framework, the Self-SiMilARiTy-Aware Generative Adversarial Framework (SMART), which leverages Generative Adversarial Networks (GANs) and a self-similarity-aware attention mechanism for denoising [18F]-fluorodeoxyglucose (18F-FDG) PET images. This study employs a combination of prospective and retrospective datasets in its design. In total, 114 subjects were included in the study, comprising 34 patients who underwent 18F-Fluorodeoxyglucose PET (FDG) PET imaging for drug-resistant epilepsy, 10 patients for frontotemporal dementia indications, and 70 healthy volunteers. To effectively denoise PET images without anatomical details from MRI, a self-similarity attention mechanism (SSAB) was devised. which learned the distinctive structural and pathological features. These SSAB-enhanced features were subsequently applied to the SMART GAN algorithm and trained to denoise the low-count PET images using the standard dose PET image acquired from each individual participant as reference. The trained GAN algorithm was evaluated using image quality measures including structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR), normalized root mean square (NRMSE), Fréchet inception distance (FID), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR).ResultsIn comparison to the standard-dose, SMART-PET had on average a SSIM of 0.984 ± 0.007, PSNR of 38.126 ± 2.631 dB, NRMSE of 0.091 ± 0.028, FID of 0.455 ± 0.065, SNR of 0.002 ± 0.001, and CNR of 0.011 ± 0.011. Regions of interest measurements obtained with datasets decimated down to 10% of the original counts, showed a deviation of less than 1.4% when compared to the ground-truth values.DiscussionIn general, SMART-PET shows promise in reducing noise in PET images and can synthesize diagnostic quality images with a 90% reduction in standard of care injected activity. These results make it a potential candidate for clinical applications in radiosensitive populations and for longitudinal neurological studies.
Effects of polyphenol-rich seed foods on lipid and inflammatory markers in patients with coronary heart disease: a systematic review
Authors: Jia Yatian , Wang Hui , Fan Wen , Lv Jie , Niu Qingmei , Zhu Ruifang , Zhang Qian 
Published: November 2024

BackgroundCoronary heart disease (CHD) is a prevalent cardiovascular condition, with its incidence and mortality rates steadily rising over time, posing a significant threat to human health. Studies have indicated that polyphenols exhibit a certain degree of protective effect against coronary heart disease. However, the findings regarding the impact of polyphenol-rich seed foods on patients with CHD have yielded inconsistent results.ObjectiveThis study investigated the effects of polyphenol-rich seed foods on blood lipids and inflammatory markers in patients with coronary heart disease.MethodsThe China National Knowledge Network, China Science and Technology Journal Database, China Biomedical Literature Database, Wanfang Database, PubMed, Cochrane Library, Embase, and Web of Science were searched for articles from the self-built database until March 16, 2024. The quality of the included studies was assessed using Edition 2 of the Cochrane Randomized Trials Risk Bias Tool, and data analysis was conducted using RevMan 5.4.ResultsThe study encompassed seven articles, with a total participation of 324 patients diagnosed with coronary heart disease. The study incorporated three seed foods abundant in polyphenols: Brazil nut, almond, and flaxseed. The meta-analysis findings revealed a significant reduction in triglyceride levels [MD = −20.03, 95% CI (−32.25, −17.44), p &lt; 0.00001] among patients diagnosed with coronary heart disease who incorporated seed-based foods abundant in polyphenols into their diet regimen. Furthermore, a notable enhancement was observed in HDL cholesterol levels [MD = 3.14, 95% CI (1.55, 4.72), p = 0.0001]. Moreover, the type of intervention substance influenced the observed effects. The consumption of almonds has been demonstrated to significantly reduce total cholesterol [MD = −15.53, 95% CI (−21.97, −9.1), p &lt; 0.00001] and LDL cholesterol [MD = −14.62, 95% CI (−20.92, −8.33), p &lt; 0.00001] in patients diagnosed with coronary heart disease. Additionally, the incorporation of flaxseed into the diet has shown an enhanced effect on reducing C-reactive protein levels.ConclusionThe consumption of polyphenol-rich seed foods can moderately improve TG and HDL-C levels in patients with coronary heart disease, while incorporating flaxseed into their diet can effectively improve inflammatory markers.
Gut microbiome’s causal role in head and neck cancer: findings from mendelian randomization
Authors: Lian Meng , Sun Minghong , Han Boxuan , Baranova Ancha , Cao Hongbao , Zhang Fuquan 
Published: November 2024

IntroductionThe gut microbiome (GM) has been implicated in cancer pathogenesis and treatment, including head and neck cancers (HNC). However, the specific microbial compositions influencing HNC and the underlying mechanisms remain largely unknown.MethodsThis study utilized published genome-wide association studies (GWAS) summary data-based two-sample Mendelian randomization (MR) to uncover the GM compositions that exert significant causal effects on HNC. Functional annotation and enrichment analysis were conducted to better understand the significant genetic variables and their connection with HNC. The HNC dataset included 2,281 cases and 314,193 controls. The GM GWAS data of 211 gut taxa (35 families, 20 orders, 16 classes, 9 phyla, and 131 genera) were obtained from the MibioGen consortium, involving 18,340 participants.ResultsMR analysis revealed four GM compositions exerting causal effects on HNC. Specifically, family Peptococcaceae.id.2024 was significantly associated with a 35% reduced risk of HNC (OR=0.65; 95%CI=0.48-0.90; P=0.0080). In contrast, genus DefluviitaleaceaeUCG-011.id.11287 (OR=1.54; 95%CI=1.13-2.09; P=0.0060), genus Gordonibacter.id.821 (OR=1.23; 95%CI=1.05-1.45; P=0.012), and genus Methanobrevibacter.id.123 (OR=1.28; 95%CI=1.01-1.62; P=0.040) showed a significant association with an increased risk of HNC. These GMs interact with genes and genetic variants involved in signaling pathways, such as GTPase regulation, influencing tumor progression and disease prognosis.ConclusionsOur study demonstrates, for the first time, the causal influence of specific gut microbiome compositions on HNC, offering significant insights for advancing clinical research and personalized treatments. The identified GMs may serve as potential biomarkers or therapeutic targets, paving the way for innovative approaches in HNC diagnosis, prevention, and therapy.
Socioeconomic inequalities in COVID-19 infection and vaccine uptake among children and adolescents in Catalonia, Spain: a population-based cohort study
Authors: López-Sánchez Irene , Perramon-Malavez Aida , Soriano-Arandes Antoni , Prats Clara , Duarte-Salles Talita , Raventós Berta , Roel Elena 
Published: November 2024

IntroductionThis study aims to investigate the relationship between deprivation, as measured by a socioeconomic deprivation index (SDI) score for census tract urban areas, and COVID-19 infections and vaccine uptake among children and adolescents before and after the vaccination rollout in Catalonia, Spain.MethodsWe conducted a population-based cohort study using primary care records. Individuals were followed 3 months before the start of the vaccination campaign in Spain and 3 months after. Children (5–11 years) and adolescents (12–15 years) with at least 1 year of prior history observation available and without missing deprivation data. For each outcome, we estimated cumulative incidence and crude Cox proportional-hazard models by SDI quintiles, and hazard ratios (HRs) of COVID-19 infection and vaccine uptake relative to the least deprived quintile, Q1.ResultsBefore COVID-19 vaccination rollout, 290,625 children and 179,685 adolescents were analyzed. Increased HR of deprivation was associated with a higher risk of COVID-19 infection in both children [Q5: 1.55 (95% CI, 1.47–1.63)] and adolescents [Q5: 1.36 (95% CI, 1.29–1.43)]. After the rollout, this pattern changed among children, with lower risk of infection in more deprived areas [Q5: 0.62 (95% CI, 0.61–0.64)]. Vaccine uptake was higher among adolescents than children, but in both age groups, non-vaccination was more common among those living in more deprived areas (39.3% and 74.6% in Q1 vs. 26.5% and 66.9% in Q5 among children and adolescents, respectively).ConclusionsChildren and adolescents living in deprived areas were at higher risk of COVID-19 non-vaccination. Socioeconomic disparities in COVID-19 infection were also evident before vaccine rollout, with a higher infection risk in deprived areas across age groups. Our findings suggest that changes in the association between deprivation and infections among children after the vaccine rollout were likely due to testing disparities.