Miracle-dz/UniFAR-FTUs huggingface dataset:
Number of medications and polypharmacy are associated with frailty in older adults: results from the Midlife in the United States study

Objectives The current study aimed to examine the association between the number of medications, polypharmacy, and frailty in community-dwelling older adults. In addition, the cutoff score for the number of medications related with frailty in this sample was determined. Methods A cross-sectional analysis was performed using data of 328 individual aged between 65 and 85 years from the Midlife in the United States (MIDUS 2): Biomarker Project, 2004–2009, a multisite longitudinal study, for 328 individuals aged between 65 and 85 years. All the participants were categorized into two groups based on the number of medications used: no polypharmacy (n = 206) and polypharmacy (n = 122). The polypharmacy was defined as having 5 or more medication per day. Frailty status was measured using a modified form of Fried frailty phenotype through the presences of the following indicators include low physical activity; exhaustion; weight loss; slow gait speed and muscle weakness. Participants were categorized into three different groups based on total score: 0 as robust, 1 to 2 as prefrail, 3 or more as frail. The relationship between no. of medications, polypharmacy, and frailty was examined using a multinomial logistic regression model. The model was adjusted for age, sex, BMI, and no. of chronic conditions. Receiver operator characteristics and area under the curve were used to determine the cutoff number of medications. Results Number of medications, and polypharmacy were associated with being frail (relative risk ratio [RRR]: 1.30; 95% confidence interval [CI]: [1.12, 1.50], p = 0.001), (RRR: 4.77; 95% CI [1.69, 13.4], p = 0.003), respectively. Number of medications with cutoff 6 medication or more was associated with being in frail category with sensitivity of 62% and specificity of 73%. Conclusion Polypharmacy was shown to be significantly related to frailty. A cutoff score of 6 or more medications distinguished frail from non-frail. Addressing polypharmacy in the older population might ameliorate the impact of physical frailty.
Early therapeutic effects of an Angiopoietin-1 mimetic peptide in middle-aged rats with vascular dementia

Background Vascular Dementia (VaD) refers to dementia caused by cerebrovascular disease and/or reduced blood flow to the brain and is the second most common form of dementia after Alzheimer’s disease. We previously found that in middle-aged rats subjected to a multiple microinfarction (MMI) model of VaD, treatment with AV-001, a Tie2 receptor agonist, significantly improves short-term memory, long-term memory, as well as improves preference for social novelty compared to control MMI rats. In this study, we tested the early therapeutic effects of AV-001 on inflammation and glymphatic function in rats subjected to VaD. Methods Male, middle-aged Wistar rats (10–12 m), subjected to MMI, were randomly assigned to MMI and MMI + AV-001 treatment groups. A sham group was included as reference group. MMI was induced by injecting 800 ± 200, 70–100 μm sized, cholesterol crystals into the internal carotid artery. Animals were treated with AV-001 (1 μg/Kg, i.p.) once daily starting at 24 h after MMI. At 14 days after MMI, inflammatory factor expression was evaluated in cerebrospinal fluid (CSF) and brain. Immunostaining was used to evaluate white matter integrity, perivascular space (PVS) and perivascular Aquaporin-4 (AQP4) expression in the brain. An additional set of rats were prepared to test glymphatic function. At 14 days after MMI, 50 μL of 1% Tetramethylrhodamine (3 kD) and FITC conjugated dextran (500 kD) at 1:1 ratio were injected into the CSF. Rats (4–6/group/time point) were sacrificed at 30 min, 3 h, and 6 h from the start of tracer infusion, and brain coronal sections were imaged using a Laser scanning confocal microscope to evaluate tracer intensities in the brain. Result Treatment of MMI with AV-001 significantly improves white matter integrity in the corpus callosum at 14 days after MMI. MMI induces significant dilation of the PVS, reduces AQP4 expression and impairs glymphatic function compared to Sham rats. AV-001 treatment significantly reduces PVS, increases perivascular AQP4 expression and improves glymphatic function compared to MMI rats. MMI significantly increases, while AV-001 significantly decreases the expression of inflammatory factors (tumor necrosis factor-α (TNF-α), chemokine ligand 9) and anti-angiogenic factors (endostatin, plasminogen activator inhibitor-1, P-selectin) in CSF. MMI significantly increases, while AV-001 significantly reduces brain tissue expression of endostatin, thrombin, TNF-α, PAI-1, CXCL9, and interleukin-6 (IL-6). Conclusion AV-001 treatment of MMI significantly reduces PVS dilation and increases perivascular AQP4 expression which may contribute to improved glymphatic function compared to MMI rats. AV-001 treatment significantly reduces inflammatory factor expression in the CSF and brain which may contribute to AV-001 treatment induced improvement in white matter integrity and cognitive function.
Retrieval of lunar polar heat flow from Chang’E-2 microwave radiometer and Diviner observations

The internal heat flow related to the Moon’s composition, interior structure, and evolution history is not well-constrained and understood on a global scale. Up to now, only two in situ heat flow experiments, Apollo 15 and 17 were deployed nearly 50 years ago. The measured high values of heat flow might be influenced by lateral heat at highland/mare boundaries and enhanced by heat production from radioactive elements enriched unit, and may also be disturbed by astronauts’ activities. In this study, we proposed a new method to retrieve heat flows at two permanently shadowed craters, Haworth and Shoemaker of the Moon’s south pole, from Chang’E-2 microwave radiometer data and Diviner observations. Our results show that the average heat flow is 4.9 ± 0.2 mW/m2. This provides a constraint for the bulk concentration of Thorium within the lunar south polar crust 656 ± 54 ppb, which helps us understand the Moon’s thermal evolution and differentiation.
The effects of sleep and targeted memory reactivation on the consolidation of relevant and irrelevant information

Introduction Sleep is assumed to facilitate the consolidation of new memories in an active process of covert reactivation of the underlying memory representations. Recent evidence suggests that this process is selective by favoring memories that are of future relevance, and can be externally triggered by learning-associated sensory cues presented during sleep [i.e., targeted memory reactivation (TMR)]. In the present study, we (1) set out to confirm the preferential sleep effect for relevant information, and then asked whether (2) simultaneous TMR of relevant and irrelevant information facilitates the advantage for relevant information, and (3) whether the preferential benefit of sleep and TMR for relevant information persists over time. Methods To test these questions, participants explicitly learned two sets of picture-location associations, of which one set was instructed (after encoding) to be relevant and the other to be irrelevant for later testing. In Experiment 1, memory was tested after ~12 h of night sleep (n = 28) or daytime wakefulness (n = 28) as well as again after ~1 week. Results Results showed overall better memory retention after sleep compared to wakefulness after 12 h as well as after 1 week. The relevant memories were overall retained better than the irrelevant memories. Interestingly, a trend toward a stronger sleep benefit for the relevant memories emerged after 1 week, although this effect failed to reach significance. In Experiment 2, learning of the relevant and irrelevant picture-location associations took place in the presence of an odor. During subsequent sleep, in the first phase of slow wave sleep (SWS), participants were either presented with the odor again (n = 23) or received an odorless vehicle (n = 20). Memory retention was assessed after the first SWS period (following awakening) as well as after ~one week. As in Experiment 1, relevant memories were overall retained better than irrelevant memories. However, TMR did not differentially affect the retention of relevant and irrelevant memories. Discussion These findings provide tentative evidence that the selective benefit of sleep for relevant memories evolves over time but is not further facilitated by TMR.
Factors and barriers that influence the matriculation of underrepresented students in medicine

Despite many initiatives over more than 4 decades, the diversity of United States physicians still does not reflect the diversity of the United States population. The present study undertakes a literature review of the last 30 years to investigate barriers and protective factors underrepresented college students encounter as applicants for medical school. Known barriers that influence matriculation into medical school were analyzed such as academic metrics and test scores. Additionally, elements that are less well studied were investigated such as factors perceived as barriers by underrepresented applicants in addition to protective factors that allow them to persist in their journey in the face of difficulties and adversity.
Parental control and adolescent internet addiction: the moderating effect of parent-child relationships

Introduction The present study investigated how maternal and paternal controls, including behavioral and psychological controls, predict adolescent Internet addiction, as well as the potential moderating effects of adolescent gender and parent-child relationships on the predictions. Methods Data were collected from 1,974 Chinese adolescents (age range = 14–22; mean = 16.47; SD = 0.87; 1,099 girls) in Guizhou Province, mainland China in November 2021. Internet addiction was measured using the ten-item Internet Addiction Test developed by Kimberly Young, and Parental control and parent-child relationships were measured by the respective subscales derived from the validated Chinese Parent-Child Subsystem Quality Scale. Results Hierarchical regression analyses revealed that after the covariates were statistically controlled, both parents' behavioral controls showed significant negative predictions on adolescent Internet addiction, while their psychological control tended to positively predict Internet addiction among adolescents, although the effect was only marginal. In addition, the impacts of maternal and paternal controls were equal, and such impacts did not vary between sons and daughters. While adolescent gender was not a significant moderator, the parent-child relationship quality significantly moderated the effects of paternal behavioral control, paternal psychological control, and maternal psychological control on adolescents' Internet addiction. Specifically, the prediction of paternal behavioral control was stronger while the effect of paternal and maternal psychological control was weaker among adolescents with a positive father-child relationship than those with a moderate or poor father-child relationship. Discussion These findings indicate the protective function of parents' behavioral control and the negative impact of psychological control on the development of adolescent Internet addiction. Further, a positive relationship between the father and the adolescent can strengthen the positive effect of paternal behavioral control and mitigate the negative effects of both parents' psychological controls.
Is sleep apnea truly associated with hearing loss? A nationwide, population-based study with STOP-BANG questionnaire

Objectives We aimed to investigate the effect of obstructive sleep apnea (OSA) on hearing ability. Methods We retrospectively reviewed the population-based survey data collected by the Korean National Health and Nutrition Examination Survey between January 1, 2019 and December 31, 2020. The data included 3,575 participants who completed the STOP-BANG questionnaire (SBQ) and pure-tone audiometry. OSA risk was assessed using the SBQ, and the hearing level was compared between the risk groups. Results Among the 3,575 participants, 2,152 (60.2%), 891 (24.9%), and 532 (14.9%) were classified as being low, intermediate, and high risk, respectively. The intermediate- and high-risk groups showed significantly worse hearing levels than the low-risk group. When age and sex were adjusted, the hearing level did not differ between the risk groups. Conclusion The study found that the presence of OSA minimally affected hearing level. Because hearing loss due to hypoxic damage develops over a long period of time, further research on the association between the duration of OSA, rather than the presence or severity of OSA, and hearing loss is needed.
Untargeted metabolomics approach and molecular networking analysis reveal changes in chemical composition under the influence of altitudinal variation in bamboo species

Bamboo species have traditionally been used as building material and potential source of bioactive substances, as they produce a wide variety of phenolic compounds, including flavonoids and cinnamic acid derivatives that are considered biologically active. However, the effects of growth conditions such as location, altitude, climate, and soil on the metabolome of these species still need to be fully understood. This study aimed to evaluate variations in chemical composition induced by altitudinal gradient (0–3000 m) by utilizing an untargeted metabolomics approach and mapping chemical space using molecular networking analysis. We analyzed 111 samples from 12 bamboo species collected from different altitudinal ranges using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). We used multivariate and univariate statistical analyses to identify the metabolites that showed significant differences in the altitude environments. Additionally, we used the Global Natural Products Social Molecular Networking (GNPS) web platform to perform chemical mapping by comparing the metabolome among the studied species and the reference spectra from its database. The results showed 89 differential metabolites between the altitudinal ranges investigated, wherein high altitude environments significantly increased the profile of flavonoids. While, low altitude environments significantly boosted the profile of cinnamic acid derivatives, particularly caffeoylquinic acids (CQAs). MolNetEnhancer networks confirmed the same differential molecular families already found, revealing metabolic diversity. Overall, this study provides the first report of variations induced by altitude in the chemical profile of bamboo species. The findings may possess fascinating active biological properties, thus offering an alternative use for bamboo.
Causal effects of gut microbiota on the risk of periodontitis: a two-sample Mendelian randomization study

Introduction The oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the development of periodontitis. However, the specific role of certain gut microbiota taxa for periodontitis has not been investigated. Mendelian Randomization is an ideal method to explore causal relationships avoiding reverse causality and potential confounding factors. Thus, we conducted a two-sample Mendelian Randomization study to comprehensively reveal the potential genetic causal effect of gut microbiota on periodontitis. Methods SNPs strongly associated with 196 gut microbiota taxa (18,340 individuals) were selected as instrument variables, and periodontitis (17,353 periodontitis cases and 28,210 controls) was used as the outcome. The causal effect was analyzed via random effect inverse variance-weighted, weighted median, and MR-Egger. The sensitivity analyses were conducted using Cochran’s Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. Results Nine gut microbiota taxa (Prevotella 7, Lachnospiraceae UCG-008, Enterobacteriales, Pasteurellales, Enterobacteriaceae, Pasteurellaceae, Bacteroidales S24.7 group, Alistipes, and Eisenbergiella) are predicted to play a causal role in enhancing the risk of periodontitis (p< 0.05). Besides, two gut microbiota taxa (Butyricicoccus and Ruminiclostridium 6) have potentially inhibitive causal effects on the risk of periodontitis (p< 0.05). No significant estimation of heterogeneity or pleiotropy is detected. Conclusion Our study demonstrates the genetic causal effect of 196 gut microbiota taxa on periodontitis and provides guidance for the clinical intervention of periodontitis.
3D macro- and microfabric analyses of Neoproterozoic diamictites from the Valjean Hills, California (United States)

The Cryogenian interval (720–635 Ma) is famous for a rich archive of diamictites, many of which were deposited during glaciations. Classic examples are exposed in the Kingston Peak Formation of the Valjean Hills, near Death Valley (United States), with previous work pointing to multiple glacial cycles in other outcrop belts. Within any glacial period, diamictites are widespread, and in addition, their mechanics of deposition are highly variable. Some are massive in appearance at outcrop or in hand specimens and apparently lack any information that allows their mode of emplacement to be elucidated. Yet, the correct interpretation for deep-time successions in this area is especially important, since it is debated whether the diamictites are either associated with a tectonically driven origin, associated with rifting at the south-western Laurentian margin alongside slope-controlled gravitational mass movement, or predominantly deposited as (sub)glacial diamictites. In this paper, we demonstrate how diamictite texture can be objectively quantified based on clast orientations, at both macroscale and microscale (micromorphology), guiding interpretations. Our method is based on a technique used for Quaternary sediments, by mapping the apparent longest axes of skeleton grains (ranging from fine-grained sand to fine-grained pebbles) in oriented thin sections and reconstructing their microfabric in a 3D space coupled with macrofabric data for each diamictite. In this way, we could identify a bimodal signal in the orientation of the longest axes for each sample. Evidence for shearing and soft sediment deformation supports either subaqueous or subglacial deposition with deformation induced by basal sliding with a paleoflow directed toward the southeast. Our combined approach of micro- and macrofabric analyses can also encourage acquiring accurate fabric data for seemingly structureless diamictites from other deep-time rock archives in an objective manner.
Learning adaptability facilitates self-regulated learning at school: the chain mediating roles of academic motivation and self-management

Studies have demonstrated that learning adaptability has emerged as an important factor for students’ utilization of self-regulated learning for successful learning, but how this association occurred is not clear yet. This study aimed to clarify the mechanism of the relationship between learning adaptability and self-regulated learning by investigating the chain mediating roles of academic motivation and self-management of 787 junior high school students under the “double reduction” background. The results showed that (1) learning adaptability had significant positive effects on junior high school students’ self-regulated learning and (2) academic motivation and self-management played independent and accumulative mediating roles in the relationship between learning adaptability and self-regulated learning. These findings help to understand how to support students in successfully coping with the new challenges brought by educational reform and promote effective adjustment to challenges, including the “double reduction. ” The key contribution of this study is to provide new insights into the literature that academic motivation and self-management separately and sequentially mediate the learning adaptability, self-regulated learning links, and learning adaptability is effective driver of self-regulated learning in the population of junior high school students.
Identification of a novel signature based on macrophage-related marker genes to predict prognosis and immunotherapeutic effects in hepatocellular carcinoma

Background Tumor-related macrophages (TAMs) have emerged as an essential part of the immune regulatory network in hepatocellular carcinoma (HCC). Constructing a TAM-related signature is significant for evaluating prognosis and immunotherapeutic response of HCC patients. Methods Informative single-cell RNA sequencing (scRNA-seq) dataset was obtained from the Gene Expression Omnibus (GEO) database, and diverse cell subpopulations were identified by clustering dimension reduction. Moreover, we determined molecular subtypes with the best clustering efficacy by calculating the cumulative distribution function (CDF). The ESTIMATE method, CIBERSORT (cell-type identification by estimating relative subsets of RNA transcripts) algorithm and publicly available tumor immune dysfunction and exclusion (TIDE) tools were used to characterize the immune landscape and tumor immune escape status. A TAM-related gene risk model was constructed through Cox regression and verified in multiple datasets and dimensions. We also performed functional enrichment analysis to detect potential signaling pathways related to TAM marker genes. Results In total, 10 subpopulations and 165 TAM-related marker genes were obtained from the scRNA-seq dataset (GSE149614). After clustering 3 molecular subtypes based on TAM-related marker genes, we found significantly different prognostic survival and immune signatures among the three subtypes. Subsequently, a 9-gene predictive signature (TPP1, FTL, CXCL8, CD68, ATP6V1F, CSTB, YBX1, LGALS3, and APLP2) was identified as an independent prognostic factor for HCC patients. Those patients with high RiskScore had a lower survival rate and benefited less from immunotherapy than those with low RiskScore. Moreover, more samples of the Cluster C subtype were enriched in the high-risk group, with higher tumor immune escape incidence. Conclusions We constructed a TAM-related signature with excellent efficacy for predicting prognostic survival and immunotherapeutic responses in HCC patients.
Application progress of CRISPR/Cas9 genome-editing technology in edible fungi

Edible fungi are not only delicious but are also rich in nutritional and medicinal value, which is highly sought after by consumers. As the edible fungi industry continues to rapidly advance worldwide, particularly in China, the cultivation of superior and innovative edible fungi strains has become increasingly pivotal. Nevertheless, conventional breeding techniques for edible fungi can be arduous and time-consuming. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) is a powerful tool for molecular breeding due to its ability to mediate high-efficiency and high-precision genome modification, which has been successfully applied to many kinds of edible fungi. In this review, we briefly summarized the working mechanism of the CRISPR/Cas9 system and highlighted the application progress of CRISPR/Cas9-mediated genome-editing technology in edible fungi, including Agaricus bisporus, Ganoderma lucidum, Flammulina filiformis, Ustilago maydis, Pleurotus eryngii, Pleurotus ostreatus, Coprinopsis cinerea, Schizophyllum commune, Cordyceps militaris, and Shiraia bambusicola. Additionally, we discussed the limitations and challenges encountered using CRISPR/Cas9 technology in edible fungi and provided potential solutions. Finally, the applications of CRISPR/Cas9 system for molecular breeding of edible fungi in the future are explored.