Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma markers predict changes in amyloid, tau, atrophy and cognition in non-demented subjects

Abstract It is currently unclear whether plasma biomarkers can be used as independent prognostic tools to predict changes associated with early Alzheimer’s disease. In this study, we sought to address this question by assessing whether plasma biomarkers can predict changes in amyloid load, tau accumulation, brain atrophy and cognition in non-demented individuals. To achieve this, plasma amyloid-β 42/40 (Aβ42/40), phosphorylated-tau181, phosphorylated-tau217 and neurofilament light were determined in 159 non-demented individuals, 123 patients with Alzheimer’s disease dementia and 35 patients with a non-Alzheimer’s dementia from the Swedish BioFINDER-2 study, who underwent longitudinal amyloid (18F-flutemetamol) and tau (18F-RO948) PET, structural MRI (T1-weighted) and cognitive testing. Our univariate linear mixed effect models showed there were several significant associations between the plasma biomarkers with imaging and cognitive measures. However, when all biomarkers were included in the same multivariate linear mixed effect models, we found that increased longitudinal amyloid-PET signals were independently predicted by low baseline plasma Aβ42/40 (P = 0.012), whereas increased tau-PET signals, brain atrophy and worse cognition were independently predicted by high plasma phosphorylated-tau217 (P < 0.004). These biomarkers performed equally well or better than the corresponding biomarkers measured in the CSF. In addition, they showed a similar performance to binary plasma biomarker values defined using the Youden index, which can be more easily implemented in the clinic. In addition, plasma Aβ42/40 and phosphorylated-tau217 did not predict longitudinal changes in patients with a non-Alzheimer’s neurodegenerative disorder. In conclusion, our findings indicate that plasma Aβ42/40 and phosphorylated-tau217 could be useful in clinical practice, research and drug development as prognostic markers of future Alzheimer’s disease pathology.
Association of bullying behaviour with smoking, alcohol use and drug use among school students in Erbil City, Iraq.

Background Substance use and bullying are prevalent among adolescents and have a wide range of adverse outcomes. The association of bullying with substance use has not been examined in Kurdistan and Iraq, which have suffered from the effects of long-term conflict and economic hardship. Aims To examine the association between each form of bullying among adolescents and substance use. Methods This cross-sectional study was conducted in a sample of public schools in Erbil City, Iraq in 2017. The study involved 1070 adolescents selected from 35 schools using a multistage cluster sampling method. A self-reported close-ended questionnaire was used for data collection. Male and female students attending grades 7-12 and aged 13-18 years were included. Results The overall prevalence of bullying behaviour was 60.0%; 30.8% were victims, 26.2% were bully-victims, and 3.0% were bullies. There was a significant association between different forms and categories of bullying and substance use. The strongest association was with the students involved in sexual bullying, followed by racial and cyber bullying. The strongest association between bullying and substance use was found in the bully-victim category, followed by victims and bullies. Conclusions Substance use and bullying behaviour seem to be widespread problems among adolescents in Erbil schools. Substance use is significantly associated with different categories of bullying behaviour. There is a need for effective school-based preventive interventions to tackle these problems. Future research needs to examine the likely direction of the association between bullying and substance use.
Passing return‐to‐sport criteria and landing biomechanics in young athletes following anterior cruciate ligament reconstruction

We sought to evaluate the sagittal plane knee joint loading patterns during a double‐leg landing task among young athletes who passed or failed return‐to‐sport (RTS) criteria following anterior cruciate ligament reconstruction reconstruction (ACLR), and in uninjured athletes. Participants completed quadriceps strength testing, a hop test battery, and the International Knee Documentation Committee subjective form following medical RTS clearance. ACLR participants “passed” RTS criteria (RTS‐PASS) if they met ≥90 limb symmetry (%) or score on all measures and were categorized as “failing” (RTS‐FAIL) if not. All participants completed three‐dimensional motion analysis testing. Sagittal plane kinematic and kinetic variables were calculated during a double‐leg drop vertical jump task. Mean limb values and limb symmetry indices (LSI; %) were calculated and compared using a one‐way analysis of variance (ANOVA) (for LSI) and mixed between‐within ANOVA (for group × limb differences). A total of 205 participants were included, with 39 in the RTS‐PASS group, 109 in the RTS‐FAIL group, and 57 control groups (CTRLs). The RTS‐FAIL group demonstrated lower symmetry values for peak vertical ground reaction force, peak internal knee extension moment, and peak knee flexion angle. Group × limb interactions were observed for peak vertical ground reaction force and peak internal knee extension moment. Involved limb values were reduced in the RTS‐PASS and RTS‐FAIL groups compared to CTRLs, while the RTS‐PASS groups had lower uninvolved limb values compared to the RTS‐FAIL and CTRLs.
Histamine triggers microglial responses indirectly via astrocytes and purinergic signaling

Histamine is a monoaminergic neurotransmitter which is released within the entire brain from ascending axons originating in the tuberomammillary nucleus in a sleep state‐dependent fashion. Besides the modulation of neuronal firing patterns, brain histamine levels are also thought to modulate functions of glial cells. Microglia are the innate immune cells and professional phagocytes of the central nervous system, and histamine was previously shown to have multiple effects on microglial functions in health and disease. Isolated microglia respond only to agonists of the Hrh2 subtype of histamine receptors (Hrh), and the expression of that isoform is confirmed by a metadata analysis of microglia transcriptomes. When we studied the effect of the histamine receptor isoforms in cortical and thalamic microglia by in situ live cell Ca2+ imaging using a novel, microglia‐specific indicator mouse line, microglial cells respond to external histamine application mainly in a Hrh1‐, and to a lower extent also in a Hrh2‐dependent manner. The Hrh1 response was sensitive to blockers of purinergic P2ry12 receptors, and since Hrh1 expression was predominantly found in astrocytes, we suggest that the Hrh1 response in microglia is mediated by astrocyte ATP release and activation of P2ry12 receptors in microglia. Histamine also stimulates microglial phagocytic activity via Hrh1‐ and P2ry12‐mediated signaling. Taken together, we provide evidence that histamine acts indirectly on microglial Ca2+ levels and phagocytic activity via astrocyte histamine receptor‐controlled purinergic signaling.
On the encoding capacity of human motor adaptation.

Primitive-based models of motor learning suggest that adaptation occurs by tuning the responses of motor primitives. Based on this idea, we consider motor learning as an information encoding procedure, that is, a procedure of encoding a motor skill into primitives. The capacity of encoding is determined by the number of recruited primitives, which depends on how many primitives are "visited" by the movement, and this leads to a rather counter-intuitive prediction that faster movement, where a larger number of motor primitives are involved, allows learning more complicated motor skills. Here we provide a set of experimental results that support this hypothesis. First, we show that learning occurs only with movement, i.e., only with non-zero encoding capacity. When participants were asked to counteract a rotating force applied to a robotic handle, they were unable to do so when maintaining a static posture but were able to adapt when making small circular movements. Our second experiment further investigated how adaptation is affected by movement speed. When adapting to a simple (low-information-content) force field, fast (high-capacity) movement did not have an advantage over slow (low-capacity) movement. However, for a complex (high-information-content) force field, the fast movement showed a significant advantage over slow movement. Our final experiment confirmed that the observed benefit of high-speed movement is only weakly affected by mechanical factors. Taken together, our results suggest that the encoding capacity is a genuine limiting factor of human motor adaptation.
Mineralogy of Some Important Soils of Sone Basin

In the old alluvial soils representing Dulhingaon, Agiaon, Kapsandi and Suhiya series (Psammentic/Udic Haplustalfs and Typic Haplusterts) which have developed on alluvium derived from the rocks like granite-gneiss, basalt, quartzite, etc., the clay minerals seem to be geogenic and pedogenic. The dominance of kaolinite in upland soils of Dulhingaon series may be due to their acidic and well drained environment, while illite in the soils of Agiaon series is due to high K content. Mica and hydrous mica are found to be derived from feldspars. A portion of kaolinite seems to be inherited from the parent material. Some of the orthoclase feldspars appear to have weathered to kaolinite. The formation of smectite appears to be under basic environment, impeded drainage and waterlogging.
Correlation Development for the Effect of Metal Contaminants on the Thermal Stability of Jatropha curcas Biodiesel

The present paper deals with the study of the effect of metal contaminants on the thermal of Jatropha curcas biodisel (JSB). Talking pyrogallol(PY) as the most effective antioxidant based on the earlier work of the authors, JCB was mixed with different transtion metals, Fe, Ni, Mn, Co, and Cu, in different concentrations. Thermal stability parameters such as insoluble formation (Ins) and activation energy (Ea), were measured using American Society for Testing and Materials (ASTM) D6468 and stability in terms of Ins and Ea as a function of the antioxidant and metal concentrations A comparison between the experimental Ins and Ea values and those predicted by the correlation shows that about 95% of the predicted data points lie within +/- 10% deviation lines of the experimental results. This is the first study of its kind being reported showing the relationship of thermal stability with antioxidant concentration and metal contaminants. The correlations developed can be used to predict the amount of antioxidants required to stablize the JCB.
Perioperative pain management and opioid-reduction in head and neck endocrine surgery: An American Head and Neck Society Endocrine Surgery Section consensus statement.

BACKGROUND This American Head and Neck Society (AHNS) consensus statement focuses on evidence-based comprehensive pain management practices for thyroid and parathyroid surgery. Overutilization of opioids for postoperative pain management is a major contributing factor to the opioid addiction epidemic however evidence-based guidelines for pain management after routine head and neck endocrine procedures are lacking. METHODS An expert panel was convened from the membership of the AHNS, its Endocrine Surgical Section, and ThyCa. An extensive literature review was performed, and recommendations addressing several pain management subtopics were constructed based on best available evidence. A modified Delphi survey was then utilized to evaluate group consensus of these statements. CONCLUSIONS This expert consensus provides evidence-based recommendations for effective postoperative pain management following head and neck endocrine procedures with a focus on limiting unnecessary use of opioid analgesics.
Using Emerging Telehealth Technology as a Future Model in Vietnam During the COVID-19 Pandemic: Practical Experience From Phutho General Hospital

Telehealth has emerged as a model of modern technology for health care services in Vietnam during the COVID-19 pandemic. To actively prevent the outbreak of COVID-19 by using a national digital transformation program, the Vietnamese Ministry of Health launched project 2628/Quyet dinh-Bo y te, which approved a scheme for remote medical examinations and treatments for 2020 to 2025. The project aims to connect 1000 hospitals to strengthen the quality of medical services by using the expertise of central hospitals to support rural areas via provincial hospitals. Phutho General Hospital (PGH) is one of leading provincial hospitals that participated in and applied the early telehealth systems in Vietnam. By using telehealth systems, PGH can offer valuable support to doctors’ activities by streamlining and facilitating their work. Telehealth was demonstrated to be feasible, acceptable, and effective at PGH in Vietnam, and it resulted in considerable improvements in health care outcomes. The COVID-19 pandemic has facilitated the acceleration and enhancement of telehealth in Vietnam. The success of telehealth in Phutho may be a useful reference for other parts of the world. However, this telehealth system focuses on the connectivity among doctors rather than the connectivity between doctors and patients, which is an area that needs further assessment.
Racial and Sexual Minority Scholar Positionality: Advancing Health Status and Life Opportunity Among Sexual Minority Men of Color

Black and Latino sexual minority men (BLSMM) scholars are well positioned to draw on their unique perspectives and expertise to address the health status and life opportunities (HSLO) of BLSMM. Increasingly, research related to the positionality of scholars of color suggests that the scholar’s stance in relation to the community being researched has important implications for the research. Despite growing recognition of the importance of scholar positionality, limited attention has been paid to the relationship between scholar-of-color positionality and improving HSLO trajectories of BLSMM. Furthermore, extant literature fails to specify the mechanisms by which scholar-of-color positionality can improve HSLO among BLSMM. This article seeks to fill this gap in research by arguing that an inadequate consideration of scholar positionality in health and life opportunity research has important implications for the HSLO of BLSMM. A multilevel, mediational model addressing factors at the micro-level (i.e., intrapersonal resources)—BLSMM scholars’ personal commitments to BLSMM communities, cultural knowledge and expertise, and shared life experiences; meso-level (i.e., scholar and affected community interactions)—historical membership, mutual interdependency and trust, and community and organizational gatekeeping; and macro-level (i.e., national policies and priorities regarding BLSMM)—national priorities regarding the health and social welfare of BLSMM, allocation of BLSMM research and program funding, societal sentiment, and national investment in the workforce development of BLSMM scholars and clinicians are detailed. In conclusion, we identify recommendations and strategies for advancing scientific, programmatic, and policy efforts, aimed at improving HSLO among communities of BLSMM.
Anabolic effects of oral leucine-rich protein with and without β-hydroxybutyrate on muscle protein metabolism in a novel clinical model of systemic inflammation-a randomized crossover trial.

BACKGROUND β-lactoglobulin (BLG) stimulates muscle protein synthesis and β-hydroxybutyrate (BHB) inhibits muscle breakdown. Whether combining the 2 can additively attenuate disease-induced muscle loss is unknown. OBJECTIVE Based on previous observations of anticatabolic effects of protein and ketone bodies during inflammation, and using a novel model combining ongoing systemic inflammation, fasting, and immobilization, we tested whether the anticatabolic muscle response to oral amino acids is altered compared with control conditions, as well as whether coadministration of oral BHB and BLG further improves the muscle anabolic response. Muscle net balance (NBphe) was the primary outcome and intramyocellular signals were assessed. METHODS In a randomized crossover design, 8 young men underwent either preconditioning with LPS (prestudy day: 1 ng/kg, study day: 0.5 ng/kg) combined with a 36-h fast and bed rest to mimic catabolic inflammatory disease (CAT) or an overnight fast (control [CTR]) prior to isocaloric nutritional interventions on 3 occasions separated by ∼6 wk (range 42 to 83 d). RESULTS NBphe increased similarly upon all conditions (interaction P = 0.65). From comparable baseline rates, both Rdphe [muscle synthesis, median ratio (95% CI): 0.44 (0.23, 0.86) P = 0.017] and Raphe [muscle breakdown, median ratio (95% CI): 0.46 (0.27, 0.78) P = 0.005] decreased following BHB + BLG compared with BLG. BLG increased Rdphe more under CAT conditions compared with CTR (interaction P = 0.02). CAT increased inflammation, energy expenditure, and lipid oxidation and decreased Rdphe and anabolic signaling [mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E-binding protein 1 (4EPB1) phosphorylation]. CONCLUSION In contrast to our initial hypothesis, NBphe increased similarly following BLG during CAT and CTR conditions; CAT however, specifically stimulated the BLG-mediated increase in protein synthesis, whereas BHB coadministration did not affect NBphe, but distinctly dampened the BLG-induced increase in muscle amino acid fluxes thereby liberating circulating amino acids for anabolic actions elsewhere.
A size-shrinkable matrix metallopeptidase-2-sensitive delivery nanosystem improves the penetration of human programmed death-ligand 1 siRNA into lung-tumor spheroids

Abstract Given the maturation of small-interfering RNA (siRNA) techniques with nanotechnology, and because overexpression of human programmed death-ligand 1 (PD-L1) is crucial for T cell inactivation and immunosuppression of the tumor microenvironment, application of siRNA–PD-L1 has demonstrated positive progress in preclinical studies; however, the limited penetration of this compound into solid tumors remains a challenge. To decrease PD-L1 expression and increase the penetration efficacy of solid tumors, we synthesized a novel tumor-microenvironment-sensitive delivery polymer by conjugating hyaluronic acid (HA) to polyethyleneimine (PEI), with a matrix metalloproteinase-2 (MMP-2)-sensitive peptide acting as the linker (HA-P-PEI), for use in delivery of PD-L1–siRNA. Concurrent synthesis of a linker-less HA-PEI compound allowed confirmation that negatively charged siRNA can be complexed onto the positively charged HA-PEI and HA-P-PEI compounds to form nanoparticles with the same particle size and uniform distribution with serum stability. We found that the size of the HA-P-PEI/siRNA nanoparticles decreased to <10 nm upon addition of MMP-2, and that H1975 cells overexpressing CD44, PD-L1, and MMP-2 aided confirmation of the delivery efficacy of the HA-P-PEI/siRNA nanocomplexes. Additionally, the use of HA-P-PEI caused less cytotoxicity than PEI alone, demonstrating its high cellular uptake. Moreover, pretreatment with MMP-2 increased nanocomplex tumor permeability, and western blot showed that HA-P-PEI/PD-L1–siRNA efficiently downregulated the PD-L1 expression in H1975 cells. These results demonstrated a novel approach for siRNA delivery and tumor penetration for future clinical applications in cancer treatment.
A case-control study of thallium exposure with the risk of premature ovarian insufficiency in women

Abstract Thallium exposure has been associated with female reproductive health, but little is known about its potential association with premature ovarian insufficiency (POI). In this study, a total of 169 patients with POI and 209 healthy women were recruited from Zhejiang province, China. Urinary thallium concentrations were significantly positively associated with the risk of POI [adjusted odds ratio (OR) = 1.63, 95% CI: 1.25–2.13, p < 0.001], geometric mean values of which were significantly higher in POI cases (0.213 μg/L, 0.302 μg/g for creatinine adjustment) than those of controls (0.153 μg/L, 0.233 μg/g for creatinine adjustment). Furthermore, the serum levels of follicle-stimulating hormone and luteinizing hormone were positively associated with urinary thallium concentrations, whereas anti-Mullerian hormone and estradiol were negatively correlated with thallium. To the best of our knowledge, this is the first study to provide evidence that thallium exposure at currently environmental levels is the potential risk factor for POI in women.
Integrative analysis of colonic biopsies from inflammatory bowel disease patients identifies an interaction between microbial bile-acid inducible gene abundance and human Angiopoietin-like 4 gene expression.

BACKGROUND AND AIMS Microbial derived-bile acids can modulate host gene expression, and their fecal abundance is decreased in active inflammatory bowel disease (IBD). We analyzed the impact of endoscopic inflammation on microbial genes involved in bile acid biotransformation, and their interaction with host transcriptome in the intestinal mucosa of IBD patients. METHODS Endoscopic mucosal biopsies were collected from non-inflamed and inflamed terminal ileum, ascending and sigmoid colon of IBD patients. Prediction of imputed metagenome functional content from 16S rRNA profile and real-time qPCR were utilized to assess microbial bile acid biotransformation gene abundance, and RNA-seq was used for host transcriptome analysis. Linear regression and partial Spearman correlation accounting for age, sex and IBD type were used to assess the association between microbial genes, inflammation and host transcriptomics in each biopsy location. A Bayesian network (BN) analysis was fitted to infer the direction of interactions between IBD traits, microbial and host genes. RESULTS Inferred microbial gene pathway involved in secondary bile acid biosynthesis (ko00121 pathway) was depleted in inflamed terminal ileum of IBD patients compared to non-inflamed tissue. In non-inflamed sigmoid colon, the relative abundance of bile acid-inducible (baiCD) microbial genes was positively correlated with the host Angiopoietin-like 4 (Angptl4) gene expression. The BN analysis suggests that the microbial baiCD gene abundance could affect Angptl4 expression, and this interaction appears to be lost in the presence of inflammation. CONCLUSIONS Endoscopic inflammation affects the abundance of crucial microbial bile acid-metabolizing genes and their interaction with Angptl4 in intestinal mucosa of IBD patients.