Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional characterization of the schizophrenia associated gene AS3MT identifies a role in neuronal development

Genome‐wide association studies (GWAS) have identified multiple genomic regions associated with schizophrenia, although many variants reside in noncoding regions characterized by high linkage disequilibrium (LD) making the elucidation of molecular mechanisms challenging. A genomic region on chromosome 10q24 has been consistently associated with schizophrenia with risk attributed to the AS3MT gene. Although AS3MT is hypothesized to play a role in neuronal development and differentiation, work to fully understand the function of this gene has been limited. In this study we explored the function of AS3MT using a neuronal cell line (SH‐SY5Y). We confirm previous findings of isoform specific expression of AS3MT during SH‐SY5Y differentiation toward neuronal fates. Using CRISPR‐Cas9 gene editing we generated AS3MT knockout SH‐SY5Y cell lines and used RNA‐seq to identify significant changes in gene expression in pathways associated with neuronal development, inflammation, extracellular matrix formation, and RNA processing, including dysregulation of other genes strongly implicated in schizophrenia. We did not observe any morphological changes in cell size and neurite length following neuronal differentiation and MAP2 immunocytochemistry. These results provide novel insights into the potential role of AS3MT in brain development and identify pathways through which genetic variation in this region may confer risk for schizophrenia.
Older adults’ subjective experiences of the COVID-19 outbreak and lockdown in Italy: A qualitative study

Abstract Objective To evaluate the subjective experience of the COVID-19 outbreak in healthy older adults and develop a model of the older population’s psychological adaptation to the COVID-19 pandemic. Methods A qualitative grounded theory approach was taken to the study design and analysis, using semi-structured interviews to collect data from 19 community-active Italian older people by telephone during the first wave of COVID-19 (May 2020). Results The theory emerging from the study conceptualized the COVID-19 subjective experience in older people as an adjustment process to the disruption of habits, social contacts, and routines that prompted a meaning-making process to face this adverse experience. Three emergent categories included ‘loss, uncertainty, and distress’ as the psychological impact of the pandemic emergency, ‘making sense of COVID-19’ as a subjective sense-making process of the pandemic, and ‘living with the pandemic’ as agency and self-management within the pandemic experience. The resulting narratives encompassed themes, i.e. risk perception, representation of the self, connection with past-time memories, and compliance with safety measures. Conclusion The results have implications for designing effective messages to promote hope, social responsibility, and commitment in aging during the COVID-19 pandemic and for health workers who wish to support the psychological health of older adults.
Fertigation of Cool Season Turfgrass Species with Anaerobic Digestate Wastewater

Wastewater, uniquely derived from the anaerobic digestion of MSW and containing high contents of essential plant nutrients, was used as a primary N source for turfgrass cultivation. Creeping bentgrass (Agrostis palustris Huds.) and Kentucky bluegrass (Poa pratensis L.) were grown under controlled growth room conditions and fertilized with nutrient solution supplied from wastewater or from a commercial soluble turf fertilizer. Bentgrass supplied with wastewater-N grew similarly to those plants supplied with commercial-N in the second of three clipping harvests. In the third harvest, bentgrass supplied with wastewater-N slightly outperformed those fertilized with commercialN. In the first harvest of bentgrass, as well as with all three harvests of bluegrass, clipping yields were comparable up to the recommended N application rate of 25 kg N·ha -1 , while at higher rates, growth with commercial-N exceeded that with wastewater-N. Poor plant growth response at high rates of wastewater addition was related to high concentrations of soluble salts in the wastewater. Field trials were also conducted on three established turfgrass plots typical of PGA regulation turf. Green-area turf was treated with fertilizer solutions supplied at 25, 50, and 100 kg·ha -1 from each of commercial-N, wastewater-N, wastewater-N + calcium nitrate, or 50 kg·ha -1 of a granular control fertilizer. Landing- and rough-area turf received half of each of these rates of N. All turf areas receiving the recommended or lower rates of N performed as well with wastewater-N versus commercial-N. Response of shoot chlorophyll content followed a similar trend as clipping yields, while soil moisture and shoot color were not significant for any treatment on any area.
Fatty acids of type 2 diabetic serum decrease the stemness properties of human adipose‐derived mesenchymal stem cells

In type 2 diabetes, dyslipidemia and increased serum free fatty acids (FFAs) exacerbate the development of the disease through a negative effect on insulin secretion. Adipose‐derived mesenchymal stem cells (AdMSCs) play a key role in regenerative medicine, and these cells can potentially be applied as novel therapeutic resources in the treatment of diabetes. In this study, AdMSCs were treated with diabetic or nondiabetic serum FFAs isolated from women of menopausal age. Serum FFAs were analyzed using gas–liquid chromatography. The expression level of the stemness markers CD49e and CD90 and the Wnt signaling target genes Axin‐2 and c‐Myc were evaluated using real‐time PCR. The proliferation rate and colony formation were also assessed using a BrdU assay and crystal violet staining, respectively. The level of glutathione was assessed using cell fluorescence staining. Compared to nondiabetic serum, diabetic serum contained a higher percentage of oleate (1.5‐fold, p < 0.01). In comparison with nondiabetic FFAs, diabetic FFAs demonstrated decreasing effects on the expression of CD90 (−51%, p < 0.001) and c‐Myc (−48%, p < 0.05), and proliferation rate (−35%, p < 0.001), colony formation capacity (−50%, p < 0.01), and GSH levels (−62%, p < 0.05). The negative effect of the FFAs of diabetic serum on the stemness characteristics may impair the regenerative capabilities of AdMSCs.
Practice—Not Task Difficulty—Mediated the Focus of Attention Effect on a Speed-Accuracy Tradeoff Task

External focus (attention to the movement effect) has been found effective in motor performance and learning. However, while some investigators have suggested that the effect of attentional focus varies with task difficulty, others reported external focus benefits regardless of difficulty. We hypothesized that attentional focus effects would vary with practice, due to changes in the individual’s processing efficiency. We had three 20-person participant groups (external focus instructions, internal focus instructions, control) practice three difficulty levels of a Fitts reciprocal tapping task over two days. Participants in the external/internal focus groups were instructed to “mentally focus on moving the pen/your hand as fast and accurately as possible,” while control participants were instructed to “mentally focus only on doing your best to achieve the task goal. ” We then analyzed the effect of attentional focus by task difficulty at the initial performance (the beginning of the practice) and after learning (the retention/transfer phase), using movement time (MT) and number of error taps (Err) as performance measures. The internal focus group made more errors than the control group only at the retention/transfer phase. We found no error differences between the external and internal focus groups, and there were no MT differences between any groups. Our primary hypothesis about the differential effect of attentional focus by practice was supported. The attentional focus effect on Err differed in the retention/transfer phase from the immediate phase, suggesting that practice mediated the attentional focus effect. We discuss how information theory may supplement understanding of attentional focus interventions in motor skill acquisition.
A plant nonenveloped double-stranded RNA virus activates and co-opts BNIP3-mediated mitophagy to promote persistent infection in its insect vector

ABSTRACT Mitophagy that selectively eliminates damaged mitochondria is an essential mitochondrial quality control mechanism. Recently, mitophagy has been shown to be induced in host cells infected by a few animal viruses. Here, we report that southern rice black-streaked dwarf virus (SRBSDV), a plant nonenveloped double-stranded RNA virus, can also trigger mitophagy in its planthopper vector to prevent mitochondria-dependent apoptosis and promote persistent viral propagation. We find that the fibrillar structures constructed by the nonstructural protein P7-1 of SRBSDV directly target mitochondria via interaction with the mitophagy receptor BNIP3 (BCL2 interacting protein 3), and these mitochondria are then sequestered within autophagosomes to form mitophagosomes. Moreover, SRBSDV infection or P7-1 expression alone can promote BNIP3 dimerization on the mitochondria, and induce autophagy via the P7-1-ATG8 interaction. Furthermore, SRBSDV infection stimulates the phosphorylation of AMP-activated protein kinase (AMPK), resulting in BNIP3 phosphorylation via the AMPKα-BNIP3 interaction. Together, P7-1 induces BNIP3-mediated mitophagy by promoting the formation of phosphorylated BNIP3 dimers on the mitochondria. Silencing of ATG8, BNIP3, or AMPKα significantly reduces virus-induced mitophagy and viral propagation in insect vectors. These data suggest that in planthopper, SRBSDV-induced mitophagosomes are modified to accommodate virions and facilitate persistent viral propagation. In summary, our results demonstrate a previously unappreciated role of a viral protein in the induction of BNIP3-mediated mitophagy by bridging autophagosomes and mitochondria and reveal the functional importance of virus-induced mitophagy in maintaining persistent viral infection in insect vectors.Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy related; BNIP3: BCL2 interacting protein 3; CASP3: caspase 3; dsRNA: double strand RNA; ER: endoplasmic reticulum; FITC: fluorescein isothiocyanate; FKBP8: FKBP prolyl isomerase 8; FUNDC1: FUN14 domain containing 1; GFP: green fluorescent protein; GST: glutathione S-transferase; padp: post-first access to diseased plants; Phos-tag: Phosphate-binding tag; PINK1: PTEN induced kinase 1; Sf9: Spodoptera frugiperda; SQSTM1: sequestosome 1; SRBSDV: southern rice black-streaked dwarf virus; STK11/LKB1: serine/threonine kinase 11; TOMM20: translocase of outer mitochondrial membrane 20; RBSDV: rice black-streaked dwarf virus; TUNEL: terminal deoxynucleotidyl dUTP nick end labeling; ULK1: unc-51 like autophagy activating kinase 1; VDAC1: voltage dependent anion channel 1.
Analysis of Metric Sexing Determination of Dry Hip Bones in Eastern Nepalese People

Skeletal characteristics differ among individuals. Each population, therefore, possesses specific standards to optimize their identification accuracy. As certain features (e.g., bones of human body and enamel of tooth and skeletal) remain intact after death, these provide the precious tools for sexing of individuals in either the field of medicine or related to prehistoric osteological collections. As the sex hormones influence different reproductive function, the size-related sexual variations exist in nature remarkably. In contrast, the hip bone is an ideal bone to use for sex determination. In spite of their critical use, the findings for the determination of metric sexing with utilization of hip bones in Nepalese people still remain unknown. We, therefore, collected human hip bones and carried out the study to determination of metric sexing. Interestingly, our findings have made the present study of interest from anatomical, anthropological, and forensic points of views.
Clozapine Treatment Is Associated With Higher Prescription Rate of Antipsychotic Monotherapy and Lower Prescription Rate of Other Concomitant Psychotropics: A Real-World Nationwide Study

Abstract Background Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10−6). Conclusions Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.
Vaccination Intention and Behavior of the General Public in China: Cross-sectional Survey and Moderated Mediation Model Analysis

Background Promoting vaccination and eliminating vaccine hesitancy are key measures for controlling vaccine-preventable diseases. Objective We aimed to understand the beliefs surrounding and drivers of vaccination behavior, and their relationships with and influence on vaccination intention and practices. Methods We conducted a web-based survey in 31 provinces in mainland China from May 24, 2021 to June 15, 2021, with questions pertaining to vaccination in 5 dimensions: attitude, subjective norms, perceived behavioral control, intention, and behavior. We performed hierarchical regression analysis and structural equation modeling based on the theory of planned behavior—in which, the variables attitude, subjective norms, and intention each affect the variable intention; the variable intention mediates the relationships of attitude and subjective norms with behavior, and the variable perceived behavioral control moderates the strength of this mediation—to test the validity of the theoretical framework. Results A total of 9924 participants, aged 18 to 59 years, were included in this study. Vaccination intention mediated the relationships of attitude and subjective norms with vaccination behavior. The indirect effect of attitude on vaccination behavior was 0.164 and that of subjective norms was 0.255, and the difference was statistically significant (P<.001). The moderated mediation analysis further indicated that perceived behavioral control would affect the mediation when used as moderator, and the interaction terms for attitude (β=–0.052, P<.001) and subjective norms (β=–0.028, P=.006) with perceived behavioral control were significant. Conclusions Subjective norms have stronger positive influences on vaccination practices than attitudes. Perceived behavioral control, as a moderator, has a substitution relationship with attitudes and subjective norms and weakens their positive effects on vaccination behavior.
The implementation of a precision case management model in a Canadian inpatient rehabilitation center: The 12-months post-implementation findings of a quality improvement project

Despite recommendations, few have reported on quality improvement initiatives to implement length of rehabilitation stay benchmarks, while actively monitoring functional outcomes. This article describes the development, implementation, and evaluation of a precision case management model across all inpatient rehabilitation client groups in a Canadian facility. To develop the length of rehabilitation-stay (LoRS) benchmarks, patient data was retrospectively analyzed. A severity specific method was used to stratify median length of stay. A target reduction on 8.6 days in LoRS was established. Functional discharge targets were also set and monitored at specific intervals via the Functional Independence Measure (FIM®). The implementation used an incremental quality improvement phased approach. Following 12-months, a statistically significant reduction in mean LoRS of 13.2 days was achieved, along with a small increase in FIM® change across all rehabilitation client groups. A similar pattern was seen across the three main client groups, where a LoRS reduction greater than the target was achieved, along with important improvements in LoRS efficiency. This study demonstrates how the implementation of a precision case management model can assist a facility in markedly reducing LoRS across inpatient groups, without compromising functional change or community discharge rates and begin its transformation to a value-based organization.
A retrospective examination of changes in drinking motives during the early COVID-19 pandemic

Objective The COVID-19 pandemic has led to substantial changes in college student alcohol use. Changes in drinking motives may explain some of these changes in drinking patterns. The purpose of the present study is to explore how drinking motives and alcohol use have changed amongst college students considering the timeframes before and after the onset of COVID-19 pandemic (i.e., March 2020) in the United States. We hypothesized that there would be significant changes in drinking motives after March 2020, which would be significantly related to changes in alcohol use. Methods Participants for the current study were undergraduate students reporting lifetime alcohol use (n = 198, M age = 21.3, 66.7% female, 86.4% White) recruited through online advertisements in classes to complete an online survey in April 2020. Participants were asked to report on their drinking motives and alcohol use considering the timeframes before and after the onset of closures and stay-at-home orders during the COVID-19 pandemic (i.e., before and since March 2020). Results Paired samples t-tests revealed that endorsement of social (t[171) = 12.79, p < . 001, d = 1.16) and conformity motives significantly decreased (t[170] = 4.46, p < .001, d = 0.31), while endorsement of coping motives significantly increased (t[172] = -2.70, p = .008, d = .15) after the onset of COVID-19. Linear regression analyses, controlling for drinking motives before March 2020, revealed that changes in enhancement (β = -.47, p < .001) and coping motives (β = -.22, p = .04) were significantly associated with changes in alcohol use quantity. Conclusions Findings of the present study support the need for interventions to target coping and social drinking to reduce risk for alcohol use.
Matrix Vesicle–Mediated Mineralization and Potential Applications

Hard tissues, including the bones and teeth, are a fundamental part of the body, and their formation and homeostasis are critically regulated by matrix vesicle–mediated mineralization. Matrix vesicles have been studied for 50 y since they were first observed using electron microscopy. However, research progress has been hampered by various technical barriers. Recently, there have been great advancements in our understanding of the intracellular biosynthesis of matrix vesicles. Mitochondria and lysosomes are now considered key players in matrix vesicle formation. The involvement of mitophagy, mitochondrial-derived vesicles, and mitochondria–lysosome interaction have been suggested as potential detailed mechanisms of the intracellular pathway of matrix vesicles. Their main secretion pathway may be exocytosis, in addition to the traditionally understood mechanism of budding from the outer plasma membrane. This basic knowledge of matrix vesicles should be strengthened by novel nano-level microscopic technologies, together with basic cell biologies, such as autophagy and interorganelle interactions. In the field of tissue regeneration, extracellular vesicles such as exosomes are gaining interest as promising tools in cell-free bone and periodontal regenerative therapy. Matrix vesicles, which are recognized as a special type of extracellular vesicles, could be another potential alternative. In this review, we outline the recent significant progress in the process of matrix vesicle–mediated mineralization and the potential clinical applications of matrix vesicles for tissue regeneration.
Predicting Combined Effects of Chemical Stressors: Population‐Level Effects of Organic Chemical Mixtures with a Dynamic Energy Budget Individual‐Based Model

Most regulatory ecological risk‐assessment frameworks largely disregard discrepancies between the laboratory, where effects of single substances are assessed on individual organisms, and the real environment, where organisms live together in populations and are often exposed to multiple simultaneously occurring substances. We assessed the capability of individual‐based models (IBMs) with a foundation in the dynamic energy budget (DEB) theory to predict combined effects of chemical mixtures on populations when they are calibrated on toxicity data of single substances at the individual level only. We calibrated a DEB‐IBM for Daphnia magna for four compounds (pyrene, dicofol, α‐hexachlorocyclohexane, and endosulfan), covering different physiological modes of action. We then performed a 17‐week population experiment with D. magna (designed using the DEB‐IBM), in which we tested mixture combinations of these chemicals at relevant concentrations, in a constant exposure phase (7‐week exposure and recovery), followed by a pulsed exposure phase (3‐day pulse exposure and recovery). The DEB‐IBM was validated by comparing blind predictions of mixture toxicity effects with the population data. The DEB‐IBM accurately predicted mixture toxicity effects on population abundance in both phases when assuming independent action at the effect mechanism level. The population recovery after the constant exposure was well predicted, but recovery after the pulse was not. The latter could be related to insufficient consideration of stochasticity in experimental design, model implementation, or both. Importantly, the mechanistic DEB‐IBM performed better than conventional statistical mixture assessment methods. We conclude that the DEB‐IBM, calibrated using only single‐substance individual‐level toxicity data, produces accurate predictions of population‐level mixture effects and can therefore provide meaningful contributions to ecological risk assessment of environmentally realistic mixture exposure scenarios. Environ Toxicol Chem 2022;41:2240–2258. © 2022 SETAC