Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Genetically Informed Methods to Clarify the Nature of the Association Between Cannabis Use and Risk for Schizophrenia.

Cohort studies and meta-analyses have documented a robust association between cannabis use, heavy use, and misuse with future risk of schizophrenia.1-3 Despite adjusting for covariates, including current psychotic symptoms, other psychopathology, and social integration,1 the ability of these models to determine the degree to which cannabis causes schizophrenia is limited and dependent on their ability to capture all relevant confounders. When evaluating efforts to reduce cannabis use as a means of preventing schizophrenia, the proportion of this association that is causal is critical. Given the high heritability of schizophrenia, we reviewed reports that relied on 4 genetic methods (Table) capable of addressing the nature of the cannabisschizophrenia association. We evaluated 3 hypotheses: (1) it is entirely causal, (2) it is partly causal and partly confounded by genetic/familial effects and/or reverse causation, or (3) it is entirely noncausal. (We are unable to review the literature regarding short-term psychiatric effects of cannabis administration.9) Confounding here refers to genetic risks that increase the probability of both using/misusing cannabis and schizophrenia, thereby explaining at least part of the association. In this example, reverse causality refers to a theoretical underlying mechanism in which schizophrenia liability or symptoms increase the risk of using cannabis. The first 2 methods are natural experiments, discordant relative designs, and mendelian randomization, that directly evaluate each hypothesis. The 2 other methods, linkage disequilibrium score regression (LDSR) and polygenic risk scores (PRSs), measure genetic associations, which, although less definitive, provide evidence of correlated genetic risks that undermine the plausibility of hypothesis 1. Each hypothesis generates distinct expectations under each method (Table). Therefore, our approach determines which of the hypothetical expectations best fit the aggregate results. By examining multiple methods with different strengths and limitations, we attempt to triangulate the observed results hoping thereby to increase confidence in our conclusions.
Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis

Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway.
Molecular Fingerprint Imaging to Identify Dental Caries Using Raman Spectroscopy

Tooth loss impairs mastication, deglutition and esthetics and affects systemic health through nutritional deficiency, weight loss, muscle weakness, delayed wound healing, and bone fragility. Approximately 90% of tooth loss is due to dental caries and periodontal disease. Accordingly, early treatment of dental caries is essential to maintaining quality of life. To date, the clinical diagnosis of dental caries has been based on each dentist’s subjective assessment, but this visual method lacks objectivity. To improve diagnostic ability, highly sensitive quantitative methods have been developed for the diagnosis and prevention of dental caries and are gradually becoming a mandatory item in modern dentistry. High-resolution Raman spectroscopy is a suitable tool for recognizing the subtle structural changes that occur in dental enamel in already developed or, more importantly, incipient dental caries. Raman analysis could soon emerge as a breakthrough in dentistry because of its high diagnostic sensitivity. In this study, we build upon our previous findings in a new analysis of dental caries using Raman spectroscopy imaging and discuss the possibility of using Raman photonic imaging in support of objective diagnostics in dentistry. Our findings support the Raman method of caries detection in comparison with other conventional or new approaches.
Convolution Kernel Operations on a Two-Dimensional Spin Memristor Cross Array

In recent years, convolution operations often consume a lot of time and energy in deep learning algorithms, and convolution is usually used to remove noise or extract the edges of an image. However, under data-intensive conditions, frequent operations of the above algorithms will cause a significant memory/communication burden to the computing system. This paper proposes a circuit based on spin memristor cross array to solve the problems mentioned above. First, a logic switch based on spin memristors is proposed, which realizes the control of the memristor cross array. Secondly, a new type of spin memristor cross array and peripheral circuits is proposed, which realizes the multiplication and addition operation in the convolution operation and significantly alleviates the computational memory bottleneck. At last, the color image filtering and edge extraction simulation are carried out. By calculating the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) of the image result, the processing effects of different operators are compared, and the correctness of the circuit is verified.
Multifaceted impulsivity in obsessive-compulsive disorder with hoarding symptoms

Abstract Objective Hoarding is common in obsessive-compulsive disorder (OCD), and OCD with hoarding may have poorer prognostic features than OCD without hoarding. The aim of this study was to investigate the relationship between multifaceted impulsivity and hoarding symptoms in individuals with OCD. This relationship is important to be able to understand the psychopathological mechanisms of hoarding symptoms in OCD patients. Methods The study included 136 individuals with OCD classified as OCD with high hoarding symptoms (OCDwHH, n = 41) and OCD with low/none hoarding symptoms (OCDwLH, n = 95), together with 94 healthy control subjects. All the participants completed the Hoarding Rating Scale-Interview, Barratt Impulsiveness Scale-11, Yale-Brown Obsessions and Compulsions Scale, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. Results The OCDwHH group had more severe anxiety (p = 0.016) and attentional impulsivity (p = 0.002) than OCDwLH. Attentional impulsivity scores were positively correlated with hoarding symptom scores (p < 0.001). Both attentional and motor impulsivity scores were positively correlated with anxiety levels (p = 0.037, p = 0.045, respectively). In partial correlation analysis, motor impulsivity was positively correlated with the severity of hoarding symptoms controlling for anxiety severity (p = 0.045). In hierarchical linear regression analysis, only attentional impulsivity predicted the severity of hoarding symptoms independently of anxiety, severity of obsessive-compulsive symptoms and motor impulsivity (β = 0.268, Adjusted R 2 = 0.114, p = 0.006). Conclusion Attentional impulsivity is associated with hoarding symptoms in OCD. Future studies that reveal this relationship may contribute to treatment modalities for the OCD patients with hoarding symptoms.
Cabozantinib-based combination therapy for the treatment of hepatocellular carcinoma

Objective Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with limited treatment options. Cabozantinib, an orally bioavailable multikinase inhibitor is now approved by Food and Drug Administration (FDA) for HCC patients. We evaluated the therapeutic efficacy of cabozantinib, either alone or in combination, in vitro and in vivo. Design Human HCC cell lines and HCC mouse models were used to assess the therapeutic efficacy and targeted molecular pathways of cabozantinib, either alone or in combination with the pan-mTOR inhibitor MLN0128 or the checkpoint inhibitor anti-PD-L1 antibody. Results Cabozantinib treatment led to stable disease in c-Met/β-catenin and Akt/c-Met mouse HCC while possessing limited efficacy on Akt/Ras and c-Myc liver tumours. Importantly, cabozantinib effectively inhibited c-MET and ERK activity, leading to decreased PKM2 and increased p21 expression in HCC cells and in c-Met/β-catenin and Akt/c-Met HCC. However, cabozantinib was ineffective in inhibiting the Akt/mTOR cascade. Intriguingly, a strong inhibition of angiogenesis by cabozantinib occurred regardless of the oncogenic drivers. However, cabozantinib had limited impact on other tumour microenvironment parameters, including tumour infiltrating T cells, and did not induce programmed death-ligand 1 (PD-L1) expression. Combining cabozantinib with MLN0128 led to tumour regression in c-Met/β-catenin mice. In contrast, combined treatment with cabozantinib and the checkpoint inhibitor anti-PD-L1 antibody did not provide any additional therapeutic benefit in the four mouse HCC models tested. Conclusion c-MET/ERK/p21/PKM2 cascade and VEGFR2-induced angiogenesis are the primary targets of cabozantinib in HCC treatment. Combination therapies with cabozantinib and mTOR inhibitors may be effective against human HCC.
Hybrid Biocomposites Based on Poly(Lactic Acid) and Silica Aerogel for Food Packaging Applications

Bionanocomposites based on poly (lactic acid) (PLA) and silica aerogel (SiA) were developed by means of melt extrusion process. PLA-SiA composite films were plasticized with 15 wt. % of acetyl (tributyl citrate) (ATBC) to facilitate the PLA processability as well as to attain flexible polymeric formulations for films for food packaging purposes. Meanwhile, SiA was added in four different proportions (0.5, 1, 3 and 5 wt.%) to evaluate the ability of SiA to improve the thermal, mechanical, and barrier performance of the bionanocomposites. The mechanical performance, thermal stability as well as the barrier properties against different gases (carbon dioxide, nitrogen, and oxygen) of the bionanocomposites were evaluated. It was observed that the addition of 3 wt. % of SiA to the plasticized PLA-ATBC matrix showed simultaneously an improvement on the thermal stability as well as the mechanical and barrier performance of films. Finally, PLA-SiA film formulations were disintegrated in compost at the lab-scale level. The combination of ATBC and SiA sped up the disintegration of PLA matrix. Thus, the bionanocomposites produced here show great potential as sustainable polymeric formulations with interest in the food packaging sector.
Sleep and the athlete: narrative review and 2021 expert consensus recommendations

Elite athletes are particularly susceptible to sleep inadequacies, characterised by habitual short sleep (<7 hours/night) and poor sleep quality (eg, sleep fragmentation). Athletic performance is reduced by a night or more without sleep, but the influence on performance of partial sleep restriction over 1–3 nights, a more real-world scenario, remains unclear. Studies investigating sleep in athletes often suffer from inadequate experimental control, a lack of females and questions concerning the validity of the chosen sleep assessment tools. Research only scratches the surface on how sleep influences athlete health. Studies in the wider population show that habitually sleeping <7 hours/night increases susceptibility to respiratory infection. Fortunately, much is known about the salient risk factors for sleep inadequacy in athletes, enabling targeted interventions. For example, athlete sleep is influenced by sport-specific factors (relating to training, travel and competition) and non-sport factors (eg, female gender, stress and anxiety). This expert consensus culminates with a sleep toolbox for practitioners (eg, covering sleep education and screening) to mitigate these risk factors and optimise athlete sleep. A one-size-fits-all approach to athlete sleep recommendations (eg, 7–9 hours/night) is unlikely ideal for health and performance. We recommend an individualised approach that should consider the athlete’s perceived sleep needs. Research is needed into the benefits of napping and sleep extension (eg, banking sleep).
Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects

To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3‐month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug‐free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β‐guanidinopropionic acid, MitoQ, and 17‐dimethylaminoethylamino‐17‐demethoxygeldanamycin (17‐DMAG), but none of these led to a change in survival in either sex.
FSH Stimulation with Short Withdrawal Improves Oocyte Competence in Italian Mediterranean Buffalo (Bubalus bubalis)

Simple Summary The high embryo production cost in buffalo, compared to cattle, is currently the major factor limiting the commercial application of ovum pick-up and in vitro embryo production technologies. This is mainly due to the lower number of follicles that develop during each estrous cycle and consequently oocytes recovered per session. In this work, we tested two different hormonal treatments based on commercial follicle-stimulating hormone (FSH) and progesterone (P4) to enhance the number of follicles and competent oocytes. Furthermore, in the second experiment, we tested three different coasting times, i.e., periods between the last FSH administration and ovarian aspiration, which is known be the key period for the final oocyte maturation and competence acquisition. The results, in terms of number of aspirated follicles, oocyte quality, blastocyst yield, and superior quality blastocyst yield, allow us to suggest the use of high doses of FSH (40 mg given six times every 12 h) combined with the shorter coasting time (28–32 h) as the ideal protocol for ovarian superstimulation in buffalo. Abstract The aim of this work was to evaluate the efficiency of different FSH doses and FSH coasting times before ovum pick-up (OPU) on follicular growth and oocyte competence in buffalo. Experiment 1 involved two different FSH treatments: 40 mg FSH given three (FSH3) or six (FSH6) times, 2 days after dominant follicle removal were tested, with OPU carried out after 40–44 h of coasting. In experiment 2, OPU was carried out after FSH6 protocol followed by 28–32 h (C1), 40–44 h (C2), or 64–68 h (C3) of coasting time. Cumulus oocyte complexes (COCs) were classified, in vitro matured, fertilized, and cultured. The results demonstrated that FSH6 increased the total number of follicles, the number and percentages of medium and large follicles, the number and the proportion of good quality oocytes, and the number of grade 1,2 and fast-developing blastocysts compared to the control. C3 decreased the percentage of good quality oocyte and blastocyst rates compared to C1 and C2. A higher percentage of fast blastocysts and average number of grade 1,2 blastocysts was observed in C1 compared to C3, with intermediate values found in C2. The improved efficiency in terms of blastocyst yields suggests the use of FSH6 + C1 protocol for ovarian superstimulation in buffalo.
A simulation framework for bio-inspired sonar sensing with Unmanned Aerial Vehicles

We introduce a unified simulation framework that generates natural sensing environments and produces biosonar echoes under various sensing scenarios. This framework produces rich sensory data with environmental information completely known, thus can be used for the training of robotic algorithms for biosonar-based Unmanned Aerial Vehicles. The simulated environment consists of random trees with full geometry of the tree foliage. To simulate a single tree, we adopt the Lindenmayer system to generate the initial branching pattern and integrate that with the available measurements of the 3D computer-aided design object files to create natural-looking branches, sub-branches, and leaves. A forest is formed by simulating trees at random locations generated by using an inhomogeneous Poisson process. While our simulated environments can be generally used for testing other sensors and training robotic algorithms, in this study we focus on testing bat-inspired Unmanned Aerial Vehicles that recreate bat’s flying behavior through biosonar sensors. To this end, we also introduce an foliage echo simulator that produces biosonar echoes while mimicking bat’s biosonar system. We demonstrate the application of the proposed simulation framework by generating real-world scenarios with multiple trees and computing the resulting impulse responses under static or dynamic motions of an Unmanned Aerial Vehicle.
Somatosensory illusions elicited by sham electromagnetic field exposure: experimental evidence for a predictive processing account of somatic symptom perception.

OBJECTIVE According to the predictive processing theory of somatic symptom generation, body sensations are determined by somatosensory input and central nervous predictions about this input. We examined how expectations shape predictions and consequently bodily perceptions in a task eliciting illusory sensations as laboratory analogue of medically unexplained symptoms. METHODS Using the framework of signal detection theory, the influence of sham Wi-Fi on (i) response bias (c) and (ii) somatosensory sensitivity (d') for tactile stimuli was examined using the somatic signal detection task (SSDT). A healthy student sample (n = 83) completed the SSDT twice (sham Wi-Fi on/off) in a randomized order after watching a film that promoted adverse health effects of electromagnetic fields (EMF). RESULTS When expecting a Wi-Fi signal to be present, participants showed a significantly more liberal response bias c (p = .010, ηp = .08) for tactile stimuli in the SSDT as evidence of a higher propensity to experience somatosensory illusions. No significant alteration of somatosensory sensitivity d' (p = .76, ηp < .002) was observed. CONCLUSIONS Negative expectations about the harmfulness of EMF may foster the occurrence of illusory symptom perceptions via alterations in the somatosensory decision criterion. The findings are in line with central tenets of the predictive processing account of somatic symptom generation. This account proposes a decoupling of percept and somatosensory input so that perception becomes increasingly dependent on predictions. This biased perception is regarded as a risk factor for somatic symptom disorders.
PP2AB55δ Responsible for the High Initial Rates of Alcoholic Fermentation in Sake Yeast Strains of Saccharomyces cerevisiae

Sake yeast strain Kyokai no. 7 (K7) and its Saccharomyces cerevisiae relatives carry a homozygous loss-of-function mutation in the RIM15 gene, which encodes a Greatwall-family protein kinase. Disruption of RIM15 in non-sake yeast strains leads to improved alcoholic fermentation, indicating that the defect in Rim15p is associated with the enhanced fermentation performance of sake yeast cells. In order to understand how Rim15p mediates fermentation control, we here focused on target-of-rapamycin protein kinase complex 1 (TORC1) and protein phosphatase 2A with the B55Δ regulatory subunit (PP2AB55δ), complexes that are known to act upstream and downstream of Rim15p, respectively. Several lines of evidence, including our previous transcriptomic analysis data, suggested enhanced TORC1 signaling in sake yeast cells during sake fermentation. Fermentation tests of the TORC1-related mutants using a laboratory strain revealed that TORC1 signaling positively regulates the initial fermentation rate in a Rim15p-dependent manner. Deletion of the CDC55 gene encoding B55δ abolished the high fermentation performance of Rim15p-deficient laboratory yeast and sake yeast cells, indicating that PP2AB55δ mediates the fermentation control by TORC1 and Rim15p. The TORC1-Greatwall-PP2AB55δ pathway similarly affected the fermentation rate in the fission yeast Schizosaccharomyces pombe, strongly suggested that the evolutionarily conserved pathway governs alcoholic fermentation in yeasts. It is likely that elevated PP2AB55δ activity accounts for the high fermentation performance of sake yeast cells. Heterozygous loss-of-function mutations in CDC55 found in K7-related sake strains may indicate that the Rim15p-deficient phenotypes are disadvantageous to cell survival. IMPORTANCE The biochemical processes and enzymes responsible for glycolysis and alcoholic fermentation by the yeast S. cerevisiae have long been the subject of scientific research. Nevertheless, the factors determining fermentation performance in vivo are not fully understood. As a result, the industrial breeding of yeast strains has required empirical characterization of fermentation by screening numerous mutants through laborious fermentation tests. To establish a rational and efficient breeding strategy, key regulators of alcoholic fermentation need to be identified. In the present study, we focused on how sake yeast strains of S. cerevisiae have acquired high alcoholic fermentation performance. Our findings provide a rational molecular basis to design yeast strains with optimal fermentation performance for production of alcoholic beverages and bioethanol. In addition, as the evolutionarily conserved TORC1-Greatwall-PP2AB55δ pathway plays a major role in the glycolytic control, our work may contribute to research on carbohydrate metabolism in higher eukaryotes.