Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease

Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson’s disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for the potential therapeutic effects within cannabis represents a direct path forward for the generation of anti-PD drugs. Using an in silico database, literature reviews, and cell based assays, GB Sciences previously identified and patented a subset of five cannabinoids and five terpenes that could potentially recapitulate the anti-PD attributes of cannabis. While this work represents a critical step towards harnessing the anti-PD capabilities of cannabis, polypharmaceutical drugs of this complexity may not be feasible as therapeutics. In this paper, we utilize a reductionist approach to identify minimal essential mixtures (MEMs) of these components that are amenable to pharmacological formulation. In the first phase, cell-based models revealed that the cannabinoids had the most significant positive effects on neuroprotection and dopamine secretion. We then evaluated the ability of combinations of these cannabinoids to ameliorate a 6-hydroxydopmamine (OHDA)-induced change in locomotion in larval zebrafish, which has become a well-established PD disease model. Equimolar mixtures that each contained three cannabinoids were able to significantly reverse the OHDA mediated changes in locomotion and other advanced metrics of behavior. Additional screening of sixty-three variations of the original cannabinoid mixtures identified five highly efficacious mixtures that outperformed the original equimolar cannabinoid MEMs and represent the most attractive candidates for therapeutic development. This work highlights the strength of the reductionist approach for the development of ratio-controlled, cannabis mixture-based therapeutics for the treatment of Parkinson’s disease.
NUMERICAL AND ANALYTICAL SOLUTIONS OF NEUTRINO-DOMINATED ACCRETION FLOWS WITH A NON-ZERO TORQUE BOUNDARY CONDITION AND ITS APPLICATIONS IN GAMMA-RAY BURSTS

A stellar-mass black hole (BH) surrounded by a neutrino-dominated accretion flow (NDAF) has been discussed in a number of works as the central engine of gamma-ray bursts (GRBs). It is widely believed that NDAF cannot liberate enough energy for bright GRBs. However, these works have been based on the assumption of a “no torque” boundary condition, which is invalid when the disk is magnetized. In this paper, we present both numerical and analytical solutions for NDAFs with non-zero boundary stresses and reexamine their properties. We find that an NDAF with such a boundary torque can be powerful enough to account for those bright short GRBs, energetic long GRBs, and ultra-long GRBs. The disk becomes viscously unstable, which makes it possible to interpret the variability of GRB prompt emission and the steep decay phase in the early X-ray afterglow. Finally, we study the gravitational waves radiated from a processing BH-NDAF. We find that the effects of the boundary torque on the strength of the gravitational waves can be ignored.
Continuous professional development programmes for school principals in the 21st century: Lessons learned from educational leadership practices

Continuous professional development (CPD) is important for educational leaders to improve institutional performance and students’ learning outcomes. Yet, organizing effective professional development programmes are often more complex than we might assume. The current study aims to explore the challenges of managing CPD for high school principals in Indonesia. Six high school principals and three officers of the Ministry of Education and Cultures (MoEC) were interviewed. Qualitative data from the interviews were analyzed and coded thematically using ATLAS.ti. Several themes and main points emerged from the transcripts of interviews. The findings revealed some challenges in managing CPD programmes at schools. They include resistance to change, technicality and workload, almost zero follow-ups, unprofessional recruitment, and unclear training syllabus. Among the suggestions to improve the CPD programmes are building personal approaches, developing professional skills, establishing a professional recruitment system, making continuous training programmes, and optimizing school organizations. This study can be used as an additional guide to implement effective CPD and can be a platform to improve the professional development of educational leaders.
Relationship between irregular diet and risk of esophageal cancer: A meta-analysis

Background: Associations between irregular diet and the risk of esophageal cancer remain unclear. The current meta-analysis was performed to determine whether the presence of irregular diet increases the risk of esophageal cancer. Methods: The data from PubMed, Cochrane Libraries, and Embase up to 23 January 2022 were included in our analysis to identify studies that investigated associations between irregular diet and the risk of esophageal cancer. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Five cohort studies and one case-control study investigating associations between irregular diet and the risk of esophageal cancer were included. None of the articles demonstrated publication bias. The summary RR was 4.181 (95% CI 2.196–7.960, I2 = 66.1%, p = 0.011). In the subgroup analysis, we found significant heterogeneity in the Non-disease-causing group, nurse group and Asian group. The above three that produce heterogeneity may be the source of heterogeneity in the results of this study. Conclusion: The current meta-analysis indicates that irregular diet increase the risk of esophageal cancer. Trial registration: (https://www.crd.york.ac.uk/prospero/), (PROSPERO, CRD42022306407)
African swine fever virus: A re-emerging threat to the swine industry and food security in the Americas

COPYRIGHT © 2022 Ruiz-Saenz, Diaz, Bonilla-Aldana, Rodríguez-Morales, Martinez-Gutierrez and Aguilar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. African swine fever virus: A re-emerging threat to the swine industry and food security in the Americas
Vitamin D3 alters macrophage phenotype and endosomal trafficking markers in dairy cattle naturally infected with Mycobacterium avium subsp. paratuberculosis

Macrophages are important host defense cells in ruminant paratuberculosis (Johne’s Disease; JD), a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP). Classical macrophage functions of pathogen trafficking, degradation, and antigen presentation are interrupted in mycobacterial infection. Immunologic stimulation by 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) enhances bovine macrophage function. The present study aimed to investigate the role of vitamin D3 on macrophage phenotype and endosomal trafficking of MAP in monocyte-derived macrophages (MDMs) cultured from JD-, JD+ subclinical, and JD+ clinically infected cattle. MDMs were pre-treated 100 ng/ml 25(OH)D3 or 4 ng/ml 1,25(OH)2D3 and incubated 24 hrs with MAP at 10:1 multiplicity of infection (MOI). In vitro MAP infection upregulated pro-inflammatory (M1) CD80 and downregulated resolution/repair (M2) CD163. Vitamin D3 generally decreased CD80 and increased CD163 expression. Furthermore, early endosomal marker Rab5 was upregulated 140× across all stages of paratuberculosis infection following in vitro MAP infection; however, Rab5 was reduced in MAP-activated MDMs from JD+ subclinical and JD+ clinical cows compared to healthy controls. Rab7 expression decreased in control and clinical cows following MDM infection with MAP. Both forms of vitamin D3 reduced Rab5 expression in infected MDMs from JD- control cows, while 1,25(OH)2D3 decreased Rab7 expression in JD- and JD+ subclinical animals regardless of MAP infection in vitro. Vitamin D3 promoted phagocytosis in MDMs from JD- and JD+ clinical cows treated with either vitamin D3 analog. Results from this study show exogenous vitamin D3 influences macrophage M1/M2 polarization and Rab GTPase expression within MDM culture.
Autoimmune antibodies in first-episode psychosis with red flags: A hospital-based case-control study protocol

Background Research is increasingly identifying an overlap between psychosis and immunological dysregulation. Certain autoantibodies are being identified in a small but probably relevant subgroup of patients with psychosis. The term “autoimmune psychosis” (AIP) and its corresponding red-flag signs present the opportunity for a new field in psychiatry to promote diagnostic workup and immunomodulating therapy in individual cases. Objectives The present protocol aims to determine the seroprevalence of autoantibodies in first-episode psychosis (FEPs) using AIP red flag signs, and to explore the frequency of autoantibody subtypes and potential mediating confounders. Methods/design This is a hospital-based case-control study. All participants will be consecutively selected from the main tertiary psychiatric hospital in Shenzhen City, China. Individuals admitted to the psychiatric ward and diagnosed with FEPs will be enrolled. Based on recent consensus, participants with red flags of AIPs will be defined as cases, while the remainder will be matched as controls. Seropositive antibodies will be detected and verified in cerebrospinal fluid (CSF) samples based on the fixed cell-based assay (CBA) method. The propensity score-adjusted odds ratios will be determined to investigate the key mediating confounders regarding autoantibody subtypes and red flag subsets. Discussion The results of this study will facilitate the early identification of AIPs in FEP patients using the red flag sign and help identify key mediators that improve the accuracy of diagnostic algorithms. It will have clinical significance to focus on serum antibodies that have been verified in CSF samples, due to its consistency with clinical practices in current psychiatry.
Mingmu Xiaoyao granules regulate the PI3K/Akt/mTOR signaling pathway to reduce anxiety and depression and reverse retinal abnormalities in rats

Objective: To investigate the effects of Mingmu Xiaoyao granules (MMXY) on the morphology and function of the retina and the mechanism of PI3K/Akt/mTOR pathway-related proteins in rats with anxiety and depression induced by chronic unpredictable mild stress (CUMS). Methods: Fifty-two male Sprague Dawley rats were randomly allocated to either a control (n = 14) or a simulated CUMS group (n = 38). The CUMS model was established successfully at 4 weeks. Six rats in each group were randomly selected to be sacrificed and their retinas isolated for histological examination. At 5 weeks, rats in the CUMS group were randomly allocated to the following groups: Model (CUMS + pure water), MMXY-H (CUMS + MMXY 7.2 g/kg/d), MMXY-L (CUMS + MMXY 3.6 g/kg/d), and CBZ (CUMS + Carbamazepine 20 mg/kg/d), with eight rats in each group. All rats were given the relevant intervention once a day. At 12 weeks, sucrose preference and open field tests were performed to evaluate the anxiety and depression status of rats. In live rats, optical coherence tomography angiography was used to measure retinal thickness and blood flow, while electroretinograms (ERGs) and visual evoked potentials (VEPs) were used to evaluate retinal function. The next day, the specimens were sacrificed for serological, histological, immunofluorescence, Western blot and transmission electron microscopy examinations to explore the mechanism of MMXY in CUMS rats. Results: MMXY improved the anxiety and depression-like behavior of rats. Results of optical coherence tomography angiography showed that MMXY improved retinal inner thickness and blood flow in CUMS rats. MMXY improved the amplitude of a- and b-waves in the scotopic and photopic ERG, as well as N2 and P2 peak time and amplitude in the flash-VEP in CUMS rats. Retinal histological staining and transmission electron microscopy showed that MMXY reversed retinal morphology and ultrastructure in CUMS rats. MMXY reduced the expression of Beclin1 and LC3I/II proteins, regulated the PI3K/Akt/mTOR pathway, inhibited autophagy, and had a protective effect on the retina in CUMS rats. Conclusion: MMXY may effectively improve retinal morphology and function as well as anxiety and depression-like behaviors in CUMS rats by regulating the PI3K/Akt/mTOR signaling pathway.
Alginate-modified mesoporous bioactive glass and its drug delivery, bioactivity, and osteogenic properties

Mesoporous bioactive glass (MBG) is widely used in bone tissue repairing and drug loading. However, burst release of drug and poor compatibility with other materials limited its application. It is an effective way to modify MBG with a polymer brush to improve the properties. Herein, an alginate-modified MBG was prepared, and then, the effects of ALG on the properties of MBG were investigated. The results demonstrate that ALG could improve the drug loading efficiency, prolong drug release times, and make orderly deposition of apatite on the surface of MBG. Furthermore, MBG@ALG significantly promoted the osteogenic differentiation of MC3T3-E1 cells, demonstrating that surface modification of MBG by ALG can improve its properties, which will further broaden the application of MBG in tissue engineering.
Mild temperatures differentiate while extreme temperatures unify gene expression profiles among populations of Dicosmoecus gilvipes in California

Accurately predicting the effects of future warming on aquatic ectotherms requires an understanding how thermal history, including average temperature and variation, affects populations of the same species. However, many laboratory studies simplify the thermal environment to focus on specific organismal responses and sacrifice environmental realism. Here, we paired laboratory-based transcriptomic RNA-seq analysis to identify thermally responsive genes with NanoString analysis of a subset of those genes to characterize natural field-based variation in thermal physiology among populations. We tested gene expression responses of three populations of field-acclimatized larval caddisflies (Dicosmoecus gilvipes) from streams in different eco-regions (mountain, valley, and coast) following exposure to current and future summertime temperatures. We hypothesized that distinct thermal histories across eco-regions could differentiate populations at baseline “control” levels of gene expression, as well as gene expression changes in response to daily warming and heat shock. Population-specific patterns of gene expression were apparent under the control and daily warming conditions suggesting that local acclimatization or local adaptation may differentiate populations, while responses to extreme temperatures were similar across populations, indicating that response to thermal stress is canalized. Underlying gene co-expression patterns in the daily warming and heat shock treatments were different, demonstrating the distinct physiological mechanisms involved with thermal acclimatization and response to thermal stress. These results highlight the importance and limitations of studies of the thermal biology of wild-caught organisms in their natural environment, and provide an important resource for researchers of caddisflies and aquatic insects in general.
A sequence-based 163plex microhaplotype assay for forensic DNA analysis

Novel genetic marker microhaplotype has led to an upsurge in forensic genetic research. This study established a 163 microhaplotype (MH) multiplex assay based on next-generation sequencing (NGS) and evaluated the assay’s performance and applicability. Our results showed that the 163 MH assay was accurate, repeatable and reliable, and could distinguish between African, European-American, Southern Asia and Eastern Asia populations. Among the 163 MH makers, 48 MHs with Ae > 3.0 in China Eastern Han were selected and confirmed to be highly polymorphic, with a combined power of discrimination of 1–8.26 × 10–44 and the combined power of exclusion in duos and trios of 1–1.26 × 10–8 and 1–8.27 × 10–16, respectively. Moreover, the mixture study demonstrated the realizability of the MHs in deconvoluting mixtures with different proportions of two to five-person. In conclusion, our findings support the use of this MH assay for ancestry inference, human identification, paternity testing and mixture deconvolution in forensic research.
Investigation of Natural Compounds for Therapeutic Potential in Streptozotocin-induced Diabetic Neuroinflammation and Neuropathic Pain

Diabetic neuropathy (DN) is a serious microvascular complication of diabetes mellitus (DM) that impacts the nervous system. Several risk factors are involved in the progression and maintenance of DN-associated pain, such as higher expression of various inflammatory mediators, e.g., tumor necrotic factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), and cyclo-oxygenase-2 (COX-2). The present research explores the neuroprotective potential of natural isolates, including berbamine, bergapten, and carveol, on the DM-induced neuroinflammation and neurodegeneration that cause neuropathic pain. The study utilized computerized techniques, including computational analysis (a docking assay and a molecular dynamic simulation) before moving to in vivo protocols. Diabetic neuropathy was induced by intraperitonial injection (IP) of streptozotocin (65 mg/kg), and the animal subjects (rats) were kept for 4 weeks for the development of DN. Once diabetic neuropathy was confirmed, the subjects were treated with berbamine, bergapten, and carveol until the sixth week (i.e., 2 weeks of treatment). At the sixth week, the rats were sacrificed, and the sciatic nerve and spinal cord of each was collected for further molecular investigation. Docking and a molecular dynamic simulation (MDS) delivered the information that the natural compounds (berbamine, bergapten, and carveol) were interacting with the selected target protein (i.e., mitogen-activated protein kinase). After IP, it was found that berbamine, bergapten, and carveol had ameliorated mechanical allodynia and thermal hyperalgesia by the 28th day of the study (2 weeks after treatment) without affecting blood glucose levels. Berbamine, bergapten, and carveol markedly elevated the levels of glutathione (GSH) and glutathione s-transferase (GST), in both the sciatic nerve and spinal cord, and also reduced lipid peroxidase (LPO) and nitric oxide (NO). The abovementioned natural isolates reduced pathologic alterations provoked through DN, a finding confirmed through histopathological assays (hematoxylin and eosin staining and immuno-histochemical analysis). Treatment down regulated higher expressions of the inflammatory mediatorcyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and nuclear factor kappa B (NF-κB), as confirmed by ELISA and polymerase chain reaction (PCR). The outcomes of berbamine, bergapten, and carveol are compared with those of pregabalin as a positive control group. Compared to pregabalin, treatment with the aforementioned three natural compounds improved nociception and reduced hyperalgesic effects, and consequently reduced pain perception and inflammation. Our results suggest the mechanism for the neuro-protective impact of berbamine, bergapten, and carveol might possibly be arbitrated via COX-2, TNF-α, and NF-κB, and regulated by mitogen-activated protein kinase, ultimately ameliorating STZ-provoked, DM-induced neuroinflammation and neurodegeneration, and associated neuropathic pain.
Are adherence to the Mediterranean diet and siesta individually or jointly associated with blood pressure in Spanish adolescents? Results from the EHDLA study

Background Both dietary and sleep patterns can influence both blood pressure levels and heart rate, but these associations have been understudied in adolescents. Furthermore, it is not known whether diet and sleep could exert a synergistic effect with respect to the maintenance of optimal BP levels in this population. Objective To investigate the relationship of blood pressure levels with the combination of higher adherence to the Mediterranean diet and the habit of siesta (daytime napping) in Spanish adolescents. Methods A cross-sectional study was conducted with data obtained through personal interviews and physical examination from a representative sample of 1,378 adolescents (12–17 years of age) from the Valle de Ricote (Region of Murcia, Spain) selected using a simple random sampling technique. Adherence to the Mediterranean diet was assessed with the Mediterranean Diet Quality Index in Children and Adolescents, and the frequency and duration of siesta were self-reported. Objective measurements of systolic and diastolic blood pressure were obtained under standardized conditions. Statistical procedures were performed with SPSS software (v.25) and included logistic and generalized regression models adjusted for sex, age, socioeconomic status, body mass index, total energy intake, nighttime sleep duration, and moderate-to-vigorous physical activity. Results Of the 698 adolescents finally studied (mean age 13.9 ± 1.5 years; 56.2% female), 37.1% (n = 259) had high adherence to the Mediterranean diet and 19.6% (n = 137) reported frequent siesta. In the completely adjusted models, compared to adolescents with low Mediterranean diet adherence and no or infrequent siesta, those with high Mediterranean diet adherence and frequent siesta were less likely to have high-normal blood pressure or hypertension (odds ratio = 0.47; 95% confidence interval: 0.26, 0.88) and showed slightly lower systolic blood pressure (ß-coef. = −2.60; 95% CI: −5.18, −0.02). Conclusion Greater adherence to the Mediterranean diet and frequent siesta have a synergistic effect on maintaining lower blood pressure levels in adolescence. These findings reinforce that adherence to both Mediterranean lifestyle behaviors early in life may be an important strategy to prevent hypertension throughout adulthood.