Miracle-dz/UniFAR-FTUs huggingface dataset:
Virtual Fencing Is Comparable to Electric Tape Fencing for Cattle Behavior and Welfare

Virtual fencing technology restricts animal movement via communicated signals without physical boundaries. Specifically, the eShepherd™ automated virtual fencing system operates via GPS technology and provides stimuli via a neckband device. An audio warning tone is emitted at the virtual boundary which is followed by an electrical pulse if the animal continues moving forward. Animal welfare is a priority consideration for the commercial implementation of virtual fencing systems. The current study assessed the effects of a virtual fence, in comparison to an electric tape fence, to contain eight groups of eight 12–14 month old steers within a 6-ha area across eight separate paddocks for 4 weeks following 1 week acclimation to the paddocks. Cattle were assessed across two cohorts (four groups/cohort) from January until March 2019 in Australia. Body weight and fecal samples from each animal were taken weekly. Fecal samples were processed for fecal cortisol metabolite (FCM) concentrations. IceQube R®'s fitted to the leg measured individual lying and standing time and the virtual fencing neckbands recorded GPS location and all administered audio and electrical stimuli. Cattle were maintained within their allocated area by both fence types across the 4-week period and those with the virtual fences were responding correctly to the audio cue with an average of 71.51 ± 2.26% of all cues across all animals being audio only. There was individual variation in rate of learning. The electric tape groups in cohort 1 showed a greater increase in body weight over 4 weeks than the virtual fence groups (P < 0.001) but this difference was not confirmed in cohort 2. The fence type statistically influenced the total daily lying time (P = 0.02) with less lying in cattle from the virtual fence groups but this difference equated to an average of <20 min per day. There were no differences between fence types in FCM concentrations (P = 0.39) and the concentrations decreased across time for all cattle (P < 0.001). These results indicate that virtual fencing technology effectively contains animals in a prescribed area across 4 weeks without substantial behavioral and welfare impacts on the cattle.
Benchmark and Parameter Sensitivity Analysis of Single-Cell RNA Sequencing Clustering Methods

Single-cell RNA-seq (scRNAseq) is a powerful tool to study heterogeneity of cells. Recently, several clustering based methods have been proposed to identify distinct cell populations. These methods are based on different statistical models and usually require to perform several additional steps, such as preprocessing or dimension reduction, before applying the clustering algorithm. Individual steps are often controlled by method-specific parameters, permitting the method to be used in different modes on the same datasets, depending on the user choices. The large number of possibilities that these methods provide can intimidate non-expert users, since the available choices are not always clearly documented. In addition, to date, no large studies have invistigated the role and the impact that these choices can have in different experimental contexts. This work aims to provide new insights into the advantages and drawbacks of scRNAseq clustering methods and describe the ranges of possibilities that are offered to users. In particular, we provide an extensive evaluation of several methods with respect to different modes of usage and parameter settings by applying them to real and simulated datasets that vary in terms of dimensionality, number of cell populations or levels of noise. Remarkably, the results presented here show that great variability in the performance of the models is strongly attributed to the choice of the user-specific parameter settings. We describe several tendencies in the performance attributed to their modes of usage and different types of datasets, and identify which methods are strongly affected by data dimensionality in terms of computational time. Finally, we highlight some open challenges in scRNAseq data clustering, such as those related to the identification of the number of clusters.
Unbalanced Roles of Fungal Aggressiveness and Host Cultivars in the Establishment of the Fusarium Head Blight in Bread Wheat

Fusarium head blight (FHB), caused mainly by Fusarium graminearum, is the foremost destructive disease of cereals worldwide. Effector-like molecules produced by F. graminearum play key roles in the infection process and are assumed to be one of the essential components of the pathogen’s aggressiveness. However, their nature and role in the disease are still largely misunderstood. As a mean to provide relevant information about the molecular determinism of F. graminearum aggressiveness, we surveyed three F. graminearum strains on three wheat cultivars contrasted by their susceptibility to FHB. F. graminearum strains revealed large differences in aggressiveness which were mostly unchanged when facing hosts of contrasted susceptibility, suggesting that their behavior rely on intrinsic determinants. Surveying the fungal mass progress and the mycotoxin production rate in the spikes did not evidence any simple relationship with aggressiveness differences, while clues were found through a qualitative and quantitative characterization of the three strain proteomes established in planta especially with regards to early synthesized putative effectors. Independently of the wheat cultivar, the three F. graminearum strains produced systematically the same protein set during the infection but substantial differences in their abundance enabled the categorization of fungal aggressiveness. Overall, our findings show that the contrasts in F. graminearum aggressiveness were not based on the existence of strain-specific molecules but rather on the ability of the strain to ensure their sufficient accumulation. Protein abundance variance was mostly driven by the strain genetics and part was also influenced by the host cultivar but strain by cultivar interactions were marginally detected, depicting that strain-specific protein accumulations did not depend on the host cultivar. All these data provide new knowledge on fungal aggressiveness determinants and provide a resourceful repertoire of candidate effector proteins to guide further research.
Honokiol Ameliorates High-Fat-Diet-Induced Obesity of Different Sexes of Mice by Modulating the Composition of the Gut Microbiota

Background: Accumulating data support the fact that the gut microbiota plays an important role in the progression of obesity and its related metabolic disease. Sex-related differences are an important consideration in the study of gut microbiota. Polyphenols can regulate gut microbiota, thereby improving obesity and its associated complications. There have been no studies conducted on the ability of honokiol (HON, an extract from Chinese herbal medicine) to regulate gut microbiota. The aim of this study was to examine whether HON supplementation would improve obesity by regulating the gut microbiota and its related metabolite levels, and whether there were sex-based differences in high-fat diet-induced obese mice. Methods: C57BL/6 mice (n = 120) were fed a normal chow diet (ND group), high-fat diet (HFD group), or HFD plus HON at 200, 400, and 800 mg/kg BW for 8 weeks. Body weight, adipose tissue weight, adipocyte diameter, insulin resistance, blood lipid and serum inflammatory cytokines, gut microbiota, and its metabolite were examined at the end of the experiment. Results: The HON supplementation reduced body weight, adipose tissue weight, adipocyte diameter, insulin resistance, blood lipid, and serum inflammatory cytokine levels in HFD-fed mice, and this effect was significant in the high-dose group. In addition, HON not only reversed gut disorders in HFD-fed mice, such as by enhanced the abundance of Akkermansia and short-chain fatty acids (SCFAs) producing Bacteroides and reduced Oscillospira, but also improved the SCFAs and endotoxin (LPS) levels, although there were sex-based differences. The correlation between several specific genera and obesity-related indexes was revealed through Spearman's correlation analysis. Moreover, HON may have dose-dependent effects on regulating gut microbiota to alleviate obesity. Conclusions: These findings suggest that HON can prevent diet-induced obesity and its associated diseases by regulating the gut microbiota and improving microbial metabolite levels. Moreover, our findings indicate that sex may be an important factor affecting HON activity.
Identifying Potential miRNAs–Disease Associations With Probability Matrix Factorization

In recent years, miRNAs have been verified to play an irreplaceable role in biological processes associated with human disease. Discovering potential disease-related miRNAs helps explain the underlying pathogenesis of the disease at the molecular level. Given the high cost and labor intensity of biological experiments, computational predictions will be an indispensable alternative. Therefore, we design a new model called probability matrix factorization (PMFMDA). Specifically, we first integrate miRNA and disease similarity. Next, the known association matrix and integrated similarity matrix are utilized to construct a probability matrix factorization algorithm to identify potentially relevant miRNAs for disease. We find that PMFMDA achieves reliable performance in the frameworks of global leave-one-out cross validation (LOOCV) and 5-fold cross validation (AUCs are 0.9237 and 0.9187, respectively) in the HMDD (V2.0) dataset, significantly outperforming a few state-of-the-art methods including CMFMDA, IMCMDA, NCPMDA, RLSMDA, and RWRMDA. In addition, case studies show that PMFMDA has good predictive performance for new associations, and the evidence can be identified by literature mining.
Length-Dependent Activation of Contractility and Ca-Transient Kinetics in Auxotonically Contracting Isolated Rat Ventricular Cardiomyocytes

Length-dependent activation (LDA) of contraction is an important mechanism of proper myocardial function that is often blunted in diseases accompanied by deficient contractility and impaired calcium homeostasis. We evaluated how the extent of LDA is related to the decreased force in healthy rat myocardium under negative inotropic conditions that affect the calcium cycle. The length-dependent effects on auxotonic twitch and Ca-transient were compared in isolated rat ventricular cardiomyocytes at room temperature (“25C”) and near-physiological temperature (“35C”) in normal Tyrode and at 25°C with thapsigargin-depleted sarcoplasmic reticulum (“25C + Thap”). At the slack length, a similar negative inotropy in “35C” and “25C + Thap” was accompanied by totally different changes in Ca-transient amplitude, time-to-peak, and time-to-decline from peak to 50% amplitude. End-systolic/end-diastolic tension-sarcomere length relationships were obtained for each individual cell, and the ratio of their slopes, the dimensionless Frank-Starling Gain index, was 2.32 ± 0.16, 1.78 ± 0.09, and 1.37 ± 0.06 in “25C,” “35C” and “25C + Thap,” respectively (mean ± S.E.M.). Ca-transient diastolic level and amplitude did not differ between “25C” and “35C” at any SL, but in “35C” it developed and declined significantly faster. In contrast, thapsigargin-induced depletion of SERCA2a significantly attenuated and retarded Ca-transient. The relative amount of Ca2+ utilized by troponin C, evaluated by the integral magnitude of a short-lived component of Ca-transient decline (“bump”), increased by ~25% per each 0.05 μm increase in SL in all groups. The kinetics of the Ca-TnC dissociation, evaluated by the bump time-to-peak, was significantly faster in “35C” and slower in “25C + Thap” vs. “25C” (respectively, 63.7 ± 5.3 and 253.6 ± 8.3% of the value in “25C,” mean ± S.E.M.). In conclusion, a similar inotropic effect can be observed in rat ventricular myocardium under totally different kinetics of free cytosolic calcium. The extent of LDA is not determined by actual peak systolic tension but is regulated by the level of peak systolic calcium and the kinetics of Ca-transient decline which, in turn, are governed by Ca-TnC dissociation and Ca2+ reuptake by the sarcoplasmic reticulum. Altogether, these findings constitute new evidence about the role of the length-dependent modulation of Ca2+ homeostasis in the mechanisms of calcium regulation of contraction and mechano-calcium feedback in the myocardium.
Quality of Life in Patients With Cushing's Disease

Cushing's disease (and by extension, Cushing's syndrome) is a rare disease due to a chronic cortisol excess, which usually has an important impact on quality of life (QoL). It can lead to numerous comorbidities that can interfere with daily life, as fatigability, myopathy, bone loss and fragility, increased cardiovascular risk, depression, and cognitive alterations. Of note, psychological alterations (including depression and anxiety) occur often, and are an important determinant of impaired quality QoL. QoL scores using different questionnaires are poorer in comparison to healthy controls, other pituitary adenomas and some chronic diseases. Even if some improvements can be observed after successful treatment, recovery does not seem to be complete, and comorbidities persist. This persistent QoL impairment has been found using both generic and disease-specific QoL questionnaires, and is also reported by the patients themselves, when asked directly. Multidisciplinary teams are essential to improve patients' well-being. Clinicians should take into account the whole scope of clinical problems and address the different comorbidites associated with the disease. Screening in the psychological sphere, with further intervention if necessary, can be helpful in the management of these patients. Interventions and programs have shown promising results, although there is a need for further development of new strategies for the benefit of these patients.
Corporate Social Responsibility and Collective OCB: A Social Identification Perspective

Although plenty of evidence has shown a positive relationship between collective organizational citizenship behavior (OCB) and unit or organizational performance, the antecedents of collective OCB are still understudied. In this study, we identify corporate social responsibility (CSR) as a new antecedent of firm-level collective OCB. Furthermore, we develop a collective social identification approach to examining the mechanism through which CSR may enhance collective OCB. Specifically, we propose and test a sequential mediation model in which CSR promotes organizational prestige. Organizational prestige, in turn, increases employees’ collective organizational identification and, consequently, enhances their collective OCB at the firm level. To test this model, we collected data from three different sources (i.e., HR director, CEO, and employees) from 160 firms in China. The results supported the hypotheses.
Capacity to Elicit Cytotoxic CD8 T Cell Activity Against Mycobacterium avium subsp. paratuberculosis Is Retained in a Vaccine Candidate 35 kDa Peptide Modified for Expression in Mammalian Cells

Studies focused on development of an attenuated vaccine against Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of paratuberculosis (Ptb) in cattle and other species, revealed that deletion of relA, a global gene regulator, abrogates the ability of Map to establish a persistent infection. In the absence of relA, cattle develop CD8 cytotoxic T cells (CTL) with the ability to kill intracellular bacteria. Analysis of the recall response to a relA mutant, Map/ΔrelA, with cells from a vaccinated steer demonstrated that a 35-kDa membrane peptide (MMP) is one of the targets of the response. This observation suggested that it might be possible to develop a peptide-based vaccine. As reported here, the gene encoding the hypothetical MMP ORF, MAP2121c, was modified for expression in mammalian cells as a first step in developing an expression cassette for incorporation into a mammalian expression vector. The modified sequence of MMP, tPA-MMP, was mutated to generate two additional sequences for the study, one with substitutions to replace five potential residues that could be glycosylated, tPA-MMP-5mut, and one with substitutions to replace the first two potential residues that could be glycosylated, tPA-MMP-2mut. The sequences were placed in an expression cassette to produce peptides for analysis. An ex vivo platform was used with flow cytometry and a bacterium viability assay to determine if modifications in the gene encoding MMP for expression in mammalian cells altered its capacity to elicit development of CD8 CTL, essential for its use in a peptide-based vaccine. Monocyte-depleted PBMC (mdPBMC) were stimulated with antigen-presenting cells (APC) pulsed with different MMP constructs. CD4 and CD8 T cells proliferated in response to stimulation with MMP (control) expressed in Escherichia coli (eMMP), tPA-MMP, and tPA-MMP-2mut. CD8 T cells retained the capacity to kill intracellular bacteria. The tPA-MMP-5mut failed to elicit a proliferative response and was not included in further studies. The data show that the expression cassettes containing MMP and MMP-2mut can be used to screen and select a mammalian expression vector for the development of an efficacious peptide-based vaccine against Ptb.
Fibromodulin – A New Target of Osteoarthritis Management?

1 Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, China, 2 Department of Orthodontics, College of Stomatology, Xi’an Jiaotong University, Xi’an, China, 3 Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United States, 4 Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States, 5 David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United States
A Clinical Case of Patient Carrying Rare Pathological PSEN1 Gene Mutation (L424V) Demonstrates the Phenotypic Heterogenity of Early Onset Familial AD

Dementia comprises several neurodegenerative disorders with similar neuropsychiatric features and Alzheimer’s disease (AD) is the most common of them. Genetic factors are strongly implicated into its etiology especially for early-onset cases (EOAD) occuring before the age of 65. About 10% of these are inherited in autosomal dominant fashion via pathogenic polymorphisms in three genes— APP, PSEN-1, and PSEN-2. Despite genotypic clarity, however, phenotypic variability exists with different symptom constellations observed in patients with identical mutations. Below, we present a case of a 39-year-old male with a family history for early onset dementia who was referred to our department with anamnesis for abrupt behavioral change 7 months prior to hospitalization—noticeable slowing of speech and reactivity, impaired occupational functioning and irritability, followed by aphasic symptoms and transient episodes of disorientation. He was followed up for 2 years and manifested rapidly progressing cognitive decline with further deterioration of speech, apraxia, acalculia, ataxia, and subsequently bradykinesia and tremor. Based on the clinical and neuroimaging findings (severe cortical atrophy), familial EOAD was suspected and a whole exome sequence (WES) analysis was performed. It identified a heterozygous missense variant Leu424Val (g.71074C > G) in PSEN-1 gene considered to be pathogenic, and only reported once until now in a Spanish patient in 2009. Despite genotype identity however, distinct phenotypic presentations were observed in the two affected subjects, with different neuroimaging findings, and the presence and absence of seizures in the Spanish and Bulgarian case, respectively. Besides, myoclonus and spastic paraparesis considered “typical” EOAD clinical features were absent. Age of symptom onset was consistent with two of the reported mutations affecting 424 codon of PSEN-1 gene and significantly earlier than the other two implying that factors influencing activity of PSEN-1 pathological forms are yet to be clarified. Furthermore, our patient had co-occurring lupus erythematosus (LE) and we suggest that this condition might be etiologically linked to the PSEN-1 mutation. In addition to illustrating the symptomatic heterogeneity of PSEN-1 caused EOAD, our study confirms that in patients presenting with early cognitive deterioration and family history for dementia, WES can be especially informative and should be considered as a first-line examination.
Machine Learning and Feature Selection Methods for Disease Classification With Application to Lung Cancer Screening Image Data

As awareness of the habits and risks associated with lung cancer has increased, so has the interest in promoting and improving upon lung cancer screening procedures. Recent research demonstrates the benefits of lung cancer screening; the National Lung Screening Trial (NLST) found as its primary result that preventative screening significantly decreases the death rate for patients battling lung cancer. However, it was also noted that the false positive rate was very high (>94%). In this work, we investigated the ability of various machine learning classifiers to accurately predict lung cancer nodule status while also considering the associated false positive rate. We utilized 416 quantitative imaging biomarkers taken from CT scans of lung nodules from 200 patients, where the nodules had been verified as cancerous or benign. These imaging biomarkers were created from both nodule and parenchymal tissue. A variety of linear, nonlinear, and ensemble predictive classifying models, along with several feature selection methods, were used to classify the binary outcome of malignant or benign status. Elastic net and support vector machine, combined with either a linear combination or correlation feature selection method, were some of the best-performing classifiers (average cross-validation AUC near 0.72 for these models), while random forest and bagged trees were the worst performing classifiers (AUC near 0.60). For the best performing models, the false positive rate was near 30%, notably lower than that reported in the NLST.The use of radiomic biomarkers with machine learning methods are a promising diagnostic tool for tumor classification. The have the potential to provide good classification and simultaneously reduce the false positive rate.
Risk Factors for Facial Appearance Dissatisfaction Among Orthognathic Patients: Comparing Patients to a Non-Surgical Sample

This study conducted a cross-sectional investigation of facial appearance dissatisfaction between patients before undergoing orthognathic surgery and a non-surgical sample to evaluate the potential influencing factors of facial appearance dissatisfaction. A sample of 354 participants completed a set of questionnaires concerning facial appearance dissatisfaction, interpersonal pressure, media pressure, and fear of negative appearance evaluation (112 patients, 242 controls). The patients reported higher facial appearance dissatisfaction, more media pressure, more interpersonal pressure, and a greater fear of negative appearance evaluation among others than the control group. Moreover, regression analyses identified interpersonal pressure and fear of negative appearance evaluation as the main predictors of facial appearance dissatisfaction whether in the orthognathic patients or the control groups. The associations between the perceptions of interpersonal pressure, fear of negative appearance evaluation, and facial appearance dissatisfaction support the possible utility of strengthening social experiences and psychological intervention in preventing and treating these appearance-concerns, especially for the orthognathic patients.