Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetics of Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) are T cells-mediated life-threatening immune reactions, most commonly induced by drug. The last decade has seen significant progress in SCARs research. Recent studies have unveiled the pathogenesis of SCARs involved in susceptible genes, including human leukocyte antigens (HLA) and drugs-T cell receptor (TCR) interaction that may trigger T cell activation with downstream immune signaling of cytokines/chemokines and specific cytotoxic proteins releases. Advances in identification of multiple genetic alleles associated with specific drugs related SCARS in different populations is an important breakthrough in recent years for prevention of SCARs. This article summarized the findings on genetic factors related to SJS/TEN, especially for HLA.
Evaluation of Tail Lesions of Finishing Pigs at the Slaughterhouse: Associations With Herd-Level Observations

The prevalence of tail lesions evaluated at the slaughterhouse varies considerably between herds. These lesions result mainly from tail biting, a harmful behavior with multifactorial origin. This study sought to investigate if a batchwise inspection of tails at slaughterhouse could be a useful method to estimate the animal welfare situation in finishing pig herds, and if so, what type and detail of tail scoring such an inspection should utilize. We investigated the distribution of different types of tail lesions and how well their scoring at slaughterhouse was associated with the situation recorded on-farm by a veterinarian as part of routine herd health visits. We also wanted to determine if animal welfare-related herd-level parameters, recorded by herd veterinarians during herd health visits, are associated with tail scoring at the slaughterhouse. A total of 10,517 pigtails from 84 herds were scored for this study. Herd data were collected from the national health classification register for pig farms in Finland and also included annual herd production quality data collected by the slaughterhouse. The scores of the tails varied considerably between the herds. On average, 48.1% (sd = 19.3) of the tails with an average length of 30.4 cm (sd = 2.7) were fully intact, 37.3% (13.9) had healed (length = 26.4, sd = 5.1 cm), 12.4% (9.0) (length = 28.9, sd = 4.3 cm) had minor acute wounds, and 2.3% (2.1) (length = 24.2, sd = 6.0 cm) had major acute wounds. Proportions of different tail lesions at slaughterhouse were associated with or tended to be associated with the following herd-level parameters in regression models: use of wood as enrichment (p < 0.1), one health parameter (leg problems other than arthritis, p < 0.05), and long-term animal welfare estimate (annual mortality, p < 0.05). Detailed tail evaluation at the slaughterhouse shows potential in estimating the tail lesions and long-term welfare level on the farm. By recording only one type of tail condition (such as tails with major acute lesions) at the slaughterhouse, it is not possible to estimate the total tail lesion situation in the herds before slaughter. A more detailed scoring similar to the one used in this trial is recommended.
Evaluation of Multilevel Surgeries in Children With Spastic Cerebral Palsy Based on Surface Electromyography

The root mean square (RMS) of the surface electromyography (sEMG) signal can respond to neuromuscular function, which displays a positive correlation with muscle force and muscle tension under positive and passive conditions, respectively. The purpose of this study was to investigate the changes in muscle force and tension after multilevel surgical treatments, functional selective posterior rhizotomy (FSPR) and tibial anterior muscle transfer surgery, and evaluate their clinical effect in children with spastic cerebral palsy (SCP) during walking. Children with diplegia (n = 13) and hemiplegia (n = 3) with ages from 4 to 18 years participated in this study. They were requested to walk barefoot at a self-selected speed on a 15-m-long lane. The patient's joints' range of motion (ROM) and sEMG signal of six major muscles were assessed before and after the multilevel surgeries. The gait cycle was divided into seven phases, and muscle activation state can be divided into positive and passive conditions during gait cycle. For each phase, the RMS of the sEMG signal amplitude was calculated and also normalized by a linear envelope (10-ms running RMS window). The muscle tension of the gastrocnemius decreased significantly during the loading response, initial swing, and terminal swing (p < 0.05), which helped the knee joint to get the maximum extension when the heel is on the ground and made the heel land smoothly. The muscle force of the gastrocnemius increased significantly (p < 0.05) during the mid-stance, terminal stance, and pre-swing, which could generate the driving force for the human body to move forward. The muscle tension of the biceps femoris and semitendinosus decreased significantly (p < 0.05) during the terminal stance, pre-swing, and initial swing. The decreased muscle tension could relieve the burden of the knee flexion when the knee joint was passively flexed. At the terminal swing, the muscle force of the tibial anterior increased significantly (p < 0.05), which could improve the ankle dorsiflexion ability and prevent foot drop and push forward. Thus, the neuromuscular function of cerebral palsy during walking can be evaluated by the muscle activation state and the RMS of the sEMG signal, which showed that multilevel surgical treatments are feasible and effective to treat SCP.
Identification of the Bisphenol A (BPA) and the Two Analogues BPS and BPF in Cryptorchidism

Objective to explore the association of plasma concentrations of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) with unilateral cryptorchidism. In addition, to analyze selected demographic and intraoperative characteristics. Design Retrospective analysis to determine plasma concentrations of total BPA, BPS and BPF using gas chromatography - mass spectrometry (GC-MS) among prepubertal boys with cryptorchidism and prebupertal male control subjects. During operation, the size, turgor and location of the cryptorchid testes were assessed. Main Outcome Measure Plasma concentrations of total BPA, BPS and BPF. Results In children with cryptorchidism, plasma levels of BPA, BPS and BPF were significantly higher compared to the control subjects. For BPA, it was: median value: 9.95 ng/mL vs. 5.54 ng/mL, p<0.05. For BPS, it was: median value: 3.93 ng/mL vs. 1.45 ng/mL, p<0.001. For BPF, it was: median value: 3.56 ng/mL vs. 1.83 ng/mL, p<0.05. In cryptorchid group, BPA was detected in 61.4% samples, BPS in 19.3% and BPF in 19.3%. All the three bisphenols were detected in plasma samples of both the healthy subjects and the study cohort. In the latter group, we found significant higher levels of BPA in boys from urban areas. We found a weak positive correlation between the levels of BPS and BPF and reduced turgor of the testes. Furthermore, results showed weak positive correlations between BPA and BPS levels and the age of the children as well as between BPS and BPF concentrations and the place of residence. Conclusions Results provide a first characterization of prepubertal boys suffering from cryptorchidism and exposed to different kind of bisphenols. Our study suggests that cryptorchid boys are widely exposed to BPA and, to a lesser extent, also to its alternatives, such as BPS and BPF.
Performance, Serum Biochemical and Immunological Parameters, and Digestive Enzyme and Intestinal Barrier-Related Gene Expression of Broiler Chickens Fed Fermented Fava Bean By-Products as a Substitute for Conventional Feed

Improving the nutritional quality of unconventional feed ingredients such as fava bean by-products can enhance their utilization by broiler chickens. Hence, the quality of fermented fava bean by-products (FFB), in addition to growth, nutrient digestibility, digestive enzyme, and intestinal barrier-related gene expression, and serum biochemical and immunological parameters were evaluated in response to different levels of FFB. A total of 500 1-day-old broiler chicks (46.00 ± 0.388 g) were allocated to five groups with 10 replicates each (100 chicks per treatment). The first group was fed a corn–soybean diet (control diet), and the other four groups were fed a diet containing 5, 15, 25, and 35% FFB for 38 days. Birds fed 25% FFB exhibited maximum body weight gain (increase by 12.5%, compared with the control group) and the most improved feed conversion ratio. Additionally, birds fed FFB at 15, 25, and 35% showed improved dry matter and crude protein digestibility. Moreover, birds fed FFB at 25 and 35% exhibited a decrease in ileal pH and an increase in fiber digestibility (p < 0.05). Upregulation of digestive enzyme genes (AMY2A, PNLIP, and CCK) was observed in groups fed with FFB. The most prominent upregulation of genes encoding tight junction proteins (claudin-1, occludin, and junctional adhesion molecules) in the duodenum was observed in chicks fed 25 and 35% FFB (increase of 0.66-, 0.31-, and 1.06-fold and 0.74-, 0.44-, and 0.92-fold, respectively). Additionally, the highest expression level of enterocyte protective genes [glucagon-like peptide (GLP-2), mucin-2 (MUC-2), and fatty acid-binding protein (FABP-6)] was detected in duodenum of chicks fed high levels of FFB. Substitution of corn–soybean diet with FFB had an inhibitory effect on cecal pathogenic microbes (Escherichia coli and Clostridium perfringens) and increased beneficial microflora (Lactobacilli and Bifidobacterium), especially at high levels. Additionally, an increase was observed in IgM and lysozyme activity, with no effect on IgA in all groups fed FFB. All levels of FFB decreased cholesterol levels. Based on our results, we concluded that substitution of corn–soybean diet with FFB can improve the growth rate and nutrient digestibility of broiler chickens, enhance their intestinal barrier functions, and increase the number of beneficial microorganisms. Using FFB at 25% had a positive effect on the growth performance of broiler chickens, and it could be utilized in poultry farms.
Impact of Metabolic Syndrome and It's Components on Prognosis in Patients With Cardiovascular Diseases: A Meta-Analysis

Background: Patients with metabolic syndrome (MetS) have a higher risk of developing cardiovascular diseases (CVD). However, controversy exists about the impact of MetS on the prognosis of patients with CVD. Methods: Pubmed, Cochrane library, and EMBASE databases were searched. Cohort Studies and randomized controlled trials post hoc analyses that evaluated the impact of MetS on prognosis in patients (≥18 years) with CVD were included. Relative risk (RR), hazard rate (HR) and 95% confidence intervals (CIs) were calculated for each individual study by random-effect model. Subgroup analysis and meta-regression analysis was performed to explore the heterogeneity. Results: 55 studies with 16,2450 patients were included. Compared to patients without MetS, the MetS was associated with higher all-cause death [RR, 1.220, 95% CI (1.103 to 1.349), P, 0.000], CV death [RR, 1.360, 95% CI (1.152 to 1.606), P, 0.000], Myocardial Infarction [RR, 1.460, 95% CI (1.242 to 1.716), P, 0.000], stroke [RR, 1.435, 95% CI (1.131 to 1.820), P, 0.000]. Lower high-density lipoproteins (40/50) significantly increased the risk of all-cause death and CV death. Elevated fasting plasma glucose (FPG) (>100 mg/dl) was associated with an increased risk of all-cause death, while a higher body mass index (BMI>25 kg/m2) was related to a reduced risk of all-cause death. Conclusions: MetS increased the risk of cardiovascular-related adverse events among patients with CVD. For MetS components, there was an increased risk in people with low HDL-C and FPG>100 mg/dl. Positive measures should be implemented timely for patients with CVD after the diagnosis of MetS, strengthen the prevention and treatment of hyperglycemia and hyperlipidemia.
A Field-Based Experiment on the Influence of Stand Density Reduction on Watershed Processes at the Caspar Creek Experimental Watersheds in Northern California

Forests are integral to sustaining clean water resources and healthy watersheds. It is critical, therefore, that managers fully understand the potential impacts of their actions on myriad ecosystem services provided by forested watersheds. While forest hydrologists have long used paired-watershed experiments to elucidate the complex interactions between forest management and watershed biogeochemical and ecohydrological processes, there is still much to learn from these studies. Here, we present an overview of the process for designing a paired-watershed study using a large harvesting experiment at the Caspar Creek Experimental Watersheds in coastal California as an example. We detail many considerations when designing such an experiment and highlight the wide range of scientific investigations that are part of the larger experiment. Paired watershed studies are a great example of community engaged scholarship and offer the unique opportunity to work with land managers to solve applied problems while simultaneously discovering new fundamental knowledge about how watersheds function.
Giardia duodenalis Induces Proinflammatory Cytokine Production in Mouse Macrophages via TLR9-Mediated p38 and ERK Signaling Pathways

Giardia duodenalis, also known as Giardia lamblia or Giardia intestinalis, is an important opportunistic, pathogenic, zoonotic, protozoan parasite that infects the small intestines of humans and animals, causing giardiasis. Several studies have demonstrated that innate immunity-associated Toll-like receptors (TLRs) are critical for the elimination of G. duodenalis; however, whether TLR9 has a role in innate immune responses against Giardia infection remains unknown. In the present study, various methods, including reverse transcriptase–quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, immunofluorescence, inhibitor assays, and small-interfering RNA interference, were utilized to probe the role of TLR9 in mouse macrophage-mediated defenses against G. lamblia virus (GLV)–free or GLV-containing Giardia trophozoites. The results revealed that in G. duodenalis–stimulated mouse macrophages, the secretion of proinflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-12 p40, was enhanced, concomitant with the significant activation of TLR9, whereas silencing TLR9 attenuated the host inflammatory response. Notably, the presence of GLV exacerbated the secretion of host proinflammatory cytokines. Moreover, G. duodenalis stimulation activated multiple signaling pathways, including the nuclear factor κB p65 (NF-κB p65), p38, ERK, and AKT pathways, the latter three in a TLR9-dependent manner. Additionally, inhibiting the p38 or ERK pathway downregulated the G. duodenalis–induced inflammatory response, whereas AKT inhibition aggravated this process. Taken together, these results indicated that G. duodenalis may induce the secretion of proinflammatory cytokines by activating the p38 and ERK signaling pathways in a TLR9-dependent manner in mouse macrophages. Our in vitro findings on the mechanism underlying the TLR9-mediated host inflammatory response may help establish the foundation for an in-depth investigation of the role of TLR9 in the pathogenicity of G. duodenalis.
Hormone-Responsive BMP Signaling Expands Myoepithelial Cell Lineages and Prevents Alveolar Precocity in Mammary Gland

Myoepithelial and luminal cells synergistically expand in the mammary gland during pregnancy, and this process is precisely governed by hormone-related signaling pathways. The bone morphogenetic protein (BMP) signaling pathway is now known to play crucial roles in all organ systems. However, the functions of BMP signaling in the mammary gland remain unclear. Here, we found that BMPR1a is upregulated by hormone-induced Sp1 at pregnancy. Using a doxycycline (Dox)-inducible BMPR1a conditional knockout mouse model, we demonstrated that loss of BMPR1a in myoepithelium results in compromised myoepithelial integrity, reduced mammary stem cells and precocious alveolar differentiation during pregnancy. Mechanistically, BMPR1a regulates the expression of p63 and Slug, two key regulators of myoepithelial maintenance, through pSmad1/5-Smad4 complexes, and consequently activate P-cadherin during pregnancy. Furthermore, we observed that loss of BMPR1a in myoepithelium results in the upregulation of a secreted protein Spp1 that could account for the precocious alveolar differentiation in luminal layer, suggesting a defective basal-to-luminal paracrine signaling mechanism. Collectively, these findings identify a novel role of BMP signaling in maintaining the identity of myoepithelial cells and suppressing precocious alveolar formation.
Esophageal Cancer Radiotherapy Dose Escalation Meta Regression Commentary: “High vs. Low Radiation Dose of Concurrent Chemoradiotherapy for Esophageal Carcinoma With Modern Radiotherapy Techniques: A Meta-Analysis”

Citation: Chow R, Lock M, Lee SL, Lo SS and Simone CB II (2021) Esophageal Cancer Radiotherapy Dose Escalation Meta Regression Commentary: “High vs. Low Radiation Dose of Concurrent Chemoradiotherapy for Esophageal Carcinoma With Modern Radiotherapy Techniques: A Meta-Analysis“. Front. Oncol. 11:700300. doi: 10.3389/fonc.2021. 700300 GENERAL COMMENTARY published: 14 July 2021 doi: 10.3389/fonc.2021. 700300
On a Combination of Alternating Minimization and Nesterov's Momentum

Alternating minimization (AM) procedures are practically efficient in many applications for solving convex and non-convex optimization problems. On the other hand, Nesterov's accelerated gradient is theoretically optimal first-order method for convex optimization. In this paper we combine AM and Nesterov's acceleration to propose an accelerated alternating minimization algorithm. We prove $1/k^2$ convergence rate in terms of the objective for convex problems and $1/k$ in terms of the squared gradient norm for non-convex problems, where $k$ is the iteration counter. Our method does not require any knowledge of neither convexity of the problem nor function parameters such as Lipschitz constant of the gradient, i.e. it is adaptive to convexity and smoothness and is uniformly optimal for smooth convex and non-convex problems. Further, we develop its primal-dual modification for strongly convex problems with linear constraints and prove the same $1/k^2$ for the primal objective residual and constraints feasibility.
Label Distribution Learning Machine

Although Label Distribution Learning (LDL) has witnessed extensive classiﬁcation applications, it faces the challenge of objective mismatch – the objective of LDL mismatches that of classiﬁcation, which has seldom been noticed in existing studies. Our goal is to solve the objective mismatch and improve the classiﬁcation performance of LDL. Speciﬁcally, we extend the margin theory to LDL and propose a new LDL method called L abel D istribution L earning M achine (LDLM). First, we deﬁne the label distribution margin and propose the S upport V ector R egression M achine (SVRM) to learn the optimal label. Second, we propose the adaptive margin loss to learn label description degrees. In theoretical analysis, we develop a generalization theory for the SVRM and analyze the generalization of LDLM. Experimental results validate the better classiﬁcation performance of LDLM.
Dual Principal Component Pursuit for Robust Subspace Learning: Theory and Algorithms for a Holistic Approach

The Dual Principal Component Pursuit (DPCP) method has been proposed to robustly recover a subspace of high relative dimension from corrupted data. Existing analyses and algorithms of DPCP, however, mainly focus on ﬁnding a normal to a single hyperplane that contains the in-liers. Although these algorithms can be extended to a subspace of higher codimension through a recursive approach that sequentially ﬁnds a new basis element of the space orthogonal to the sub-space, this procedure is computationally expensive and lacks convergence guarantees. In this paper, we consider a DPCP approach for simultaneously computing the entire basis of the orthogonal complement subspace (we call this a holistic approach ) by solving a non-convex non-smooth optimization problem over the Grassmannian. We provide geometric and statistical analyses for the global optimality and prove that it can tolerate as many outliers as the square of the number of inliers, under both noiseless and noisy settings. We then present a Riemannian regularity condition for the problem, which is then used to prove that a Riemannian subgradient method converges linearly to a neighborhood of the orthogonal sub-space with error proportional to the noise level.
High Confidence Generalization for Reinforcement Learning

We present several classes of reinforcement learning algorithms that safely generalize to Markov decision processes (MDPs) not seen during training. Speciﬁcally, we study the setting in which some set of MDPs is accessible for training. For various deﬁnitions of safety, our algorithms give probabilistic guarantees that agents can safely generalize to MDPs that are sampled from the same distribution but are not necessarily in the training set. These algorithms are a type of Seldo-nian algorithm (Thomas et al., 2019), which is a class of machine learning algorithms that return models with probabilistic safety guarantees for user-speciﬁed deﬁnitions of safety.
An Efficient Convolutional Blind Source Separation Algorithm for Speech Signals under Chaotic Masking

As the main method of information transmission, it is particularly important to ensure the security of speech communication. Considering the more complex multipath channel transmission situation in the wireless communication of speech signals and separating or extracting the source signal from the convolutional signal are crucial steps in obtaining source information. In this paper, chaotic masking technology is used to guarantee the transmission safety of speech signals, and a fast fixed-point independent vector analysis algorithm is used to solve the problem of convolutional blind source separation. First, the chaotic masking is performed before the speech signal is sent, and the convolutional mixing process of multiple signals is simulated by impulse response filter. Then, the observed signal is transformed to the frequency domain by short-time Fourier transform, and instantaneous blind source separation is performed using a fast fixed-point independent vector analysis algorithm. The algorithm can preserve the high-order statistical correlation between frequencies to solve the permutation ambiguity problem in independent component analysis. Simulation experiments show that this algorithm can efficiently complete the blind extraction of convolutional signals, and the quality of recovered speech signals is better. It provides a solution for the secure transmission and effective separation of speech signals in multipath transmission channels.