Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of VIP and Sonic Hedgehog Signaling Pathways in Mediating Epithelial Wound Healing, Sensory Nerve Regeneration, and Their Defects in Diabetic Corneas

Diabetic keratopathy, a sight-threatening corneal disease, comprises several symptomatic conditions including delayed epithelial wound healing, recurrent erosions, and sensory nerve (SN) neuropathy. We investigated the role of neuropeptides in mediating corneal wound healing, including epithelial wound closure and SN regeneration. Denervation by resiniferatoxin severely impaired corneal wound healing and markedly upregulated proinflammatory gene expression. Exogenous neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP) partially reversed resiniferatoxin’s effects, with VIP specifically inducing interleukin-10 expression. Hence, we focused on VIP and observed that wounding induced VIP and VIP type 1 receptor (VIPR1) expression in normal (NL) corneas, but not corneas from mice with diabetes mellitus (DM). Targeting VIPR1 in NL corneas attenuated corneal wound healing, dampened wound-induced expression of neurotrophic factors, and exacerbated inflammatory responses, while exogenous VIP had the opposite effects in DM corneas. Remarkably, wounding and diabetes also affected the expression of Sonic Hedgehog (Shh) in a VIP-dependent manner. Downregulating Shh expression in NL corneas decreased while exogenous Shh in DM corneas increased the rates of corneal wound healing. Furthermore, inhibition of Shh signaling dampened VIP-promoted corneal wound healing. We conclude that VIP regulates epithelial wound healing, inflammatory response, and nerve regeneration in the corneas in an Shh-dependent manner, suggesting a therapeutic potential for these molecules in treating diabetic keratopathy.
Regarding ICNIRP’S Evaluation of the National Toxicology Program’s Carcinogenicity Studies on Radiofrequency Electromagnetic Fields

Dear Editor: IN THE International Commission on Non-Ionizing Radiation Protection (ICNIRP) note (ICNIRP 2019) on the evaluation of the recent carcinogenicity studies of radiofrequency electromagnetic fields (RF-EMF) in experimental animals, the authors made several incorrect statements that appear to be written to justify retaining exposure standards that were established more than 20 y ago. In fact, the ICNIRP note concludes, “. if the research was shown to have relevance to humans, this would represent a crucial issue for ICNIRP to incorporate into the advice and guidance that it provides to the community through a range of formats, such as its RF EMFexposure guidelines. ” This correspondence focuses on correcting ICNIRP’s false claims about the methodology, interpretation, and relevance of the National Toxicology Program studies on cell phone RF radiation (NTP 2018a and b). Several issues raised in the ICNIRP note were addressed by Melnick (2019) and in the NTP response to the initial reviews of the cancer findings in rats that are included in the NTP report of partial findings of the carcinogenesis studies of cell phone radiofrequency radiation (Wyde et al. 2016) but were ignored in the ICNIRP note.
Parsaclisib Is a Next-Generation Phosphoinositide 3-Kinase δ Inhibitor with Reduced Hepatotoxicity and Potent Antitumor and Immunomodulatory Activities in Models of B-Cell Malignancy

The clinical use of first-generation phosphoinositide 3-kinase (PI3K)δ inhibitors in B-cell malignancies is hampered by hepatotoxicity, requiring dose reduction, treatment interruption, and/or discontinuation of therapy. In addition, potential molecular mechanisms by which resistance to this class of drugs occurs have not been investigated. Parsaclisib (INCB050465) is a potent and selective next-generation PI3Kδ inhibitor that differs in structure from first-generation PI3Kδ inhibitors and has shown encouraging anti–B-cell tumor activity and reduced hepatotoxicity in phase 1/2 clinical studies. Here, we present preclinical data demonstrating parsaclisib as a potent inhibitor of PI3Kδ with over 1000-fold selectivity against other class 1 PI3K isozymes. Parsaclisib directly blocks PI3K signaling–mediated cell proliferation in B-cell lines in vitro and in vivo and indirectly controls tumor growth by lessening immunosuppression through regulatory T-cell inhibition in a syngeneic lymphoma model. Diffuse large B-cell lymphoma cell lines overexpressing MYC were insensitive to proliferation blockade via PI3Kδ signaling inhibition by parsaclisib, but their proliferative activities were reduced by suppression of MYC gene transcription. Molecular structure analysis of the first- and next-generation PI3Kδ inhibitors combined with clinical observation suggests that hepatotoxicity seen with the first-generation inhibitors could result from a structure-related off-target effect. Parsaclisib is currently being evaluated in multiple phase 2 clinical trials as a therapy against various hematologic malignancies of B-cell origin (NCT03126019, NCT02998476, NCT03235544, NCT03144674, and NCT02018861). SIGNIFICANCE STATEMENT The preclinical properties described here provide the mechanism of action and support clinical investigations of parsaclisib as a therapy for B-cell malignancies. MYC overexpression was identified as a resistance mechanism to parsaclisib in DLBCL cells, which may be useful in guiding further translational studies for the selection of patients with DLBCL who might benefit from PI3Kδ inhibitor treatment in future trials. Hepatotoxicity associated with first-generation PI3Kδ inhibitors may be an off-target effect of that class of compounds.
The Effects of Adding Different HALS on the Curing Process, Film Properties and Lightfastness of Refined Oriental Lacquer

Oriental lacquer is a natural polymeric coating with a satiny texture and excellent characteristics, such as chemical resistance and durability. However, the poor lightfastness resulted in the natural aromatic structures of the urushiol structures limited its suitability for outdoor application. This study aimed at the improvement of the lightfastness by adding the different hindered amine light stafbilizers (HALS) with 2 phr addition as well as the effects on the coating and film property of the refined oriental lacquers (RL). The Cryptomeria japonica plate, glass sheets, and the other substrates were used for finishing. The results showed that the lightfastness of RL film was obviously improved by adding 2 phr HALS of Bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (H90) containing -NH group and Bis (1,2,2,6,6-pentamethyl-4-piperidinyl)-[[3,5-bis(1,1-dimethyl ethyl) -4-hydroxyphenyl] methyl] butylmalonate (H60) containing -NCH3 groups. The HALS additions increased the pH value of RL and improved the activities of laccase-catalyzed reaction. Meanwhile, the oxidative polymerization of the side chains of RL was inhibited, caused by a radical scavenging ability of HALS. The changes in the drying process affected not only the curing time, but also the film properties. Among the 2 phr additions of different HALS, the film containing H90 had the best lightfastness. Meanwhile, it kept the most similar properties with RL and shortened the drying time of RL, and it was selected as the best HALS addition under 2 phr in this study.
Crescimento aéreo e radicular de arroz de terras altas em função da adubação fosfatada e bioestimulante

O uso de fitorreguladores que estimulam maior crescimento radicular pode favorecer a absorcao de fosforo em arroz cultivado no sistema de terras altas. Objetivou-se avaliar o crescimento aereo e radicular de arroz submetido a diferentes doses de fosforo na presenca e ausencia de bioestimulante. O experimento foi conduzido em casa de vegetacao da Faculdade de Ciencias Agronomicas-UNESP, em Botucatu-SP. Os tratamentos constaram de 6 doses de P na semeadura (0, 12,5, 25, 50, 100 e 200 mg dm-3), na presenca e ausencia de Stimulate® aplicado via sementes (cultivar Primavera). Aos 78 dias apos emergencia, as plantas foram cortadas na altura do colo para determinacao da area foliar e materia seca de folhas e colmo. As amostras de raizes coletadas no mesmo dia tiveram o diâmetro medio radicular e massa da materia seca determinadas. O delineamento experimental utilizado foi inteiramente casualizado, com tres repeticoes, em esquema fatorial 2x6. Foram feitas analises de variância e regressao, e ajustaram-se equacoes lineares e quadraticas significativas ate 5% de probabilidade pelo teste F, que apresentaram os maiores coeficientes de determinacao (R2). Com o aumento das doses de P, a producao de massa e area foliar das plantas de arroz foi menor na presenca do bioestimulante. Para o acumulo de fosforo na parte aerea e determinacoes do sistema radicular, comportamento semelhante foi observado. Conclui-se que o uso de Stimulate® no tratamento de sementes, tanto para a producao de fitomassa como nas determinacoes do sistema radicular, foi eficiente apenas em baixas quantidades de adubo aplicado.
The Clinical Impact of Low-Volume Lymph Nodal Metastases in Early-Stage Cervical Cancer: The Senticol 1 and Senticol 2 Trials

Background: With the development of the sentinel node technique in early-stage cervical cancer, it is imperative to define the clinical significance of micrometastases (MICs) and isolated tumor cells (ITCs). Methods: We included all patients who participated in the Senticol 1 and Senticol 2 studies. We analyzed the factors associated with the presence of low-volume metastasis, the oncological outcomes of patients with MIC and ITC and the correlation of recurrences and risk factors. Results: Twenty-four patients (7.5%) had low-volume metastasis. The risk factors associated with the presence of low-volume metastasis were a higher stage (p = 0.02) and major stromal invasion (p = 0.01) in the univariate analysis. The maximum specificity and sensitivity were found at a cutoff of 8 mm of stromal invasion. In multivariate analysis, the higher stage (p = 0.02) and the positive lymphovascular space invasion (p = 0.02) were significantly associated with the MIC and ITC. Patients with low-volume metastasis had similar disease-free survival (DFS) (92.7%) to node-negative patients (93.6%). The addition of adjuvant treatment in presence of low-volume metastasis did not modify the DFS. Conclusions: These results confirm our previous analysis of Senticol 1: the presence of low-volume metastasis did not decrease the DFS in early-stage cervical cancer patients.
Connectivity over a disease risk gradient enables recovery of rainforest frogs.

Chytridiomycosis has been a key driver of global frog declines and extinctions, particularly for high-altitude populations across Australia and the Americas. While recent evidence shows some species are recovering, the extent of such recoveries and the mechanisms underpinning them remain poorly resolved. We surveyed the historical latitudinal and elevational range of four Australian rainforest frogs that disappeared from upland sites between 1989 and 1994 to establish their contemporary distribution and elevational limits, and investigate factors affecting population recovery. Five rainforest streams were surveyed from mountain-base to summit (30 sites in total), with swabs collected from the target species (Litoria dayi, L. nannotis, L. rheocola and L. serrata) to determine their infection status, and dataloggers deployed to measure microclimatic variation across the elevational gradient. Infection probability increased with elevation and canopy cover as it was tightly and inversely correlated with stream-side air temperature. Occupancy patterns suggest varying responses to this disease threat gradient. Two species - L. rheocola and L. serrata - were found over their full historical elevational range (≥ 1000 m asl), while L. dayi was not detected above 400 m (formerly known up to 900 m asl) and L. nannotis was not detected above 800 m (formerly known up to 1200 m asl). Site occupancy probability was negatively related to predicted infection prevalence for L. dayi, L. nannotis and L. rheocola, but not L. serrata, which appears to now tolerate high fungal burdens. This study highlights the importance of environmental refuges and connectivity across disease risk gradients for the persistence and natural recovery of frogs susceptible to chytridiomycosis. Likewise, in documenting both interspecific variation in recovery rates and intraspecific differences between sites, this study suggests interactions between disease threats and host selection exist that could be manipulated. For example, translocations may be warranted where connectivity is poor or the increase in disease risk is too steep to allow recolonization, combined with assisted selection or use of founders from populations that have already undergone natural selection.
COVID-19 and the Advancement of Digital Physical Therapist Practice and Telehealth

D uring the COVID-19 pandemic, each day challenges us with sobering realities in the economy, health care, and politics in our society. The global pandemic has thrust the physical therapy profession and our society into digital physical therapist practice and telehealth. In light of the uncertainty with COVID-19, physical therapists are required to socially distance themselves at least 6 feet apart in health care institutions, and patients and clients cannot access necessary physical therapy services in the community due to shelter-in-place and stay-at-home restrictions. Furthermore, this unique situation magnifies the challenges and opportunities in digital practice, as practitioners may lack the necessary telehealth competencies identified in the literature. Therefore, it is especially important for physical therapy practitioners to consider key recommendations for safe and effective digital practice delivery.
Combining independent de novo assemblies to optimize leaf transcriptome of Persian walnut

Transcriptome resources can facilitate to increase yield and quality of walnuts. Finding the best transcriptome assembly has not been the subject of walnuts research as yet. This research generated 240,179,782 reads from 11 walnut leaves according to cDNA libraries. The reads provided a complete de novo transcriptome assembly. Fifteen different transcriptome assemblies were constructed from five different well-known assemblers used in scientific literature with different k-mer lengths (Bridger, BinPacker, SOAPdenovo-Trans, Trinity and SPAdes) as well as two merging approaches (EvidentialGene and Transfuse). Based on the four quality metrics of assembly, the results indicated an efficiency in the process of merging the assemblies after being generated by de novo assemblers. Finally, EvidentialGene was recognized as the best assembler for the de novo assembly of the leaf transcriptome in walnut. Among a total number of 183,191 transcripts which were generated by EvidentialGene, there were 109,413 transcripts capable of protein potential (59.72%) and 104,926 were recognized as ORFs (57.27%). In addition, 79,185 transcripts were predicted to exist with at least one hit to the Pfam database. A number of 3,931 transcription factors were identified by BLAST searching against PlnTFDB. Furthermore, 6,591 of the predicted peptide sequences contained signaling peptides, while 92,704 contained transmembrane domains. Comparison of the assembled transcripts with transcripts of the walnut and published genome assembly for the ‘Chandler’ cultivar using the BLAST algorithm led to identify a total number of 27,304 and 19,178 homologue transcripts, respectively. De novo transcriptomes in walnut leaves can be developed for the future studies in functional genomics and genetic studies of walnuts.
Toward reliable measurements of perceptual scales in multiple contexts

A central question in psychophysical research is how perceptual differences between stimuli translate into physical differences and vice versa. Characterizing such a psychophysical scale would reveal how a stimulus is converted into a perceptual event, particularly under changes in viewing conditions (e.g., illumination). Various methods exist to derive perceptual scales, but in practice, scale estimation is often bypassed by assessing appearance matches. Matches, however, only reflect the underlying perceptual scales but do not reveal them directly. Two recently developed methods, MLDS (Maximum Likelihood Difference Scaling) and MLCM (Maximum Likelihood Conjoint Measurement), promise to reliably estimate perceptual scales. Here we compared both methods in their ability to estimate perceptual scales across context changes in the domain of lightness perception. In simulations, we adopted a lightness constant, a contrast, and a luminance-based observer model to generate differential patterns of perceptual scales. MLCM correctly recovered all models. MLDS correctly recovered only the lightness constant observer model. We also empirically probed both methods with two types of stimuli: (a) variegated checkerboards that support lightness constancy and (b) center-surround stimuli that do not support lightness constancy. Consistent with the simulations, MLDS and MLCM provided similar scale estimates in the first case and divergent estimates in the second. In addition, scales from MLCM–and not from MLDS–accurately predicted asymmetric matches for both types of stimuli. Taking experimental and simulation results together, MLCM seems more apt to provide a valid estimate of the perceptual scales underlying judgments of lightness across viewing conditions.
“Frozen evolution” of an RNA virus suggests accidental release as a potential cause of arbovirus re-emergence

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an arthropod-borne virus of ruminants, emerged in livestock in northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of euros. Although the outbreak was successfully controlled through vaccination by early 2010, puzzlingly, a closely related BTV-8 strain re-emerged in France in 2015, triggering a second outbreak that is still ongoing. The origin of this virus and the mechanisms underlying its re-emergence are unknown. Here, we performed phylogenetic analyses of 164 whole BTV-8 genomes sampled throughout the two outbreaks. We demonstrate consistent clock-like virus evolution during both epizootics but found negligible evolutionary change between them. We estimate that the ancestor of the second outbreak dates from the height of the first outbreak in 2008. This implies that the virus had not been replicating for multiple years prior to its re-emergence in 2015. Given the absence of any known natural mechanism that could explain BTV-8 persistence over this long period without replication, we hypothesise that the second outbreak could have been initiated by accidental exposure of livestock to frozen material contaminated with virus from approximately 2008. Our work highlights new targets for pathogen surveillance programmes in livestock and illustrates the power of genomic epidemiology to identify pathways of infectious disease emergence.
Microbial Adaptation Due to Gastric Bypass Surgery: The Nutritional Impact

Bariatric surgery leads to sustained weight loss and the resolution of obesity-related comorbidities. Recent studies have suggested that changes in gut microbiota are associated with the weight loss induced by bariatric surgery. Several studies have observed major changes in the microbial composition following gastric bypass surgery. However, there are inconsistencies between the reported alterations in microbial compositions in different studies. Furthermore, it is well established that diet is an important factor shaping the composition and function of intestinal microbiota. However, most studies on gastric bypass have not assessed the impact of dietary intake on the microbiome composition in general, let alone the impact of restrictive diets prior to bariatric surgery, which are recommended for reducing liver fat content and size. Thus, the relative impact of bariatric surgery on weight loss and gut microbiota remains unclear. Therefore, this review aims to provide a deeper understanding of the current knowledge of the changes in intestinal microbiota induced by bariatric surgery considering pre-surgical nutritional changes.
Herpes simplex virus type 2 trivalent protein vaccine containing glycoproteins C, D and E protects guinea pigs against HSV-1 genital infection

ABSTRACT A vaccine to prevent genital herpes is an unmet public health need. We previously reported that a trivalent vaccine containing herpes simplex virus type 2 (HSV-2) glycoproteins C, D, and E (gC2, gD2, gE2) produced in baculovirus and administered with CpG/alum as adjuvants blocks immune evasion mediated by gC2 and gE2 and virus entry by gD2. The vaccine protected guinea pigs against HSV-2 vaginal infection. We evaluated whether the HSV-2 vaccine cross-protects against HSV-1 because many first-time genital herpes infections are now caused by HSV-1. Guinea pigs were mock immunized or immunized with the trivalent vaccine and challenged intravaginally with a different HSV-1 isolate in two experiments. Guinea pigs immunized with the trivalent vaccine developed genital lesions on fewer days than the mock group: 2/477 (0.4%) days compared to 15/424 (3.5%) in experiment one, and 0/135 days compared to 17/135 (12.6%) in experiment two (both P < .001). No animal in the trivalent group had HSV-2 DNA detected in vaginal secretions: 0/180 days for trivalent compared to 4/160 (2.5%) for mock (P < .05) in experiment one, and 0/65 days for trivalent compared to 4/65 (6%) for mock in experiment two. Therefore, a vaccine designed to prevent HSV-2 also protects against HSV-1 genital infection.
Social-Psychological Factors in Food Consumption of Rural Residents: The Role of Perceived Need and Habit within the Theory of Planned Behavior

To address the problem of malnutrition in poor rural areas of China, this study aims to examine the effects of social-psychological factors in food consumption of rural residents in poor counties of Southwest China. In addition, it investigates the role of perceived need and habit within the theory of planned behavior (TPB) in predicting food consumption. A survey with random sampling was conducted on rural residents (n = 424), and the theoretical frameworks of both the standard and extended TPB were applied for comparison purposes. Structural equation modeling was applied to test the relationships among constructs. Consumption of five food items was studied, respectively: meat, eggs, dairy, fish, and fruits. Results showed that incorporation of perceived need and habit substantially increased the explanatory power of the TPB, but these factors only had significant direct effects on intention rather than behavior. Perceived need and habit are stronger predictors of intention than any other TPB construct for consumption of all food items except for meat. We found indirect effects of the constructs in the extended TPB model on consumption to be different across food items. Practical implications to improve consumption of different food items were proposed accordingly.
Nutritional composition and antioxidant capacity of several edible mushrooms grown in the Southern Vietnam.

Mushrooms are a good source of nutrients. They are popular in daily food over the world. This study was conducted to evaluate the nutritive values, total phenolic compounds and antioxidant activity of five popular Vietnamese edible mushrooms (Pleurotus ostreatus, Volvariella volvacea, Lentinula edodes, Auricularia polytricha and Ganoderma lucidum). Protein, lipid, ash and total carbohydrate contents ranged from 7.2 – 36.6%, 1.7 – 3.0%, 1.4 – 9.0% and 52.3 – 88.6%, respectively, on a dry weight basis. P. ostreatus, V. volvacea, L. edodes and G. lucidum contained large amounts of total free phenolic compounds, which exhibited significant antioxidant capacity of the extracts. In addition, the total bound phenolic content of G. lucidum was also high resulting in high antioxidant capacity of the extract. The findings show that the edible mushrooms can be used not only as nutritious foods but also as pharmaceutical medicines with high antioxidants.