Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging Translational Opportunities in Comparative Oncology With Companion Canine Cancers: Radiation Oncology

It is estimated that more than 6 million pet dogs are diagnosed with cancer annually in the USA. Both primary care and specialist veterinarians are frequently called upon to provide clinical care that improves the quality and/or quantity of life for affected animals. Because these cancers develop spontaneously in animals that often share the same environment as their owners, have intact immune systems and are of similar size to humans, and because the diagnostic tests and treatments for these cancers are similar to those used for management of human cancers, canine cancer provides an opportunity for research that simultaneously helps improve both canine and human health care. This is especially true in the field of radiation oncology, for which there is a rich and continually evolving history of learning from the careful study of pet dogs undergoing various forms of radiotherapy. The purpose of this review article is to inform readers of the potential utility and limitations of using dogs in that manner; the peer-reviewed literature will be critically reviewed, and current research efforts will be discussed. The article concludes with a look toward promising future directions and applications of this pet dog “model. ”
Well-Being Lessons for Improving Charities’ Online Recruitment

In an increasingly competitive context, attracting and retaining the best employees are a real preoccupation and a big challenge for organizations. Online recruitment (OR) is a growing trend, and corporate websites are an important instrument for talent attraction, but academic research on this topic is still scarce, especially in the voluntary sector. To shed light on the topic, this study examines and compares the 100 best companies to work for, published by Fortune, and the 100 largest charities, reported by Forbes. The comparative study focuses the attention and quantifies the web section devoted to careers, concretely information related to goods practices affecting the workers well-being. The results indicated, as essential in the OR process of charities, to understand the relevance of their web content because that affects the intentions of potential applicants. The work concludes that benchmarking efforts can be helpful for increasing the charities’ attractiveness in the labor market in the near future.
An Artificial Intelligent Signal Amplification System for in vivo Detection of miRNA

MicroRNAs (miRNA) have been identified as oncogenic drivers and tumor suppressors in every major cancer type. In this work, we design an artificial intelligent signal amplification (AISA) system including double-stranded SQ (S, signal strand; Q, quencher strand) and FP (F, fuel strand; P, protect strand) according to thermodynamics principle for sensitive detection of miRNA in vitro and in vivo. In this AISA system for miRNA detection, strand S carries a quenched imaging marker inside the SQ. Target miRNA is constantly replaced by a reaction intermediate and circulatively participates in the reaction, similar to enzyme. Therefore, abundant fluorescent substances from S and SP are dissociated from excessive SQ for in vitro and in vivo visualization. The versatility and feasibility for disease diagnosis using this system were demonstrated by constructing two types of AISA system to detect Hsa-miR-484 and Hsa-miR-100, respectively. The minimum target concentration detected by the system in vitro (10 min after mixing) was 1/10th that of the control group. The precancerous lesions of liver cancer were diagnosed, and the detection accuracy were larger than 94% both in terms of location and concentration. The ability to establish this design framework for AISA system with high specificity provides a new way to monitor tumor progression and to assess therapeutic responses.
Measuring the Interaction Between the Macro- and Micro-Vasculature

Structural and functional dysfunction in both the macro- and microvasculature are a feature of essential hypertension. In a healthy cardiovascular system, the elastic properties of the large arteries ensure that pulsations in pressure and flow generated by cyclic left ventricular contraction are dampened, so that less pulsatile pressure and flow are delivered at the microvascular level. However, in response to aging, hypertension, and other disease states, arterial stiffening limits the buffering capacity of the elastic arteries, thus exposing the microvasculature to increased pulsatile stress. This is thought to be particularly pertinent to high flow/low resistance organs such as the brain and kidney, which may be sensitive to excess pressure and flow pulsatility, damaging capillary networks, and resulting in target organ damage. In this review, we describe the clinical relevance of the pulsatile interaction between the macro- and microvasculature and summarize current methods for measuring the transmission of pulsatility between the two sites.
Long Non-coding RNA SNHG12 Functions as a Competing Endogenous RNA to Regulate MDM4 Expression by Sponging miR-129-5p in Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC), the most common histological subtype of kidney cancer, shows poor prognosis, and non-sensitivity to radiotherapy or chemotherapy. The lncRNA small nucleolar RNA host gene 12 (SNHG12) has been revealed to play a carcinogenic role in various neoplasms, but the underlying mechanism in ccRCC is still unclear. To explore the potential role of SNHG12 in ccRCC, the data downloaded from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) Data Portal was used to compare the expression of SNHG12 in tumors and adjacent normal tissues. MRNA microarray and quantitative real-time PCR revealed that SNHG12 was overexpressed in the ccRCC tissues and cell lines. Functional inhibition of SNHG12 suppressed the viability and mobility of ccRCC cells. Mechanistically, dual luciferase assay and RNA immunoprecipitation (RIP) assay showed that miR-129-5p could bind to SNHG12 directly. There was a negative relationship between SNHG12 and miR-129-5p. What's more, we used bioinformatics-based prediction software to predict the target genes of miR-129-5p. Through data analysis and experimental verification, we found MDM4, a regulatory factor in p53 pathway, was involved in this ceRNA network. Our findings demonstrated that SNHG12 served as a sponge for miR-129-5p to regulate the expression of MDM4 and p53 pathway in the development of ccRCC.
In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease

Trypanosoma cruzi infection causes Chagas disease, which affects 7 million people worldwide. Two drugs are available to treat it: benznidazole and nifurtimox. Although both are efficacious against the acute stage of the disease, this is usually asymptomatic and goes undiagnosed and untreated. Diagnosis is achieved at the chronic stage, when life-threatening heart and/or gut tissue disruptions occur in ~30% of those chronically infected. By then, the drugs' efficacy is reduced, but not their associated high toxicity. Given current deficiencies in diagnosis and treatment, a vaccine to prevent infection and/or the development of symptoms would be a breakthrough in the management of the disease. Current vaccine candidates are mostly based on the delivery of single antigens or a few different antigens. Nevertheless, due to the high biological complexity of the parasite, targeting as many antigens as possible would be desirable. In this regard, an epitope-based vaccine design could be a well-suited approach. With this aim, we have gone through publicly available databases to identify T. cruzi epitopes from several antigens. By means of a computer-aided strategy, we have prioritized a set of epitopes based on sequence conservation criteria, projected population coverage of Latin American population, and biological features of their antigens of origin. Fruit of this analysis, we provide a selection of CD8+ T cell, CD4+ T cell, and B cell epitopes that have <70% identity to human or human microbiome protein sequences and represent the basis toward the development of an epitope-based vaccine against T. cruzi.
Anticancer activity of Yashada Bhasma (bioactive nanoparticles of zinc): A human pancreatic cancer cell line study

Background: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related mortality. Efforts to improve cancer treatment through nanotechnology are at the developmental stage, and it will be gracious if the drug with anticancer property itself is a nanoparticle. Bhasma is organomineral complexes which are bioactive nanoparticles. Yashada Bhasma (incinerated processed zinc) is widely used in Ayurveda for various diseases, and there are evidence that ZnO nanoparticles are promising antitumor agent. However, no studies have been conducted on the effectiveness of Yashada Bhasma in pancreatic cancer. Materials and Methods: Two types of test drugs, Parada Marita Yashada Bhasma(PMY) and Vanaspati Jarita Marita Yashada Bhasma (JMY), were prepared as per the guidelines of pharmaceutics of Ayurveda. Particle size analyses of Yashada Bhasma and Zeta potential study was carried out initially. Further human pancreatic cancer cell line (MIA PaCa-2) study was done using in vitro sulforhodamine B assay, keeping adriamycinas control. After 48 h of incubation, antiproliferative effects were assessed. Results: JMY and adriamycin showed dose-dependent growth inhibition of cancer cells. Both Yashada Bhasma samples showed a cytostatic effect at this concentration. Conclusion: The study leads to new avenues for cancer treatment by developing such unique and highly effective bioactive nano-sized therapeutic agent.
What do professionals need for an Open-Paediatric Intensive Care Unit (PICU)? A focus group study on PICU professionals

Background PICU is a complex stressful, high- tech environment for professionals, parents and critically ill children. Literature suggests that knowing the context is crucial in determine the suitable interventions to act. Professionals’ needs in the Italian context need to be investigated. The aim of the study was to highlight the healthcare professionals’ perceptions of their needs regarding the concept of Open PICUs and the presence of parents during their child’s stay in the PICU, without highly restricted visiting policies. Methods Qualitative approach ( multi-professional focus group) was used. The transcription and categorization followed the principles of “content analysis”. Criteria concerning validity, reliability, confirmability and replicability have been satisfied.
Gender Difference in Gender Bias: Transcranial Direct Current Stimulation Reduces Male’s Gender Stereotypes

Stereotypes exist in the interactions between different social groups, and gender stereotypes are particularly prevalent. Previous studies have suggested that the medial prefrontal cortex (mPFC) is involved in the social cognition that plays an important role in gender stereotypes, but the specific causal effect of the mPFC remains controversial. In this study, we aimed to use transcranial direct current stimulation (tDCS) to identify a direct link between the mPFC and gender bias. Implicit stereotypes were measured by the gender implicit association test (IAT), and explicit prejudice was measured by the Ambivalent Sexism Inventory (ASI). We found that male and female participants had different behavioral and neural correlates of gender stereotypes. Anodal tDCS significantly reduced male participants’ gender D-IAT scores compared with cathodal and sham stimulation, while the stimulation had an insignificant effect in female participants. The reduction in male participants’ gender bias mainly resulted from a decrease in the difference in reaction time (RT) between congruent and incongruent blocks. Regarding the explicit bias measurement, male and female participants had distinct attitudes, but tDCS had no effect on ASI. Our results revealed that the mPFC played a causal role in controlling implicit gender stereotypes, which is consistent with previous observations and complements past lesion, neuroimaging, and transcranial magnetic stimulation (TMS) studies and suggests that males and females have different neural bases for gender stereotypes.
Estimation of User-Applied Isometric Force/Torque Using Upper Extremity Force Myography

Hand force estimation is critical for applications that involve physical human-machine interactions for force monitoring and machine control. Force Myography (FMG) is a potential technique to be used for estimating hand force/torque. The FMG signals reflect the volumetric changes in the arm muscles due to muscle contraction or expansion. This paper investigates the feasibility of employing force-sensing resistors (FSRs) worn on the arm to measure the FMG signals for isometric force/torque estimation. Nine participants were recruited in this study and were asked to exert isometric force along three perpendicular axes, torque about the same three axes, and force and torque simultaneously. During the tests, the isometric force and torque were measured using a 6-degree-of-freedom (DoF) (i.e., force in three axes and torque around the same axes) load cell for ground truth labels whereas the FMG signals were recorded using a total number of 60 FSRs, which were embedded into four bands worn on the different locations of the arm. A two-stage regression strategy was employed to enhance the performance of the FMG bands, where three regression algorithms including general regression neural network (GRNN), support vector regression (SVR), and random forest regression (RF) models were employed, respectively, in the first stage and GRNN was used in the second stage. Two cases were considered to explore the performance of the FMG bands in estimating: (1) 3-DoF force and 3-DoF torque at once and (2) 6-DoF force and torque. In addition, the impact of sensor placement and the spatial coverage of FMG measurements were studied. This preliminary investigation demonstrates promising potential of FMG to estimate multi-DoF isometric force/torque. Specifically, R2 accuracies of 0.83 for the 3-DoF force, 0.84 for 3-DoF torque, and 0.77 for the combination of force and torque (6-DoF) regressions were obtained using the four bands on the arm in cross-trial evaluation.
The Differences of Serum Metabolites Between Patients With Early-Stage Alzheimer's Disease and Mild Cognitive Impairment

Background: Mild cognitive impairment (MCI) is regarded as a transition phase between normal aging and Alzheimer's disease (AD). Identification of novel and non-invasive biomarkers that can distinguish AD at an early stage from MCI is warranted for therapeutic and support planning. The goal of this study was to identify the differences of serum metabolomic profiles between MCI and early-stage AD, which could be potential non-invasive biomarkers for early diagnosis of AD. Methods: The subjects enrolled in the study were classified into two diagnostic groups: MCI (n = 40) and early-stage AD (n = 40). Targeted metabolomics analysis of serum samples was performed using the Biocrates Absolute-IDQ P180 kit. Targeted metabolic data were analyzed by TargetLynx, and MetIDQ software was applied to integrate the metabolites by automated calculation of metabolite concentrations. Results: The datasets of targeted metabolite analysis were analyzed by the orthogonal-projection-to-latent-structure–discriminant-analysis (OPLS-DA) model. The OPLS-DA score plots demonstrated considerable separation between the MCI and early-stage AD patients. The levels of pimelylcarnitine, putrescine, SM (OH) C24:1, and SM C24:0 were significantly lower, whereas the levels of acetylornithine, methionine sulfoxide, and PC ae C44:3 were significantly higher in early-stage AD patients as compared with MCI patients. Receiver operating characteristic curve analysis of a combination of three lipid metabolites [SM (OH) C24:1, SM C24:0, and PC ae C44:3] showed an acceptable discrimination between the early-stage AD and MCI patients (area under the curve = 0.788). Conclusions: Our results characterized the differences of serum metabolic profiles between MCI and early-stage AD patients. The positive findings from this study indicate that the minimally invasive method of blood sampling may help to identify patients with AD at an early stage from those with MCI.
Assessing Worry About Affording Healthcare in a General Population Sample

This study adapted a measure on worry about affording healthcare. The financial costs of healthcare are increasingly being shifted to patients. Financial burden from healthcare costs can be material (such as bankruptcy) or psychological. Psychological distress can be either worry about affording future care or distress due to material consequences and, despite evidence from clinical psychology that differentiates these types of emotional symptoms, this distinction has largely been ignored for financial burden in healthcare. We adapted a worry about affording healthcare scale for use in the general population (n = 398) to facilitate comparisons between disease groups and across countries. Participants completed a survey through an online platform. The worry about affording healthcare measure showed good reliability and validity through associations with quality of life (QOL) and measures of other types of financial burden. Worry about affording healthcare was also associated with cost-related non-adherence to medical care. Future research on patient QOL should consider worry about affording healthcare.
Putative Iron-Sulfur Proteins Are Required for Hydrogen Consumption and Enhance Survival of Mycobacteria

Aerobic soil bacteria persist by scavenging molecular hydrogen (H2) from the atmosphere. This key process is the primary sink in the biogeochemical hydrogen cycle and supports the productivity of oligotrophic ecosystems. In Mycobacterium smegmatis, atmospheric H2 oxidation is catalyzed by two phylogenetically distinct [NiFe]-hydrogenases, Huc (group 2a) and Hhy (group 1h). However, it is currently unresolved how these enzymes transfer electrons derived from H2 oxidation into the aerobic respiratory chain. In this work, we used genetic approaches to confirm that two putative iron-sulfur cluster proteins encoded on the hydrogenase structural operons, HucE and HhyE, are required for H2 consumption in M. smegmatis. Sequence analysis show that these proteins, while homologous, fall into distinct phylogenetic clades and have distinct metal-binding motifs. H2 oxidation was reduced when the genes encoding these proteins were deleted individually and was eliminated when they were deleted in combination. In turn, the growth yield and long-term survival of these deletion strains was modestly but significantly reduced compared to the parent strain. In both biochemical and phenotypic assays, the mutant strains lacking the putative iron-sulfur proteins phenocopied those of hydrogenase structural subunit mutants. We hypothesize that these proteins mediate electron transfer between the catalytic subunits of the hydrogenases and the menaquinone pool of the M. smegmatis respiratory chain; however, other roles (e.g., in maturation) are also plausible and further work is required to resolve their role. The conserved nature of these proteins within most Hhy- or Huc-encoding organisms suggests that these proteins are important determinants of atmospheric H2 oxidation.
The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial

Background: Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS). We tested the hypothesis that melatonin use before and during the first cycle of ACBC is better than placebo at improving the DPMS function assessed by changes in the 0–10 Numerical Pain Scale (NPS) during the conditioned pain modulating task (CPM-task) (primary outcome). The effects of melatonin were evaluated in the following secondary endpoints: heat pain threshold (HPT), heat pain tolerance (HPTo), and neuroplasticity state assessed by serum brain-derived neurotrophic factor (BDNF), tropomyosin kinase receptor B, and S100B-protein and whether melatonin’s effects on pain and neuroplasticity state are due more so to its impact on sleep quality. Methods: Thirty-six women, ages 18 to 75 years old, scheduled for their first cycle of ACBC were randomized to receive 20mg of oral melatonin (n = 18) or placebo (n = 18). The effect of treatment on the outcomes was analyzed by delta (Δ)-values (from pre to treatment end). Results: Multivariate analyses of covariance revealed that melatonin improved the function of the DPMS. The Δ-mean (SD) on the NPS (0–10) during the CPM-task in the placebo group was −1.91 [−1.81 (1.67) vs. −0.1 (1.61)], and in the melatonin group was −3.5 [−0.94 (1.61) vs. −2.29 (1.61)], and the mean difference (md) between treatment groups was 1.59 [(95% CI, 0.50 to 2.68). Melatonin’s effect increased the HPTo and HPT while reducing the (Δ)-means of the serum neuroplasticity marker in placebo vs. melatonin. The Δ-BDNF is 1.87 (7.17) vs. −20.44 (17.17), respectively, and the md = 22.31 [(95% CI = 13.40 to 31.22)]; TrKB md = 0.61 [0.46 (0.17) vs. −0.15 (0.18); 95% CI = 0.49 to 0.73)] and S00B-protein md = −8.27[(2.89 (11.18) vs. −11.16 (9.75); 95% CI = −15.38 to −1.16)]. However, melatonin’s effect on pain and the neuroplastic state are not due to its effect on sleep quality. Conclusions: These results suggest that oral melatonin, together with the first ACBC counteracts the dysfunction in the inhibitory DPMS and improves pain perception measures. Also, it shows that changes in the neuroplasticity state mediate the impact of melatonin on pain. Clinical Trial Registration: www.ClinicalTrials. gov, identifier NCT03205033.
New Light on Chloroplast Redox Regulation: Molecular Mechanism of Protein Thiol Oxidation

Thiol-based redox regulation is a posttranslational protein modification that plays a key role in adjusting chloroplast functions in response to changing light conditions. Redox-sensitive target proteins are reduced upon illumination, which turns on (or off in a certain case) their enzyme activities. A redox cascade via ferredoxin, ferredoxin-thioredoxin reductase, and thioredoxin has been classically recognized as the key system for transmitting the light-induced reductive signal to target proteins. By contrast, the molecular mechanism underlying target protein oxidation, which is observed during light to dark transitions, remains undetermined over the past several decades. Recently, the factors and pathways for protein thiol oxidation in chloroplasts have been reported, finally shedding light on this long-standing issue. We identified thioredoxin-like2 as one of the protein-oxidation factors in chloroplasts. This protein is characterized by its higher redox potential than that of canonical thioredoxin, that is more favorable for target protein oxidation. Furthermore, 2-Cys peroxiredoxin and hydrogen peroxide are also involved in the overall protein-oxidation machinery. Here we summarize the newly uncovered “dark side” of chloroplast redox regulation, giving an insight into how plants rest their photosynthetic activity at night.