Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined Vaccination with NY-ESO-1 Protein, Poly-ICLC, and Montanide Improves Humoral and Cellular Immune Responses in Patients with High-Risk Melanoma

Vaccination with NY-ESO-1, poly-ICLC, and montanide induces integrated antigen-specific humoral and cellular responses in patients with high-risk, resected melanoma. In the future, this strategy could be combined with checkpoint blockade immunotherapy, the current standard of care for these patients. Given its ability to induce both humoral and cellular immune responses, NY-ESO-1 has been considered a suitable antigen for a cancer vaccine. Despite promising results from early-phase clinical studies in patients with melanoma, NY-ESO-1 vaccine immunotherapy has not been widely investigated in larger trials; consequently, many questions remain as to the optimal vaccine formulation, predictive biomarkers, and sequencing and timing of vaccines in melanoma treatment. We conducted an adjuvant phase I/II clinical trial in high-risk resected melanoma to optimize the delivery of poly-ICLC, a TLR-3/MDA-5 agonist, as a component of vaccine formulation. A phase I dose-escalation part was undertaken to identify the MTD of poly-ICLC administered in combination with NY-ESO-1 and montanide. This was followed by a randomized phase II part investigating the MTD of poly-ICLC with NY-ESO-1 with or without montanide. The vaccine regimens were generally well tolerated, with no treatment-related grade 3/4 adverse events. Both regimens induced integrated NY-ESO-1–specific CD4+ T-cell and humoral responses. CD8+ T-cell responses were mainly detected in patients receiving montanide. T-cell avidity toward NY-ESO-1 peptides was higher in patients vaccinated with montanide. In conclusion, NY-ESO-1 protein in combination with poly-ICLC is safe, well tolerated, and capable of inducing integrated antibody and CD4+ T-cell responses in most patients. Combination with montanide enhances antigen-specific T-cell avidity and CD8+ T-cell cross-priming in a fraction of patients, indicating that montanide contributes to the induction of specific CD8+ T-cell responses to NY-ESO-1.
Growth Performance and Carcass Traits Responses to Dried Distillers’ Grain with Solubles Feeding of Growing Awassi Ram Lambs

Simple Summary Corn grain is considered to be the most important crop in the world. Corn dried distiller grains with solubles is a by-product of ethanol production. It is included at 0, 125, or 25 g/kg in lambs’ diets. This inclusion reduced the cost of diet, indicating the good possibility of using it in small ruminant diets. Abstract This study considers the impact of dried distillers’ grain with solubles (DDGS) in diets of lambs. Randomly; 27 lambs were distributed to one of three diets. Diets were: a control diet (CON; n = 9), a 125 (DDGS125; n = 9) or a 250 g/kg DDGS (DDGS250; n = 9) of dietary dry matter (DM). The lambs were fed using these diets for 91 days. To assess carcass traits; five lambs were randomly selected at the end of the study. No significant differences were detected in intake and digestibility of DM; crude protein and fiber. Average daily gain did not differ among diets. Carcass characteristics did not differ among diets. With the exception of shear force and redness, which were greater in DDGS250 than in DDGS125 and CON diets, meat quality parameters were unaffected. Eye muscle area decreased in DDGS125 than in DDGS250 and CON diet. These results demonstrate that the feeding of lambs on DDGS at 125 or 250 g/kg DM did not have any impact on growth. These diets only had a simple effect on the characteristics of carcass and meat quality. These results suggest that it would be suitable to introduce these feeds into sheep nutrition in the future.
Tooth Malformations, DMFT Index, Speech Impairment and Oral Habits in Patients with Fetal Alcohol Syndrome

Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder with severe negative lifetime consequences. Although knowledge about the harmfulness of alcohol consumption during pregnancy has spread, the prevalence of fetal alcohol spectrum disorder is very high. Our study aims at identifying fetal alcohol syndrome (FAS)-associated dental anomalies or habits, which need early attention. Methods: Sixty children (30 FAS; 30 controls) were examined prospectively. Swallowing pattern, oral habits, breastfeeding, speech therapy, ergotherapy, physiotherapy, exfoliation of teeth, DMFT (decayed, missing, filled teeth) index, modified DDE (developmental defects of enamel) index and otitis media were recorded. Results: Swallowing pattern, exfoliation of teeth, and otitis media were not significantly different. Significant differences could be found concerning mouthbreathing (p = 0.007), oral habits (p = 0.047), age at termination of habits (p = 0.009), speech treatment (p = 0.002), ergotherapy, physiotherapy, and breastfeeding (p ≤ 0.001). DMFT (p ≤ 0.001) and modified DDE (p = 0.001) index showed significantly higher values for children with fetal alcohol syndrome. Conclusions: Children with fetal alcohol syndrome have a higher need for early developmental promotion such as speech treatment, ergotherapy, and physiotherapy. Mouthbreathing, habits, and lack of breastfeeding may result in orthodontic treatment needs. High DMFT and modified DDE indexes hint at a higher treatment and prevention need in dentistry.
Psychological Pathway from Obesity-Related Stigma to Anxiety via Internalized Stigma and Self-Esteem among Adolescents in Taiwan

The objective of this research was to examine the pathway from public stigma, to perceived stigma, to depression in adolescents via internalized stigma. Adolescents in grade 7 through 9 from a junior high school in Changhua County in Taiwan completed self-administered surveys from March to July in 2018. Adolescents were asked questions regarding depressive symptoms, obesity-related perceived stigma, and internalized stigma. Structural equation modeling was used to fit the pathway model. The pathway was first analyzed with the full sample and then stratified by actual and perceived weight status. Our final analytic sample consisted of 464 adolescents. The pathway model suggested an acceptable model fit. Perceived weight stigma (PWS) was significantly associated with internalized stigma regardless of actual or self-perceived weight status. Internalized stigma was significantly associated with anxiety for both actual (β = 0.186) and self-perceived nonoverweight (non-OW) participants (β = 0.170) but not for overweight (OW) participants (neither actual nor self-perceived). For OW adolescents, perceived weight stigma was associated with anxiety. However, the internalization process did not exist. It may be that the influence of perceived weight stigma is larger than internalized stigma on anxiety. It may also be that the level of internalization was not yet high enough to result in anxiety.
Are changes in ADHD course reflected in differences in IQ and executive functioning from childhood to young adulthood?

Abstract Background Attention-deficit hyperactivity disorder (ADHD) is associated with poorer cognitive functioning. We used a developmental, genetically-sensitive approach to examine intelligence quotient (IQ) from early childhood to young adulthood among those with different ADHD courses to investigate whether changes in ADHD were reflected in differences in IQ. We also examined executive functioning in childhood and young adulthood among different ADHD courses. Methods Study participants were part of the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2232 twins. We assessed ADHD in childhood (ages 5, 7, 10 and 12) and young adulthood (age 18). We examined ADHD course as reflected by remission, persistence and late-onset. IQ was evaluated at ages 5, 12 and 18, and executive functioning at ages 5 and 18. Results ADHD groups showed deficits in IQ across development compared to controls; those with persistent ADHD showed the greatest deficit, followed by remitted and late-onset. ADHD groups did not differ from controls in developmental trajectory of IQ, suggesting changes in ADHD were not reflected in IQ. All ADHD groups performed more poorly on executive functioning tasks at ages 5 and 18; persisters and remitters differed only on an inhibitory control task at age 18. Conclusions Differences in ADHD course – persistence, remission and late-onset – were not directly reflected in changes in IQ. Instead, having ADHD at any point across development was associated with lower average IQ and poorer executive functioning. Our finding that individuals with persistent ADHD have poorer response inhibition than those who remitted requires replication.
Antimicrobial Activity of Oregano Essential Oil Incorporated in Sodium Alginate Edible Films: Control of Listeria monocytogenes and Spoilage in Ham Slices Treated with High Pressure Processing

The aim of the study was to evaluate the efficacy of oregano essential oil (OEO) incorporated in Na-alginate edible films when applied to sliced ham inoculated with a cocktail of Listeria monocytogenes strains, with or without pretreatment by high pressure processing (HPP). Microbiological, physicochemical and sensory analyses (in Listeria-free slices) were performed, while, the presence/absence and the relative abundance of each Listeria strain, was monitored by pulsed field gel electrophoresis (PFGE). The OEO incorporation in the films, caused approximately 1.5 log reduction in Listeria population at 8 and 12 °C at the end of the storage period, and almost 2.5 log reduction at 4 °C. The HPP treatment caused 1 log reduction to the initial Listeria population, while levels kept on decreasing throughout the storage for all the tested temperatures. The pH of the samples was higher in the cases where HPP was involved, and the samples were evaluated as less spoiled. Furthermore, the presence of OEO in the films resulted in color differences compared to the control samples, whilst the aroma of these samples was improved. In conclusion, the combined application of HPP and OEO edible films on the slices, led to a significant reduction or absence of the pathogen.
Comparative Characterization of Protein Hydrolysates from Three Edible Insects: Mealworm Larvae, Adult Crickets, and Silkworm Pupae

A comparative characterization of proteins from three edible insects—Tenebrio molitor (mealworm) larvae, Gryllus bimaculatus (cricket), and Bombyx mori (silkworm) pupae—was performed in this study. Proteins were extracted from edible insects and their hydrolysates were prepared through enzymatic hydrolysis with commercial enzymes (Flavourzyme: 12%; Alcalase: 3%). Solubility was significantly higher following enzymatic hydrolysis, while foamability was lower compared to those of the protein control. Angiotensin-converting enzyme was significantly inhibited after enzymatic hydrolysis, especially following Alcalase treatment, with IC50 values of 0.047, 0.066, and 0.065 mg/mL for G. bimaculatus, T. molitor larvae, and B. mori pupae, respectively. Moreover, the Alcalase-treated group of B. mori pupae and the T. molitor larvae group treated with a mixture of enzymes showed the effective inhibition of α-glucosidase activity. The anti-inflammatory activity of the insect hydrolysates was assessed via nitric oxide production from macrophages, and B. mori pupae samples exhibited significant activity regardless of the method of hydrolysis. These results indicate the functional properties of protein and hydrolysates from three species of edible insects, which may be useful in their future exploitation.
Nasal Cytokine Profiles of Patients Hospitalised with Respiratory Wheeze Associated with Rhinovirus C

Background: Rhinovirus C is an important pathogen of asthmatic and non-asthmatic children hospitalised with episodic wheeze. Previous studies on other respiratory viruses have shown that several host cytokines correlate with duration of hospitalisation, but this has yet to be investigated in children with RV-C infection. We determined the nasal cytokine profiles of these children and investigated their relationship with RV-C load and clinical outcome. Flocked nasal swabs were collected from children aged 24–72 months presenting to the Emergency Department at Princess Margaret Hospital with a clinical diagnosis of acute wheeze and an acute upper respiratory tract viral infection. RV-C load was determined by quantitative RT-PCR and cytokine profiles were characterised by a commercial human cytokine 34-plex panel. RV-C was the most commonly detected virus in pre-school-aged children hospitalised with an episodic wheeze. RV-C load did not significantly differ between asthmatic and non-asthmatic patients. Both groups showed a Th2-based cytokine profile. However, Th17 response cytokines IL-17 and IL-1β were only elevated in RV-C-infected children with pre-existing asthma. Neither RV-C load nor any specific cytokines were associated illness severity in this study. Medically attended RV-C-induced wheeze is characterised by a Th2 inflammatory pattern, independent of viral load. Any therapeutic interventions should be aimed at modulating the host response following infection.
Simulated climate change decreases nutrient resorption from senescing leaves

Nutrient resorption is the process whereby plants recover nutrients from senescing leaves and reallocate them to storage structures or newer tissues. Elemental resorption of foliar N and P has been shown to respond to temperature and precipitation, but we know remarkably little about the influence of warming and drought on the resorption of these and other essential plant macro‐ and micronutrients, which could alter the ability of species to recycle their nutrients. We conducted a 5 year manipulative field study to simulate predicted climate change conditions and studied the effects of warming (W), rainfall reduction (RR), and their combination (W+RR) on nutrient resorption efficiency in five coexisting shrub species in a semiarid shrubland. Both mature and senesced leaves showed significant reductions in their nutrient contents and an altered stoichiometry in response to climate change conditions. Warming (W, W+RR) reduced mature leaf N, K, Ca, S, Fe, and Zn and senesced leaf N, Ca, Mg, S, Fe, and Zn contents relative to ambient temperature conditions. Warming increased mature leaf C/N ratios and decreased N/P and C/P ratios and increased senesced leaf C/N and C/P ratios. Furthermore, W and W+RR reduced nutrient resorption efficiencies for N (6.3%), K (19.8%), S (70.9%) and increased Ca and Fe accumulation in senesced leaves (440% and 35.7%, respectively) relative to the control treatment. Rainfall reduction decreased the resorption efficiencies of N (6.7%), S (51%), and Zn (46%). Reductions in nutrient resorption efficiencies with warming and/or rainfall reduction were rather uniform and consistent across species. The negative impacts of warming and rainfall reduction on foliar nutrient resorption efficiency will likely cause an impairment of plant nutrient budgets and fitness across coexisting native shrubs in this nutrient‐poor habitat, with probable implications for key ecosystem functions such as reductions in nutrient retention in vegetation, litter decomposition, and nutrient cycling rates.
Conservation and Divergence in the Meiocyte sRNAomes of Arabidopsis, Soybean, and Cucumber1[OPEN]

Soybean meiocyte-specific small RNAs display a positive association with the coding region of genes that are transcriptionally upregulated during meiosis. Meiosis is a critical process for sexual reproduction. During meiosis, genetic information on homologous chromosomes is shuffled through meiotic recombination to produce gametes with novel allelic combinations. Meiosis and recombination are orchestrated by several mechanisms including regulation by small RNAs (sRNAs). Our previous work in Arabidopsis (Arabidopsis thaliana) meiocytes showed that meiocyte-specific sRNAs (ms-sRNAs) have distinct characteristics, including positive association with the coding region of genes that are transcriptionally upregulated during meiosis. Here, we characterized the ms-sRNAs in two important crops, soybean (Glycine max) and cucumber (Cucumis sativus). Ms-sRNAs in soybean have the same features as those in Arabidopsis, suggesting that they may play a conserved role in eudicots. We also investigated the profiles of microRNAs (miRNAs) and phased secondary small interfering RNAs in the meiocytes of all three species. Two conserved miRNAs, miR390 and miR167, are highly abundant in the meiocytes of all three species. In addition, we identified three novel cucumber miRNAs. Intriguingly, our data show that the previously identified phased secondary small interfering RNA pathway involving soybean-specific miR4392 is more abundant in meiocytes. These results showcase the conservation and divergence of ms-sRNAs in flowering plants, and broaden our understanding of sRNA function in crop species.
Tumor-Associated Fibroblasts Promote HER2-Targeted Therapy Resistance through FGFR2 Activation

Purpose: Despite the therapeutic success of existing HER2-targeted therapies, tumors invariably relapse. This study aimed at identifying new mechanisms responsible for HER2-targeted therapy resistance. Experimental Design: We have used a platform of HER2-targeted therapy–resistant cell lines and primary cultures of healthy and tumor-associated fibroblasts (TAF) to identify new potential targets related to tumor escape from anti-HER2 therapies. Results: We have shown that TAFs promote resistance to HER2-targeted therapies. TAFs produce and secrete high levels of FGF5, which induces FGFR2 activation in the surrounding breast cancer cells. FGFR2 transactivates HER2 via c-Src, leading to resistance to HER2-targeted therapies. In vivo, coinoculating nonresistant cell lines with TAFs results in more aggressive and resistant tumors. Resistant cells activate fibroblasts and secrete FGFR ligands, creating a positive feedback loop that fuels resistance. FGFR2 inhibition not only inhibits HER2 activation, but also induces apoptosis in cells resistant to HER2-targeted therapies. In vivo, inhibitors of FGFR2 reverse resistance and resensitize resistant cells to HER2-targeted therapies. In HER2 patients' samples, α-SMA, FGF5, and FGFR2 contribute to poor outcome and correlate with c-Src activation. Importantly, expression of FGF5 and phospho-HER2 correlated with a reduced pathologic complete response rate in patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab, which highlights the significant role of TAFs/FGF5 in HER2 breast cancer progression and resistance. Conclusions: We have identified the TAF/FGF5/FGFR2/c-Src/HER2 axis as an escape pathway responsible for HER2-targeted therapy resistance in breast cancer, which can be reversed by FGFR inhibitors.
Increased density and age‐related sharing of synapses at the cone to OFF bipolar cell synapse in the mouse retina

Neural circuits in the adult nervous system are characterized by stable, cell type‐specific patterns of synaptic connectivity. In many parts of the nervous system these patterns are established during development through initial over‐innervation by multiple pre‐ or postsynaptic targets, followed by a process of refinement that takes place during development and is in many instances activity dependent. Here we report on an identified synapse in the mouse retina, the cone photoreceptor➔type 4 bipolar cell (BC4) synapse, and show that its development is distinctly different from the common motif of over‐innervation followed by refinement. Indeed, the majority of cones are contacted by single BC4 throughout development, but are contacted by multiple BC4s through ongoing dendritic elaboration between 1 and 6 months of age—well into maturity. We demonstrate that cell density drives contact patterns downstream of single cones in Bax null mice and may serve to maintain constancy in both the dendritic and axonal projective field.
EZH2 Loss Drives Resistance to Carboplatin and Paclitaxel in Serous Ovarian Cancers Expressing ATM

Mechanisms of intrinsic resistance of serous ovarian cancers to standard treatment with carboplatin and paclitaxel are poorly understood. Seventeen primary serous ovarian cancers classified as responders or nonresponders to standard treatment were screened with DigiWest protein array analysis for 279 analytes. Histone methyl transferase EZH2, an interaction partner of ataxia telangiectasia mutated (ATM), was found as one of the most significantly represented proteins in responsive tumors. Survival analysis of 616 patients confirmed a better outcome in patients with high EZH2 expression, but a worse outcome in patients with low EZH2 and high-ATM–expressing tumors compared with patients with low EZH2 and low-ATM–expressing tumors. A proximity ligation assay further confirmed an association between ATM and EZH2 in tumors of patients with an increased disease-free survival. Knockdown of EZH2 resulted in treatment-resistant cells, but suppression of both EZH2 and ATM, or ATM alone, had no effect. DigiWest protein analysis of EZH2-knockdown cells revealed a decrease in proteins involved in mitotic processes and checkpoint regulation, suggesting that deregulated ATM may induce treatment resistance. Implications: Ovarian cancer is a malignancy with high mortality rates, with to date, no successful molecular characterization strategies. Our study uncovers in a comprehensive approach the involvement of checkpoint regulation via ATM and EZH2, potentially providing a new therapeutic perspective for further investigations.
Information Needs and Information Gathering Behaviour of Medical Doctors in Maiduguri, Nigeria

Survey data describes the results of an investigation on the information needs and information gathering behaviour of Medical doctors in Maiduguri, Nigeria. A total of 158 Medical doctors (128) males and 30 (females) were used for the study. The overall response rate was around 70.2 percent. Medical doctors need specific medical information to enhance their knowledge on a day-to-day basis, particularly with the information explosion such as e-mail and internet facilities. Medical doctors prefer the use of publishers catalogues as the most important source for new developments in their relevant fields. Many do not have access to local data bases that are supposed to have remarkable impact on their information gathering behaviour.
Safety of peripheral administration of vasopressor medications: A systematic review

Vasopressor medications have traditionally been administered via central venous catheters (CVCs), primarily due to concerns of peripheral extravasation of vasoconstrictive medications. Recent studies have suggested that vasopressor administration via peripheral intravenous catheters (PiVCs) may be a feasible and safe alternative. This systematic review evaluates the safety of delivering vasopressor medications via PiVCs.
Heuristic neural network approach in histological sections detection of hydatidiform mole

Abstract. A heuristic-based, multineural network (MNN) image analysis as a solution to the problematical diagnosis of hydatidiform mole (HM) is presented. HM presents as tumors in placental cell structures, many of which exhibit premalignant phenotypes (choriocarcinoma and other conditions). HM is commonly found in women under age 17 or over 35 and can be partial HM or complete HM. Appropriate treatment is determined by correct categorization into PHM or CHM, a difficult task even for expert pathologists. Image analysis combined with pattern recognition techniques has been applied to the problem, based on 15 or 17 image features. The use of limited data for training and validation set was optimized using a k-fold validation technique allowing performance measurement of different MNN configurations. The MNN technique performed better than human experts at the categorization for both the 15- and 17-feature data, promising greater diagnostic consistency, and further improvements with the availability of larger datasets.