Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate

Introduction While there has been considerable progress in the development of vaccines against SARS-CoV-2, largely based on the S (spike) protein of the virus, less progress has been made with vaccines delivering different viral antigens with cross-reactive potential. Methods In an effort to develop an immunogen with the capacity to induce broad antigen presentation, we have designed a multi-patch synthetic candidate containing dominant and persistent B cell epitopes from conserved regions of SARS-CoV-2 structural proteins associated with long-term immunity, termed CoV2-BMEP. Here we describe the characterization, immunogenicity and efficacy of CoV2-BMEP using two delivery platforms: nucleic acid DNA and attenuated modified vaccinia virus Ankara (MVA). Results In cultured cells, both vectors produced a main protein of about 37 kDa as well as heterogeneous proteins with size ranging between 25-37 kDa. In C57BL/6 mice, both homologous and heterologous prime/boost combination of vectors induced the activation of SARS-CoV-2-specific CD4 and CD8 T cell responses, with a more balanced CD8+ T cell response detected in lungs. The homologous MVA/MVA immunization regimen elicited the highest specific CD8+ T cell responses in spleen and detectable binding antibodies (bAbs) to S and N antigens of SARS-CoV-2. In SARS-CoV-2 susceptible k18-hACE2 Tg mice, two doses of MVA-CoV2-BMEP elicited S- and N-specific bAbs as well as cross-neutralizing antibodies against different variants of concern (VoC). After SARS-CoV-2 challenge, all animals in the control unvaccinated group succumbed to the infection while vaccinated animals with high titers of neutralizing antibodies were fully protected against mortality, correlating with a reduction of virus infection in the lungs and inhibition of the cytokine storm. Discussion These findings revealed a novel immunogen with the capacity to control SARS-CoV-2 infection, using a broader antigen presentation mechanism than the approved vaccines based solely on the S antigen.
MLNet: a multi-level multimodal named entity recognition architecture

In the field of human–computer interaction, accurate identification of talking objects can help robots to accomplish subsequent tasks such as decision-making or recommendation; therefore, object determination is of great interest as a pre-requisite task. Whether it is named entity recognition (NER) in natural language processing (NLP) work or object detection (OD) task in the computer vision (CV) field, the essence is to achieve object recognition. Currently, multimodal approaches are widely used in basic image recognition and natural language processing tasks. This multimodal architecture can perform entity recognition tasks more accurately, but when faced with short texts and images containing more noise, we find that there is still room for optimization in the image-text-based multimodal named entity recognition (MNER) architecture. In this study, we propose a new multi-level multimodal named entity recognition architecture, which is a network capable of extracting useful visual information for boosting semantic understanding and subsequently improving entity identification efficacy. Specifically, we first performed image and text encoding separately and then built a symmetric neural network architecture based on Transformer for multimodal feature fusion. We utilized a gating mechanism to filter visual information that is significantly related to the textual content, in order to enhance text understanding and achieve semantic disambiguation. Furthermore, we incorporated character-level vector encoding to reduce text noise. Finally, we employed Conditional Random Fields for label classification task. Experiments on the Twitter dataset show that our model works to increase the accuracy of the MNER task.
Pancreatic stellate cells in pancreatic cancer: as potential targets for future therapy

Pancreatic cancer is a strongly malignant gastrointestinal carcinoma characterized by late detection, high mortality rates, poor patient prognosis and lack of effective treatments. Consequently, there is an urgent need to identify novel therapeutic strategies for this disease. Pancreatic stellate cells, which constitute a significant component of the mesenchymal cellular layer within the pancreatic tumor microenvironment, play a pivotal role in modulating this environment through their interactions with pancreatic cancer cells. This paper reviews the mechanisms by which pancreatic stellate cells inhibit antitumor immune responses and promote cancer progression. We also discuss preclinical studies focusing on these cells, with the goal of providing some theoretical references for the development of new therapeutic approaches for pancreatic cancer.
Stimulatory effect of fluoxetine and desipramine, but not mirtazapine on C26 colon carcinoma hepatic metastases formation: association with cytokines

Due to the high prevalence of depression among cancer patients, antidepressant medications are frequently administered as adjuvant treatment. However, the safety of such medications in the development of metastasis is unclear. In this study, we investigated the effects of fluoxetine, desipramine, and mirtazapine on the liver metastasis of murine C26 colon carcinoma (cc). Balb/c male mice were administered these antidepressants intraperitoneally (i.p.) for 14 days following intrasplenic injections of C26 colon carcinoma cells. Desipramine and fluoxetine, but not mirtazapine, significantly increased the number of tumor foci and total volume of the tumor in liver tissue. This effect was associated with a decrease in the ability of splenocytes to produce interleukin (IL)-1β and interferon (IFN)-γ and an increase in their ability to produce interleukin (IL)-10. Similar changes were observed in plasma IL-1β, IFN-γ, and IL-10 levels. The current study demonstrates that the stimulatory effect of desipramine and fluoxetine, but not mirtazapine, on experimental colon cancer liver metastasis is associated with a suppression of immune defenses against the tumor.
Young transgender individuals' lived experiences of facing life's challenges: a qualitative study in Iran

Introduction In recent years, several studies have addressed the challenges and psychological issues that transgender individuals face. However, only a few studies have explored the experiences of this population in Iran. Life experiences are heavily influenced by the dominant religious and cultural conditions and common beliefs in a society. The present study aimed to investigate transgender individuals' lived experiences of facing life's challenges in Iran. Methods This is a qualitative study with a descriptive and phenomenological design conducted from February to April 2022. Data were collected using semi-structured, in-depth interviews with 23 transgender individuals (13 AFAB and 10 AMAB). The collected data were analyzed using Colaizzi's method. Results Analysis of the qualitative data resulted in the emergence of three themes and 11 subthemes. The three main themes included mental health disparities (fear of having one's secret revealed, depression and despair, suicidal thoughts, and secrecy in the family), gender dysphoria (contradictory gender identity and contradictory behaviors), and stigma and insecurity (sexual abuse, social discrimination, disrupted occupational performance, a lack of support, disrepute, and disgrace). Conclusions The findings of the study indicated that transgender people in Iran are exposed to considerable mental health disparities. In addition to disrepute, infamy, and stigma, transgender people face sexual abuse, social discrimination, and a lack of family social support. The results of the present study can help mental health experts and the healthcare system as a whole to adjust their mental and physical health programs according to the needs and experiences of transgender people and their families. It is recommended that future research address the problems and psychological challenges that transgender people's families have to confront.
Novel microRNAs modulating ecto-5′-nucleotidase expression

Introduction The expression of immune checkpoint molecules (ICMs) by cancer cells is known to counteract tumor-reactive immune responses, thereby promoting tumor immune escape. For example, upregulated expression of ecto-5′-nucleotidase (NT5E), also designated as CD73, increases extracellular levels of immunosuppressive adenosine, which inhibits tumor attack by activated T cells. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Thus, the binding of miRNAs to the 3′-untranslated region of target mRNAs either blocks translation or induces degradation of the targeted mRNA. Cancer cells often exhibit aberrant miRNA expression profiles; hence, tumor-derived miRNAs have been used as biomarkers for early tumor detection. Methods In this study, we screened a human miRNA library and identified miRNAs affecting the expression of ICMs NT5E, ENTPD1, and CD274 in the human tumor cell lines SK-Mel-28 (melanoma) and MDA-MB-231 (breast cancer). Thereby, a set of potential tumor-suppressor miRNAs that decreased ICM expression in these cell lines was defined. Notably, this study also introduces a group of potential oncogenic miRNAs that cause increased ICM expression and presents the possible underlying mechanisms. The results of high-throughput screening of miRNAs affecting NT5E expression were validated in vitro in 12 cell lines of various tumor entities. Results As result, miR-1285-5p, miR-155-5p, and miR-3134 were found to be the most potent inhibitors of NT5E expression, while miR-134-3p, miR-6859-3p, miR-6514-3p, and miR-224-3p were identified as miRNAs that strongly enhanced NT5E expression levels. Discussion The miRNAs identified might have clinical relevance as potential therapeutic agents and biomarkers or therapeutic targets, respectively.
Prediction of posttraumatic functional recovery in middle-aged and older patients through dynamic ensemble selection modeling

Introduction Age-specific risk factors may delay posttraumatic functional recovery; complex interactions exist between these factors. In this study, we investigated the prediction ability of machine learning models for posttraumatic (6 months) functional recovery in middle-aged and older patients on the basis of their preexisting health conditions. Methods Data obtained from injured patients aged ≥45 years were divided into training–validation (n = 368) and test (n = 159) data sets. The input features were the sociodemographic characteristics and baseline health conditions of the patients. The output feature was functional status 6 months after injury; this was assessed using the Barthel Index (BI). On the basis of their BI scores, the patients were categorized into functionally independent (BI >60) and functionally dependent (BI ≤60) groups. The permutation feature importance method was used for feature selection. Six algorithms were validated through cross-validation with hyperparameter optimization. The algorithms exhibiting satisfactory performance were subjected to bagging to construct stacking, voting, and dynamic ensemble selection models. The best model was evaluated on the test data set. Partial dependence (PD) and individual conditional expectation (ICE) plots were created. Results In total, nineteen of twenty-seven features were selected. Logistic regression, linear discrimination analysis, and Gaussian Naive Bayes algorithms exhibited satisfactory performances and were, therefore, used to construct ensemble models. The k-Nearest Oracle Elimination model outperformed the other models when evaluated on the training–validation data set (sensitivity: 0.732, 95% CI: 0.702–0.761; specificity: 0.813, 95% CI: 0.805–0.822); it exhibited compatible performance on the test data set (sensitivity: 0.779, 95% CI: 0.559–0.950; specificity: 0.859, 95% CI: 0.799–0.912). The PD and ICE plots showed consistent patterns with practical tendencies. Conclusion Preexisting health conditions can predict long-term functional outcomes in injured middle-aged and older patients, thus predicting prognosis and facilitating clinical decision-making.
Psoriasis immunometabolism: progress on metabolic biomarkers and targeted therapy

Psoriasis is a common inflammatory disease that affects mainly the skin. However, the moderate to severe forms have been associated with several comorbidities, such as psoriatic arthritis, Crohn’s disease, metabolic syndrome and cardiovascular disease. Keratinocytes and T helper cells are the dominant cell types involved in psoriasis development via a complex crosstalk between epithelial cells, peripheral immune cells and immune cells residing in the skin. Immunometabolism has emerged as a potent mechanism elucidating the aetiopathogenesis of psoriasis, offering novel specific targets to diagnose and treat psoriasis early. The present article discusses the metabolic reprogramming of activated T cells, tissue-resident memory T cells and keratinocytes in psoriatic skin, presenting associated metabolic biomarkers and therapeutic targets. In psoriatic phenotype, keratinocytes and activated T cells are glycolysis dependent and are characterized by disruptions in the TCA cycle, the amino acid metabolism and the fatty acid metabolism. Upregulation of the mammalian target of rapamycin (mTOR) results in hyperproliferation and cytokine secretion by immune cells and keratinocytes. Metabolic reprogramming through the inhibition of affected metabolic pathways and the dietary restoration of metabolic imbalances may thus present a potent therapeutic opportunity to achieve long-term management of psoriasis and improved quality of life with minimum adverse effects.
Care-seeking correlates of acute respiratory illness among sheltered adults experiencing homelessness in Seattle, WA, 2019: a community-based cross-sectional study

Objective Multifarious barriers to accessing healthcare services among people experiencing homelessness (PEH) lead to delays in seeking care for acute infections, including those caused by respiratory viruses. PEH are at high risk of acute respiratory illness (ARI)-related complications, especially in shelter settings that may facilitate virus spread, yet data characterizing healthcare utilization for ARI episodes among sheltered PEH remained limited. Methods We conducted a cross-sectional study of viral respiratory infection among adult residents at two homeless shelters in Seattle, Washington between January and May 2019. We assessed factors associated with seeking medical care for ARI via self-report. We collected illness questionnaires and nasal swabs were tested for respiratory viruses by reverse transcription quantitative real-time PCR (RT-qPCR). Results We observed 825 encounters from 649 unique participants; 241 (29.2%) encounters reported seeking healthcare for their ARI episode. Seasonal influenza vaccine receipt (adjusted prevalence ratio [aPR] 1.39, 95% CI 1.02–1.88), having health insurance (aPR 2.77, 95% CI 1.27–6.02), chronic lung conditions (aPR 1.55, 95% CI 1.12-2.15), and experiencing influenza-like-illness symptoms (aPR 1.63, 95% CI 1.20 - 2.20) were associated with increased likelihood of seeking care. Smoking (aPR 0.65, 95% CI 0.45-0.92) was associated with decreased likelihood of seeking care. Discussion Findings suggest that care seeking for viral respiratory illness among PEH may be supported by prior engagement with primary healthcare services. Strategies to increase healthcare utilization may lead to earlier detection of respiratory viruses.
Mitigation of heat stress effects on laying hens' performances, egg quality, and some blood parameters by adding dietary zinc-enriched yeasts, parsley, and their combination

Objective Finding natural, handy and efficient nutritional solutions to prevent and mitigate negative effects caused by environmental heat stress and to be applied to large-scale laying hen industry. Research design A 3-weeks trial was conducted on 128 laying hens TETRA-SL LL (50 weeks of age) housed in 8 cages/group, 4 laying hens/cage, 32 laying hens/group, under heat stress conditions (34±1°C). The basal diet on corn and soybean meal was formulated to be isocaloric and isonitrogenic. Compared to Control group diet (C), experimental groups E1 included 1% zinc-enriched yeast; E2 included 2% parsley and E3 included 1% zinc-enriched yeast combined with 2% parsley to minimize the heat stress effects. Methods The parsley and the zinc-enriched yeast were analysed for their chemical composition, total polyphenols, antioxidant capacity, minerals, vitamin E and incorporated into the ration structure. Production parameters, egg quality, biochemical and haematological profiles of blood samples were analysed during the trial. Results A statistically significant (p < 0.05) average egg weight was noticed on E2 and E3 compared to Control group, and also during the 1st week compared to the 2nd and the 3rd experimental weeks. Average daily feed intake values were highly significant (p < 0.001) on E3 group compared to C, E1, E2, and on the 2nd week compared to the 3rd experimental week (p < 0.021). Feed conversion rate was highly significant (p < 0.001) during the 2nd and the 3rd experimental weeks compared to the 1st week. The average daily egg production was highly significant (p < 0.001) within 1st week compared to the 2nd and 3rd weeks. A highly significant (p < 0.001) yolk coloration was noticed on E2 and E3 groups. The malondialdehyde (MDA) concentration decreased significantly (p < 0.05) to all experimental groups compared to Control group during the 14th and 28th days of storage. Conclusion These findings suggest that the two ingredients minimized the heat stress effects on production performance parameters with a demonstrated antioxidant capacity role by delaying the lipid peroxidation during different storage time periods.
In vitro activities of antimicrobial combinations against planktonic and biofilm forms of Stenotrophomonas maltophilia

Objectives To investigate the in vitro activity of antibiotic combinations against Stenotrophomonas maltophilia isolates and their associated biofilms. Methods Thirty-two S. maltophilia clinical isolates with at least twenty-five different pulsotypes were tested. The antibacterial activity of various antibiotic combinations against seven randomly selected planktonic and biofilm-embedded S. maltophilia strains with strong biofilm formation was assessed using broth methods. Extraction of bacterial genomic DNA and PCR detection of antibiotic resistance and biofilm-related genes were also performed. Results The susceptibility rates of levofloxacin (LVX), fosfomycin (FOS), tigecycline (TGC) and sulfamethoxazole-trimethoprim (SXT) against 32 S. maltophilia isolates were 56.3, 71.9, 71.9 and 90.6%, respectively. Twenty-eight isolates were detected with strong biofilm formation. Antibiotic combinations, including aztreonam-clavulanic (ATM-CLA) with LVX, ceftazidime-avibactam (CZA) with LVX and SXT with TGC, exhibited potent inhibitory activity against these isolates with strong biofilm formation. The antibiotic resistance phenotype might not be fully caused by the common antibiotic-resistance or biofilm-formation gene. Conclusion S. maltophilia remained resistant to most antibiotics, including LVX and β-lactam/β-lactamases; however, TGC, FOS and SXT still exhibited potent activity. Although all tested S. maltophilia isolates exhibited moderate-to-strong biofilm formation, combination therapies, especially ATM-CLA with LVX, CZA with LVX and SXT with TGC, exhibited a higher inhibitory activity for these isolates.
Effects of dietary inclusion of dry distillers grains with solubles on performance, carcass characteristics, and nitrogen metabolism in meat sheep: a meta-analysis

We conducted a meta-analysis in this scientific study to determine the effects of feeding meat sheep dry distillers grains with solubles (DDGS). Thirty-three peer-reviewed articles that met our inclusion requirements and were published between 1997 and 2021 were examined. To calculate the variation in performance, fermentation, carcass features, and nitrogen efficiency between the DDGS and control (no DDGS) treatments, we used 940 sheep weighing an average of 29.1 ± 1.5 kg. We used a hierarchical mixed model to conduct a meta-regression, subset, and dose–response analysis, while taking into consideration categorical variables like breed (pure or cross-breed), and continuous factors, like CP, NDF, and DDGS inclusion rate. Our findings indicate that sheep fed DDGS had higher (p < 0.05) final body weight (51.4 vs. 50.4 kg), neutral detergent fiber digestibility (55.9 vs. 53.8%), and total-tract ether extract digestibility (81.7 vs. 78.7%) than sheep on a control diet. No effects were observed on DMI, CP, and rumen fermentation, but dietary DDGS tended to increase (p = 0.07) HC weight (25.53 vs. 24.6 kg) and meat (redness) color (16.6 vs. 16.3) among treatment comparisons. Dietary DDGS was associated with higher N intake (29.9 vs. 26.8 g/d), fecal N (8.2 vs. 7.8 g/d), and digestibility (71.9 vs. 68.5%). Urinary nitrogen was significantly (p < 0.05) affected linearly by increasing the intake of DDGS in the diet. Based on the dose–response analysis, dietary DDGS inclusion should not exceed 20% to avoid negative effects on performance, nitrogen metabolism, and meat color. Dietary protein from DDGS should not exceed 17% to prevent reduced TVFA concentrations. Breed strongly influenced (p < 0.05) RMD in performance, and inconsistent responses were observed between crossbreed and purebred sheep comparisons. Despite these inconsistencies, no publication bias was observed, but a high variance (Ω2) among comparisons-between-studies was detected. This meta-analysis showed evidence in support of the hypothesis that feeding meat sheep DDGS at a rate of 20% can improve their performance, digestibility, carcass weight, and meat color.