Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioinformatic Analysis Reveals Central Role for Tumor-Infiltrating Immune Cells in Uveal Melanoma Progression

Tumor-infiltrating immune cells are capable of effective cancer surveillance, and their abundance is linked to better prognosis in numerous tumor types. However, in uveal melanoma (UM), extensive immune infiltrate is associated with poor survival. This study aims to decipher the role of different tumor-infiltrating cell subsets in UM in order to identify potential targets for future immunotherapeutic treatment. We have chosen the TCGA-UVM cohort as a training dataset and GSE22138 as a testing dataset by mining publicly available databases. The abundance of 22 immune cell types was estimated using CIBERSORTx. Then, to determine the significance of tumor-infiltrating cell subsets in UM, we built a multicell type prognostic signature, which was validated in the testing cohort. The created signature was built upon the negative prognostic role of CD8+ T cells and M0 macrophages and the positive role of neutrophils. Based on the created signature score, we divided the patients into low- and high-risk groups. Kaplan-Meier, Cox, and ROC analyses demonstrated superior performance of our risk score compared to either clinical or pathologic characteristics of both cohorts. Further, we found the molecular pathways associated with cancer immunoevasion and metastasis to be enriched in the high-risk group, explaining both the lack of adequate immune surveillance despite increased infiltration of CD8+ T cells as well as the higher metastatic potential. Genes associated with tryptophan metabolism (IDO1 and KYNU) and metalloproteinases were among the most differentially expressed between the high- and low-risk groups. Our correlation analyses interpreted in context of published in vitro data strongly suggest the central role of CD8+ T cells in shifting the UM tumor microenvironment towards suppressive and metastasis-promoting. Therefore, we propose further investigations of IDO1 and metalloproteinases as novel targets for immunotherapy in lymphocyte-rich metastatic UM patients.
Preference and Practice of Traditional Medicine and Associated Factors in Jimma Town, Southwest Ethiopia

Background Traditional medicine is the sum total of knowledge, talents, and practices that are used to uphold health, as well as to avert, identify, improve, or treat illnesses. Sociodemographic/economic characteristics, culture, and environment can influence the preference and practice of traditional medicine. Objective To assess the preference and practices of traditional medicine and associated factors. Methods A community-based cross-sectional study was conducted among 271 residents of Jimma town. The data were collected by interviewing selected households. The households were selected by a simple random sampling technique. The data were analysed using SPSS version 20. Descriptive statistics were used for organizing, describing, and summarizing the data. Chi-square (X2) test was used to identify factors associated with the preference and practice of traditional medicine. Results More than half (221(81.5%)) of the participants practiced traditional medicine. Religion (X2 = 17.18; p=0.001), marital status (X2 = 15.42; p=0.001), occupation (X2 = 19.74; p=0.001), and educational level (X2 = 28.39; p ≤ 0.001) were the sociodemographic factors determining the use of traditional medicine. However, 25 (9.2%) of the participants preferred to use traditional medicine. Affordability (25 (100%)), religious affiliation (21 (84%)), and distance from home (20 (80%)) were some reasons for preference. Educational level (X2 = 15.56; p=0.04), marital status (X2 = 12.39; p=0.04), and occupation (X2 = 15.61; p=0.003) were the factors affecting their preference for traditional medicine. Conclusion A majority of the participants practiced traditional medicine use. Religion, marital status, occupation, and educational level were factors affecting the practice of the participants. More than half of the participants did not prefer to use traditional medicine. Affordability, religious affiliation, and distance from home were some reasons for preferring traditional medicine.
A platform for locoregional T-cell immunotherapy to control HNSCC recurrence following tumor resection

Surgical resection of head and neck squamous-cell carcinoma (HNSCC) is associated with high rates of local and distant recurrence, partially mitigated by adjuvant therapy. A pre-existing immune response in the patient’s tumor is associated with better outcomes following treatment with conventional therapies, but improved options are needed for patients with poor anti-tumor immunity. We hypothesized that local delivery of tumor antigen-specific T-cells into the resection cavity following surgery would direct T-cells to residual antigens in the margins and draining lymphatics and present a platform for T-cell-targeted immunotherapy. We loaded T-cells into a biomaterial that conformed to the resection cavity and demonstrated that it could release T-cells that retained their functional activity in-vitro, and in a HNSCC model in-vivo. Locally delivered T-cells loaded in a biomaterial were equivalent in control of established tumors to intravenous adoptive T-cell transfer, and resulted in the systemic circulation of tumor antigen-specific T-cells as well as local accumulation in the tumor. We demonstrate that adjuvant therapy with anti-PD1 following surgical resection was ineffective unless combined with local delivery of T-cells. These data demonstrate that local delivery of tumor-specific T-cells is an efficient option to convert tumors that are unresponsive to checkpoint inhibitors to permit tumor cures.
Risk communication and community engagement strategies for COVID-19 in 13 African countries

Background: Coronavirus disease 2019 (COVID-19) outbreak is a major threat facing health systems globally and African countries are not an exception. Stakeholders, governments, and national authorities have mounted responses to contain the pandemic. This study aimed to catalogue the risk communication and community engagement (RCCE) strategies as well as the challenges facing RCCE in 13 African countries. Methods: We conducted a narrative review of evidence to answer the aim of the study. The search was conducted in March 2021 and evidence published between December 2019 and February 2021 were included. Data reported in this article were obtained from reports, literature in peer-reviewed journals, grey literature and other data sources in 13 African countries. The 13 countries include Ethiopia, Ghana, Kenya, Algeria, Angola, Cote d’Ivoire, the Democratic Republic of the Congo, Mauritius, Nigeria, South Africa, Tanzania, Uganda, and Zambia. The authors also snowball further data to gather information for this review. Results: Most of the priority African countries have RCCE strategies to contain the transmission and spread of the coronavirus. Our findings revealed RCCE strategies in the 13 African countries focused on training and capacity building, risk communication systems, internal and partners’ coordination, community engagement, public communication, contending uncertainty, addressing misperceptions and managing misinformation. However, the RCCE response activities were not without challenges, which included distrust in government, cultural, social, and religious resistance, and inertia among others. Conclusion: With the similar RCCE approaches and interventions seen across the countries, it is clear that countries are learning from each other and from global health organizations to develop COVID-19 RCCE programs. It is important for African countries to address the challenges facing RCCE in order to effectively contain the pandemic and to prepare for future public health emergencies.
Nuclear factor-&kgr;B and basic fibroblast growth factor augment pannus formation in rheumatoid synovitis

Background Rheumatoid arthritis (RA) is a multisystem autoimmune disease that causes marked deformity in the small joints. Aim of the work The aim of this work is to determine the role of nuclear factor-&kgr;B (NF-&kgr;B) and basic fibroblast growth factor (bFGF) in the histological changes of RA synovial specimens. Patients and methods This study was carried out on 25 RA patients who were subjected to surgery and 10 control participants with post-traumatic knee joint injury. The paraffin blocks were sectioned and the slides were stained conventionally with hematoxylin and eosin (H&E) and immunohistochemical markers for NF-&kgr;B and bFGF. Interpretation, scoring, and statistical correlation of the histological findings were performed. Results Histological examination and scoring of the specimens from both groups indicated a highly significant statistical increase in the number of synovial cell layers, vascular density (5.2±2.5 vs. 1.1±1.1 and 5.7±1.1 vs. 1.5±0.7 respectively; P<0.01), fibrosis (5.9±3.3 vs. 0.5±0.4), perivascular lymphocytic infiltrate (2±1.5 vs. 0), lymphoid aggregates (3.9±0.4 vs. 0), free lymphocytes (2.8±1.3 vs. 0.45±0.4), and immunohistochemical staining for NF-&kgr;B and bFGF (P<0.001) in RA patients in comparison with the control group. The number of synovial cell layers and lymphocytic aggregates showed a positive correlation with NF-&kgr;B and bFGF staining. Similarly, perivascular lymphocytic infiltrate correlated positively with bFGF staining (P<0.001). Conclusion NF-&kgr;B and bFGF played a crucial role in augmenting and maintaining pannus formation in the synovium of RA patients.
Sertraline Induced Oromandibular Dystonia and Galactorrhea: A Case Report.

Selective Serotonin Reuptake Inhibitors (SSRI) are used frequently not only for their treatment efficacy, but also they are considered more tolerable and safe than other drugs used for anxiety and depression. However, studies and case reports have shown that extrapyramidal symptoms (EPS), which generally occur due to the use of antipsychotic drugs, also appear because of SSRI use. EPS induced by SSRIs appear in approximately 1 in 1000 or less (Sonmez & Kosger 2015). The most common EPS associated with SSRI use are akathisia, dystonia, parkinsonism and dyskinesia. Although nonpuerperal lactation or galactorrhea is a common side effect attributable to the use of antipsychotic drugs, it is also encountered with SSRI use (Suthar et al. 2018). However, it is essential to pay attention to the rare side effects of commonly used drugs such as SSRIs. In this case report, we present a case of oromandibular dystonia and galactorrhea due to sertraline use in a young female patient.
Self‐reported sleep and sleep deficiency: Results from a large initiative of sailors attached to U.S. Navy warships

Chronic insufficient sleep is known to lead to a broad range of negative consequences (e.g. poor health and cognitive performance). While insufficient sleep and associated fatigue are present in many diverse populations, it is of special concern in high‐risk military environments, where a mishap can result in catastrophic outcomes. Although many studies have been conducted to characterise sleep in general military populations, relatively few have been conducted using a large representative sample of sailors assigned to United States Naval warships. The present cross‐sectional study characterises self‐reported sleep parameters in sailors (N = 11,738) and explores the role of possible contributors to insufficient sleep. The results indicate that sailors, across a variety of different subgroups, do not obtain the amount of sleep that they report requiring for feeling well‐rested. Of the many potential factors thwarting sleep, workload and an uncomfortable mattress are the most promising candidates to target for improvement.
Danshensu alleviates bleomycin-induced pulmonary fibrosis by inhibiting lung fibroblast-to-myofibroblast transition via the MEK/ERK signaling pathway

ABSTRACT Pulmonary fibrosis (PF) is a chronic pulmonary interstitial disease, and its pathological process is closely related to fibroblast–myofibroblast differentiation. Danshensu (DSS) has been reported to exert an anti-fibrotic effect in heart and liver. However, it is unknown whether DSS has an equally anti-fibrotic effect on lungs. To evaluate the effect of DSS on PF and demonstrate its possible molecular mechanisms, we established an in vitro model on TGF-β1 (5 ng/mL)-stimulated NIH3T3 cells and in vivo model on bleomycin (BLM) (5 mg/kg)-induced PF mice. In vitro, our results revealed that 50 μM DSS effectively inhibited the fibroblast proliferation, migration and differentiation into myofibroblast. In vivo, our results showed that DSS (28 and 56 mg/kg) reduced damaged lung structures, infiltrated inflammatory cells and accumulated areas of collagen deposition. Moreover, we showed that DSS decreased the fibroblast-specific protein 1 (FSP-1) – and α-SMA-positive areas. Meanwhile, we indicated that DSS reduced the expression of TGF-β1, α-SMA and COL-I in the lung tissues of mice. To further explore the mechanism of DSS on alleviating PF, we detected the MEK/ERK signaling pathway. Our results showed that DSS reduced the phosphorylation of MEK1/2 and ERK1/2, indicating that DSS might inhibit the MEK/ERK signaling pathway. Taken together, these results demonstrated that DSS could suppress lung fibroblast proliferation, migration and differentiation to myofibroblasts, possibly through suppressing the MEK/ERK signaling pathway, which suggested that DSS might be a potential therapeutic drug for PF treatment. Grafical abstract
Actual and perceived motor competence mediate the relationship between physical fitness and technical skill performance in young soccer players

ABSTRACT This study examined the role of fundamental movement skills (FMS) and perceived competence in the relationship between physical fitness and technical soccer skills in children. Seventy boys aged 7-12 years of age (Mean ± SD = 9 ± 2 years) who were regularly engaged in grassroots soccer participated in the present study. The Test of Gross Motor Development-2 (Ulrich, 2001. Test of gross motor development (2nd ed.). Austin, TX: PRO-ED) was used to assess FMS and the Perceived Physical Ability Scale for Children (Colella, Morano, Bortoli, & Robazza, 2008. A physical self-efficacy scale for children. Social Behavior and Personality: an International Journal, 36, 841–848) was used to assess perceived competence. Technical skill was determined from three tests reflecting dribbling, passing and shooting. Z-scores of each measure were summed, creating a composite measure of technical skill. Three measures of physical fitness were employed; 15m sprint time, standing long jump, and seated medicine ball (1kg) throw. Z-scores for each measure were summed creating a composite measure of physical fitness. The relationship between technical skill and FMS, fitness, perceived competence and age was examined via path analysis. Results indicated two significant mediated pathways: from physical fitness to technical skills via FMS, and from physical fitness to technical skills via perceived competence. Once these mediators had been accounted for, there was no direct link from physical fitness to technical skills. Coaches should therefore seek to avoid one-sided delivery of practice by not solely focusing on football type drills, and focusing on a range of activities which enhance a broad foundation of FMS and promote strategies to positively influence a child’s perception of their own competence. Highlights Fundamental movement skills (FMS) are considered the foundation for physical activity and sport performance yet they tend to be overlooked, in favour of physical fitness, in the development of soccer talent. We examined mediating effects of FMS and perceived competence in the relationship between physical fitness and technical soccer skills in 70, 7-12 year old grassroots soccer players. We suggests there is no direct effect of physical fitness on technical skills in soccer but both FMS and perceived competence act as mediators of the physical fitness-technical skill relationship in children aged 7-12 years old. Coaches should therefore look to develop a broad base of FMS and a higher perception of competence to improve children's technical soccer skills.
NF‐κB/IKK activation by small extracellular vesicles within the SASP

Cellular senescence plays an important role in different biological and pathological conditions. Senescent cells communicate with their microenvironment through a plethora of soluble factors, metalloproteases and extracellular vesicles (EV). Although much is known about the role that soluble factors play in senescence, the downstream signalling pathways activated by EV in senescence is unknown. To address this, we performed a small molecule inhibitor screen and have identified the IκB kinases IKKε, IKKα and IKKβ as essential for senescence mediated by EV (evSASP). By using pharmacological inhibitors of IKKε, IKKα and IKKβ, in addition to CRISPR/Cas9 targeting their respective genes, we find these pathways are important in mediating senescence. In addition, we find that senescence activation is dependent on canonical NF‐κB transcription factors where siRNA targeting p65 prevent senescence. Importantly, these IKK pathways are also relevant to ageing as knockout of IKKA, IKKB and IKKE avoid the activation of senescence. Altogether, these findings open a new potential line of investigation in the field of senescence by targeting the negative effects of the evSASP independent of particular EV contents.
Transcriptional Response of Wolbachia to Dengue Virus Infection in Cells of the Mosquito Aedes aegypti

Aedes aegypti is a vector of several pathogenic viruses, including dengue, Zika, chikungunya, and yellow fever viruses, which are of importance to human health. Wolbachia is an endosymbiotic bacterium currently used in transinfected mosquitoes to suppress replication and transmission of dengue viruses. However, the mechanism of Wolbachia-mediated virus inhibition is not fully understood. ABSTRACT Aedes aegypti transmits one of the most significant mosquito‐borne viruses, dengue virus (DENV). The absence of effective vaccines and clinical treatments and the emergence of insecticide resistance in A. aegypti necessitate novel vector control strategies. A new approach uses the endosymbiotic bacterium Wolbachia pipientis to reduce the spread of arboviruses. However, the Wolbachia-mediated antiviral mechanism is not well understood. To shed light on this mechanism, we investigated an unexplored aspect of Wolbachia-virus-mosquito interaction. We used RNA sequencing to examine the transcriptional response of Wolbachia to DENV infection in A. aegypti Aag2 cells transinfected with the wAlbB strain of Wolbachia. Our results suggest that genes encoding an endoribonuclease (RNase HI), a regulator of sigma 70-dependent gene transcription (6S RNA), essential cellular, transmembrane, and stress response functions and primary type I and IV secretion systems were upregulated, while a number of transport and binding proteins of Wolbachia, ribosome structure, and elongation factor-associated genes were downregulated due to DENV infection. Furthermore, bacterial retrotransposon, transposable, and phage-related elements were found among the up- and downregulated genes. We show that Wolbachia elicits a transcriptional response to virus infection and identify differentially expressed Wolbachia genes mostly at the early stages of virus infection. These findings highlight Wolbachia’s ability to alter its gene expression in response to DENV infection of the host cell. IMPORTANCE Aedes aegypti is a vector of several pathogenic viruses, including dengue, Zika, chikungunya, and yellow fever viruses, which are of importance to human health. Wolbachia is an endosymbiotic bacterium currently used in transinfected mosquitoes to suppress replication and transmission of dengue viruses. However, the mechanism of Wolbachia-mediated virus inhibition is not fully understood. While several studies have shown mosquitoes’ transcriptional responses to dengue virus infection, none have investigated these responses in Wolbachia, which may provide clues to the inhibition mechanism. Our results suggest changes in the expression of a number of functionally important Wolbachia genes upon dengue virus infection, including those involved in stress responses, providing insights into the endosymbiont’s reaction to virus infection.
Factors associated with mortality in patients with COVID‐19 admitted to intensive care: a systematic review and meta‐analysis

Identification of high‐risk patients admitted to intensive care with COVID‐19 may inform management strategies. The objective of this meta‐analysis was to determine factors associated with mortality among adults with COVID‐19 admitted to intensive care by searching databases for studies published between 1 January 2020 and 6 December 2020. Observational studies of COVID‐19 adults admitted to critical care were included. Studies of mixed cohorts and intensive care cohorts restricted to a specific patient sub‐group were excluded. Dichotomous variables were reported with pooled OR and 95%CI, and continuous variables with pooled standardised mean difference (SMD) and 95%CI. Fifty‐eight studies (44,305 patients) were included in the review. Increasing age (SMD 0.65, 95%CI 0.53–0.77); smoking (OR 1.40, 95%CI 1.03–1.90); hypertension (OR 1.54, 95%CI 1.29–1.85); diabetes (OR 1.41, 95%CI 1.22–1.63); cardiovascular disease (OR 1.91, 95%CI 1.52–2.38); respiratory disease (OR 1.75, 95%CI 1.33–2.31); renal disease (OR 2.39, 95%CI 1.68–3.40); and malignancy (OR 1.81, 95%CI 1.30–2.52) were associated with mortality. A higher sequential organ failure assessment score (SMD 0.86, 95%CI 0.63–1.10) and acute physiology and chronic health evaluation‐2 score (SMD 0.89, 95%CI 0.65–1.13); a lower PaO2:FIO2 (SMD −0.44, 95%CI −0.62 to −0.26) and the need for mechanical ventilation at admission (OR 2.53, 95%CI 1.90–3.37) were associated with mortality. Higher white cell counts (SMD 0.37, 95%CI 0.22–0.51); neutrophils (SMD 0.42, 95%CI 0.19–0.64); D‐dimers (SMD 0.56, 95%CI 0.43–0.69); ferritin (SMD 0.32, 95%CI 0.19–0.45); lower platelet (SMD −0.22, 95%CI −0.35 to −0.10); and lymphocyte counts (SMD −0.37, 95%CI −0.54 to −0.19) were all associated with mortality. In conclusion, increasing age, pre‐existing comorbidities, severity of illness based on validated scoring systems, and the host response to the disease were associated with mortality; while male sex and increasing BMI were not. These factors have prognostic relevance for patients admitted to intensive care with COVID‐19.