Miracle-dz/UniFAR-FTUs huggingface dataset:
Design of Fungal Co-Cultivation Based on Comparative Metabolomics and Bioactivity for Discovery of Marine Fungal Agrochemicals

Microbial co-cultivation is employed for awakening silent biosynthetic gene clusters (BGCs) to enhance chemical diversity. However, the selection of appropriate partners for co-cultivation remains a challenge. Furthermore, competitive interactions involving the suppression of BGCs or upregulation of known, functional metabolite(s) during co-cultivation efforts is also common. Herein, we performed an alternative approach for targeted selection of the best co-cultivation pair. Eight marine sediment-derived fungi were classified as strong or weak, based on their anti-phytopathogenic potency. The fungi were co-cultured systematically and analyzed for their chemical profiles and anti-phytopathogenic activity. Based on enhanced bioactivity and a significantly different metabolite profile including the appearance of a co-culture specific cluster, the co-culture of Plenodomus influorescens (strong) and Pyrenochaeta nobilis (weak) was prioritized for chemical investigation. Large-scale co-cultivation resulted in isolation of five polyketide type compounds: two 12-membered macrolides, dendrodolide E (1) and its new analog dendrodolide N (2), as well as two rare azaphilones spiciferinone (3) and its new analog 8a-hydroxy-spiciferinone (4). A well-known bis-naphtho-γ-pyrone type mycotoxin, cephalochromin (5), whose production was specifically enhanced in the co-culture, was also isolated. Chemical structures of compounds 1–5 were elucidated by NMR, HRMS and [α]D20 analyses. Compound 5 showed the strongest anti-phytopathogenic activity against Xanthomonas campestris and Phytophthora infestans with IC50 values of 0.9 and 1.7 µg/mL, respectively.
Identification of a nomogram based on long non-coding RNA to improve prognosis prediction of esophageal squamous cell carcinoma

Purpose: Esophageal squamous cell carcinoma (ESCC) remains a common aggressive malignancy in the world. Several long non-coding RNAs (lncRNAs) are reported to predict the prognosis of ESCC. Therefore, an in-depth research is urgently needed to further investigate the prognostic value of lncRNAs in ESCC. Results: From the training set, we identified a eight-lncRNA signature (including AP000487, AC011997, LINC01592, LINC01497, LINC01711, FENDRR, AC087045, AC137770) which separated the patients into two groups with significantly different overall survival (hazard ratio, HR = 3.79, 95% confidence interval, 95% CI [2.56-5.62]; P < 0.001). The signature was applied to the validation set (HR = 2.73, 95%CI [1.65-4.53]; P < 0.001) and showed similar prognostic values. Stratified, univariate and multivariate Cox regression analysis indicated that the signature was an independent prognostic factor for patients with ESCC. A nomogram based on the lncRNAs signature, age, grade and stage was developed and showed good accuracy for predicting 1-, 3- and 5-year survival probability of ESCC patients. We found a strong correlation between the gene significance for the survival time and T stage. Eight modules were constructed, among which the key module most closely associated with clinical information was identified. Conclusions: Our eight-lincRNA signature and nomogram could be practical and reliable prognostic tools for esophageal squamous cell carcinoma. Methods: We downloaded the lncRNA expression profiles of ESCC patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets and separated to training and validation cohort. The univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to identify a lncRNA-based signature. The predictive value of the signature was assessed using the Kaplan-Meier method, receiver operating characteristic (ROC) curves and area under curve (AUC). Weighted gene co-expression network analysis (WGCNA) was applied to predict the intrinsic relationship between gene expressions. In addition, we further explored the combination of clinical information and module construction.
Impact of lower limb osteoarthritis on health-related quality of life: A cross-sectional study to estimate the expressed loss of utility in the Spanish population

Objective Osteoarthritis of the lower limb (OALL) worsens health-related quality of life (HRQL), but this impact has not been quantified with standardized measures. We intend to evaluate the impact of OALL on HRQL through measures based on individual preferences in comparison to the general population. Methods A cross-sectional study was designed. A total of 6234 subjects aged 50 years or older without OALL were selected from the Spanish general population (National Health Survey 2011–12). An opportunistic sample of patients aged 50 years or older diagnosed with hip (n = 331) or knee osteoarthritis (n = 393), using the American Rheumatism Association criteria, was recruited from six hospitals and 21 primary care centers in Vizcaya, Madrid and Tenerife between January and December 2015. HRQL was measured with the EQ-5D-5L, and the results were transformed into utility scores. Sociodemographic variables (age, sex, social group, cohabitation), number of chronic diseases, and body mass index were considered. The clinical stage of OALL was collected using the Western Ontario and McMaster Universities Osteoarthritis Index and the Oxford hip score and Oxford knee score. Generalized linear models were constructed using the utility index as the dependent variable. Results HRQL expressed by OALL patients was significantly worse than this of the general population. After adjustment for sociodemographic and clinical characteristics, the mean utility loss was -0.347 (95% CI: -0.390, -0.303) for osteoarthritis of the hip and -0.295 (95% CI: -0.336, -0.255) for osteoarthritis of the knee. OALL patients who were treated at a hospital had an additional utility loss of -0.112 (95% CI: -0.158, -0.065). Conclusion OALL has a great impact on HRQL. People with OALL perceive a utility loss of approximately 0.3 points compared to the general population without osteoarthritis, which is very high in relation to the utility loss reported for other chronic diseases and for arthritis in general.
Sympathetic improvement of cancer vaccine efficacy

ABSTRACT The link between stress, other psychological factors and response to cancer, or even the cancer incidence and metastasis, is well established. The inhibition of β-Adrenergic receptors (β-AR) using β-blockers was demonstrated to have an inhibitory effect on cancer recurrence. Direct effects on the stress-induced suppression of anti-tumor immune responses were also shown. In a recent issue of Cancer Immunology Research, Daher and colleagues studied the molecular mechanism behind this protective effect in the context of cancer vaccination. They provided evidence that the β-AR signaling affected the priming of naïve CD8 + T cells in their myeloma model, rather than effector CD8 + T cells which downregulated the expression of β-AR after activation and became insensitive to such signaling. Blocking the β-adrenergic signaling during vaccination led to increased expansion and effector functions of antigen-specific CD8 + T cells and reduced tumor growth. This has implications for the clinical use of β-blockers as adjuvants to enhance cancer vaccination and other types of immunotherapy.
Molecular Detection of Rabies Lyssaviruses from Dogs in Southeastern Nigeria: Evidence of TransboundaryTransmission of Rabies in West Africa

Despite being the first country to register confirmed cases of Mokola and Lagos bat lyssaviruses (two very distant lyssaviruses), knowledge gaps, particularly on the molecular epidemiology of lyssaviruses, still exist in Nigeria. A total of 278 specimens were collected from dogs in southeastern Nigeria between October 2015 and July 2016, and 23 (8.3%) of these tested positive for lyssaviruses with the direct fluorescent antibody test (DFA). The lyssaviruses were genetically characterized by amplifying the highly conserved nucleoprotein (N) gene of the rabies lyssaviruses (RABVs) of the viral genome. Phylogenetic analyses of the nucleotide sequences showed that all the RABV sequences in this study were of the Africa-2 lineage. Our results demonstrated that transboundary transmission of rabies lyssavirus is a key event, given that one of the RABV sequences (MN196576) clustered with rabies variants from neighboring Niger Republic. Furthermore, three RABVs from dogs from Anambra State clustered separately forming a novel and distinct group. Our results demonstrated that transboundary transmission of RABLVs is a key driver in the spread of rabies in West Africa. In order for the successful control of this zoonotic disease, a multinational stepwise surveillance and elimination of rabies in Africa by 2030 is probably the solution for regional elimination.
TRIM66 promotes malignant progression of prostate carcinoma through the JAK/STAT pathway

Prostate cancer is the fifth leading cause of cancer‐related deaths in males globally. Tripartite Motif Containing 66 (TRIM66) functions as transcriptional repressor and exerts its effect at least partially through promotion of deacetylase. TRIM66 has been previously reported to play an oncogenic role in a number of human cancers. Here, we investigated the potential oncogenic properties of TRIM66 in prostate cancer. We report that shRNA‐mediated knockdown of TRIM66 significantly suppressed viability and proliferation of both PC‐3 and DU145 prostate cancer cell lines. Furthermore, TRIM66 deficiency inhibited migration and invasion of prostate cancer cells. Mechanistically, TRIM66 positively regulated signal transducer and activator of transcription 2 (STAT2) and interleukin‐2 (IL‐2) expression. The predominance of STAT2–IL‐2 in mediating the oncogenic properties of TRIM66 was determined using a rescue assay, wherein overexpression of either STAT2 or IL‐2 almost completely abolished the inhibitory effects on cell proliferation, migration and invasion elicited by TRIM66 deficiency in prostate cancer cells. Our study highlights the importance of the TRIM66–STAT2–IL‐2 signaling axis in the tumor biology of prostate cancer.
Family members and health care workers' perspectives on motivational factors of participation in physical activity for people with intellectual disability: A qualitative study.

BACKGROUND People with intellectual disabilities (ID) have lower levels of physical activity than the general population. The aim of this study was to understand the motivational factors of participation in physical activity for people with ID from the perspectives of the family members and staff. METHOD An abductive qualitative design was used. Social Cognitive Theory constituted the theoretical frame of reference of the study. Two focus group interviews with health care workers and family members and two individual interviews with health care workers were conducted at their workplace. A thematic analysis was performed. RESULTS Three main themes were identified. According to support persons, motivation could be promoted at the individual level by fun, mastery, social setting, technology and knowledge about health behaviours. At a contextual level, physical activity was mediated by engagement with support individuals and available resources. At an interactional level, individuals were more motivated if the interaction was featured by joint activities, predictability and the use of rewards. CONCLUSIONS Motivation for participation in physical activity might be promoted at the individual, contextual and interactional levels. The interactions between individuals with ID and their support persons should work in a supportive way and strengthen mastery experiences. Support and engagement in the context could serve as a prerequisite for motivation and participation in physical activity and should be considered when developing interventions for physical activity for individuals with ID.
Salivary human beta-defensins and cathelicidin levels in relation to periodontitis and type 2 diabetes mellitus

Abstract Objective: Type 2 diabetes mellitus (T2DM) is a well-defined risk factor of periodontitis and it can affect expression of human beta-defensins (hBDs) and cathelicidin (LL-37) as well. The aim of the present study was to evaluate the impact of periodontitis and T2DM on salivary concentrations of these antimicrobial peptides. Material and methods: Unstimulated saliva samples, together with full-mouth periodontal recordings were collected from 92 individuals with periodontitis (63 with T2DM and 21 smokers) and 86 periodontally healthy controls (58 with T2DM and 21 smokers). Salivary hBD-1, -2, -3, LL-37, and advanced glycalization end products (AGE) concentrations were measured by enzyme-linked immunosorbent assay. Results: Among the periodontitis patients, T2DM group demonstrated lower levels of hBD-1 (p = .006), hBD-2 (p < .001) and hBD-3 (p < .001), and higher levels of LL-37 (p < .001) compared to systemically healthy controls. When only periodontally healthy controls were included into the analysis, higher hBD-1 (p = .002) and LL-37 (p < .001) levels were found in T2DM patients in comparison to systemically healthy controls. Salivary LL-37 levels were associated with HbA1c and periodontitis, while hBD-2, hBD-3 and levels associated only with HbA1c. Conclusion: In the limits of this study, hyperglycaemia can be proposed as a regulator of salivary hBD and cathelicidin levels. Periodontitis, on the other hand, affects only salivary LL-37 levels.
Does culture shape face perception in autism? Cross-cultural evidence of the own-race advantage from the UK and Japan.

Autism spectrum disorders (ASD) are associated with face perception atypicalities, and atypical experience with faces has been proposed as an underlying explanation. Studying the own-race advantage (ORA) for face recognition can reveal the effect of experience on face perception in ASD, although the small number of studies in the area present mixed findings. The current study probed the ORA in ASD by comparing two cultural groups simultaneously for the first time. Children with ASD in the UK (N=16) and Japan (N=26) were compared to age and ability matched TD children in the UK (N=16) and Japan (N=26). Participants completed a two-alternative forced-choice task, whereby they had to recognise a just-seen face from a foil which was manipulated in one of four ways (IC: identity change; EE: easy eyes; HE: hard eyes; HM: hard mouth). Face stimuli were Asian and Caucasian, and thus the same stimuli were own and other-race depending on the cultural group. The ASD groups in the UK and Japan did not show impaired face recognition abilities, or impairments with recognising faces depending on manipulations to the eye region, and importantly they showed an ORA. There was considerable heterogeneity in the presence of the ORA in ASD and TD and also across cultures. Children in Japan had higher accuracy than children in the UK, and TD children in Japan did not show an ORA. The present cross-cultural study challenges the view that atypical experiences with faces lead to a reduced/absent ORA in ASD.
Is visceral abdominal fat area a better indicator for hyperglycemic risk? Results from the Pinggu Metabolic Disease Study

The aim of the present study was to analyze the strength of association between fasting plasma glucose (FPG), 2‐h postprandial glucose (2h PPG), hemoglobin A1c (HbA1c), disposition index (DI) and nine anthropometrics measures, to explore the best indicator for hyperglycemia.
On the correlation between telomere shortening rate and life span

Whittemore et al. (1) find significant correlations between maximum life span (MLS) and telomere shortening rate (TSR) in mammalian and avian species. This interesting study comes to the conclusion that “critical telomere shortening and the consequent onset of telomeric DNA damage and cellular senescence are a general determinant of species life span. ” An important issue, however, has not been dealt with by the authors. The use of linear regressions (those used by the authors) assumes that samples are independent, but this is not the case in interspecies studies. In fact, the samples (i.e., the values for each species) have different grades of dependency, which derive from their phylogenetic relationship (2). This is why all tests should be performed using phylogenetic corrections, like phylogenetic-independent contrast (3 … [↵][1]1Email: ion.udroiu{at}uniroma3.it. [1]: #xref-corresp-1-1
CD209 and Not CD28 or STAT6 Polymorphism Mediates Clinical Malaria and Parasitemia among Children from Nigeria

Malaria remains a significant disease, causing epic health problems and challenges all over the world, especially in sub-Saharan Africa. CD209 and CD28 genes act as co-stimulators and regulators of the immune system, while the STAT6 gene has been reported to mediate cytokine-induced responses. Single nucleotide polymorphisms of these genes might lead to differential disease susceptibility among populations at risk for malaria, due to alterations in the immune response. We aim to identify key drivers of the immune response to malaria infection among the three SNPs: CD209 (rs4804803), CD28 (rs35593994) and STAT6 (rs3024974). After approval and informed consent, we genotyped blood samples from a total of 531 children recruited from Nigeria using the Taqman SNP genotyping assay and performed comparative analysis of clinical covariates among malaria-infected children. Our results reveal the CD209 (rs4804803) polymorphism as a susceptibility factor for malaria infection, significantly increasing the risk of disease among children, but not CD28 (rs35593994) or STAT6 (rs3024974) polymorphisms. Specifically, individuals with the homozygous mutant allele (rs4804803G/G) for the CD209 gene have a significantly greater susceptibility to malaria, and presented with higher mean parasitemia. This observation may be due to a defective antigen presentation and priming, leading to an ineffective downstream adaptive immune response needed to combat infection, as well as the resultant higher parasitemia and disease manifestation. We conclude that the CD209 gene is a critical driver of the immune response during malaria infection, and can serve as a predictor of disease susceptibility or a biomarker for disease diagnosis.
Ultra-rapid cooling of ibex sperm by spheres method does not induce a vitreous extracellular state and increases the membrane damages

Sperm cryopreservation by ultra-rapid cooling based on dropping small volumes of sperm suspension directly into liquid nitrogen, has been successful in some wild ruminant species, including the Iberian ibex (Capra pyrenaica). In ultra-rapid cooling, the contents of these droplets are expected to enter a stable, glass-like state, but to the best of our knowledge no information exists regarding the presence or absence of ice formation in the extracellular milieu when using this technique. Different modifications to the extracellular milieu likely inflict different types of damage on the plasmalemma, the acrosome and mitochondrial membranes. The aims of the present work were: 1) to examine the physical state of the extracellular milieu after cryopreservation at slow and ultra-rapid cooling rates—and thus determine whether ultra-rapid cooling vitrifies the extracellular milieu; and 2) to compare, using conventional sperm analysis techniques and scanning and transmission electron microscopy, the damage to sperm caused by these two methods. Sperm samples were obtained by the transrectal ultrasound-guided massage method (TUMASG) from anesthetized Iberian ibexes, and cryopreserved using slow and ultra-rapid cooling techniques. Sperm motility (22.95 ± 3.22% vs 4.42 ± 0.86%), viability (25.64 ± 3.71% vs 12.8 ± 2.50%), acrosome integrity (41.45± 3.73% vs 27.00 ± 1.84%) and mitochondrial membrane integrity (16.52 ± 3.75% vs 4.00 ± 0.65%) were better after slow cooling (P<0.001) than after ultra-rapid technique. Cryo-scanning electron microscopy (Cryo-SEM) suggested that the vitrified state was not achieved by ultra-rapid cooling, and that the ice crystals formed were smaller and had more stretchmarks (P<0.001) than after slow cooling. Scanning electron microscopy revealed no differences in the types of damage caused by the examined techniques, although transmission electron microscopy showed the damage to the plasmalemma and mitochondrial membrane to be worse after ultra-rapid cooling. In conclusion ultra-rapid cooling provoked more membrane damage than slow cooling, perhaps due to the extracellular ice crystals formed.
Effectiveness of supervised early exercise program in patients with arthroscopic rotator cuff repair

Abstract Background: Based on the available evidence, it is difficult to make a clinical decision about the best exercise program and to establish the most favorable time to start postoperative treatment after rotator cuff (RC) repair. The aim of this trial is to evaluate the effects of adding a supervised early exercise program to standard treatment for functional improvement and pain relief compared with standard treatment alone in patients with arthroscopic RC repair. Method/design: A total of 118 patients between the ages of 18 and 50 years with arthroscopic RC repair will be randomized to 2 treatment arms. The control group will receive a standard exercise program based on a consensus statement on shoulder rehabilitation developed by the American Society of Shoulder and Elbow Therapists. The intervention group will receive a supervised early exercise program in combination with standard treatment. This supervised exercise program will be based on electromyographic evidence. Three evaluations will be performed: before surgery, at 6 weeks, and at 12 weeks. The primary outcome measure will be the shoulder function by the Constant–Murley questionnaire, and the secondary outcome measures will be the upper limb function by the disabilities of the arm, shoulder, and hand questionnaire; pain by the visual analog scale; and the shoulder range of motion by a goniometer. Discussion: We hypothesize that patients who receive a supervised early exercise program in combination with standard treatment will benefit more in respect to shoulder function, pain reduction, and range of motion than those who receive a standard exercise program. If this is confirmed, our study can be used clinically to enhance the recovery of patients with arthroscopic RC repair. Trial registration: Brazilian registry of clinical trials UTN number U1111-1224-4143. Registered December 18, 2018.