Miracle-dz/UniFAR-FTUs huggingface dataset:
Extensive Genetic Diversity and Widespread Azole Resistance in Greenhouse Populations of Aspergillus fumigatus in Yunnan, China

The origin and prevalence of azole-resistant Aspergillus fumigatus have been attracting increasing attention from biologists, clinicians, and public health agencies. Current evidence suggests agricultural fungicide use as a major cause. ABSTRACT Aspergillus fumigatus is the main cause of invasive aspergillosis (IA) with a high annual global incidence and mortality rate. Recent studies have indicated an increasing prevalence of azole-resistant A. fumigatus (ARAF) strains, with agricultural use of azole fungicides as a potential contributor. China has an extensive agricultural production system and uses a wide array of fungicides for crop production, including in modern growth facilities such as greenhouses. Soils in greenhouses are among the most intensively cultivated. However, little is known about the occurrence and distribution of ARAF in greenhouse soils. Here, we investigated genetic variation and triazole drug susceptibility in A. fumigatus from greenhouses around metropolitan Kunming in Yunnan, southwest China. Abundant allelic and genotypic variations were found among 233 A. fumigatus strains isolated from nine greenhouses in this region. Significantly, ∼80% of the strains were resistant to at least one medical triazole drug, with >30% showing cross-resistance to both itraconazole and voriconazole. Several previously reported mutations associated with triazole resistance in the triazole target gene cyp51A were also found in our strains, with a strong positive correlation between the frequency of mutations at the cyp51A promoter and that of voriconazole resistance. Phylogenetic analyses of cyp51A gene sequences showed evidence for multiple independent origins of azole-resistant genotypes of A. fumigatus in these greenhouses. Evidence for multiple origins of azole resistance and the widespread distributions of genetically very diverse triazole-resistant strains of A. fumigatus in greenhouses calls for significant attention from public health agencies. IMPORTANCE The origin and prevalence of azole-resistant Aspergillus fumigatus have been attracting increasing attention from biologists, clinicians, and public health agencies. Current evidence suggests agricultural fungicide use as a major cause. In southwest China, greenhouses are used to produce large amounts of fruits, flowers, and vegetables for consumers throughout China as well as those in other countries, primarily in southeast Asia. Here, we found a very high frequency (∼80%) of triazole-resistant A. fumigatus in our sample, the highest reported so far, with a significant proportion of these strains resistant to both tested agricultural fungicides and medical triazole drugs. In addition, we found novel allelic and genotypic diversities and evidence for multiple independent origins of azole-resistant genotypes of A. fumigatus in greenhouse populations in this region. Our study calls for a systematic evaluation of the effects of azole fungicide usage in greenhouses on human health.
Toxicity after volumetric modulated arc therapy for lung cancer: a monocentric retrospective study

Background Intensity-modulated radiotherapy (RT) is now widely implemented and has replaced classical three-dimensional (3D)-RT in many tumor sites, as it allows a better target dose conformity and a better sparing of organs a risk (OAR), at the expense, however, of increasing the volume of low dose to normal tissues. Clinical data on toxicities using volumetric modulated arc therapy (VMAT) in lung cancer remain scarce. We aimed to report both acute (APT) and late (LPT) pulmonary and acute (AET) and late (LET) oesophageal toxicities in such setting. Methods All patients treated for a primary lung cancer with VMAT +/− chemotherapy (ChT) in our center from 2014 to 2018 were retrospectively included. Usual clinical, treatment and dosimetric features were collected. Univariate analysis was performed using the receiver operative characteristics approach while multivariate analysis (MVA) relied on logistic regression, calculated with Medcalc 14.8. 1. Results In total, 167 patients were included, with a median age of 66 years (39–88 years). Median radiation dose was 66 Gy (30–66 Gy); 82% patients received concomitant (32.3%), induction (25.7%) or induction followed by concomitant ChT (24%). After a median follow-up of 14.0 months, the G ≥2 APT, AET, LPT and LET rates were 22.2%, 30.0%, 16.8% and 5.4%, respectively with low grade ≥3 toxicity rates (respectively, 3%, 6.6%, 3% and 0%). On MVA, APT was significantly associated with V30 to the homolateral lung, AET with age, LPT with MEVS while no feature remained significantly correlated with LET. Conclusions Low rates of pulmonary and esophageal toxicity were observed in our cohort. Larger prospective studies are needed to confirm these results.
Associations of Lifestyle and Anthropometric Factors With the Risk of Herpes Zoster: A Nationwide Population-Based Cohort Study

Abstract The role of lifestyle in development of herpes zoster remains unclear. We examined whether smoking status, alcohol consumption, body mass index, or physical activity were associated with zoster risk. We followed a population-based cohort of 101,894 respondents to the 2010 Danish National Health Survey (baseline, May 1, 2010) until zoster diagnosis, death, emigration, or July 1, 2014, whichever occurred first. We computed hazard ratios for zoster associated with each exposure, using Cox regression with age as the time scale and adjusting for potential confounders. Compared with never smokers, hazards for zoster were increased in former smokers (1.17, 95% confidence interval (CI): 1.06, 1.30), but not in current smokers (1.00, 95% CI: 0.89, 1.13). Compared with low-risk alcohol consumption, neither intermediate-risk (0.95, 95% CI: 0.84, 1.07) nor high-risk alcohol consumption (0.99, 95% CI: 0.85, 1.15) was associated with zoster. We also found no increased hazard associated with weekly binge drinking versus not (0.93, 95% CI: 0.77, 1.11). Risk of zoster varied little by body mass index (referent = normal weight) and physical activity levels (referent = light level), with hazard ratios between 0.96 and 1.08. We observed no dose-response association between the exposures and zoster. The examined lifestyle and anthropometric factors thus were not risk factors for zoster.
The neurochemistry of social reward during development: What have we learned from rodent models?

Social rewards are fundamental to survival and overall health. Several studies suggest that adequate social stimuli during early life are critical for developing appropriate socioemotional and cognitive skills, whereas adverse social experiences negatively affect the proper development of brain and behavior, by increasing the susceptibility to develop neuropsychiatric conditions. Therefore, a better understanding of the neural mechanisms underlying social interactions, and their rewarding components in particular, is an important challenge of current neuroscience research. In this context, preclinical research has a crucial role: Animal models allow to investigate the neurobiological aspects of social reward in order to shed light on possible neurochemical alterations causing aberrant social reward processing in neuropsychiatric diseases, and they allow to test the validity and safety of innovative therapeutic strategies. Here, we discuss preclinical research that has investigated the rewarding properties of two forms of social interaction that occur in different phases of the lifespan of mammals, that is, mother–infant interaction and social interactions with peers, by focusing on the main neurotransmitter systems mediating their rewarding components. Together, the research performed so far helped to elucidate the mechanisms of social reward and its psychobiological components throughout development, thus increasing our understanding of the neurobiological substrates sustaining social functioning in health conditions and social dysfunction in major psychiatric disorders.
Positive fluid balance as an early biomarker for acute kidney injury: a prospective study in critically ill adult patients

OBJECTIVES: Positive fluid balance is frequent in critically ill patients and has been considered a potential biomarker for acute kidney injury (AKI). This study aimed to evaluate positive fluid balance as a biomarker for the early detection of AKI in critically ill patients. METHODS: This was a prospective cohort study. The sample was composed of patients ≥18 years old who stayed ≥3 days in an intensive care unit. Fluid balance, urinary output and serum creatinine were assessed daily. AKI was diagnosed by the Kidney Disease Improving Global Outcome criteria. RESULTS: The final cohort was composed of 233 patients. AKI occurred in 92 patients (40%) after a median of 3 (2-6) days following ICU admission. When fluid balance was assessed as a continuous variable, a 100-ml increase in fluid balance was independently associated with a 4% increase in the odds of AKI (OR 1.04; 95% CI 1.01-1.08). Positive fluid balance categorized using different thresholds was always significantly associated with subsequent detection of AKI. The mixed effects model showed that increased fluid balance preceded AKI by 4 to 6 days. CONCLUSION: These results suggest that a positive fluid balance might be an early biomarker for AKI development in critically ill patients.
Association Between Central and Peripheral Age-Related Hearing Loss and Different Frailty Phenotypes in an Older Population in Southern Italy.

Importance The association between age-related hearing loss (ARHL) and physical or cognitive frailty has been poorly explored. These associations could define new perspectives for delaying frailty-related processes in older age. Objective To examine whether peripheral ARHL and age-related central auditory processing disorder (CAPD) are independently associated with physical or cognitive frailty. Design, Setting, and Participants This cross-sectional study analyzed registry data from December 31, 2014, on 1929 older (≥65 years) participants of the Salus in Apulia Study (Southern Italy) who underwent audiologic, physical, and neuropsychological assessment. Data analysis was performed from December 12, 2019, to January 4, 2020. Main Outcomes and Measures Prevalence of peripheral ARHL in older individuals with physical and/or cognitive frailty and those without frailty assessed using the Fried criteria (physical) and the Mini-Mental State Examination (cognitive). Multivariable logistic regression models were used to assess associations of audiologic variables with frailty phenotype. Results Data from 1929 participants (mean [SD] age, 73.6 [6.3] years; 974 male [50.5%]) were eligible for the analyses. The prevalence of peripheral ARHL was higher in the physical frailty group (96 [26.6%]) than in the nonfrail group (329 [21.0%]) (difference, 5.61 percentage points; 95% CI, 0.63-10.59 percentage points) and in the cognitive frailty group (40 [38.8%]) than in the nonfrail group (385 [21.1%]) (difference, 17.75 percentage points; 95% CI, 8.2-27.3 percentage points). Age-related CAPD was more prevalent in the physical frailty group (62 [17.2%]) than in the nonfrail group (219 [14.0%]) (difference, 3.21 percentage points; 95% CI, -1.04 to 7.46 percentage points) and in the cognitive frailty group (28 [27.2%]) than in the nonfrail group (253 [13.9%]) (difference, 13.33 percentage points; 95% CI, 4.10-22.21 percentage points). In the multivariable models, age-related CAPD was associated with cognitive frailty in the fully adjusted model (odds ratio [OR], 1.889; 95% CI, 1.094-3.311). There was also an inverse association between the unitary increase in Synthetic Sentence Identification With the Ipsilateral Competitive Message scores, indicating a lower likelihood of this disorder, and cognitive frailty (OR, 0.989; 95% CI, 0.988-0.999). Peripheral ARHL was associated with cognitive frailty only in the partially adjusted model (OR, 1.725; 95% CI, 1.008-2.937). Conclusions and Relevance In this cross-sectional study of 1929 participants, age-related CAPD was independently associated with cognitive frailty. Whether the management of ARHL may help prevent the development of different frailty phenotypes or improve their clinical consequences should be addressed in longitudinal studies and, eventually, well-designed randomized clinical trials.
Diagnosis and treatment of 471 patients with 2019 novel coronavirus disease (COVID-19)

Background While the 2019 novel coronavirus disease (COVID-19) outbreak has been largely kept under control in China, it remains a global pandemic, and the source, transmission route, and treatments of SARS-COV-2 are still being investigated. Here, we summarized the clinical features, diagnosis, treatment, and prognosis of COVID-19 patients based on our clinical practice. Methods The clinical and imaging findings, treatments, and follow-up data of 471 patients with COVID-19 who were discharged from the Wuhan Jinyintan Hospital prior to February 6, 2020, were retrospectively analyzed. Results Among these patients, there were 2 mild cases, 282 moderate cases, 181 severe cases, and 6 critical cases. There were 250 males and 221 females aged 17 to 90 years. The median age was 54 years in the severe/critical group, which was significantly older than in the mild/moderate group (P<0.05). 44.59% of them had one or more underlying diseases. The most common symptoms were fever, cough, expectoration, and dyspnea. The median body temperature in the severe/critical group was 39°C, which was significantly higher than in the mild/moderate group (P<0.05). The incidences of lymphopenia and CD4+ T lymphocytopenia were 53.5% and 41.86%, respectively. Ground-glass opacity and small patchy shadows were the most common findings on chest computed tomography (CT). Compared with the mild/moderate group, the severe/critical group showed higher proportions of severe lymphocytopenia and CD4+ T lymphocytopenia, along with more ground-glass shadows and large-scale consolidation. After anti-infection, oxygen therapy, and symptomatic support, lymphocytes and CD4+ T lymphocytes were markedly increased, all patients were discharged. The median time of nucleic acid conversion and hospital stay were 9 and 12 days, respectively, which were significantly longer in the severe/critical group than in the mild/moderate group. Of the 390 cases followed, only 19 were hospitalized again due to other diseases. All patients recovered well from COVID-19, with negative nucleic acid test results. Conclusions Lymphocytopenia and CD4+ T lymphocytopenia were found to be associated with COVID-19 and thus may be important indicators in evaluating the severity and prognosis. Multidisciplinary management including antiviral treatment, immune regulation, and symptomatic support is effective, and yields a low recurrence rate.
Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings

Background: N,N-dimethyltryptamine is a short-acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date have addressed the neural and psychological effects of N,N-dimethyltryptamine alone, either administered intravenously or inhaled in freebase form, and none have been conducted in natural settings. Aims: Our primary aim was to study the acute effects of inhaled N,N-dimethyltryptamine in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. “set“ and “setting“), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming N,N-dimethyltryptamine in familiar and comfortable settings. Methods: We combined state-of-the-art wireless electroencephalography with psychometric questionnaires to study the neural and subjective effects of naturalistic N,N-dimethyltryptamine use in 35 healthy and experienced participants. Results: We observed that N,N-dimethyltryptamine significantly decreased the power of alpha (8–12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1–4 Hz) and gamma (30–40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of some features of mystical-type experiences. N,N-dimethyltryptamine also increased global synchrony and metastability in the gamma band while decreasing those measures in the alpha band. Conclusions: Our results are consistent with previous studies of psychedelic action in the human brain, while at the same time the results suggest potential electroencephalography markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.
A novel MLSA allelic profile ‘A15’ of Mycoplasma mycoides subsp mycoides in Niger

ABSTRACT Mycoplasma mycoides subsp. mycoides (Mmm) is the aetiological agent of contagious bovine pleuropneumonia (CBPP). The aim of the present study was to identify the profiles of the Mmm strains isolated in Niger using the ‘Multilocus Sequence Analysis’ (MLSA) typing technique based on polymorphism analysis of housekeeping and non‐coding genes. The investigation was conducted on samples (n=22) comprising of lung tissues, lymph node and pleural fluids. Following classical PCR, Mmm positive amplicons (n=6) were identified. These positive amplicons were then amplified using eight loci of the PG1 reference strain (LocPG1‐0001, Loc‐PG1‐0103, Loc‐PG1‐0287, Loc‐PG1‐0431, Loc‐PG1‐0489, Loc‐PG1‐0523, Loc‐PG1‐0710 and Loc‐PG1‐0827). Sequencing followed by the determination of the profile of each strain by the combination of the allele numbers revealed three different MLSA profiles namely; A11, E01 and A15. The profiles A11 and E01 were previously identified. The novel profile identified in this study was named profile A15. The difference was detected while comparing sequences of non‐coding loci. This novel profile was named ‘A15’ according to the similarities with African reference strain profile ‘A00’ at the seven loci level (loc‐0103, loc‐0287, loc‐0431, loc‐0489, loc‐0523, loc‐0710 and loc‐0827). For CBPP control measures, identification and molecular characterization of Mmm strains is very important. Thus, the use of MLSA technique is relevant to identify profiles of Mmm circulating in Niger. Other countries where CBPP is still endemic are encouraged to use a MLSA scheme to address this issue and, most importantly, to rapidly trace back the origin of outbreaks, which will help reduce the transmission and spread of the disease. In addition, mapping the profiles of strains circulating in each of the countries of the sub‐region is necessary for effective control of CBPP.
Mechanisms underlying pro-arrhythmic abnormalities arising from Pitx2-induced electrical remodelling: an in silico intersubject variability study

Background Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)-dependent gene regulation induces atrial fibrillation (AF) with different mechanisms. The purpose of this study was to identify Pitx2-induced changes in ionic currents that cause action potential (AP) shortening and lead to triggered activity. Methods Populations of computational atrial AP models were developed based on AP recordings from sinus rhythm (SR) and AF patients. Models in the AF population were divided into triggered and untriggered AP groups to evaluate the relationship between each ion current regulated by Pitx2 and triggered APs. Untriggered AP models were then divided into shortened and unshortened AP groups to determine which Pitx2-dependent ion currents contribute to AP shortening. Results According to the physiological range of AP biomarkers measured experimentally, populations of 2,885 SR and 4,781 AF models out of the initial pool of 30,000 models were selected. Models in the AF population predicted AP shortening and triggered activity observed in experiments in Pitx2-induced remodelling conditions. The AF models included 925 triggered AP models, 1,412 shortened AP models and 2,444 unshortened AP models. Intersubject variability in IKs and ICaL primarily modulated variability in AP duration (APD) in all shortened and unshortened AP models, whereas intersubject variability in IK1 and SERCA mainly contributed to the variability in AP morphology in all triggered and untriggered AP models. The incidence of shortened AP was positively correlated with IKs and IK1 and was negatively correlated with INa, ICaL and SERCA, whereas the incidence of triggered AP was negatively correlated with IKs and IK1 and was positively correlated with INa, ICaL and SERCA. Conclusions Electrical remodelling due to Pitx2 upregulation may increase the incidence of shortened AP, whereas electrical remodelling arising from Pitx2 downregulation may favor to the genesis of triggered AP.
Salivary Metalloproteinase-8 and Metalloproteinase-9 Evaluation in Patients Undergoing Fixed Orthodontic Treatment before and after Periodontal Therapy

(1) Background: Metalloproteinase-8 (MMP-8) and metalloproteinase-9 (MMP-9) are members of a family of proteases of major importance during orthodontic tooth movement. Their levels increase during orthodontic therapy and in periodontally affected tissues. Orthodontic fixed appliances retain dental plaque and can cause gingival inflammation. When gingival inflammation is present, the forces produced during orthodontic tooth movement can aggravate tissue reaction and cause the destruction of supportive periodontal tissue. This study aimed to identify biomarkers that facilitate the assessment of periodontal status during orthodontic treatment. (2) Methods: Our study was conducted on 111 patients who were about to receive fixed orthodontic treatment. We determined the salivary levels of MMP-8 and MMP-9 and bleeding on probing (BOP) before applying the orthodontic fixed appliance (T1), one week after appliance placement (T2), and during orthodontic treatment, one month after non-surgical periodontal treatment (T3). (3) Results: Patients undergoing orthodontic treatment show a significant increase in BOP, MMP-8, and MMP-9 levels one week after orthodontic appliance placement (T2) and a decrease in these parameters one month after periodontal treatment (T3). Statistically significant correlations were found between MMP-8 levels and BOP values at T1, T2, and T3. (4) Conclusion: In our study patients undergoing orthodontic treatment show a significant increase in BOP, MMP-8, and MMP-9 levels one week after orthodontic appliance placement and a decrease in these parameters one month after periodontal treatment. Strong positive statistically significant correlations were found between MMP-8 levels and BOP and medium positive statistically significant correlations between MMP-9 and BOP values before and after orthodontic treatment and periodontal treatment. MMP-8, MMP-9, and BOP could be used to assess the periodontal status of orthodontic patients.
Care for unplanned extubation prevention: analysis of the validity of an instrument's content.

OBJECTIVES to analyze the validity of a nursing care instrument content for unplanned extubation prevention in Intensive Care Units. METHODS a methodological study carried out with 40 nurses, containing 26 interventions distributed in the components: agitation/delirium/pain management; respiratory device stability; weaning from sedation and spontaneous breathing assessment; human resource management. Content Validity Index, average and universal proportion, and Fleiss' Kappa coefficient were applied. RESULTS Brazilian female experts stood out, with an average age of 44.9 years and a standard deviation of 7.75 years. Two interventions did not reach a valid Content Validation Index (≥0.78), when considering the set of evaluated criteria. A universal agreement of 4.0% was identified among Brazilians and 26.6% among foreigners. CONCLUSIONS the instrument is relevant and represents "unplanned extubation prevention in Intensive Care Units", which can be implemented in Brazil and in Latin countries, in Brazilian and foreign versions.