Miracle-dz/UniFAR-FTUs huggingface dataset:
Confirmation of botulism diagnosis in Australian bird samples by ELISA and RT rtPCR

We developed a sandwich ELISA that detects Clostridium botulinum C and D toxins and reverse-transcription real-time PCRs (RT-rtPCRs) that detect botulinum C and D toxin genes, respectively, to replace the mouse bioassay. The toxin genes were closely associated with the toxin molecules and used as surrogates for the presence of toxin. Samples (638) from 103 clinical cases of birds (302) with suspected botulinum toxicity came from wild birds and poultry (9 cases). Samples tested included blood serum, other body fluids, various tissues, gut contents, maggots, water, and sediment. Botulism was diagnosed in 34 cases (all of which had positive samples in the ELISA, the C toxin gene RT-rtPCR, or both assays). Botulism was suspected in 16 cases (each of which had 1 positive sample either in the ELISA or the C toxin gene RT-rtPCR). In the remaining 53 cases, no samples were positive, but botulism could not be excluded in 32 of these cases, whereas there was no indication of botulism or another diagnosis in 21 cases. The D toxin gene was not detected in any of the clinical samples. No C or D toxin genes were detected in 71 pooled cloacal swabs from 213 healthy migratory birds. The use of an ELISA that detects botulinum C and D toxins in combination with a RT-rtPCR for the botulinum C toxin gene can help confirm the diagnosis of botulism in birds.
Identification of two methylated fragments of an SDC2 CpG island using a sliding window technique for early detection of colorectal cancer

Colorectal cancer (CRC) is one of the most common cancer types globally with a 5‐year survival rate of < 50% in China. Aberrant DNA methylation is one of the hallmarks of tumor initiation, progression, and metastasis. Here, we investigated the clinical performance of two differentially methylated regions (DMRs) in SDC2 CpG islands for the detection of CRC. A sliding window technique was used to identify the DMRs, and methylation‐specific PCR assay was used to assess the DMRs in 198 CRC samples and 54 normal controls. Two DMRs (DMR2 and DMR5) were identified using The Cancer Genome Atlas (TCGA) data, and the hypermethylation of DMR2 and DMR5 was detected in 90.91% (180/198) and 89.90% (178/198) of CRC samples, respectively. When combining DMR2 and DMR5, the sensitivity for CRC detection was 94.4% higher than that of DMR2 or DMR5 alone. Based on the above results, we propose using DMR2 and DMR5 as a sensitive biomarker to detect CRC.
Distinct clinical manifestations of obsessive-compulsive disorder are associated with cortical thickness alteration

Background: Although brain structural changes have been reported in patients with obsessive-compulsive disorder (OCD), results from previous studies have been inconsistent. A growing number of studies have focused on obsessive beliefs and impulsivity which could be involved in the occurrence and maintenance of OCD symptoms. The present study aimed to examine whether there are distinct brain structural changes in patients with different OCD subgroups. Methods: Eighty-nine patients with OCD and 42 healthy controls were recruited to undergo structural magnetic resonance imaging brain scan. OCD patients were classified into subgroups according to scores of the Obsessive Belief Questionnaire (OBQ-44) and the Barratt Impulsiveness Scale (BIS-11) using cluster analysis. Group comparisons in cortical thickness and subcortical volumes between all OCD patients and healthy controls, as well as between subgroups of OCD patients and healthy controls, were carried out. Results: OCD patients with more obsessive beliefs and attentional impulsivity (OCD_OB_AT) had reduced cortical thickness at the inferior parietal gyrus, the superior and middle temporal gyrus and the insula compared with OCD patients with higher score on the non-planning impulsivity (OCD_NP, corrected p < 0.05). The whole group of OCD patients and both subgroups showed reduced cortical thickness at the superior parietal gyrus compared with controls (uncorrected p < 0.01, number of vertices > 100). Conclusion: Our results suggest that apart from distinct phenomenology, there are distinct neural correlates of different OCD subgroups based on obsessive beliefs and impulsivity. These neural correlates may have clinical significance and should be considered in future research.
MicroRNA-101 inhibits renal tubular epithelial-to-mesenchymal transition by targeting TGF-β1 type I receptor

MicroRNAs (miRNAs/miRs) are key regulators of renal interstitial fibrosis (RIF). The present study was designed to identify miRNAs associated with the development of RIF, and to explore the ability of these identified miRNAs to modulate the renal tubular epithelial-to-mesenchymal transition (EMT) process. To this end, miRNAs that were differentially expressed between normal and fibrotic kidneys in a rat model of mercury chloride (HgCl2)-induced RIF were detected via an array-based approach. Bioinformatics analyses revealed that miR-101 was the miRNA that was most significantly downregulated in the fibrotic renal tissue samples, and this was confirmed by RT-qPCR, which also demonstrated that this miRNA was downregulated in transforming growth factor (TGF)-β1-treated human proximal tubular epithelial (HK-2) cells. When miR-101 was overexpressed, this was sufficient to reverse TGF-β1-induced EMT in HK-2 cells, leading to the upregulation of the epithelial marker, E-cadherin, and the downregulation of the mesenchymal marker, α-smooth muscle actin. By contrast, the downregulation of miR-101 using an inhibitor exerted the opposite effect. The overexpression of miR-101 also suppressed the expression of the miR-101 target gene, TGF-β1 type I receptor (TβR-I), and thereby impaired TGF-β1/Smad3 signaling, while the opposite was observed upon miR-101 inhibition. To further confirm the ability of miR-101 to modulate EMT, the HK-2 cells were treated with the TβR-I inhibitor, SB-431542, which significantly suppressed TGF-β1-induced EMT in these cells. Notably, miR-101 inhibition exerted a less pronounced effect upon EMT-related phenotypes in these TβR-I inhibitor-treated HK-2 cells, supporting a model wherein miR-101 inhibits TGF-β1-induced EMT by suppressing TβR-I expression. On the whole, the present study demonstrates that miR-101 is capable of inhibiting TGF-β1-induced tubular EMT by targeting TβR-I, suggesting that it may be an important regulator of RIF.
Romanian Guidelines for Nonpharmacological Therapy of IBS.

BACKGROUND AND AIMS The nonpharmacological therapy in irritable bowel syndrome (IBS) is expanding rapidly. Practitioners and medical educators need to be aware of progress and changes in knowledge of this topic. The Romanian Society of Neurogastroenterology aimed to create guidelines based on best evidence on the use of nonpharmacological therapy in IBS. METHODS A group of experts was constituted. This was divided in eleven subgroups dedicated to eleven categories of nonpharmacological therapy. The subgroups searched the literature and formulated statements and recommendations. These were submitted to vote in order to obtain consensus. RESULTS The outcome of this activity is represented by the guidelines of the Romanian Society of Neurogastroenterology, presented in this paper. The recommendations are seen as complementary to the pharmacological therapy and are not intended to recommend avoiding pharmacological drugs. CONCLUSIONS These guidelines were elaborated by a Delphi process and represent a useful tool for physicians managing patients with IBS.
Psychosocial determinants of quit motivation in older smokers from deprived backgrounds: a cross-sectional survey

Objectives To identify psychosocial determinants of quit motivation in older deprived smokers. The evidence may be used to optimise smoking cessation interventions for the target population. Design Cross-sectional survey using online recruitment methods including Facebook-targeted advertising. Setting UK, 2019. Participants Current smokers aged 50 years or older and from a socioeconomically deprived background. Main outcome measures Measures included motivation to stop smoking, smoking history, perceived social support, self-efficacy for quitting, self-exempting beliefs and lung cancer risk perception. Multivariable regression was used to analyse factors associated with quit motivation. Results Of a total 578 individuals who consented to take part, 278 (48.1%) did not meet the inclusion criteria. Of the 300 eligible participants, most were recruited using Facebook (94.0%), were aged 50–64 years (83.7%) and women (85.7%). Most participants were renting from a housing association (72.0%) and had low education (61.0%). Higher motivation to quit was statistically significantly associated with a higher intensity of previous quit attempts (p=0.03), higher quit confidence (p=0.01), higher smoking self-efficacy (p=0.01), a lower risk-minimising beliefs score (p=0.01) and using traditional nicotine replacement therapy (NRT) when trying to stop smoking or cut down (p<0.001). Conclusion Older smokers from deprived backgrounds face complex barriers to quitting smoking. Interventions are needed to increase self-efficacy for quitting, modify risk-minimising beliefs and target elements of previous quit attempts (ie, the use of NRT) that are associated with motivation to stop smoking.
Using Natural Language Processing to Automatically Assess Feedback Quality: Findings From 3 Surgical Residencies

Supplemental Digital Content is available in the text. Purpose Learning is markedly improved with high-quality feedback, yet assuring the quality of feedback is difficult to achieve at scale. Natural language processing (NLP) algorithms may be useful in this context as they can automatically classify large volumes of narrative data. However, it is unknown if NLP models can accurately evaluate surgical trainee feedback. This study evaluated which NLP techniques best classify the quality of surgical trainee formative feedback recorded as part of a workplace assessment. Method During the 2016–2017 academic year, the SIMPL (Society for Improving Medical Professional Learning) app was used to record operative performance narrative feedback for residents at 3 university-based general surgery residency training programs. Feedback comments were collected for a sample of residents representing all 5 postgraduate year levels and coded for quality. In May 2019, the coded comments were then used to train NLP models to automatically classify the quality of feedback across 4 categories (effective, mediocre, ineffective, or other). Models included support vector machines (SVM), logistic regression, gradient boosted trees, naive Bayes, and random forests. The primary outcome was mean classification accuracy. Results The authors manually coded the quality of 600 recorded feedback comments. Those data were used to train NLP models to automatically classify the quality of feedback across 4 categories. The NLP model using an SVM algorithm yielded a maximum mean accuracy of 0.64 (standard deviation, 0.01). When the classification task was modified to distinguish only high-quality vs low-quality feedback, maximum mean accuracy was 0.83, again with SVM. Conclusions To the authors’ knowledge, this is the first study to examine the use of NLP for classifying feedback quality. SVM NLP models demonstrated the ability to automatically classify the quality of surgical trainee evaluations. Larger training datasets would likely further increase accuracy.
Degradation of the Endothelial Glycocalyx Contributes to Metabolic Acidosis in Children Following Cardiopulmonary Bypass Surgery

Supplemental Digital Content is available in the text. OBJECTIVES: Cardiopulmonary bypass surgery is complicated by metabolic acidosis, microvascular dysfunction, and capillary leak. The glycocalyx—a layer of proteins and sugars lining the vascular endothelium—is degraded during cardiopulmonary bypass. We aimed to describe the kinetics of glycocalyx degradation during and following cardiopulmonary bypass. We hypothesized that cleavage of negatively charged fragments of the glycocalyx would directly induce metabolic acidosis through changes in the strong ion gap (defined using Stewart's physicochemical approach to acid-base chemistry). We also investigated whether glycocalyx degradation was associated with failure of endothelial function and cardiovascular dysfunction. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed surgical/medical PICU. PATIENTS: Twenty-seven term infants and children requiring cardiopulmonary bypass surgery for the correction/palliation of congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recruited 27 patients, 5 days to 57 months old. We prospectively sampled plasma prior to, during, and following cardiopulmonary bypass at predefined time points. We measured plasma concentrations of interleukin-6 (inflammatory marker), heparan sulfate (negatively charged glycocalyx glycosaminoglycan), and syndecan-1 (neutrally charged glycocalyx protein). We defined the following outcome measures: metabolic acidosis (strong ion gap), renal dysfunction (fold change in creatinine), capillary leak (fluid bolus volume), cardiovascular dysfunction (Vasoactive Inotropic Score), and length of ventilation. In linear regression models, maximum measured heparan sulfate concentration (negatively charged) was associated with metabolic acidosis (p = 0.016), renal dysfunction (p = 0.009), and length of ventilation (p = 0.047). In contrast, maximum measured syndecan-1 concentration (neutrally charged) was not associated with these clinical endpoints (p > 0.30 for all). CONCLUSIONS: Our data show that metabolic acidosis (increased strong ion gap) is associated with plasma concentration of heparan sulfate, a negatively charged glycosaminoglycan cleaved from the endothelial glycocalyx during cardiopulmonary bypass. In addition, cleavage of heparan sulfate was associated with renal dysfunction, capillary leak, and global markers of cardiovascular dysfunction. These data highlight the importance of designing translational therapies to protect the glycocalyx in cardiopulmonary bypass.
Evaluating disorders of gut-brain interaction in eating disorders.

OBJECTIVE Eating disorders commonly co-occur with gastrointestinal problems. This case-control study aimed to (a) document the prevalence of disorders of gut-brain interaction (DGBI) in eating disorders, (b) examine the specific impact of disordered eating behaviors on the risk of DGBI, and (c) explore the impact of current eating disorder psychopathology on DGBI. METHOD We included 765 cases with eating disorders and 1,240 controls. DGBI were assessed via the ROME III questionnaire. Prevalences of DGBI were calculated across eating disorder diagnoses (anorexia nervosa, bulimia nervosa, and multiple eating disorders) and in controls. The association between disordered eating behaviors and DGBI was examined using logistic regression models. Lastly, we compared the total number of DGBI in individuals with high versus low current eating disorder symptoms. RESULTS A large majority (88.2-95.5%) of individuals with eating disorders reported at least one DGBI and 34.8-48.7% reported three or more DGBI. Of the DGBI categories, functional bowel disorders were the most commonly endorsed category, and of the individual DGBI, irritable bowel syndrome was the most frequently reported (43.9-58.8%). All investigated disordered eating behaviors showed a positive association with most DGBI categories. Finally, individuals reporting high current eating disorder symptoms reported higher mean number of DGBI (3.03-3.34) than those with low current symptoms (1.60-1.84). DISCUSSION The directionality and mechanisms underlying the nature of the relationship between gastrointestinal and eating disorder symptoms is worthy of further study and clinicians should adopt an integrated approach by attending to both gastrointestinal and eating disorder symptoms in their patients.
Immune evasion in HPV− head and neck precancer–cancer transition is driven by an aneuploid switch involving chromosome 9p loss

Significance We report somatic copy-number alterations (SCNAs) that contribute to an immune microenvironment switch during human papillomavirus-negative head and neck cancer (HNSC) development. Specific and nonspecific SCNA levels were examined in a large prospective oral precancer (188 patients) cohort, 2 HNSC (343, 196 patients) cohorts, and 32 cell lines. Chromosome 9p21.3 loss in precursor lesions, the genomic driver of malignant transition, was enhanced by cumulative 9p-arm gene-dosage decreases, cell-intrinsic senescence suppression, and extrinsic decreases in chemokine, cytokine, and NF-κB pathways. Furthermore, 9p-arm loss and JAK2-PD-L1 codeletion were associated with PD-1 inhibitor resistance. These data reveal an oncogenic immune paradox, aneuploid checkpoint to neoplastic transformation, and immune interception and therapeutic strategies for HPV− HNSC and possibly other CN-driven tumors or diseases. An aneuploid-immune paradox encompasses somatic copy-number alterations (SCNAs), unleashing a cytotoxic response in experimental precancer systems, while conversely being associated with immune suppression and cytotoxic-cell depletion in human tumors, especially head and neck cancer (HNSC). We present evidence from patient samples and cell lines that alterations in chromosome dosage contribute to an immune hot-to-cold switch during human papillomavirus-negative (HPV−) head and neck tumorigenesis. Overall SCNA (aneuploidy) level was associated with increased CD3+ and CD8+ T cell microenvironments in precancer (mostly CD3+, linked to trisomy and aneuploidy), but with T cell-deficient tumors. Early lesions with 9p21.3 loss were associated with depletion of cytotoxic T cell infiltration in TP53 mutant tumors; and with aneuploidy were associated with increased NK-cell infiltration. The strongest driver of cytotoxic T cell and Immune Score depletion in oral cancer was 9p-arm level loss, promoting profound decreases of pivotal IFN-γ-related chemokines (e.g., CXCL9) and pathway genes. Chromosome 9p21.3 deletion contributed mainly to cell-intrinsic senescence suppression, but deletion of the entire arm was necessary to diminish levels of cytokine, JAK-STAT, and Hallmark NF-κB pathways. Finally, 9p arm-level loss and JAK2-PD-L1 codeletion (at 9p24) were predictive markers of poor survival in recurrent HPV− HNSC after anti–PD-1 therapy; likely amplified by independent aneuploidy-induced immune-cold microenvironments observed here. We hypothesize that 9p21.3 arm-loss expansion and epistatic interactions allow oral precancer cells to acquire properties to overcome a proimmunogenic aneuploid checkpoint, transform and invade. These findings enable distinct HNSC interception and precision-therapeutic approaches, concepts that may apply to other CN-driven neoplastic, immune or aneuploid diseases, and immunotherapies.
Population Dynamics of Intermediate-Host Snails in the White Nile River, Sudan: A Year-Round Observational Descriptive Study

We aimed to explore the population dynamics of snail in 3 sites of the White Nile in Sudan. More specifically, we aimed to investigate the annual patterns of snail populations that act as intermediate hosts of schistosomes and monthly snail infection rates and ecological characteristics presumably related to snail populations. We collected snails for 1 year monthly at 3 different shore sites in the vicinity of El Shajara along the White Nile river in Khartoum State, Sudan. In addition, we measured air and water temperatures, water turbidities, vegetation coverages, and water depths and current speeds. Most of the collected snails were Biomphalaria pfeifferi and Bulinus truncatus. The population densities of snails and their infection rates varied across survey sites. The collected snails liberated S. mansoni and S. haematobium cercariae as well as Amphistome and Echinostome cercariae. Infected snails were found during March–June. The ecological characteristics found to be associated with the absence of snails population were: high turbidity, deep water, low vegetation coverage (near absence of vegetation), high water temperature, and high current speed. To our knowledge, this is the first longitudinal study of the snail population and ecological characteristics in the main basin of the White Nile river.
Exploring reversible oxidation of oxygen in a manganese oxide

Nominal Na0.6(Li0.2Mn0.8)O2 with the layered P3 structure (s.g. R3m) showed XPS evidence of holes in the O-2p bands on removal of Na+ ions. A large voltage plateau at 4.1 V versus Na+/Na faded significantly over 50 cycles although the capacity in the range 20 ≤ V < 4.5 V remained unchanged. Oxidation of the O-2p bands is not reversible.
Automatic Time Series Modelling and Forecasting: A Replication Case Study of Forecasting Real GDP, the Unemployment Rate, and the Impact of Leading Economic Indicators

We test and report on time series modelling and forecasting using several U.S. Leading Economic Indicators (LEI) as an input to forecasting real U.S. GDP and the unemployment rate. These time series have been addressed before, but our results are more statistically significant using more recently developed time series modelling techniques and software. Montgomery, Zarnowitz, Tsay, and Tiao (1998) modeled the U.S. unemployment rate as a function of the weekly unemployment claims time series, 1948 – 1992. In this replication case study, we apply the Hendry and Doornik automatic time series PC-Give (AutoMetrics) methodology to the well-studied macroeconomics series, U.S. real GDP and the unemployment rate. The Autometrics system substantially reduces regression sum of squares measures relative to traditional variations on the random walk with drift model. The LEI are a statistically significant input to real GDP. A similar conclusion is found for the impact of the LEI and weekly unemployment claims series leading the unemployment rate series. We tested the forecasting ability of best univariate and best bivariate models over 60- and 120-period rolling windows and report considerable forecast error reductions. The adaptive averaging autoregressive model forecast ADA-AR and the adaptive learning forecast, ADL, produced the smallest root mean square errors and lowest mean absolute errors.