Miracle-dz/UniFAR-FTUs huggingface dataset:
Based on Molecular Subtypes, Immune Characteristics and Genomic Variation to Constructing and Verifying Multi-Gene Prognostic Characteristics of Colorectal Cancer

Background: Colon cancer (COAD) has been identified as being among the most prevalent tumors globally and ranked the third major contributor to cancer-related mortality. COAD is a molecularly heterogeneous disease. There are great differences in clinical manifestations and prognosis among different molecular subtypes. Methods:379 TCGA-COAD samples were divided into four subtypes: primary proliferative, with collective, crypt-like, and EMT invasion. The differences among the four subtypes were analyzed from the multidimensional perspectives of immunity, genomic variation, and prognosis. The limma package was utilized to identify differentially expressed genes (DEGs) amongst different molecular subtypes. Phenotype-related coexpressed gene modules were identified using WGCNA. The polygenic prognosis model was created utilizing the lasso Cox analysis and verified by time-dependent subject operating characteristics (ROC). Results: There are some differences in prognosis, TMB and common gene variation, immune score, and immunotherapy/chemotherapy between proliferative and three invasive molecular subtypes. 846 differential genes (DEGs) were obtained by limma packet analysis. Differential gene analysis was utilized to screen the DEGs among distinct subtypes, which were significantly enriched in the pathways related to tumorigenesis and development. Co-expression network analysis found 46 co-expressed genes correlated with proliferative and three invasive phenotypes. Based on differentially co-expressed genes, we developed a prognostic risk model of 8-genes signature, which exhibited strong stability regardless of external and internal validation. RT-PCR experiments proved the expression of eight genes in tumor and normal samples. Conclusion: We have developed an eight-gene signature prognostic stratification system. Furthermore, we proposed that this classifier can serve as a molecular diagnostic tool to assess the prognosis of colon cancer patients.
Validation of a Standard Protocol to Assess the Fermentative and Chemical Properties of Saccharomyces cerevisiae Wine Strains

This paper reports on a common experiment performed by 17 Research Units of the Italian Group of Microbiology of Vine and Wine (GMVV), which belongs to the Scientific Society SIMTREA, with the aim to validate a protocol for the characterization of wine strains of Saccharomyces cerevisiae. For this purpose, two commercial S. cerevisiae strains (EC 1118 and AWRI796) were used to carry out inter-laboratory-scale comparative fermentations using both synthetic medium and grape musts and applying the same protocol to obtain reproducible, replicable, and statistically valid results. Ethanol yield, production of acetic acid, glycerol, higher alcohols, and other volatile compounds were assessed. Moreover, the Fourier transform infrared spectroscopy was also applied to define the metabolomic fingerprint of yeast cells from each experimental trial. Data were standardized as unit of compounds or yield per gram of sugar (glucose and fructose) consumed throughout fermentation, and analyzed through parametric and non-parametric tests, and multivariate approaches (cluster analysis, two-way joining, and principal component analysis). The results of experiments carried out by using synthetic must showed that it was possible to gain comparable results from three different laboratories by using the same strains. Then, the use of the standardized protocol on different grape musts allowed pointing out the goodness and the reproducibility of the method; it showed the main traits of the two yeast strains and allowed reducing variability amongst independent batches (biological replicates) to acceptable levels. In conclusion, the findings of this collaborative study contributed to the validation of a protocol in a specific synthetic medium and in grape must and showed how data should be treated to gain reproducible and robust results, which could allow direct comparison of the experimental data obtained during the characterization of wine yeasts carried out by different research laboratories.
Stoichiometry of the Gene Products From the Tetrachloroethene Reductive Dehalogenase Operon pceABCT

Organohalide respiration (OHR) is a bacterial anaerobic process that uses halogenated compounds, e.g., tetrachloroethene (PCE), as terminal electron acceptors. Our model organisms are Dehalobacter restrictus strain PER-K23, an obligate OHR bacterium (OHRB), and Desulfitobacterium hafniense strain TCE1, a bacterium with a versatile metabolism. The key enzyme is the PCE reductive dehalogenase (PceA) that is encoded in the highly conserved gene cluster (pceABCT) in both above-mentioned strains, and in other Firmicutes OHRB. To date, the functions of PceA and PceT, a dedicated molecular chaperone for the maturation of PceA, are well defined. However, the role of PceB and PceC are still not elucidated. We present a multilevel study aiming at deciphering the stoichiometry of pceABCT individual gene products. The investigation was assessed at RNA level by reverse transcription and (quantitative) polymerase chain reaction, while at protein level, proteomic analyses based on parallel reaction monitoring were performed to quantify the Pce proteins in cell-free extracts as well as in soluble and membrane fractions of both strains using heavy-labeled reference peptides. At RNA level, our results confirmed the co-transcription of all pce genes, while the quantitative analysis revealed a relative stoichiometry of the gene transcripts of pceA, pceB, pceC, and pceT at ~ 1.0:3.0:0.1:0.1 in D. restrictus. This trend was not observed in D. hafniense strain TCE1, where no substantial difference was measured for the four genes. At proteomic level, an apparent 2:1 stoichiometry of PceA and PceB was obtained in the membrane fraction, and a low abundance of PceC in comparison to the other two proteins. In the soluble fraction, a 1:1 stoichiometry of PceA and PceT was identified. In summary, we show that the pce gene cluster is transcribed as an operon with, however, a level of transcription that differs for individual genes, an observation that could be explained by post-transcriptional events. Despite challenges in the quantification of integral membrane proteins such as PceB and PceC, the similar abundance of PceA and PceB invites to consider them as forming a membrane-bound PceA2B protein complex, which, in contrast to the proposed model, seems to be devoid of PceC.
Helicobacter canis: A Review of Microbiological and Clinical Features

Helicobacter canis, an enterohepatic Helicobacter, has proven its role in human diseases and has been rediscussed in recent years as its zoonotic potential is increasingly described. Routine microbiological detection of this pathogen is a difficult task as its culture may fail due to fastidious growth. It is therefore supposed that many clinical laboratories under-recognize H. canis infections. A review of all clinical and microbiological literature currently available from previous relevant H. canis human clinical cases, mainly bacteremia, added with a clinical case observed at the Cliniques universitaires Saint-Luc, was performed. Clinical features of H. canis reports show the presence of underlying clinical conditions in 89% of the cases, bacteremia in 83%, associated fever in 58%, and recent close contact with pets in 83%, especially dogs. The observed microbiological trends from 10 cases of bacteremia were a median of 4 days until positive blood culture bottle detection, subcultures showing a thin layer of small colonies under microaerophilic atmosphere at 35–42°C after 3–4 days of growth, and an identification requiring 16S rRNA sequencing given the difficulties observed with MALDI-TOF MS. Low MICs were observed for penicillins, amoxicillin/clavulanic acid, carbapenems, and metronidazole in opposition to high MICs for ciprofloxacin. A frequent association of H. canis and bacteremia in immunocompromised patients with recurrent fever in contact with pets, especially dogs, was identified. Considering the fastidious growing capacities, final identification from blood cultures may not be expected before 7 days. Intravenous ceftriaxone, oral doxycycline, or metronidazole has been suggested as efficient therapeutic choices.
Prevalence and Prognostic Significance of Malnutrition in Hypertensive Patients in a Community Setting

Background Malnutrition is a significantly poor prognostic factor for a variety of cardiovascular diseases. However, its prevalence and prognostic value in hypertensive patients is still unclear. The present study sought to determine the prevalence and prognostic value of malnutrition in hypertensive patients in a community setting. Methods We included 9,949 hypertensive patients from the National Health and Nutrition Examination Survey (NHANES) (2005–2014). The Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Naples Prognostic Score (NPS) were applied to assess the nutritional status of participants. A Cox regression model was established to examine the association between malnutrition and cardiovascular and all-cause mortality. Results In all, 19.9, 3.9, and 82.9% hypertensive patients were considered to have malnutrition as evaluated by the CONUT, NRI, and NPS, respectively. Malnutrition assessed by CONUT and NRI was independently associated with cardiovascular mortality (HR [95% CI]) for mild and moderate-to-severe degree of malnutrition, respectively: 1.41 (1.04–1.91) and 5.79 (2.34–14.29) for CONUT; 2.60 (1.34–5.07) and 3.30 (1.66–6.56) for NRI (all P < 0.05), and for all-cause mortality (HR [95% CI]) for mild and moderate-to-severe degree of malnutrition, respectively: 1.48 (1.30–1.70) and 4.87 (3.40–6.98) for CONUT; 1.72 (1.24–2.39) and 2.60 (1.96–3.44) for NRI (all P < 0.01). Naples Prognostic Score could only independently predict all-cause mortality. Conclusions Malnutrition was common among hypertensive patients and was closely associated with both long-term cardiovascular and all-cause mortality.
Higher Abdominal Adiposity Is Associated With Lower Muscle Strength in Chilean Adults

Handgrip strength (HGS) is a well-established indicator of muscle strength and a reasonable clinical predictor of metabolic health and diseases. This study explores the association between relative muscular strength and abdominal obesity (AO) in healthy Chilean adults. A convenience sample was recruited (n = 976) between 2018 and 2020. The HGS was determined by dynamometry. The anthropometry (weight, height, waist, and mid-arm circumference) and physical activity were also measured. The relative HGS (RHGS) was calculated by dividing the maximum HGS of the dominant hand by the body mass index. The AO was defined as a waist circumference (WC) >88 cm for women, and >102 cm for men. From the sample, 52.6% were women, 56.4% had excessive weight, and 42.7% had AO. The absolute and RHGS were greater in men compared to women (p < 0.001) and were decreased with age in both sexes. We observed a moderate negative correlation between WC and RHGS (rho = −0.54, and rho = −0.53, for men and women, respectively). The RHGS was lower in individuals with AO, independent of age and sex (p < 0.05). For each cm increase in WC, the odds of low RHGS (<25th percentile) increased by 12 and 9% for men and women, respectively. The AO is related to higher odds for low RHGS (OR: 1.72; 95% CI: 1.23–2.41). In our sample of healthy adults, a higher AO was associated with a lower muscle strength measured by dynamometry.
Alcohol-Related Elevation of Liver Transaminase Is Associated With Gut Microbiota in Male

Alcoholic liver damage has become a widespread health problem as alcohol consumption increases and is usually identified by elevated liver transaminase. We conducted this study to investigate the role of the gut microbiome in the individual susceptibility to alcoholic liver injury. We divided the participants into four groups based on alcohol consumption and liver transaminase elevation, which were drinking case group, drinking control group, non-drinking case group, and non-drinking control group. The drinking case group meant participants who were alcohol consumers with elevated liver transaminase. We found that alpha and beta diversities of the drinking case group differed from the other three groups. Species Faecalibacterium prausnitzii and Roseburia hominis were significantly in lower abundance in the drinking case group and were proved the protective effect against inflammatory liver damage in the former study. Ruminococcus gnavus exhibited the most positive association to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and contributed to liver inflammation.
No Association Between Loneliness, Episodic Memory and Hippocampal Volume Change in Young and Healthy Older Adults: A Longitudinal European Multicenter Study

Background Loneliness is most prevalent during adolescence and late life and has been associated with mental health disorders as well as with cognitive decline during aging. Associations between longitudinal measures of loneliness and verbal episodic memory and brain structure should thus be investigated. Methods We sought to determine associations between loneliness and verbal episodic memory as well as loneliness and hippocampal volume trajectories across three longitudinal cohorts within the Lifebrain Consortium, including children, adolescents (N = 69, age range 10–15 at baseline examination) and older adults (N = 1468 over 60). We also explored putative loneliness correlates of cortical thinning across the entire cortical mantle. Results Loneliness was associated with worsening of verbal episodic memory in one cohort of older adults. Specifically, reporting medium to high levels of loneliness over time was related to significantly increased memory loss at follow-up examinations. The significance of the loneliness-memory change association was lost when eight participants were excluded after having developed dementia in any of the subsequent follow-up assessments. No significant structural brain correlates of loneliness were found, neither hippocampal volume change nor cortical thinning. Conclusion In the present longitudinal European multicenter study, the association between loneliness and episodic memory was mainly driven by individuals exhibiting progressive cognitive decline, which reinforces previous findings associating loneliness with cognitive impairment and dementia.
The Verticillium dahliae Spt-Ada-Gcn5 Acetyltransferase Complex Subunit Ada1 Is Essential for Conidia and Microsclerotia Production and Contributes to Virulence

Verticillium dahliae is a destructive soil-borne pathogen of many economically important dicots. The genetics of pathogenesis in V. dahliae has been extensively studied. Spt-Ada-Gcn5 acetyltransferase complex (SAGA) is an ATP-independent multifunctional chromatin remodeling complex that contributes to diverse transcriptional regulatory functions. As members of the core module in the SAGA complex in Saccharomyces cerevisiae, Ada1, together with Spt7 and Spt20, play an important role in maintaining the integrity of the complex. In this study, we identified homologs of the SAGA complex in V. dahliae and found that deletion of the Ada1 subunit (VdAda1) causes severe defects in the formation of conidia and microsclerotia, and in melanin biosynthesis and virulence. The effect of VdAda1 on histone acetylation in V. dahliae was confirmed by western blot analysis. The deletion of VdAda1 resulted in genome-wide alteration of the V. dahliae transcriptome, including genes encoding transcription factors and secreted proteins, suggesting its prominent role in the regulation of transcription and virulence. Overall, we demonstrated that VdAda1, a member of the SAGA complex, modulates multiple physiological processes by regulating global gene expression that impinge on virulence and survival in V. dahliae.
Comparative Study on Residents' Health-Promoting Lifestyle and Life Satisfaction in Wuhan Before and After the COVID-19 Pandemic

The Coronavirus Disease-19 (COVID-19) pandemic has dramatically affected residents' life. Whether the COVID-19 pandemic has significantly influenced the residents' health-promoting lifestyle, and life satisfaction is an urgent problem to be studied. Based on Health Belief Model (HBM), this paper explored and compared the responses of residents' health-promoting lifestyle and life satisfaction on the influence of the COVID-19 pandemic. Data were collected from a sample of 2,054 residents in Wuhan by questionnaire survey. The results show that the total score of health-promoting lifestyle after the COVID-19 pandemic has increased significantly compared with that before the COVID-19 pandemic, and the scores of all dimensions of health-promoting lifestyle have improved. Among them, the scores of exercises, self-actualization, and stress management are significantly higher than those before the COVID-19 pandemic. However, the score of residents' life satisfaction has shown a downward trend. There were also significant differences in life satisfaction on the demographic variables, such as gender, age, education level, marital status, and family average income. The findings are of great significance in promoting residents' health-promoting lifestyles and life satisfaction in the context of the extraordinary pandemic.
Intersegmental Interactions Give Rise to a Global Network

Animal motor behaviors require the coordination of different body segments. Thus the activity of the networks that control each segment, which are distributed along the nerve cord, should be adequately matched in time. This temporal organization may depend on signals originated in the brain, the periphery or other segments. Here we evaluate the role of intersegmental interactions. Because of the relatively regular anatomy of leeches, the study of intersegmental coordination in these animals restricts the analysis to interactions among iterated units. We focused on crawling, a rhythmic locomotive behavior through which leeches move on solid ground. The motor pattern was studied ex vivo, in isolated ganglia and chains of three ganglia, and in vivo. Fictive crawling ex vivo (crawling) displayed rhythmic characteristics similar to those observed in vivo. Within the three-ganglion chains the motor output presented an anterior-posterior order, revealing the existence of a coordination mechanism that occurred in the absence of brain or peripheral signals. An experimental perturbation that reversibly abolished the motor pattern in isolated ganglia produced only a marginal effect on the motor activity recorded in three-ganglion chains. Therefore, the segmental central pattern generators present in each ganglion of the chain lost the autonomy observed in isolated ganglia, and constituted a global network that reduced the degrees of freedom of the system. However, the intersegmental phase lag in the three-ganglion chains was markedly longer than in vivo. This work suggests that intersegmental interactions operate as a backbone of correlated motor activity, but additional signals are required to enhance and speed coordination in the animal.
Blunted Post-COVID-19 Humoral Immunity in Patients With CNS Demyelinating Disorders on Anti-CD20 Treatments

With unclear characteristics of post-infection and post-vaccination immunity, the multiple sclerosis community lacks evidence to guide patients on their continued coronavirus disease 2019 (COVID-19) infection risk. As disease modifying treatments all modulate the immune system, we expect their use to alter acquired immunity to COVID-19, but the specific impact of individual treatments is unclear. To address this, we analyzed the patient and COVID-19 specific characteristics associated with post-infection humoral immunity in 58 patients with central nervous system (CNS) demyelinating disorders in the Boston metropolitan area. Univariate analysis of variance was performed using Mann Whitney U test for continuous variables, and Chi Square or Fisher Exact test for nominal variables. Univariate and stepwise multivariate nominal logistic regression identified clinical characteristics associated with COVID-19 specific nucleocapsid IgG antibody formation post-infection. Our cohort demonstrated a 42% post-infection seropositive rate with a significantly higher rate observed with shorter duration between infection and antibody collection and use of natalizumab over no/other treatment. Use of anti-CD20 treatments compared to no/other treatment was associated with a significantly lower rate of seropositivity. However, only shorter duration between infection and antibody collection as well as use of no/other treatment compared to anti-CD20 treatment were found to be independently associated with increased likelihood of post-infection seropositivity. Additionally, we demonstrate durability of antibody response up to 9 months in a small subset of patients. Thus, our data supports that patients with CNS demyelinating disorders regardless of DMT are able to form a measurable antibody response after COVID-19 infection, and that patients on anti-CD20 treatments form less robust immunity after COVID-19 infection.
Case Report: Proteinase 3 Antineutrophil Cytoplasmic Antibody-Associated Ulcerative Colitis Presenting as Recurrent Intestinal Pseudo-Obstruction in a Teenage Patient With in situ Proteinase 3 Immunohistochemical Staining

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with the colorectum as its major target organ. Involvement of the upper gastrointestinal tract in UC is rare and presents with nonspecific endoscopic and microscopic characteristics. Recent studies have demonstrated proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) to be a serological marker for differentiating UC from Crohn's disease in children and for detecting disease activity and nonresponse to steroid therapy and antitumor necrotizing factor-α agents. Herein, we report a 13-year-old female patient mainly presenting with recurrent bilious vomiting who was initially diagnosed with acute gastroenteritis. Intestinal pseudo-obstruction was confirmed through observation of a patent but segmentally dilated jejunum in the barium follow-through examination and other imaging; such obstruction can be attributed to backwash ileitis, superior mesenteric artery syndrome, ileus due to hypokalemia, or PR3-associated enteritis. Laboratory data revealed leukocytosis with neutrophil predominance and serum antinuclear antibody and PR3-ANCA positivity. Overlapping syndrome with autoimmune diseases was suspected. Pathology revealed a crypt abscess with aggregates of neutrophils consistent with UC but did not indicate vasculitis. The in situ immunohistochemical staining revealed PR3 density mainly in the colon and focally in the duodenum. To our knowledge, this is the first case report with in situ pathological evidence of PR3 in inflamed intestinal tissues in a patient with UC and with rare initial presentation of intestinal pseudo-obstruction–induced recurrent bilious vomiting. Whether the clinical features of the present case constitute overlap syndrome with other autoimmune disease or a disease variation of UC warrants further investigation. Notably, the patient's serum PR3-ANCA titers remained high in coincidence with increased disease activity and nonresponse to steroid therapy, but became lower after infliximab treatment. PR3-ANCA as a potential serum biomarker to aid in making differential diagnoses of UC in children, correlating disease activity, and predicting therapeutic responses was also reviewed.