Miracle-dz/UniFAR-FTUs huggingface dataset:
Diverse roles of microbial indole compounds in eukaryotic systems

Indole and its derivatives are widespread across different life forms, functioning as signalling molecules in prokaryotes and with more diverse roles in eukaryotes. A majority of indoles found in the environment are attributed to bacterial enzymes converting tryptophan into indole and its derivatives. The involvement of indoles among lower organisms as an interspecies and intraspecies signal is well known, with many reports showing that inter‐kingdom interactions involving microbial indole compounds are equally important as they influence defence systems and even the behaviour of higher organisms. This review summarizes recent advances in our understanding of the functional properties of indole and indole derivatives in diverse eukaryotes. Furthermore, we discuss current perspectives on the role of microbial indoles in human diseases such as diabetes, obesity, atherosclerosis, and cancers. Deciphering the function of indoles as biomarkers of metabolic state will facilitate the formulation of diet‐based treatments and open unique therapeutic opportunities.
Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort

ABSTRACT Background RBC long-chain omega-3 (n–3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction. Objectives The objective of this study was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease (CVD) in predicting risk of all-cause mortality. Methods Framingham Offspring Cohort participants without prevalent CVD having RBC FA measurements and relevant baseline clinical covariates (n = 2240) were evaluated during 11 y of follow-up. A forward, stepwise approach was used to systematically evaluate the association of 8 standard risk factors (age, sex, total cholesterol, HDL cholesterol, hypertension treatment, systolic blood pressure, smoking status, and prevalent diabetes) and 28 FA metrics with all-cause mortality. A 10-fold cross-validation process was used to build and validate models adjusted for age and sex. Results Four of 28 FA metrics [14:0, 16:1n–7, 22:0, and omega-3 index (O3I; 20:5n–3 + 22:6n–3)] appeared in ≥5 of the discovery models as significant predictors of all-cause mortality. In age- and sex-adjusted models, a model with 4 FA metrics was at least as good at predicting all-cause mortality as a model including the remaining 6 standard risk factors (C-statistic: 0.778; 95% CI: 0.759, 0.797; compared with C-statistic: 0.777; 95% CI: 0.753, 0.802). A model with 4 FA metrics plus smoking and diabetes (FA + Sm + D) had a higher C-statistic (0.790; 95% CI: 0.770, 0.811) compared with the FA (P < 0.01) or Sm + D models alone (C-statistic: 0.766; 95% CI: 0.739, 0.794; P < 0.001). A variety of other highly correlated FAs could be substituted for 14:0, 16:1n–7, 22:0, or O3I with similar predicted outcomes. Conclusions In this community-based population in their mid-60s, RBC FA patterns were as predictive of risk for death during the next 11 y as standard risk factors. Replication is needed in other cohorts to validate this FA fingerprint as a predictor of all-cause mortality.
Acceptability and uptake of HIV self‐testing in emergency care settings: A systematic review and meta‐analysis

Emergency departments (ED) interface with large numbers of patients that are often missed by conventional HIV testing approaches. ED‐based HIV self‐testing (HIVST) is an innovative engagement approach which has potential for testing gains among populations that have failed to be reached. This systematic review and meta‐analysis evaluated acceptability and uptake of HIVST, as compared to standard provider‐delivered testing approaches, among patients seeking care in ED settings.
The functional reach test in people with multiple sclerosis: a reliability and validity study

ABSTRACT Background Limits of stability (LOS) is a major component of balance dysfunction in people with multiple sclerosis (MS). The functional reach test (FRT) is a clinical LOS assessment; however, its psychometric properties have not been investigated in people with MS yet. Objectives: To investigate: (1) the intrarater, interrater, and test–retest reliability of the FRT in people with MS; (2) the minimum detectable change (MDC) in the FRT distances; (3) the concurrent and discriminant validity of the FRT; and (4) the cutoff distance that best discriminates people with MS from healthy people and fallers from non-fallers with MS. Methods Forty-three people with MS and 36 healthy people participated in this study. The FRT was administered along with the instrumented LOS test, Berg Balance Scale, Four Square Step Test, Timed Up and Go Test, and Expanded Disability Status Scale. The FRT was repeated by the same rater after 2 min from the first test session to determine the intrarater reliability and was simultaneously conducted by two independent raters to determine the interrater reliability. The FRT was also repeated after 7–10 days to determine the test–retest reliability. The reliability was quantified using intraclass correlation coefficients (ICC), Bland-Altman plots, and the MDC. The validity was assessed by correlating the FRT distances with the scores of other measures and by comparing the FRT distances between the MS group and healthy people, and between the fallers and non-fallers in the MS group. Results The FRT demonstrated good to excellent intrarater, interrater, and test–retest reliability with an ICC (3,1) of 0.80–0.88 (p < .001), an ICC (3,2) of 0.94–0.97 (p < .001), an ICC (2,3) of 0.84–0.86 (p < .001), respectively. Bland–Altman analyses showed no systematic bias between the assessments. The MDC was 8.28 centimeters. The FRT was correlated with the other outcome measures (correlation coefficients ranged from 0.31 to 0.79, p < .05 for all). Significant differences in the FRT distances were found between people with MS and healthy people; however, no significant difference was found between the fallers and non-fallers with MS (p < .001 and p = .09, respectively). The cutoff distance of 35.5 centimeters best discriminates healthy people from people with MS while of 28.5 centimeters did not discriminate between the fallers and non-fallers with MS. Conclusions The FRT is a reliable, valid, and easy-to-administer tool for assessing LOS in people with MS.
Therapeutic Implications of Germline Testing in Patients With Advanced Cancers

PURPOSE Tumor mutational profiling is increasingly performed in patients with advanced cancer. We determined the extent to which germline mutation profiling guides therapy selection in patients with advanced cancer. METHODS Patients with cancer undergoing tumor genomic profiling were prospectively consented for germline cancer predisposition gene analysis (2015-2019). In patients harboring germline likely pathogenic or pathogenic (LP/P) alterations, therapeutic actionability was classified using a precision oncology knowledge base. Patients with metastatic or recurrent cancer receiving germline genotype–directed therapy were determined. RESULTS Among 11,947 patients across > 50 malignancies, 17% (n = 2,037) harbored a germline LP/P variant. By oncology knowledge base classification, 9% (n = 1042) had an LP/P variant in a gene with therapeutic implications (4% level 1; 4% level 3B; < 1% level 4). BRCA1/2 variants accounted for 42% of therapeutically actionable findings, followed by CHEK2 (13%), ATM (12%), mismatch repair genes (11%), and PALB2 (5%). When limited to the 9,079 patients with metastatic or recurrent cancer, 8% (n = 710) harbored level 1 or 3B genetic findings and 3.2% (n = 289) received germline genotype–directed therapy. Germline genotype–directed therapy was received by 61% and 18% of metastatic cancer patients with level 1 and level 3B findings, respectively, and by 54% of BRCA1/2, 75% of mismatch repair, 43% of PALB2, 35% of RAD51C/D, 24% of BRIP1, and 19% of ATM carriers. Of BRCA1/2 patients receiving a poly(ADP-ribose) polymerase inhibitor, 45% (84 of 188) had tumors other than breast or ovarian cancer, wherein the drug, at time of delivery, was delivered in an investigational setting. CONCLUSION In a pan-cancer analysis, 8% of patients with advanced cancer harbored a germline variant with therapeutic actionability with 40% of these patients receiving germline genotype–directed treatment. Germline sequence analysis is additive to tumor sequence analysis for therapy selection and should be considered for all patients with advanced cancer.
Chromosome-Scale Assembly of the Complete Genome Sequence of Leishmania (Mundinia) martiniquensis, Isolate LSCM1, Strain LV760

Leishmania (Mundinia) martiniquensis is a kinetoplastid parasite that was first isolated in 1995 on Martinique. We report the first complete genome for Leishmania martiniquensis from Asia, isolate LSCM1, strain LV760, which was sequenced using combined short-read and long-read technologies. This will facilitate greater understanding of the evolution of the geographically dispersed subgenus Mundinia. ABSTRACT Leishmania (Mundinia) martiniquensis is a kinetoplastid parasite that was first isolated in 1995 on Martinique. We report the first complete genome for Leishmania martiniquensis from Asia, isolate LSCM1, strain LV760, which was sequenced using combined short-read and long-read technologies. This will facilitate greater understanding of the evolution of the geographically dispersed subgenus Mundinia.
Mediating Role of Resilience on Nursing Faculty and Student QoL during COVID-19

COVID-19 greatly impacted nursing education and required nursing faculty and students to quickly adapt to changes caused by disease mitigation. The purpose of this study was to examine the mediating effects of resilience between the influence of demographics and school-related risk factors and nursing faculty and student quality of life (QoL) during the COVID-19 pandemic. A secondary data analysis was conducted using structural equation modeling to examine the mediating role of resilience on latent variables. Resilience had a positive, direct effect on nursing faculty and student QoL. Having a designated home workspace and being well-prepared for online learning had positive, indirect effects on QoL, mediated through resilience. Assisting children with schoolwork had a negative impact on the psychological and environmental QoL domains. Remarkably, having a caregiver role positively influenced the psychological QoL domain. Supporting and promoting faculty and nursing students’ health and well-being is imperative during and after the pandemic.
Decreased KATP channel activity contributes to the low glucose threshold for insulin secretion of rat neonatal islets

Transitional hypoglycemia in normal newborns occurs in the first 3 days of life and has clinical features consistent with hyperinsulinism. We found a lower threshold for glucose-stimulated insulin secretion from freshly isolated embryonic day (E)22 rat islets, which persisted into the first postnatal days. The threshold reached the adult level by postnatal day (P)14. Culturing P14 islets also decreased the glucose threshold. Freshly isolated P1 rat islets had a lower threshold for insulin secretion in response to BCH (2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid), a non-metabolizable leucine analog, and diminished insulin release in response to tolbutamide, an inhibitor of β-cell KATP channels. These findings suggested that decreased KATP channel function could be responsible for the lower glucose threshold for insulin secretion. Single-cell transcriptomic analysis did not reveal a lower expression of KATP subunit genes in E22 compared to P14 β-cells. The investigation of electrophysiological characteristics of dispersed β-cells showed that early neonatal and cultured cells had fewer functional KATP channels per unit membrane area. Our findings suggest that decreased surface density of KATP channels may contribute to the observed differences in glucose threshold for insulin release.
Hidradenitis Suppurativa From a Patient Perspective Including Symptoms and Self-Treatment

Introduction Hidradenitis Suppurativa (HS) is a chronic inflammatory disordercommonly affecting body folds. It can significantly impair quality of life due to the physical, psychological, and socialturmoil experienced by patients. Treatment remains a challenge.Limited data on the HS patient experience, such as self-treatment exists. Methods This was a single-center cross-sectional study, utilizing a paper-based survey. Surveys were mailed out to all HS patients from the dermatology clinic and completed on a voluntary basis. Demographics, disease characteristics, medical and family history, treatments tried, and life quality were documented. Results The response rate was 49.4% (41/83), with a female predominance (26/41). Eighty-five percent (35/41) were Caucasian with an average age and BMI of 39.0 ± 16.78 and 30.71 ± 7.02, respectively. In total, 24.4% (10/41), 56.0% (23/41), and 19.5% (8/41) had Hurley I, II, and III, respectively. Lesions affected the genital region (75.6%), thigh/groin (68.2%), and axilla (46.3). Almost half (49%) of patients experienced an average of 1-2 flares per month. The most bothersome symptoms were pain (92.7%), discharge (68.3%), malodor (63.4%), and itch (61%). Depression (53.7%), severe facial acne (14.6%), and hypertension (14.6%) were the most common co-morbidities. Treatments used included antibiotics (82.9%) and surgical excision (34.2%) were. Over 90% of patients reportedself-treatment of lesions by squeezing (80.5%), soaking (53.7%), and lancing (41.4%). Conclusions This study provides insight into the patient perspective of HS. We identify itch as a symptom that is not frequently associated with HS and reveal how commonly patients utilize various types of self-treatment in their experience of disease.
Chinese registry of rheumatoid arthritis: IV. Correlation and consistency of rheumatoid arthritis disease activity indices in China

Supplemental Digital Content is available in the text Abstract Background: Disease activity indices (DAIs) including disease activity score 28 (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) have been widely used in clinical practice and research studies of rheumatoid arthritis (RA). The objective of our study was to evaluate the correlation and concordance among different DAIs in Chinese patients with RA. Methods: A cross-sectional study, including patients enrolled in the Chinese registry of rheumatoid arthritis from November 2016 to August 2018, was conducted. The correlations were evaluated using Spearman correlation coefficient and concordance with Bland-Altman plots, quadratic weighted kappa, and discordance rates in the crosstab. For other indices, the optimal cutoff points corresponding to SDAI remission were explored through receiver operating characteristic curve analysis. Results: A total of 30,501 patients were included, of whom 80.46% were women. Most individuals were with moderate disease activity or high disease activity. High correlations among DAS28-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP), SDAI and CDAI were observed. Similarly, the weighted kappa value among the indices was high. In Bland-Altman plots, a positive difference between DAS28-ESR and DAS28-CRP was observed, with an absolute difference of >1.2 in 3079 (10.09%) patients. In crosstab, approximately 30% of the patients were classified into different groups. Concordance values between SDAI remission and the optimal cutoff points of DAS28-ESR, DAS28-CRP, and CDAI were 3.06, 2.37, and 3.20, respectively. Conclusions: Although DAIs had high correlations and weighted kappa values, the discordance between DAIs was significant in Chinese patients with RA. The four DAIs are not interchangeable.
Expression analysis and tissue localization of IgZ in the grouper Epinephelus coioides after Vibrio alginolyticus infection and vaccination.

The orange-spotted grouper (Epinephelus coioides) is an important marine farmed fish in China. It is affected by the bacterial pathogen Vibrio alginolyticus, which causes high mortality and substantial economic losses. We studied the transcriptional changes of the IgZ gene in E. coioides following V. alginolyticus stimulation and investigated the distribution of IgZ in different tissues. The highest expression level of IgZ occurred in the head kidney. When fish were stimulated with live and inactivated V. alginolyticus, the expression levels of IgZ in the head kidney, spleen, intestine, gills and blood cells were significantly upregulated. In an in situ hybridization study, IgZ mRNA-positive cells were detected in the head kidney, spleen and gill, but positive signals were not detected in the liver and intestine. IgZ-labelled cells increased in the head kidney, spleen and gills post-infection with V. alginolyticus for 21 days. The present study provides additional evidence that IgZ is involved in mucosal immune responses and helps explain the role of IgZ in E. coioides defence against V. alginolyticus infection.
Reconstructing Unsteady Flow Data From Representative Streamlines via Diffusion and Deep-Learning-Based Denoising

We propose VFR-UFD, a new deep learning framework that performs vector field reconstruction (VFR) for unsteady flow data (UFD). Given integral flow lines (i.e., streamlines), we first generate low-quality UFD via diffusion. VFR-UFD then leverages a convolutional neural network to reconstruct spatiotemporally coherent, high-quality UFD. The core of VFR-UFD lies in recurrent residual blocks that iteratively refine and denoise the input vector fields at different scales, both locally and globally. We take consecutive time steps as input to capture temporal coherence and apply streamline-based optimization to preserve spatial coherence. To show the effectiveness of VFR-UFD, we experiment with several vector field data sets to report quantitative and qualitative results and compare VFR-UFD with two VFR methods and one compression algorithm.
Abortion quality of care from the client perspective: a qualitative study in India and Kenya

Abstract Quality healthcare is a key part of people’s right to health and dignity, yet access to high-quality care can be limited by legal, social and economic contexts. There is limited consensus on what domains constitute quality in abortion care and the opinions of people seeking abortion have little representation in current abortion quality measures. In this qualitative study, we conducted 45 interviews with abortion clients in Mumbai, India, and in Eldoret and Thika, Kenya, to assess experiences with abortion care, definitions of quality and priorities for high-quality abortion care. Among the many aspects of care that mattered to clients, the client–provider relationships emerged as essential. Clients prioritized being treated with kindness, respect and dignity; receiving information and counselling that was personalized to their individual situation and reassurance and support from their provider throughout the entire abortion process, including follow-up after the abortion. Many clients also noted the importance of skilled providers and appropriate care. There were similarities across the two country contexts, yet there were some differences in how clients defined high-quality care; therefore, specific political and cultural influences must be considered when implementing measurement and improving person-centred quality of care. These domains, particularly interpersonal interactions, should be prioritized in India and Kenya when health systems, facilities and providers design person-centred measures for quality in abortion care.
Regular arrangement of collecting venules (RAC) as an endoscopic marker for exclusion of Helicobacter pylori (H. pylori) infection: A systematic review and meta‐analysis

Helicobacter pylori (H. pylori) is the most common cause of gastric cancer. Growing evidence suggests that the regular arrangement of collecting venules (RAC) can be used as an endoscopic marker to diagnose H. pylori infection. However, data on the diagnostic accuracy of RAC for H. pylori infection are conflicting. We performed a systematic review and meta‐analysis of relevant studies to determine the diagnostic accuracy and clinical utility of RAC for the diagnosis of H. pylori infection.
The effects of testosterone on gene expression of cell‐adhesion molecules and scaffolding proteins: The role of sex in early development

Sex‐specific differences in brain plasticity appear to be organised by testosterone, which is particularly important during the early stages of development. The main purpose of the present study was to examine the sex differences in mRNA and protein levels of selected cell‐adhesion molecules and scaffolding proteins on postnatal days 5 (P5) and 9 (P9) in the rat hippocampus, as well as evaluate the effects of testosterone treatment (100 nM, 48 hr) on synaptic proteins in SH‐SY5Y (neuron‐like) and U‐87MG (astrocyte‐like) cells. The gene expression levels of Neuroligin 3 and ‘SH3 and multiple ankyrin repeat domains protein’ 1 and 3 (SHANK1 and SHANK3) were significantly lower in males compared to females at P5. At P9, a similar significant trend towards a decrease in mRNA expression and protein levels of SHANK3 was found in males. Testosterone treatment induced a significant decrease of Neuroligin 1‐3 mRNA expression in both SH‐SY5Y and U‐87MG cells. SHANK1 and SHANK3 mRNA levels significantly decreased in U‐87MG cells response to testosterone presence. The presented results demonstrate that the association of selected postsynaptic cell‐adhesion molecules and scaffolding proteins is sex‐related. Testosterone appears to be particularly involved in the developmental mechanisms related to neuroplasticity.
Synaptic density in carriers of C9orf72 mutations: a [11C]UCB‐J PET study

Synaptic loss is an early and clinically relevant feature of many neurodegenerative diseases. Here we assess three adults at risk of frontotemporal dementia from C9orf72 mutation, using [11C]UCB‐J PET to quantify synaptic density in comparison with 19 healthy controls and one symptomatic patient with behavioural variant frontotemporal dementia. The three pre‐symptomatic C9orf72 carriers showed reduced synaptic density in the thalamus compared to controls, and there was an additional extensive synaptic loss in frontotemporal regions of the symptomatic patient. [11C]UCB‐J PET may facilitate early, pre‐symptomatic assessment, monitoring of disease progression and evaluation of new preventive treatment strategies for frontotemporal dementia.
Pan-cancer analysis reveals an immunological role and prognostic potential of PXN in human cancer

Paxillin (PXN) is a protein involved in numerous physiological processes, and its presence is closely related to the occurrence and development of many types of tumors. However, no studies have analyzed PXN from a pan-cancer perspective. We analyzed PXN expression, immune cell infiltration, prognosis, and biological function across different types of tumors included in The Cancer Genome Atlas and Gene Expression Omnibus datasets. The results showed that expression of PXN varies in different tumors. Expression of PXN strongly correlated with prognosis in patients with tumors; higher PXN expression usually was linked to poor overall and disease-free survival. Expression of PXN in breast invasive carcinoma and lymphoid neoplasm diffuse large B-cell lymphoma was related to the degree of CD8+ T-cell infiltration, and infiltration of cancer-associated fibroblasts, such as kidney renal papillary cell carcinoma and brain lower-grade glioma, was also observed in other tumors. The results of pan-cancer analysis showed that abnormal PXN expression was related to poor prognosis, immune infiltration, and protein phosphorylation in different tumor types. Therefore, the PXN gene may become a potential biomarker of clinical tumor prognosis.