Miracle-dz/UniFAR-FTUs huggingface dataset:
Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.
Galactic chemical evolution

In this paper we review the current ideas about the formation of our Galaxy. In particular, the main ingredients necessary to build chemical evolution models (star formation, initial mass function and stellar yields) are described and discussed. A critical discussion about the main observational constraints available is also presented. Finally, our model predictions concerning the evolution of the abundances of several chemical elements (H, D, He, C, N, O, Ne, Mg, Si, Ca and Fe) are compared with observations relative to the solar neighborhood and the whole disk. We show that from this comparison we can constrain the history of the formation and evolution of the Milky Way as well as the nucleosynthesis theories concerning the Big Bang and the stars.
Inflammation-induced TRIM21 represses hepatic steatosis by promoting the ubiquitination of lipogenic regulators

Nonalcoholic steatohepatitis (NASH) is a leading cause for chronic liver diseases. Current therapeutic options are limited due to an incomplete mechanistic understanding of how steatosis transitions to NASH. Here we show that the TRIM21 E3 ubiquitin ligase is induced by the synergistic actions of proinflammatory TNF-α and fatty acids in livers of humans and mice with NASH. TRIM21 ubiquitinates and degrades ChREBP, SREBP1, ACC1, and FASN, key regulators of de novo lipogenesis, and A1CF, an alternative splicing regulator of the high-activity ketohexokinase-C (KHK-C) isoform and rate-limiting enzyme of fructose metabolism. TRIM21-mediated degradation of these lipogenic activators improved steatosis and hyperglycemia as well as fructose and glucose tolerance. Our study identifies TRIM21 as a negative regulator of liver steatosis in NASH and provides mechanistic insights into an immunometabolic crosstalk that limits fatty acid synthesis and fructose metabolism during metabolic stress. Thus, enhancing this natural counteracting force of steatosis through inhibition of key lipogenic activators via TRIM21-mediated ubiquitination may provide a therapeutic opportunity to treat NASH.
A comparison of three‐film analysis software for stereotactic radiotherapy patient‐specific quality assurance

Abstract Aim The aim of this study was to investigate the suitability of three radiochromic film analysis software for stereotactic radiotherapy patient‐specific quality assurance (PSQA): FilmQA Pro v5.0, SNC Patient v6.2, and eFilmQA v5.0. Methods Film calibration was conducted for each software followed by three sets of measurements. The first set assessed calibration accuracy by comparing measured and delivered doses at increments different from those used for calibration. The second set used each software to conduct PSQA through gamma analysis on 10 stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) patients. The third set utilized SNC Patient and eFilmQA to carry out gamma analysis on a collection of four digital test images, eliminating delivery and scanning uncertainties from impacting the analysis. Key supporting features within each software for conducting gamma analysis were identified. Results Overall, FilmQA Pro and eFilmQA were deemed comparable and favoured over SNC Patient due to the presence of key features such as triple‐channel dosimetry, auto‐optimization, and dose scaling. FilmQA Pro has a substantial user base and established reputation. eFilmQA, having been introduced more recently, serves as a viable alternative to FilmQA Pro, having been further refined for stereotactic radiotherapy PSQA. Conclusion This study investigated the suitability of three film analysis software (FilmQA Pro, eFilmQA, and SNC Patient) for stereotactic radiotherapy PSQA. Results from the investigation indicated that both FilmQA Pro and eFilmQA are comparably suitable and are preferred over SNC Patient. Both FilmQA Pro and eFilmQA are recommended for radiotherapy clinics.
Understanding the annual cycle in global steric height

Steric variability in the ocean includes diabatic changes in the surface layer due to air‐sea buoyancy fluxes and adiabatic changes due to advection, which are dominant in the subsurface ocean. Here the annual signal in subsurface steric height (η′below 200 db) is computed on a global scale using temperature and salinity profiles from Argo floats. The zonal average of Δη′ over a season (e.g., ηMarch′−ηDecember′ ) is compared to the wind‐forced vertical advection contribution (Δηw′) both in the global ocean and in different basins. The results show agreement that extends beyond the tropics. The estimate of Δηw′ is based on the Ekman pumping and assumes that the seasonal vertical velocity is constant over the depth range of interest. This assumption is consistent with annual isopycnal displacements inferred from Argo profiles. The contribution of horizontal advection to Δη′is significant in some regions and consistent with differences between Δη′ and Δηw′.
Effect of NPS Loadings from Livestock on Small Watersheds

Abstract The objective of this paper was to quantit atively analyze the effect of concentrated animal feeding operations (CAFO) NPS pollu tion on a small watershe dwater quality. Monitoring was conducted from March to October, 2013. Monthly flow rate and selected water quality at each monitoring site were measured during dry days. Rainy day monitori ng also was conducted. Modeli ng was conducted to evaluate the effect of CAFO NPS po llution on the wate rquality at the watershed outlet. The highest and mean concentration of se lected water quality indices during rainy days were hi gher than those in dry daysin general. The highest TN concentration measured at the CAFP pollution discharge point was 237.831 mg/L. The results revealed that the CAFO NPSpollution sources could be equally blamed for the water quality degradation of the stream. However, the effect of the NPS pollut ion from CAFOs seeme dnot to be very influential to the watershed water quality at the outlet. SWAT modeling revealed that the TN load was reduced by 18.95 %, 23.39 % and30.53 % at the watershed outlet if the TN load at the CAFO NPS pollution discharge point reduced by 20 %, 40 % and 60 %, respec tively. It was though tthat the natural attenuation processes play ed an important role. The modeling was based only on the assumption of the load redu ction and not verified bythe monitored data. Therefore, it was suggested that a long term monitoring studies for the evaluation of the impact of CAFO NPS pollution on the watershed water quality be conducted.Keywords:Livestock; NPS Pollution; Pollution Load; SWAT*
Spatio-Temporal Explanation of 3D-EEGNet for Motor Imagery EEG Classification Using Permutation and Saliency

Recently, convolutional neural network (CNN)-based classification models have shown good performance for motor imagery (MI) brain-computer interfaces (BCI) using electroencephalogram (EEG) in end-to-end learning. Although a few explainable artificial intelligence (XAI) techniques have been developed, it is still challenging to interpret the CNN models for EEG-based BCI classification effectively. In this research, we propose 3D-EEGNet as a 3D CNN model to improve both the explainability and performance of MI EEG classification. The proposed approach exhibited better performances on two MI EEG datasets than the existing EEGNet, which uses a 2D input shape. The MI classification accuracies are improved around 1.8% and 6.1% point in average on the datasets, respectively. The permutation-based XAI method is first applied for the reliable explanation of the 3D-EEGNet. Next, to find a faster XAI method for spatio-temporal explanation, we design a novel technique based on the normalized discounted cumulative gain (NDCG) for selecting the best among a few saliency-based methods due to their higher time complexity than the permutation-based method. Among the saliency-based methods, DeepLIFT was selected because the NDCG scores indicated its results are the most similar to the permutation-based results. Finally, the fast spatio-temporal explanation using DeepLIFT provides deeper understanding for the classification results of the 3D-EEGNet and the important properties in the MI EEG experiments.
Field intercomparison of continuous ambient FRM and FEM NO2 instruments in the Athabasca Oil Sands Region, Alberta, Canada and the potential impact on ambient regulatory compliance

ABSTRACT The Canadian Federal Government promulgated new and lower NO2 Ambient Air Quality Standards (CAAQS) that went into effect in 2020 with additional decreases scheduled for 2025. The new hourly and annual NO2 CAAQS are 60 and 17 ppb, respectively, and the 2025 hourly and annual CAAQS are 42 and 12 ppb, respectively. The province of Alberta has also promulgated Ambient Air Quality Objectives (AAAQO) for NO2 currently set to 159 and 24 ppb on an hourly and annual basis, respectively. The Wood Buffalo Environmental Association (WBEA) in northeastern Alberta, Canada monitors NO2 at 21 community and industrial sites throughout the Athabasca Oil Sands Region (AOSR), for regulatory compliance using Thermo-Environmental (TEI) Model 42i Federal Reference Method (FRM) designated NO-NO2-NOx analyzers. The 42i measures NO directly via NO-O3 chemiluminescence, and NOx following the reduction of oxidized nitrogen to NO by a heated internal molybdenum converter. The difference between the NOx and NO channels is reported as NO2. This study presents the results of a three-year (2018–2021) WBEA comparison of four continuous NO2 analyzers: TEI 42i FRM; the API Model T500U cavity attenuated phase shift (CAPS) Federal Equivalent Method (FEM); a total reactive odd nitrogen analyzer (TEI Model 42i-Y); and a TEI 42i equipped with an external photolytic converter. The study showed that NO2 data from all analyzers were highly correlated and in general agreement, with r2 values (vs. the CAPS) ranging from 0.990–0.997 and slopes ranging from 0.933–0.992. Mean NO2 concentrations over the study period ranged from 7.2–7.5 ppb. Differences between the TEI 42i, TEI 42i-Y, and PhoNO, relative to the CAPS were all positive and highly significant (p < 0.0001), based upon nonparametric tests. The potential impact from the selection of different FRM/FEM measurement methods on current and future Canadian 2025 regulatory compliance in the region is evaluated. Implications: The study objective was to compare/evaluate different regulatory NO2 measurement techniques from a regional monitoring authority in a routine network operational context. Relatively small NO2 differences resulted in significant differences with respect to regulatory compliance triggers, particularly hourly standards based on daily extreme value statistics (e.g., 99th percentiles). For example, mean hourly NO2 △ differences ranged from 0.02–0.26 ppb over the study period but resulted in 2–3 ppb differences in the 3-year hourly CAAQS metrics. These differences could affect regulatory CAAQS and LARP compliance (management level) at monitoring sites observed during 2019 annual and 2020 hourly LARP trigger exceedances.
Obstructive Sleep Apnea and its Association with Stroke: A Brief Review

Obstructive sleep apnea (OSA) has been associated with many of the known risk factors for stroke including hypertension, diabetes and atrial fibrillation. There is also a large body of literature that suggests that OSA and stroke are independently associated. In this review, we will discuss the literature supporting OSA not only a risk factor for stroke, but also show how untreated OSA has been associated with worse outcomes in those who suffer from stroke and OSA.
Factors associated with high exclusive breastfeeding rates among preterm infants under 34 weeks of gestation in Da Nang, Vietnam: A retrospective cohort study

Background Preterm infants have higher mortality than full-term infants. While breastfeeding dramatically reduces preterm death, it is limited by biological and practice barriers, particularly for babies born before 34 weeks gestational age. Da Nang Hospital for Women and Children developed a quality improvement approach to improve breastfeeding of preterm infants by strengthening feeding support, non-separation, and kangaroo mother care (KMC). Methods To determine breastfeeding outcomes following discharge and explore factors associated with improved feeding, mothers of infants under 34 weeks gestational age born October 2021 to March 2022 and discharged alive were interviewed at six months and their medical records were reviewed. Results Out of 104 preterm infants included, all were exclusively breastfed at discharge and one month, 86.5% at three months, and 63.5% at six months; 47.1% received immediate skin-to-skin contact, 31.7% immediate and continuous KMC, and the remaining 68.3% continuous KMC beginning at a median of three days. Exclusive breastfeeding at six months was associated with the mother antenatally seeking breastfeeding information (odds ratio (OR) = 14.5; 95% confidence interval (CI) = 1.2-173.6), avoiding bottle-feeding at home (OR = 7.7; 95% CI = 1.7-33.7) and reduced with each day delay between birth and full breastfeeding (OR = 0.8; 95% CI = 0.6-0.9). Conclusions Hospital environments that limit mother-baby separations and feeding delays, including rooming-in of mothers and infants, KMC, and breastfeeding support from birth, enabled 100% of preterm infants born before 34 weeks gestational age to breastfeed exclusively with continued rates higher than previously reported. Addressing antenatal and post-natal factors limiting practice can further improve longer-term breastfeeding outcomes. The approach can be adapted to achieve high exclusive breastfeeding rates, regardless of gestational age.
PP2A inhibition causes synthetic lethality in BRCA2-mutated prostate cancer models via spindle assembly checkpoint reactivation

Mutations in the BRCA2 tumor suppressor gene have been associated with an increased risk of developing prostate cancer. One of the paradoxes concerning BRCA2 is the fact that its inactivation affects genetic stability and is deleterious for cellular and organismal survival, while BRCA2-mutated cancer cells adapt to this detriment and malignantly proliferate. Therapeutic strategies for tumors arising from BRCA2 mutations may be discovered by understanding these adaptive mechanisms. In this study, we conducted forward genetic synthetic viability screenings in Caenorhabditis elegans brc-2 (Cebrc-2) mutants and found that Ceubxn-2 inactivation rescued the viability of Cebrc-2 mutants. Moreover, loss of NSFL1C, the mammalian ortholog of CeUBXN-2, suppressed the spindle assembly checkpoint (SAC) activation and promoted the survival of BRCA2-deficient cells. Mechanistically, NSFL1C recruited USP9X to inhibit the polyubiquitination of AURKB and reduce the removal of AURKB from the centromeres by VCP, which is essential for SAC activation. SAC inactivation is common in BRCA2-deficient prostate cancer patients, but PP2A inhibitors could reactivate the SAC and achieve BRCA2-deficient prostate tumor synthetic lethality. Our research reveals the survival adaptation mechanism of BRCA2-deficient prostate tumor cells and provides different angles for exploring synthetic lethal inhibitors in addition to targeting DNA damage repair pathways.
DTaP-IPV-HB-Hib vaccine (Hexaxim): an update 10 years after first licensure

ABSTRACT Introduction Hexaxim® is fully liquid, hexavalent, combination vaccine that provides immunization against diphtheria, tetanus, pertussis (whooping cough), polio, hepatitis B, and invasive diseases caused by Haemophilus influenzae type b. Combination vaccines such as Hexaxim reduce the number of injections needed, improving both vaccination compliance and operational efficiency. Areas covered Safety and immunogenicity data were reviewed from >25 clinical trials involving approximately 7200 infants/toddlers, identified using PubMed searches to April 2023. These trials have evaluated a diverse range of primary series and booster schedules, including antibody persistence, co-administration of Hexaxim with other routine pediatric vaccines, and specific populations (born to Tdap-vaccinated women, preterm, and immunocompromised infants). Lastly, post-marketing surveillance and real-world effectiveness data were assessed. Expert opinion An extensive program of clinical development prior to licensure demonstrated favorable vaccine safety and good immunogenicity of each antigen, and Hexaxim was first approved for use in 2012. In the 10 years since licensure, Hexaxim has been adopted widely, with more than 180 million doses distributed worldwide. The widespread use of this hexavalent vaccine is a crucial tool in the ongoing and future control of six pediatric infectious diseases globally.
Association Between Pretreatment Chest Imaging and Immune Checkpoint Inhibitor Pneumonitis Among Patients With Lung Cancer.

BACKGROUND Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI treatment in 2% to 5% of patients; however, risk factors for developing ICI pneumonitis (ICI-p) remain undefined. METHODS We conducted a retrospective cohort study of consecutive patients with lung cancer who received at least one dose of ICI from 2015 through 2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and a pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort. Univariate and multivariable survival analyses using the Fine-Gray competing risk model were used to examine the associations. RESULTS A total of 471 patients with lung cancer were included, of which 402 had non-small cell lung cancer and 69 had small cell lung cancer; 39 (8%) patients in the overall cohort developed ICI-p. Preexisting interstitial abnormalities and prior chest radiation were both significantly associated with ICI-p on univariate analysis (hazard ratio [HR], 8.91; 95% CI, 4.69-16.92; P<.001; and HR, 2.81; 95% CI, 1.50-5.28; P=.001). On multivariable analyses, interstitial abnormalities remained a strong independent risk factor for ICI-p when controlling for chest radiation and type of immunotherapy (HR, 9.77; 95% CI, 5.17-18.46; P<.001). Among patients with ICI-p (n=39), those with severe (grade 3-5) pneumonitis had worse overall survival compared with those with mild (grade 1 or 2) pneumonitis (P=.001). Abnormal pulmonary function test results at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI-p. CONCLUSIONS Preexisting interstitial abnormalities on chest CT and prior chest radiation are independent risk factors that are strongly associated with ICI-p in patients with lung cancer. These findings highlight a potential need for closer observation for ICI-p among patients with these risk factors.
Left atrial mechanics evaluated by two-dimensional strain analysis: alterations in essential hypertension

Background: Hypertension is a cardiovascular risk factor that predisposes to cardiac structural alterations namely increased left ventricular (LV) wall thickness, reduced LV compliance and diastolic dysfunction, with consequent left atrial (LA) dilation and functional impairment. In this article, we evaluated differences in left atrial structure and function using two-dimensional speckle tracking echocardiography in patients with hypertension compared with controls. Methods: This was a retrospective cross-sectional study of 208 hypertensive patients and 157 controls who underwent a comprehensive transthoracic echocardiogram. Patients with hypertension were stratified by the presence of left ventricular hypertrophy (LVH). Results: Non-LVH hypertension patients had lower left atrial reservoir strain (LASRES) (34.78 ± 29.78 vs. 29.78 ± 6.08; P = 0.022) and conduit strain (LASCD) (19.66 ± 7.29 vs. 14.23 ± 4.59; P = 0.014) vs. controls despite similar left atrial volumes (LAV). Left atrial contractile strain (LASCT) was not significantly different between non-LVH hypertension patients and controls (15.12 ± 3.77 vs. 15.56 ± 3.79; P = 0.601). Left atrial mechanical dispersion was significantly higher in the LVH group compared with the non-LVH hypertension group (42.26 ± 13.01 vs. 50.06 ± 14.95; P = 0.009). In multivariate regression analysis, LVH correlated with left atrial mechanical dispersion (P = 0.016). An age–hypertension interaction independently correlated with LASCT (P < 0.001). Conclusion: Hypertension results in functional left atrial changes even before development of LV hypertrophy and structural left atrial changes with increased left atrial volume. We demonstrate both a likely hypertension-associated left atrial myopathy that prevents age-related compensatory increase in left atrial contractile function, and impact of LVH in hypertension on left atrial dyssynchrony.
A narrow T cell receptor repertoire instructs thymic differentiation of MHC class Ib–restricted CD8+ regulatory T cells

Although most CD8+ T cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here, we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Tregs) by a surprisingly restricted set of T cell receptors (TCRs) that recognize MHC-E (mouse Qa-1) and several dominant self-peptides. Recognition and elimination of pathogenic target cells that express these Qa-1–self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression. Immunization with synthetic agonist peptides that mobilize CD8 Tregs in vivo efficiently inhibit antigraft antibody responses and markedly prolong heart and kidney organ graft survival. Definition of TCR-dependent differentiation and target recognition by this lineage of CD8 Tregs may open the way to new therapeutic approaches to inhibit pathogenic antibody responses.