Miracle-dz/UniFAR-FTUs huggingface dataset:
Group 2 innate lymphoid cells contribute to IL-33-mediated alleviation of cardiac fibrosis

Rationale: The major cause of heart failure is myocardium death consequent to detrimental cardiac remodeling and fibrosis following myocardial infarction. The cardiac protective cytokine interleukin (IL)-33, which signals by ST2 receptor binding, is associated with group 2 innate lymphoid cell (ILC2) activation and regulates tissue homeostasis and repair following tissue injury in various tissues. However, the distribution and role of IL-33-responsive ILC2s in cardiac fibrosis remain unclear. In this study, we elucidated the roles of IL-33-responsive cardiac-resident ILC2s and IL-33-mediated immunomodulatory functions in cardiac fibrosis. Methods: We examined the distribution of cardiac ILC2s by using flow cytometry. The roles of IL-33-mediated ILC2 expansion in cardiac fibrosis was evaluated in the mouse model of catecholamine-induced cardiac fibrosis. ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice were implemented to determine the contribution of endogenous ILC in the progression of cardiac fibrosis. Histopathological assessments, speckle tracking echocardiography, and transcriptome profile analysis were performed to determine the effects of IL-33-mediated cardiac protective functions. Results: We identified the resident cardiac ILC2s, which share similar cell surface marker and transcriptional factor expression characteristics as peripheral blood and lung tissue ILC2s. IL-33 treatment induced ILC2 expansion via ST2. In vivo, ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice developed exacerbated cardiac fibrosis following catecholamine-induced stress cardiac injury. IL-33 treatment expanded cardiac ILC2s and revealed protective effects against cardiac tissue damage with reduced cardiomyocyte death, immune cell infiltration, tissue fibrosis, and improved myocardial function. Transcriptome analysis revealed that IL-33 attenuated extracellular matrix synthesis- and fibroblast activation-associated gene expressions. IL13-knockout or epidermal growth factor receptor (EGFR) inhibition abolished IL-33-mediated cardiac protective function, confirming IL-13 and EGFR signaling as crucial for IL-33-mediated cardioprotective responses. Moreover, ILC2-produced BMP-7 served as a novel anti-fibrotic factor to inhibit TGF-β1-induced cardiac fibroblast activation. Conclusion: Our findings indicate the presence of IL-33-responsive ILC2s in cardiac tissue and that IL-33-mediated ILC2 expansion affords optimal cardioprotective function via ILC2-derived factors. IL-33-mediated immunomodulation is thus a promising strategy to promote tissue repair and alleviate cardiac fibrosis following acute cardiac injury.
The Rise of Minimally Invasive Surgery: 16 Year Analysis of the Progressive Replacement of Open Surgery with Laparoscopy

Objective: The expansion of Minimally Invasive Surgery (MIS) has been exponential since the introduction of laparoscopic surgery in the late 1980s. This shift in operative technique has led many to believe that surgery residents are not developing the skills needed to adequately perform open operations. Methods: We performed a retrospective review of the Accreditation Council for Graduating Medical Education national operative case log database of general surgery residents from January 2003 to December 2019. We compared the open vs. laparoscopic case numbers for six different operations, including cholecystectomy, appendectomy, inguinal hernia repair, colectomy, gastrectomy, and Nissen fundoplication. The Cochran-Armitage test was used to assess the linear trend in the procedures performed. Results: Total average residency case volumes for the procedures studied have increased from 270 to 368 (36%) over the 16-year period with MIS steadily representing a greater proportion of these cases. From 2003 to 2018, MIS representation increased in all studied procedures: cholecystectomy (88% to 94%, p = 0.048), inguinal hernia repair (20% to 47%, p ≤ 0.001), appendectomy (38% to 93%, p ≤ 0.001), colectomy (8% to 43%, p ≤ 0.001), gastrectomy (43% to 84%, p = 0.048), and Nissen (71% to 91%, p = 0.21). Conclusion: While the overall operative volume has increased nationally for surgical residents, the representation of open cases has steadily declined since the advent of MIS. The experience needed in open surgery during resident training is still to be determined and may be necessary now that laparoscopy is progressively replacing open operations.
Mitophagy Modulation, a New Player in the Race against ALS

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that usually results in respiratory paralysis in an interval of 2 to 4 years. ALS shows a multifactorial pathogenesis with an unknown etiology, and currently lacks an effective treatment. The vast majority of patients exhibit protein aggregation and a dysfunctional mitochondrial accumulation in their motoneurons. As a result, autophagy and mitophagy modulators may be interesting drug candidates that mitigate key pathological hallmarks of the disease. This work reviews the most relevant evidence that correlate mitophagy defects and ALS, and discusses the possibility of considering mitophagy as an interesting target in the search for an effective treatment for ALS.
A laboratory evaluation of a novel hot water cabinet for the decontamination of sides of beef.

Summary A hot water cabinet based on an idealized distributor design for the decontamination of sides of beef is described and a laboratory evaluation of this novel cabinet is reported. Beef sides were inoculated with E. coli and exposed to mean water temperatures at the surface tissue (Tf) of 83.5, 74.2, 66.0 and 44.5°C for 10 or 20 s. Mean log10 reductions of bacteria for 10-s exposures were 2.23, 1.40, 0.91 and 0.2. For 20 s, reductions were 2.98, 2.14, 1.17 and 0.1. There was a significant (P < 0.05) linear relationship between log reductions and Tf which varied with exposure time. At a Tf of 83.5°C with exposure times greater than 20 s, carcass bloom was judged to be permanently and adversely affected. At shorter times or with lower temperatures this did not occur. Evaporative heat losses were well correlated with the pressure driving force (r= 0.89) and gravity driving force (r= 0.92) for air interchange between the cabinet and its surrounds. The running cost using the distributor cabinet was one-third of that of an existing spray cabinet when compared at the maximum reduction of log 1.3 (95%) achieved by the spray cabinet. An additional advantage of the distributor cabinet is its constructional simplicity.
Assessing the Relationship between Verbal and Nonverbal Cognitive Abilities Using Resting-State EEG Functional Connectivity

The present study investigates the relationship between individual differences in verbal and non-verbal cognitive abilities and resting-state EEG network characteristics. We used a network neuroscience approach to analyze both large-scale topological characteristics of the whole brain as well as local brain network characteristics. The characteristic path length, modularity, and cluster coefficient for different EEG frequency bands (alpha, high and low; beta1 and beta2, and theta) were calculated to estimate large-scale topological integration and segregation properties of the brain networks. Betweenness centrality, nodal clustering coefficient, and local connectivity strength were calculated as local network characteristics. We showed that global network integration measures in the alpha band were positively correlated with non-verbal intelligence, especially with the more difficult part of the test (Raven’s total scores and E series), and the ability to operate with verbal information (the “Conclusions” verbal subtest). At the same time, individual differences in non-verbal intelligence (Raven’s total score and C series), and vocabulary subtest of the verbal intelligence tests, were negatively correlated with the network segregation measures. Our results show that resting-state EEG functional connectivity can reveal the functional architecture associated with an individual difference in cognitive performance.
Analgesic Efficacy of Nefopam as an Adjuvant in Patient-Controlled Analgesia for Acute Postoperative Pain After Laparoscopic Colorectal Cancer Surgery

Despite rapid advancements in laparoscopic surgical techniques and perioperative management, postoperative pain remains a significant clinical issue. We examined the analgesic efficacy of nefopam as an adjuvant in patient-controlled analgesia (PCA) for acute postoperative pain in patients undergoing laparoscopic colorectal cancer surgery. We retrospectively analyzed the medical records of 120 patients who did or did not receive 80 mg of nefopam as an adjuvant in fentanyl PCA; they were allocated to the nefopam (n = 60) or non-nefopam group (n = 60). The demographic, clinical, and anesthetic data, with data on pain severity and opioid administration at the postoperative anesthesia care unit (PACU) on postoperative days (PODs) 1, 3, and 5, were compared between the groups. The pain score and opioid administration did not differ at the PACU or on PODs 1, 3, or 5. The day of PCA discontinuation, time to pass flatus, length of the hospital stay, and incidence of nausea/vomiting, dizziness, and headache also did not differ between the groups. Fentanyl PCA with 80 mg of nefopam as an adjuvant did not have a superior analgesic effect after laparoscopic colorectal cancer surgery.
Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis

Acute kidney injury is a common clinical problem with no definitive or specific treatment. Therefore, the molecular mechanisms of acute kidney injury must be fully understood to develop novel treatments. Nuciferine, a major bioactive compound isolated from the lotus leaf, possesses extensive pharmacological activities. Its effect on folic acid‐induced acute kidney injury, however, remains unknown. Here, we aimed to clarify the pharmacological effects of nuciferine and its mechanisms of action in acute kidney injury.
Specificity of Molecular Fragments Binding to S100B versus S100A1 as Identified by NMR and Site Identification by Ligand Competitive Saturation (SILCS)

S100B, a biomarker of malignant melanoma, interacts with the p53 protein and diminishes its tumor suppressor function, which makes this S100 family member a promising therapeutic target for treating malignant melanoma. However, it is a challenge to design inhibitors that are specific for S100B in melanoma versus other S100-family members that are important for normal cellular activities. For example, S100A1 is most similar in sequence and structure to S100B, and this S100 protein is important for normal skeletal and cardiac muscle function. Therefore, a combination of NMR and computer aided drug design (CADD) was used to initiate the design of specific S100B inhibitors. Fragment-based screening by NMR, also termed “SAR by NMR,” is a well-established method, and was used to examine spectral perturbations in 2D [1H, 15N]-HSQC spectra of Ca2+-bound S100B and Ca2+-bound S100A1, side-by-side, and under identical conditions for comparison. Of the 1000 compounds screened, two were found to be specific for binding Ca2+-bound S100A1 and four were found to be specific for Ca2+-bound S100B, respectively. The NMR spectral perturbations observed in these six data sets were then used to model how each of these small molecule fragments showed specificity for one S100 versus the other using a CADD approach termed Site Identification by Ligand Competitive Saturation (SILCS). In summary, the combination of NMR and computational approaches provided insight into how S100A1 versus S100B bind small molecules specifically, which will enable improved drug design efforts to inhibit elevated S100B in melanoma. Such a fragment-based approach can be used generally to initiate the design of specific inhibitors for other highly homologous drug targets.
Constraint Closure Drove Major Transitions in the Origins of Life

Life is an epiphenomenon for which origins are of tremendous interest to explain. We provide a framework for doing so based on the thermodynamic concept of work cycles. These cycles can create their own closure events, and thereby provide a mechanism for engendering novelty. We note that three significant such events led to life as we know it on Earth: (1) the advent of collective autocatalytic sets (CASs) of small molecules; (2) the advent of CASs of reproducing informational polymers; and (3) the advent of CASs of polymerase replicases. Each step could occur only when the boundary conditions of the system fostered constraints that fundamentally changed the phase space. With the realization that these successive events are required for innovative forms of life, we may now be able to focus more clearly on the question of life’s abundance in the universe.
Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis

The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage therapy against bacteria has been around for more than a century and, although its implementation was abandoned after the introduction of drugs, it is now making a comeback and gaining renewed interest in Western medicine as an alternative to treat drug-resistant pathogens. Mycobacteriophages are genetically diverse viruses that specifically infect mycobacterial hosts, including members of the M. tuberculosis complex. This review describes general features of mycobacteriophages and their mechanisms of killing M. tuberculosis, as well as their advantages and limitations as therapeutic and prophylactic agents against drug-resistant M. tuberculosis strains. This review also discusses the role of human lung micro-environments in shaping the availability of mycobacteriophage receptors on the M. tuberculosis cell envelope surface, the risk of potential development of bacterial resistance to mycobacteriophages, and the interactions with the mammalian host immune system. Finally, it summarizes the knowledge gaps and defines key questions to be addressed regarding the clinical application of phage therapy for the treatment of drug-resistant tuberculosis.
Correlation between Volatile Aroma Compounds and Sensory Attributes of Minimally Processed Herbs

Consumers choose herbs by their characteristic flavour although they perceive only a fraction of their volatiles aroma compounds. Few studies have focused on comparing aroma determined in sensory analysis and volatiles identified in instrumental analysis. This study aims to assess consumersâ€™ preference by identifying the correlation between the two parameters. Pearson coefficient was applied on the aroma scores and the content of volatile aroma compounds previously determined for parsley ( Petroselinum crispum ), dill ( Anethum graveolens ), and lovage ( Levisticum officinale ). We found that assessors preferred parsley rich in I²-phellandrene but low in 1.3. 8-p-menthatriene and d-limonene. They liked I²-phellandrene in dill but disliked I±-phellandrene. Consumers favoured I±-phellandrene in lovage alongside I±-terpinolene, and d-limonene but disfavoured I²-myrcene. Â Our findings confirmed a significant correlations between sensory aroma and the content of volatile aroma compounds.
Prevalence and factors associated with multimorbidity among primary care patients with decreased renal function

Objectives To establish the prevalence of multimorbidity in people with chronic kidney disease (CKD) stages 1–5 and transiently impaired renal function and identify factors associated with multimorbidity. Design and setting Prospective cohort study in UK primary care. Participants 861 participants aged 60 and older with decreased renal function of whom, 584 (65.8%) had CKD and 277 (32.2%) did not have CKD. Interventions Participants underwent medical history and clinical assessment, and blood and urine sampling. Primary and secondary outcome measures Multimorbidity was defined as presence of ≥2 chronic conditions including CKD. Prevalence of each condition, co-existing conditions and multimorbidity were described and logistic regression was used to identify predictors of multimorbidity. Results The mean (±SD) age of participants was 74±7 years, 54% were women and 98% were white. After CKD, the next most prevalent condition was hypertension (n = 511, 59.3%), followed by obesity (n = 265, 30.8%) ischemic heart disease (n = 145, 16.8%) and diabetes (n = 133, 15.4%). Having two co-existing conditions was most common (27%), the most common combination of which was hypertension and obesity (29%). One or three conditions was the next most prevalent combination (20% and 21% respectively). The prevalence of multimorbidity was 73.9% (95%CI 70.9–76.8) in all participants and 86.6% (95%CI 83.9–89.3) in those with any-stage CKD. Logistic regression found a significant association between increasing age (OR 1.07, 95%CI 1.04–0.10), increasing BMI (OR 1.15, 95%CI 1.10–1.20) and decreasing eGFR (OR 0.99, 95%CI 0.98–1.00) with multimorbidity. Conclusions This analysis is the first to provide an accurate estimate of the prevalence of multimorbidity in a screened older primary care population living with or at risk of CKD across all stages. Hypertension and obesity were the most common combination of conditions other than CKD that people were living with, suggesting that there may be multiple reasons for closely monitoring health status in individuals with CKD.
Dynamics of polymer solutions and melts. Reptation predictions and scaling of relaxation times

The bond fluctuation model on the simple cubic lattice is studied by Monte Carlo simulations on a multitransputer array, for polymer volume fractions φ in the range 0.025≤φ≤0.500 and chain lengths N in the range 20≤N≤200. Extensive data are presented on the dynamics of monomer displacements, center‐of‐gravity displacements, and relaxation times. This study is complementary to previous work, in which the crossover scaling properties of the chain linear dimensions, structure factor, and self‐diffusion constant were tested for the same athermal model. The simulation technique takes both excluded volume interactions and entanglement constraints into account, but ignores hydrodynamic forces. Our results describe the crossover from Rouse behavior of swollen chains (τ∼N1+2ν, ν being the exponent describing the radius R of the chains, R∼Nν ) to reptation, τ∼N3. Since the excluded volume screening length is found to be smaller than the tube diameter by a factor of about 3, the rescaled times Wτ/N1+2ν decrease firs.
Phenotype and Natural History of Children With Coexistent Inflammatory Bowel Disease and Celiac Disease.

BACKGROUND Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. METHODS This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. RESULTS Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97-8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn's disease and CeD than in patients with Crohn's disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13-33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). CONCLUSIONS Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.
A review of nicotine-containing electronic cigarettes - trends in use, effects, contents, labelling accuracy and detection methods.

Electronic cigarettes (ECs) are thought to be less harmful than traditional combustible cigarettes and were originally intended to help smokers quit. Over the past two decades, they have especially gained popularity with the younger generation. To date, there are over 7000 unique e-liquid flavours available and over 400 different e-cigarette brands. The accuracy of nicotine strength labelling in e-liquids was assessed in this work. Twenty-three studies from around the world were chosen to assess the level and frequency of nicotine mislabelling in 545 e-liquid products. Nicotine strengths were most commonly mislabelled by between 5 and 20%, with the majority testing lower than what the label indicated. Fifteen European e-liquids that were assessed were labelled as 20 mg/ml or less, yet when tested they contained more than 20 mg/ml of nicotine. One e-liquid that was supposed to contain no nicotine in fact contained 23.91 mg/ml of nicotine. Furthermore, the difference between the medians of the available labelled and experimental nicotine concentrations was significant (p < 0.001, Wilcoxon Signed Ranks test). Preliminary studies show that high nicotine levels delivered via aerosol increase the risk for nicotine poisoning and cause airway inflammation. Other EC ingredients, such as flavourings, contribute to EVALI and "popcorn lung". There is evidence that certain flavourings, such as menthol, reinforce the effects of nicotine and modify drug absorption and metabolism. There is a global need for better quality control in EC products in order to make these safe for consumers.
Effect of lipophilicity on drug distribution and elimination: Influence of obesity

For a given passively‐distributed lipophilic drug, the extent of in vivo distribution (pharmacokinetic volume of distribution, Vd) in obese individuals increases in relation to the degree of obesity. The present study had the objective of evaluating drug distribution in relation to in vitro lipophilicity, and the relative increase in Vd associated with obesity across a series of drugs.
Exploring the Nexus of Energy Burden, Social Capital, and Environmental Quality in Shaping Health in US Counties

The United States spends more on health care than any other OECD country, yet the nation’s health is declining. Recent research has identified multiple sources for this decline, including one’s position in social and economic structures, environmental quality, and individual and collective social capital. This paper assesses the primary hypotheses that the health effects of household energy burden, social capital and environmental quality on aggregated community health levels remain while controlling for other determinants. The analysis moves beyond prior research by integrating multiple secondary data sources to assess those effects across US counties. Three indicators of public health are analyzed (premature mortality, self-reported health, and life expectancy). The county-level energy burden is measured by the percent of household income spent on housing energy bills for low- and moderate-income households. In addition to energy burden, social capital, environmental quality and other determinants are included in the analysis. The results produced by multivariate regression models support the primary hypotheses, even while a number of control variables also have a significant effect on health. The paper concludes that public health is associated with a complex nexus of factors, including environmental quality and social capital, and that energy burden needs to be among the considerations.