Miracle-dz/UniFAR-FTUs huggingface dataset:
Linking statistical shape models and simulated function in the healthy adult human heart

Cardiac anatomy plays a crucial role in determining cardiac function. However, there is a poor understanding of how specific and localised anatomical changes affect different cardiac functional outputs. In this work, we test the hypothesis that in a statistical shape model (SSM), the modes that are most relevant for describing anatomy are also most important for determining the output of cardiac electromechanics simulations. We made patient-specific four-chamber heart meshes (n = 20) from cardiac CT images in asymptomatic subjects and created a SSM from 19 cases. Nine modes captured 90% of the anatomical variation in the SSM. Functional simulation outputs correlated best with modes 2, 3 and 9 on average (R = 0.49 ± 0.17, 0.37 ± 0.23 and 0.34 ± 0.17 respectively). We performed a global sensitivity analysis to identify the different modes responsible for different simulated electrical and mechanical measures of cardiac function. Modes 2 and 9 were the most important for determining simulated left ventricular mechanics and pressure-derived phenotypes. Mode 2 explained 28.56 ± 16.48% and 25.5 ± 20.85, and mode 9 explained 12.1 ± 8.74% and 13.54 ± 16.91% of the variances of mechanics and pressure-derived phenotypes, respectively. Electrophysiological biomarkers were explained by the interaction of 3 ± 1 modes. In the healthy adult human heart, shape modes that explain large portions of anatomical variance do not explain equivalent levels of electromechanical functional variation. As a result, in cardiac models, representing patient anatomy using a limited number of modes of anatomical variation can cause a loss in accuracy of simulated electromechanical function.
The effect of fatiguing lower-body exercise on punch forces in highly-trained boxers

ABSTRACT This study aimed to examine the effect of intense intermittent lower-body and trunk exercise (rowing) on punching performance in 28 highly-trained male amateur boxers. Straight- and bent-arm punch performances were assessed with a custom-built punch integrator using a 3-min maximal-effort punch test, completed in both non-fatigued (ROWpre) and fatigued (ROWpost) states. A within-subject repeated measures design was implemented; subjects completed ROWpre, then 9 × 1-min bouts of rowing (1-min rest intervals), followed by ROWpost. Peak punch force and force-time variables, including impulse and rate of force development (RFD; calculated to five time points), were assessed. Differences between ROWpre and ROWpost for each punch type (jab, cross, lead- and rear-hand hook) were tested with a linear mixed model, and effect sizes (Cohen’s d) were calculated. Results showed significant (p < 0.05) reductions in punch force in ROWpost compared to ROWpre for all punch types as well as significant delays in the time to reach specific force levels, and relative percentages of peak force (RFD) in all punches except the jab. It is likely that fatigue of the lower body and trunk muscles impaired ground reaction force, and thus punch force, production. This effect was larger in punches that involved a greater degree of trunk rotation, crosses and hooks, than in the jab which relies predominantly on arm extension. These findings reveal the negative effect of fatigue on punch force production, and provide evidence that lower-body and trunk force are important for generating punch force. Highlights The ability of the lower body to generate force affects the magnitude of punch force produced in trained boxers. A bout of intense rowing exercise significantly reduces punch force, and rate of force development. This should be carefully considered when programming and scheduling boxing specific training sessions and strength and conditioning sessions. While non-specific fatigue affected the punch performance of boxers, the authors call for further research to examine the effects of fatigue sustained during a boxing bout in comparison to non-boxing muscular fatigue and a non-exercise control.
Identifying geographically differentiated features of Ethopian Nile tilapia (Oreochromis niloticus) morphology with machine learning

Visual characteristics are among the most important features for characterizing the phenotype of biological organisms. Color and geometric properties define population phenotype and allow assessing diversity and adaptation to environmental conditions. To analyze geometric properties classical morphometrics relies on biologically relevant landmarks which are manually assigned to digital images. Assigning landmarks is tedious and error prone. Predefined landmarks may in addition miss out on information which is not obvious to the human eye. The machine learning (ML) community has recently proposed new data analysis methods which by uncovering subtle features in images obtain excellent predictive accuracy. Scientific credibility demands however that results are interpretable and hence to mitigate the black-box nature of ML methods. To overcome the black-box nature of ML we apply complementary methods and investigate internal representations with saliency maps to reliably identify location specific characteristics in images of Nile tilapia populations. Analyzing fish images which were sampled from six Ethiopian lakes reveals that deep learning improves on a conventional morphometric analysis in predictive performance. A critical assessment of established saliency maps with a novel significance test reveals however that the improvement is aided by artifacts which have no biological interpretation. More interpretable results are obtained by a Bayesian approach which allows us to identify genuine Nile tilapia body features which differ in dependence of the animals habitat. We find that automatically inferred Nile tilapia body features corroborate and expand the results of a landmark based analysis that the anterior dorsum, the fish belly, the posterior dorsal region and the caudal fin show signs of adaptation to the fish habitat. We may thus conclude that Nile tilapia show habitat specific morphotypes and that a ML analysis allows inferring novel biological knowledge in a reproducible manner.
Maternal diet high in linoleic acid alters offspring fatty acids and cardiovascular function in a rat model

Abstract Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and its relationship to circulating FA and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1·44 % energy from LA) or high LA (HLA; 6·21 % energy from LA) diets for 10 weeks before pregnancy and during gestation/lactation. Offspring, weaned at postnatal day 25, were fed LLA or HLA diets and euthanised at postnatal day 40 (n 6–8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. α-Linolenic acid (ALA) and EPA were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic pressure–volume relationship (PVR), and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after occlusion. Thus, maternal HLA diets impact lipids, FA and cardiac function in offspring, with postnatal diet modifying FA and cardiac function in the female offspring.
Effect of formulation and heat treatment on 5-hydroxymethylfurfural formation and quality parameters in dulce de leche

ABSTRACT This work assessed the effect of formulation and heat treatment on the formation of HMF, non-enzymatic browning and rheology of dulce de leche (DL). Laboratory scale trials were developed with different DL formulas: whole powdered milk, skimmed milk, and lactose-free skimmed milk, and added sucrose, subjected to different processing temperatures (110°C, 120°C, and 130°C). Additionally, an alternative formulation was designed in which half the sucrose was replaced by 50% tagatose. DL samples were compared with three commercial products in terms of water activity, soluble solids content, pH, colour, apparent viscosity, and HMF concentration. HMF formation in DL was mitigated (35%) in a lactose-free formulation by lowering the process temperature. Moreover, HMF formation was reduced up to 80% replacing sucrose by tagatose without affecting the quality parameters (pH, soluble solids, colour, and apparent viscosity). Decrease in processing temperature and the use of tagatose are viable alternatives for HMF mitigation in DL.
Fluoxetine affects cytosolic cAMP, ATP, Ca2+ responses to forskolin, and survival of human ovarian granulosa tumor COV434 cells

Fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, exhibits various other mechanisms of action in numerous cell types and has been shown to induce cell death in cancer cells, paving the way for its potential use in cancer therapy. The aim of this study was to determine the off-target effects of the anti-depressant drug FLX, on the human ovarian granulosa tumor COV434 cells stimulated by forskolin (FSK), by measuring the real-time kinetics of intracellular cyclic AMP (cAMP), ATP level, cytoplasmic calcium ([Ca2+]cyt) and survival of COV434 cells. We show that incubating COV434 cells with FLX (between 0.6 and 10 µM) induces a decrease in intracellular cAMP response to FSK, a drop in ATP content and stimulates cytoplasmic Ca2+ accumulation in COV434 cells. Only the highest concentrations of FLX (5–10 µM) diminished cell viability. The present report is the first to identify an action mechanism of FLX in human tumor ovarian cells COV434 cells and thus opening the way to potential use of fluoxetine as a complementary tool, in granulosa tumor treatments.
Different therapeutic associations of renin-angiotensin system inhibitors with coronavirus disease 2019 compared with usual pneumonia

Background/Aims Although it is near concluded that renin-angiotensin system inhibitors do not have a harmful effect on coronavirus disease 2019 (COVID-19), there is no report about whether angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) offer any protective role. This study aimed to compare the association of ARBs and ACEIs with COVID-19-related mortality. Methods All patients with COVID-19 in Korea between January 19 and April 16, 2020 were enrolled. The association of ARBs and ACEIs with mortality within 60 days were evaluated. A comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of pneumonia patients hospitalized in 2019 in Korea. Results Among 10,448 COVID-19 patients, ARBs and ACEIs were prescribed in 1,231 (11.7%) and 57 (0.6%) patients, respectively. After adjusting for age, sex, and history of comorbidities, the ARB group showed neutral association (HR, 1.034; 95% CI, 0.765 to 1.399; p = 0.8270) and the ACEI groups showed no significant associations likely owing to the small population size (HR, 0.736; 95% CI, 0.314 to 1.726; p = 0.4810). When comparing HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia in 2019, the trend of ACEIs showed similar benefits, whereas the protective effect of ARBs observed in the retrospective cohort was absent in COVID-19 patients. Meta-analyses showed significant positive correlation with survival of ACEIs, whereas a neutral association between ARBs and mortality. Conclusions Although ARBs or ACEIs were not associated with fatal outcomes, potential beneficial effects of ARBs observed in pneumonia were attenuated in COVID-19.
Cytosolic d‐type CpG‐oligonucleotides induce a type I interferon response by activating the cGAS‐STING signaling pathway

Cytosolic DNA receptor cyclic GMP‐AMP (cGAMP) synthase (cGAS) has been shown to be critically involved in the detection of cytosolic, self‐ and non‐self‐DNA, initiating a type I IFN response through the adaptor protein Stimulator of Interferon Genes (STING) and interferon regulatory factor 3 (IRF3). Current studies propose that canonical binding of dsDNA by cGAS depends on DNA length, but not on base sequence. In contrast, activation of TLR9 is sequence dependent. It requires unmethylated CpG dinucleotides in microbial DNA, which is mimicked by synthetic oligodeoxynucleotides (ODN). Here, we provide evidence that d‐type ODN (D‐ODN), but not K‐type ODN (K‐ODN), bind to human cGAS and activate downstream signaling. Transfection of D‐ODN into a TLR9‐deficient, human monocytic cell line (THP‐1) induced phosphorylation of IRF3 and secretion of IFN. This response was absent in cells with CRISPR/Cas9‐mediated cGAS‐ or STING‐deficiency. Utilizing a protein pulldown approach, we further demonstrate direct binding of D‐ODN to cGAS. Induction of a type I IFN response by D‐ODN was confirmed in human primary monocytes and monocyte‐derived macrophages. These results are relevant to our understanding of self–nonself‐discrimination by cGAS and to the pharmacologic effects of ODN, which currently are investigated in clinical studies.
Limited Significance of Antifactor H Antibodies in Patients with Membranous Nephropathy.

Primary membranous nephropathy, the most common causes of nephrotic syndrome in White adults, results from glomerular damage secondary to deposition of Igs and complement components in the glomerular basement membrane. In 70% – 80% of patients with membranous nephropathy, the disease is due to antibodies against the phospholipase A2 receptor (PLA2R) present on the podocyte cell surface (1). These antibodies are predominantly of the IgG4 subclass. However, the complement activating properties of IgG4 through the classic pathway of complement at the surface level are considered minimal. Yet, large amounts of complement proteins are present in the glomeruli of patients with membranous nephropathy, suggesting that the complement proteins in membranous nephropathy may be derived from activation of the alternative pathway or the lectin pathway of complement (1)
Neonatal coagulopathies: A review of established and emerging treatments

Despite the relative frequency of both bleeding and clotting disorders among patients treated in the neonatal intensive care unit, few clear guidelines exist for treatment of neonatal coagulopathies. The study and treatment of neonatal coagulopathies are complicated by the distinct hemostatic balance and clotting components present during this developmental stage as well as the relative scarcity of studies specific to this age group. This mini-review examines the current understanding of neonatal hemostatic balance and treatment of neonatal coagulopathies, with particular emphasis on emerging treatment methods and areas in need of further investigative efforts.
Measuring the Impact of the COVID-19 Pandemic on Sexually Transmitted Diseases Public Health Surveillance and Program Operations in the State of California

An assessment describing COVID-19’s impact on sexually transmitted disease public health surveillance, sexually transmitted disease testing, and clinical services throughout the state of California was conducted. Background As public health personnel and resources are redirected to COVID-19, sexually transmitted diseases (STD) programs have been unable to sustain pre–COVID-19 activities. Methods We used California (CA) surveillance data to describe trends in case reporting for gonorrhea, chlamydia, and syphilis of any stage in the pre– versus post–COVID-19 eras (January–June 2019 and January–June 2020). We also analyzed data from an electronic survey administered by the CA STD Control Branch to local health jurisdictions in April, June, and September of 2020, assessing the impact of COVID-19 on STD programs. Results There were sharp declines in cases of all reportable bacterial STDs occurring in conjunction with the March 19, 2020 CA stay-at-home order, most of which did not return to baseline by July. Comparing January–June 2020 to January–June of 2019, there were decreases in reported cases of chlamydia (31%), late syphilis (19%), primary/secondary syphilis (15%), early nonprimary nonsecondary syphilis (14%), and gonorrhea (13%). The largest percentage declines in STD case reporting were among Hispanic, Asian/Pacific Islander, and Black persons. Seventy-eight percent of local health jurisdiction respondents indicated that half or more of their workforce had been redeployed to COVID-19 by September 2020. Conclusions During the COVID-19 era, STD case reporting and programmatic functions have diminished throughout CA. Because this may contribute to decreases or delays in STD diagnosis and treatment—with resultant increases in STD transmission—providers and public health officials should prepare for potential increases in STD-related morbidity in the months and years to come.
Accurate contact-based modelling of repeat proteins predicts the structure of new repeats protein families

Repeat proteins are abundant in eukaryotic proteomes. They are involved in many eukaryotic specific functions, including signalling. For many of these proteins, the structure is not known, as they are difficult to crystallise. Today, using direct coupling analysis and deep learning it is often possible to predict a protein’s structure. However, the unique sequence features present in repeat proteins have been a challenge to use direct coupling analysis for predicting contacts. Here, we show that deep learning-based methods (trRosetta, DeepMetaPsicov (DMP) and PconsC4) overcomes this problem and can predict intra- and inter-unit contacts in repeat proteins. In a benchmark dataset of 815 repeat proteins, about 90% can be correctly modelled. Further, among 48 PFAM families lacking a protein structure, we produce models of forty-one families with estimated high accuracy.
An investigation of conventional microbial culture for the Naja atra bite wound, and the comparison between culture-based 16S Sanger sequencing and 16S metagenomics of the snake oropharyngeal bacterial microbiota

Naja atra is a major venomous snake found in Taiwan. The bite of this snake causes extensive wound necrosis or necrotizing soft tissue infection. Conventional microbial culture-based techniques may fail to identify potential human pathogens and render antibiotics ineffective in the management of wound infection. Therefore, we evaluated 16S Sanger sequencing and next-generation sequencing (NGS) to identify bacterial species in the oropharynx of N. atra. Using conventional microbial culture methods and the VITEK 2 system, we isolated nine species from snakebite wounds. On the basis of the 16S Sanger sequencing of bacterial clones from agar plates, we identified 18 bacterial species in the oropharynx of N. atra, including Morganella morganii, Proteus vulgaris, and Proteus mirabilis, which were also present in the infected bite wound. Using NGS of 16S metagenomics, we uncovered more than 286 bacterial species in the oropharynx of N. atra. In addition, the bacterial species identified using 16S Sanger sequencing accounted for only 2% of those identified through NGS of 16S metagenomics. The bacterial microbiota of the oropharynx of N. atra were modeled better using NGS of 16S metagenomics compared to microbial culture-based techniques. Stenotrophomonas maltophilia, Acinetobacter baumannii, and Proteus penneri were also identified in the NGS of 16S metagenomics. Understanding the bacterial microbiota that are native to the oropharynx of N. atra, in addition to the bite wound, may have additional therapeutic implications regarding empiric antibiotic selection for managing N. atra bites.
Optimal inflammatory bowel disease management during the global coronavirus disease 2019 pandemic

Purpose of review This review aims to summarize the current evidence regarding the risks and implications of coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD) and discuss optimal management of IBD during this pandemic. Recent findings Patients with IBD are not at increased risk of COVID-19 but several risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection) have been identified, such as active IBD, obesity, and corticosteroid use. COVID-19 outcomes are similar among patients with IBD and the overall population. Although biologics have not been shown to increase the risk of severe COVID-19 complications, several risk factors have been associated with negative COVID-19 outcomes in patients with IBD, including older age, obesity, the presence of comorbidities, active disease, and corticosteroid use. IBD therapy should, therefore, be continued with the aim of attaining or maintaining remission, except for corticosteroids, which should be held or reduced to the minimal effective dose. Although it has been recommended that immunosuppressive therapy be held during a case of COVID-19, the half-lives of these drugs and data on the timing of restarting therapy limit the strength of these recommendations. We recommend COVID-19 vaccination for IBD patients whenever available, as benefits to the individual and to society outweigh the risks. Summary As our understanding of SARS-CoV-2 and COVID-19 continues to evolve, we are learning more about its impact in patients with IBD and how to better manage patients in this setting. Managing IBD during this pandemic has also highlighted the importance of restructuring services in order to adapt to current and potential future outbreaks. The COVID-19 pandemic has transformed IBD care through the expansion of telemedicine and development of novel approaches to remote monitoring.
Delay discounting and obesity in food insecure and food secure women.

OBJECTIVES The relation between food insecurity (FI) and delay discounting (DD) and probability discounting (PD) for food and money was tested in women. In addition, discounting was tested as a variable that mediates the relation between obesity and FI. METHOD Women recruited from a community sample (N = 92) completed questionnaires. They completed the food choice questionnaire, the monetary choice questionnaire, measures for food and money probability discounting (which quantify sensitivity to risk aversion), and demographic measures. RESULTS Women with FI had higher rates of obesity and higher food DD compared to food-secure women. However, DD for money or probability discounting for food or money did not significantly differ between FI and food secure groups when controlling for significant covariates. Neither DD or PD significantly mediated the relation between FI and obesity. CONCLUSIONS These results suggest that FI is associated with greater impulsive food choice, but its association with other monetary discounting and probability discounting for food and money appears contingent upon other demographic factors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).