Miracle-dz/UniFAR-FTUs huggingface dataset:
Determination and prospective validation of cut-off values for the diagnosis of liver cirrhosis for point shear-wave elastography/acoustic radiation force impulse imaging using the ACUSON Sequoia ultrasound system

Objectives Point shear-wave elastography (pSWE) alias acoustic radiation force impulse (ARFI) imaging is a well-established ultrasound-based technique for the non-invasive assessment of liver tissue stiffness. As cut-off values for liver cirrhosis cannot be transferred from one ultrasound system to another, this study aimed at determining cut-off values for the newly developed Siemens ACUSON Sequoia ultrasound system. Methods In a pilot study phase, two independent examiners conducted 10 pSWE measurements in an elasticity phantom and 32 healthy individuals for the determination of inter-examiner agreement. Afterwards, 22 cirrhotic patients and 57 patients with chronic liver disease undergoing liver biopsy underwent pSWE. Patient characteristics and stiffness values were compared for individuals with and without liver cirrhosis. Diagnostic accuracies of cut-off values for the diagnosis of liver cirrhosis were calculated using areas under the receiver operating characteristics analysis and Youden’s index. In a subsequent validation study phase, these cut-off values were validated prospectively in 107 cirrhotic and 68 non-cirrhotic patients. Results Inter-examiner agreement was excellent for measurements in the elasticity phantom (intra-class correlation coefficient [ICC] = 0.998; P < 0.001), and good for measurements in patients (ICC = 0.844; P < 0.001). The best cut-off value for the diagnosis of liver cirrhosis was 1.405 m/s with an AUC of 0.872, a sensitivity of 88.2% and a specificity of 88.2% (P < 0.001). Conclusion ARFI elastography using the Siemens ACUSON Sequoia showed a good inter-examiner agreement. The optimal cut-off value was lower than the cut-off values described for former generations of ultrasound devices. These preliminary results should be confirmed in larger patient collectives with histology as the reference standard.
Heart failure patients without echocardiography are more commonly diagnosed in hospital care and are associated with higher mortality compared to primary care

Abstract Objective This Swedish study aimed to assess the prevalence, associated clinical factors, and mortality rates of heart failure patients diagnosed without echocardiograms in both hospital and primary care settings. Design We conducted a retrospective population-based study using data from the Region Halland healthcare database in Sweden covering 330,000 residents. Subjects From 2013–2019, 3,903 patients received an incidental heart failure diagnosis without an echocardiogram and they were followed for one year. Main outcome measures Using logistic and Cox regression analyses, we evaluated the prevalence, clinical characteristics, and all-cause mortality at intervals of 30, 100, and 365 days post-diagnosis. Results In this Swedish cohort, the one-year all-cause mortality rate was markedly higher for patients diagnosed in hospitals (42%) compared to those in primary care (20%, p < 0.001). Patients diagnosed in primary care were older and had fewer comorbidities and lower NT-proBNP levels. Hospital-diagnosed patients faced a significantly higher mortality rate in the initial 30 days but saw similar rates to primary care patients thereafter. Conclusion In a Swedish region, heart failure diagnoses without echocardiograms were more common in hospitals, and these patients initially faced worse prognoses. After the first month, however, the prognosis of hospital-diagnosed patients mirrored that of those diagnosed in primary care. These findings emphasize the need for improved diagnostic and treatment approaches in both care settings to enhance outcomes.
South Africa's male homicide epidemic hiding in plain sight: exploring sex differences and patterns in homicide risk in a retrospective descriptive study of postmortem investigations

Background South Africa has homicide rates six times the global average, predominantly among men, but little is known about male victims. As part of the country's first ever study of male homicide we compared 2017 male and female victim profiles for selected covariates, against global averages and previous estimates for 2009. Methods We conducted a retrospective descriptive study of routine data collected through postmortem investigations, calculating age-standardised mortality rates for manner of death by age, sex and province and male-to-female incidence rate ratios with 95% confidence intervals. We then used generalised linear models and linear regression models to assess the association between sex and victim characteristics including age and mechanism of injury (guns, stabs and blunt force) within and between years. Findings 87% of 19,477 homicides in 2017 were males, equating to seven male deaths for every female, with sharp force and firearm discharge the most common external causes. Rates were higher among males than females at all ages, and up to eight times higher among males aged 15-44 years. Provincial rates varied overall and by sex, with the highest comparative risk for men vs. women in the Western Cape Province (11.4 males for every 1 female). Male homicides peaked during December and were highest on weekends, underscoring the prominent role of alcohol as a risk factor. Significantly more males tested positive for alcohol than females. Interpretation The massive, disproportionate and enduring homicide risk borne by adult South African men highlights the negligible prevention response. Only through challenging the normative perception of male invulnerability can we begin to address the enormous burden of violence impacting men. There is an urgent need to address the insidious effect of such societal norms alongside implementing structural interventions to overcome the root causes of poverty and inequality and better control alcohol and firearms.
A conserved nutrient responsive axis mediates autophagic degradation of miRNA–mRNA hybrids in blood cell progenitors

Abstract In animals, microRNAs are amongst the primary non-coding RNAs involved in regulating the gene expression of a cell. Most mRNAs in a cell are targeted by one or many miRNAs. Although several mechanisms can be attributed to the degradation of miRNA and mRNA within a cell, but the involvement of autophagy in the clearance of miRNA and its target mRNA is not known. We discover a leucine-responsive axis in blood cell progenitors that can mediate an autophagy-directed degradation of miRNA-bound mRNA in Drosophila melanogaster and Homo sapiens. This previously unknown miRNA clearance axis is activated upon amino acid deprivation that can traffic miRNA–mRNA-loaded Argonaute for autophagic degradation in a p62-dependent manner. Thus, our research not only reports a novel axis that can address the turnover of a catalytically active miRISC but also elucidates a slicer-independent mechanism through which autophagy can selectively initiate the clearance of target mRNA.
Clinical, Functional, and Nutritional Efficacy of a Glutamine-Enriched Oligomeric Diet in Patients with Rectal Cancer

Abstract Aims This work aims to evaluate the efficacy of nutritional supplementation with a glutamine-enriched oligomeric diet (GEOD) compared to a standard polymeric diet (SPD) in terms of oncology treatment-related diarrhea (OTRD) (frequency and consistency of stools), gastrointestinal toxicity, and functional and nutritional progress. Methods This prospective cohort study compared two groups of patients with rectal cancer in treatment with neoadjuvant chemotherapy and radiotherapy who were at risk of malnutrition. Patients were randomized to receive either 400 ml of GEOD or of SPD from the start of radiotherapy to 30 days after its completion. Results Eighty patients were recruited, 40 per arm. The GEOD arm had improved stool consistency and a greater reduction in the number of stools compared to the SPD arm (p < 0.001). The relative risk (RR) of developing diarrhea in the GEOD arm was 0.059 (95% CI 0.015-0.229). There was a reduced risk of developing intestinal mucositis in the GEOD arm compared to the SPD arm [RR 0.202 (95% CI 0.102 − 0.399)]. The GEOD arm had greater improvements in functional and nutritional status (p < 0.001). Conclusions GEOD had a protective effect in terms of the development of gastrointestinal toxicity associated with chemotherapy and radiotherapy treatment in patients with rectal cancer.
ANALYSIS OF MICROBIAL BIOFILM COMMUNITY COMPOSITION WITHIN CONSTRUCTED WETLANDS

96 Introduction 96 Methods and Materials 101 Constructed Wetland Microcosm Operation 101 Microcosm Destructive Sampling 102 DNA Extraction 103 PCR 103 DGGE 104 DGGE Data Analysis 105 Results 107 Discussion 110 Acknowledgements 114 6. THE INFLUENCE OF SULFATE REDUCING BACTERIA AND AMMONIA OXIDIZING BACTERIA ON NUTRIENT CYCLING IN CONSTRUCTED WETLAND MICROCOSMS 120 Contribution of Authors and Co-authors 118 Manuscript Information Page 119 Abstract 12
Spray-dried nanocrystal-loaded polymer microparticles for long-term release local therapies: an opportunity for poorly soluble drugs

Abstract Nano- and micro-technologies can salvage drugs with very low solubility that were doomed to pre-clinical and clinical failure. A unique design approach to develop drug nanocrystals (NCs) loaded in extended release polymeric microparticles (MPs) for local treatments is presented here through the case of a potential osteoarthritis (OA) drug candidate for intra-articular (IA) administration. Optimizing a low-shear wet milling process allowed the production of NCs that can be subsequently freeze-dried (FD) and redispersed in a hydrophobic polymer-organic solvent solution to form spray-dried MPs. Results demonstrated a successful development of a ready-to-upscale formulation containing PLGA MPs with high drug NC encapsulation rates that showed a continuous and controlled drug release profile over four months. The screenings and procedures described allowed for identifying and overcoming common difficulties and challenges raised along the drug reduction to nano-size and spray-drying process. Above all, the technical knowledge acquired is intended for formulation scientists aiming to improve the therapeutic perspectives of poorly soluble drugs. Graphical Abstract
Foot and Ankle Bone Marrow Edema Assessment in Long Distance Runners

Background: The clinical significance of foot and ankle bone marrow edema (BME) is poorly understood. Methods: Magnetic resonance imaging (MRI) and the visual analog scale (VAS) pain scores were collected for 17 runners who participated in the Twin Cities Marathon, immediately postmarathon and at a 6-week follow-up. Bone marrow edema lesions were classified using lesion frequency, anatomical location, and grading scale change to calculate a BME score for each affected bone. Spearman rank correlation coefficient test was used to identify a possible correlation between VAS and postmarathon BME. A paired Student t test was used to detect differences between total mileage ran 6 weeks postmarathon in participants with or without BME. Results: After completing the marathon, 8 BME lesions were identified in 5 participants (29.4%; 5/17), 3 were men, and 2 were women, with a mean age of 33.8 years (range: 24-52), and BMI of 22.9 ± 4. All lesions were resolved on 6-week follow-up imaging. VAS pain scores did not correlate with postmarathon BME. A significant difference in total miles logged over 6 weeks postmarathon could not be found among participants with and without BME. Conclusion: Foot and ankle BME changes identified by MRI were not correlated to clinical symptoms and may resolve with self-directed activity in less time than other areas of the lower extremity. Level of Evidence: Level II, Prospective Cohort Study.
Associations between emotional support and cardiovascular risk factors and subclinical atherosclerosis in middle-age.

OBJECTIVE To test the hypothesis of low emotional support being associated with lifestyle and biomedical cardiovascular disease (CVD) risk factors, estimated risk of CVD morbidity and mortality, and subclinical atherosclerosis in middle-aged healthy adults. METHODS AND MEASURES Cross-sectional data were obtained from participants aged 40-60 years who had one or more conventional CVD risk factor. They underwent assessment based on questionnaires, clinical examination, blood sampling, and carotid ultrasound of plaque formation and carotid intima-media wall thickness (cIMT). Based on the Interview Schedule for Social Interaction, the participants were categorised as either low in emotional support (n = 884) or as a referent (n = 2570). Logistic regression analyses were conducted to study the associations. RESULTS Logistic regression analyses showed that low emotional support was significantly associated with smoking, alcohol consumption and physical inactivity (OR = 1.53 - 1.94), estimated risk of CVD morbidity and mortality (OR = 1.56 - 1.68), and plaque formation (OR = 1.39). No significant associations were found regarding biomedical CVD risk factors or cIMT. CONCLUSION The findings suggest that low social support is associated with lifestyle CVD risk factors, estimated risk of CVD morbidity and mortality, and subclinical atherosclerosis in middle-aged healthy adults, encouraging causal evaluation with longitudinal data investigating an impact of emotional support on mechanisms underlying CVD.
Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation

Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage‐mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3‐associated phagocytosis (LAP), a non‐canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G‐protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL‐induced efferocytosis, anti‐colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3‐associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.
Integration of single‐cell and bulk RNA‐sequencing to analyze the heterogeneity of hepatocellular carcinoma and establish a prognostic model

Abstract Background The highly heterogeneous nature of hepatocellular carcinoma (HCC) results in different responses and prognoses to the same treatment in patients with similar clinical stages. Aims Thus, it is imperative to investigate the association between HCC tumor heterogeneity and treatment response and prognosis. Methods and Results At first, we downloaded scRNA‐seq, bulk RNA‐seq, and clinical data from TCGA and GEO databases. We conducted quality control, normalization using SCTransform, dimensionality reduction using PCA, batch effect removal using Harmony, dimensionality reduction using UMAP, and cell annotation‐based marker genes on the scRNA‐seq data. We recognized tumor cells, identified tumor‐related genes (TRGs), and performed cell communication analysis. Next, we developed a prognostic model using univariable Cox, LASSO, and multivariate Cox analyses. The signature was evaluated using survival analysis, ROC curves, C‐index, and nomogram. Last, we studied the predictability of the signature in terms of prognosis and immunotherapeutic response for HCC, assessed a variety of drugs for clinical treatment, and used the qRT‐PCR analysis to validate the mRNA expression levels of prognostic TRGs. Conclusion To conclude, this study expounded upon the influence of tumor cell heterogeneity on the prediction of treatment outcomes and prognosis in HCC. This, in turn, enhances the predictive ability of the TNM staging system and furnishes novel perspectives on the prognostic assessment and therapy of HCC.
A Global Outlook on Child Sexual Abuse and Sexually Explicit Material Online During COVID-19: Trends and Interdisciplinary Prevention Methods

ABSTRACT This scoping review investigates the impact of COVID-19 on global and national trends in online child sexually explicit material (CSEM) trafficking and production in addition to online child sexual abuse (OCSA). Globally, CSEM consumption increased dramatically during the pandemic, as well as trafficking of self-generated material. The hypothesized reasons for the increase in OCSA and CSEM that guided this review included stay-at-home orders, COVID-19-related precautions, technology use increase, economic instability, and lack of available victim and legal resources. Current global and national law enforcement procedures to prevent the proliferation of online sexual abuse are reviewed with suggestions for preventing further increases in CSEM production, distribution, and consumption at the micro and macro levels.
Cardiomyopathy in patients with acute ischemic stroke and methamphetamine use: Relevance for cardioembolic stroke and outcome

Methamphetamine use has emerged as a major risk factor of cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate the relevance of methamphetamine use and cardiomyopathy in patients with acute ischemic stroke. We performed a retrospective study of consecutive patients with acute ischemic stroke admitted at our medical center between 2019 and 2022. All patients were screened for methamphetamine use and cardiomyopathy defined as left ventricular ejection fraction [≤] 45%. Methamphetamine use was identified by self-reported history of use and/or positive urine drug screen. Logistic regression model was performed to analyze the relevance of methamphetamine-associated cardiomyopathy and cardioembolic stroke. Among 973 consecutive patients screened for the study, 48 (4.9%) were identified to have methamphetamine use. Compared with Non-meth group (n=892), the patients in the Meth group were significantly younger (53.2 {+/-} 10.0 vs. 69.7 {+/-} 15.2, p <0.001), more likely male (76.6% vs. 50.0%, p <0.001), and associated with significantly higher rate of cardiomyopathy (30.4% vs. 14.0%, p <0.01). They were also less likely to have history of atrial fibrillation (8.7% vs. 33.4%, p<0.01) or hyperlipidemia (28.3% vs. 51.7%, p <0.01). Compared with patients with cardiomyopathy without methamphetamine use, those with methamphetamine use and cardiomyopathy had better functional outcome at 3 months, likely due to younger age and fewer comorbidities. In the logistic regression model, methamphetamine-associated cardiomyopathy was found to be a significant risk factor of cardioembolic stroke (OR 2.88, 95% CI 1.81-4.58, p < 0.0001). Our results demonstrate that methamphetamine use increases the risk of cardiomyopathy and cardioembolic stroke in young adults.
Temporal contact patterns and the implications for predicting superspreaders and planning of targeted outbreak control

Epidemic models often heavily simplify the dynamics of human-to-human contacts, but the resulting bias in outbreak dynamics - and hence requirements for control measures - remains unclear. Even if high resolution temporal contact data were routinely used for modelling, the role of this temporal network structure towards outbreak control is not well characterised. We address this by assessing dynamic networks across varied social settings and developing a novel metric to measure contact retention over time and to identify highly connected individuals. Using 11 networks from 5 settings studied over 3-10 days, we estimated that more than 80% of the individuals in most settings were highly connected for only short periods. This suggests a challenge to identify 'superspreaders', and more individuals would need to be targeted as part of outbreak interventions to achieve the same reduction in transmission as predicted from a static network. Taking into account repeated contacts over multiple days, we estimated simple resource planning models might overestimate the number of contacts made by an infector by 20%-70%. In workplaces and schools, contacts in the same department accounted for most of the retained contacts. Hence, outbreak control measures would be better off targeting specific sub-populations in these settings to reduce transmission. In contrast, no obvious type of contact dominated the retained contacts in hospitals, so reducing the risk of disease introduction is critical to avoid disrupting the interdependent work functions.
Electrophysiologically-defined excitation-inhibition autism neurosubtypes

Excitation-inhibition (E:I) imbalance has long been considered one of the primary neurobiological theories explaining autism. However, the theory has been bolstered heavily by research on high-penetrance genetic mechanisms which are only found in a small proportion of the autism population. Thus, how well does E:I imbalance explain idiopathic autism? Here we find that idiopathic autistic males can be split into two distinct E:I-defined 'neurosubtypes'. These E:I neurosubtypes can be identified in EEG data via an E:I-sensitive metric known as the Hurst exponent (H). Half of autistic individuals fall into the first E:I neurosubtype and can be described as having elevated E:I ratio relative to typically-developing (TD) comparison group. The remaining other half of autistic males fall into a second E:I neurosubtype with the opposite pattern of reduced E:I ratio relative to TD. Finally, E:I neurosubtypes show differential relationships between H and behavioral and demographic variables consisting of age, intelligence, and autism symptomatology. This work suggests that different types of E:I imbalance can manifest in idiopathic autistic males. Such differential E:I biomarkers may be indicative of distinctive etiological or compensatory mechanisms and differential underlying micro- and macroscale neural organization with differential phenotypic impact.
Heavy metals (Cd, Cu, Pb and Zn) in two species of limpets (Patella rustica and Patella candei crenata) in the Canary Islands, Spain

Nowadays, indigenous molluscs are being utilized more and more as biomonitors. Thus, in order to assess the concentrations of Cd, Cu, Pb and Zn in the Canarian Archipelago (Spain), we have utilized two species of limpets (Patella rustica and Patella candei crenata). We also tested the relationship between the metal levels and biometric parameters such as size and weight. The mean total concentrations of Cd, Cu, Pb, and Zn in P. rustica were 0.37 ± 0.05, 1.77 ± 0.09, 1.27 ± 0.07 and 8.84 ± 0.71 μg g dry wt. (mean ± S.E.) respectively; whereas P. candei crenata as follows; 0.71 ± 0.10, 2.94 ± 0.11, 0.09 ± 0.01 and 33.74 ± 1.15 μg g dry wt. (mean ± S.E.). We found significant differences for metal concentrations between the eastern islands and the western islands for both species. We did not observed evidences that more inhabited islands (Tenerife and Gran Canaria), had the highest metal concentration levels. Natural inputs from the upwelling region and other factors like size, food availability and/or excretion could have contributed to the variability. P. rustica presented negative correlations between metal concentrations and body weight and size, whereas, P. candei crenata showed negative correlations with Pb and with the biometric parameters. P. candei crenata revealed also positive correlation between Cd concentration and size.