Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in marrow adipose tissue with short-term changes in weight in premenopausal women with anorexia nervosa.

OBJECTIVE In anorexia nervosa, a psychiatric disease characterized by self-induced starvation and a model of chronic undernutrition, levels of subcutaneous (SAT) and visceral (VAT) adipose tissue are low, whereas marrow adipose tissue (MAT) levels are elevated compared to normal-weight women. The reason for this paradoxical elevation of an adipose tissue depot in starvation is not known. We sought to understand changes in MAT in response to sub-acute changes in weight and to compare these changes with those of other fat depots and body composition parameters. DESIGN AND METHODS We conducted a 12-month longitudinal study including 46 premenopausal women (n=26 with anorexia nervosa and n=20 normal-weight controls) with a mean (SEM) age of 28.2+/-0.8 years. We measured MAT, SAT, VAT, and bone mineral density (BMD) at baseline and after 12 months. RESULTS At baseline, SAT (p<0.0001), VAT (p<0.02) and BMD of the spine and hip (p<0.0002) were significantly lower and vertebral and metaphyseal MAT (p<0.001) significantly higher in anorexia nervosa compared to controls. Weight gain over 12 months was associated with increases not only in SAT and VAT, but also epiphyseal MAT (p<0.03). Changes in epiphyseal MAT were positively associated with changes in BMD (p<0.02). CONCLUSIONS In contrast to the steady-state, in which MAT levels are higher in anorexia nervosa and MAT and BMD are inversely associated, short-term weight gain is associated with increases in both MAT and BMD. These longitudinal data demonstrate the dynamic nature of this fat depot and provide further evidence of its possible role in mineral metabolism.
The Self-Assembling Peptide P11-4 Prevents Collagen Proteolysis in Dentin

The major goal in restorative dentistry is to develop a true regenerative approach that fully recovers hydroxyapatite crystals within the caries lesion. Recently, a rationally designed self-assembling peptide P11-4 (Ace-QQRFEWEFEQQ-NH2) has been developed to enhance remineralization on initial caries lesions, yet its applicability on dentin tissues remains unclear. Thus, the present study investigated the interaction of P11-4 with the organic dentin components as well as the effect of P11-4 on the proteolytic activity, mechanical properties of the bonding interface, and nanoleakage evaluation to artificial caries-affected dentin. Surface plasmon resonance and atomic force microscopy indicated that P11-4 binds to collagen type I fibers, increasing their width from 214 ± 4 nm to 308 ± 5 nm (P < 0.0001). P11-4 also increased the resistance of collagen type I fibers against the proteolytic activity of collagenases. The immediate treatment of artificial caries-affected dentin with P11-4 enhanced the microtensile bonding strength of the bonding interface (P < 0.0001), reaching values close to sound dentin and decreasing the proteolytic activity at the hybrid layer; however, such effects decreased after 6 mo of water storage (P < 0.05). In conclusion, P11-4 interacts with collagen type I, increasing the resistance of collagen fibers to proteolysis, and improves stability of the hybrid layer formed by artificial caries-affected dentin.
Differential Enriched Scan 2 (DEScan2): a fast pipeline for broad peak analysis

Nowadays, the analysis of RNA-seq and BS-Seq can be considered well established, whereas the analysis of broad peaks data as Sono-Seq/ATAC-Seq and histone modification (HM) ChIP-Seq is still challenging. To fill the gap in existing methods, we present DEScan2 a novel bioconductor package [2] for the analysis of broad peaks data. The method consists of three main steps: 1) a peak caller, 2) peak filtering and alignment across replicates and 3) a method to efficiently compute a count matrix of the filtered peaks. Using an already published ATAC-Seq dataset for chromatin accessibility our method shows interesting results, also by comparing it with other well-known tools for this kind of data analysis.
Associations Between Dietary Protein Sources, Plasma BCAA and Short-Chain Acylcarnitine Levels in Adults

Elevated plasma branched-chain amino acids (BCAA) and C3 and C5 acylcarnitines (AC) levels observed in individuals with insulin resistance (IR) might be influenced by dietary protein intakes. This study explores the associations between dietary protein sources, plasma BCAA levels and C3 and C5 ACs in normal weight (NW) or overweight (OW) individuals with or without metabolic syndrome (MS). Data from 199 men and women aged 18–55 years with complete metabolite profile were analyzed. Associations between metabolic parameters, protein sources, plasma BCAA and AC levels were tested. OW/MS+ consumed significantly more animal protein (p = 0.0388) and had higher plasma BCAA levels (p < 0.0001) than OW/MS− or NW/MS− individuals. Plasma BCAA levels were not associated with BCAA intakes in the whole cohort, while there was a trend for an association between plasma BCAA levels and red meat or with animal protein in OW/MS+. These associations were of weak magnitude. In NW/MS− individuals, the protein sources associated with BCAA levels varied greatly with adjustment for confounders. Plasma C3 and C5 ACs were associated with plasma BCAA levels in the whole cohort (p < 0.0001) and in subgroups based on OW and MS status. These results suggest a modest association of meat or animal protein intakes and an association of C3 and C5 ACs with plasma BCAA levels, obesity and MS.
Efficacy of neuropsychological rehabilitation on numerical and calculation abilities: A developmental case study

Abstract Present single case proves the effectiveness of a theory-based cognitive treatment on numerical and calculation abilities in developmental age. Both evaluation and treatment were designed on the bases of current models of numerical cognition, in particular Von Aster’s developmental model. At the age of 7.4 years, HT was referred for a serious delay in the acquisition of numerical skills involving all numerical and calculation skills (written calculations, numerical knowledge, accuracy, rapidity). Following the rules of neuropsychological rehabilitation, HT was submitted to an early, intensive, HT-tailored treatment based on analogic representation of amount. After 12 months of treatment, HT showed statistically significant increasing in all the investigated variables: however, even if he correctly performed various numerical tasks, he remained significantly slower compared to his peers. Present case demonstrated the efficacy of theory-based, individually-tailored developmental dyscalculia. Early diagnosis and early intervention are urgently needed to get clinically significant change and to prevent behavioral and emotional symptoms.
Evaluation of carbon dioxide induction methods for the euthanasia of day‐old cull broiler chicks

ABSTRACT This study was conducted to evaluate the efficacy of 5 different CO2 euthanasia induction techniques for day‐old cull chicks in minimizing distress and inducing a rapid loss of sensibility and death. Each induction treatment was characterized for concentration change over time, maximum concentration, and time to reach maximum. Sixteen chicks were euthanized with the gradual treatments to establish validity of treatment. Then, all 5 treatments were evaluated for effect on distress, insensibility, and death. Day‐of‐hatch cull chicks (n = 110) were euthanized in pairs by either immersion into 100% CO2 or gradual induction to 100% CO2 at displacement rates of 7, 14, 21, or 28% of chamber volume added per min (% vol/min). CO2 concentration was measured at chick level. Live focal observations and video recordings were used to assess latency to behavioral responses: head shaking (HS) and gasping (GS) as indicators of distress; loss of posture (LOP) as an indicator of insensibility; and cessation of rhythmic breathing (CRB) and movement (COM), indicating death. All behaviors occurred at the earliest with immersion compared to gradual treatments, and time between first signs of distress and LOP was shorter for immersion than gradual treatments. Gradual treatments showed a linear decrease in latency to HS, GS, and LOP as displacement rate increased. Latency to CRB decreased quadratically with increasing displacement rate, while COM decreased linearly. Within gradual treatments, HS and GS occurred at CO2 concentrations between 0.43 and 1.14%, LOP between 11.1 and 17.5%, while CRB and COM occurred between 61.8 and 78.4%. Overall, immersion induced distress, insensibility, and death significantly faster and with the shortest interval between distress and insensibility. For gradual treatment, insensibility and death occurred faster with increasing displacement rates. Behavioral signs of distress were observed with all treatments, and occurred at concentrations lower than those causing insensibility. In conclusion, immersion into 100% CO2 environment resulted in the shortest time of distress and fastest time to death compared to gradual displacement rates of any speed measured.
Dynamic wildlife occupancy models using automated acoustic monitoring data

Abstract Automated acoustic monitoring of wildlife has been used to characterize populations of sound‐producing species across large spatial scales. However, false negatives and false positives produced by automated detection systems can compromise the utility of these data for researchers and land managers, particularly for research programs endeavoring to describe colonization and extinction dynamics that inform land use decision‐making. To investigate the suitability of automated acoustic monitoring for dynamic occurrence models, we simulated underlying occurrence dynamics, calling patterns, and the automated acoustic detection process for a hypothetical species under a range of scenarios. We investigated an automated species detection aggregation method that considered a suite of options for creating encounter histories. From these encounter histories, we generated parameter estimates and computed bias for occurrence, colonization, and extinction rates using a dynamic occupancy modeling framework that accounts for false positives via small amounts of manual confirmation. We were able to achieve relatively unbiased estimates for all three state parameters under all scenarios, even when the automated detection system was simulated to be poor, given particular encounter history aggregation choices. However, some encounter history aggregation choices resulted in unreliable estimates; we provide caveats for avoiding these scenarios. Given specific choices during the detection aggregation process, automated acoustic monitoring data may provide an effective means for tracking species occurrence, colonization, and extinction patterns through time, with the potential to inform adaptive management at multiple spatial scales.
Effects of a lifestyle intervention on markers of cardiometabolic risk and oxidized lipoproteins among obese adolescents with prediabetes

Abstract Objective Obesity and hyperglycaemia contribute to the atherosclerotic process in part through oxidative modifications to lipoprotein particles. The present study aimed to evaluate the effects of a lifestyle intervention on markers of oxidized lipoproteins in obese Latino adolescents with prediabetes. Design Pre–post design. Setting Participants were enrolled into a 12-week lifestyle intervention. Measurements pre- and post-intervention included anthropometrics and body composition, lipid panel, oxidized LDL (oxLDL), oxidized HDL (oxHDL), intake of fresh fruits and vegetables, and cardiorespiratory fitness. Participants Thirty-five obese Latino adolescents (seventeen females, eighteen males; mean age 15·5 (sd 1·0) years; mean BMI percentile 98·5 (sd 1·2)) with prediabetes. Results Intervention participation resulted in significant reductions in weight (−1·2 %, P = 0·042), BMI and BMI percentile (−2·0 and −0·4 %, respectively, P < 0·001), body fat (−7·0 %, P = 0·025), TAG (−11·8 %, P = 0·032), total cholesterol (−5·0 %, P = 0·002), VLDL-cholesterol (−12·5 %, P = 0·029), and non-HDL-cholesterol (−6·7 %, P = 0·007). Additionally, fitness (6·4 %, P < 0·001) and intake of fruits and vegetables (42·4 %, P = 0·025) increased significantly. OxLDL decreased significantly after the intervention (51·0 (sd 14·0) v. 48·7 (sd 12·8) U/l, P = 0·022), while oxHDL trended towards a significant increase (395·2 (sd 94·6) v. 416·1 (sd 98·4) ng/ml, P = 0·056). Conclusions These data support the utility of lifestyle intervention to improve the atherogenic phenotype of Latino adolescents who are at high risk for developing premature CVD and type 2 diabetes.
Adenosine Metabolism in COPD: A Study on Adenosine Levels, 5′-Nucleotidase, Adenosine Deaminase and Its Isoenzymes Activity in Serum, Lymphocytes and Erythrocytes

Abstract Adenosine is a signaling molecule which is produced in high concentrations during airway inflammation. Airway inflammation is a characteristic feature of COPD. Therefore, the current study was designed to evaluate the changes in adenosine metabolism in COPD and correlate these changes with severity of the disease. The study was conducted on 50 healthy controls (25 healthy non-smokers and 25 healthy smokers) and 46 COPD patients (21 moderate, 15 severe and 10 very severe). The patients were sub-divided into moderate, severe and very severe categories as per the GOLD spirometric classification. Blood was collected from each subject and serum, lymphocytes and erythrocytes were separated. The adenosine levels and activities of 5′-nucleotidase, adenosine deaminase and its isoenzymes were assessed in serum, lymphocytes and erythrocytes. The data were analyzed statistically. A p value < 0.05 was considered as significant. In healthy smokers and COPD patients the adenosine levels increased. In COPD patients 5′-nucleotidase activity increased significantly in serum, lymphocytes and erythrocytes. The activities of ADA and isoenzymes decreased significantly in serum of healthy smokers and COPD patients, in lymphocytes and erythrocytes of very severe COPD patients and of ADA and ADA2 in lymphocytes and erythrocytes of moderate and severe COPD patients. The FEV1 (% of predicted) showed a significant negative correlation with adenosine levels and 5′-nucleotidase activity in serum, lymphocytes and erythrocytes and significant positive correlation with ADA and isoenzymes activity in serum and lymphocytes of COPD patients. We conclude that the adenosine metabolism changes in COPD. The adenosine levels and 5′-nucleotidase activity increase, and ADA activity decreases with severity of the disease.
Misconceptions and Illness Perceptions in Cardiac Patients and Their Spouses: A Pilot Study

Aim: The aims of the present study were concerned with the characterization of illness perceptions of heart disease and cardiac misconceptions in patients and their partners. We also examined the associations between illness perceptions and cardiac misconceptions with sociodemographic information and mood. Method: The participants were 46 cardiac patients, 32 with a participating partner; all completed an anonymous self-administered questionnaire. A combined methodology (qualitative and quantitative) was used. The variables were assessed by using several self-report instruments and, in the case of patients’ illness perceptions, also by collecting drawings of the heart. Results: The results indicated that illness perceptions differed according to sex, age and professional status of the patients and that these perceptions were related to personality traits. The partners reported higher levels of concern towards illness than patients. The analysis of the patients’ drawings of the heart suggests that area and height are associated with specific illness perceptions. Conclusion: Overall, the present study provides a modest but significant contribution to describe illness perceptions and cardiac misconceptions of patients and their partners and their association with recovery outcomes.
The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.
Disruption of sialic acid metabolism drives tumor growth by augmenting CD8+ T cell apoptosis

Sialylated glycan structures are known for their immunomodulatory capacities and their contribution to tumor immune evasion. However, the role of aberrant sialylation in colorectal cancer and the consequences of complete tumor desialylation on anti‐tumor immunity remain unstudied. Here, we report that CRISPR/Cas9‐mediated knock out of the CMAS gene, encoding a key enzyme in the sialylation pathway, in the mouse colorectal cancer MC38 cell line completely abrogated cell surface expression of sialic acids (MC38‐Sianull) and, unexpectedly, significantly increased in vivo tumor growth compared to the control MC38‐MOCK cells. This enhanced tumor growth of MC38‐Sianull cells could be attributed to decreased CD8+ T cell frequencies in the tumor microenvironment only, as immune cell frequencies in tumor‐draining lymph nodes remained unaffected. In addition, MC38‐Sianull cells were able to induce CD8+ T cell apoptosis in an antigen‐independent manner. Moreover, low CMAS gene expression correlated with reduced recurrence‐free survival in a human colorectal cancer cohort, supporting the clinical relevance of our work. Together, these results demonstrate for the first time a detrimental effect of complete tumor desialylation on colorectal cancer tumor growth, which greatly impacts the design of novel cancer therapeutics aimed at altering the tumor glycosylation profile.
Large-scale validation of miRNAs by disease association, evolutionary conservation and pathway activity

ABSTRACT The validation of microRNAs (miRNAs) identified by next generation sequencing involves amplification-free and hybridization-based detection of transcripts as criteria for confirming valid miRNAs. Since respective validation is frequently not performed, miRNA repositories likely still contain a substantial fraction of false positive candidates while true miRNAs are not stored in the repositories yet. Especially if downstream analyses are performed with these candidates (e.g. target or pathway prediction), the results may be misleading. In the present study, we evaluated 558 mature miRNAs from miRBase and 1,709 miRNA candidates from next generation sequencing experiments by amplification-free hybridization and investigated their distributions in patients with various disease conditions. Notably, the most significant miRNAs in diseases are often not contained in the miRBase. However, these candidates are evolutionary highly conserved. From the expression patterns, target gene and pathway analyses and evolutionary conservation analyses, we were able to shed light on the complexity of miRNAs in humans. Our data also highlight that a more thorough validation of miRNAs identified by next generation sequencing is required. The results are available in miRCarta (https://mircarta.cs.uni-saarland.de).
Artificial Intelligence–Based Classification of Breast Lesions Imaged With a Multiparametric Breast MRI Protocol With Ultrafast DCE-MRI, T2, and DWI

Objectives We investigated artificial intelligence (AI)–based classification of benign and malignant breast lesions imaged with a multiparametric breast magnetic resonance imaging (MRI) protocol with ultrafast dynamic contrast-enhanced MRI, T2-weighted, and diffusion-weighted imaging with apparent diffusion coefficient mapping. Materials and Methods We analyzed 576 lesions imaged with MRI, including a consecutive set of biopsied malignant (368) and benign (149) lesions, and an additional set of 59 benign lesions proven by follow-up. We used deep learning methods to interpret ultrafast dynamic contrast-enhanced MRI and T2-weighted information. A random forests classifier combined the output with patient information (PI; age and BRCA status) and apparent diffusion coefficient values obtained from diffusion-weighted imaging to perform the final lesion classification. We used receiver operating characteristic (ROC) analysis to evaluate our results. Sensitivity and specificity were compared with the results of the prospective clinical evaluation by radiologists. Results The area under the ROC curve was 0.811 when only ultrafast dynamics was used. The final AI system that combined all imaging information with PI resulted in an area under the ROC curve of 0.852, significantly higher than the ultrafast dynamics alone (P = 0.002). When operating at the same sensitivity level of radiologists in this dataset, this system produced 19 less false-positives than the number of biopsied benign lesions in our dataset. Conclusions Use of adjunct imaging and PI has a significant contribution in diagnostic performance of ultrafast breast MRI. The developed AI system for interpretation of multiparametric ultrafast breast MRI may improve specificity.
Drugs in lactation

Although most medications can be taken safely during breastfeeding, potential risks of infant toxicity do exist because all medications will be excreted into the breast milk to some extent. The amount of medication excreted in the milk depends mainly on (i) within‐drug variation, such as dosing; (ii) between‐drug variation including chemical characteristics of the medication; and (iii) host factors, such as maternal pharmacokinetics (PK), including variations of pregnancy‐associated changes and their post‐partum recovery. Neonatal drug exposure is usually assessed by calculating an expected total infant daily dose through breast milk and comparing it to the normal therapeutic dose. However, clinical PK studies in this population are challenging to conduct. Recently, research methods using population PK analyses and physiologically‐based PK modeling and simulation techniques have been recognized as a complementary approach to the conventional PK studies in this field. These efforts are important for rational risk assessment balancing the toxicity risk against the benefits of human milk. Health benefits of lactation for both mother and child are significant and a decision to withhold from this should not be taken lightly. In case limited information is present, additional expertise from pharmacists or clinical pharmacologist with expertise in this area should be sought.