Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiovascular Drift and Maximal Oxygen Uptake during Running and Cycling in the Heat

ABSTRACT Introduction Greater cardiovascular (CV) drift occurs during cycling compared to running in temperate conditions. CV drift also corresponds to proportional reductions in maximal oxygen uptake (V˙O2max) during heat stress. Whether exercise mode differentially affects CV drift—and accompanying declines in V˙O2max—during heat stress is uncertain. The purpose of this study was to test the hypothesis that a greater magnitude of CV drift, accompanied by a greater decrement in V˙O2max, occurs during cycling compared to running in hot conditions. Methods 7 active men (mean ± SD; age = 25 ± 6 yr, percent body fat = 11.9% ± 2.4%) completed a control graded exercise test (GXT) on a cycle ergometer and treadmill. Then on separate, counterbalanced occasions they completed 15 or 45 min of cycling or running at 60% V˙O2max in 35°C, immediately followed by a GXT to measure V˙O2max (4 trials total). The separate 15- and 45-min trials were designed to measure CV drift and V˙O2max over the same time interval. Results Heart rate increased 19% and 17% and stroke volume decreased 20% and 15% between 15 and 45 min during running and cycling, respectively, but modes were not different (all P > 0.05). Despite a 1.8°C larger core-to-skin thermal gradient during running, decrements in V˙O2peak were not different between exercise modes (95% CI for difference in change scores between 15 and 45 min: −0.2, 0.3). Conclusions CV strain (indexed as CV drift) during prolonged exercise in the heat corresponds to reduced V˙O2max, irrespective of exercise mode or the thermal gradient. As such, the upward drift in heart rate associated with CV drift reflects increased relative metabolic intensity (%V˙O2max) during prolonged cycling or running in the heat.
Clinico-Biological Implications of Modified Levels of Cytokines in Chronic Lymphocytic Leukemia: A Possible Therapeutic Role

B-cell chronic lymphocytic leukemia (B-CLL) is the main cause of mortality among hematologic diseases in Western nations. B-CLL is correlated with an intense alteration of the immune system. The altered functions of innate immune elements and adaptive immune factors are interconnected in B-CLL and are decisive for its onset, evolution, and therapeutic response. Modifications in the cytokine balance could support the growth of the leukemic clone via a modulation of cellular proliferation and apoptosis, as some cytokines have been reported to be able to affect the life of B-CLL cells in vivo. In this review, we will examine the role played by cytokines in the cellular dynamics of B-CLL patients, interpret the contradictions sometimes present in the literature regarding their action, and evaluate the possibility of manipulating their production in order to intervene in the natural history of the disease.
The effect of hand motion and object orientation on the automatic detection of orientation: A visual mismatch negativity study

We investigated the effects of voluntary hand movements and continuously present objects on the automatic detection of deviant stimuli in a passive oddball paradigm. The visual mismatch negativity (vMMN) component of event-related potentials (ERPs) was measured as the index of automatic deviant detection. The stimuli were textures consisting of parallel, oblique bars with frequent (standard) and infrequent (deviant) orientation. Traditional vMMN was measured by the difference between ERPs to frequent (standard) and infrequent (deviant) textures. Additionally, we measured ‘genuine’ vMMN by comparing the ERPs to deviant and control textures in the equal probability procedure. Compatible and incompatible hand movement directions to the standard texture had no influence on ‘traditional’ vMMN and elicited no ‘genuine’ vMMN. However, the deviant texture elicited ‘genuine’ vMMN if the orientation of a continuously present rectangle was different from the standard (and identical to the deviant) texture orientation. Our results suggest that the direction of voluntary hand movement and the orientation of task-irrelevant visual patterns do not acquire common memory representation, but a continuously present object contributes to the detection of sequential regularity violation.
N-(2-Hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H- benzimidazol-1-yl)propyl]piperidine-4-Carboxamide (D2AAK4), a Multi-Target Ligand of Aminergic GPCRs, as a Potential Antipsychotic

N-(2-hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol -1-yl)propyl]piperidine-4-carboxamide (D2AAK4) is a multitarget ligand of aminergic G protein-coupled receptors (GPCRs) identified in structure-based virtual screening. Here we present detailed in vitro, in silico and in vivo investigations of this virtual hit. D2AAK4 has an atypical antipsychotic profile and low affinity to off-targets. It interacts with aminergic GPCRs, forming an electrostatic interaction between its protonatable nitrogen atom and the conserved Asp 3.32 of the receptors. At the dose of 100 mg/kg D2AAK4 decreases amphetamine-induced hyperactivity predictive of antipsychotic activity, improves memory consolidation in passive avoidance test and has anxiogenic properties in elevated plus maze test (EPM). Further optimization of the virtual hit D2AAK4 will be aimed to balance its multitarget profile and to obtain analogs with anxiolytic activity.
Misexpression of a transcriptional repressor candidate provides a molecular mechanism for the suppression of awns by Tipped 1 in wheat

Abstract Awns are bristle-like structures formed at the tip of the lemma on the florets of some cereal grasses. Wild-type wheat is awned, but awnletted and awnless variants have been selected and nowadays all forms are cultivated. In this study, we dissected the genetic control underlying variation of this characteristic feature by association mapping in a large panel of 1110 winter wheat cultivars of worldwide origin. We identified the B1 (Tipped 1) locus on chromosome 5A as the major determinant of awnlessness globally. Using a combination of fine-mapping and expression analysis, we identified a putative C2H2 zinc finger protein with an EAR domain, characteristic of transcriptional repressors, as a likely candidate for Tipped 1. This gene was found to be up-regulated in awnless B1 compared with awned b1 plants, indicating that misexpression of this transcriptional regulator may contribute to the reduction of awn length in B1 plants. Taken together, our study provides an entry point towards a better molecular understanding of the evolution of morphological features in cereals through selection and breeding.
Albumin in decompensated cirrhosis: new concepts and perspectives

The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays a major role in the development of multiorgan dysfunction. Such abnormality is mainly due to the systemic spread of bacteria and/or bacterial products from the gut and danger-associated molecular patterns from the diseased liver triggering the release of proinflammatory mediators by activating immune cells. The exacerbation of these processes underlies the development of acute-on-chronic liver failure. A further mechanism promoting multiorgan dysfunction and failure likely consists with a mitochondrial oxidative phosphorylation dysfunction responsible for systemic cellular energy crisis. The systemic proinflammatory and pro-oxidant state of patients with decompensated cirrhosis is also responsible for structural and functional changes in the albumin molecule, which spoil its pleiotropic non-oncotic properties such as antioxidant, scavenging, immune-modulating and endothelium protective functions. The knowledge of these abnormalities provides novel targets for mechanistic treatments. In this respect, the oncotic and non-oncotic properties of albumin make it a potential multitarget agent. This would expand the well-established indications to the use of albumin in decompensated cirrhosis, which mainly aim at improving effective volaemia or preventing its deterioration. Evidence has been recently provided that long-term albumin administration to patients with cirrhosis and ascites improves survival, prevents complications, eases the management of ascites and reduces hospitalisations. However, variant results indicate that further investigations are needed, aiming at confirming the beneficial effects of albumin, clarifying its optimal dosage and administration schedule and identify patients who would benefit most from long-term albumin administration.
Interleukin‐6 signaling requires only few IL‐6 molecules: Relation to physiological concentrations of extracellular IL‐6

The aim of this study was to give quantitative insight into the number of cytokine molecules needed to activate a target cell and relate this to the physiological consequences of the amounts of cytokines typically detectable in humans. As a model system blood interleukin‐6 (IL‐6) was chosen since this cytokine is one of the most studied and clinically monitored cytokines, and because of the tools for the present investigations such as fully bioactive iodinated recombinant IL‐6, cellular cytokine binding assays, and bioassays have been thoroughly validated.
Maternal caesarean section infection (MACSI) in Sierra Leone: a case–control study

Abstract Sierra Leone is the country with highest maternal mortality and infections are the underlying cause in 11% of maternal deaths, but the real burden remains unknown. This study aims to determine the incidence and risk factors of surgical site infection (SSI) post-caesarean section (CS) in women admitted to Princess Christian Maternity Hospital (PCMH) in Freetown, Sierra Leone. A prospective case–control (1:3 ratio) study was implemented from 1 May 2018 to 30 April 2019 and 11 women presenting with suspected or confirmed infection post-CS were screened for inclusion as a case. For each case, three patients undergoing CS on the same day and admitted to the same ward, but not presenting with SSI, were selected as controls. The post-CS infection rate was 10.9%. Two hundred and fifty-four clinically confirmed cases were enrolled and matched with 762 control patients. By multivariable analysis, the risk factors for SSI were: being single (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.36–1.66), low education level (OR 1.68, 95% CI 1.55–1.84), previous CS (OR 1.27, 95% CI 1.10–1.52), presenting with premature membranes rupture (OR 1.49, 95% CI 1.18–1.88), a long decision–incision time (OR 2.08, 95% CI 1.74–2.24) and a high missing post-CS antibiotic doses rate (OR 2.52, 95% CI 2.10–2.85).
Using a machine learning approach to predict mortality in critically ill influenza patients: a cross-sectional retrospective multicentre study in Taiwan

Objectives Current mortality prediction models used in the intensive care unit (ICU) have a limited role for specific diseases such as influenza, and we aimed to establish an explainable machine learning (ML) model for predicting mortality in critically ill influenza patients using a real-world severe influenza data set. Study design A cross-sectional retrospective multicentre study in Taiwan Setting Eight medical centres in Taiwan. Participants A total of 336 patients requiring ICU-admission for virology-proven influenza at eight hospitals during an influenza epidemic between October 2015 and March 2016. Primary and secondary outcome measures We employed extreme gradient boosting (XGBoost) to establish the prediction model, compared the performance with logistic regression (LR) and random forest (RF), demonstrated the feature importance categorised by clinical domains, and used SHapley Additive exPlanations (SHAP) for visualised interpretation. Results The data set contained 76 features of the 336 patients with severe influenza. The severity was apparently high, as shown by the high Acute Physiology and Chronic Health Evaluation II score (22, 17 to 29) and pneumonia severity index score (118, 88 to 151). XGBoost model (area under the curve (AUC): 0.842; 95% CI 0.749 to 0.928) outperformed RF (AUC: 0.809; 95% CI 0.629 to 0.891) and LR (AUC: 0.701; 95% CI 0.573 to 0.825) for predicting 30-day mortality. To give clinicians an intuitive understanding of feature exploitation, we stratified features by the clinical domain. The cumulative feature importance in the fluid balance domain, ventilation domain, laboratory data domain, demographic and symptom domain, management domain and severity score domain was 0.253, 0.113, 0.177, 0.140, 0.152 and 0.165, respectively. We further used SHAP plots to illustrate associations between features and 30-day mortality in critically ill influenza patients. Conclusions We used a real-world data set and applied an ML approach, mainly XGBoost, to establish a practical and explainable mortality prediction model in critically ill influenza patients.
Childhood maltreatment and problematic alcohol use in young adulthood: the roles of cognitive vulnerability to depression and depressive symptoms

ABSTRACT Background Childhood maltreatment (CM) has been repeatedly linked to future problem drinking. Depression has been identified as a potential factor contributing to problematic alcohol use in maltreated individuals. However, depression has been operationalized as the presence or number of depression symptoms in the majority of previous studies. The role of other relevant measures of depression, such as depressive implicit associations, is not well understood. Objectives The present study addresses this gap in the literature by examining the mediating role of both depression symptoms and depressive implicit associations. Methods A community sample of young adults (N = 208, mean age = 19.7, 78.4% females) completed self-report measures of CM, depression symptoms, and problem drinking. Depressive implicit associations were assessed by a computer-based implicit association test (IAT). Structural equation modeling (SEM) was used to examine the direct link between CM and problem drinking as well as indirect links through depression symptoms and depressive implicit associations. Results CM was significantly associated with both depression symptoms (β = 0.35, p < .001) and depressive implicit associations (β = 0.36, p < .001). Additionally, CM was associated with problem drinking indirectly via depression symptoms during young adulthood (β = .06, p = .019). Conclusion Our study provides evidence for the role of depression symptoms, but not for depressive implicit associations, in linking CM and problem drinking. Treating depression in individuals with a history of CM may help to prevent problem drinking in this vulnerable population.
Concordance of SNP- and allele-based typing workflows in the context of a large-scale international Salmonella Enteritidis outbreak investigation

A large European multi-country Salmonella enterica serovar Enteritidis outbreak associated with Polish eggs was characterized by whole-genome sequencing (WGS)-based analysis, with various European institutes using different analysis workflows to identify isolates potentially related to the outbreak. The objective of our study was to compare the output of six of these different typing workflows (distance matrices of either SNP-based or allele-based workflows) in terms of cluster detection and concordance. To this end, we analysed a set of 180 isolates coming from confirmed and probable outbreak cases, which were representative of the genetic variation within the outbreak, supplemented with 22 unrelated contemporaneous S . enterica serovar Enteritidis isolates. Since the definition of a cluster cut-off based on genetic distance requires prior knowledge on the evolutionary processes that govern the bacterial populations in question, we used a variety of hierarchical clustering methods (single, average and complete) and selected the optimal number of clusters based on the consensus of the silhouette, Dunn2, and McClain–Rao internal validation indices. External validation was done by calculating the concordance with the WGS-based case definition (SNP-address) for this outbreak using the Fowlkes–Mallows index. Our analysis indicates that with complete-linkage hierarchical clustering combined with the optimal number of clusters, as defined by three internal validity indices, the six different allele- and SNP-based typing workflows generate clusters with similar compositions. Furthermore, we show that even in the absence of coordinated typing procedures, but by using an unsupervised machine learning methodology for cluster delineation, the various workflows that are currently in use by six European public-health authorities can identify concordant clusters of genetically related S . enterica serovar Enteritidis isolates; thus, providing public-health researchers with comparable tools for detection of infectious-disease outbreaks.
On Time: A Qualitative Study of Swedish Students’, Parents’ and Teachers’ Views on School Attendance, with a Focus on Tardiness

Tardiness is a common problem in many schools. It can be understood as an individual risk for future problematic behavior leading to absenteeism, school dropout, exclusion and later health problems. Tardiness can also be examined in relation to a broader social-ecological perspective on health. The aim of this study was to analyze students’, school staff’s and parents’ views on students’ tardiness in two Swedish schools. A focus group interview design was used with 21 school personnel, 21 students in grade nine and two parents. The data were analyzed by using thematic content analysis. The results illustrated the main theme—It depends on…—regarding what will happen if a student arrives late to school lessons. This finding is further explained by the subthemes about teachers’ signals and reactions and the responses from teachers and students. The conclusion showed the importance of organizing the school day more predictably for the students. Late arrival is a sign of shortcomings in a school organization. It is necessary to develop guidelines related to how to handle students’ late arrival based on predictable viewpoints but even more so on how to promote students’ sense of belonging and their interest in and motivation for going to school.
Micronucleus Assay: The State of Art, and Future Directions

During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing radiation-induced DNA damage. In this minireview, we focus on the position of MN among the other genotoxicity tests, its usefulness in different applications and visibility by international organizations, such as International Atomic Energy Agency, Organization for Economic Co-operation and Development and International Organization for Standardization. In addition, the mechanism of micronuclei formation is discussed. Finally, foreseen directions of the MN development are pointed, such as automation, buccal cells MN and chromothripsis phenomenon.
Similarities and Differences between Clear Cell Tubulo-Papillary and Conventional Clear Cell Renal Cell Carcinoma: A Comparative Phenotypical and Mutational Analysis

Background: Clear cell tubulo-papillary renal cell carcinoma (cctpRCC) is characterized by clear cell morphology, but differs from conventional clear cell carcinoma (ccRCC) for its indolent clinical behavior and genetic background. The differential diagnosis between the two is based on histology and immunohistochemistry (IHC). Methods: We performed a comparative case-control histological, IHC, and genetic analysis by next generation sequencing (NGS), to point out the differences in 10 cases of cctpRCC, and six controls of ccRCC with low stage and grade. Results: All 16 cases showed the IHC profile with cytokeratin 7, racemase, and carbonic anhydrase IX expected for the histological features of each tumor type. By contrast, the NGS mutation analysis that covered 207 amplicons of 50 oncogenes or tumor suppressor genes provided conflicting results. Among the 10 cctpRCC cases, eight (80%) were wild type for all of the genes in the panel, while two (20%) harbored VHL mutations typical of ccRCC. Three of the six (50%) ccRCC control cases showed expected VHL mutations; two (33%) harbored pathogenic mutations in the p53 or the CKIT genes; and one (16%) was wild type. Conclusion: We can assume that histology and ICH are not sufficient for a definitive diagnosis of cctpRCC or ccRCC. Although with a panel covering 50 genes, we found that 80% of cctpRCC were genetically silent; thus, suggesting an indolent biology of these tumors. The differential diagnosis between ccptRCC and ccRCC for the choice of the best therapeutic strategy likely requires the comprehensive evaluation of histology, IHC, and at least VHL mutations.
How Did Parents View the Impact of the Curriculum-Based HealthLit4Kids Program Beyond the Classroom?

The HealthLit4Kids program aims to build health literacy in a participatory and contextually relevant way. Whole-of-school and curriculum strategies aim to empower and build capacity to make informed health choices amongst students, teachers, parents, and their local community. The aim of this study was to evaluate the HealthLit4Kids program from the perspective of parents, using a Self-Determination Theory framework. This is one component within a larger evaluation of the program. Parents at four Australian primary schools were interviewed post-program. Qualitative data collected through parent interviews were analyzed thematically to identify themes, and coding checks were completed by experienced qualitative researchers. The three key themes identified were student engagement, behaviour change, and parent engagement. Findings also indicated that parents placed a high value on effective communication from schools and raised a range of health areas such as food and nutrition, physical activity, and mental health with the interviewer. Parent opinions of the HealthLit4Kids program were positive, with many reporting a perceived increase in their children’s ability to understand, communicate and act on health-related knowledge at home. The HealthLit4Kids program requires further research to determine its viability as an optimal pedagogical strategy for the health literacy development of primary school-aged children.