Miracle-dz/UniFAR-FTUs huggingface dataset:
Is Hemoglobin Mass at Age 16 a Predictor for National Team Membership at Age 25 in Cross-Country Skiers and Triathletes?

We recently measured the development of hemoglobin mass (Hbmass) in 10 Swiss national team endurance athletes between ages 16–19. Level of Hbmass at age 16 was an important predictor for Hbmass and endurance performance at age 19. The aim was to determine how many of these young athletes were still members of Swiss national teams (NT) at age 25, how many already terminated their career (TC), and whether Hbmass at ages 16 and 19 was different between the NT and TC group. We measured Hbmass using the optimized carbon monoxide re-breathing technique in 10 high-performing endurance athletes every 0.5 years beginning at age 16 and ending at age 19. At age 25, two athletes were in the NT group and eight athletes in the TC group. Mean absolute, body weight-, and lean body mass (LBM) related Hbmass at age 16 was 833 ± 61 g, 13.7 ± 0.2 g/kg and 14.2 ± 0.2 g/kg LBM in the NT group and 742 ± 83 g, 12.2 ± 0.7 g/kg and 12.8 ± 0.8 g/kg LBM in the TC group. At age 19, Hbmass was 1,042 ± 89 g, 14.6 ± 0.2 g/kg and 15.4 ± 0.2 g/kg LBM in the NT group and 863 ± 109 g, 12.7 ± 1.1 g/kg and 13.5 ± 1.1 g/kg LBM in the TC group. Body weight- and LBM related Hbmass were higher in the NT group than in the TC group at ages 16 and 19 (p < 0.05). These results indicate, that Hbmass at ages 16 and 19 possibly could be an important predictor for later national team membership in endurance disciplines.
Multi-modal Mapping of the Face Selective Ventral Temporal Cortex–A Group Study With Clinical Implications for ECS, ECoG, and fMRI

Face recognition is impaired in patients with prosopagnosia, which may occur as a side effect of neurosurgical procedures. Face selective regions on the ventral temporal cortex have been localized with electrical cortical stimulation (ECS), electrocorticography (ECoG), and functional magnetic resonance imagining (fMRI). This is the first group study using within-patient comparisons to validate face selective regions mapping, utilizing the aforementioned modalities. Five patients underwent surgical treatment of intractable epilepsy and joined the study. Subdural grid electrodes were implanted on their ventral temporal cortices to localize seizure foci and face selective regions as part of the functional mapping protocol. Face selective regions were identified in all patients with fMRI, four patients with ECoG, and two patients with ECS. From 177 tested electrode locations in the region of interest (ROI), which is defined by the fusiform gyrus and the inferior temporal gyrus, 54 face locations were identified by at least one modality in all patients. fMRI mapping showed the highest detection rate, revealing 70.4% for face selective locations, whereas ECoG and ECS identified 64.8 and 31.5%, respectively. Thus, 28 face locations were co-localized by at least two modalities, with detection rates of 89.3% for fMRI, 85.7% for ECoG and 53.6 % for ECS. All five patients had no face recognition deficits after surgery, even though five of the face selective locations, one obtained by ECoG and the other four by fMRI, were within 10 mm to the resected volumes. Moreover, fMRI included a quite large volume artifact on the ventral temporal cortex in the ROI from the anatomical structures of the temporal base. In conclusion, ECS was not sensitive in several patients, whereas ECoG and fMRI even showed activation within 10 mm to the resected volumes. Considering the potential signal drop-out in fMRI makes ECoG the most reliable tool to identify face selective locations in this study. A multimodal approach can improve the specificity of ECoG and fMRI, while simultaneously minimizing the number of required ECS sessions. Hence, all modalities should be considered in a clinical mapping protocol entailing combined results of co-localized face selective locations.
Comparative studies of the seven human coronavirus envelope proteins using topology prediction and molecular modelling to understand their pathogenicity

Human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 are less virulent and cause mild, self-limiting respiratory tract infections, while SARS-CoV, MERS-CoV, and SARS-CoV-2, are more virulent and have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoVs infections, may provide insight into this disparate severity of the disease. Topology prediction programs and 3D modelling software was used to predict and visualize structural aspects of the hCoV E protein related to its functions. All seven hCoV E proteins largely adopted different topologies, with some distinction between the more virulent and less virulent ones. The 3D models refined this distinction, showing the PDZ-binding motif (PBM) of SARS-CoV, MERS-CoV, and SARS-CoV-2 to be more flexible than the PBM of hCoVs 229E, NL63, OC43, and HKU1. We speculate that the increased flexibility of the PBM may provide the more virulent hCoVs with a greater degree of freedom, which can allow them to bind to different host proteins and can contribute to a more severe form of the disease. This is the first paper to predict the topologies and model 3D structures of all seven hCoVs E proteins, providing novel insights for possible drug and/or vaccine development.
Large spontaneous spin splitting in gate-controlled two-dimensional electron gases at normal In0.75Ga0.25As/In0.75Al0.25As heterojunctions

Amounts of spontaneous spin splittings were estimated from low-temperature magnetoresistances in two-dimensional electron gases created at In0.75Ga0. 25As/In0.75Al0. 25As heterojunctions under a gate bias. Typical sheet electron densities and mobilities in the raw wafers were ∼1.0×1012/cm2 and 2–5×105 cm2/V s at 1.5 K, respectively. A maximum spin-orbit coupling constant αzero of ∼30(×10−12 eV m) was obtained for the van der Pauw sample. In gated Hall-bar samples, a decrease in the αzero value with decreasing gate voltage (Vg) was first confirmed in a normal heterojunction. The main origin for such a large αzero, which is a few times larger than any previously reported, was found to be a structure-dependent so-called interface contribution in the Rashba term.
The Knockout for G Protein-Coupled Receptor-Like PfSR25 Increases the Susceptibility of Malaria Parasites to the Antimalarials Lumefantrine and Piperaquine but Not to Medicine for Malaria Venture Compounds

Previously we have reported that the G protein-coupled receptor (GPCR)-like PfSR25 in Plasmodium falciparum is a potassium (K+) sensor linked to intracellular calcium signaling and that knockout parasites (PfSR25-) are more susceptible to oxidative stress and antimalarial compounds. Here, we explore the potential role of PfSR25 in susceptibility to the antimalarial compounds atovaquone, chloroquine, dihydroartemisinin, lumefantrine, mefloquine, piperaquine, primaquine, and pyrimethamine and the Medicine for Malaria Venture (MMV) compounds previously described to act on egress/invasion (MMV006429, MMV396715, MMV019127, MMV665874, MMV665878, MMV665785, and MMV66583) through comparative assays with PfSR25- and 3D7 parasite strains, using flow cytometry assays. The IC50 and IC90 results show that lumefantrine and piperaquine have greater activity on the PfSR25- parasite strain when compared to 3D7. For MMV compounds, we found no differences between the strains except for the compound MMV665831, which we used to investigate the store-operated calcium entry (SOCE) mechanism. The results suggest that PfSR25 may be involved in the mechanism of action of the antimalarials lumefantrine and piperaquine. Our data clearly show that MMV665831 does not affect calcium entry in parasites after we depleted their internal calcium pools with thapsigargin. The results demonstrated here shed light on new possibilities on the antimalarial mechanism, bringing evidence of the involvement of the GPCR-like PfSR25.
Aptamer Turn-On SERS/RRS/Fluorescence Tri-mode Platform for Ultra-trace Urea Determination Using Fe/N-Doped Carbon Dots

Sensitive and selective methods for the determination of urea in samples such as dairy products are important for quality control and health applications. Using ammonium ferric citrate as a precursor, Fe/N-codoped carbon dots (CDFeN) were prepared by a hydrothermal procedure and characterized in detail. CDFeN strongly catalyzes the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) by H2O2 to turn on an indicator molecular reaction, forming an oxidized tetramethylbenzidine (TMBox) probe with surface-enhanced Raman scattering, resonance Rayleigh scattering, and fluorescence (SERS, RRS, and FL) signals at 1,598 cm−1, 370 nm, and 405 nm, respectively. The urea aptamer (Apt) can turn off the indicator reaction to reduce the tri-signals, and the addition of urea turns on the indicator reaction to linearly enhance the SERS/RRS/FL intensity. Thus, a novel Apt turn-on tri-mode method was developed for the assay determination of ultra-trace urea with high sensitivity, good selectivity, and accuracy. Trace adenosine triphosphate and estradiol can also be determined by the Apt-CDFeN catalytic analytical platform.
Tenofovir Disoproxil Fumarate Is Superior to Entecavir in Reducing Hepatitis B Surface Antigen for Chronic Hepatitis B in China: 2-Year Comprehensive Comparative Result of a Matched Comparative Study

Aim: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are equally recommended as the first-line antiviral treatments for chronic hepatitis B (CHB) at present. We aimed to compare the long-term efficacy and safety between ETV and TDF therapy in CHB patients who had not received nucleoside analog treatment. Method: In this single-center retrospective study, 414 patients who received ETV (290 patients) or TDF (124 patients) therapy at our center from January 2017 to May 2019 were included. To reduce the imbalance of baseline variables, propensity score matching (PSM) was employed to yield 124 pairs of patients at a ratio of 1:1 based on the treatment regimen. Result: After PSM, the cumulative rate of patients who achieved complete virological response (CVR) was not different by drug therapy at each inspection time (1, 3, 6, 12, 18, and 24 months). Subgroup analysis on HBeAg status and level of HBV DNA demonstrated that evolution of proportion of achieving CVR was not significantly different between groups. Despite the insignificant incidence of HBsAg seroclearance in either group, patients in TDF group achieved higher on-treatment HBsAg decline at each inspection time (1, 3, 6, 9, 12, 18, and 24 months), 0.39, 0.51, 0.61, 0.64, 0.68, 0.76, and 0.91 log IU/mL, respectively; while the corresponding reduction were 0.27, 0.37, 0.40, 0.45, 0.48, 0.55, and 0.66 log IU/mL in ETV group (p < 0.05). In subgroup analysis, we found that the significant difference still existed in patients with high baseline HBsAg level (>3 log IU/mL). Additionally, the proportion of patients who achieved on-treatment HBsAg decline >1 log IU/mL in TDF and ETV group was 33.3 and 17.1% (p < 0.01) at the 12th month, 44.4 and 29.5% (p = 0.03) at the 24th month, respectively. Mean increase in serum creatinine from baseline was 0.10 and 0.08 mg/dL in TDF and ETV group (p = 0.11), with no patient experienced acute kidney injury. Conclusions: TDF has higher potency in reducing HBsAg than ETV in this study. Considering the effect still existed in patients with high HBsAg level (>3 log IU/mL), TDF might be a superior therapeutic regimen combining with its relatively safety.
Motivational and Emotional Orientation, Engagement, and Achievement in Mathematics. A Case Study With One Sixth-Grade Classroom Working With an Electronic Textbook on Fractions

Interactive and adaptive scaffolds implemented in electronic mathematics textbooks bear high potential for supporting students individually in learning mathematics. In this paper, we argue that emotional and behavioral engagement may account for the effectiveness of such digital curriculum resources. Following the general model for determinants and course of motivated action, we investigated the relationship between students’ domain-specific motivational and emotional orientations (person)—while working with an electronic textbook on fractions (situation), their emotional and behavioral engagement while learning (action), and their achievement after tuition (outcome). We conducted a case-study with N = 27 students from one sixth-grade classroom, asking about the relationship between students’ motivational and emotional orientations and their emotional and behavioral engagement, and whether emotional and behavioral engagement are unique predictors of students’ cognitive learning outcomes while working with an e-textbook. For that, we designed a four-week-intervention on fractions using an e-textbook on iPads. Utilizing self-reports and process data referring to students’ interactions with the e-textbook we aimed to describe if and how students make use of the offered learning opportunities. Despite being taught in the same classroom, results indicated large variance in students’ motivational and emotional orientations before the intervention, as well as in their emotional and behavioral engagement during the intervention. We found substantial correlations between motivational and emotional orientations (i.e., anxiety, self-concept, and enjoyment) and emotional engagement (i.e., intrinsic motivation, competence and autonomy support, situational interest, and perceived demand)—with positive orientations being associated with positive emotional engagement, as expected. Although the correlations between orientations and behavioral engagement (i.e., task, exercise, and hint count, problem solving time, and feedback time) also showed the expected directions, effect sizes were smaller than for emotional engagement. Generalized linear mixed models revealed that emotional engagement predicted cognitive learning outcomes uniquely, while for behavioral engagement the interaction with prior knowledge was a significant predictor. Taken together, they accounted for a variance change of 44% in addition to prior knowledge. We conclude that when designing digital learning environments, promoting engagement—in particular in students who share less-promizing prerequisites—should be considered a key feature.
Wnt Inhibition Sensitizes PD-L1 Blockade Therapy by Overcoming Bone Marrow-Derived Myofibroblasts-Mediated Immune Resistance in Tumors

Cancer-associated fibroblasts (CAFs) has been recognized as one cause of tumor resistance to immune checkpoint blockade therapy, but the underlying mechanisms still remain elusive. In the present study, a bone marrow-derived CAF (BMF) -rich tumor model is successfully established by subcutaneously mixed inoculation of BMFs and tumor cells into mice and the BMF-mixed tumor xenografts are demonstrated to be resistant to anti-PD-L1 antibody immunotherapy compared to the mere tumor xenografts. In vitro assays via the co-culture system of BMFs and tumor cells indicate that the co-cultured BMFs are induced to overexpress PD-L1, while there is no such a phenomenon in the co-cultured cancer cells. The further knock-out of PD-L1 in BMFs rescues the sensitivity of BMF-mixed tumor xenografts to PD-L1 blockade therapy. Mechanistically, via the microarray assay, we identify that the upregulation of PD-L1 in BMFs stimulated by cancer cells is medicated by the activation of the Wnt/β-catenin signaling pathway in BMFs. Moreover, the administration of Wnt/β-catenin signaling inhibitors, including XAV-939 and Wnt-C59, distinctly inhibits the upregulation of PD-L1 expression in the co-cultured BMFs. The further combination administration of XAV-939 significantly potentiates the therapeutic outcome of PD-L1 blockade therapy in BMF-mixed tumors. In summary, our study demonstrates that Wnt inhibition augments PD-L1 blockade efficacy by overcoming BMF-mediated immunotherapy resistance.
Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein–Barr Virus-Specific T Cell Therapy

Background: Increasing evidence indicates a role for Epstein–Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment. Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy. Methods: We assessed participants 2 and 3 years after completion of T cell therapy. Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product. Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.
The PI3K∂-Selective Inhibitor Idelalisib Induces T- and NK-Cell Dysfunction Independently of B-Cell Malignancy-Associated Immunosuppression

B-cell receptors, multiple receptor tyrosine kinases, and downstream effectors are constitutively active in chronic lymphocytic leukemia (CLL) B cells. Activation of these pathways results in resistance to apoptosis and enhanced survival of the leukemic cells. Idelalisib is a highly selective inhibitor of the PI3K p110∂ isoform and is approved for the treatment of CLL in patients with relapsed/refractory disease or in those harboring 17p deletions or tp53 mutations. Despite the initial excitement centered around high response rates in clinical trials of idelalisib, its therapeutic success has been hindered by the incidence of severe opportunistic infections. To examine the potential contribution of idelalisib to the increased risk of infection, we investigated the effects of idelalisib on the immune cell compartments of healthy donors (HDs) and CLL patients. PI3K∂ blockade by idelalisib reduced the expression levels of inhibitory checkpoint molecules in T cells isolated from both HDs and CLL patients. In addition, the presence of idelalisib in cultures significantly decreased T-cell-mediated cytotoxicity and granzyme B secretion, as well as cytokine secretion levels in both cohorts. Furthermore, idelalisib reduced the proliferation and cytotoxicity of HD NK cells. Collectively, our data demonstrate that both human T and NK cells are highly sensitive to PI3K∂ inhibition. Idelalisib interfered with the functions of T and NK cell cells from both HDs and CLL patients. Therefore, idelalisib might contribute to an increased risk of infections regardless of the underlying B-cell malignancy.
Long-Lived Species of Bivalves Exhibit Low MT-DNA Substitution Rates

Bivalves represent valuable taxonomic group for aging studies given their wide variation in longevity (from 1–2 to >500 years). It is well known that aging is associated to the maintenance of Reactive Oxygen Species homeostasis and that mitochondria phenotype and genotype dysfunctions accumulation is a hallmark of these processes. Previous studies have shown that mitochondrial DNA mutation rates are linked to lifespan in vertebrate species, but no study has explored this in invertebrates. To this end, we performed a Bayesian Phylogenetic Covariance model of evolution analysis using 12 mitochondrial protein-coding genes of 76 bivalve species. Three life history traits (maximum longevity, generation time and mean temperature tolerance) were tested against 1) synonymous substitution rates (dS), 2) conservative amino acid replacement rates (Kc) and 3) ratios of radical over conservative amino acid replacement rates (Kr/Kc). Our results confirm the already known correlation between longevity and generation time and show, for the first time in an invertebrate class, a significant negative correlation between dS and longevity. This correlation was not as strong when generation time and mean temperature tolerance variations were also considered in our model (marginal correlation), suggesting a confounding effect of these traits on the relationship between longevity and mtDNA substitution rate. By confirming the negative correlation between dS and longevity previously documented in birds and mammals, our results provide support for a general pattern in substitution rates.
The Self-Regulation of Learning – Self-Report Scale for Sport Practice: Validation of an Italian Version for Football

Self-regulation of learning (SRL) is a key psychological factor that supports young athletes aiming to reach the elite level by promoting their involvement in deliberate practice. We contributed to the validation of the Italian version of the Bartulovic et al. (2017) Self-Regulation of Learning – Self-Report Scale for Sport Practice by testing its factorial structure, reliability, and measurement invariance among elite and non-elite football players, involving 415 male professional, semi-professional, and amateur youth academy players (Mage = 16.2, SD = 1.51). The original six-factor structure (planning, reflection, effort, self-efficacy, self-monitoring, and evaluation) did not fit the data well and a five-factor solution (where self-monitoring and evaluation items load on the same factor, named “self-supervision”) was a better fit. This five-factor solution was measurement invariant across groups of elite and non-elite athletes. We found that elite athletes scored significantly higher than non-elite ones in each SRL subprocess. Implications for future validation studies and for the use of this tool are discussed.
Use of Artificial Intelligence and Machine Learning for Discovery of Drugs for Neglected Tropical Diseases

Neglected tropical diseases continue to create high levels of morbidity and mortality in a sizeable fraction of the world’s population, despite ongoing research into new treatments. Some of the most important technological developments that have accelerated drug discovery for diseases of affluent countries have not flowed down to neglected tropical disease drug discovery. Pharmaceutical development business models, cost of developing new drug treatments and subsequent costs to patients, and accessibility of technologies to scientists in most of the affected countries are some of the reasons for this low uptake and slow development relative to that for common diseases in developed countries. Computational methods are starting to make significant inroads into discovery of drugs for neglected tropical diseases due to the increasing availability of large databases that can be used to train ML models, increasing accuracy of these methods, lower entry barrier for researchers, and widespread availability of public domain machine learning codes. Here, the application of artificial intelligence, largely the subset called machine learning, to modelling and prediction of biological activities and discovery of new drugs for neglected tropical diseases is summarized. The pathways for the development of machine learning methods in the short to medium term and the use of other artificial intelligence methods for drug discovery is discussed. The current roadblocks to, and likely impacts of, synergistic new technological developments on the use of ML methods for neglected tropical disease drug discovery in the future are also discussed.