Miracle-dz/UniFAR-FTUs huggingface dataset:
Ablation of Calsequestrin-1, Ca2+ unbalance, and susceptibility to heat stroke

Introduction: Ca2+ levels in adult skeletal muscle fibers are mainly controlled by excitation-contraction (EC) coupling, a mechanism that translates action potentials in release of Ca2+ from the sarcoplasmic reticulum (SR) release channels, i.e. the ryanodine receptors type-1 (RyR1). Calsequestrin (Casq) is a protein that binds large amounts of Ca2+ in the lumen of the SR terminal cisternae, near sites of Ca2+ release. There is general agreement that Casq is not only important for the SR ability to store Ca2+, but also for modulating the opening probability of the RyR Ca2+ release channels. The initial studies: About 20 years ago we generated a mouse model lacking Casq1 (Casq1-null mice), the isoform predominantly expressed in adult fast twitch skeletal muscle. While the knockout was not lethal as expected, lack of Casq1 caused a striking remodeling of membranes of SR and of transverse tubules (TTs), and mitochondrial damage. Functionally, CASQ1-knockout resulted in reduced SR Ca2+ content, smaller Ca2+ transients, and severe SR depletion during repetitive stimulation. The myopathic phenotype of Casq1-null mice: After the initial studies, we discovered that Casq1-null mice were prone to sudden death when exposed to halogenated anaesthetics, heat and even strenuous exercise. These syndromes are similar to human malignant hyperthermia susceptibility (MHS) and environmental-exertional heat stroke (HS). We learned that mechanisms underlying these syndromes involved excessive SR Ca2+ leak and excessive production of oxidative species: indeed, mortality and mitochondrial damage were significantly prevented by administration of antioxidants and reduction of oxidative stress. Though, how Casq1-null mice could survive without the most important SR Ca2+ binding protein was a puzzling issue that was not solved. Unravelling the mystery: The mystery was finally solved in 2020, when we discovered that in Casq1-null mice the SR undergoes adaptations that result in constitutively active store-operated Ca2+ entry (SOCE). SOCE is a mechanism that allows skeletal fibers to use external Ca2+ when SR stores are depleted. The post-natal compensatory mechanism that allows Casq1-null mice to survive involves the assembly of new SR-TT junctions (named Ca2+ entry units) containing Stim1 and Orai1, the two proteins that mediate SOCE.
Exploring the contextual factors, behaviour change techniques, barriers and facilitators of interventions to improve oral health in people with severe mental illness: A qualitative study

People with severe mental illness (SMI) have significantly poorer oral health compared to people without SMI and interventions targetted to improve oral health in this population failed to show any long-term improvement. Interventions are influenced by many contextual factors ranging from individual to systems level. This study aimed to understand the contextual factors, behaviour change techniques of the available oral health interventions and explore the barriers to and facilitators for engagement with these interventions from the perspectives of people with SMI (service users) and related service providers. Intervention details were extracted from 12 intervention studies identified from a previous systematic review using the template for intervention description and replication checklist (TIDieR) and behaviour change techniques (BCTs) were coded using the behaviour change technique taxonomy v1. Sixteen individual BCTs were identified and out of which “4.1 instructions on how to perform the behaviour” (n = 9) and “6.1 demonstration of behaviour” (n = 6) were most frequently used BCTs. Video vignettes prepared from the different intervention components identified from existing studies were shown to service users and service providers in dyadic or one-to-one interview format to elicit their views on barriers and facilitators for engagement with the intervention components. Interviews were analysed using Framework analysis and were guided by theoretical domains framework (TDF); and capability, opportunity and motivation (COM-B) model of behaviour change. Main facilitators identified to increase capability, opportunity and motivation of service users were the involvement of carers/care coordinators and integration of dental and mental health care, provision of oral health/hygiene information/products at an appropriate level and provision of tailored support according to individual needs and preferences. Barriers identified were related to lack of communication skills of the service providers, provision of coordinated care, lack of support in visiting a dentist and navigating the payment system and long follow up times. Appropriate training was considered as a facilitator, and staff turnovers and workload were considered as main barriers by the service providers. The findings suggest that comprehensive interventions that target barriers and enhance facilitators from individual to systems level are needed to improve oral health outcomes of people with SMI.
A model for periodic blazars

We describe a scenario to explain blazar periodicities with timescales of $\sim$ few years. The scenario is based on a binary super-massive black hole (SMBH) system in which one of the two SMBH carries a jet. We discuss the various mechanisms that can cause the jet to precess and produce corkscrew patterns through space with a scale of $\sim$ few pc. It turns out that the dominant mechanism responsible for the precession is simply the imprint of the jet-carrying SMBH orbital speed on the jet. Gravitational deflection and Lense-Thirring precession (due to the gravitational field of the other SMBH) are second order effects. We complement the scenario with a kinematical jet model which is inspired to the spine-sheath structure observed in M87. One of the main advantages of such a structure is that it allows the peak of the synchrotron emission to scale with frequency according to $\nu F\propto \nu^{\xi}$ as the viewing angle is changed, where $\xi$ is not necessarily 3 or 4 as in the case of jets with uniform velocity, but can be $\xi \sim 1$. Finally, we apply the model to the source PG1553+113, which has been recently claimed to show a $T_{\rm obs}=(2.18\pm 0.08)\text{ yr}$ periodicity. We are able to reproduce the optical and gamma-ray light curves and multiple synchrotron spectra simultaneously. We also give estimates of the source mass and size.
Maize monoculture causes niacin deficiency in free-living European brown hares and impairs local population development

Maize (Zea mays) is the most produced crop worldwide and the second most important bio-energy plant. Huge maize monoculture is considered a threat to biodiversity in agricultural landscapes and may also contribute to the decline of European brown hares (Lepus europaeus, Pallas 1778). Indeed, the intensification of agriculture has been identified as one of the main factors responsible for the decline of brown hare populations. A reason why large maize cultures can be particularly detrimental to animals consuming this plant is its poor nutritional value with respect to niacin. In this study, we investigated the effects of the proportion of area under maize crops on liver concentrations of niacin in free-living hares, on the reproductive output of does (females), and on the development of local populations, at nine study sites in Lower Austria. Hare numbers were estimated from spotlight counts in spring and autumn. Liver samples and uteri were obtained from hares shot in the same areas during regular autumn hunts. Number of offspring born to an individual female during the preceding reproductive period was determined by counting placental scars. Our results show a significant negative effect of the area under maize crops on liver concentrations of niacin of does and on their reproductive output. Further, we found a significant negative effect of the area under maize on the development of a population. Altogether, our findings indicate that high proportions of the area under maize crops contribute to the decline of brown hares by reduced fecundity of does and impaired development of local populations.
Specific location of galactosylation in an afucosylated antiviral monoclonal antibody affects its FcγRIIIA binding affinity

Monoclonal antibodies (mAbs) comprise an essential type of biologic therapeutics and are used to treat diseases because of their anti-cancer and anti-inflammatory properties, and their ability to protect against respiratory infections. Its production involves post-translational glycosylation, a biosynthetic process that conjugates glycans to proteins, which plays crucial roles in mAb bioactivities including effector functions and pharmacokinetics. These glycans are heterogeneous and have diverse chemical structures whose composition is sensitive to manufacturing conditions, rendering the understanding of how specific glycan structures affect mAb bioactivity challenging. There is a need to delineate the effects of specific glycans on mAb bioactivity to determine whether changes in certain glycosylation profiles (that can occur during manufacturing) will significantly affect product quality. Using enzymatic transglycosylation with chemically-defined N-glycans, we show that galactosylation at a specific location of N-glycans in an afucosylated anti-viral mAb is responsible for FcγRIIIA binding and antibody-dependent cell-mediated cytotoxicity (ADCC) activity. We report a facile method to obtain purified asymmetric mono-galactosylated biantennary complex N-glycans, and their influence on bioactivity upon incorporation into an afucosylated mAb. Using ELISA, surface plasmon resonance and flow cytometry, we show that galactosylation of the α6 antenna, but not the α3 antenna, consistently increases FcγRIIIA binding affinity. We confirm its relevance in an anti-viral model of respiratory syncytial virus (RSV) using an adapted ADCC reporter assay. We further correlate this structure-function relationship to the interaction of the galactose residue of the α6 antenna with the protein backbone using 2D-1H-15N-NMR, which showed that galactosylation of at this location exhibited chemical shift perturbations compared to glycoforms lacking this galactose residue. Our results highlight the importance of identifying and quantifying specific glycan isomers to ensure adequate quality control in batch-to-batch and biosimilar comparisons.
Shortcomings of applying data science to improve professional football performance: Takeaways from a pilot intervention study

Positional tracking data allows football practitioners to derive features that describe patterns of player behavior and quantify performance. Existing research using tracking data has mostly focused on what occurred on the pitch, such as the determinants of effective passing. There have yet to be studies attempting to use findings from data science to improve performance. Therefore, 24 professional players (mean age = 21.6 years, SD = 5.7) were divided into a control team and an intervention team which competed against each other in a pre-test match. Metrics were gathered via notational analysis (number of passes, penalty box entries, shots on goal), and positional tracking data including pass length, pass velocity, defensive disruption (D-Def), and the number of outplayed opponents (NOO). D-Def and NOO were used to extract video clips from the pre-test that were shown to the intervention team as a teaching tool for 2 weeks prior to the post-test match. The results in the post-test showed no significant improvements from the pre-test between the Intervention Team and the Control Team for D-Def (F = 1.100, p = 0.308, η2 = 0.058) or NOO (F = 0.347, p = 0.563, η2 = 0.019). However, the Intervention Team made greater numerical increases for number of passes, penalty box entries, and shots on goal in the post-test match. Despite a positive tendency from the intervention, results indicate the transfer of knowledge from data science to performance was lacking. Future studies should aim to include coaches' input and use the metrics to design training exercises that encourage the desired behavior.
Benign thyroid disease and the risk of breast cancer: An updated systematic review and meta-analysis

Background The correlation between benign thyroid disease (BTD) and breast cancer (BC) has long been discussed. However, the definite relationship and potential mechanism between them are still disputed. The current meta-analysis aimed at performing a comprehensive assessment of the relationship between different types of benign thyroid disease and the risk of breast cancer, furthermore, assessing whether benign thyroid disease exerts an influence on the aggressiveness of breast cancer. Method A systematic literature search (PubMed, Web of Science, MEDLINE, and Embase databases) identified studies to evaluate the correlation between BTD and BC risk. Data were analyzed using version 16.0 STATA software, including the odds ratio (OR) and its corresponding 95% confidence intervals (CIs). Publication bias and quality assessment were conducted for the included studies. Result Overall, 18 studies involving 422,384 patients with BTD were incorporated. The outcome showed that autoimmune thyroiditis (OR: 2.56, 95%CI: 1.95–3.37, I2 = 0.0%, p=0.460), goiter (OR: 2.13, 95%CI: 1.19-3.79, I2 = 80.6%, p=0.000), and Graves’ disease (OR: 5.01, 95%CI: 1.49-16.82, I2 = 0.0%, p=0.358) was connected with a higher risk of BC. Both hypothyroidism (OR: 0.82, 95%CI: 0.64-1.04, I2 = 85.0%, p=0.000) and hyperthyroidism (OR: 1.07, 95%CI: 0.93-1.24, I2 = 24.9%, p=0.206) had no significant association with the risk of BC. Additionally, the pooled analysis showed no apparent correlation between BTD and aggressiveness of BC. However, subgroup analysis indicated a positive relationship between BTD and aggressiveness of BC in the Europe subgroup (HR: 2.05, 95%CI: 1.32-3.17, I2 = 86.4%, p=0.000). Conclusion Autoimmune thyroiditis, goiter, and Graves’ disease are connected with an increased risk of BC. Furthermore, subgroup analysis suggested that BTD increases the aggressiveness of BC in the European population geographically. Nevertheless, further research is needed to prove these discoveries.
The Ifng antisense RNA 1 (IFNG-AS1) and growth arrest-specific transcript 5 (GAS5) are novel diagnostic and prognostic markers involved in childhood ITP

Background/aim: IFNG-AS1 is a long noncoding RNA that works as an enhancer for the Interferon-gamma (IFN-γ) transcript. GAS5 (growth arrest-specific 5) is a lncRNA that is associated with glucocorticoid resistance. Aberrant expressions of IFNG-AS1 and GAS5 are directly linked to numerous autoimmune disorders but their levels in childhood ITP are still obscure. This study aims to elucidate expressions of target lncRNAs in childhood ITP and their association with pathophysiology and clinical features of the disease as well as their association with types and treatment responses. Method: The fold changes of target lncRNAs in blood samples from children with ITP and healthy controls were analyzed using quantitative real-time PCR (qRT-PCR). Results: There were overexpressed lncRNAs IFNG-AS1 and GAS5 in serum of childhood ITP patients [(median (IQR) = 3.08 (0.2–22.39) and 4.19 (0.9–16.91) respectively, Also, significant higher IFNG-AS1 and GAS5 (p < 0.05) were present in persistent ITP (3–12 months) [ median (IQR) = 4.58 (0.31–22.39) and 3.77 (0.87–12.36) respectively] or chronic ITP (>12 months) [ median (IQR) = 5.6 (0.25–12.59) and 5.61 (1.15–16.91) respectively] when compared to newly diagnosed <3 months patients [IFNG-AS1 median (IQR) = 1.21 (0.2–8.95), and GAS5 median (IQR) = 1.07 (0.09–3.55)]. Also, significant higher lncRNAs IFNG-AS1 and GAS5 were present in patients with partial response to treatment [IFNG-AS1 median (IQR) = 4.15 (0.94–19.25), and GAS5 (median (IQR) = 4.25 (0.81–16.91)] or non-response [IFNG-AS1 median (IQR) = 4.19 (1.25–22.39) and GAS5 median (IQR) = 5.11 (2.34–15.27)] when compared to patients who completely responded to treatment (IFNG-AS1 median (IQR) = 2.09 (0.2–14.58) and GAS5 (median (IQR) = 2.51 (0.09–10.33). In addition, following therapy, the expressions of IFNG-AS1 and GAS5 are significantly negatively correlated with platelet count. Conclusion: Findings suggest that lncRNAs IFNG-AS1 and GAS5 are novel diagnostic and prognostic genetic markers for childhood ITP that can aid in a precise prediction of the disease’s progress at the time of diagnosis and could be a useful tool for treatment planning.
What breaks the flow of reading? A study on characteristics of attentional disruption during digital reading

Reading is increasingly taking place on digital media, which are vectors of attentional disruption. This manuscript aims to characterize attentional disruption during reading on a computer screen in an ecological environment. To this end, we collected information relating to reader interruptions (number, type, duration, position, mental effort, and valence) and self-caught mind wandering (occurrence, position) throughout the reading session for high and low media multitaskers in their own specific ecological environment, at home. Comprehension of the narrative text was assessed both with surface and inferential questions. In total, 74 participants (M = 22.16, SD = 2.35) took part in the experiment. They reported attentional disruptions on average every 4 mins during reading. Moreover, there were more attentional disruptions during the first half of the text. Most interruptions were short and little mental effort was required to process them. We made a distinction between media-related and media-unrelated related interruptions. Multiple linear regression analyses showed that media-unrelated interruptions were actually related to better performance for both inferential and surface level questions. Furthermore, media-related interruptions were more frequent for high than low media multitaskers. Pleasure experienced when reading the text was also a significant predictor of comprehension. The results are discussed with regard to Long-Term Working Memory and strategies that the readers could have implemented to recover the thread of their reading.
Biomass production and nutrient use efficiency in white Guinea yam (Dioscorea rotundata Poir.) genotypes grown under contrasting soil mineral nutrient availability

Yam (Dioscorea spp.) is of great importance to food security, especially in West Africa. However, the loss of soil fertility due to dwindling fallow lands with indigenous nutrient supply poses a challenge for yam cultivation. This study aimed to determine shoot and tuber biomass and nutrient use efficiency of white Guinea yam (Dioscorea rotundata) grown under low- and high-NPK conditions. Six white Guinea yam genotypes were used in field experiments conducted at Ibadan, Nigeria. Experiments were conducted with low soil NPK conditions with zero fertilizer input and high soil NPK conditions with mineral fertilizer input. Differences in response to soil NPK conditions, nutrient uptake, and nutrient use efficiency (apparent nutrient recovery efficiency) were observed among the tested genotypes. The genotypes TDr1499 and TDr1649, with high soil fertility susceptibility index (SFSI>1) and an increase in shoot and tuber biomass with fertilizer input, were recognized as susceptible to soil NPK conditions. There was a marked difference in apparent nutrient recovery efficiency; however, there was no varietal difference in physiological efficiency. Differences in apparent nutrient recovery efficiency among genotypes affected the fertilizer response (or susceptibility to soil NPK conditions) and the nutrient uptake. In contrast, the genotype TDr2029, with SFSI<1 and low reduction in shoot and tuber production between non-F and +F conditions, was recognized as a less susceptible genotype to soil NPK status. It was revealed that NPK fertilization did not reduce tuber dry matter content, regardless of genotype differences in susceptibility to soil NPK conditions. Hence, this could be helpful to farmers because it implies that yield can be increased without reducing tuber quality through a balanced application of soil nutrients. Our results highlight genotypic variation in sensitivity to the soil NPK availability, nutrient uptake, and nutrient use efficiency white Guinea yam. Differences in susceptibility to soil NPK conditions could be due to the genotypic variations in nutrient recovery efficiency white Guinea yam. Our findings could contribute to breeding programs for the development of improved white Guinea yam varieties that enhance productivity in low soil fertility conditions with low and high-input farming systems.
Comparison of out-of-plane short axis with in-plane long axis for ultrasound-guided radial arterial cannulation: A systematic review with trial sequential analysis of randomised controlled trials

Background It is controversial whether the short-axis out-of-plane or long-axis in-plane approach is a better needling technique for ultrasound-guidance radial artery cannulation. We aimed to compare the efficacy and safety of the two approaches for ultrasound-guided radial artery cannulation. Methods A systematic search of Medline, Embase, the Cochrane Library, and Web of Science for relevant articles published until 1 May 2021 was conducted. Randomised controlled trials comparing the long-axis in-plane with short-axis out-of-plane approaches were included. Review Manager software version 5.4, STATA version 14.2, and trial sequential analysis (TSA) version 0.9. 5.10 Beta were used for statistical analysis. Risk of bias and methodological quality of all studies included in this review were assessed according to the Cochrane Collaboration tool for the risk of bias. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity. Results The rate of cannula insertion success on the first attempt was similar between the short-axis out-of-plane and long-axis in-plane approaches (RR = 1.03; 95% CI: 0.83 to 1.28; P = 0.79; I2 = 83.0%). No significant differences were observed in total time to successful cannulation between the two approaches (MD = –3.9; 95% CI:-18.30 to 10.49; P = 0.6; I2 = 97%). However, the required information size for the success rate of the first attempt and total time to successful cannulation was not reached. Conclusion It remains inconclusive whether short-axis out-of-plane is a better choice for radial arterial cannulation than the long-axis in-plane approach. Inexperienced operators may need more attempts and longer ultrasound location time with the short-axis out-of-plane technique. Systematic review registration [https://www.crd. york.ac. uk/prospero/], identifier [CRD42021236098].