Miracle-dz/UniFAR-FTUs huggingface dataset:
Skeletal muscle mitochondrial adaptations to maximal strength training in older adults.

Maximal Strength Training (MST) results in robust improvements in skeletal muscle force production, efficiency, and mass. However, the effects of MST on muscle mitochondria is still unknown. Accordingly, the purpose of this study was to examine, from the molecular level to whole-muscle, mitochondrial adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older adults using immunoblotting, spectrophotometry, high-resolution respirometry in permeabilized muscle fibers, in vivo31P magnetic resonance spectroscopy (31P-MRS) and gas exchange. As anticipated, MST resulted in an increased isometric knee-extensor force from 133±36 to 147±49 Nm (P<0.05) and quadriceps muscle volume from 1410±103 to 1555±455 cm3 (P<0.05). Mitochondrial complex (I-V) protein abundance and citrate synthase activity were not significantly altered by MST. Assessed ex vivo, maximal ADP-stimulated respiration (state 3CI+CII, PRE: 23±6 and POST: 14±5 ρM·mg-1·s-1, P<0.05), was decreased by MST, predominantly, as a result of a decline in complex I linked respiration (P<0.05). Additionally, state 3 free-fatty acid linked respiration was decreased following MST (PRE: 19±5 and POST: 14±3 ρM·mg-1·s-1, P<0.05). Assessed in vivo, MST slowed the PCr recovery time constant (PRE: 49±13 and POST: 57±16 s, P<0.05) and lowered, by ~20% (P=0.055), the quadriceps peak rate of oxidative ATP synthesis, but did not significantly alter the oxidation of lipid. Although these, likely qualitative, mitochondrial adaptations are potentially negative in terms of skeletal muscle energetic capacity, they need to be considered in light of the many improvements in muscle function that MST affords older adults.
The Number and Position of Orai3 Units within Heteromeric Store-Operated Ca2+ Channels Alter the Pharmacology of ICRAC

Store-operated heteromeric Orai1/Orai3 channels have been discussed in the context of aging, cancer, and immune cell differentiation. In contrast to homomeric Orai1 channels, they exhibit a different pharmacology upon application of reactive oxygen species (ROS) or 2-aminoethoxydiphenyl borate (2-APB) in various cell types. In endogenous cells, subunit composition and arrangement may vary and cannot be defined precisely. In this study, we used patch-clamp electrophysiology to investigate the 2-APB profile of store-operated and store-independent homomeric Orai1 and heteromeric Orai1/Orai3 concatenated channels with defined subunit compositions. As has been shown previous, one or more Orai3 subunit(s) within the channel result(s) in decreased Ca2+ release activated Ca2+ current (ICRAC). Upon application of 50 µM 2-APB, channels with two or more Orai3 subunits exhibit large outward currents and can be activated by 2-APB independent from storedepletion and/or the presence of STIM1. The number and position of Orai3 subunits within the heteromeric store-operated channel change ion conductivity of 2-APB-activated outward current. Compared to homomeric Orai1 channels, one Orai3 subunit within the channel does not alter 2-APB pharmacology. None of the concatenated channel constructs were able to exactly simulate the complex 2-APB pharmacology observed in prostate cancer cells. However, 2-APB profiles of prostate cancer cells are similar to those of concatenated channels with Orai3 subunit(s). Considering the presented and previous results, this indicates that distinct subtypes of heteromeric SOCE channels may be selectively activated or blocked. In the future, targeting distinct heteromeric SOCE channel subtypes may be the key to tailored SOCE-based therapies.
Aquatic stem group myriapods close a gap between molecular divergence dates and the terrestrial fossil record

Significance Most arthropod diversity is now found on land, with hexapods (insects), arachnids, and myriapods being major terrestrial radiations. Molecular dating consistently predicts that these groups have earlier evolutionary origins than are recorded by fossils. A reason for this difference between molecular- and fossil-based age estimates is that few candidates for marine or freshwater stem groups of these terrestrial lineages have been identified. A Devonian euthycarcinoid arthropod preserves details of the head shared by myriapods, adding support to the theory that they are each other’s closest relative. The fossil record of euthycarcinoids in the Cambrian, including trackways made on tidal flats, clarifies the marine-to-terrestrial transition in the myriapod lineage and reconciles molecular and fossil-based estimates for the timing of myriapod origins. Identifying marine or freshwater fossils that belong to the stem groups of the major terrestrial arthropod radiations is a longstanding challenge. Molecular dating and fossils of their pancrustacean sister group predict that myriapods originated in the Cambrian, much earlier than their oldest known fossils, but uncertainty about stem group Myriapoda confounds efforts to resolve the timing of the group’s terrestrialization. Among a small set of candidates for membership in the stem group of Myriapoda, the Cambrian to Triassic euthycarcinoids have repeatedly been singled out. The only known Devonian euthycarcinoid, Heterocrania rhyniensis from the Rhynie and Windyfield cherts hot spring complex in Scotland, reveals details of head structures that constrain the evolutionary position of euthycarcinoids. The head capsule houses an anterior cuticular tentorium, a feature uniquely shared by myriapods and hexapods. Confocal microscopy recovers myriapod-like characters of the preoral chamber, such as a prominent hypopharynx supported by tentorial bars and superlinguae between the mandibles and hypopharynx, reinforcing an alliance between euthycarcinoids and myriapods recovered in recent phylogenetic analysis. The Cambrian occurrence of the earliest euthycarcinoids supplies the oldest compelling evidence for an aquatic stem group for either Myriapoda or Hexapoda, previously a lacuna in the body fossil record of these otherwise terrestrial lineages until the Silurian and Devonian, respectively. The trace fossil record of euthycarcinoids in the Cambrian and Ordovician reveals amphibious locomotion in tidal environments and fills a gap between molecular estimates for myriapod origins in the Cambrian and a post-Ordovician crown group fossil record.
PCSK9 Regulates Nox2-Mediated Platelet Activation via CD36 Receptor in Patients with Atrial Fibrillation

Background: High levels of proprotein convertase subtilisin/kexin 9 (PCSK9) is predictive of cardiovascular events (CVEs) in atrial fibrillation (AF). We hypothesized that PCSK9 may directly induce platelet activation (PA). Methods: We measured platelet aggregation, recruitment, Thromboxane B2 (TxB2) formation and soluble P-selectin levels as markers of PA and soluble Nox2-derived peptide (sNox2-dp), H2O2, isoprostanes and oxidized Low-Density-Lipoprotein (oxLDL) to analyze oxidative stress (OS) in 88 patients having PCSK9 values < (n = 44) or > (n = 44) 1.2 ng/mL, balanced for age, sex and cardiovascular risk factors. Furthermore, we investigated if normal (n = 5) platelets incubated with PCSK9 (1.0–2.0 ng/mL) alone or with LDL (50 µg/mL) displayed changes of PA, OS and down-stream signaling. Results: PA and OS markers were significantly higher in patients with PCSK9 levels > 1.2 ng/mL compared to those with values < 1.2 ng/mL (p < 0.001). Levels of PCSK9 significantly correlated with markers of PA and OS. Platelets incubation with PCSK9 increased PA, OS and p38, p47 and Phospholipase A2 (PLA2) phosphorylation. These changes were amplified by adding LDL and blunted by CD36 or Nox2 inhibitors. Co-immunoprecipitation analysis revealed an immune complex of PCSK9 with CD36. Conclusions: We provide the first evidence that PCSK9, at concentration found in the circulation of AF patients, directly interacts with platelets via CD36 receptor and activating Nox2: this effect is amplified in presence of LDL.
MEHP interferes with mitochondrial functions and homeostasis in skeletal muscle cells

Abstract Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer frequently leached out from polyvinyl chloride (PVC) products and is quickly metabolized to its monoester equivalent mono(2-ethylhexyl) phthalate (MEHP) once enters organisms. Exposure to DEHP/MEHP through food chain intake has been shown to modified metabolism but its effect on the development of metabolic myopathy of skeletal muscle (SKM) has not been revealed so far. Here, we found that MEHP repressed myogenic terminal differentiation of proliferating myoblasts (PMB) and confluent myoblasts (CMB) but had weak effect on this process once it had been initiated. The transition of mitochondria (MITO) morphology from high efficient filamentary network to low efficient vesicles was triggered by MEHP, implying its negative effects on MITO functions. The impaired MITO functions was further demonstrated by reduced MITO DNA (mtDNA) level and SDH enzyme activity as well as highly increased reactive oxygen species (ROS) in cells after MEHP treatment. The expression of metabolic genes, including PDK4, CPT1b, UCP2, and HO1, was highly increased by MEHP and the promoters of PDK4 and CPT1b were also activated by MEHP. Additionally, the stability of some subunits in the oxidative phosphorylation system (OXPHOS) complexes was found to be reduced by MEHP, implying defective oxidative metabolism in MITO and which was confirmed by repressed palmitic acid oxidation in MEHP-treated cells. Besides, MEHP also blocked insulin-induced glucose uptake. Taken together, our results suggest that MEHP is inhibitory to myogenesis and is harmful to MITO functions in SKM, so its exposure should be avoided or limited.
Hypoxia regulates the differentiation and anti‐tumor effector functions of γδT cells in oral cancer

Hypoxia within the tumor microenvironment (TME) is a key factor contributing to immunosuppression in tumors, co‐relating with poor treatment outcome and decreased overall survival in advanced oral cancer (OC) patients. Vδ2 is a dominant subset of gamma delta T cells (γδT cells) present in the peripheral blood which exhibits potent anti‐tumor cytotoxicity and is evolving as a key player of anti‐cancer cellular therapy. However, the fate of γδT cells in hypoxic oral tumors remains elusive. In the present study, we compared the effect of hypoxia (1% O2) and normoxia (21% O2) on the expansion, proliferation, activation status, cytokine secretion and cytotoxicity of γδT cells isolated from OC patients and healthy individuals. Hypoxia‐exposed γδT cells exhibited reduced cytotoxicity against oral tumor cells. Our data demonstrated that hypoxia reduces the calcium efflux and the expression of degranulation marker CD107a in γδT cells, which explains the decreased anti‐tumor cytotoxicity of γδT cells observed under hypoxia. Hypoxia‐exposed γδT cells differentiated to γδT17 [γδ T cells that produce interleukin (IL)‐17] cells, which corroborated our observations of increased γδT17 cells observed in the oral tumors. Co‐culture of γδT cells with CD8 T cells in the presence of hypoxia showed that programmed cell death ligand 1 (PD‐L1)high γδT cells brought about apoptosis of programmed cell death 1 (PD‐1)high CD8 T cells which could be significantly reversed upon blocking PD‐1. Thus, future immunotherapeutic treatment modality for oral cancer may use a combined approach of blocking the PD‐1/PD‐L1 signaling and targeting hypoxia‐inducible factor 1α, which may help in reversing hypoxia‐induced immunosuppression.
Comparison of Side to Side vs End to Side Arteriovenous Fistula in upper limb for Hemodialysis

Introduction: Various methods of arteriovenous fistula (AVF) creation are in vogue, each having their own pros and cons. This study is aimed at comparing two most common methods of AVF creation side to side (STS) and end to side (ETS). Materials and Methods: This retrospective comparative study was conducted between January 2017 to January 2018. 57 patients were included in the study-they underwent AVF creation either by STS or by ETS method. Results: All total primary failure rate in the study was 12.28%, there was no statistically significant difference among two groups in regards to demography, operative time or complications except the finding that ETS has significant lower rate of postoperative venous hypertension than STS group. Conclusion: STS AVF has significantly higher rate of venous hypertension than ETS AVF.
Relative Effectiveness of the Cell-Cultured Quadrivalent Influenza Vaccine Compared to Standard, Egg-derived Quadrivalent Influenza Vaccines in Preventing Influenza-like Illness in 2017–2018

Abstract Background Influenza antigens may undergo adaptive mutations during egg-based vaccine production. In the 2017–2018 influenza season, quadrivalent, inactivated cell-derived influenza vaccine (ccIIV4) vaccine was produced using A(H3N2) seed virus propagated exclusively in cell culture, thus lacking egg adaptive changes. This United States study estimated relative vaccine effectiveness (rVE) of ccIIV4 vs egg-derived quadrivalent vaccines (egg-derived IIV4) for that season. Methods Vaccination, outcome, and covariate data were ascertained retrospectively from a electronic medical record (EMR) dataset and analyzed. The study cohort included patients ≥ 4 years of age. rVE was estimated against influenza-like illness (ILI) using diagnostic International Classification of Diseases, Ninth or Tenth Revision codes. The adjusted odds ratios used to derive rVE estimates were estimated from multivariable logistic regression models adjusted for age, sex, race/ethnicity, geographic region, and health status. Results Overall, 92 187 individuals had a primary care EMR record of ccIIV4 and 1 261 675 had a record of egg-derived IIV4. In the ccIIV4 group, 1705 narrowly defined ILI events occurred, and 25 645 occurred in the standard egg-derived IIV4 group. Crude rVE was 9.2% (95% confidence interval [CI], 4.6%–13.6%). When adjusted for age, sex, health status, comorbidities, and geographic region, the estimated rVE changed to 36.2% (95% CI, 26.1%–44.9%). Conclusions ccIIV4, derived from A(H3N2) seed virus propagated exclusively in cell culture, was more effective than egg-derived IIV4 in preventing ILI during the 2017–2018 influenza season. This result suggests that cell-derived influenza vaccines may have greater effectiveness than standard egg-derived vaccines.
Irreversible Electroporation in Pancreatic Cancer

Pancreatic cancer is the deadliest of the gastrointestinal tract with 5-year survival rates of less than 5%. Given common asymptomatic early disease course, most patients (50%) present with an already metastatic disease, while only 20% can undergo potentially curative resection. The remaining 30% present with locally advanced disease, defined as extended vascular encasement, where the risk of surgical therapy often outweighs its benefits. Traditional thermal local ablative modalities (RFA, MWA, or cryotherapy) have the disadvantage that they are not applicable in proximity to vital vascular structures, which are abundant in the peripancreatic region. Irreversible electroporation (IRE) is an emerging non-thermal alternative that induces apoptosis of tumor cells by the delivery of short repetitive impulses of high-voltage electric current. Given its mostly non-thermal modality, IRE is not hampered by a heat-sink-effect and is applicable with little risk around vascular structures, bile and pancreatic ducts. Recent research suggests that local tumor destruction through IRE improves overall survival, progression-free survival and quality of life in patients with locally advanced pancreatic cancer.
Accurate staging of reproduction development in Cadenza wheat by non-destructive spike analysis

Abstract Wheat is one of the most important crops in the world; however, loss of genetic variability and abiotic stress caused by variable climatic conditions threaten future productivity. Reproduction is critical for wheat yield; however, pollen development is amongst the developmental stages most sensitive to stresses such as heat, cold, or drought. A better understanding of how anther and pollen development is regulated is needed to help produce more resilient crops and ensure future yield increases. However, in cereals such as wheat, barley, and rice, flowers form within the developing pseudostem and therefore accurate staging of floral materials is extremely challenging. This makes detailed phenotypic and molecular analysis of floral development very difficult, particularly when limited plant material is available, for example with mutant or transgenic lines. Here we present an accurate approach to overcome this problem, by non-destructive staging of reproduction development in Cadenza, the widely used spring wheat research variety. This uses a double-scale system whereby anther and pollen development can be predicted in relation to spike size and spike position within the pseudostem. This system provides an easy, reproducible method that facilitates accurate sampling and analysis of floral materials, to enable anther and pollen developmental research.
Tipping the Scales: Factors Influencing the Decision to Report Child Maltreatment in Primary Care

Child maltreatment (CM) is an important public health issue linked to significant physical and mental health complications across the life span. Given the association between CM and health, general practitioners (GPs) and primary care nurses (PNs) are well-placed to identify and respond to this issue and are mandated to report suspected CM in many jurisdictions. Research has found that primary care doctors and nurses need support when responding to CM. This scoping review sought to answer the following question: What factors influence GPs and PNs decision to report CM when fulfilling their mandatory reporting duty? By exploring these factors, areas where support is needed were pinpointed. A systematic search was run across four databases: Medline (Ovid), PsycINFO, Embase, and CINAHL. Articles that reported on studies conducted in a location that had mandatory reporting legislation specific to CM and had a study population sampled from primary care were included in analysis. Thirty-three articles met the inclusion criteria. This review found that four principal factors influenced the decision to report CM: personal threshold of suspicion of abuse, relationship with the family, faith in the child protection system, and education and discussion. We conclude that improving the support and training to address these four areas may be beneficial for GPs and PNs in responding to CM.
Making football safer for women: a systematic review and meta-analysis of injury prevention programmes in 11 773 female football (soccer) players

Objective To evaluate the effects of injury prevention programmes on injury incidence in any women’s football code; explore relationships between training components and injury risk; and report injury incidence for women’s football. Design Systematic review and meta-analysis. Data sources Nine databases searched in August 2019. Eligibility criteria Randomised controlled trials evaluating any injury prevention programme (eg, exercise, education, braces) were included. Study inclusion criteria were: ≥20 female football players in each study arm (any age, football code or participation level) and injury incidence reporting. Results Twelve studies, all in soccer, met inclusion criteria, with nine involving adolescent teams (aged <18 years). All studies (except one) had a high risk of bias. Eleven studies examined exercise-based programmes, with most (9/11) including multiple (≥2) training components (eg, strength, plyometric, balance exercises). Multicomponent exercise programmes reduced overall (any reported) injuries (incidence rate ratio (IRR) 0.73, 95% CI 0.59 to 0.91) and ACL injuries (IRR 0.55, 95% CI 0.32 to 0.92). For exercise-based strategies (single-component and multicomponent), hamstring injuries were also reduced (IRR 0.40, 95% CI 0.17 to 0.95). While exercise-based strategies resulted in less knee, ankle and hip/groin injuries, and the use of multiple training components was associated with greater reductions in overall and knee injuries, further studies would be required to increase the precision of these results. The incidence of overall injuries in women’s football was 3.4 per 1000 exposure hours; with ankle injuries most common. Conclusion In women’s football, there is low-level evidence that multicomponent, exercise-based programmes reduce overall and ACL injuries by 27% and 45%, respectively. PROSPERO registration number CRD42018093527.
Prediction models for cardiovascular disease risk in the hypertensive population: a systematic review.

OBJECTIVE The aim of this study was to identify, describe, and evaluate the available cardiovascular disease risk prediction models developed or validated in the hypertensive population. METHODS MEDLINE and the Web of Science were searched from database inception to March 2019, and all reference lists of included articles were reviewed. RESULTS A total of 4766 references were screened, of which 18 articles were included in the review, presenting 17 prediction models specifically developed for hypertensive populations and 25 external validations. Among the 17 prediction models, most were constructed based on randomized trials in Europe or North America to predict the risk of fatal or nonfatal cardiovascular events. The most common predictors were classic cardiovascular risk factors such as age, diabetes, sex, smoking, and SBP. Of the 17 models, only one model was externally validated. Among the 25 external validations, C-statistics ranged from 0.58 to 0.83, 0.56 to 0.75, and 0.64 to 0.78 for models developed in the hypertensive population, the general population and other specific populations, respectively. Most of the development studies and validation studies had an overall high risk of bias according to PROBAST. CONCLUSION There are a certain number of cardiovascular risk prediction models in patients with hypertension. The risk of bias assessment showed several shortcomings in the methodological quality and reporting in both the development and validation studies. Most models developed in the hypertensive population have not been externally validated. Compared with models developed for the general population and other specific populations, models developed for the hypertensive population do not display a better performance when validated among patients with hypertension. Research is needed to validate and improve the existing cardiovascular disease risk prediction models in hypertensive populations rather than developing completely new models.