Miracle-dz/UniFAR-FTUs huggingface dataset:
Location location location: muscle glycogen content and endurance exercise

The percutaneous muscle biopsy technique was developed in Sweden in the 1960s and spawned a decade of revelatory investigations on the interaction between diet, exercise and muscle glycogen. This culminated in the pioneering study that showed the importance of muscle glycogen content for endurance exercise following dietary carbohydrate manipulation (Bergström et al., 1967). These studies have laid the foundations for scientific work in this area, including the use of carbohydrate loading and periodization strategies to enhance muscle glycogen storage capacities. In particular, the muscle biopsy technique has allowed research to elucidate the relationships between muscle glycogen and exercise intensity and duration, individual training status, carbohydrate feeding and carbohydrate restriction (Hearris, et al., 2018). The muscle biopsy is considered a ‘gold standard’ when it comes to biochemical, molecular, histochemical, and histomorphometric muscle analyses. Traditionally, muscle glycogen content has been evaluated using whole-muscle homogenates from muscle biopsies. However, muscle is not a uniform tissue and is composed of multiple fibre types (type I, type IIa, type IIx) which have distinct glycogen contents while it has been known for some time that glycogen is not only differentially located between different muscle fibres but also within subcellular compartments. Whole-muscle quantification, therefore, might not be the most accurate method to elucidate the complex pathways through which muscle glycogen availability may influence exercise performance, and instead, single-fibre and subcellular localisation may further enhance understanding of this topic.
COVID-19 and Heart Failure With Preserved Ejection Fraction.

Patients with preexisting cardiovascular disease (CVD) who develop coronavirus disease 2019 (COVID-19) have worse outcomes than patients without CVD.1 Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly or indirectly lead to myocardial injury. Although fulminant viral myocarditis due to COVID-19 appears to be uncommon, recent data, although limited, suggest that direct myocardial injury may occur in some individuals. This Viewpoint contextualizes the emerging data on the risk of heart failure, particularly heart failure with preserved ejection fraction (HFpEF), in patients during both the acute phase of COVID-19 illness and the chronic phase of recovery in COVID-19 survivors. This is important to elucidate, because infection with COVID-19 may be associated with HFpEF through several pathways: COVID-19 may cause HFpEF via direct viral infiltration, inflammation, or cardiac fibrosis; it may unmask subclinical HFpEF in individuals with underlying risk factors; or it may exacerbate preexisting HFpEF. Key issues are discussed involving the link between COVID-19 and risk of HFpEF due to their shared inflammatory pathophysiology and cardiometabolic risk profiles (Figure) and the potential for an increase in the individualand population-level effects of HFpEF in the aftermath of the pandemic.
The role of frailty in geriatric cranial neurosurgery for primary central nervous system neoplasms.

OBJECTIVE Frailty is a clinical state of increased vulnerability due to age-associated decline and has been well established as a perioperative risk factor. Geriatric patients have a higher risk of frailty, higher incidence of brain cancer, and increased postoperative complication rates compared to nongeriatric patients. Yet, literature describing the effects of frailty on short- and long-term complications in geriatric patients is limited. In this study, the authors evaluate the effects of frailty in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. METHODS The authors conducted a retrospective cohort study of geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm between 2010 and 2017 by using the Nationwide Readmission Database. Demographics and frailty were queried at primary admission, and readmissions were analyzed at 30-, 90-, and 180-day intervals. Complications of interest included infection, anemia, infarction, kidney injury, CSF leak, urinary tract infection, and mortality. Nearest-neighbor propensity score matching for demographics was implemented to identify nonfrail control patients with similar diagnoses and procedures. The analysis used Welch two-sample t-tests for continuous variables and chi-square test with odds ratios. RESULTS A total of 6713 frail patients and 6629 nonfrail patients were identified at primary admission. At primary admission, frail geriatric patients undergoing cranial neurosurgery had increased odds of developing acute posthemorrhagic anemia (OR 1.56, 95% CI 1.23-1.98; p = 0.00020); acute infection (OR 3.16, 95% CI 1.70-6.36; p = 0.00022); acute kidney injury (OR 1.32, 95% CI 1.07-1.62; p = 0.0088); urinary tract infection prior to discharge (OR 1.97, 95% CI 1.71-2.29; p < 0.0001); acute postoperative cerebral infarction (OR 1.57, 95% CI 1.17-2.11; p = 0.0026); and mortality (OR 1.64, 95% CI 1.22-2.24; p = 0.0012) compared to nonfrail geriatric patients receiving the same procedure. In addition, frail patients had a significantly increased inpatient length of stay (p < 0.0001) and all-payer hospital cost (p < 0.0001) compared to nonfrail patients at the time of primary admission. However, no significant difference was found between frail and nonfrail patients with regard to rates of infection, thromboembolism, CSF leak, dural tear, cerebral infarction, acute kidney injury, and mortality at all readmission time points. CONCLUSIONS Frailty may significantly increase the risks of short-term acute complications in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. Long-term analysis revealed no significant difference in complications between frail and nonfrail patients. Further research is warranted to understand the effects and timeline of frailty in geriatric patients.
Evolution of a Record-Setting AT-Rich Genome: Indel Mutation, Recombination, and Substitution Bias

Abstract Genome-wide nucleotide composition varies widely among species. Despite extensive research, the source of genome-wide nucleotide composition diversity remains elusive. Yeast mitochondrial genomes (mitogenomes) are highly A + T rich, and they provide a unique opportunity to study the evolution of AT-biased landscape. In this study, we sequenced ten complete mitogenomes of the Saccharomycodes ludwigii yeast with 8% G + C content, the lowest genome-wide %(G + C) in all published genomes to date. The S. ludwigii mitogenomes have high densities of short tandem repeats but severely underrepresented mononucleotide repeats. Comparative population genomics of these record-setting A + T-rich genomes shows dynamic indel mutations and strong mutation bias toward A/T. Indel mutations play a greater role in genomic variation among very closely related strains than nucleotide substitutions. Indels have resulted in presence–absence polymorphism of tRNAArg (ACG) among S. ludwigii mitogenomes. Interestingly, these mitogenomes have undergone recombination, a genetic process that can increase G + C content by GC-biased gene conversion. Finally, the expected equilibrium G + C content under mutation pressure alone is higher than observed G + C content, suggesting existence of mechanisms other than AT-biased mutation operating to increase A/T. Together, our findings shed new lights on mechanisms driving extremely AT-rich genomes.
Dimethoate Induces DNA Damage and Mitochondrial Dysfunction Triggering Apoptosis in Rat Bone-Marrow and Peripheral Blood Cells

Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats. Significant micronuclei induction and metaphase chromosome abnormalities in bone marrow cells exposed to three different DM doses (20, 40 and 60 mg/kg-bw) at multiple treatment durations (24, 48 and 72 h) indicated positive dose response relationship, confirming its genotoxic and cytotoxic potential. Significant mitotic index decrease was seen in dosed animals compared to vehicle control. The study used peripheral blood comet assay, indicating DM-mediated damage to DNA at all exposure levels in a time responsive manner. These assays were found to be an effective, precise, and fast technique with applied value in biomonitoring studies. Cell cycle and apoptosis along with mitochondrial membrane potential (MMP) in flow cytometric analyses confirmed DM exposure decreased MMP, affected the cell cycle, and inflicted DNA damage, which led to cellular apoptosis of leukocytes culminating into immunotoxic effects. The in silico experiments consequently augmented that DM showed acceptable binding energy value for Cyclin A2, suggesting that it could inhibit the cell cycle progression by inhibiting cyclin A2.
Iris Colour and the Risk of Developing Uveal Melanoma

Uveal melanoma (UM) is a global disease which especially occurs in elderly people. Its incidence varies widely between populations, with the highest incidence among Caucasians, and a South-to-North increase in Europe. As northern Europeans often have blond hair and light eyes, we wondered whether iris colour may be a predisposing factor for UM and if so, why. We compared the distribution of iris colour between Dutch UM patients and healthy Dutch controls, using data from the Rotterdam Study (RS), and reviewed the literature regarding iris colour. We describe molecular mechanisms that might explain the observed associations. When comparing a group of Dutch UM patients with controls, we observed that individuals from Caucasian ancestry with a green/hazel iris colour (Odds Ratio (OR) = 3.64, 95% Confidence Interval (CI) 2.57–5.14) and individuals with a blue/grey iris colour (OR = 1.38, 95% CI 1.04–1.82) had a significantly higher crude risk of UM than those with brown eyes. According to the literature, this may be due to a difference in the function of pheomelanin (associated with a light iris colour) and eumelanin (associated with a brown iris colour). The combination of light-induced stress and aging may affect pheomelanin-carrying melanocytes in a different way than eumelanin-carrying melanocytes, increasing the risk of developing a malignancy.
EFFECTS OF FK506 ON THE HEALING OF DIAPHYSEAL, CRITICAL SIZE DEFECTS IN THE RAT FEMUR

There is much interest in understanding the influence of the immune system on bone healing, including a number of reports suggesting a beneficial effect of FK506 (tacrolimus) in this regard. The influence of FK506 in a rat, femoral, critical size defect was examined using locally implanted, recombinant, human (rh) BMP-2 and adenovirally-transduced, autologous, adipose-derived mesenchymal stromal cells (AD-MSCs) expressing BMP-2. FK506 was delivered systemically using an implanted osmotic pump. Empty defects and those implanted with unmodified AD-MSCs did not heal in the presence or absence of FK506. Defects treated with rhBMP-2 healed with a large callus containing thin cortices and wispy trabeculae; this, too, was unaffected by FK506. A third of defects implanted with adenovirally-transduced AD-MSCs healed, but this improved to 100 % in the presence of FK506. New bone formed in response to BMP-2 synthesised endogenously by the genetically modified cells had a slimmer callus than those healed by rhBMP-2, with improved cortication and advanced reconstitution of marrow. These results suggest that FK506 may have had little effect on the intrinsic biology of bone healing, but improved healing in response to adenovirally-transduced cells by inhibiting immune responses to the first-generation adenovirus used here. Because the genetically modified cells produced bone of higher quality at far lower doses of BMP-2, this approach should be explored in subsequent research.
Computational approaches to the neuroscience of social perception

Abstract Across multiple domains of social perception—including social categorization, emotion perception, impression formation and mentalizing—multivariate pattern analysis (MVPA) of functional magnetic resonance imaging (fMRI) data has permitted a more detailed understanding of how social information is processed and represented in the brain. As in other neuroimaging fields, the neuroscientific study of social perception initially relied on broad structure–function associations derived from univariate fMRI analysis to map neural regions involved in these processes. In this review, we trace the ways that social neuroscience studies using MVPA have built on these neuroanatomical associations to better characterize the computational relevance of different brain regions, and discuss how MVPA allows explicit tests of the correspondence between psychological models and the neural representation of social information. We also describe current and future advances in methodological approaches to multivariate fMRI data and their theoretical value for the neuroscience of social perception.
A Multidisciplinary Investigation of the Applicability of the Pleistocene Herpetofaunal Stability Model to Collared Lizards (Crotaphytus collaris)

Recent paleontological evidence suggests the North American herpetofauna has been remarkably stable taxonomically and biogeographically throughout the Pleistocene. However, this paper uses paleontological, ecological, and molecular genetic data to argue that the thermophilous and xerically-adapted Collared Lizard (Crotaphytus collaris) did not persist in the northern parts of its range during glacial phases of the Pleistocene. First, a careful review of the paleontological data used to support the stability model reveals no northern fossils unambiguously dated to glacial phases. Second, environmental conditions inferred for the Ozark Plateau and Flint Hills during glacial phases were not compatible with fitness requirements of collared lizards. Third, phylogeographic analyses of an intraspecific mtDNA gene tree suggest a recent invasion of the Ozarks and Flint Hills. Finally, microsatellite data are statistically consistent with a Holocene invasion but not with long-term occupation of the Ozarks or the Flint Hills by collared lizards. These combined data sets provide strong evidence that collared lizards are able to occupy northern parts of their range only during the warmer, drier interglacials. Other thermophilous and xerically-adapted reptilian species might be expected to show similar historical patterns.
Diurnal dynamics of non-photochemical quenching in Arabidopsis npq mutants assessed by solar-induced fluorescence and reflectance measurements in the field.

Solar-induced fluorescence (SIF) is highly relevant in mapping photosynthesis from remote-sensing platforms. This requires linking SIF to photosynthesis and understanding the role of non-photochemical quenching (NPQ) mechanisms under field conditions. Hence, active and passive fluorescence were measured in Arabidopsis thaliana with altered NPQ in outdoor conditions. Plants had mutations in either violaxanthin de-epoxidase (npq1) or PsbS protein (npq4), resulting in reduced NPQ capacity. Parallel measurements of NPQ, photosystem II efficiency, SIF and spectral reflectance (ρ) were conducted diurnally on one sunny summer day and two consecutive days during a simulated cold spell. Results showed that both npq mutants had higher levels of SIF compared to wild type. Changes in reflectance were related to changes in the violaxanthin-antheraxanthin-zeaxanthin cycle and not to PsbS-mediated conformational changes. When plants were exposed to cold temperatures, rapid onset of photoinhibition strongly quenched SIF in all lines. Using well-characterized npq mutants of Arabidopsis, we could show for the first time the quantitative link between SIF, photosynthetic efficiency, NPQ components and leaf reflectance. We discuss the functional potential and limitations of SIF and reflectance measurements for estimating photosynthetic efficiency and NPQ in the field.
A Novel Weighted Clustering Algorithm Supported by a Distributed Architecture for D2D Enabled Content-Centric Networks

Next generation cellular systems need efficient content-distribution schemes. Content-sharing via Device-to-Device (D2D) clustered networks has emerged as a popular approach for alleviating the burden on the cellular network. In this article, we utilize Content-Centric Networking and Network Virtualization to propose a distributed architecture, that supports efficient content delivery. We propose to use clustering at the user level for content-distribution. A weighted multifactor clustering algorithm is proposed for grouping the D2D User Equipment (DUEs) sharing a common interest. The proposed algorithm is evaluated in terms of energy efficiency, area spectral efficiency, and throughput. The effect of the number of clusters on these performance parameters is also discussed. The proposed algorithm has been further modified to allow for a tradeoff between fairness and other performance parameters. A comprehensive simulation study demonstrates that the proposed clustering algorithm is more flexible and outperforms several classical and state-of-the-art algorithms.
Formation of the Reproductive Behavior of Healthcare Students Depending on Their Mothers' Realized Plans.

INTRODUCTION A socio-demographic analysis of marriage and family requires conducting deep studies penetrating the essence of the processes among the population. The issue of birth-rate, as a basic factor that determines the reproduction of the population, takes a central position in the demographic studies. The study of the influence of the mothers' reproductive behaviour on their daughters' repro-ductive attitude is of an undisputed interest. This study deals with mothers' realized plans as a factor in their daughters' family planning. MATERIALS AND METHODS This cross-sectional study was carried out in 2018 through a direct group anonymous inquiry among 395 female students. The statistical processing of the data was made with descriptive, alternative, correlation and variance analyses. RESULTS The students' reproductive behaviour is statistically significantly dependent on their mothers' realized family plans. Moth-ers' education and the real number of children are statistically significant factors for their daughters' views about the ideal and planned number of children. CONCLUSION This study of the reproductive behaviour of the students advances the knowledge in the field by revealing that it is statisti-cally significantly dependent on their mothers' realized plans.
Computed tomography aortic valve calcium scoring for the assessment of aortic stenosis progression

Objective CT quantification of aortic valve calcification (CT-AVC) is useful in the assessment of aortic stenosis severity. Our objective was to assess its ability to track aortic stenosis progression compared with echocardiography. Methods Subjects were recruited in two cohorts: (1) a reproducibility cohort where patients underwent repeat CT-AVC or echocardiography within 4 weeks and (2) a disease progression cohort where patients underwent annual CT-AVC and/or echocardiography. Cohen’s d-statistic (d) was computed from the ratio of annualised progression and measurement repeatability and used to estimate group sizes required to detect annualised changes in CT-AVC and echocardiography. Results A total of 33 (age 71±8) and 81 participants (age 72±8) were recruited to the reproducibility and progression cohorts, respectively. Ten CT scans (16%) were excluded from the progression cohort due to non-diagnostic image quality. Scan-rescan reproducibility was excellent for CT-AVC (limits of agreement −12% to 10 %, intraclass correlation (ICC) 0.99), peak velocity (−7% to +17%; ICC 0.92) mean gradient (−25% to 27%, ICC 0.96) and dimensionless index (−11% to +15%; ICC 0.98). Repeat measurements of aortic valve area (AVA) were less reliable (−44% to +28%, ICC 0.85). CT-AVC progressed by 152 (65–375) AU/year. For echocardiography, the median annual change in peak velocity was 0.1 (0.0–0.3) m/s/year, mean gradient 2 (0–4) mm Hg/year and AVA −0.1 (−0.2–0.0) cm2/year. Cohen’s d-statistic was more than double for CT-AVC (d=3.12) than each echocardiographic measure (peak velocity d=0.71 ; mean gradient d=0.66; AVA d=0.59, dimensionless index d=1.41). Conclusion CT-AVC is reproducible and demonstrates larger increases over time normalised to measurement repeatability compared with echocardiographic measures.
Imbalance of Lysine Acetylation Contributes to the Pathogenesis of Parkinson’s Disease

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. The neuropathological features of PD are selective and progressive loss of dopaminergic neurons in the substantia nigra pars compacta, deficiencies in striatal dopamine levels, and the presence of intracellular Lewy bodies. Interactions among aging and genetic and environmental factors are considered to underlie the common etiology of PD, which involves multiple changes in cellular processes. Recent studies suggest that changes in lysine acetylation and deacetylation of many proteins, including histones and nonhistone proteins, might be tightly associated with PD pathogenesis. Here, we summarize the changes in lysine acetylation of both histones and nonhistone proteins, as well as the related lysine acetyltransferases (KATs) and lysine deacetylases (KDACs), in PD patients and various PD models. We discuss the potential roles and underlying mechanisms of these changes in PD and highlight that restoring the balance of lysine acetylation/deacetylation of histones and nonhistone proteins is critical for PD treatment. Finally, we discuss the advantages and disadvantages of different KAT/KDAC inhibitors or activators in the treatment of PD models and emphasize that SIRT1 and SIRT3 activators and SIRT2 inhibitors are the most promising effective therapeutics for PD.
Aquaporin-4 Expression during Toxic and Autoimmune Demyelination

The water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood–brain interface. Following the discovery that AQP4 is a possible autoantigen in neuromyelitis optica, the function of AQP4 in health and disease has become a research focus. While several studies have addressed the expression and function of AQP4 during inflammatory demyelination, relatively little is known about its expression during non-autoimmune-mediated myelin damage. In this study, we used the toxin-induced demyelination model cuprizone as well as a combination of metabolic and autoimmune myelin injury (i.e., Cup/EAE) to investigate AQP4 pathology. We show that during toxin-induced demyelination, diffuse AQP4 expression increases, while polarized AQP4 expression at the astrocyte endfeet decreases. The diffuse increased expression of AQP4 was verified in chronic-active multiple sclerosis lesions. Around inflammatory brain lesions, AQP4 expression dramatically decreased, especially at sites where peripheral immune cells penetrate the brain parenchyma. Humoral immune responses appear not to be involved in this process since no anti-AQP4 antibodies were detected in the serum of the experimental mice. We provide strong evidence that the diffuse increase in anti-AQP4 staining intensity is due to a metabolic injury to the brain, whereas the focal, perivascular loss of anti-AQP4 immunoreactivity is mediated by peripheral immune cells.