Miracle-dz/UniFAR-FTUs huggingface dataset:
Pulmonary Function is Associated with Distal Aortic Calcium, Not Proximal Aortic Distensibility. MESA Lung Study

Forced expiratory volume in one second strongly predicts mortality from cardiovascular disease. FEV1 has been associated with aortic stiffness a strong independent predictor of cardiovascular mortality. However, the anatomical site and possible mechanisms linking aortic stiffness and lung function are unknown. We therefore examined if FEV1 and CT percent emphysema were associated with calcification of the abdominal aorta or reduced distensibility of the proximal thoracic aorta.The Multi-Ethnic Study of Atherosclerosis (MESA) measured aortic calcification on cardiac and abdominal CT scans and proximal aortic distensibility using magnetic resonance among participants aged 45–84 years without clinical cardiovascular disease. Spirometry was measured following ATS/ERS guidelines and percent emphysema was measured in the lung fields of cardiac CT scans. Multivariate analyses adjusted for age, sex, race/ethnicity and cardiovascular risk factors. Of 1,917 participants with aortic distensibility measures, 13% were current and 38% were former smokers. Eighteen percent had airflow limitation without asthma. FEV1 was associated with the extent of distal aortic calcification (0.76; 95%CI 0.60–0.97, p = 0.02) but not proximal aortic calcification or proximal aortic distensibility (−0.04 mmHg−1; 95%CI −0.16–0.09 mmHg−1, p = 0.60). Percent emphysema was associated with neither measure. FEV1 was associated with severity of distal aortic calcification where it was present independently of smoking and other cardiovascular risk factors but not with distensibility or calcification of the proximal aorta.
Patterns of persistent genital human papillomavirus infection among women worldwide: A literature review and meta‐analysis

Persistent high‐risk human papillomavirus (HR‐HPV) infection is the strongest risk factor for high‐grade cervical precancer. We performed a systematic review and meta‐analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta‐regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV‐16, 31, 33 and 52 being most persistent. Weighted median duration of any‐HPV detection was 9.8 months. HR‐HPV (9.3 months) persisted longer than low‐risk HPV (8.4 months), and HPV‐16 (12.4 months) persisted longer than HPV‐18 (9.8 months). Among populations of HPV‐positive women with normal cytology, the median duration of any‐HPV detection was 11.5 and HR‐HPV detection was 10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6 to 12 months. Repeat HPV testing at 12‐month intervals could identify women at increased risk of high‐grade cervical precancer due to persistent HPV infections.
Evaluation of Muscle Mechanical Capacities Through the Two-Load Method: Optimization of the Load Selection

Abstract Pérez-Castilla, A, Jaric, S, Feriche, B, Padial, P, and García-Ramos, A. Evaluation of muscle mechanical capacities through the 2-load method: Optimization of the load selection. J Strength Cond Res 32(5): 1245–1253, 2018—Recent research has revealed that the force-velocity relationship obtained from the “2-load method” (i.e., functional movements tested against just 2 external loads) could be a feasible method for the selective assessment of muscle force, velocity, and power-producing capacities. The study investigated the reliability and concurrent validity of the outcomes of the 2-load method observed from (a) farther vs. closer data points (20–70% 1 repetition maximum [1RM], 30–60% 1RM, and 40–50% 1RM) and (b) force-biased (50–70% 1RM) vs. velocity-biased (20–40% 1RM) data points. Twenty-two men were tested on a ballistic bench press throw performed against 6 incremental loads ranging from 20 to 70% of the bench press 1RM. The 2-load methods were constructed based on pairs of individually selected external loads and compared with the outcome of the force-velocity regression method applied to all 6 loads. The reliability and validity of the force-velocity relationship parameters decreased with the proximity of the data points (40–50% 1RM < 30–60% 1RM < 20–70% 1RM). The velocity-biased and force-biased loads (i.e., lighter and heavier loads, respectively) revealed a similar but relatively moderate reliability and validity. Overall, the farthest pair of loads (i.e., 20% 1RM and 70% 1RM) revealed the highest reliability (CV = 5.5%, ICC = 0.89) and validity (r = 0.98) among all the 2-load methods evaluated. These results demonstrate that the 20–70% 1RM 2-load method could be a feasible approach for testing individual muscle mechanical capacities, whereas the observed outcomes could be most reliable and valid when obtained from the farthest pairs of applied loads.
Allosteric modulation of ATP-gated P2X receptor channels

Abstract Seven mammalian purinergic receptor subunits, denoted P2X1–P2X7, and several spliced forms of these subunits have been cloned. When heterologously expressed, these cDNAs encode ATP-gated non-selective cation channels organized as trimers. All activated receptors produce cell depolarization and promote Ca2+ influx through their pores and indirectly by activating voltage-gated calcium channels. However, the biophysical and pharmacological properties of these receptors differ considerably, and the majority of these subunits are also capable of forming heterotrimers with other members of the P2X receptor family, which confers further different properties. These channels have three ATP binding domains, presumably located between neighboring subunits, and occupancy of at least two binding sites is needed for their activation. In addition to the orthosteric binding sites for ATP, these receptors have additional allosteric sites that modulate the agonist action at receptors, including sites for trace metals, protons, neurosteroids, reactive oxygen species and phosphoinositides. The allosteric regulation of P2X receptors is frequently receptor-specific and could be a useful tool to identify P2X members in native tissues and their roles in signaling. The focus of this review is on common and receptor-specific allosteric modulation of P2X receptors and the molecular base accounting for allosteric binding sites.
Nonconsensus West Nile Virus Genomes Arising during Mosquito Infection Suppress Pathogenesis and Modulate Virus Fitness In Vivo

ABSTRACT West Nile virus (WNV) is similar to other RNA viruses in that it forms genetically complex populations within hosts. The virus is maintained in nature in mosquitoes and birds, with each host type exerting distinct influences on virus populations. We previously observed that prolonged replication in mosquitoes led to increases in WNV genetic diversity and diminished pathogenesis in mice without remarkable changes to the consensus genome sequence. We therefore sought to evaluate the relationships between individual and group phenotypes in WNV and to discover novel viral determinants of pathogenesis in mice and fitness in mosquitoes and birds. Individual plaque size variants were isolated from a genetically complex population, and mutations conferring a small-plaque and mouse-attenuated phenotype were localized to the RNA helicase domain of the NS3 protein by reverse genetics. The mutation, an Asp deletion, did not alter type I interferon production in the host but rendered mutant viruses more susceptible to interferon compared to wild type (WT) WNV. Finally, we used an in vivo fitness assay in Culex quinquefasciatus mosquitoes and chickens to determine whether the mutation in NS3 influenced fitness. The fitness of the NS3 mutant was dramatically lower in chickens and moderately lower in mosquitoes, indicating that RNA helicase is a major fitness determinant of WNV and that the effect on fitness is host specific. Overall, this work highlights the complex relationships that exist between individual and group phenotypes in RNA viruses and identifies RNA helicase as an attenuation and fitness determinant in WNV.
Glycated albumin level during late pregnancy as a predictive factor for neonatal outcomes of women with diabetes

Abstract Purpose: To investigate the association between glycated albumin (GA) in diabetic mothers and complications in their children, and to determine GA cutoff values for predicting complications in infants. Materials and methods: This hospital-based case-control study involved 71 Japanese diabetic mothers and their children. Mean GA values were compared between mothers of infants with and without complications, and relationship with number of complications was analyzed by Pearson’s correlation. Receiver operating characteristic analysis determined GA cutoff values for complications in infants. Results: GA was significantly higher in mothers of children with neonatal hypoglycemia (15.8 ± 3.2 versus 12.6 ± 1.2%, p <.001), respiratory disorders (15.7 ± 3.6 versus 12.9 ± 1.9%, p <.001), hypocalcemia (15.9 ± 3.7 versus 13.1 ± 1.8%, p <.001), polycythemia (15.7 ± 2.3 versus 13.8 ± 2.1%, p =.009), myocardial hypertrophy (16.1 ± 3.7 versus 13.1 ± 2.3%, p <.001), and large-for-date status (15.8 ± 2.4 versus 13.7 ± 3.1%, p = .006), showing significant positive correlation with number of complications in infants (r = .704, 95%CI: 0.579–0.797, p < .001). Cut-off values were within the limits of 13.6–14.7%. Conclusions: GA is useful for predicting pregnancy outcomes in mothers with diabetes and must be maintained at low levels to prevent complications in infants.
Metacarpal Growth During Adolescence in a Longitudinal South African Cohort

To monitor the drift of the periosteal and endocortical surfaces during metacarpal growth longitudinally, radiogrammetry was carried out on hand‐wrist X‐rays of 572 children from the Birth to Twenty Bone Health Cohort annually from ages 9 to 21 years. This is the largest collection of longitudinal X‐rays in African children. The second metacarpal bone length, bone width, and medullary width were measured using digital vernier calipers on a total of 4730 X‐rays. Superimposition by Translation and Rotation (SITAR) was used to obtain age at peak metacarpal length velocity (PLV). Bone width and medullary width were modeled using SITAR against both chronological age and age from PLV. In black and white females, tempo and velocity of metacarpal length growth was synchronized. Black males, however, attained PLV 7 months later than white males (p < 0.0001). Compared to white males, black males had a longer second metacarpal (p < 0.05), and greater bone width size (p < 0.02), tempo (p < 0.0009), and velocity (p < 0.0001). Medullary width growth velocity in black participants peaked 2 years prior to attainment of PLV and exceeded that of their white peers (p < 0.0001) in whom it peaked 6 to 12 months post‐PLV attainment. Black adolescents therefore had wider bones with relatively thinner cortices and wider medullary cavities than their white peers. Ethnic and sex differences also occurred in the timing of medullary width contraction that accompanied expansion in bone width and cortical thickness. In black males, medullary width contraction commenced approximately 3 years later than in black females, whereas in white males this occurred a year later than in white females. The ethnic and sex differences in bone acquisition reported in this study may differentially affect bone mass in later life. © 2017 American Society for Bone and Mineral Research.
IL‐22 binding protein regulates murine skin inflammation

IL22 is a cytokine expressed by haematopoietic cells of both the innate and adaptive arm of the immune system. [1] Shortly after it was discovered in 2000, the existence of IL22 binding protein (IL22BP) was reported, a soluble decoy receptor transcribed from the gene IL22RA2. [2] IL-22BP binds with very high affinity to IL22 in such a way that it no longer can dock with the IL22 receptor (IL22R). [3] It was soon established that IL22 does not directly influence immune cells but rather the epithelial cells of the skin, lungs, and gut as well as cells of the liver, joints, pancreas, and kidney. [4] These tissues express IL22RA1, one of the two subunits of the IL-22R, whereas the other subunit, IL10RB, is expressed throughout the body. The IL22 pathway is implicated in several chronic inflammatory diseases, such as psoriasis, inflammatory bowel disease, and multiple sclerosis (MS). Interestingly, IL22BP has a protective role in a mouse model of inlammation-induced colon cancer but a disease promoting net effect in a model of MS.[5,6] Its role in inflammatory skin diseases has so far not been addressed.
Efficacy of basal‐bolus insulin regimens in the inpatient management of non‐critically ill patients with type 2 diabetes: A systematic review and meta‐analysis

Hyperglycemia during hospitalization is associated with increased rates of complications and longer hospital stays. Various insulin regimens are used in the inpatient diabetes management of non‐critically ill patients. In this systematic review and meta‐analysis, we aimed to assess the efficacy and safety of basal‐bolus insulin therapy (BBI) by summarizing evidence from studies of BBI versus sliding scale insulin therapy (SSI) in the management of hospitalized non‐critically ill type 2 diabetes patients. We searched MEDLINE, EMBASE, Scopus, and the Cochrane Library for studies comparing BBI therapy with SSI therapy in hospitalized non‐critically ill patients with type 2 diabetes. Primary outcome was mean daily blood glucose (BG) during admission. Secondary outcomes were incidence of hypoglycemia and length of hospital stay. Results of included randomized controlled trials (RCT) were pooled and meta‐analysed to provide estimates of the efficacy of BBI therapy. Five RCTs and seven observational studies were included in the review. Meta‐analysis of RCTs showed significantly lower mean daily BG with BBI than SSI. Mean difference in daily BG between the two regimens ranged from 14 to 29 mg/dl. BBI therapy was associated with increased risk of mild hypoglycemia (BG ≤ 70 mg/dl, RR 5.75; 95% CI 2.79‐11.83), (BG ≤ 60 mg/dl, RR 4.21; 95% CI 1.61‐11.02) compared with SSI therapy. There was no difference in risk of severe hypoglycemia (BG ≤ 40 mg/dl) and no difference in mean length of stay. In conclusion, basal‐bolus insulin in the inpatient diabetes management results in significantly lower mean daily BG than sliding scale insulin but is associated with increased risk of mild hypoglycemia.
3‐Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons

During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3‐hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD+/NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain‐derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons. The mechanism by which 3OHB induces Bdnf gene expression involves generation of reactive oxygen species, activation of the transcription factor NF‐κB, and activity of the histone acetyltransferase p300/EP300. Because BDNF plays important roles in synaptic plasticity and neuronal stress resistance, our findings suggest cellular signaling mechanisms by which 3OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets.
Integrating In Vitro, Modeling, and In Vivo Approaches to Investigate Warfarin Bioequivalence

We demonstrate the use of modeling and simulation to investigate bioequivalence (BE) concerns raised about generic warfarin products. To test the hypothesis that the loss of isopropyl alcohol and slow dissolution in acidic pH has significant impact on the pharmacokinetics of warfarin sodium tablets, we conducted physiologically based pharmacokinetic absorption modeling and simulation using formulation factors or in vitro dissolution profiles as input parameters. Sensitivity analyses indicated that warfarin pharmacokinetics was not sensitive to solubility, particle size, density, or dissolution rate in pH 4.5, but was affected by dissolution rate in pH 6.8 and potency. Virtual BE studies suggested that stressed warfarin sodium tablets with slow dissolution rate in pH 4.5 but having similar dissolution rate in pH 6.8 would be bioequivalent to the unstressed warfarin sodium tablets. A four‐way, crossover, single‐dose BE study in healthy subjects was conducted to test the same hypothesis and confirmed the simulation conclusion.
Neural Substrates and Social Consequences of Interpersonal Gratitude: Intention Matters

Voluntary help during a time of need fosters interpersonal gratitude, which has positive social and personal consequences such as improved social relationships, increased reciprocity, and decreased distress. In a behavioral and a functional magnetic resonance imaging (fMRI) experiment, participants played a multiround interactive game where they received pain stimulation. An anonymous partner interacted with the participants and either intentionally or unintentionally (i.e., determined by a computer program) bore part of the participants’ pain. In each round, participants either evaluated their perceived pain intensity (behavioral experiment) or transferred an amount of money to the partner (fMRI experiment). Intentional (relative to unintentional) help led to lower experience of pain, higher reciprocity (money allocation), and increased interpersonal closeness toward the partner. fMRI revealed that for the most grateful condition (i.e., intentional help), value-related structures such as the ventromedial prefrontal cortex (vmPFC) showed the highest activation in response to the partner’s decision, whereas the primary sensory area and the anterior insula exhibited the lowest activation at the pain delivery stage. Moreover, the vmPFC activation was predictive of the individual differences in reciprocal behavior, and the posterior cingulate cortex (PCC) activation was predictive of self-reported gratitude. Furthermore, using multivariate pattern analysis (MVPA), we showed that the neural activation pattern in the septum/hypothalamus, an area associated with affiliative affect and social bonding, and value-related structures specifically and sensitively dissociated intentional help from unintentional help conditions. These findings contribute to our understanding of the psychological and neural substrates of the experience of interpersonal gratitude and the social consequences of this emotion.
Deep brain stimulation for the treatment of uncommon tremor syndromes

ABSTRACT Introduction: Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson’s disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. Areas covered: In this article, we conducted a PubMed search using different combinations between the terms ‘Uncommon tremors’, ‘Dystonic tremor’, ‘Holmes tremor’ ‘Midbrain tremor’, ‘Rubral tremor’, ‘Cerebellar tremor’, ‘outflow tremor’, ‘Multiple Sclerosis tremor’, ‘Post-traumatic tremor’, ‘Neuropathic tremor’, and ‘Deep Brain Stimulation/DBS’. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert commentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features.
Associations of short-term exposure to ambient air pollutants with emergency ambulance calls for the exacerbation of essential arterial hypertension

Abstract We investigated the association between daily emergency ambulance calls (EAC) for elevated blood pressure that occurred during the time intervals of 8:00–13:59, 14:00–21:59, and 22:00–7:59, and exposure to CO, PM10, and ozone. We used Poisson regression to explore the association between the risk of EAC and short-term variation of pollutants, adjusting for seasonality and weather variables. Before noon, the risk was associated with an interquartile range (IQR) (7.9 μg/m3) increase in PM10 at lag 2–4 days below the median (RR = 1.08, p = 0.031) and with an IQR (0.146 mg/m3) increase in CO at lag 6–7 below the median (RR = 1.05, p = 0.028). During 14:00–21:59, the risk was associated with an IQR (18.8 μg/m3) increase in PM10 on the previous day below the median (RR = 1.04, p = 0.031). At night, EAC were negatively affected by lower O3 (lag 0–2) below the median (per IQR decrease RR = 1.10, p = 0.018) and a higher PM10 at lag 0–1 above the median for the elderly (RR = 1.07, p = 0.030).
New Insights into the Role of Autophagy in Tumor Immune Microenvironment

The tumor microenvironment is a complex system that is affected by various factors, including hypoxia, acidosis, and immune and inflammatory responses, which have significant effects on tumor adhesion, invasion, metastasis, angiogenesis, and autophagy. In this hostile tumor microenvironment, autophagy of tumor cells can promote tumor growth and metastasis. As autophagy is a double-edged sword in tumors, treatment of cancer via regulation of autophagy is extremely complicated. Therefore, understanding the relationship between tumor autophagy and the tumor microenvironment is extremely important. As the immune milieu plays an important role in tumor development, immunotherapy has become a promising form of cancer therapy. A multi-pronged treatment approach using immunotherapy and molecular targets may become the major direction for future cancer treatments. This article reviews existing knowledge regarding the immune factors in the tumor microenvironment and the status of tumor autophagy research.
Mobilities II

In this second report I discuss research published in 2014 and early 2015. I examine recent debates about elemental geographies, including research on the mobilities associated with air and water, and on how aluminium, steel and carbon facilitate movement. The report then highlights the vibrant materialities and mobilities underpinning events, examining different approaches to processual and molecular mobilities, including work which is critical of the suggestion that everything is moving. In the final section I examine the centrality of mobility to academic practices and biographies, and here I discuss the life and work of the influential cultural studies scholar Stuart Hall.
An extended ANFIS architecture and its learning properties for type-1 and interval type-2 models

In this paper, an extended ANFIS architecture is proposed. By incorporating an extra layer for the fuzzification process, the extended architecture is able to fit both type-1 and interval type-2 models. The learning properties of the proposed architecture based on the least-squares estimate method are studied on selected type-1 and interval type-2 ANFIS models. We show that the least-squares estimate method in general behaves differently for interval type-2 ANFIS models compared to type-1 ANFIS models, producing larger errors for interval type-2 ANFIS.