Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of Cardiovascular Involvement in Patients with Primary Sjögren's Syndrome: a large-scale cross-sectional cohort study.

OBJECTIVE To evaluate the presence of cardiovascular involvement and analyze potential risk factors independently associated with cardiovascular involvement in primary Sjögren's syndrome (PSS) patients. METHODS We recruited a cohort of 367 PSS patients and 367 age- and gender-matched controls from the First Affiliated Hospital of Wenzhou Medical University. Demographic, clinical and laboratory data, and overt cardiovascular involvement events were recorded. Potential risk factors associated with cardiovascular involvement were determined by multivariate analyses. RESULTS PSS patients had a significantly higher cardiovascular involvement rate than that of the controls (61.6% versus 29.7%; p<0.01). Compared with PSS patients without cardiovascular involvement, those with cardiovascular involvement were significantly older; had higher rates of hypertension, diabetes, hypoalbuminemia, and hyperlipemia; were more likely to have extraglandular organ involvement; and had a higher level of C-reactive protein (CRP) (all p<0.05). In the multivariate analysis, age, hypertension, and extraglandular organ involvement were found to be risk factors independently correlated with cardiovascular events in PSS patients. CONCLUSIONS PSS patients are more vulnerable to cardiovascular diseases (CVDs). In addition to traditional CVD risk factors such as age and hypertension, extraglandular organ involvement was found to be independently associated with cardiovascular involvement in PSS patients, which suggests the need for early detection and prevention measures to improve the prognosis in those patients.
Gabapentin alleviates chronic spontaneous pain and acute hypoxia‐related pain in a mouse model of sickle cell disease

Pain is the main complication of sickle cell disease (SCD). Individuals with SCD experience acute pain episodes and chronic daily pain, both of which are managed with opioids. Opioids have deleterious side effects and use‐associated stigma that make them less than ideal for SCD pain management. After recognizing the neuropathic qualities of SCD pain, clinically‐approved therapies for neuropathic pain, including gabapentin, now present unique non‐opioid based therapies for SCD pain management. These experiments explored the efficacy of gabapentin in relieving evoked and spontaneous chronic pain, and hypoxia/reoxygenation (H/R)‐induced acute pain in mouse models of SCD. When administered following H/R, a single dose of gabapentin alleviated mechanical hypersensitivity in SCD mice by decreasing peripheral fibre activity. Gabapentin treatment also alleviated spontaneous ongoing pain in SCD mice. Longitudinal daily administration of gabapentin failed to alleviate H/R‐induced pain or chronic evoked mechanical, cold or deep tissue hypersensitivity in SCD mice. Consistent with this observation, voltage‐gated calcium channel (VGCC) α2δ1 subunit expression was similar in sciatic nerve, dorsal root ganglia and lumbar spinal cord tissue from SCD and control mice. Based on these data, gabapentin may be an effective opioid alternative for the treatment of chronic spontaneous and acute H/R pain in SCD.
Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells

Since many oncogenes, including BCR-ABL, may promote the acquisition and maintenance of the glycolytic phenotype, we tested whether treatment of BCR-ABL-driven human leukemia cells with imatinib, a selective BCR-ABL inhibitor, can modulate the expression of key glycolytic enzymes and mitochondrial complex subunits thus causing alterations of glucose metabolism. BCR-ABL-driven K562 and KCL-22 cells were incubated with increasing concentrations of imatinib to preliminarily test drug sensitivity. Then untreated and treated cells were analyzed for levels of BCR-ABL signaling mediators and key proteins of glycolytic cascade and oxidative phosphorylation. Effective inhibition of BCR-ABL caused a concomitant reduction of p-ERK1/2, p-AKT, phosphorylated form of STAT3 (at Tyr705 and Ser727), c-Myc and cyclin D1 along with an increase of cleaved PARP and caspase 3 at 48 h after treatment. Furthermore, a strong reduction of the hexokinase II (HKII), phosphorylated form of PKM2 (at Tyr105 and Ser37) and lactate dehydrogenase A (LDH-A) was observed in response to imatinib along with a strong upregulation of mitochondrial complexes (OXPHOS). According to these findings, a significant reduction of glucose consumption and lactate secretion along with an increase of intracellular ATP levels was observed in response to imatinib. Our findings indicate that imatinib treatment of BCR-ABL-driven human leukemia cells reactivates mitochondrial oxidative phosphorylation thus allowing potential co-targeting of BCR-ABL and OXPHOS.
Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice

Metformin is today the first choice treatment for type‐2 diabetes, but has also protective effects in several renal disease models. Previously, we have demonstrated that the protective effects in response to unilateral ureteral obstruction (UUO) are independent of organic cation transporters (OCTs), the transporters responsible for the metformin uptake into the renal cells. The mechanisms behind the renoprotective effects are incompletely understood, but our previous results indicate that the renoprotective effects at least partly could be dependent on actions of metformin outside the renal cells. In this study, we investigate whether the renoprotective effects of metformin can be mediated via systemic immunomodulatory actions. We demonstrated that metformin can affect the immune system in the kidney as well as in the peripheral blood and spleen following UUO. UUO kidneys showed infiltration of immune cells including monocytes, B cells, and T cells, but metformin limited infiltration of all cell types. UUO animals had increased spleen sizes, but this increase was attenuated by metformin. Metformin treatment surprisingly resulted in a higher proportion of monocytes with infiltratory capacity 7 days after UUO. Other studies have suggested that metformin regulates monocyte maturation through signal transducer and activator of transcription 3 (STAT3) activation, as also indicated by our results. In conclusion, our results demonstrate that metformin limits the infiltration of immune cells into the kidney, as well as modulates immune cell composition at a systemic level.
Time course of serum cobalamin, folate, and total iron binding capacity concentrations in pregnant bitches and association with hematological variables and survival

Abstract Background Hypocobalaminemia, hypofolatemia and iron deficiency are associated with pregnancy‐related anemia (PRA) and neonatal survival (NS) in women. Similar associations have not been investigated in pregnant bitches. Objectives To investigate time course and associations of serum cobalamin, folate and iron status indicators with hematological variables and NS in pregnant bitches. Animals Forty‐eight pregnant bitches. Methods A prospective cohort study. Pregnancy was confirmed by abdominal ultrasonography twice during mid‐ and late pregnancy, concurrently with blood sampling. Associations among pregnancy stage, NS and laboratory variables were assessed by generalized estimating equations. Results Compared with midpregnancy, serum cobalamin (adjusted mean [95% confidence interval, CI]) decreased at late pregnancy (430 pg/mL [394‐466] versus 330 pg/mL [303‐357], respectively; P < .001), whereas serum folate did not. Every increment of 1 in parity number or litter size corresponded to 28.6 pg/mL (95% CI, 5.6‐51.6; P = .02) and 20.3 pg/mL (95% CI, 10.9‐29.7; P < .001) decrease in serum cobalamin concentration. Compared with midpregnancy, serum iron (P < .001) and transferrin saturation (P = .01) increased at late pregnancy. The decrease in red blood cell count (P < .001) at late pregnancy was significantly, albeit weakly, correlated with decreasing serum folate concentration (r = 0.33; P = .02). None of the measures was associated with NS. Conclusions and Clinical Significance Pregnancy‐related anemia was common at late pregnancy. Unlike in women, in pregnant bitches, serum iron and transferrin saturation were increased at late pregnancy. Future studies are warranted to investigate the clinical ramifications of hypocobalaminemia in pregnant bitches and the utility of prophylactic folate administration in mitigating PRA.
A Novel SNP in EIF2AK4 Gene Is Associated with Thermal Tolerance Traits in Chinese Cattle

Simple Summary China harbors two lineages of cattle (Bos taurus and Bos indicus) that display pronounced geographical distribution differences. Northern Chinese cattle predominantly belong to B. taurus and southern Chinese cattle belong to B. indicus. Both B. taurus and B. indicus contribute to the admixture of cattle in central China. Thermal stress induces oxidative stress and DNA damage in mammals. In general, B. indicus are more resistant to thermal stress than B. taurus. Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4), which pertains to the family of serine–threonine kinase, is a candidate gene for thermal stress. However, the effects of the bovine EIF2AK4 gene on the thermal tolerance traits of Chinese cattle breeds remain unknown. Our results suggest that a variant of the EIF2AK4 gene is associated with thermal tolerance traits in Chinese cattle. Abstract Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4, also known as GCN2), which pertains to the family of serine–threonine kinase, is involved in oxidative stress and DNA damage repair. A missense single-nucleotide polymorphism (SNP) (NC_037337.1 g.35615224 T > G) in exon 6 of the EIF2AK4 gene which encodes a p.Ile205Ser substitution was observed in the Bovine Genome Variation Database and Selective Signatures (BGVD). The purpose of the current study is to determine the allelic frequency distribution of the locus and analyze its association with thermal tolerance in Chinese indigenous cattle. In our study, the allelic frequency distribution of the missense mutation (NC_037337.1 g.35615224 T > G) in Chinese cattle was analyzed by sequencing 1105 individuals of 37 breeds including 35 Chinese indigenous cattle breeds and two exotic breeds. In particular, association analysis was carried out between the genotypes and three environmental parameters including annual mean temperature (T), relative humidity (RH), and temperature–humidity index (THI). The frequency of the mutant allele G (NC_037337.1 g.35615224 T > G) gradually decreased from the southern cattle groups to the northern cattle groups, whereas the frequency of the wild-type allele T showed an opposite pattern, consistent with the distribution of indicine and taurine cattle in China. In accordance with the association analysis, genotypes were significantly associated with T (P < 0.01), RH (P < 0.01), and THI (P < 0.01), suggesting that the cattle with genotype GG were found in regions with higher T, RH, and THI. Thus, our results suggest that the mutation (NC_037337.1 g.35615224 T > G) of the EIF2AK4 gene is associated with thermal tolerance traits in Chinese cattle.
Age related differences in balance approached by a novel dual-task test of anticipatory postural control strategies

Introduction Assessment of balance is key to identifying individuals with postural control deficits and an increased fall risk. Subjects may compensate for their deficits by utilizing other strategies; to avoid this, it is recommended to assess postural control using a dual-task test. In most dual-task tests, it is difficult to monitor the performance in the secondary task and the individual’s task prioritisation. This study evaluated a new dual-task testing approach. Materials and methods A convenience sample of 54 community-dwelling elderly (age 65+ years) and a reference group of 20 young participants were included in the study. They performed a test in which they could utilize cues to improve their baseline performance, provided their level of postural control allowed them residual attention capacity for this cognitive task. Results Significant performance differences were seen between the young and the elderly. The young group improved their performance time by 23.9% (10.7) and 7.1% (14.2) with a cue and a reverse cue, respectively, whereas the elderly failed to improve their performance time. The test was unable to distinguish between individuals within the elderly group due to a floor effect. Discussion The test reveals an individual’s capacity to use cues for anticipatory postural control strategies in a dual-task setting and thereby estimates automatization of postural control. While the young subjects were capable of improving their performance during dual-task conditions, the elderly subjects apparently had no residual attentional capacity allowing them to utilize the facilitating cues. Within the elderly group, the dual-task aspects of the test added no value with respect to differentiation in the level of postural control.
Continuous Authentication using Stylometry

Static authentication, where user identity is checked once at login time, can be circumvented no matter how strong the authentication mechanism is. Through attacks such as man-in-the-middle and its variants, an authenticated session can be hijacked later after the initial login process has been completed. In the last decade, continuous authentication (CA) using biometrics has emerged as a possible remedy against session hijacking. CA consists of testing the authenticity of the user repeatedly throughout the authenticated session as data becomes available. CA is expected to be carried out unobtrusively, due to its repetitive nature, which means that the authentication information must be collectible without any active involvement of the
Effects of Covertly Measured Home Exercise Adherence on Patient Outcomes Among Older Adults With Chronic Knee Pain.

BACKGROUND Assessment of home exercise adherence and the degree to which adherence influences changes in patient outcomes is limited by the use of self-reported measures. OBJECTIVES To determine the relationship between adherence to a home strengthening program, covertly measured by accelerometers in ankle cuff weights, and changes in self-reported pain, physical function, and knee extensor strength among people with chronic knee pain. METHODS This is a secondary analysis of data from a clinical measurement study in 54 adults, aged 45 years or older, with chronic knee pain who completed a 12-week, home-based quadriceps-strengthening program. A triaxial accelerometer was concealed in the ankle cuff weight used for exercises to assess exercise adherence. Associations between exercise adherence and changes in pain and function (measured using the Western Ontario and McMaster Universities Osteoarthritis Index) and peak isometric knee extensor strength were examined using mixed-effects and linear regression models and fractional polynomials. RESULTS Exercise adherence declined from a median of 90% (interquartile range, 70%-100%) in weeks 0 to 2 to 65% (interquartile range, 25%-90%) in weeks 10 to 12. Significant improvements were observed in knee pain (mean change, -3.2 units; 95% confidence interval [CI]: -2.4, -3.9 units), function (mean change, -10.1 units; 95% CI: -7.8, -12.4 units), and knee extensor strength (mean change, 0.34 Nm/kg; 95% CI: 0.26, 0.42 Nm/kg) across the group over the same period. Exercise adherence was not associated with changes in pain, function, and knee extensor strength over 2-week periods or over the entire 12 weeks. CONCLUSION Covertly measured adherence to a home strengthening program was not associated with changes in patient outcomes. These findings challenge the notion that greater exercise adherence leads to greater improvement in patient outcomes during a short-term intervention. J Orthop Sports Phys Ther 2019;49(7):548-556. doi:10.2519/jospt.2019. 8843.
A Clinical Drug‐Drug Interaction Study Assessing a Novel Drug Transporter Phenotyping Cocktail With Adefovir, Sitagliptin, Metformin, Pitavastatin, and Digoxin

A new probe drug cocktail containing substrates of important drug transporters was tested for mutual interactions in a clinical trial. The cocktail consisted of (predominant transporter; primary phenotyping metric): 10 mg adefovir‐dipivoxil (OAT1; renal clearance (CLR)), 100 mg sitagliptin (OAT3; CLR), 500 mg metformin (several renal transporters; CLR), 2 mg pitavastatin (OATP1B1; clearance/F), and 0.5 mg digoxin (intestinal P‐gp, renal P‐gp, and OATP4C1; peak plasma concentration (Cmax) and CLR). Using a randomized six‐period, open change‐over design, single oral doses were administrated either concomitantly or separately to 24 healthy male and female volunteers. Phenotyping metrics were evaluated by noncompartmental analysis and compared between periods by the standard average bioequivalence approach (boundaries for ratios 0.80–1.25). Primary metrics supported the absence of relevant interactions, whereas secondary metrics suggested that mainly adefovir was a victim of minor drug‐drug interactions (DDIs). All drugs were well tolerated. This cocktail may be another useful tool to assess transporter‐based DDIs in vivo.
How Intelligence Affects Fertility 30 Years On: Retherford and Sewell Revisited — With Polygenic Scores and Numbers of Grandchildren

Abstract Using newly available polygenic scores for educational attainment and cognitive ability, this paper investigates the possible presence and causes of a negative association between IQ and fertility in the Wisconsin Longitudinal Study sample, an issue that Retherford and Sewell first addressed 30 years ago. The effect of the polygenic score on the sample’s reproductive characteristics was indirect: a latent cognitive ability measure, comprised of both educational attainment and IQ, wholly mediated the relationship. Age at first birth mediated the negative effect of cognitive ability on sample fertility, which had a direct (positive) effect on the number of grandchildren. Significantly greater impacts of cognitive ability on the sample’s fertility characteristics were found among the female subsample. This indicates that, in this sample, having a genetic disposition toward higher cognitive ability does not directly reduce number of offspring; instead, higher cognitive ability is a risk factor for prolonging reproductive debut, which, especially for women, reduces the fertility window and, thus, the number of children and grandchildren that can be produced. By estimating the effect of the sample’s reproductive characteristics on the strength of polygenic selection, it was found that the genetic variance component of IQ should be declining at a rate between −. 208 (95% CI [−.020, −.383]) and −. 424 (95% CI [−.041, −.766]) points per decade, depending on whether GCTA-GREML or classical behavior genetic estimates of IQ heritability are used to correct for ‘missing’ heritability.
A new experimental model of muscle pain in humans based on short‐wave diathermy

Experimental models of pain in humans are crucial for understanding pain mechanisms. The most often used muscle pain models involve the injection of algesic substances, such as hypertonic saline solution or nerve growth factor or the induction of delayed onset muscle soreness (DOMS) by an unaccustomed exercise routine. However, these models are either invasive or take substantial time to develop, and the elicited level of pain/soreness is difficult to control. To overcome these shortcomings, we propose to elicit muscle pain by a localized application of short‐wave diathermy (SWD).
Psychological trajectories of mothers and fathers following their child's diagnosis of a life-threatening illness or injury: A longitudinal investigation.

OBJECTIVE Explore the mental health trajectories of parents following their child's life-threatening illness/injury. METHODS Participants were 217 parents (mean age: 34.9-40.0; 66 fathers) of 165 children who presented to a tertiary hospital with a life-threatening illness/injury. Parents completed questionnaires about their mental health and psychosocial stressors within 4 weeks of the child's illness/injury (T1), and 4 months (T2), 7 months (T3), and 19 months (T4) postdiagnosis. RESULTS For both mothers and fathers, mental health symptoms were elevated at diagnosis declining to normal levels by T3, with a pattern of increase at T4. Fathers demonstrated a faster decline in symptoms between T1 and T2, and fathers, but not mothers, experienced a relapse in depressive symptoms at T4. Fathers reported higher rates of work changes. CONCLUSIONS These findings have important implications for the design and timing of parental interventions to support families of children with life-threatening disease/injury.
Comparison of glycemic control after pancreas transplantation for Type 1 and Type 2 diabetic recipients at a high volume center

The number of pancreas transplants (PTX) in patients with Type 2 diabetes (T2DM) has increased in response to excellent outcomes in appropriately selected patients. Not all pancreas transplant centers share an enthusiasm for performing PTX for T2DM out of concern for increased complication rates. This study aims to clarify the characteristics of T2DM recipients with successful outcomes to clarify which candidates are more suitable for PTX as means of maximizing access to this highly effective therapy for Type 2 patients.
Systematic Performance Optimization of Cone-Beam Back-Projection on the Kepler Architecture

Filtered back-projection algorithms are widely used for the reconstruction of volumetric data from cone-beam projections in interventional C-arm computed tomography. Furthermore, general-purpose GPUs have become a popular tool for accelerating the reconstruction during time-critical clinical procedures. In this work, we focus on the systematic performance optimization of cone-beam back-projection on the latest architecture of CUDA-enabled GPUs. Our optimization approach is based on the identification of the major performance bottleneck through the analysis of specifically modified kernels. Our main contribution is a smart restructuring of the backprojection algorithm that facilitates the simultaneous processing of a large number of projections and improves the hit rate of the texture cache at the same time. We use the well-known RabbitCT benchmark to demonstrate the outstanding performance of our implementation on a single Kepler-based GeForce GTX 680 GPU. Our implementation performs the back-projection of 496 input projections onto a cubic 5123 volume in less than one second, which is three times as fast as the best competing implementation. Our back-projection implementation is also able to reconstruct a cubic 10243 volume in about six seconds, which is six times as fast as the best competing implementation known to us.