Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronotherapy with a glucokinase activator profoundly improves metabolism in obese Zucker rats

Circadian rhythms play a critical role in regulating metabolism, including daily cycles of feeding/fasting. Glucokinase (GCK) is central for whole-body glucose homeostasis and oscillates according to a circadian clock. GCK activators (GKAs) effectively reduce hyperglycemia, but their use is also associated with hypoglycemia, hyperlipidemia, and hepatic steatosis. Given the circadian rhythmicity and natural postprandial activation of GCK, we hypothesized that GKA treatment would benefit from being timed specifically during feeding periods. Acute treatment of obese Zucker rats with the GKA AZD1656 robustly increased flux into all major metabolic pathways of glucose disposal, enhancing glucose elimination. Four weeks of continuous AZD1656 treatment of obese Zucker rats improved glycemic control; however, hepatic steatosis and inflammation manifested. In contrast, timing AZD1656 to feeding periods robustly reduced hepatic steatosis and inflammation in addition to improving glycemia, whereas treatment timed to fasting periods caused overall detrimental metabolic effects. Mechanistically, timing AZD1656 to feeding periods diverted newly synthesized lipid toward direct VLDL secretion rather than intrahepatic storage. In line with increased hepatic insulin signaling, timing AZD1656 to feeding resulted in robust activation of AKT, mTOR, and SREBP-1C after glucose loading, pathways known to regulate VLDL secretion and hepatic de novo lipogenesis. In conclusion, intermittent AZD1656 treatment timed to feeding periods promotes glucose disposal when needed the most, restores metabolic flexibility and hepatic insulin sensitivity, and thereby avoids hepatic steatosis. Thus, chronotherapeutic approaches may benefit the development of GKAs and other drugs acting on metabolic targets. Description The ability of the glucokinase activator AZD1656 to improve metabolism is highly dependent on a dosing regimen timed to feeding. Timing treatment Glucokinase activators (GKAs) have been investigated in clinical trials for improvement of glucose control but most were abandoned because of adverse side effects. Kroon et al. now show that timing administration of a small-molecule GKA to feeding periods resulted in improved glycemic control and attenuated hepatosteatosis and inflammation in obese Zucker rats. In contrast, although continuous treatment during both feeding and fasting improved blood glucose it led to hepatosteatosis and inflammation, and treatment during fasting worsened glycemic control and systemic inflammation. This study suggests that chronotherapy with GKAs may provide an avenue to rescue this class of antidiabetics.
Genetics and Molecular Biology

Nitric Oxide (NO) has important biological functions, and its production may be influenced by genetic polymorphisms. Since NO mediates the drug response, the same genetic polymorphism that alter NO levels may also impact drug therapy. The vast majority of studies in the literature that assess the genetic influence on NO-related drug response focus on NOS3 (which encodes endothelial nitric oxide synthase), however several other proteins are interconnected in the same pathway and may also impact NO availability and drug response. The aim of this study was to review the literature regarding genetic polymorphisms that influence NO in response to pharmacological agents located in genes other than NOS3. Articles were obtained from Pubmed and consisted of 17 manuscripts that assessed polymorphisms of the following targets: Arginases 1 and 2 (ARG1 and ARG2), dimethylarginine dimethylaminohydrolases 1 and 2 (DDAH1 and DDAH2), and vascular endothelial growth factor (VEGF). Here we analyze the main results of these articles, which show promising evidences that may suggest that the NO-driven pharmacological response is affected by more than the eNOS gene. The search for genetic markers may result in better understanding of the variability of drug response and turn pharmacotherapy involving NO safer and more effective.
Spontaneous Coronary Artery Dissection: Review of Possible Pathophysiological Risk Factors

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS) that typically affects the younger and healthier female population without the typical ACS risk factors such as hypertension, diabetes, or hyperlipidemia. The clinical presentation of SCAD can be diverse and the diagnosis is typically by coronary angiography but also can require advanced imaging such as intravascular ultrasound or optical coherence tomography. Past studies have shown the atypical patient characteristics of SCAD patients among ACS patients. The main challenge is that the exact pathophysiology of SCAD is unknown. Potential pathophysiological risk factors are discussed including fibromuscular dysplasia, other arteriopathies, pregnancy and female sex hormone changes, migraines, inflammatory conditions, and stress. The current understanding of these risk factors along with potential pathophysiological mechanisms are discussed. There still remain many areas of additional investigation in understanding this rare cause of ACS.
The Kormendy relation of galaxies in the Frontier Fields clusters: Abell S1063 and MACS J1149.5+2223

We analyse the Kormendy relations (KRs) of the two Frontier Fields clusters, Abell S1063, at z = 0.348, and MACS J1149.5+2223, at z = 0.542, exploiting very deep Hubble Space Telescope photometry and Very Large Telescope (VLT)/Multi Unit Spectroscopic Explorer (MUSE) integral field spectroscopy. With this novel data set, we are able to investigate how the KR parameters depend on the cluster galaxy sample selection and how this affects studies of galaxy evolution based on the KR. We define and compare four different galaxy samples according to (a) Sersic indices: early-type (‘ETG’), (b) visual inspection: ‘ellipticals’, (c) colours: ‘red’, (d) spectral properties: ‘passive’. The classification is performed for a complete sample of galaxies with m_(F814W) ≤ 22.5 ABmag (M* ≳ 10^(10.0) M⊙). To derive robust galaxy structural parameters, we use two methods: (1) an iterative estimate of structural parameters using images of increasing size, in order to deal with closely separated galaxies and (2) different background estimations, to deal with the intracluster light contamination. The comparison between the KRs obtained from the different samples suggests that the sample selection could affect the estimate of the best-fitting KR parameters. The KR built with ETGs is fully consistent with the one obtained for ellipticals and passive. On the other hand, the KR slope built on the red sample is only marginally consistent with those obtained with the other samples. We also release the photometric catalogue with structural parameters for the galaxies included in the present analysis.
Diagonal similarity and equivalence for matrices over groups with 0

the cyclic products of matrices and diagonal similarity. In this paper we consider diagonal similarity for matrices, which may be infinite, and whose elements lie in a (possible non-commutative) group G with O. Let H be a subgroup of a group G and let A be an irreducible square matrix with entries in GO. In Theorem 3.4, we give necessary and sufficient conditions for the existence of a matrix B with entries in H O which is diagonally similar to A. If H is a complete lattice ordered group whose positive cone H+ is normal in G, we give necessary and sufficient conditions for the existence of a matrix ' B in (H+)O which is diagonally similar to A; see Theorems 4.1 and 4.2. Our Theorem 4.1 reduces to a result due to AFRIAT [1J, [2J Theorem 2 and FIEDLER-PTAK [4J Theorem 2.2 in the case when G and H are the additive group of reals, there is no absorbing (zero) element and A is a finite matrix. Let A be a rectangular matrix, possible infinite, with entries in GO, such that each row and column has at least one element in G. We construct a square matrix Alp of larger siz::, which is always completely reducible, Corollary 5.4. In Theorem 5.6, we show that two recta:ngular matrices A and B are diagonally equivalent if and only if Alp and Blp are diagonally similar. Thus it is possible to derive theorems on diagonal equivalence for arbitrary rectangular matrices from theorems on the diagonal similarity of irreducible square matrices, e.g. Theorem 6.3. In particular, as a corollary to either Theorem 6.2 or Theorem 6.3 we obtain a slightly improved version of the remarkable result by LALLEMENT-PETRICH ([6J, Theorem 1 (b)-= (e),
On long range axion hairs for black holes

The physics of black holes can suggest new ways to test the existence of axions. Much work has been done so far to analyse the phenomenon of superradiance associated with axions in the ergoregion surrounding rotating black holes. In this work, we instead investigate how Chern–Simons axion couplings of the form and , well motivated by particle physics and string theory, can induce long range profiles for light axion fields around charged black holes, with or without spin. We extend known solutions describing axion hairs around spherically symmetric, asymptotically flat dyonic black hole configurations, charged under gauge symmetries, by including non-minimal couplings with gravity. The axion acquires a profile controlled by the black hole conserved charges, and we analytically determine how it influences the black hole horizon and its properties. We find a Smarr formula applying to our configurations. We then generalise known solutions describing axion hairs around slowly rotating black hole configurations with charge. To make contact with phenomenology, we briefly study how long range axion profiles induce polarised deflection of light rays, and the properties of ISCOs for the black hole configurations we investigate.
Ultrasound-Guided Erector Spinae Block Versus Ultrasound-Guided Thoracic Paravertebral Block for Pain Relief in Patients With Acute Thoracic Herpes Zoster: A Randomized Controlled Trial.

BACKGROUND Severe acute pain is a significant risk factor for postherpetic neuralgia (PHN). The importance of early management in alleviating zoster pain cannot be overstated. OBJECTIVES This study aimed to determine the efficiency and safety of one bolus injection thoracic paravertebral block (PVB) and erector spinae plane block (ESB) in individuals with acute thoracic herpes zoster (HZ) in preventing PHN. STUDY DESIGN A prospective randomized controlled trial. SETTING Tanta University Hospitals, Tanta, Egypt. METHODS Ninety participants over the age of 50 years with chest wall herpetic eruption, lasting shorter than a week along with moderate to severe pain, who got adequate antiviral medication. Patients were chosen at random and classified into 3 equal groups. Group C (control group) did not receive any intervention. Group ESB received US-guided ESB with 25 mg bupivacaine 0.5%, plus 8 mg dexamethasone (10 mL volume). Group PVB received US-guided PVB with 25 mg bupivacaine 0.5%, plus 8 mg dexamethasone (10 mL volume). RESULTS Numerical rating scale (NRS) showed insignificant differences at baseline. NRS for pain at 1, 3, 4, 12, and 24 weeks was significantly reduced in group ESB compared to group C and in group PVB than group C and insignificantly different between group ESB and group PVB. Doses of pregabalin and acetaminophen were comparable at 1 week among the studied groups. Doses of pregabalin and acetaminophen at 3, 4, 12, and 24 weeks were significantly lesser in group ESB compared to group C and in group PVB than group C and insignificantly different between group ESB and group PVB. After 3 months, the incidence of persistent herpetic pain was not significantly different between the study groups. After 6 months, the incidence of persistent herpetic pain was statistically significantly lower in groups ESB and PVB than in group C (P = 0.037 and 0.015, respectively) without significant difference between group ESB and group PVB. LIMITATIONS Small sample size, single center study. CONCLUSIONS Both ESB and PVB were effective in controlling acute pain and persistent herpetic pain after 6 months (which was evident by lower NRS for pain and doses of pregabalin and acetaminophen), but ESB is safer (no reported pneumothorax and hypotension).
Is the Interpolated-Twitch Technique-Derived Voluntary Activation Just Neural? Novel Perspectives from Mechanomyographic Data

ABSTRACT Purpose Voluntary activation (VA) determined by interpolation-twitch technique could be affected by the characteristics of the in-series elastic components. To overcome this possible bias, a novel approach based on the mechanomyographic (MMG) signal to detect voluntary activation (VAMMG) has been proposed. We examined the changes in VA and VAMMG after passive stretching to check the influence of neural and mechanical factors in the force output. Methods Twenty-six healthy men underwent VA assessment using the interpolated-twitch technique before and after unilateral passive stretching of the plantarflexors (five 45-s on + 15-s off). In addition to the force signal, the MMG signal was detected on gastrocnemius medialis, gastrocnemius lateralis, and soleus. From the force and MMG signal analysis, VA and VAMMG were calculated in the stretched and contralateral nonstretched limbs. Joint passive stiffness was also defined. Results In the stretched limb, passive stretching increased dorsiflexion range (mean ± SD = +18% ± 10%, P < 0.001, ES = 1.54) but reduced joint passive stiffness (−22% ± 8%, P < 0.001, ES = −1.75), maximum voluntary contraction (−15% ± 7%, P < 0.001, ES = −0.87), VA (−7% ± 3%, P < 0.001, ES = −2.32), and VAMMG (~−5% ± 2%, P < 0.001, ES = −1.26/−1.14). In the contralateral nonstretched limb, passive stretching increased dorsiflexion range (+10% ± 6%, P < 0.001, ES = 0.80) but reduced joint passive stiffness (−3% ± 2%, P = 0.041, ES = −0.27), maximum voluntary contraction (−4% ± 3%, P = 0.035, ES = −0.24), VA (−4% ± 2%, P < 0.001, ES = −1.77), and VAMMG (~− 2% ± 1%, P < 0.05, ES = −0.54/−0.46). The stretch-induced changes in VA correlated with VAMMG (R ranging from 0.447 to 0.583 considering all muscles) and with joint passive stiffness (stretched limb: R = 0.503; contralateral nonstretched limb: R = 0.530). Conclusions VA output is overall influenced by both neural and mechanical factors, not distinguishable using the interpolated-twitch technique. VAMMG is a complementary index to assess the changes in VA not influenced by mechanical factors and to examine synergistic muscles.
Educational and Clinical Associations With Longitudinal Cognitive Function and Brain Imaging in American Indians

Background and Objectives Little is known about incidence of vascular and Alzheimer dementias in American Indians. Methods We conducted a large, heterogeneous, population-based, longitudinal cohort study of brain aging in community-dwelling American Indians aged 64–95 years from 11 tribes across 3 states, with neurologic examinations, 1.5T MRI, and extensive cognitive testing. Visit 1 in 2010–2013 (n = 817) and visit 2 in 2017–2019 (n = 403) included all willing, surviving participants. Standardized cognitive tests at both visits included Modified Mini-Mental Status Examination (MMSE), Wechsler Adult Intelligence Scale digit symbol coding (WAIS), Controlled Oral Word Association (COWA), and California Verbal Learning Test short form (CVLT). Test materials added at follow-up included Wide Range Achievement (reading) Test (WRAT) and National Alzheimer Coordinating Center Uniform Data Set cognitive battery (v3 form C2), including Montreal Cognitive Assessment (MoCA). MRI neuroradiologists coded infarcts, hemorrhages, white matter hyperintensities, sulcal atrophy, and ventricle enlargement. Results The mean time between examinations was 6.7 years (SD 1.1, range 3.8–9.1 years). Years of formal education had modest correlation with WRAT reading score (r = 0.45). Prevalence and incidence (respectively) of infarcts were 32% and 12.8/1,000 person-years (PYs) hemorrhages 6% and 4.4/1000 PY worsening sulci 74% and 19.0/1000 PY worsening ventricle 79% and 30.1/1000 PY worsening leukoaraiosis 44% and 26.1/1000 PY. Linear losses per year in cognitive scores were 0.6% MMSE, 1.2% WAIS, 0.6% COWA, and 2.2% CVLT. The mean MoCA scores were 18.9 (SD 4.3). Discussion These are the first data on longitudinal cognitive and imaging changes in American Indians and first reports of Alzheimer disease–related features. The mean scores in MoCA were similar or lower than standard cutoffs used to diagnose dementia in other racial/ethnic groups, suggesting that standardized cognitive tests may not perform well in this population. Test validation, adaptation, and score adjustment are warranted. Years of education were a poor proxy for premorbid function, suggesting novel methods for cognitive score contextualization is also needed in this population. Evaluation of selective survival suggests attrition from death, and frailty should be accounted for in causal analyses. Overall, these data represent a unique opportunity to examine neurology topics of critical importance to an understudied population.
New Insights into Time Series Analysis III: Setting constraints on period analysis

E-science of photometric data requires automatic procedures and a precise recognition of periodic patterns to perform science as well as possible on large data. Analytical equations that enable us to set the best constraints to properly reduce processing time and hence optimize signal searches play a crucial role in this matter. These are increasingly important because the production of unbiased samples from variability indices and statistical parameters has not been achievable so far. We discuss the constraints used in periodic signals detection methods as well as the uncertainties in the estimation of periods and amplitudes. The frequency resolution necessary to investigate a time series is assessed with a new approach that estimates the necessary sampling resolution from shifts on the phase diagrams for successive frequency grid points.We demonstrate the underlying meaning of the oversampling factor. We reassess the frequency resolutions required to find the variability periods of EA stars and use the new resolutions to analyse a small sample of EA up Catalina stars, i.e. EA stars previously classified as having insufficient number of observations at the eclipses. As a result, the variability periods of four EA up stars were determined. Moreover, we have a new approach to estimate the amplitude and period variations. From these estimations information about the intrinsic variations of the sources are obtained. For a complete characterization of the light curve signal the period uncertainty and period variation must be determined. Constraints on periodic signal searches were analysed and delimited.
Clinical and Radiological Risk Factors of Early Recurrent Lumbar Disc Herniation at Six Months or Less: A Clinical Retrospective Analysis in One Medical Center.

BACKGROUND Recurrent LDH (rLDH) is one of the most common causes of unsatisfactory outcomes after discectomy, which usually needs secondary surgery and leads to physical and psychological suffering for patients and substantial costs for society. OBJECTIVES This study was conducted to analyze the risk factors of early rLDH (<= 6 months) and to reduce the incidence of early rLDH. STUDY DESIGN A clinical retrospective study. METHODS A total of 1,228 patients received percutaneous endoscopic lumbar discectomy surgery from January 2013 through December 2016; there was a minimum 5-year follow-up. Seventy-seven of them (6.27%) developed recurrences and were included in this study. According to the differences in recurrent time, patients were divided into 2 groups (<= 6 months and > 6 months). Clinical and radiological parameters were retrospectively collected through chart review and preoperative imaging. All related risk factors were collected and analyzed relative to the time of recurrent herniation. RESULTS Patients with rLDH at <= 6 months and > 6 months were 49 and 28, respectively. Recurrence most often occurred within 6 months postoperatively, which was 63.6% of the total patients with rLDH. Of those risk factors, Modic changes, disc height index (DHI), and facet orientation (FO) showed significant statistical differences P = 0.003, P = 0.036, and P = 0.007, respectively). A logistic regression analysis was performed and showed there was an independent significant relationship between Modic changes (P = 0.042) and FO (P = 0.005) and early rLDH. LIMITATIONS First, this was a retrospective nonrandomized study, and the number of patients with rLDH included in this study was relatively small. Second, limited risk factors were assessed in this study, and some relevant risk factors that were identified as significant independent predictors in other studies were not included in this study, such as canal diameter, annular defect size, migrated disc, and foraminoplasty. Third, this study compared the clinical and radiological parameters of patients with rLDH at different times, and one case-control study is needed for further study, especially in terms of standardized sampling and data classification. CONCLUSION This study demonstrated that the recurrence rate of LDH at 5-year follow-up was 6.27% and there was a significant statistical relationship between FO, DHI, and Modic changes and early rLDH. Surgeons should take FO angles, DHI, and Modic change into consideration before surgery to achieve a satisfactory postoperative outcome and a relatively lower early recurrence rate. More patients and further investigation should be taken to assess the risk factors for early rLDH.
A retrospective comparative study of microwave ablation and sublobectomy in the treatment of early subpleural nonsmall cell lung cancer

Abstract Objective Microwave ablation (MWA) is a safe and effective local therapy, however, its efficacy in stage I subpleural nonsmall cell lung cancer (NSCLC) compared to that of sublobar resection (SLR) is unclear. This study aimed to compare the efficacy of the two treatments for stage I NSCLC ≤1 cm from the pleura. Methods After propensity score matching (PSM), 70 patients with stage I subpleural NSCLC who underwent either SLR or MWA (35 patients each) from 2014 to 2018 were included. The margin pathology of SLR was negative. MWA reached a sufficient ablative margin. MWA group were stratified according to the minimal ablative margin, with 10 patients each in the 5–10 mm group and the >10 mm group after PSM. The local recurrence-free survival (LRFS), relapse-free survival (RFS), overall survival (OS), and treatment-related complications were compared. Results For patients with stage I subpleural NSCLC, the LRFS of patients in the SLR group (35.657 ± 0.338 months, 95% CI: 34.995–36.319) was significantly better than that in the MWA group (31.633 ± 1.574 months, 95% CI: 28.548–34.719, p = 0.021). The RFS was also significantly better in the SLR group (35.629 ± 0.338 months, 95% CI: 34.966–36.292) than in the MWA group (29.387 ± 1.866 months, 95% CI: 25.730–33.044, p = 0.007), but there were no significant differences in terms of the 3-year OS (p = 0.079) and incidence of complications (14.3% vs. 11.4%, p = 0.653). The minimal ablative margin of >10 mm was not significantly associated with the LRFS (p = 0.929). Conclusion MWA for stage I subpleural NSCLC showed similar survival outcomes and complication rates to SLR, but poorer local tumor control.