Miracle-dz/UniFAR-FTUs huggingface dataset:
The PPARGC1A Gly482Ser polymorphism is associated with elite long-distance running performance

ABSTRACT Success in long-distance running relies on multiple factors including oxygen utilisation and lactate metabolism, and genetic associations with athlete status suggest elite competitors are heritably predisposed to superior performance. The Gly allele of the PPARGC1A Gly482Ser rs8192678 polymorphism has been associated with endurance athlete status and favourable aerobic training adaptations. However, the association of this polymorphism with performance amongst long-distance runners remains unclear. Accordingly, this study investigated whether rs8192678 was associated with elite status and competitive performance of long-distance runners. Genomic DNA from 656 Caucasian participants including 288 long-distance runners (201 men, 87 women) and 368 non-athletes (285 men, 83 women) was analysed. Medians of the 10 best UK times (Top10) for 10 km, half-marathon and marathon races were calculated, with all included athletes having personal best (PB) performances within 20% of Top10 (this study’s definition of “elite”). Genotype and allele frequencies were compared between athletes and non-athletes, and athlete PB compared between genotypes. There were no differences in genotype frequency between athletes and non-athletes, but athlete Ser allele carriers were 2.5% faster than Gly/Gly homozygotes (p = 0.030). This study demonstrates that performance differences between elite long-distance runners are associated with rs8192678 genotype, with the Ser allele appearing to enhance performance.
AN ATLAS OF SOUTHERN MK STANDARDS FROM 5800 TO 10,200A

An atlas of stellar spectra covering the wavelength range from 5800A to 10,200A is presented of 126 southern MK standard stars, covering the luminosity classes I, III, and V. Some peculiar stars are included for comparison purposes. The spectra were obtained at a resolution of 4.3A per pixel using a Cassegrain mounted Boller and Chivens spectrograph equipped with a Reticon detector. The quality and utility of the data are discussed and examples of the spectra are presented. The atlas is available in digital format through the NSSDC.
In Vitro–In Vivo Extrapolation of Hepatic Biotransformation Data for Fish. III. An In‐depth Case Study with Pyrene

Computational models that predict chemical bioaccumulation in fish generally account for biotransformation using an apparent first‐order whole‐body rate constant (kB; d–1). The use of such models requires, therefore, that methods exist for estimating kB, ideally without the need to expose live animals. One promising approach for estimating kB involves the extrapolation of measured in vitro intrinsic clearance (CLIN VITRO,INT) to the whole animal (in vitro–in vivo extrapolation, [IVIVE]). To date, however, the accuracy of such predictions has been difficult to assess due to uncertainties associated with one or more extrapolation factors and/or a mismatch between fish used to generate in vitro data and those used to conduct in vivo exposures. In the present study we employed a combined in vitro and in vivo experimental approach to evaluate the IVIVE procedure using pyrene (PYR) as a model chemical. To the extent possible, measured rates of CLIN VITRO,INT were extrapolated to estimates of kB using extrapolation factors based on measured values. In vitro material (liver S9 fraction) was obtained from fish exposed to PYR in a controlled bioconcentration study protocol. Fish from the same study were then used to estimate in vivo kB values from an analysis of chemical depuration data. Averaged across four study groups, kB values estimated by IVIVE underestimated those determined from in vivo data by 2.6‐fold. This difference corresponds to a 4.1‐fold underestimation of true in vivo intrinsic clearance, assuming the liver is the only site of biotransformation. These findings are consistent with previous work performed using mammals and have important implications for use of measured CLIN VITRO,INT values in bioaccumulation assessments with fish. Environ Toxicol Chem 2023;42:1501–1515. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.
Temperature dependence of threshold of strained quantum well lasers

The temperature dependence of threshold current of strained quantum well lasers is analyzed both experimentally and theoretically. The measurements are performed on ridge waveguide In0.2Ga0. 8As/GaAs multiquantum well lasers emitting near 1 μm. The carrier densities at threshold of these lasers are measured using very short current pulse injection. A simplified calculation of the radiative, nonradiative recombination rates and the relationship between gain and carrier density in strained quantum well lasers is described. The results of the calculation are compared with experimental results.
Data-driven ion-independent relative biological effectiveness modeling using the beam quality Q

Beam quality Q = Z2/E (Z = ion charge, E = energy), an alternative to the conventionally used linear energy transfer (LET), enables ion-independent modeling of the relative biological effectiveness (RBE) of ions. Therefore, the Q concept, i.e. different ions with similar Q have similar RBE values, could help to transfer clinical RBE knowledge from better-studied ion types (e.g. carbon) to other ions. However, the validity of the Q concept has so far only been demonstrated for low LET values. In this work, the Q concept was explored in a broad LET range, including the so-called overkilling region. The particle irradiation data ensemble (PIDE) was used as experimental in vitro dataset. Data-driven models, i.e. neural network (NN) models with low complexity, were built to predict RBE values for H, He, C and Ne ions at different in vitro endpoints taking different combinations of clinically available candidate inputs: LET, Q and linear-quadratic photon parameter α x/β x. Models were compared in terms of prediction power and ion dependence. The optimal model was compared to published model data using the local effect model (LEM IV). The NN models performed best for the prediction of RBE at reference photon doses between 2 and 4 Gy or RBE near 10% cell survival, using only α x/β x and Q instead of LET as input. The Q model was not significantly ion dependent (p > 0.5) and its prediction power was comparable to that of LEM IV. In conclusion, the validity of the Q concept was demonstrated in a clinically relevant LET range including overkilling. A data-driven Q model was proposed and observed to have an RBE prediction power comparable to a mechanistic model regardless of particle type. The Q concept provides the possibility of reducing RBE uncertainty in treatment planning for protons and ions in the future by transferring clinical RBE knowledge between ions.
Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury

Abstract Background: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. Methods: Male Sprague–Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. Results: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. Conclusion: PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Dendritic cell-based immunotherapy: a potential player in oral cancer therapeutics.

Background & aim: Dendritic cell (DC)-based immunotherapy modulates a patient's immune system for recognition and subsequent removal of tumor cells. DC-mediated anticancer therapy has been considered in several studies/ongoing trials for multiple types of cancer. Our aim is to describe the potential and current status of DC-based immunotherapy in oral cancer therapeutics. Materials & methods: An internet-based literature search with relevant search terms from 2012 to 2022 post-screening resulted in 58 articles that were considered for systematic review. Results & conclusion: Evaluation of DC based immunotherapy exploiting the critical immune cells in well-equipped laboratories with adequately trained and skilled experts along with a synergistic approach that is affordable and approachable to the patients can prove as an efficient anticancer therapy.
Comparison of the pericapsular nerve group block with the intra-articular and quadratus lumborum blocks in primary total hip arthroplasty: a randomized controlled trial

Background The pericapsular nerve group (PENG) block, quadratus lumborum block (QLB), and intra-articular (IA) local anesthetic injection have been shown to provide effective analgesia in total hip arthroplasty (THA). This randomized study aimed to compare the analgesic efficacy, motor protection, and quality of recovery associated with the PENG block, QLB, and IA injection. Methods Eighty-nine patients who underwent a unilateral primary THA under spinal anesthesia were randomly assigned to the PENG (n = 30), QLB (n = 30), or IA (n = 29) group. The primary outcome was the numerical rating scale (NRS) score over the first 48 h postoperatively. The secondary outcomes were postoperative opioid consumption, quadriceps and adductor muscle strength, and quality of recovery (QoR-40). Results The dynamic (with movement) NRS scores at 3 and 6 h postoperatively were significantly lower in the PENG and QLB groups compared to the IA group (P = 0.002 and P < 0.001, respectively). The time to first opioid analgesia requirement was longer in the PENG and QLB groups than in the IA group (P = 0.009 and P = 0.016, respectively). A provided better preservation was found in the the PENG group than in the QLB group in terms of quadriceps muscle strength at 3 h postoperatively (P = 0.007) and time to mobilization (P = 0.003). No significant differences in the QoR-40 scores were seen. Conclusions The PENG and QLB groups showed similar analgesic effects and both showed more effective analgesia 6 h postoperatively than the IA group. All the groups showed similar postoperative quality of recovery.
Effects of epidural analgesia on the course of labor.

OBJECTIVE The aim of this study was to assess the effects of epidural analgesia on the course of labor. SUBJECTS AND METHODS The material for the study was obtained from the analysis of 300 medical records of patients delivering under epidural analgesia in the period 2015-2019. A questionnaire by the authors was used as the research tool. Statistical analysis was performed using Fisher's test, Pearson's Chi-square test of independence, and Cramer's V-test. RESULTS The first stage of labor in primiparas usually lasted six to nine hours, and in multiparas under five hours (p = 0.041). The second stage was shorter in multiparas (p < 0.001). Our five-year analysis demonstrated that the second stage of labor was longer from year to year (p = 0.087). The fetal station had an effect on the duration of the first stage of labor (p = 0.057). After administration of epidurals, the majority of the women bore the pain well (p = 0.052). CONCLUSIONS Epidural analgesia reduces labor pain, but may also disturb the natural rhythm of labor. This happens even if the moment of application of the analgesia is chosen with the guidance of obstetric indications, and may result in the necessity for surgical intervention.
Naturally occurring substitution of an amino acid in a plant virus gene-silencing suppressor enhances viral adaptation to increasing thermal stress

Cereal yellow dwarf virus (CYDV-RPV) encodes a P0 protein that functions as a viral suppressor of RNA silencing (VSR). The strength of silencing suppression is highly variable among CYDV-RPV isolates. In this study, comparison of the P0 sequences of CYDV-RPV isolates and mutational analysis identified a single C-terminal amino acid that influenced P0 RNA-silencing suppressor activity. A serine at position 247 was associated with strong suppressor activity, whereas a proline at position 247 was associated with weak suppressor activity. Amino acid changes at position 247 did not affect the interaction of P0 with SKP1 proteins from Hordeum vulgare (barley) or Nicotiana benthamiana. Subsequent studies found P0 proteins containing a P247 residue were less stable than the P0 proteins containing an S247 residue. Higher temperatures contributed to the lower stability and in planta and the P247 P0 proteins were subject to degradation via the autophagy-mediated pathway. A P247S amino acid residue substitution in P0 increased CYDV-RPV replication after expression in agroinfiltrated plant leaves and increased viral pathogenicity of P0 generated from the heterologous Potato virus X expression vector system. Moreover, an S247 CYDV-RPV could outcompete the P247 CYDV-RPV in a mixed infection in natural host at higher temperature. These traits contributed to increased transmission by aphid vectors and could play a significant role in virus competition in warming climates. Our findings underscore the capacity of a plant RNA virus to adapt to climate warming through minor genetic changes in gene-silencing suppressor, resulting in the potential for disease persistence and prevalence.
Uncertainty in Control Design for Flexible System

This article focuses the research on the description of plant uncertainty in robust control design. The limitation of multiplicative uncertainties in controller was pointed out by analyzing the modal perturbation in weak damping flexible system and principles for designing robust stability controllers for flexible systems were given at the same time. An implementation was used to indicate that weakly damped harmonic modal perturbation can be described clearly with coprime factor perturbation,which is good for robust design.
Epidemic models featuring behaviour change

This paper considers a model for the spread of an epidemic in a closed population whose members are in either a high-risk or a low-risk activity group. Further, members of the high-risk group may change their behaviour by entering the low-risk group. Both stochastic and deterministic models are examined. A limiting model, appropriate when there is a large number of initially susceptible individuals, is used to provide a threshold analysis. The epidemic is compared to a single group epidemic, and to suitably parametrised two-group epidemics, using a coupling method. The total size distribution and effects of changing the behaviour change rate are considered.
Optimal model reduction and frequency-weighted extension

In this paper the quadratically optimal model reduction problem for single-input, single-output systems is considered. The reduced order model is determined by minimizing the integral of the magnitude-squared of the transfer function error. It is shown that the numerator coefficients of the optimal approximant satisfy a weighted least squares problem and, on this basis, a two-step iterative algorithm is developed combining a least squares solver with a gradient minimizer. The existence of globally optimal stable solutions to the optimization problem is established, and convergence of the algorithm to stationary values of the cost function is proved. The formulation is extended to handle the frequency-weighted optimal model reduction problem. Three examples demonstrate the optimization algorithm.
Leap or lag: left atrial appendage closure and guidelines

Abstract Atrial fibrillation (AF) is associated with life-threatening thromboembolism. Most emboli stem from thrombosis in the left atrial appendage (LAA). The current treatment of choice is oral anticoagulants (OACs), but a small proportion of patients cannot take OACs predominantly because of the so-called unacceptable bleeding risks. However, many who initially accept OACs subsequently stop therapy or reduce the OAC treatment to a potentially non-effective dose leaving them exposed to thromboembolic risk. A relatively simple alternative therapy involves the catheter-based insertion of a LAA closure (LAAC) device to prevent thromboembolism from the LAA. There is a considerable evidence base for this therapy consisting of clinical trials and observational data which suggests comparable therapeutic efficacy with a possible small excess of ischaemic strokes. Although LAAC has been very closely examined by regulators and approved for market release, guidelines from most professional societies give only weak recommendations for use of this device which may be the only known effective therapy available to some at-risk AF patients. Guidance materials from the same societies more enthusiastically endorse LAAC. Clinical practice is running well ahead of the guidelines because equipoise has been lost by physicians faced with patients for whom they have no other effective therapy. Guideline writers are correct in providing recommendations which are less strong for LAAC than for OACs, for those who are able and willing to take OAC treatment, but for those who are not, a stronger recommendation is needed. But, should the guidelines lag behind or leap ahead of the available evidence?
Draft Genome Sequences of 18 Bacteroidetes Strains Isolated from a Human Stool Sample

We announce the draft genome sequences of 12 Bacteroides, 4 Phocaeicola, and 2 Parabacteroides strains, among which was a newly isolated species, Bacteroidaceae bacterium UO.H1004. These isolates produce health-benefiting short-chain fatty acids (SCFAs) and the neurotransmitter γ-aminobutyric acid (GABA) in various concentrations. ABSTRACT We announce the draft genome sequences of 12 Bacteroides, 4 Phocaeicola, and 2 Parabacteroides strains, among which was a newly isolated species, Bacteroidaceae bacterium UO.H1004. These isolates produce health-benefiting short-chain fatty acids (SCFAs) and the neurotransmitter γ-aminobutyric acid (GABA) in various concentrations.
The Relationship Between Elastin Crosslinking and Alveolar Wall Rupture in Human Pulmonary Emphysema.

INTRODUCTION To better define the role of mechanical forces in pulmonary emphysema, we employed methods recently developed in our laboratory to identify microscopic level relationships between airspace size and elastin-specific desmosine and isodesmosine (DID) crosslinks in normal and emphysematous human lungs. METHODS Free DID in wet tissue (a biomarker for elastin degradation) and total DID in formalin-fixed, paraffin embedded (FFPE) tissue sections were measured using liquid chromatography-tandem mass spectrometry and correlated with alveolar diameter, as determined by the mean linear intercept (MLI) method. RESULTS There was a positive correlation between free lung DID and MLI (p<0.0001) in formalin-fixed lungs, and elastin breakdown was greatly accelerated when airspace diameter exceeded 400 µm. In FFPE tissue, DID density was markedly increased beyond 300 µm (p<0.0001) and leveled off around 400 µm. Elastic fiber surface area similarly peaked at around 400 µm, but to a much lesser extent than DID density, indicating that elastin crosslinking is markedly increased in response to early increases in airspace size. CONCLUSIONS These findings support the hypothesis that airspace enlargement is an emergent phenomenon in which initial proliferation of DID crosslinks to counteract alveolar wall distention is followed by a phase transition involving rapid acceleration of elastin breakdown, alveolar wall rupture, and progression to an active disease state that is less amenable to therapeutic intervention.
Advances in the discovery of drugs that treat pulmonary arterial hypertension

ABSTRACT Introduction Distal pulmonary arterial remodeling and elevated pulmonary vascular resistance are characteristic of pulmonary arterial hypertension (PAH). Current approved vasodilator-specific PAH therapy that includes phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids has demonstrated dramatic enhancement in functional capacity, quality of life, and invasive hemodynamics. However, none of these treatments are curative, underscoring the need to identify new pathophysiologic signaling pathways. Areas covered The author provides a comprehensive review on current knowledge and recent development in the understanding of PAH. Furthermore, the author discusses PAH potential genetic causes as well as novel molecular signaling pathways. This article also reviews the currently approved PAH specific therapy based on pivotal clinical trials and ongoing clinical trials using novel compounds that specifically target PAH pathogenesis. Expert opinion The discovery of novel signaling pathways – growth factors, tyrosine kinases, BMPs, estrogen, and serotonin – involved in the PAH pathobiology will lead within the next 5 years to the approval of new therapeutic agents targeting these different pathways. If proven beneficial, these new agents may reverse or at least prevent the progression of this devastating and lethal disease.
Metagenomes and Metagenome-Assembled Genome Sequences from Nitrogen-Fixing Alder Nodules

Bacterial nitrogen (N) fixation in alder nodules is a key process providing nitrogen to nutrient-limited arctic biomes. Here, 45 prokaryotic metagenome-assembled genome (MAG) sequences from root nodules of arctic alder are reported. ABSTRACT Bacterial nitrogen (N) fixation in alder nodules is a key process providing nitrogen to nutrient-limited arctic biomes. Here, 45 prokaryotic metagenome-assembled genome (MAG) sequences from root nodules of arctic alder are reported.
Inactivation of Human Aldehyde Oxidase by Small Sulfhydryl-Containing Reducing Agents

Human aldehyde oxidase (hAOX1) is a molybdoflavoenzyme that belongs to the xanthine oxidase (XO) family. hAOX1 is involved in phase I drug metabolism, but its physiologic role is not fully understood to date, and preclinical studies consistently underestimated hAOX1 clearance. In the present work, we report an unexpected effect of the common sulfhydryl-containing reducing agents, e.g., dithiothreitol (DTT), on the activity of hAOX1 and mouse aldehyde oxidases. We demonstrate that this effect is due to the reactivity of the sulfido ligand bound at the molybdenum cofactor with the sulfhydryl groups. The sulfido ligand coordinated to the Mo atom in the XO family of enzymes plays a crucial role in the catalytic cycle and its removal results in the total inactivation of these enzymes. Because liver cytosols, S9 fractions, and hepatocytes are commonly used to screen the drug candidates for hAOX1, our study suggests that DTT treatment of these samples should be avoided, otherwise false negative results by an inactivated hAOX1 might be obtained. SIGNIFICANCE STATEMENT This work characterizes the inactivation of human aldehyde oxidase (hAOX1) by sulfhydryl-containing agents and identifies the site of inactivation. The role of dithiothreitol in the inhibition of hAOX1 should be considered for the preparation of hAOX1-containing fractions for pharmacological studies on drug metabolism and drug clearance.