Miracle-dz/UniFAR-FTUs huggingface dataset:
Plant genome evolution in the genus Eucalyptus driven by structural rearrangements that promote sequence divergence

Genomes have a highly organised architecture (non-random organisation of functional and non-functional genetic elements within chromosomes) that is essential for many biological functions, particularly, gene expression and reproduction. Despite the need to conserve genome architecture, a surprisingly high level of structural variation has been observed within species. As species separate and diverge, genome architecture also diverges, becoming increasingly poorly conserved as divergence time increases. However, within plant genomes, the processes of genome architecture divergence are not well described. Here we use long-read sequencing and de novo assembly of 33 phylogenetically diverse, wild and naturally evolving Eucalyptus species, covering 1-50 million years of diverging genome evolution to measure genome architectural conservation and describe architectural divergence. The investigation of these genomes revealed that following lineage divergence genome architecture is highly fragmented by rearrangements. As genomes continue to diverge, the accumulation of mutations and subsequent divergence beyond recognition of rearrangements becomes the primary driver of genome divergence. The loss of syntenic regions also contribute to genome divergence, but at a slower pace than rearrangements. We hypothesise that duplications and translocations are potentially the greatest contributors to Eucalyptus genome divergence.
Apical-basal distribution of different subtypes of spiral ganglion neurons in the cochlea and the changes during aging

Sound information is transmitted from the cochlea to the brain mainly by type I spiral ganglion neurons (SGNs), which consist of different subtypes with distinct physiological properties and selective expression of molecular markers. It remains unclear how these SGN subtypes distribute along the tonotopic axis, and whether the distribution pattern changes during aging that might underlie age-related hearing loss (ARHL). We investigated these questions using immunohistochemistry in three age groups of CBA/CaJ mice of either sex, including 2–5 months (young), 17–19 months (middle-age), and 28–32 months (old). Mouse cochleae were cryo-sectioned and triple-stained using antibodies against Tuj1, calretinin (CR) and calbindin (CB), which are reportedly expressed in all type I, subtype Ia, and subtype Ib SGNs, respectively. Labeled SGNs were classified into four groups based on the expression pattern of stained markers, including CR+ (subtype Ia), CB+ (subtype Ib), CR+CB+ (dual-labeled Ia/Ib), and CR-CB- (subtype Ic) neurons. The distribution of these SGN groups was analyzed in the apex, middle, and base regions of the cochleae. It showed that the prevalence of subtype Ia, Ib and dual-labeled Ia/Ib SGNs are high in the apex and low in the base. In contrast, the distribution pattern is reversed in Ic SGNs. Such frequency-dependent distribution is largely maintained during aging except for a preferential reduction of Ic SGNs, especially in the base. These findings corroborate the prior study based on RNAscope that SGN subtypes show differential vulnerability during aging. It suggests that sound processing of different frequencies involves distinct combinations of SGN subtypes, and the age-dependent loss of Ic SGNs in the base may especially impact high-frequency hearing during ARHL.
LDHA-regulated tumor-macrophage symbiosis promotes glioblastoma progression

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase (LDH) inhibitor stiripentol (an FDA-approved anti-seizure drug for Dravet Syndrome) emerges as the top hit. Combined profiling and functional studies demonstrate that LDHA-directed ERK pathway activates YAP1/STAT3 transcriptional co-activators in glioblastoma cells to upregulate CCL2 and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.
Directed physiological networks in the human prefrontal cortex at rest and post transcranial photobiomodulation

Abstract Cerebral infra-slow oscillation (ISO) is a source of vasomotion in endogenic (E; 0.005–0.02 Hz), neurogenic (N; 0.02–0.04 Hz), and myogenic (M; 0.04–0.2 Hz) frequency bands. In this study, we quantified changes in prefrontal concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics, and electroencephalogram (EEG) powers as electrophysiological activity, using concurrent measurements of 2-channel broadband near-infrared spectroscopy and EEG on the forehead of 22 healthy participants at rest. After preprocessing, the multi-modality signals were analyzed using generalized partial directed coherence to construct unilateral neurophysiological networks among the three neurophysiological metrics (with simplified symbols of HbO, CCO, and EEG) in each E/N/M frequency band. The links in these networks represent neurovascular, neurometabolic, and metabolicvascular coupling (NVC, NMC, and MVC). The results illustrate that the demand for oxygen by neuronal activity and metabolism (EEG and CCO) drives the hemodynamic supply (HbO) in all E/N/M bands in the resting prefrontal cortex. Furthermore, to investigate the effect of transcranial photobiomodulation (tPBM), we performed a sham-controlled study by delivering an 800-nm laser beam to the left and right prefrontal cortex of the same participants. After performing the same data processing and statistical analysis, we obtained novel and important findings: tPBM delivered on either side of the prefrontal cortex triggered the alteration or reversal of directed network couplings among the three neurophysiological entities (i.e., HbO, CCO, and EEG frequency-specific powers) in the physiological network in the E and N bands, demonstrating that during the post-tPBM period, both metabolism and hemodynamic supply drive electrophysiological activity in directed network coupling of the PFC. Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.
Can strength training or tai ji quan training reduce frailty in postmenopausal women treated with chemotherapy? A secondary data analysis of the GET FIT trial

Abstract Purpose : To determine whether strength training or tai ji quan can reduce frailty in older, postmenopausal women treated with chemotherapy for cancer. Methods : We conducted a secondary data analysis from a 3-arm, single-blind, randomized controlled trial where older (50+ years), postmenopausal women cancer survivors were randomized to supervised group exercise programs: tai ji quan, strength training, or stretching control for 6 months. We assessed frailty using a 4-criteria model consisting of weakness, fatigue, inactivity, and slowness. Using logistic regression, we determined whether the frailty phenotype (pre-frailty or frailty) decreased post-intervention, how many and which frailty criteria decreased, and what characteristics identified women most likely to reduce frailty. Results : Data from 386 women who completed baseline and 6-month testing were used (mean age of 62.0 ± 6.4 years). The odds of improving overall frailty phenotype over 6 months was significantly higher in the strength training group compared to controls (OR [95%CI]: 1.86 [1.09, 3.17]), but not for for tai ji quan (1.44 [0.84, 2.50]). Both strength training (OR 1.99 [1.10, 3.65]) and tai ji quan (OR 2.10 [1.16, 3.84]) led to significantly higher odds of reducing > 1 frailty criterion compared to controls. Strength training led to a three-fold reduction in inactivity (p <0.01), and tai ji quan to a two-fold reduction in fatigue (p=0.08) versus control. Higher baseline BMI, comorbidity score, and frailty status characterized women more likely to reduce frailty than other women. Conclusions: Strength training appears superior to tai ji quan and stretching with respect to reducing overall frailty phenotype among postmenopausal women treated with chemotherapy for cancer, but tai ji quan favorably impacted the number of frailty criteria. Implications for Cancer Survivors : Supervised, group exercise training that emphasizes strength training and/or tai ji quan may help combat accelerated aging and reduce frailty after cancer treatment.
Prediction of short-acting beta-agonist usage in patients with asthma using temporal-convolutional neural networks

Abstract Objective Changes in short-acting beta-agonist (SABA) use are an important signal of asthma control and risk of asthma exacerbations. Inhaler sensors passively capture SABA use and may provide longitudinal data to identify at-riskpatients. We evaluate the performance of several ML models in predicting daily SABA use for participants with asthma and determine relevant features for predictive accuracy. Methods Participants with self-reported asthma enrolled in a digital health platform (Propeller Health, WI), which included a smartphone application and inhaler sensors that collected the date and time of SABA use. Linear regression, random forests, and temporal convolutional networks (TCN) were applied to predict expected SABA puffs/person/day from SABA usage and environmental triggers. The models were compared with a simple baseline model using explained variance (R2), as well as using average precision (AP) and area under the receiving operator characteristic curve (ROC AUC) for predicting days with ≥1–10 puffs. Results Data included 1.2 million days of data from 13 202 participants. A TCN outperformed other models in predicting puff count (R2 = 0.562) and day-over-day change in puff count (R2 = 0.344). The TCN predicted days with ≥10 puffs with an ROC AUC score of 0.952 and an AP of 0.762 for predicting a day with ≥1 puffs. SABA use over the preceding 7 days had the highest feature importance, with a smaller but meaningful contribution from air pollutant features. Conclusion Predicted SABA use may serve as a valuable forward-looking signal to inform early clinical intervention and self-management. Further validation with known exacerbation events is needed.
Mechanistic and evolutionary insights into isoform-specific ‘supercharging’ in DCLK family kinases

Catalytic signaling outputs of protein kinases are dynamically regulated by an array of structural mechanisms, including allosteric interactions mediated by intrinsically disordered segments flanking the conserved catalytic domain. The doublecortin-like kinases (DCLKs) are a family of microtubule-associated proteins characterized by a flexible C-terminal autoregulatory ‘tail’ segment that varies in length across the various human DCLK isoforms. However, the mechanism whereby these isoform-specific variations contribute to unique modes of autoregulation is not well understood. Here, we employ a combination of statistical sequence analysis, molecular dynamics simulations, and in vitro mutational analysis to define hallmarks of DCLK family evolutionary divergence, including analysis of splice variants within the DCLK1 sub-family, which arise through alternative codon usage and serve to ‘supercharge’ the inhibitory potential of the DCLK1 C-tail. We identify co-conserved motifs that readily distinguish DCLKs from all other calcium calmodulin kinases (CAMKs), and a ‘Swiss Army’ assembly of distinct motifs that tether the C-terminal tail to conserved ATP and substrate-binding regions of the catalytic domain to generate a scaffold for autoregulation through C-tail dynamics. Consistently, deletions and mutations that alter C-terminal tail length or interfere with co-conserved interactions within the catalytic domain alter intrinsic protein stability, nucleotide/inhibitor binding, and catalytic activity, suggesting isoform-specific regulation of activity through alternative splicing. Our studies provide a detailed framework for investigating kinome-wide regulation of catalytic output through cis-regulatory events mediated by intrinsically disordered segments, opening new avenues for the design of mechanistically divergent DCLK1 modulators, stabilizers, or degraders.
How sharp is the sharp Archean Moho? Example from eastern Superior Province

The Superior Province of North America has not experienced major internal deformation for nearly 2.8 Gyr, preserving the Archean crust in its likely original state. We present seismological evidence for a sharp (less than 1 km) crust‐mantle boundary beneath three distinct Archean terranes and for a more vertically extensive boundary at sites likely affected by the 1.2–0.9 Ga Grenville orogeny. At all sites crustal thickness is smaller than expected for the primary crust produced by melting under higher mantle potential temperature conditions of Archean time. Reduced thickness and an abrupt contrast in seismic properties at the base of the undisturbed Archean crust are consistent with density sorting and loss of the residues through gravitational instability facilitated by higher temperatures in the upper mantle at the time of formation. Similar sharpness of crust‐mantle boundary in disparate Archean terranes suggests that it is a universal feature of the Archean crustal evolution.
Simian Varicella Virus Infection and Reactivation in Rhesus Macaques Trigger Cytokine and Aβ40/42 Alterations in Serum and Cerebrospinal Fluid

Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aβ42/Aβ40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aβ42/Aβ40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aβ42/Aβ40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease.
Estudio analítico-comparado sobre las políticas educativas en educación para la salud en la Unión Europea.

This paper deals with a comparative study of material Educatio- nal Policies in Health Education in the countries of the European Union for the purpose of seeing take shape in Spain. The EU legislation states that if you want to advance as a knowledge society and compete effectively in a global economy, Europe is vital to have an education and training of high quality. In the European Union, education policy is the responsibility of each country, but among all set common goals and share best practices. For this reason this study is to compare the educational policies on health education in some countries of the European Union (Spain, Uk, France and Germany) and to compare the practices in each of them to this take the best of each country mode. The general objective pursued is to analyze and compare the situation of education policies in health education in the schools of the European Union and in particular the Uk, France, Germany and Spain. Throughout this paper we will see that health education in school is
Effective coverage of newborn postnatal care in Ethiopia: Measuring inequality and spatial distribution of quality-adjusted coverage

Neonatal health is a significant global public health concern, and the first two days of life are crucial for newborn survival. Most studies on newborn postnatal care have focused on crude coverage measures, which limit the evaluation of care quality. However, evidence suggests a shift towards emphasising effective coverage, which incorporates the quality of care when measuring intervention coverage. This research aimed to assess the effective coverage of newborn postnatal care in Ethiopia while also examining its inequalities and spatial distribution. The study used secondary data from the 2016 Ethiopian Demographic and Health Survey, which was a cross-sectional community-based study. A total weighted sample of 4169 women was used for analyses. We calculated crude coverage, which is the proportion who received a postnatal check within 48 hours of birth and quality-adjusted coverage (effective coverage), which is the proportion who received a postnatal check within 48 hours of birth and reported receipt of 6 or more contents of care provided by health care providers. Concentration index and concentration curves were used to estimate the socioeconomic-related inequalities in quality-adjusted newborn postnatal care. The spatial statistic was analysed by using Arc-GIS. The crude coverage of newborn postnatal care was found to be 13.2%, while the effective coverage was 9%. High-quality postnatal care was disproportionately concentrated among the rich. A spatial variation was found in quality-adjusted coverage of newborn postnatal care across regions. The findings suggest that there is a significant gap in the coverage and quality of postnatal care for newborns across regions in Ethiopia. The low rates of coverage and effective coverage, combined with the concentration of high-quality care among the rich and the spatial variation across regions, highlight the need for targeted interventions and policies to address the inequalities in access to high-quality postnatal care for newborns.
Comparing MRI volume measurement techniques for pituitary macroadenoma: Investigating volume reduction and its relationship with biochemical control

Pituitary adenomas are one of the most common types of primary intracranial tumors. Measuring pituitary adenoma volume is fundamental for effective management. This study aimed to assess the reliability of the ellipsoid method in comparison with the perimeter method for measuring pituitary macroadenoma volume. In addition, we investigated the correlation between adenoma size reduction and biochemical control in functioning adenomas. This was a retrospective cross-sectional cohort study including 113 patients with pituitary macroadenomas. MRI was obtained for volume measurement by ellipsoid and perimeter methods using two types of DICOM viewer software. Both ellipsoid and perimeter methods exhibit positive, strong, and significant correlations in pituitary macroadenomas in pre-treatment and post-treatment volume (Spearman correlation coefficient 0.95, p-value <0.0001). There was no significant difference in the mean post-treatment pituitary adenoma volume measurements utilizing the ellipsoid and the perimeter methods in different treatment modalities. There were significant differences in the pre-treatment volume measurements between the two methods, both in NFPA and prolactinoma. No correlation was found between volume variability measured by ellipsoid and perimeter methods and the degree of hormonal control in functioning pituitary adenomas. Both the ellipsoid and perimetric methods can be utilized for pituitary adenoma volume measurements as they demonstrate a strong and positive correlation. However, it is important to note that the ellipsoid method tends to result in overestimated tumor volume. There was no correlation between the adenoma size reduction and the degree of biochemical response in functioning adenomas.
Examining the efficacy of intravenous ibuprofen and meperidine for preventing post-operative shivering after laparoscopic cholecystectomy with general anesthesia

Postoperative shivering is a common complication that can lead to increased postoperative complications. This study aimed to compare the effectiveness of intravenous ibuprofen and meperidine in preventing shivering following laparoscopic cholecystectomy. A total of 120 patients, aged 20-70 and classified as ASA I–II, were enrolled in this triple-blind clinical trial. The participants were randomly assigned to one of three groups: ibuprofen (800mg IV), meperidine (30 mg), or placebo (normal saline 2 ml), administered 30 minutes before the end of surgery. The occurrence of postoperative shivering was assessed and recorded at regular intervals (0, 5, 10, 15, 30, and 60 minutes after surgery). Additionally, postoperative pain levels were measured using a visual analog scale (VAS), sedation levels were evaluated using the Ramsay Sedation Scale (RSS), and the incidence of postoperative nausea and vomiting was documented. The prevalence and severity of postoperative shivering were not statistically significant between groups. The VAS was significantly lower in the meperidine group than the ibuprofen group throughout the study (p <0.001). The VAS was significantly lower in the ibuprofen group than the placebo group at 0 and 15 minutes after surgery. Although the incidence of nausea was slightly higher in the meperidine group, the difference was not statistically significant (p=0.75). Sedation scores were consistently lower in the ibuprofen group and higher in the meperidine group compared to the other groups (p<0.0001) The meperidine group had a significantly higher sedation score indicative of deep sleepiness (score of 4) than the other groups. Intravenous ibuprofen demonstrated comparable efficacy to meperidine in controlling shivering. Additionally, the incidence of nausea, vomiting, and sleepiness was lower in the intravenous ibuprofen group, suggesting it is a potential alternative to meperidine.
Association of “Big Five” Personality with Perceived Stress in Medical Postgraduates: A Cross-sectional Study

Background: Medical postgraduates are exposed to more time in patient care and thereby higher stress. Personality is one of the important factors associated with stress. Studies exist in profiling personality traits and also assessing stress in medical professionals. However, in India, to the best of our knowledge, there are only few studies linking personality traits with stress in different branches of medicine. Aim : The aim of the study was to study the association between big five personality traits and stress among medical postgraduates. Setting and Design This was a cross-sectional study in medical college. Materials and MethodsBig five inventory, perceived stress scale 14. Statistical Analysis Used Chi-square, t-test, analysis of variance, correlation. Results Personality pattern among postgraduates were low on openness (P = 0.000), neuroticism (P = 0.001), and high agreeableness (P = 0.007) compared to general population. Among the different branches pre-paraclinical branches have low openness (P = 0.004), medical branches have high agreeableness (P = 0.000), low openness (P = 0.000), surgical branches have low openness (P = 0.004), and neuroticism (P = 0.003). Married students have high neuroticism (P = 0.007). Perceived stress is high in all variables compared to general population. Among different subjects of medical sciences, it is significantly high in pre-paraclinical (P = 0.001) and clinical branches (P = 0.001). Negative correlation exists between conscientiousness (r = ? 0.233, P = 0.025), extraversion (r = ? 0.204, P = 0.050), and positive correlation between neuroticism (r = +0.607, P = 0.000) with perceived stress. Conclusions:Medical postgraduates have low openness, neuroticism, and high agreeableness. Perceived stress is high in medical postgraduates in all demographic variables compared to the general population.