Miracle-dz/UniFAR-FTUs huggingface dataset:
Thriving through Adversity: The Role of Passion and Emotions in the Resilience Process.

Two cross-sectional (Studies 1, N = 283, and 2, N = 275) and one prospective (Study 3, N = 238) studies investigated the role of passion (for academia) and emotions in the process of resilience in the education domain and in life in general. Participants were examined when facing a stressful situation related to their passion for academia (end of term exam period, a timed education task). All three studies showed that harmonious passion, through its positive relationship with positive emotions, was positively associated with high positive outcomes in the education domain (satisfaction with one's studies, subjective and objective performance in one's studies) and in life in general via the subjective evaluation of one's life and general health indicators (subjective vitality, fewer negative physical symptoms). On the other hand, obsessive passion was related to mixed effects on resilience. Specifically, obsessive passion related to low levels of functioning (Studies 1 and 3) and also hindered the positive outcomes (Studies 1 to 3) through its positive relationships with positive and negative emotions, respectively. In sum, under stress, harmonious passion facilitates high levels of resilience across life domains, whereas obsessive passion yields low levels of resilience across life or no resilience at all.
Genomic evidence reveals intraspecific divergence of the hot‐spring snake (Thermophis baileyi), an endangered reptile endemic to the Qinghai‐Tibet plateau

Understanding how and why species evolve requires knowledge on intraspecific divergence. In this study, we examined intraspecific divergence in the endangered hot‐spring snake (Thermophis baileyi), an endemic species on the Qinghai‐Tibet Plateau (QTP). Whole‐genome resequencing of 58 sampled individuals from 15 populations was performed to identify the drivers of intraspecific divergence and explore the potential roles of genes under selection. Our analyses resolved three groups, with major intergroup admixture occurring in regions of group contact. Divergence probably occurred during the Pleistocene as a result of glacial climatic oscillations, Yadong‐Gulu rift, and geothermal fields differentiation, while complex gene flow between group pairs reflected a unique intraspecific divergence pattern on the QTP. Intergroup fixed loci involved selected genes functionally related to divergence and local adaptation, especially adaptation to hot spring microenvironments in different geothermal fields. Analysis of structural variants, genetic diversity, inbreeding, and genetic load indicated that the hot‐spring snake population has declined to a low level with decreased diversity, which is important for the conservation management of this endangered species. Our study demonstrated that the integration of demographic history, gene flow, genomic divergence genes, and other information is necessary to distinguish the evolutionary processes involved in speciation.
Bile acids regulate the epithelial Na+ channel in native tissues through direct binding at multiple sites

Bile acids, originally known to emulsify dietary lipids, are now established signalling molecules that regulate physiological processes. Signalling targets several proteins that include the ion channels involved in regulating intestinal motility and bile viscosity. Studies show that bile acids regulate the epithelial sodium channel (ENaC) in cultured cell models and heterologous expression systems. ENaC plays both local and systemic roles in regulating extracellular fluids. Here we investigated whether bile acids regulate ENaC expressed in native tissues. We found that taurocholic acid and taurohyodeoxycholic acid regulated ENaC in both the distal nephron and distal colon. We also tested the hypothesis that regulation occurs through direct binding. Using photoaffinity labelling, we found evidence for specific binding to both the β and γ subunits of the channel. In functional experiments, we found that the α subunit was sufficient for regulation. We also found that regulation by at least one bile acid was voltage‐sensitive, suggesting that one binding site may be closely associated with the pore‐forming helices of the channel. Our data provide evidence that bile acids regulate ENaC by binding to multiple sites to influence the open probability of the channel.
Conserved age‐related increases in hippocampal PDE11A4 cause unexpected proteinopathies and cognitive decline of social associative memories

In humans, associative memories are more susceptible to age‐related cognitive decline (ARCD) than are recognition memories. Reduced cAMP/cGMP signaling in the hippocampus may contribute to ARCD. Here, we found that both aging and traumatic brain injury‐associated dementia increased the expression of the cAMP/cGMP‐degrading enzyme phosphodiesterase 11A (PDE11A) in the human hippocampus. Further, age‐related increases in hippocampal PDE11A4 mRNA and protein were conserved in mice, as was the increased vulnerability of associative versus recognition memories to ARCD. Interestingly, mouse PDE11A4 protein in the aged ventral hippocampus (VHIPP) ectopically accumulated in the membrane fraction and filamentous structures we term “ghost axons. ” These age‐related increases in expression were driven by reduced exoribonuclease‐mediated degradation of PDE11A mRNA and increased PDE11A4‐pS117/pS124, the latter of which also drove the punctate accumulation of PDE11A4. In contrast, PDE11A4‐pS162 caused dispersal. Importantly, preventing age‐related increases in PDE11 expression via genetic deletion protected mice from ARCD of short‐term and remote long‐term associative memory (aLTM) in the social transmission of food preference assay, albeit at the expense of recent aLTM. Further, mimicking age‐related overexpression of PDE11A4 in CA1 of old KO mice caused aging‐like impairments in CREB function and remote social—but not non‐social—LTMs. RNA sequencing and phosphoproteomic analyses of VHIPP identified cGMP‐PKG—as opposed to cAMP‐PKA—as well as circadian entrainment, glutamatergic/cholinergic synapses, calcium signaling, oxytocin, and retrograde endocannabinoid signaling as mechanisms by which PDE11A deletion protects against ARCD. Together, these data suggest that PDE11A4 proteinopathies acutely impair signaling in the aged brain and contribute to ARCD of social memories.
Patient perspectives on primary care for multimorbidity: An integrative review

Improving healthcare for people with multiple chronic or ongoing conditions is receiving increased attention, particularly due to the growing number of people experiencing multimorbidity (MM) and concerns about the sustainability of the healthcare system. Primary care has been promoted as an important resource for supporting people with MM to live well with their conditions and to prevent unnecessary use of health care services. However, traditional primary care has been criticized for not centring the needs and preferences of people with MM themselves. Our aim was to conduct a review that centred on the perspective of people with MM in multiple ways, including having patient partners co‐lead the design, conduct and reporting of findings, and focusing on literature that reported the perspective of people with MM, irrespective of it being experimental or nonexperimental.
Evaluating the effectiveness of a comprehensive education on low back pain treatment outcomes: A controlled clinical study

Objectives To investigate the effect of integrating an individualized, evidence-based low back pain comprehensive education package on low back pain treatment outcomes. Design Single-blind, controlled clinical study using the alternate allocation of patients. Setting Outpatient clinic. Subjects In total, 54 participants with chronic low back pain (46.75 ± 11.11 years, 80% females) were randomized to intervention (n = 27) or a control group (n = 27). Intervention The intervention group received additional four one-hour low back pain-related education sessions to eight 45 minutesstandard physical therapy sessions over 4 weeks. Outcome measures Assessed at baseline, post-intervention, and 3 months. Outcome measures included pain intensity (Visual Analogue Scale), knowledge (Low Back Pain Knowledge Questionnaire), attitude (the Back Pain Attitudes Questionnaire), disability (the Oswestry Disability Index), mental health symptoms (Depression Anxiety Stress Scale, DASS-21 scale), and fear-avoidance (Fear-Avoidance Beliefs Questionnaire). Results The intervention group showed significantly lower pain intensity ((4 weeks (3.58 ± 1.50 vs. 5.54 ± 1.92), 3 months (3.21 ± 1.74 vs. 5.69 ± 2.51)), higher knowledge ((4 weeks (21.67 ± 2.12 vs. 11.62 ± 3.47), three months (22.08 ± 3.40 vs. 12.23 ± 3.24)), lower negative attitudes ((4 weeks (99.29 ± 11.02 vs. 134.31 ± 12.97), 3 months (102.92 ± 15.58 vs. 132.42 ± 17.79)), lower disability ((4 weeks (26.30 ± 11.37 vs. 45.14 ± 18.67), 3 months (22.83 ± 16.06 vs. 44.13 ± 15.02)), lower stress score ((4 weeks (3.54 ± 3.01 vs. 8.81 ± 5.19), 3 months (3.21 ± 3.22 vs. 7.21 ± 4.36)), lower anxiety ((4 weeks (2.63 ± 3.16 vs. 6.42 ± 4.75), three months (2.63 ± 3.80 vs. 5.73 ± 4.44)), lower depression ((4 weeks (2.42 ± 2.15 vs. 6.42 ± 3.68), three months (2.63 ± 4.18 vs. 7.08 ± 4.41)), and lower fear-avoidance ((4 weeks (13.88 ± 12.32 vs. 50.88 ± 23.25), three months (15.50 ± 16.75 vs. 54.65 ± 31.81)). Conclusion Integrating low back pain comprehensive education into standard physical therapy might optimize the treatment outcomes of low back pain.
STATUS OF HIGGS BOSON SEARCHES AT THE TEVATRON

Over the last years the Tevatron Run-II has extended several limits on Higgs boson masses and coupling which were pioneered during the LEP accelerator operation between 1989 and 2000. Higgs boson searches will also be at the forefront of research at the LHC. This review concisely discusses the experimental constraints set by the CDF and DO collaborations in winter 2008/2009 at the beginning of the LHC era. Model-independent and modeldependent limits on Higgs boson masses and couplings have been set and interpretations are discussed both in the Standard Model and in extended models. Recently, for the first time the Tevatron excludes a SM Higgs boson mass range (160-170 GeV) beyond the LEP limit at 95% CL. The experimental sensitivities are estimated for the completion of the Tevatron programme.
Self-reported emotional health and social support but not executive function are associated with participation after stroke

ABSTRACT Background Participation restrictions continue to be prevalent for community-dwelling stroke survivors. Research is needed to understand the associated post-stroke factors that limit or facilitate optimal participation and quality of life. Objectives To investigate emotional health, executive functioning (EF), and social support as predictors of participation restrictions post-stroke. Methods Cross-sectional data collected from participants ≥ 6 months after mild stroke with and without aphasia (N = 114) were analyzed using three participation outcome measures: Reintegration to Normal Living Index (RNL), Activity Card Sort (ACS), and the Stroke Impact Scale (SIS) Version 2.0 Participation/Role Function domain. Predictor variables investigated were emotional health (SIS Emotion domain scores), EF (Delis Kaplan Executive Function System Trail Making Condition 4: DKEFS), social support (Medical Outcomes Study Social Support Survey: MOS-SSS), stroke severity (National Institutes of Health Stroke Scale: NIHSS), and education level. Results Using multiple regression, these predictors accounted for 26.4% to 40% of the variance for the three participation outcomes. Emotional health was a significant independent predictor across all three measures. Social support was a significant predictor of participation as measured on the RNL. Executive function was not a significant predictor of participation when controlling for the other predictor variables. Conclusions Emotional health and social support should be considered as modifiable factors that could optimize meaningful participation and quality of life.
Constructing functional models from biophysically-detailed neurons

Improving biological plausibility and functional capacity are two important goals for brain models that connect low-level neural details to high-level behavioral phenomena. We develop a method called “oracle-supervised Neural Engineering Framework” (osNEF) to train biologically-detailed spiking neural networks that realize a variety of cognitively-relevant dynamical systems. Specifically, we train networks to perform computations that are commonly found in cognitive systems (communication, multiplication, harmonic oscillation, and gated working memory) using four distinct neuron models (leaky-integrate-and-fire neurons, Izhikevich neurons, 4-dimensional nonlinear point neurons, and 4-compartment, 6-ion-channel layer-V pyramidal cell reconstructions) connected with various synaptic models (current-based synapses, conductance-based synapses, and voltage-gated synapses). We show that osNEF networks exhibit the target dynamics by accounting for nonlinearities present within the neuron models: performance is comparable across all four systems and all four neuron models, with variance proportional to task and neuron model complexity. We also apply osNEF to build a model of working memory that performs a delayed response task using a combination of pyramidal cells and inhibitory interneurons connected with NMDA and GABA synapses. The baseline performance and forgetting rate of the model are consistent with animal data from delayed match-to-sample tasks (DMTST): we observe a baseline performance of 95% and exponential forgetting with time constant τ = 8.5s, while a recent meta-analysis of DMTST performance across species observed baseline performances of 58 − 99% and exponential forgetting with time constants of τ = 2.4 − 71s. These results demonstrate that osNEF can train functional brain models using biologically-detailed components and open new avenues for investigating the relationship between biophysical mechanisms and functional capabilities.
MASS SUBSTRUCTURE IN ABELL 3128

We perform a detailed two-dimensional weak gravitational lensing analysis of the nearby (z = 0.058) galaxy cluster Abell 3128 using deep ugrz imaging from the Dark Energy Camera (DECam). We have designed a pipeline to remove instrumental artifacts from DECam images and stack multiple dithered observations without inducing a spurious ellipticity signal. We develop a new technique to characterize the spatial variation of the point-spread function that enables us to circularize the field to better than 0.5% and thereby extract the intrinsic galaxy ellipticities. By fitting photometric redshifts to sources in the observation, we are able to select a sample of background galaxies for weak-lensing analysis free from low-redshift contaminants. Photometric redshifts are also used to select a high-redshift galaxy subsample with which we successfully isolate the signal from an interloping z = 0.44 cluster. We estimate the total mass of Abell 3128 by fitting the tangential ellipticity of background galaxies with the weak-lensing shear profile of a Navarro–Frenk–White (NFW) halo and also perform NFW fits to substructures detected in the 2D mass maps of the cluster. This study yields one of the highest resolution mass maps of a low-z cluster to date and is the first step in a larger effort to characterize the redshift evolution of mass substructures in clusters.
A two-step mechanism governing PARP1-DNA retention by PARP inhibitors

PARP inhibitors (PARPi) have emerged as promising cancer therapeutics capable of targeting specific DNA repair pathways, but their mechanism of action with respect to PARP1-DNA retention remains unclear. Here, we developed single-molecule assays to directly monitor the retention of PARP1 on DNA lesions in real time. Our study reveals a two-step mechanism by which PARPi modulate the retention of PARP1 on DNA lesions, consisting of a primary step of catalytic inhibition via binding competition with NAD+ followed by an allosteric modulation of bound PARPi. While clinically relevant PARPi exhibit distinct allosteric modulation activities that can either increase retention of PARP1 on DNA or induce its release, their retention potencies are predominantly determined by their ability to outcompete NAD+ binding. These findings provide a mechanistic basis for improved PARPi selection according to their characteristic activities and enable further development of more potent inhibitors.
Comparative analysis of genomic inbreeding parameters and runs of homozygosity islands in several fancy and meat rabbit breeds

Abstract Runs of homozygosity (ROH) are defined as long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROH and their length are indicators of the level and origin of inbreeding. In this study, we analysed SNP chip datasets (obtained using the Axiom OrcunSNP Array) of a total of 702 rabbits from 12 fancy breeds and four meat breeds to identify ROH with different approaches and calculate several genomic inbreeding parameters. The highest average number of ROH per animal was detected in Belgian Hare (~150) and the lowest in Italian Silver (~106). The average length of ROH ranged from 4.001 ± 0.556 Mb in Italian White to 6.268 ± 1.355 Mb in Ermine. The same two breeds had the lowest (427.9 ± 86.4 Mb, Italian White) and the highest (921.3 ± 179.8 Mb, Ermine) average values of the sum of all ROH segments. More fancy breeds had a higher level of genomic inbreeding (as defined by ROH) than meat breeds. Several ROH islands contain genes involved in body size, body length, pigmentation processes, carcass traits, growth, and reproduction traits (e.g.: AOX1, GPX5, IFRD1, ITGB8, NELL1, NR3C1, OCA2, TRIB1, TRIB2). Genomic inbreeding parameters can be useful to overcome the lack of information in the management of rabbit genetic resources. ROH provided information to understand, to some extent, the genetic history of rabbit breeds and to identify signatures of selection in the rabbit genome.
Predictive factors of mortality in damage control surgery for abdominal trauma

ABSTRACT Introduction: damage control surgery (DCS) is well recognized as a surgical strategy for patients sustaining severe abdominal trauma. Literature suggests the indications, operative times, therapeutic procedures, laboratory parameters and intraoperative findings have a direct bearing on the outcomes. Objective: to analyze the clinical profile of patients undergoing DCS and determine predictors of morbidity and mortality. Methods: a retrospective cohort study was conducted on all patients undergoing DCS following abdominal trauma from November 2015 and December 2021. Data on subjects’ demographics, baseline presentation, mechanism of injury, associated injuries, injury severity scores, laboratory parameters, operative details, postoperative complications, length of stay and mortality were assessed. A binary logistic regression analysis was performed to determine potential risk factors for mortality. Results: During the study period, 696 patients underwent trauma laparotomy. Of these, 8.9% (n=62) were DCS, with more than 80% due to penetrating mechanisms. Overall mortality was 59.6%. In the logistic regression stratified by survival, several variables were significantly associated with mortality, including hypotension, and altered mental status at admission, intraoperative cardiorespiratory arrest, need for resuscitative thoracotomy, metabolic acidosis, hyperlactatemia, coagulopathy, fibrinolysis, and severity of the trauma injury scores. Conclusion: DCS may be appropriate in critically injured patients; however, it remains associated with significant morbidity and high mortality, even at specialized trauma care centers. From pre and postoperative clinical and laboratory parameters, it was possible to predict the risk of death in the studied sample.
Individualized Risk Prediction for Improved Chronic Wound Management

Significance: Chronic wounds are associated with significant morbidity, marked loss of quality of life, and considerable economic burden. Evidence-based risk prediction to guide improved wound prevention and treatment is limited by the complexity in their etiology, clinical underreporting, and a lack of studies using large high-quality datasets. Recent Advancements: The objective of this review is to summarize key components and challenges in the development of personalized risk prediction tools for both prevention and management of chronic wounds, while highlighting several innovations in the development of better risk stratification. Critical Issues: Regression-based risk prediction approaches remain important for assessment of prognosis and risk stratification in chronic wound management. Advances in statistical computing have boosted the development of several promising machine learning (ML) and other semiautomated classification tools. These methods may be better placed to handle large number of wound healing risk factors from large datasets, potentially resulting in better risk prediction when combined with conventional methods and clinical experience and expertise. Future Directions: Where the number of predictors is large and heterogenous, the correlations between various risk factors complex, and very large data sets are available, ML may prove a powerful adjuvant for risk stratifying patients predisposed to chronic wounds. Conventional regression-based approaches remain important, particularly where the number of predictors is relatively small. Translating estimated risk derived from ML algorithms into practical prediction tools for use in clinical practice remains challenging.
Measuring the latent reservoir for HIV-1: Quantification bias in near full-length genome sequencing methods

Antiretroviral therapy (ART) effectively inhibits HIV-1 replication but is not curative due to the persistence of a latent viral reservoir in resting CD4+ T cells. This reservoir is a major barrier to cure. Sequencing studies have revealed that the population of proviruses persisting in ART-treated individuals is dominated by defective proviruses that cannot give rise to viral rebound due to fatal defects including large deletions and APOBEC3-mediated hypermutation. Near full genome sequencing (nFGS) of individual proviruses is used in reservoir assays to provide an estimate of the fraction of proviruses that are intact. nFGS methods rely on a long-distance outer PCR capturing most (~9 kb) of the genome, followed by nested inner PCRs. The outer PCR is carried out at limit dilution, and interpretation of the results is based on the assumption that all proviruses are quantitatively captured. Here, we evaluate nFGS methods using the intact proviral DNA assay (IPDA), a multiplex digital droplet PCR assay that quantitates intact and defective proviruses with single molecule sensitivity using only short, highly efficient amplicons. We analyzed proviral templates of known sequence to avoid the additional complication of sequence polymorphism. With the IPDA, we quantitated molecular yields at each step of nFGS methods. We demonstrate that nFGS methods are inefficient and miss ~70% of full-length proviruses due to amplification failure at the initial outer PCR step. In contrast, proviruses with large internal deletions encompassing 70% of the genome can be quantitatively amplified under the same conditions. Accurate measurement of the latent reservoir of HIV-1 is essential for evaluating the efficacy of cure strategies, and the bias against full length proviruses in nFGS methods must be considered.