Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating within-flock transmission rate parameter for H5N2 highly pathogenic avian influenza virus in Minnesota turkey flocks during the 2015 epizootic

Abstract Better control of highly pathogenic avian influenza (HPAI) outbreaks requires deeper understanding of within-flock virus transmission dynamics. For such fatal diseases, daily mortality provides a proxy for disease incidence. We used the daily mortality data collected during the 2015 H5N2 HPAI outbreak in Minnesota turkey flocks to estimate the within-flock transmission rate parameter (β). The number of birds in Susceptible, Exposed, Infectious and Recovered compartments was inferred from the data and used in a generalised linear mixed model (GLMM) to estimate the parameters. Novel here was the correction of these data for normal mortality before use in the fitting process. We also used mortality threshold to determine HPAI-like mortality to improve the accuracy of estimates from the back-calculation approach. The estimated β was 3.2 (95% confidence interval (CI) 2.3–4.3) per day with a basic reproduction number of 12.8 (95% CI 9.2–17.2). Although flock-level estimates varied, the overall estimate was comparable to those from other studies. Sensitivity analyses demonstrated that the estimated β was highly sensitive to the bird-level latent period, emphasizing the need for its precise estimation. In all, for fatal poultry diseases, the back-calculation approach provides a computationally efficient means to obtain reasonable transmission parameter estimates from mortality data.
Does Removal of Work Stress Explain Improved Sleep Following Retirement? The Finnish Retirement and Aging (FIREA) study.

STUDY OBJECTIVES Relief from work stress has been hypothesized to explain improvements in sleep duration and quality following retirement, but this has not been confirmed with longitudinal studies. By using repeat sleep data, we examined the role of removal of work-related stressors in changes in sleep at retirement. METHODS The study population consisted of 2,053 participants from the Finnish Retirement and Aging study. Participants' sleep duration, sleep difficulties (difficulties falling asleep, difficulties maintaining sleep, waking up too early in the morning, nonrestorative sleep), daytime tiredness, and sleep loss due to worry were assessed using surveys conducted once a year before and after retirement (average number of repeat surveys 3.5 [range 2-5] per participant). We used Poisson regression with generalized estimating equations to examine the associations between work-related stressors (job strain, low work time control, effort-reward imbalance, and organizational injustice) and changes in sleep at retirement. RESULTS An increase in sleep duration and decrease in waking up too early in the morning, nonrestorative sleep, daytime tiredness, and sleep loss due to worry were observed shortly after retirement. No systematic associations across the work-related stressors and changes in sleep characteristics were observed. Higher number of work-related stressors before retirement was not associated with a greater magnitude of favorable changes in any of the post-retirement sleep characteristics investigated. CONCLUSIONS This longitudinal study suggests that perceived sleep improves shortly after retirement, and that these changes are mainly driven by factors other than relief from work stress.
Interaction of aloe active compounds with calf thymus DNA

Natural anthraquinone compounds have emerged as potent anticancer chemotherapeutic agents because of their promising DNA‐binding properties. Aloe vera is among one of the very well‐known medicinal plants, and the anthraquinone derivatives like aloe emodin (ALM), aloins (ALN), and aloe emodin‐8‐glucoside (ALMG) are known to have immense biological activities. Here, we have used biophysical methods to elucidate the comparative DNA‐binding abilities of these three molecules. Steady‐state fluorescence study indicated complexation between calf thymus DNA (ctDNA) and both the molecules ALM and ALMG whereas ALN showed very weak interaction with DNA. Displacement assays with ctDNA‐bound intercalator (ethidium bromide) and a groove binder (Hoechst 33258) indicated preferential binding of both ALM and ALMG to minor groove of DNA. Isothermal titration calorimetric (ITC) data suggested spontaneous exothermic single binding mode of both the molecules: ALM and ALMG. Entropy is the most important factor which contributed to the standard molar Gibbs energy associated with relatively small favorable enthalpic contribution. The equilibrium constants of binding to ctDNA were (6.02 ± 0.10) × 104 M−1 and (4.90 ± 0.11) × 104 M−1 at 298.15 K, for ALM and ALMG, respectively. The enthalpy vs temperature plot yielded negative standard molar heat capacity value, and a strong negative correlation between enthalpy and entropy terms was observed which indicates the enthalpy entropy compensation behavior in both systems. All these thermodynamic phenomena indicate that hydrophobic force is the key factor which is involved in the binding process. Moreover, the enhancement of thermal stability of DNA helix by ALM and ALMG fully agreed to the complexation of these molecules with DNA.
Prevalence and risk factors of postoperative delirium in elderly hip fracture patients

Objective To explore the risk factors associated with postoperative delirium (PD) in elderly patients following total hip arthroplasty (THA) for hip fracture. Methods This prospective study enrolled elderly patients (≥ 65 years) with hip fractures who underwent THA under general anaesthesia, and who had a complete set of postoperative observations. Detailed medical history and perioperative characteristics were recorded. During the postoperative period, patients were assessed twice daily for PD using the Confusion Assessment Method. Results A total of 572 patients were eligible for inclusion in the study. Of these, 120 patients (21.0%) were diagnosed with PD and 452 patients (79.0%) did not experience PD. Multivariate stepwise logistic regression analyses showed that older age, a history of stroke, lower albumin, higher blood glucose, higher total bilirubin, higher C-reactive protein, longer surgery duration and higher volume of red blood cell transfusions were independent risk factors for PD. Conclusions Correcting the modifiable risk factors might help prevent PD. Strategies might include nutritional support, tight blood glucose control, improvement of liver function, preoperative infection control and minimizing surgical injury or blood loss.
Analyzing Information Distribution in Complex Systems

Information theory is often utilized to capture both linear as well as nonlinear relationships between any two parts of a dynamical complex system. Recently, an extension to classical information theory called partial information decomposition has been developed, which allows one to partition the information that two subsystems have about a third one into unique, redundant and synergistic contributions. Here, we apply a recent estimator of partial information decomposition to characterize the dynamics of two different complex systems. First, we analyze the distribution of information in triplets of spins in the 2D Ising model as a function of temperature. We find that while redundant information obtains a maximum at the critical point, synergistic information peaks in the disorder phase. Secondly, we characterize 1D elementary cellular automata rules based on the information distribution between neighboring cells. We describe several clusters of rules with similar partial information decomposition. These examples illustrate how the partial information decomposition provides a characterization of the emergent dynamics of complex systems in terms of the information distributed across their interacting units.
Response regulator–mediated MAPKKK heteromer promotes stress signaling to the Spc1 MAPK in fission yeast

A novel mechanism is uncovered by which two MAPKKKs form a heteromer to physically interact with a downstream MAPKK and transmit stress signals to the Spc1 MAPK in fission yeast. Unexpectedly, the MAPKKK heteromer is stabilized by a response regulator independently of its usual function as a terminal effector of phosphorelay signaling.
Dietary Habits Bursting into the Complex Pathogenesis of Autoimmune Diseases: The Emerging Role of Salt from Experimental and Clinical Studies

The incidence and prevalence of autoimmune diseases have increased in Western countries over the last years. The pathogenesis of these disorders is multifactorial, with a combination of genetic and environmental factors involved. Since the epidemiological changes cannot be related to genetic background, which did not change significantly in that time, the role of environmental factors has been reconsidered. Among these, dietary habits, and especially an excessive salt, typical of processed foods, has been implicated in the development of autoimmune diseases. In this review, we summarize current evidence, deriving both from experimental models and clinical studies, on the capability of excessive salt intake to exacerbate proinflammatory responses affecting the pathogenesis of immune-mediated diseases. Data on several diseases are presented, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and Crohn’s disease, with many of them supporting a proinflammatory effect of salt. Likewise, a hypertonic microenvironment showed similar effects in experimental models both in vivo and in vitro. However, murine models of spontaneous autoimmune polyneuropathy exposed to high salt diet suggest opposite outcomes. These results dictate the need to further analyse the role of cooking salt in the treatment and prevention of autoimmune diseases, trying to shape a fine tuning between the possible advantages of a restricted salt intake and the changes in circulating metabolites, mediators, and hormones which come along salt consumption and could in turn influence autoimmunity.
Psychometric evaluation of the Energy Conservation Strategies Survey

Objective: To examine the internal consistency and test-retest reliability of the Energy Conservation Strategies Survey (ECSS), a tool that was specifically designed to determine if people with multiple sclerosis who attended the six-week energy conservation course actually implemented the strategies taught to them. Design: The instrument ECSS was administered at six weeks and seven weeks post intervention to evaluate the test-retest reliability, while data from six weeks post intervention were utilized to assess the internal consistency of the ECSS. Setting: Community locations in Illinois and Minnesota, USA. Subjects: Data from 53 participants with multiple sclerosis living in the community were utilized for the psychometric study. Measures: Energy Conservation Strategies Survey. Results: The internal consistency of 0.92 reveals that all the items are consistent with each other and measure a single construct. Inferential analyses using intraclass correlation coefficient indicates good test-retest reliability (intraclass correlation coefficient (ICC)=0.79). Conclusion: Findings of the study suggest that the ECSS exhibits high internal consistency and good test-retest reliability. The study implies that the ECSS could be valuable in measuring changes in behavior over time among people with multiple sclerosis after the completion of the six-week energy conservation course provided by occupational therapists.
Immunohistochemical identification of resistin in the uterus of ewes subjected to different diets: Preliminary results

Resistin is a polypeptide hormone of the adipokine-family, primarily, but not exclusively, produced by the adipose tissue. Recent studies suggested that resistin may affect the male and female reproductive activity. The study aim was to immunohistochemically evaluate the presence and distribution of resistin in the ovine uterus. Uterine samples were collected from two groups of ewes at the end of an experimental trial during which the animals of the first group (CTRL) were fed only by grazing while those of the second one (EXP) were supplemented with barley and corn. Using a monoclonal antibody against resistin, tested by Western Blot, the immunopositive reaction was identified in the cytoplasm of epithelial lining cells and uterine glands. The endogenous production of resistin seemed to be affected by different diet, as evidenced by staining differences between the CTRL and EXP groups. Our findings support the existence of a peripheral resistin system in the sheep uterus. It is possible that this system is involved in the functionality of the uterus, which is also affected by the animal’s nutritional status.
The future: genes, physical activity and health

The assigned title for the Lindhard presentation was to examine the future of genes, physical activity and health. The current review is a summary of this presentation. Caution is expressed that technology is improving so rapidly that a future view is limited to a few years as opposed to the 100 years passing since Lindhard’s achievements. The near futuristic opportunities and challenges for four major topic topics are reviewed here. Concerns are expressed over current usage of the terms ‘control’ group and ‘non‐responders’ in exercise research. Our view is that ‘control’ needs to be differentiated between its usage for treatments of exercise to restore natural functions in individuals with less than healthy levels of physical activity and the inherited genome’s expectation for physical activity levels to maintain normal function. For the second discussed topic, it is proposed that the term ‘non‐responders’ should be replaced by the term ‘low sensitivity’ as there may be no such human who is a non‐responder to every exercise adaptation. The third futuristic topic is exercise prescription as envisioned for individualized medicine. However, numerous limitations and challenges exist to truly optimal exercise medicine at the level of one individual. Finally, preventative physical activity medicine is discussed. Physical activity as a therapy now exists to prevent most of the chronic diseases. The future needs to understand the molecular basis for how the body becomes dysfunctional when its level of physical activity does not match the norm of physical activity that selected our inherited genome.
Structural investigation of selective binding dynamics for the pheromone-binding protein 1 of the grapevine moth, Lobesia botrana.

The European grapevine moth, Lobesia botrana (Denis & Schiffermüller), is a serious pest in vineyards in North and South America. Mating disruption techniques have been used to control and monitor L. botrana on the basis of its sexual communication. This needs a well-tuned olfactory system, in which it is believed that pheromone-binding proteins (PBPs) are key players that transport pheromones in the antennae of moths. In this study, the selectivity of a PBP, named as LbotPBP1, was tested by fluorescence binding assays against 11 sex pheromone components and 6 host plant volatiles. In addition, its binding mechanism was predicted on the basis of structural analyses by molecular docking and complex and steered molecular dynamics (SMD). Our results indicate that LbotPBP1 binds selectively to sex pheromone components over certain host plant volatiles, according to both in vitro and in silico tests. Thus, chain length (14 carbon atoms) and functional groups (i.e., alcohol and ester) appear to be key features for stable binding. Likewise, residues such as Phe12, Phe36, and Phe118 could participate in unspecific binding processes, whilst Ser9, Ser56, and Trp114 could participate in the specific recognition and stabilization of sex pheromones instead of host plant volatiles. Moreover, our SMD approach supported 11-dodecenyl acetate as the best ligand for LbotPBP1. Overall, the dynamics simulations, contact frequency analysis and SMD shed light on the binding mechanism of LbotPBP1 and could overcome the imprecision of molecular docking, supporting the in vitro binding assays. Finally, the role of LbotPBP1 in the chemical ecology of L. botrana is discussed.
Chemical disarming of isoniazid resistance in Mycobacterium tuberculosis

Significance Mycobacterium tuberculosis (Mtb) causes the disease tuberculosis (TB), which kills more people than any other infection. The emergence of drug-resistant Mtb strains has exacerbated this already alarming epidemic. We have identified a small molecule, C10, that potentiates the activity of the frontline antibiotic isoniazid (INH) and prevents the selection for INH-resistant mutants. We find that C10 can even reverse INH resistance in Mtb. Therefore, our study reveals vulnerabilities that can be exploited to reverse INH resistance in Mtb. Mycobacterium tuberculosis (Mtb) killed more people in 2017 than any other single infectious agent. This dangerous pathogen is able to withstand stresses imposed by the immune system and tolerate exposure to antibiotics, resulting in persistent infection. The global tuberculosis (TB) epidemic has been exacerbated by the emergence of mutant strains of Mtb that are resistant to frontline antibiotics. Thus, both phenotypic drug tolerance and genetic drug resistance are major obstacles to successful TB therapy. Using a chemical approach to identify compounds that block stress and drug tolerance, as opposed to traditional screens for compounds that kill Mtb, we identified a small molecule, C10, that blocks tolerance to oxidative stress, acid stress, and the frontline antibiotic isoniazid (INH). In addition, we found that C10 prevents the selection for INH-resistant mutants and restores INH sensitivity in otherwise INH-resistant Mtb strains harboring mutations in the katG gene, which encodes the enzyme that converts the prodrug INH to its active form. Through mechanistic studies, we discovered that C10 inhibits Mtb respiration, revealing a link between respiration homeostasis and INH sensitivity. Therefore, by using C10 to dissect Mtb persistence, we discovered that INH resistance is not absolute and can be reversed.
Coping, mood and health-related quality of life: a cross-sectional study in Chinese patients with advanced lung cancer

Objectives The ways patients cope with advanced cancer can influence their health-related quality of life (HRQoL). This study aims to examine the mediating role of positive and negative mood in the relationship between coping and HRQoL in patients with advanced lung cancer. Methods A consecutive sample of 261 patients (mean age: 59.99±9.53) diagnosed with stage III or IV lung cancer was recruited from the inpatient unit in a hospital that specialises in chest-related disease in Shanghai, China. Participants completed measurements including Medical Coping Modes Questionnaire, Positive and Negative Affect Schedule, and 5-level EuroQol 5-dimension instrument. Results Although the total effects of confrontation on HRQoL were not significant, competing indirect effects via mood were identified: (1) positive indirect effects through positive mood were found for confrontation on mobility, usual activities, pain/discomfort and overall utility index (indirect effect=0.01, 95% CI 0.003 to 0.03); (2) negative indirect effects through negative mood were found for confrontation on mobility, pain/discomfort, anxiety/depression and overall utility index (indirect effect=−0.01, 95% CI −0.03 to −0.001). Resigned acceptance was negatively associated with HRQoL, and indirect effects via mood were identified: (1) negative indirect effects through positive mood were found for resigned acceptance on mobility, self-care, usual activities, pain/discomfort and overall utility index (indirect effect=−0.01, 95% CI −0.03 to −0.003); (2) negative indirect effects through negative mood were found for resigned acceptance on domains of HRQoL and overall utility index (indirect effect=−0.04, 95% CI −0.06 to −0.02). Conclusions Confronting advanced lung cancer can fuel ambivalent emotional experiences. Nevertheless, accepting the illness in a resigned way can be maladaptive for health outcomes. The findings suggest interventions that facilitate adaptive coping, reduce negative mood and enhance positive mood, as this could help to improve or maintain HRQoL in patients with advanced lung cancer.
Arterial stiffness during whole‐body passive heat stress in healthy older adults

We tested the hypothesis that whole‐body passive heat stress reduces arterial stiffness in older adults. At preheat stress (baseline) and when core temperature was elevated by 0.6 ± 0.2°C (mild) and 1.2 ± 0.3°C (moderate), arterial stiffness was measured in eight healthy younger (26 ± 5 years) and eight healthy older (70 ± 4 years) adults in the supine position. Arterial stiffness was estimated from carotid‐to‐femoral pulse wave velocity (cfPWV, applanation tonometry). cfPWV was higher at baseline in older adults (8.8 ± 2.3 m/sec vs. 5.6 ± 0.9 m/sec, P < 0.01) and this difference was maintained throughout passive heat stress (P < 0.01). cfPWV did not change (P ≥ 0.49) with passive heat stress in either younger (at moderate heat stress: 6.0 ± 1.0 m/sec) or older (at moderate heat stress: 8.5 ± 1.6 m/sec) adults. However, the influence of baseline cfPWV on the change in cfPWV during mild (r = −0.66, P = 0.04) and moderate (r = −0.87, P < 0.01) heat stress were inversely related in older adults, and the strength of these relations was not statistically different (P = 0.08). In younger adults, the influence of baseline cfPWV on the change in cfPWV during mild heat stress was also inversely related (r = −0.79, P = 0.01), while the strength of this relation was attenuated at moderate heat stress (r = −0.24, P = 0.30). Changes in arterial stiffness during passive heat stress in adults aged ≥65 year are likely dependent on the magnitude of baseline arterial stiffness and not necessarily age.
Chronic Kidney Disease and Kidney Cancer Surgery: New Perspectives.

PURPOSE To provide a contemporary understanding of chronic kidney disease (CKD) and its relevance to kidney cancer surgery. To resolve points of discrepancy regarding the survival benefits of partial nephrectomy (PN) vs radical nephrectomy (RN) by critically evaluating the results of prospective and retrospective studies in the urologic literature. MATERIALS/METHODS A comprehensive literature search for relevant articles listed in MEDLINE® (2002-2018) was performed using keywords radical nephrectomy, partial nephrectomy, glomerular filtration rate (GFR), kidney function, and chronic kidney disease. Selected review articles and society guidelines about CKD pertinent to urology and nephrology were also assessed. RESULTS Complete evaluation of the potential consequences of CKD involves assessment of cause, GFR level, and degree of albuminuria. CKD is commonly defined in the urologic literature solely as a GFR <60mL/min/1.73m2, thereby ignoring the significance of CKD cause and the presence/degree of albuminuria. Although this GFR level is relevant for preoperative assessment of patients undergoing surgery for kidney tumors, recent studies suggest that GFR <45mL/min/1.73m2 represents a more discerning postoperative prognostic threshold. Reported survival benefits of PN over RN demonstrated in retrospective studies are likely influenced by selection bias. The lack of survival benefit in the PN cohort of the only randomized trial of PN versus RN is consistent with data demonstrating that patients in both arms of the study had relatively low risk of mortality from CKD, when accounting for etiology of CKD and post-operative GFR levels. CONCLUSIONS The prognostic risk of CKD for kidney cancer patients is increased whenever the preoperative GFR is <60 ml/min/1.73m2 or the postoperative GFR is <45mL/min/1.73m2. Additional factors including non-surgical causes of CKD and degree of albuminuria can also dramatically alter the consequences of CKD following kidney cancer surgery. Urologists must have a comprehensive knowledge of CKD in order to assess the risks/benefits of PN versus RN when managing tumors with increased complexity and/or oncologic aggressiveness.