Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiscale modeling of the neuromuscular system: Coupling neurophysiology and skeletal muscle mechanics

Mathematical models and computer simulations have the great potential to substantially increase our understanding of the biophysical behavior of the neuromuscular system. This, however, requires detailed multiscale, and multiphysics models. Once validated, such models allow systematic in silico investigations that are not necessarily feasible within experiments and, therefore, have the ability to provide valuable insights into the complex interrelations within the healthy system and for pathological conditions. Most of the existing models focus on individual parts of the neuromuscular system and do not consider the neuromuscular system as an integrated physiological system. Hence, the aim of this advanced review is to facilitate the prospective development of detailed biophysical models of the entire neuromuscular system. For this purpose, this review is subdivided into three parts. The first part introduces the key anatomical and physiological aspects of the healthy neuromuscular system necessary for modeling the neuromuscular system. The second part provides an overview on state‐of‐the‐art modeling approaches representing all major components of the neuromuscular system on different time and length scales. Within the last part, a specific multiscale neuromuscular system model is introduced. The integrated system model combines existing models of the motor neuron pool, of the sensory system and of a multiscale model describing the mechanical behavior of skeletal muscles. Since many sub‐models are based on strictly biophysical modeling approaches, it closely represents the underlying physiological system and thus could be employed as starting point for further improvements and future developments.
Low Vitamin D Status Is Associated With Impaired Bone Quality and Increased Risk of Fracture‐Related Hospitalization in Older Australian Women

The vitamin D debate relates in part to ideal public health population levels of circulating 25‐hydroxyvitamin D (25OHD) to maintain bone structure and reduce fracture. In a secondary analysis of 1348 women aged 70 to 85 years at baseline (1998) from the Perth Longitudinal Study of Aging in Women (a 5‐year calcium supplementation trial followed by two 5‐year extensions), we examined the dose‐response relations of baseline plasma 25OHD with hip DXA BMD at year 1, lumbar spine BMD, and trabecular bone score (TBS) at year 5, and fracture‐related hospitalizations over 14.5 years obtained by health record linkage. Mean baseline plasma 25OHD was 66.9 ± 28.2 nmol/L and 28.5%, 36.4%, and 35.1% of women had levels <50, 50 to 74.9, and ≥75 nmol/L, respectively. Generalized additive models showed that total hip and femoral neck BMD and TBS, but not spine BMD, were higher with increasing plasma 25OHD up to 100 nmol/L. Compared with those with 25OHD <50 nmol/L, women with 25OHD ≥75 nmol/L had significantly higher total hip and femoral neck BMD at year 1 (3.3% to 3.9%) and TBS at year 5 (2.0%), all P < 0.05. During the follow‐up, 27.6% of women experienced any fracture‐related hospitalization and 10.6% hip fracture‐related hospitalization. Penalized spline regression models showed a decrease in risk with increased 25OHD levels up to 65 nmol/L and 75 nmol/L for hip fracture and any fracture‐related hospitalization, respectively. Cox regression grouped analyses showed that compared with women with 25OHD <50 nmol/L, those with 25OHD levels 50 to 74.9 and ≥75 nmol/L had significantly lower risk for hip fracture [HR 0.60 (95% CI, 0.40 to 0.91) and 0.61 (95% CI, 0.40 to 0.92), respectively], and any fracture‐related hospitalization [HR 0.77 (95% CI, 0.59 to 0.99) and 0.70 (95% CI, 0.54 to 0.91), respectively]. In older white women, 25OHD levels >50 nmol/L are a minimum public health target and 25OHD levels beyond 75 nmol/L may not have additional benefit to reduce fracture risk. © 2019 American Society for Bone and Mineral Research.
A Comparative Analysis of Manual and Computer Constant Comparison Methods: Using Data from a Constructivist Inquiry of Experiences Working with Ethnic Agencies

A dilemma one may face in analyzing qualitative data is whether to use a manual approach with index cards or a computer data management tool like ATLAS.ti. This paper compares the two approaches in organizing and analyzing data using the same data set. The data were collected and first analyzed in a constructivist inquiry course according to the methods laid out by Rodwell (1998). This process involved unitizing data onto index cards and these cards were then sorted into categories during the constant comparison process. Later, the same data were linked to ATLAS.ti where they were unitized and categorized simultaneously. Constant comparison took place when all the data were coded. A comparison of the two methods allowed the author to determine the strengths and limitations for the various stages of constant comparison.
Responding to an Unexpected In-Flight Event: Physiological Arousal, Information Processing, and Performance

Objective The study was designed to investigate whether a simulated unexpected abnormal flight event can lead to startle and explore differences in behavioral responses between expected and unexpected abnormal flight events. Background Recent research suggests startle (an autonomic response to an acute stimulus) following unexpected abnormal flight events can impact pilot performance and can increase the probability of a negative outcome following the event. Method Information processing, physiological measures, and performance differences between responses to expected and unexpected flight events were compared. General aviation (GA) pilots flew a series of flights in a fixed-base flight simulator including two experimental flights which included an unexpected and an expected, engine failure. During the flights, heart rate, eye tracking, and flight data were recorded. Results During the unexpected engine failure, pilots showed greater increases in heart rate and pupil dilation. Significant differences in scanning were evident with fewer areas scanned following the unexpected event. During the unexpected engine failure, performance was impaired when compared to the expected events. However, poor performance was not associated with higher levels of arousal. Conclusion The study provides an empirical demonstration of impaired pilot response to unexpected events with associated symptoms consistent with the induction of startle. The present research builds on Landman et al.’s conceptual model of startle and surprise. Application Standardized training protocols may not adequately prepare pilots to deal with the unexpected effects of startle in real-world encounters. Introducing greater variety into training events may be useful. The effects of startle in disrupting well-trained responses may also occur in areas other than aviation where critical events may occur unexpectedly or present in an unfamiliar manner.
Epigenetic Regulation of Plant Gametophyte Development

Unlike in animals, the reproductive lineage cells in plants differentiate from within somatic tissues late in development to produce a specific haploid generation of the life cycle—male and female gametophytes. In flowering plants, the male gametophyte develops within the anthers and the female gametophyte—within the ovule. Both gametophytes consist of only a few cells. There are two major stages of gametophyte development—meiotic and post-meiotic. In the first stage, sporocyte mother cells differentiate within the anther (pollen mother cell) and the ovule (megaspore mother cell). These sporocyte mother cells undergo two meiotic divisions to produce four haploid daughter cells—male spores (microspores) and female spores (megaspores). In the second stage, the haploid spore cells undergo few asymmetric haploid mitotic divisions to produce the 3-cell male or 7-cell female gametophyte. Both stages of gametophyte development involve extensive epigenetic reprogramming, including siRNA dependent changes in DNA methylation and chromatin restructuring. This intricate mosaic of epigenetic changes determines, to a great extent, embryo and endosperm development in the future sporophyte generation.
A Potent and Effective Suicidal Listeria Vaccine Platform

Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. ABSTRACT Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8+ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection.
Taming Global Governance Idea Chaos

sense of what a book is about. But first a prologue of 16 generalized items from the 1990-2004 period, many written by Fellows of the World Academy of Art and Science (WAAS), and originally abstracted for Future Survey, a monthly publication of the World Future Society that I edited between 1979 and 2008. While not exhaustive, the abstracts offered in this prologue are sufficient to highlight how global governance was envisioned during this period, and to indicate how global governance thinking was broader and bolder one to two decades ago, arguably both for better and for worse. Several books from this period are also included in the Normative Futures section.
Exporting MOOSE Models to Rational Rose UML

In software re-engineering projects very often you have the source code of an application but you miss its programmer, the design and the documentation. In order to understand these systems you need reverse engineering tools. UMLDesignExtractoris the prototype of a reverse engineering tool generating UML class diagrams from object-oriented code. UMLDesignExtractoris built on top of MOOSE and is written in S MALLTALK . For the graphical output it uses the API of Rational Rose, a professional UML modeler. In the following chapters you find a survey on the involved technologies and architectures as well as a detailed description of the application UMLDesignExtractor , illustrated with four case studies.
Structural and Functional Analyses of Cone Snail Toxins

Cone snails are marine gastropod mollusks with one of the most powerful venoms in nature. The toxins, named conotoxins, must act quickly on the cone snails´ prey due to the fact that snails are extremely slow, reducing their hunting capability. Therefore, the characteristics of conotoxins have become the object of investigation, and as a result medicines have been developed or are in the trialing process. Conotoxins interact with transmembrane proteins, showing specificity and potency. They target ion channels and ionotropic receptors with greater regularity, and when interaction occurs, there is immediate physiological decompensation. In this review we aimed to evaluate the structural features of conotoxins and the relationship with their target types.
Nutritional Interventions to Improve Clinical Outcomes in Ovarian Cancer: A Systematic Review of Randomized Controlled Trials

Among all gynaecological neoplasms, ovarian cancer has the highest rate of disease-related malnutrition, representing an important risk factor of postoperative mortality and morbidity. Hence, the importance of finding effective nutritional interventions is crucial to improve ovarian cancer patient’s well-being and survival. This systematic review of randomized controlled trials (RCTs) aims at assessing the effects of nutritional interventions on clinical outcomes such as overall survival, progression-free survival, length of hospital stay (LOS), complications following surgery and/or chemotherapy in ovarian cancer patients. Three electronic bibliographic databases (MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials) were used to conduct a systematic literature search based on fixed inclusion and exclusion criteria, until December 2018. A total of 14 studies were identified. Several early postoperative feeding interventions studies (n = 8) were retrieved mainly demonstrating a reduction in LOS and an ameliorated intestinal recovery after surgery. Moreover, innovative nutritional approaches such as chewing gum intervention (n = 1), coffee consumption (n = 1), ketogenic diet intervention (n = 2) or fruit and vegetable juice concentrate supplementation diet (n = 1) and short-term fasting (n = 1) have been shown as valid and well-tolerated nutritional strategies improving clinical outcomes. However, despite an acceptable number of prospective trials, there is still a lack of homogeneous and robust endpoints. In particular, there is an urgent need of RCTs evaluating overall survival and progression-free survival during ovarian oncology treatments. Further high-quality studies are warranted, especially prospective studies and large RCTs, with more homogeneous types of intervention and clinical outcomes, including a more specific sampling of ovarian cancer women, to identify appropriate and effective nutritional strategies for this cancer, which is at high risk of malnutrition.
Altered cytochrome 2E1 and 3A P450‐dependent drug metabolism in advanced ovarian cancer correlates to tumour‐associated inflammation

Previous work has focussed on changes in drug metabolism caused by altered activity of CYP3A in the presence of inflammation and, in particular, inflammation associated with malignancy. However, drug metabolism involves a number of other P450s, and therefore, we assessed the effect of cancer‐related inflammation on multiple CYP enzymes using a validated drug cocktail.
Guanine Quadruplex DNA Regulates Gamma Radiation Response of Genome Functions in the Radioresistant Bacterium Deinococcus radiodurans

Deinococcus radiodurans can recover from extensive DNA damage caused by many genotoxic agents. It lacks LexA/RecA-mediated canonical SOS response. Therefore, the molecular mechanisms underlying the regulation of DNA damage response would be worth investigating in this bacterium. D. radiodurans genome is GC-rich and contains numerous islands of putative guanine quadruplex (G4) DNA structure-forming motifs. Here, we showed that in vivo stabilization of G4 DNA structures can impair DNA damage response processes in D. radiodurans. Essential cellular processes such as transcription, DNA synthesis, and protein translation, which are also an integral part of the double-strand DNA break repair pathway, are affected by the arrest of G4 DNA structure dynamics. Thus, the role of DNA secondary structures in DNA damage response and radioresistance is demonstrated. ABSTRACT Guanine quadruplex (G4) DNA/RNA are secondary structures that regulate the various cellular processes in both eukaryotes and bacteria. Deinococcus radiodurans, a Gram-positive bacterium known for its extraordinary radioresistance, shows a genomewide occurrence of putative G4 DNA-forming motifs in its GC-rich genome. N-Methyl mesoporphyrin (NMM), a G4 DNA structure-stabilizing drug, did not affect bacterial growth under normal conditions but inhibited the postirradiation recovery of gamma-irradiated cells. Transcriptome sequencing analysis of cells treated with both radiation and NMM showed repression of gamma radiation-responsive gene expression, which was observed in the absence of NMM. Notably, this effect of NMM on the expression of housekeeping genes involved in other cellular processes was not observed. Stabilization of G4 DNA structures mapped at the upstream of recA and in the encoding region of DR_2199 had negatively affected promoter activity in vivo, DNA synthesis in vitro and protein translation in Escherichia coli host. These results suggested that G4 DNA plays an important role in DNA damage response and in the regulation of expression of the DNA repair proteins required for radioresistance in D. radiodurans. IMPORTANCE Deinococcus radiodurans can recover from extensive DNA damage caused by many genotoxic agents. It lacks LexA/RecA-mediated canonical SOS response. Therefore, the molecular mechanisms underlying the regulation of DNA damage response would be worth investigating in this bacterium. D. radiodurans genome is GC-rich and contains numerous islands of putative guanine quadruplex (G4) DNA structure-forming motifs. Here, we showed that in vivo stabilization of G4 DNA structures can impair DNA damage response processes in D. radiodurans. Essential cellular processes such as transcription, DNA synthesis, and protein translation, which are also an integral part of the double-strand DNA break repair pathway, are affected by the arrest of G4 DNA structure dynamics. Thus, the role of DNA secondary structures in DNA damage response and radioresistance is demonstrated.
Psychometric development of a new body image scale for breast cancer survivors

Abstract The purpose of this study was to psychometrically test a body image scale for breast cancer survivors (BCS). Data (n = 1127 BCSs) were obtained via telephone and mailed questionnaires. Psychometric testing was conducted using Cronbach’s alpha, item-total correlations, factor analysis, linear regression, and Pearson’s correlations. Data demonstrated a unidimensional seven-item scale with Cronbach’s alpha = 0.88 and item-total correlations ranging from 0.367 to 0.829. Construct validity was demonstrated with 48% of the variance in well-being explained by constructs in the conceptual model [F(14,784) = 48.35, p < . 001]. The body image scale demonstrated high internal consistency reliability, unidimensionality, and construct validity.
Impact of Evidence‐Based Stroke Care on Patient Outcomes: A Multilevel Analysis of an International Study

Background The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence‐based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0–2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or “defect‐free” care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18–1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62–3.09). Defect‐free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0–1) (odds ratio, 1.22; 95% CI, 1.04–1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions Use of evidence‐based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments. Clinical Trial Registration URL: https://www.clinicaltrials. gov. Unique Identifier: NCT02162017.
Role of coronary angiography in patients with a non-diagnostic electrocardiogram following out of hospital cardiac arrest: Rationale and design of the multicentre randomized controlled COUPE trial

Background: Coronary artery disease (CAD) is a major cause of out-of-hospital cardiac arrest (OHCA). The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following cardiac arrest in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. Aims: We aim to assess whether emergency CAG and PCI, when indicated, will improve survival with good neurological outcome in post-OHCA patients without STEMI who remain comatose. Methods: COUPE is a prospective, multicentre and randomized controlled clinical trial. A total of 166 survivors of OHCA without STEMI will be included. Potentially non-cardiac aetiology of the cardiac arrest will be ruled out prior to randomization. Randomization will be 1:1 for emergency (within 2 h) or deferred (performed before discharge) CAG. Both groups will receive routine care in the intensive cardiac care unit, including therapeutic hypothermia. The primary efficacy endpoint is a composite of in-hospital survival free of severe dependence, which will be evaluated using the Cerebral Performance Category Scale. The safety endpoint will be a composite of major adverse cardiac events including death, reinfarction, bleeding and ventricular arrhythmias. Conclusions: This study will assess the efficacy of an emergency CAG versus a deferred one in OHCA patients without STEMI in terms of survival and neurological impairment.
Assessment of Pollen Diversity Available to Honey Bees (Hymenoptera: Apidae) in Major Cropping Systems During Pollination in the Western United States

Abstract Global western honey bee, Apis mellifera (L.) (Hymenoptera: Apidae), colony declines pose a significant threat to food production worldwide. Poor nutrition resulting from habitat loss, extensive monocultures, and agricultural intensification is among the several suggested drivers for colony declines. Pollen is the primary source of protein for honey bees; therefore, both pollen abundance and diversity are critical for colony growth and survival. Many cropping systems that employ honey bee colonies for pollination may lack sufficient pollen diversity and abundance to provide optimal bee nutrition. In this observational study, we documented the diversity and relative abundance of pollen collected by honey bees in five major pollinator-dependent crops in the western United States. We sampled pollen from pollen traps installed on honey bee colonies in the following cropping systems—almond, cherry, highbush blueberry, hybrid carrot, and meadowfoam. The pollen diversity was estimated by documenting the number of different pollen pellet colors and plant taxa found in each pollen sample. The lowest pollen diversity was found in almond crop. Relatively higher quantities of pollen collection were collected in almond, cherry, and meadowfoam cropping systems. The information gleaned from this study regarding pollen diversity and abundance may help growers, land managers, and beekeepers improve pollen forage available to bees in these cropping systems.