Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during short-term bed rest.

Short periods of bed rest lead to the loss of muscle mass and quality. It has been speculated that dietary feeding pattern may have an impact upon muscle protein synthesis rates and, therefore, modulate the loss of muscle mass and quality. We subjected 20 healthy men (age: 25 ± 1 yr, body mass index: 23.8 ± 0.8 kg/m2) to 1 wk of strict bed rest with intermittent (4 meals/day) or continuous (24 h/day) enteral tube feeding. Participants consumed deuterium oxide for 7 days before bed rest and throughout the 7-day bed rest period. Prior to and immediately after bed rest, lean body mass (dual energy X-ray absorptiometry), quadriceps cross-sectional area (CSA; CT), maximal oxygen uptake capacity (V̇o2peak), and whole body insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Muscle biopsies were collected 7 days before, 1 day before, and immediately after bed rest to assess muscle tracer incorporation. Bed rest resulted in 0.3 ± 0.3 vs. 0.7 ± 0.4 kg lean tissue loss and a 1.1 ± 0.6 vs. 0.8 ± 0.5% decline in quadriceps CSA in the intermittent vs. continuous feeding group, respectively (both P < 0.05), with no differences between groups (both P > 0.05). Moreover, feeding pattern did not modulate the bed rest-induced decline in insulin sensitivity (-46 ± 3% vs. 39 ± 3%; P < 0.001) or V̇o2peak (-2.5 ± 2.2 vs. -8.6 ± 2.2%; P < 0.010) (both P > 0.05). Myofibrillar protein synthesis rates during bed rest did not differ between the intermittent and continuous feeding group (1.33 ± 0.07 vs. 1.50 ± 0.13%/day, respectively; P > 0.05). In conclusion, dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during 1 wk of bed rest in healthy men.
Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases

ABSTRACT Introduction: Mitochondrial-derived peptides (MDPs) are encoded within the mitochondrial genome. They signal within the cell or are released to act as autocrine/paracrine/endocrine cytoprotective factors playing a key role in the cellular stress response. The first reported and better characterized MDP is humanin (HN), which exerts robust protective effects against a myriad of cytotoxic stimuli in many cell types. These effects have led to the evaluation of HN and its analogs as therapeutic targets for several chronic diseases. Areas covered: We describe the latest findings on the mechanism of action of HN and discuss the role of HN as therapeutic target for neurodegenerative and cardiovascular diseases, diabetes, male infertility, and cancer. Since HN can be detected in circulation, we also depict its value as a biomarker for these diseases. Expert opinion: HN analogs and peptide mimetics have been developed over the last decade and show promising results in preclinical models of degenerative diseases. Local administration of gene therapy vectors that overexpress or silence endogenous HN could also hold therapeutic potential. Controversy on the role of HN in cancer progression and chemoresistance should be addressed before the translation of these therapeutic approaches.
Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low‐Dose Prasugrel or Clopidogrel

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates (ADIRs) and average daily bleeding rates (ADBRs) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low‐dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient‐days of follow‐up and assessed within different clinical phases: acute (0–3 days), subacute (4–30 days), and late (31–365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4–2.9) higher than ADBRs. ADIRs were significantly higher in the clopidogrel arm than in the low‐dose prasugrel arm in the subacute phase (P adj<0.001) without a difference in ADBRs (P adj=0.35). In the late phase, ADIRs remained significantly higher with clopidogrel (P adj<0.001), whereas ADBRs were significantly higher with low‐dose prasugrel (P adj<0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1‐year follow‐up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low‐dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL: http://www.clinicaltrials. gov. Unique identifier: NCT01777503.
Downregulation of carboxylesterase contributes to cyflumetofen resistance in Tetranychus cinnabarinus (Boisduval).

BACKGROUND Increased expression or point mutations of carboxyl/cholinesterases (CCEs) have been involved in many cases of insecticide and acaricide resistance. However, it has been only rarely documented that downregulation of CCE genes is associated with resistance, although many insecticides and acaricides need hydrolytic activation in vivo. Previously, expression analysis of a laboratory-selected cyflumetofen-resistant strain of Tetranychus cinnabarinus indicated that resistance was associated with increased expression of a CCE gene of TcCCE04, but also the downregulation of two CCE genes, TcCCE12 and TcCCE23. RESULTS Synergism experiments revealed the importance of ester hydrolysis in cyflumetofen toxicity, because treatment with S,S,S-tributylphosphorotrithioate (DEF) caused strong inhibition of cyflumetofen hydrolysis, in both the susceptible and resistant strains. Moreover, silencing expression of TcCCE12 and TcCCE23 via RNAi further decreased the susceptibility of mites to cyflumetofen significantly, suggesting that downregulated CCE genes could be involved in cyflumetofen resistance. In addition, it was shown that recombinant TcCCE12 protein could hydrolyze cyflumetofen effectively. CONCLUSION Decreased esterase activity via downregulation of specific CCE genes most likely contributes to cyflumetofen resistance by decreased activation of cyflumetofen to its active metabolite. Mixtures of cyflumetofen and esterase-inhibition acaricides (e.g. organophosphates or carbamates) should be avoided in field applications. © 2019 Society of Chemical Industry.
Mindfulness and metacognition in facing with fear of recurrence: A proof‐of‐concept study with breast‐cancer women

Fear of recurrence is a crucial issue in cancer care. On the one hand, the increase of cancer‐survival rates and complexity of care is exposing patients to this type of fear. On the other hand, it is a distressing and recurrent psychosocial risk that affects quality of life and adherence to follow‐up. Patients should have access to targeted psychological interventions aimed at reducing or preventing fear of recurrence. This mixed‐methods pilot study reports the preliminary results of a novel mindfulness‐ and metacognition‐based intervention specifically targeting fear of recurrence.
Supplementary Information Appendix for Symbiotic Organs Shaped by Distinct Modes of Genome Evolution in Cephalopods

Pacific Biosciences Research Center, University of Hawaii, Honolulu, Hawaii, 96822, USA. Department of Microbiology and Cell Science, University of Florida, Space Life Science Lab, Merritt Island, Florida, 32953, USA. Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA 06269. Department of Molecular Evolution and Development, University of Vienna, Austria. Ecology, Evolution, and Marine Biology Department, University of California, Santa Barbara, CA 93106. 6 Laboratory of Biometry and Evolutionary Biology, University of Lyon, Villeurbanne, France. Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA. McDonnell Genome Institute, Washington University, 63108, Molecular Genetics Unit, Okinawa Institute of Science and Technology, Japan. Department of Molecular and Cell Biology, University of California Berkeley, California 94720, USA. Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.
Effect of donor variation on osteogenesis and vasculogenesis in hydrogel cocultures

To introduce a functional vascular network into tissue‐engineered bone equivalents, human endothelial colony forming cells (ECFCs) and multipotent mesenchymal stromal cells (MSCs) can be cocultured. Here, we studied the impact of donor variation of human bone marrow‐derived MSCs and cord blood‐derived ECFCs on vasculogenesis and osteogenesis using a 3D in vitro coculture model. Further, to make the step towards cocultures consisting of cells derived from a single donor, we tested how induced pluripotent stem cell (iPSC)‐derived human endothelial cells (iECs) performed in coculture models. Cocultures with varying combinations of human donors of MSCs, ECFCs, or iECs were prepared in Matrigel. The constructs were cultured in an osteogenic differentiation medium. Following a 10‐day culture period, the length of the prevascular structures and osteogenic differentiation were evaluated for up to 21 days of culture. The particular combination of MSC and ECFC donors influenced the vasculogenic properties significantly and induced variation in osteogenic potential. In addition, the use of iECs in the cocultures resulted in prevascular structure formation in osteogenically differentiated constructs. Together, these results showed that close attention to the source of primary cells, such as ECFCs and MSCs, is critical to address variability in vasculogenic and osteogenic potential. The 3D coculture model appeared to successfully generate prevascularized constructs and were sufficient in exceeding the ~200 μm diffusion limit. In addition, iPSC‐derived cell lineages may decrease variability by providing a larger and potentially more uniform source of cells for future preclinical and clinical applications.
Recollections of positive early caregiving relate to sympathetic nervous system activation and chronic inflammation in subsequent generations

To understand links between early experience and biomarkers of peripheral physiology in adulthood, this study examined associations between quality of early caregiving and markers of sympathetic activation and chronic inflammation in a sample of 52 low-income mothers and their preschool-aged children. Mothers reported on levels of positive caregiving experienced during childhood using the Structural Analysis of Social Behavior-Intrex. Mother and child sympathetic activation was indexed via pre-ejection period (PEP) at rest, during a dyadic social engagement task, and for children, while interacting with an unfamiliar adult. C-reactive protein (CRP) was collected using whole blood spots to assess levels of low-grade chronic inflammation. Results showed that mothers who reported experiencing more warm guidance and support for autonomy in early childhood displayed lower resting sympathetic nervous system activation (i.e., longer PEP) and lower chronic inflammation (i.e., CRP levels). Further, lower maternal chronic inflammation levels were associated with lower sympathetic activation (i.e., longer PEP) in their children at rest, and during social interactions with mother and a female stranger.
Boosting Potassium-Ion Battery Performance by Encapsulating Red Phosphorus in Free-Standing Nitrogen-Doped Porous Hollow Carbon Nanofibers.

Potassium-ion batteries (KIBs) are a promising alternative to lithium-ion batteries (LIBs) for large-scale renewable energy storage owning to the natural abundance and low cost of potassium. However, the biggest challenge for KIBs application lies in the lack of suitable electrode materials that can deliver long cycle life and high reversible capacity. In this work, we realized unprecedented long cycle life with high reversible capacity (465 mAh g-1 at 2 A g-1 after 800 cycles) as well as outstanding rate capability (342 mAh g-1 at 5 A g-1) for KIBs by embedding red P into free-standing nitrogen-doped porous hollow carbon nanofibers (red P@N-PHCNFs). This design circumvents the problems of pulverization and aggregation of P particles. The in situ transmission electron microscopy (TEM) investigation reveals the structural robustness of the composite fibers during potassiation. The formation of P-C chemical bonds as well as nitrogen doping in the carbon matrix can facilitate the sturdy contact and enhance the adsorption energy of P atoms evidenced by DFT results. In situ Raman and ex situ XRD demonstrate that the final discharge product of the red P@N-PHCNFs is K4P3.
Ursolic acid: Pharmacokinetics process in vitro and in vivo, a mini review

Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. UA has a widespread pharmacologic effect, including antitumor, anti‐inflammatory, anti‐oxidant, anti‐apoptotic, anti‐allergy, and anti‐carcinogenic effects. UA can be used as an alternative medicine for the treatment and prevention of many diseases. However, the bioavailability of UA by oral administration is low since it is absorbed by the intestine through passive diffusion. Therefore, some novel technologies are used to produce UA preparations that can change the pharmacokinetics process and increase its solubility and bioavailability. At present, pharmacokinetic studies on UA are few. In this paper, we will review the pharmacokinetics features of free UA and some novel UA preparations in vitro and in vivo, in order to provide a reference for rational utilization and drug design of UA.
B‐cell phenotype and function in infants with egg allergy

harmonized severity scoring system for acute allergic reactions. Position Paper. Allergy. 2018;73:1792‐1800. 3. Bilo BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JNG & The EAACI Interest Group on Insect Venom Hypersensitivity. Diagnosis of Hymenoptera venom allergy. EAACI Position Paper. Allergy. 2005;60: 1339‐1349. 4. Ring J, Messmer K. Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet. 1977;1:466‐469. 5. Lim S, Crawley E, Woo P, Barnes PJ. Haplotype associated with low interleukin‐10 production in patients with severe asthma. Lancet. 1998;352:113. 6. Chatterjee R, Batra J, Kumar A, et al. Interleukin‐10 promoter polymorphisms and atopic asthma in North Indians. Clin Exp Allergy. 2005;35:914‐919. 7. Meiler F, Zumkehr J, Klunker S, Rückert B, Akdis CA, Akdis M. In vivo switch to IL‐10‐secreting T regulatory cells in high dose allergen exposure. J Exp Med. 2008;205:2887‐2898. 8. Trajkov D, Mirkovska-Stojkovikj J, Arsov T, et al. Association of cytokine gene polymorphism with bronchial asthma in Macedonians. Iran J Allergy Asthma Immunol. 2008;7:143‐156. 9. Karakış GP, Sin BA, Tutkak H, Köse K, Mısırlıgil Z. Genetic aspect of venom allergy: association with HLA Class I and Class II antigens. Ann Agric Environ Med. 2010;17:119‐123.
Arrestin-3 scaffolding of the JNK3 cascade suggests a mechanism for signal amplification

Significance Scaffold proteins are key regulators of signal transduction that bind multiple proteins of a signaling pathway. This simple tethering model explains how the scaffold colocalizes the components for signal propagation, but it is unclear whether scaffolds ensure signal amplification. Here, we use arrestin-3 and the ASK1-MKK4/7-JNK3 kinase cascade as a model system to explore whether scaffolding amplifies signaling. Our studies suggest a model of scaffold-dependent signal amplification that may be conceptually applicable to other scaffold-dependent signaling pathways. Scaffold proteins tether and orient components of a signaling cascade to facilitate signaling. Although much is known about how scaffolds colocalize signaling proteins, it is unclear whether scaffolds promote signal amplification. Here, we used arrestin-3, a scaffold of the ASK1-MKK4/7-JNK3 cascade, as a model to understand signal amplification by a scaffold protein. We found that arrestin-3 exhibited >15-fold higher affinity for inactive JNK3 than for active JNK3, and this change involved a shift in the binding site following JNK3 activation. We used systems biochemistry modeling and Bayesian inference to evaluate how the activation of upstream kinases contributed to JNK3 phosphorylation. Our combined experimental and computational approach suggested that the catalytic phosphorylation rate of JNK3 at Thr-221 by MKK7 is two orders of magnitude faster than the corresponding phosphorylation of Tyr-223 by MKK4 with or without arrestin-3. Finally, we showed that the release of activated JNK3 was critical for signal amplification. Collectively, our data suggest a “conveyor belt” mechanism for signal amplification by scaffold proteins. This mechanism informs on a long-standing mystery for how few upstream kinase molecules activate numerous downstream kinases to amplify signaling.
Effect of low dose ketamine to prevent remifentanil-induced cough: a randomized, double-blind, placebo controlled trial.

BACKGROUND A reflex cough is often observed after an intravenous (IV) bolus of remifentanil. Since ketamine was reported to be effective in modulating the cough reflex, this prospective, randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy of pretreatment with ketamine on remifentanil-induced cough. METHODS 320 patients undergoing general anesthesia for elective surgery were randomly allocated into two groups to receive either IV ketamine 0.1 mg/kg (ketamine group, n = 156) or 0.9% saline (saline group, n = 154) 1 min before administration of remifentanil at a target effect-site concentration of 5 ng/ml. Severity of cough was graded (mild, 1-2; moderate, 3-4; and severe, 5 or >5). RESULTS The overall incidence of cough was significantly higher in the saline group (43/154 patients; 0.28, 95% CI 0.21, 0.36) than that in the ketamine group (18/156 patients; 0.12, 95% CI 0.07, 0.18) (P < 0.001). However, there was no significant difference in the severity and the onset time of cough between the groups. CONCLUSIONS IV ketamine 0.1 mg/kg one minute before remifentanil was effective in suppressing remifentanil-induced cough without affecting the severity and onset time.
Cardiovascular Disease Hospitalizations in Louisiana Parishes’ Elderly before, during and after Hurricane Katrina

The research on how health and health care disparities impact response to and recovery from a disaster, especially among diverse and underserved populations is in great need for a thorough evaluation. The time series analysis utilizing most complete national databases of medical records is an indispensable tool in assessing the destruction and health toll brought about by natural disasters. In this study, we demonstrated such an application by evaluating the impact of Hurricane Katrina in 2005 on cardiovascular disease (CVD), a primary cause of mortality among older adults that can be aggravated by natural disasters. We compared CVD hospitalizations before, during and after Katrina between white and black residents of three most populated parishes in Louisiana: Orleans and Jefferson, which were severely affected by the landfall and subsequent floods, and East Baton Rouge, which hosted many of the evacuees. We abstracted 383,552 CVD hospitalization records for Louisiana’s patients aged 65+ in 2005–2006 from the database maintained by the Center of Medicare & Medicaid Services. Daily time series of CVD-related hospitalization rates at each study parish were compiled, and the changes were characterized using segmented regression. In Orleans Parish, directly affected by the hurricane, hospitalization rates peaked on the 6th day after landfall with an increase (mean ± SD) from 7.25 ± 2.4 to 18.5 ± 17.3 cases/day per 10,000 adults aged 65+ (p < 0.001) and returned to pre-landfall level after ~2 months. Disparities in CVD rates between black and white older adults were exacerbated during and following landfall. In Orleans Parish, a week after landfall, the CVD rates increased to 26.3 ± 23.7 and 16.6 ± 11.7 cases/day per 10,000 people (p < 0.001) for black and white patients, respectively. The abrupt increase in CVDs is likely due to psychosocial and post-traumatic stress caused by the disaster and inadequate response. Inequities in resource allocation and access have to be addressed in disaster preparation and mitigation.
A systematic review of iodine deficiency among women in the UK

Abstract Objective The present study reviewed the literature on iodine status among women of childbearing age and pregnant women in the UK. Particular attention was given to study quality and methods used to assess iodine status. Design A systematic review was conducted to examine the literature and critically evaluate study design. Setting Studies were identified in PubMed, Web of Science, Scopus and Ovid MEDLINE databases, as well as from secondary references. Participants Women of childbearing age or pregnant, living in the UK. Results Fifty-seven articles were identified and twelve articles were selected, including a total of 5283 women. Nine studies conducted urinary iodine assessments, three studies conducted dietary assessments only, and seven studies classified their target population as iodine deficient according to WHO criteria. Conclusions No single study from the selected articles could produce nationally representative results regarding the prevalence of iodine deficiency among the female population in the UK. Consideration of the evidence as a whole suggests that women of childbearing age and pregnant women in the UK are generally iodine insufficient. Further large-scale research is required for more accurate and reliable evidence on iodine status in the UK.
Gadolinium Leakage in Ocular Structures Is Common in Lacunar Infarction

Background and Purpose— We investigated the frequency and pattern of blood-brain barrier, as well as blood-retina barrier, impairment in acute lacunar infarction as demonstrated by hyperintense acute reperfusion marker and gadolinium leakage in ocular structures (GLOS), respectively, on fluid-attenuated inversion recovery images. Methods— Acute lacunar infarction patients who underwent repeated magnetic resonance imaging after intravenous contrast agent administration were identified and the presence of GLOS in the anterior chamber and vitreous body and hyperintense acute reperfusion marker noted on fluid-attenuated inversion recovery. Results— Overall, 24 acute lacunar infarction patients (median age 64.5 years; interquartile range, 54–78 years) were included. On contrast-enhanced fluid-attenuated inversion recovery, GLOS was observed in 11 (45.8%) patients: in 4 (16.7%) in the anterior chamber only and in 7 (29.2%) in the anterior chamber and vitreous body. In all patients, GLOS was bilateral and symmetrical. In patients with GLOS in the anterior chamber only, the time between initial and follow-up magnetic resonance imaging was significantly shorter (7.5 [interquartile range, 4.25–11.5] hours) compared with patients with GLOS in the anterior chamber and vitreous body (28 [interquartile range, 10–43] hours; P=0.047). Hyperintense acute reperfusion marker could not be demonstrated in any of the patients. Conclusions— In acute lacunar infarction patients, unlike hyperintense acute reperfusion marker, GLOS is a frequent finding and shows a similar temporal evolution like in larger ischemic stroke.