Miracle-dz/UniFAR-FTUs huggingface dataset:
Oral Administration of Sodium Nitrate to Metabolic Syndrome Patients Attenuates Mild Inflammatory and Oxidative Responses to Acute Exercise

The beneficial effects of exercise for the treatment and prevention of metabolic syndrome pathologies have been related to its anti-inflammatory and antioxidant effects. Dietary nitrate supplementation is an emerging treatment strategy to alleviate the symptoms of metabolic syndrome affections and to improve vascular function. In this double-blind crossover trial, metabolic syndrome patients performed two exercise tests for 30 min at 60–70% maximal heart rate after the intake of a placebo or a nitrate-enriched beverage. Acute exercise increased the plasma concentration of TNFα, intercellular adhesion molecule ICAM1, PGE1, PGE2 and the newly detected 16-hydroxypalmitic acid (16-HPAL) in metabolic syndrome patients. The cytokine and oxylipin production by peripheral blood mononuclear cells (PBMCs) and neutrophils could be responsible for the plasma concentrations of TNFα and IL6, but not for the plasma concentration of oxylipins nor its post-exercise increase. The intake of sodium nitrate 30 min before exercise increased the concentration of nitrate and nitrite in the oral cavity and plasma and reduced the oxygen cost of exercise. Additionally, nitrate intake prevented the enhancing effects of acute exercise on the plasma concentration of TNFα, ICAM1, PGE1, PGE2 and 16-HPAL, while reducing the capabilities of PBMCs and neutrophils to produce oxylipins.
Mechanism of electroacupuncture-induced reduction of acute lung injury induced by endotoxic shock in rabbits: the relationship with Nrf2/ARE pathway

Objective To investigate the relationship between the mechanism of electroacupuncture (EA)-induced reduction of acute lung injury induced by endotoxic shock (ES) and nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in rabbits.Methods Forty healthy male New Zealand white rabbits,aged 2 months,weighing 1.5-2.0 kg,were randomly divided into 4 groups (n =10 each) using a random number table:sham operation group (group S),group ES,EA at acupoints + ES group (group EA),and EA at non-acupoints + ES group (group NA-EA). The animals were anesthetized with iv 20％ urethane 5 ml/kg,tracheostomized and kept spontaneous breathing.ES was induced by iv administration of lipopolysaccharide (LPS) 5 mg/kg in ES,EA and NA-EA groups.The equal volume of normal saline was given in group S.Bilateral 30 min EA (wave length 0.2-0.6 ms,frequency 2/100 Hz,intensity ≤2-3 mA) stimulation of Zusanli and Feishu was performed once a day for 4 days before establishment of endotoxic shock model and during the process of establishment of endotoxic shock model in EA group.In NA-EA group,EA was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Feishu according to the method previously described in group EA.The rabbits were sacrificed at 6 h after LPS or normal saline administration,and lungs were removed for microscopic examination and for determination of wet to dry lung weight ratio (W/D ratio),malondialdehyde (MDA) contents,superoxide dismutase (SOD) activities,and expression of Nrf2 mRNA in lung tissues and Nrf2 in nucleoprotein and total protein.The pathological changes of lung were scored.The ratio of Nrf2 expression in nucleoprotein to Nrf2 expression in total protein (N/T ratio) was calculated.Results Compared with group S,W/D ratio,MDA contents,and lung injury scores were significantly increased,the activities of SOD were decreased,the expression of Nrf2 mRNA in lung tissues and Nrf2 in nucleoprotein and total protein was up-regulated,and N/T ratio was increased in ES,EA and NA-EA groups.Compared with group ES,W/D ratio,MDA contents,and lung injury scores were significantly decreased,the activities of SOD were increased,the expression of Nrf2 mRNA in lung tissues and Nrf2 in nucleoprotein and total protein was up-regulated,and N/T ratio was increased in EA group,and no significant changes were found in NA-EA group.Conclusion The mechanism by which EA reduces acute lung injury induced by ES may be related to activation of Nrf2/ARE pathway and enhancement of antioxidant capacity in rabbits. Key words: Electroacupuncture; NF-E2-related factor 2; Response elements; Shock, septic; Respiratory distress syndrome, adult
Novel functions of SUN1

Mutations in several genes encoding nuclear envelope associated proteins cause Emery-Dreifuss muscular dystrophy (EDMD). We analyzed fibroblasts from a patient who had a mutation in the EMD gene (p.L84Pfs*6) leading to loss of Emerin and a heterozygous mutation in SUN1 (p.A203V). The second patient harbored a heterozygous mutation in LAP2alpha (p.P426L) and a further mutation in SUN1 (p.A614V). p.A203V is located in the N-terminal domain of SUN1 facing the nucleoplasm and situated in the vicinity of the Nesprin-2 and Emerin binding site. p.A614V precedes the SUN domain which interacts with the KASH domain of Nesprins in the periplasmic space and forms the center of the LINC complex. At the cellular level we observed alterations in the amounts for several components of the nuclear envelope (NE) in patient fibroblasts and further phenotypic characteristics generally attributed to laminopathies such as increased sensitivity to heat stress. The defects were more severe than observed in EDMD cells with mutations in a single gene. In particular, in patient fibroblasts carrying the p.A203V mutation in SUN1 the alterations were aggravated. Moreover, both patient fibroblasts exhibited reduced interaction of SUN1 with Lamin A/C and when expressed ectopically in wild-type fibroblasts the SUN1 mutant proteins exhibited reduced interactions with Emerin as well. Nuclear export of mRNPs through the NPC can be roughly classified into two forms: bulk and specific export, involving an NXF1-dependent pathway and CRM1-dependent pathway, respectively. Here, we show that mammalian cells require SUN1 for efficient nuclear mRNP export. The results show that both SUN1 and SUN2 interact with hnRNP F/H and hnRNP K/J. SUN1 depletion inhibits the mRNP export, with accumulations of both hnRNPs and poly(A)+RNA in the nucleus. LMB treatment indicates that SUN1 functions in mRNA export independent of the CRM1-dependent pathway. SUN1 mediates mRNA export through its association with mRNP complex by a direct interaction with NXF1. Overexpression of GFP fused SUN1 N-terminus leads to the formation of GFP-SUN1-NT positive aggregates which contain NXF1. Additionally, SUN1 associates with the NPC through a direct interaction with Nup153, a nuclear pore component involved in mRNA export. Taken together, our results reveal that the INM protein SUN1 has additional functions aside from being a central component of the LINC complex and that it is an integral component of the mammalian mRNA export pathway suggesting a model whereby SUN1 recruits NXF1-containing mRNP onto the nuclear envelope, and hands it over to Nup153.
DIVERSIFICATION IN THE NEOTROPICS: PHYLOGENETIC PATTERNS AND HISTORICAL PROCESSES

We summarize two symposia that brought together a broad spectrum of talks on how molec- ular data are expanding our understanding of the patterns, processes and timing of avian diversification in the Neotropics. Presenters are associated with natural history museums, which ensure that genetic data are associated with vouchered specimens. Molecular systematics is a rapidly evolving field which promises to bring new understandings of the evolutionary process in the years to come. Accepted 21 December 2007.
Outer Membrane Proteins as a Carrier for Detoxified Lipooligosaccharide Conjugate Vaccines for NontypeableHaemophilus influenzae

ABSTRACT Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media and respiratory tract infections. Outer membrane proteins (OMP) and lipooligosaccharide (LOS) are major surface antigens of NTHi and potential vaccine candidates. De-O-acylated LOS (dLOS) or oligosaccharide (OS) was coupled to total OMP to form dLOS-OMP and OS-OMP conjugates, while a dLOS-tetanus toxoid (TT) was synthesized for comparison. These conjugates were evaluated in mice and rabbits for immunogenicity. dLOS-OMP elicited a better boostable antibody response against LOS than did dLOS-TT, while OS-OMP was not immunogenic. Formulation of the conjugates with Ribi adjuvant significantly enhanced the immunogenicity of dLOS-OMP and dLOS-TT but not that of OS-OMP. In addition, rabbit antisera elicited by dLOS-OMP but not dLOS-TT (or OMP alone) demonstrated bactericidal activity against 40% of the NTHi strains tested. These results indicate that dLOS is a better derivative of LOS than OS and that OMP is a good carrier for NTHi LOS-based conjugate vaccines.
Medication Dosing Safety for Pediatric Patients: Recognizing Gaps, Safety Threats, and Best Practices in the Emergency Medical Services Setting. A Position Statement and Resource Document from NAEMSP

Abstract Background Millions of patients receive medications in the Emergency Medical Services (EMS) setting annually, and dosing safety is critically important. The need for weight-based dosing in pediatric patients and variability in medication concentrations available in the EMS setting may require EMS providers to perform complex calculations to derive the appropriate dose to deliver. These factors can significantly increase the risk for harm when dose calculations are inaccurate or incorrect. Methods We conducted a scoping review of the EMS, interfacility transport and emergency medicine literature regarding pediatric medication dosing safety. A priori, the authors identified four research topics: (1) what are the greatest safety threats that result in significant dosing errors that potentially result in harm to patients, (2) what practices or technologies are known to enhance dosing safety, (3) can data from other settings be extrapolated to the EMS environment to inform dosing safety, and (4) what impact could standardization of medication formularies have on enhancing dosing safety. To address these topics, 17 PICO (Patient, Intervention, Comparison, Outcome) questions were developed and a literature search was performed. Results After applying exclusion criteria, 70 articles were reviewed. The methods for the investigation, findings from these articles and how they inform EMS medication dosing safety are summarized here. This review yielded 11 recommendations to improve safety of medication delivery in the EMS setting. Conclusion These recommendations are summarized in the National Association of EMS Physicians® position statement: Medication Dosing Safety for Pediatric Patients in Emergency Medical Services.
Voxelwise and Patientwise Correlation of 18F-FDOPA PET, Relative Cerebral Blood Volume, and Apparent Diffusion Coefficient in Treatment-Naïve Diffuse Gliomas with Different Molecular Subtypes

Visual Abstract Our purpose was to identify correlations between 18F-fluorodihydroxyphenylalanine (18F-FDOPA) uptake and physiologic MRI, including relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC), in gliomas with different molecular subtypes and to evaluate their prognostic values. Methods: Sixty-eight treatment-naïve glioma patients who underwent 18F-FDOPA PET and physiologic MRI were retrospectively selected (36 with isocitrate dehydrogenase wild-type [IDHwt], 16 with mutant 1p/19q noncodeleted [IDHm-noncodel], and 16 with mutant codeleted [IDHm-codel]). Fluid-attenuated inversion recovery hyperintense areas were segmented and used as regions of interest. For voxelwise and patientwise analyses, Pearson correlation coefficients (rvoxelwise and rpatientwise) between the normalized SUV (nSUV), rCBV, and ADC were evaluated. Cox regression analysis was performed to investigate the associations between overall survival and rvoxelwise, maximum or median nSUV, median rCBV, or median ADC. Results: For IDHwt and IDHm-noncodel gliomas, nSUV demonstrated significant positive correlations with rCBV (rvoxelwise = 0.25 and 0.31, respectively; rpatientwise = 0.50 and 0.70, respectively) and negative correlations with ADC (rvoxelwise = −0.19 and −0.19, respectively; rpatientwise = −0.58 and −0.61, respectively) in both voxelwise and patientwise analyses. IDHm-codel gliomas demonstrated a significant positive correlation between nSUV and ADC only in voxelwise analysis (rvoxelwise = 0.18). In Cox regression analysis, rvoxelwise between nSUV and rCBV (hazard ratio, 28.82) or ADC (hazard ratio, 0.085) had significant associations with overall survival for only IDHwt gliomas. Conclusion: IDHm-codel gliomas showed distinctive patterns of correlations between amino acid PET and physiologic MRI. Stronger correlations between nSUV and rCBV or ADC may result in a worse prognosis for IDHwt gliomas.
Lipoic acid rejuvenates aged intestinal stem cells by preventing age‐associated endosome reduction

The age‐associated decline of adult stem cell function is closely related to the decline in tissue function and age‐related diseases. However, the underlying mechanisms that ultimately lead to the observed functional decline of stem cells still remain largely unexplored. This study investigated Drosophila midguts and found a continuous downregulation of lipoic acid synthase, which encodes the key enzyme for the endogenous synthesis of alpha‐lipoic acid (ALA), upon aging. Importantly, orally administration of ALA significantly reversed the age‐associated hyperproliferation of intestinal stem cells (ISCs) and the observed decline of intestinal function, thus extending the lifespan of Drosophila. This study reports that ALA reverses age‐associated ISC dysfunction by promoting the activation of the endocytosis–autophagy network, which decreases in aged ISCs. Moreover, this study suggests that ALA may be used as a safe and effective anti‐aging compound for the treatment of ISC‐dysfunction‐related diseases and for the promotion of healthy aging in humans.
Equine Alphaherpesviruses Require Activation of the Small GTPases Rac1 and Cdc42 for Intracellular Transport

Viruses utilize host cell signaling to facilitate productive infection. Equine herpesvirus type 1 (EHV-1) has been shown to activate Ca2+ release and phospholipase C upon contact with α4β1 integrins on the cell surface. Signaling molecules, including small GTPases, have been shown to be activated downstream of Ca2+ release, and modulate virus entry, membrane remodeling and intracellular transport. In this study, we show that EHV-1 activates the small GTPases Rac1 and Cdc42 during infection. The activation of Rac1 and Cdc42 is necessary for virus-induced acetylation of tubulin, effective viral transport to the nucleus, and cell-to-cell spread. We also show that inhibitors of Rac1 and Cdc42 did not block virus entry, but inhibited overall virus infection. The Rac1 and Cdc42 signaling is presumably orthogonal to Ca2+ release, since Rac1 and Cdc42 inhibitors affected the infection of both EHV-1 and EHV-4, which do not bind to integrins.
Changes in Weight and Nutritional Habits in Adults with Obesity during the “Lockdown” Period Caused by the COVID-19 Virus Emergency

Our aim is evaluating the changes in weight and dietary habits in a sample of outpatients with obesity after 1 month of enforced lockdown during the COVID-19 pandemic in Northern Italy. In this observational retrospective study, the patients of our Obesity Unit were invited to answer to a 12-question multiple-choice questionnaire relative to weight changes, working activity, exercise, dietary habits, and conditions potentially impacting on nutritional choices. A multivariate regression analysis was performed to evaluate the associations among weight/BMI changes and the analyzed variables. A total of 150 subjects (91.5%) completed the questionnaire. Mean self-reported weight gain was ≈1.5 kg (p < 0.001). Lower exercise, self-reported boredom/solitude, anxiety/depression, enhanced eating, consumption of snacks, unhealthy foods, cereals, and sweets were correlated with a significantly higher weight gain. Multiple regression analyses showed that increased education (inversely, β = −1.15; 95%CI −2.13, −0.17, p = 0.022), self-reported anxiety/depression (β = 1.61; 0.53, 2.69, p = 0.004), and not consuming healthy foods (β = 1.48; 0.19, 2.77, p = 0.026) were significantly associated with increased weight gain. The estimated direct effect of self-reported anxiety/depression on weight was 2.07 kg (1.07, 3.07, p < 0.001). Individuals with obesity significantly gained weight 1 month after the beginning of the quarantine. The adverse mental burden linked to the COVID-19 pandemic was greatly associated with increased weight gain.
Feeding habits of blackmouth catshark Galeus melastomus Rafinesque, 1810 and velvet belly lantern shark Etmopterus spinax (Linnaeus, 1758) in the western Mediterranean

Summary Feeding habits of blackmouth catshark Galeus melastomus and velvet belly lantern shark Etmopterus spinax were studied throughout the Spanish Mediterranean, from the Alboran Sea to the Gulf of Lion, between 400 and 790 m depth. Diets were studied taking into account size and depth differences. Included within the trophic guild of non-migratory macroplankton feeders, both species preferably exploited mesopelagic resources (mainly natantian decapods, euphausiids, mesopelagic fish and cephalopods). G. melastomus mostly preyed on decapod crustaceans (46% in terms of IRI), with cephalopods, euphausiids and mesopelagic fish as a secondary prey item. The diet of E. spinax was composed primarily of mesopelagic fish (61.4% in terms of IRI), with decapod crustaceans and cephalopods of secondary importance. Both species showed ontogenetic changes in their diets: small blackmouth catshark specimens (between 150 and 350 mm total length) mainly consumed cephalopods, medium size individuals (351–450 mm TL) consumed decapod crustaceans, while larger specimens (larger than 451 mm TL) seemed to be more generalist-feeders. Smaller specimens of E. spinax (150– 250 mm TL) mostly fed on small crustaceans and cephalopods, whilst an increase in the consumption of mesopelagic fish (mycthophids and Stomiiformes) was detected in larger individuals (251–450 mm TL). Diet of G. melastomus also changed throughout the narrow depth range explored, mainly consumed euphausiids and mesopelagic fish between 400 and 500 m depth, whilst preferably exploiting natantian decapods and cephalopods below 500 m of depth. However, this trend may be correlated to the larger-deeper trend found for this species. Slight but not significant differences were found in E. spinax diet by depth, with euphausiids mainly consumed at lower depths (400–500 m). In a multispecies MDS analysis, diets of G. melastomus and E. spinax were separated and the ANOSIM test proved evidence for significant differences in the diets of the two species (R = 0.25; P = 0.05), mainly attributed to the stronger pelagic habits of E. spinax in comparison with G. melastomus. Low overlap (by Schoener Index) also occurred when comparing specimens of the same size range. In general, the higher occurrence of benthic prey in the diet of G. melastomus (i.e. the brachyuran crab Geryon longipes, the thalassinid shrimp Calocaris macandrae) than in E. spinax pointed to a stronger pelagic behavior for the velvet belly lantern shark. Both multivariate analysis and the Levins Index pointed to a narrow niche breadth for the two sharks. A trend of increasing fullness was found for both species in the highly productive areas of the Alboran Sea and Vera Gulf, probably related to higher resource availability, enhanced by local upwellings.
ADSSL1 myopathy is the most common nemaline myopathy in Japan with variable clinical features

Objective To elucidate the prevalence of Japanese ADSSL1 myopathy and determine the clinicopathologic features of the disease. Methods We searched for ADSSL1 variants in myopathic patients from January 1978 to March 2019 in our repository and assessed the clinicopathologic features of patients with variants. Results We identified 63 patients from 59 families with biallelic variants of ADSSL1. Among the 7 distinct variants identified, c.781G>A and c.919delA accounted for 53.2% and 40.5% of alleles, respectively, suggesting the presence of common founders, while the other 5 were novel. Most of the identified patients displayed more variable muscle symptoms, including symptoms in the proximal and/or distal leg muscles, tongue, masseter, diaphragm, and paraspinal muscles, in adolescence than previously reported patients. Dysphagia with masticatory dysfunction developed in 26 out of 63 patients; hypertrophic cardiomyopathy developed in 12 out of 48 patients; and restrictive ventilatory insufficiency developed in 26 out of 34 patients in later stages. Radiologically, fat infiltration into the periphery of vastus lateralis, gastrocnemius, and soleus muscles was observed in all patients. Pathologically, nemaline bodies in addition to increased lipid droplets and myofibrillar disorganization were commonly observed in all patients, suggesting that the disease may be classified as nemaline myopathy. This finding revealed that ADSSL1 myopathy is the most frequent among all genetically diagnosable nemaline myopathies in our center. Conclusions ADSSL1 myopathy is characterized by more variable manifestations than previously reported. It is the most common among all genetically diagnosable nemaline myopathies in our center, although mildly increased lipid droplets are also constantly observed features.
Lung ultrasound and diaphragmatic excursion assessment for evaluating perioperative atelectasis and aeration loss during video-assisted thoracic surgery: a feasibility study.

BACKGROUND Although lung-protective strategies are widely used in thoracic surgery, postoperative atelectasis can still occur. Both lung ultrasound (LUS) and diaphragmatic excursion assessments are accurate and noninvasive for bedside imaging and examination. This study aimed to test the feasibility of using LUS during the perioperative period of video-assisted thoracic surgery (VATS) and to continuously evaluate aeration changes through LUS examination and diaphragmatic excursion assessment. METHODS Between January 2019 and May 2019, data were prospectively collected from patients that were scheduled to undergo a VATS with one-lung ventilation (OLV). LUS was performed at four specific timepoints: before the induction of general anesthesia (timepoint A), 5 minutes after intubation (timepoint B), at the end of surgery (timepoint C), and 15 minutes after extubation (timepoint D). Diaphragmatic excursion assessment was performed only at the first (timepoint A) and last timepoints (timepoint D) for the use of paralytics during surgery. RESULTS This study included 80 consecutive patients (37 men, 43 women). Among them were patients undergoing lobectomy (14 patients; 17.5%), segmentectomy (35 patients, 43.8%), wedge resection (19 patients; 23.8%), or mediastinal tumor resection (12 patients, 15.0%). LUS was possible for all patients. As a result, LUS helped detect postoperative atelectasis in 12 patients (15.0%). Among them were 4 (33.3%) lung resection patients and 8 (66.7%) mediastinal tumor resection patients. Pneumothorax and small effusions were also diagnosed through LUS examination. There was significant aeration loss throughout the surgery from the start of induction (P<0.001). We discovered that changes in LUS scores were found to be associated with an increase of diaphragmatic excursions after assessment (Spearman's r=-0.54, P<0.001). CONCLUSIONS LUS is feasible during all phases of the perioperative period in VATS and can facilitate the early investigation of perioperative atelectasis. Perioperative LUS and diaphragmatic excursion assessment are also feasible for the continuous assessment of aeration loss in patients undergoing VATS.