Miracle-dz/UniFAR-FTUs huggingface dataset:
The Gut-Microbiome in Gulf War Veterans: A Preliminary Report

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study; GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different gut microbiome patterns among the three groups and within the GWI +/−GI groups. Specifically, GW controls had a greater abundance of firmicutes and the GWI+GI group had a greater abundance of the phyla bacteroidetes, actinobacteria, euryarchaeota, and proteobacteria as well as higher abundances of the families Bacteroidaceae, Erysipelotrichaceae, and Bifidobacteriaceae. The GWI+GI group also showed greater plasma levels of the inflammatory cytokine TNF-RI and they endorsed significantly more chemical weapons exposure during the war and reported significantly greater chronic pain, fatigue and sleep difficulties than the other groups. Studies with larger samples sizes are needed to confirm these initial findings.
Sleep quality and nocturnal pain in patients with hip osteoarthritis

Abstract Osteoarthritis (OA) is a common condition of the hip. Patients with hip OA often report nocturnal pain, yet little is known how it affects sleep quality. The purpose of this paper was to assess how hip arthritis affects sleep quality. We hypothesized that hip pain caused by hip OA affects sleep quality in adult patients. This is a prospective, cross-sectional study of patients who were diagnosed with hip OA. Patients were evaluated using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), hip outcome score (HOS), and modified Harris hip score (mHHS). Sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI). A multiple regression model was used to assess factors associated with poor sleep quality. A total of 106 patients were analyzed. All patients had a Tonnis grade of 2 or 3 and American Society of Anesthesiologists (ASA) classification of 2. WOMAC, HOS, and mHHS were significantly and negatively correlated with PSQI. The multiple regression model, WOMAC, short form health survey vitality, ASA classification, and history of obstructive sleep apnea were associated with poor sleep quality (R = 0.60, P < .001). Patients with hip OA, who report a symptomatic hip, are susceptible to reduced sleep quality. There is a correlation between worsening HOSs and sleep quality. The WOMAC score is a significant predictor of poor sleep quality. Patients with poor hip metrics should be screened for sleep disturbance.
Computational fluid dynamics simulation to compare large volume irrigation and continuous spraying during nasal irrigation

Nasal irrigation is now widely recognized as a treatment for chronic rhinosinusitis and during the postoperative period. However, there are no guidelines for performing irrigation. This study used computational fluid dynamics (CFD) simulation objective physical parameters to optimize and increase the efficiency of nasal irrigation and to compare large‐volume, manual, and gravity pressure irrigation vs small‐volume continuous spraying.
Biogeochemical and physical controls on methane fluxes from two ferruginous meromictic lakes

Meromictic lakes with anoxic bottom waters often have active methane cycles whereby methane is generally produced biogenically under anoxic conditions and oxidized in oxic surface waters prior to reaching the atmosphere. Lakes that contain dissolved ferrous iron in their deep waters (i.e., ferruginous) are rare, but valuable, as geochemical analogues of the conditions that dominated the Earth's oceans during the Precambrian when interactions between the iron and methane cycles could have shaped the greenhouse regulation of the planet's climate. Here, we explored controls on the methane fluxes from Brownie Lake and Canyon Lake, two ferruginous meromictic lakes that contain similar concentrations (max. >1 mM) of dissolved methane in their bottom waters. The order Methanobacteriales was the dominant methanogen detected in both lakes. At Brownie Lake, methanogen abundance, an increase in methane concentration with respect to depths closer to the sediment, and isotopic data suggest methanogenesis is an active process in the anoxic water column. At Canyon Lake, methanogenesis occurred primarily in the sediment. The most abundant aerobic methane‐oxidizing bacteria present in both water columns were associated with the Gammaproteobacteria, with little evidence of anaerobic methane oxidizing organisms being present or active. Direct measurements at the surface revealed a methane flux from Brownie Lake that was two orders of magnitude greater than the flux from Canyon Lake. Comparison of measured versus calculated turbulent diffusive fluxes indicates that most of the methane flux at Brownie Lake was non‐diffusive. Although the turbulent diffusive methane flux at Canyon Lake was attenuated by methane oxidizing bacteria, dissolved methane was detected in the epilimnion, suggestive of lateral transport of methane from littoral sediments. These results highlight the importance of direct measurements in estimating the total methane flux from water columns, and that non‐diffusive transport of methane may be important to consider from other ferruginous systems.
Cache Locking Content Selection Algorithms for ARINC-653 Compliant RTOS

Avionic software is the subject of stringent real time, determinism and safety constraints. Software designers face several challenges, one of them being the interferences that appear in common situations, such as resource sharing. The interferences introduce non-determinism and delays in execution time. One of the main interference prone resources are cache memories. In single-core processors, caches comprise multiple private levels. This breaks the isolation principle imposed by avionic standards, such as the ARINC-653. This standard defines partitioned architectures where one partition should never directly interfere with another one. In cache-based architectures, one partition can modify the cache content of another partition. In this paper, we propose a method based on cache locking to reduce the non-determinism and the contention on lower level memories while improving the time performances.
Altered Ascending Aorta Hemodynamics in Patients After Arterial Switch Operation for Transposition of the Great Arteries

Patients with transposition of the great arteries (TGA) have an altered aortic geometry after an arterial switch operation (ASO), with neo‐aortic root dilatation as an important complication. Geometry‐related aortic hemodynamics have been assumed to contribute to pathology of the ascending aorta (AAo).
Minimal Rewiring: Efficient Live Expansion for Clos Data Center Networks

Clos topologies have been widely adopted for large-scale data center networks (DCNs), but it has been difﬁcult to support incremental expansions for Clos DCNs. Some prior work has claimed that the structure of Clos topologies hinders incremental expansion. We demonstrate that it is indeed possible to design ex-pandable Clos DCNs, and to expand them while they are carrying live trafﬁc, without incurring packet loss. We use a layer of patch panels between blocks of switches in a Clos DCN, which makes physical rewiring feasible, and we describe how to use integer linear programming (ILP) to minimize the number of patch-panel connections that must be changed, which makes expansions faster and cheaper. We also describe a block-aggregation technique that makes our ILP approach scalable. We tested our “minimal-rewiring” solver on two kinds of ﬁne-grained expansions using 2250 synthetic DCN topologies, and found that the solver can handle 99% of these cases while changing under 25% of the connections. Compared to prior approaches, this solver (on average) reduces the average number of “stages” per expansion from 4 to 1 . 29, and reduces the number of wires changed by an order of magnitude or more – a signiﬁcant improvement to our operational costs, and to our exposure (during expansions) to capacity-reducing faults.
Nanoscale coupling of junctophilin-2 and ryanodine receptors regulates vascular smooth muscle cell contractility

Significance The junctophilins are a family of structural proteins that organize intracellular membrane junctions, such as coupling between the endoplasmic/sarcoplasmic reticulum and plasma membrane. The junctophilins are critically important for cardiac and skeletal muscle function, but little is known about how these proteins influence vascular smooth muscle cells (SMCs). We found that one isotype, junctophilin-2 (JPH2), is abundant in SMCs and is essential for maintaining a subcellular Ca2+ signaling pathway that is critically important for regulation of membrane potential and contractility. Our data also show that impaired expression of JPH2 results in hypercontractility of small cerebral arteries. These findings suggest that loss-of-function mutations or decreased expression of JPH2 could contribute to vascular pathologies such as systemic hypertension and vascular cognitive impairment. Junctophilin proteins maintain close contacts between the endoplasmic/sarcoplasmic reticulum (ER/SR) and the plasma membrane in many types of cells, as typified by junctophilin-2 (JPH2), which is necessary for the formation of the cardiac dyad. Here, we report that JPH2 is the most abundant junctophilin isotype in native smooth muscle cells (SMCs) isolated from cerebral arteries and that acute knockdown diminishes the area of sites of interaction between the SR and plasma membrane. Superresolution microscopy revealed nanometer-scale colocalization of JPH2 clusters with type 2 ryanodine receptor (RyR2) clusters near the cell surface. Knockdown of JPH2 had no effect on the frequency, amplitude, or kinetics of spontaneous Ca2+ sparks generated by transient release of Ca2+ from the SR through RyR2s, but it did nearly abolish Ca2+ spark-activated, large-conductance, Ca2+-activated K+ (BK) channel currents. We also found that JPH2 knockdown was associated with hypercontractility of intact cerebral arteries. We conclude that JPH2 maintains functional coupling between RyR2s and BK channels and is critically important for cerebral arterial function.
Safety and Pharmacokinetics of a Four Monoclonal Antibody Combination against Botulinum C and D Neurotoxins

Botulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance known. BoNTs are also classified as tier 1 biothreat agents due to their high potency and lethality. The existence of seven BoNT serotypes (A to G), which differ by 35% to 68% in amino acid sequences, necessitates the development of serotype-specific countermeasures. ABSTRACT Botulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance known. BoNTs are also classified as tier 1 biothreat agents due to their high potency and lethality. The existence of seven BoNT serotypes (A to G), which differ by 35% to 68% in amino acid sequences, necessitates the development of serotype-specific countermeasures. We present results of a phase 1 clinical study of an anti-toxin to BoNT serotypes C and D, NTM-1634, which consists of an equimolar mixture of four fully human IgG1 monoclonal antibodies (MAbs), each binding to nonoverlapping epitopes on BoNT serotypes C and D, resulting in potent toxin neutralization in rodents. This first in-human study evaluated the safety and pharmacokinetics of escalating doses of NTM-1634 administered intravenously to healthy adults. Three cohorts of eight healthy subjects received single intravenous doses of NTM-1634 at 0.33 mg/kg, 0.66 mg/kg, or 1 mg/kg or placebo. Follow-up examinations and pharmacokinetics evaluations were continued up to 121 days postinfusion. Subjects were monitored by using physical examinations, hematology and chemistry blood tests, and electrocardiograms. Pharmacokinetics parameters were estimated using noncompartmental methods. The results demonstrated that the materials were safe and well tolerated with the expected half-lives for human MAbs and with minimal antidrug antibodies detected over the dose ranges and duration of the study. (This study has been registered at ClinicalTrials.gov under identifier NCT03046550.)
Definition and Coordination of Roles and Responsibilities Among Cancer Center Clinic and Research Personnel.

PURPOSE Effective enrollment and treatment of patients in cancer clinical trials require definition and coordination of roles and responsibilities among clinic and research personnel. MATERIALS AND METHODS We developed a survey that incorporated modified components of the Survey of Physician Attitudes Regarding the Care of Cancer Survivors. Surveys were administered to clinic nursing staff and research personnel at a National Cancer Institute-designated comprehensive cancer center. Results were analyzed using χ2-tests, t tests, and analyses of variance. RESULTS Surveys were completed by 105 staff members (n = 50 research staff, n = 55 clinic staff; 61% response rate). Research staff were more likely to feel that they had the skills to answer questions, convey information, and provide education for patients on trials (all P < .05). Both clinic and research staff reported receipt of communication about responsibilities in fewer than 30% of cases, although research staff reported provision of such information in more than 60% of cases. Among 20 tasks related to care of patients in trials, no single preferred model of responsibility assignment was selected by the majority of clinic staff for nine tasks (45%) or by research staff for three tasks (15%). Uncertainty about which team coordinates care was reported by three times as many clinic staff as research staff (P = .01). There was also substantial variation in the preferred model for delivery of care to patients in trials (P < .05). CONCLUSION Knowledge, attitudes, and perception of care and responsibilities for patients on clinical trials differ between and among clinic and research personnel. Additional research about how these findings affect efficiency and quality of care on clinical trials is needed.
Does relatively low iodine intake contribute to thyroid cancer? An ecological comparison of epidemiology

Abstract Research on the relationship between iodine intake and thyroid cancer (TC) risk is limited, and the findings are inconclusive. The objective of this study was to provide emerging evidence for the association between iodine intake and TC risk in a Chinese population. An ecological study of epidemiology is used to compare the iodine intake among populations with different TC incidence in Zhoushan, China. Incidence rates of TC were investigated and compared among four counties of the Zhoushan Islands from 2014 to 2018. Iodized salt consumption rate and the level of urinary iodine concentration (UIC) were analyzed for pupils and pregnant women from four counties. During 2014 to 2018, a total of 2495 new cases of TC were diagnosed in Zhoushan Islands. The mean crude incidence rate of TC was 51.29 per 100,000 inhabitants, and the standardized (world population) incidence rate (SIR) was 31.34 per 100,000 population. Incidence rates (SIR and crude incidence rates) were significantly higher in women than in men (χ2 test, P < .05). Both male and female, the incidence of TC in Daishan County is higher than the other three counties of Zhoushan. Iodized salt consumption rate and median UIC in pupils and pregnant women in Daishan County was significantly lower than the other three counties (χ2 test and Kruskal–Wallis test, all P < .05). The population with high TC incidence has a lower iodized salt consumption and a lower level of UIC compare with the relative low TC incidence populations. The low consumption of iodized salt with mild iodine deficiency may contribute to explain the exceptionally high incidence of TC in Daishan County. Further subtle designed studies are needed to provide additional insights into the epidemiology and etiology of TC and help identify the safe limit of iodine intake for prevention.
Effectiveness, cost-utility, and benefits of a multicomponent therapy to improve the quality of life of patients with fibromyalgia in primary care

Abstract Introduction: Fibromyalgia (FM) is a chronic condition characterized by chronic pain, fatigue and loss of function which significantly impairs quality of life. Although treatment of FM remains disputed, some studies point at the efficacy of interdisciplinary therapy. This study aims to analyze the effectiveness, cost-utility and benefits of a multicomponent therapy on quality of life (main variable), functional impact, mood and pain in people suffering from FM that attend primary care centers (PCCs) of the Catalan Institute of Health (ICS). Methods and analysis: A 2-phase, mixed methods study has been designed following Medical Research Council guidance. Phase 1: Pragmatic randomized clinical trial with patients diagnosed with FM that attend one of the 11 PCCs of the ICS Gerència Territorial Terres de l’Ebre. We estimate a total sample of 336 patients. The control group will receive usual clinical care, while the multicomponent therapy group (MT group) will receive usual clinical care plus group therapy (consisting of health education, exercise and cognitive-behavioural therapy) during 12 weeks in 2-hourly weekly sessions. Analysis: the standardized mean response and the standardized effect size will be assessed at 3, 9, and 15 months after the beginning of the study using multiple linear regression models. Utility measurements will be used for the economic analysis. Phase 2: Qualitative socio constructivist study to evaluate the intervention according to the results obtained and the opinions and experiences of participants (patients and professionals). We will use theoretical sampling, with 2 discussion groups of participants in the multicomponent therapy and 2 discussion groups of professionals of different PCCs. A thematic content analysis will be carried out. Ethics and dissemination: This study protocol has been approved by the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (code P18/068). Articles will be published in international, peer-reviewed scientific journals. Trial registration: Clinical-Trials.gov: NCT04049006.
Vitamin D Receptor and Role of Vitamin D Supplementation in Advanced Gallbladder Cancer: A Prospective Study from Northern India.

BACKGROUND The proposed role of Vitamin D Receptor (VDR) in various cancers underscores the importance of vitamin D compounds as a novel therapeutic agent in the prevention of occurrence and progression of cancer. Vitamin D Receptor (VDR) expression in gallbladder cancer (GBC) has not been widely analyzed yet. In the present study, an attempt has been made to study VDR expression and the role of vitamin D supplementation during palliative chemotherapy in advanced GBC. METHODS Expression of VDR was analyzed in benign cholecystectomy specimens (n=11), and GBC specimens (n=32). Thirty patients with advanced GBC were subjected to palliative chemotherapy. Out of them, 19 patients were supplemented with Vitamin D and 11 patients were not. Effect of vitamin D supplementation on the change in vitamin D scores and improvement in quality of life (QOL) were assessed by EORTC QLQ c30 version 3.0. and the difference in outcome between the two groups were studied. RESULTS Mean intensity, staining and immunoreactivity scores signifying VDR expression were decreased in the studied population of GBC when compared to benign disease. In palliative setting, vitamin D supplementation significantly improved the quality of life. However, the effect on disease- specific survival, although present, was not statistically significant. CONCLUSION VDR expression downregulation is associated with increasing malignant process. Vitamin D may act as sensitizers for tumor cell death besides downplaying potential harmful effects of palliative chemotherapy thus reducing the associated morbidity. This study assumes importance as the first clinical study reporting VDR expression in GBC tissue and the possible role of vitamin D supplementation in patients with advanced disease.
HAMLET, a Protein Complex from Human Milk, Has Bactericidal Activity and Enhances the Activity of Antibiotics against Pathogenic Streptococci

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex derived from human milk that was first described for its tumoricidal activity. Later studies showed that HAMLET also has direct bactericidal activity against select species of bacteria, with highest activity against Streptococcus pneumoniae. ABSTRACT HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex derived from human milk that was first described for its tumoricidal activity. Later studies showed that HAMLET also has direct bactericidal activity against select species of bacteria, with highest activity against Streptococcus pneumoniae. Additionally, HAMLET in combination with various antimicrobial agents can make a broad range of antibiotic-resistant bacterial species sensitive to antibiotics. Here, we show that HAMLET has direct antibacterial activity not only against pneumococci but also against Streptococcus pyogenes (group A streptococci [GAS]) and Streptococcus agalactiae (group B streptococci [GBS]). As with pneumococci, HAMLET treatment of GAS and GBS resulted in depolarization of the bacterial membrane, followed by membrane permeabilization and death, which was able to be inhibited by calcium and sodium transport inhibitors. Treatment of clinical antibiotic-resistant isolates of S. pneumoniae, GAS, and GBS with sublethal concentrations of HAMLET in combination with antibiotics decreased the MICs of the antibiotics into the sensitive range. This effect could also be blocked by ion transport inhibitors, suggesting that HAMLET’s bactericidal and combination treatment effects used similar mechanisms. Finally, we show that HAMLET potentiated the effects of erythromycin against erythromycin-resistant bacteria more effectively than penicillin G potentiated killing bacteria resistant to erythromycin. These results show that HAMLET effectively (i) kills three different species of pathogenic streptococci by similar mechanisms and also (ii) potentiates the activities of macrolides and lincosamides more effectively than combination treatment with beta-lactams. These findings suggest a potential therapeutic role for HAMLET in repurposing antibiotics currently causing treatment failures in patients.