Miracle-dz/UniFAR-FTUs huggingface dataset:
Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention

Regimen adherence remains a major hurdle to the success of daily oral drug regimens for the treatment and prevention of human immunodeficiency virus (HIV) infection. Long-acting drug formulations requiring less-frequent dosing offer an opportunity to improve adherence and allow for more forgiving options with regard to missed doses. ABSTRACT Regimen adherence remains a major hurdle to the success of daily oral drug regimens for the treatment and prevention of human immunodeficiency virus (HIV) infection. Long-acting drug formulations requiring less-frequent dosing offer an opportunity to improve adherence and allow for more forgiving options with regard to missed doses. The administration of long-acting formulations in a clinical setting enables health care providers to directly track adherence. MK-8591 (4′-ethynyl-2-fluoro-2′-deoxyadenosine [EFdA]) is an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) drug candidate under investigation as part of a regimen for HIV treatment, with potential utility as a single agent for preexposure prophylaxis (PrEP). The active triphosphate of MK-8591 (MK-8591-TP) exhibits protracted intracellular persistence and, together with the potency of MK-8591, supports its consideration for extended-duration dosing. Toward this end, drug-eluting implant devices were designed to provide prolonged MK-8591 release in vitro and in vivo. Implants, administered subcutaneously, were studied in rodents and nonhuman primates to establish MK-8591 pharmacokinetics and intracellular levels of MK-8591-TP. These data were evaluated against pharmacokinetic and pharmacodynamic models, as well as data generated in phase 1a (Ph1a) and Ph1b clinical studies with once-weekly oral administration of MK-8591. After a single administration in animals, MK-8591 implants achieved clinically relevant drug exposures and sustained drug release, with plasma levels maintained for greater than 6 months that correspond to efficacious MK-8591-TP levels, resulting in a 1.6-log reduction in viral load. Additional studies of MK-8591 implants for HIV treatment and prevention are warranted.
Adverse drug reactions during hepatitis C treatment with direct‐acting antivirals: The role of medication errors, their impact on treatment discontinuation and their preventability. New insights from the Campania Region (Italy) spontaneous reporting system

Medication errors, such as unnecessary treatment discontinuation during treatment with direct‐acting antivirals (DAAs), can lead to imbalances in the benefit‐to‐risk ratio. This risk is especially high when the medication error leads to adverse drug reactions (ADRs). However, to date, evidence on the frequency of this phenomenon is scarce. This study aims to provide better insight into ADRs possibly due to medication errors leading to DAA discontinuation and their preventability.
A theory for space-charge-limited currents with application to electrical precipitation

The flow of steady electric currents in the interior of any medium is governed by three laws 1. Poisson's law which essentially relates space charge to potential. 2. Conservation of charge. 3. A law of the type of Ohm's law connecting current flow and potential gradient. In most solid and liquid conductors of technical interest, Poisson's law can be satisfactorily approximated by the simpler equation of Laplace, and Ohm's law applies with the conductivity taken as constant. In gases, however, these simplifications cannot be made and hence the problem of calculating such electrical parameters as the current-voltage relationship, field strength, and charge density is much more difficult.
Chronic kidney disease and cause-specific hospitalisation: a matched cohort study using primary and secondary care patient data

Background Although chronic kidney disease (CKD) is associated with various outcomes, the burden of each condition for hospital admission is unknown. Aim To quantify the association between CKD and cause-specific hospitalisation. Design and setting A matched cohort study in primary care using Clinical Practice Research Datalink linked to Hospital Episode Statistics in England. Method Patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥3 months) and a comparison group of patients without known CKD (matched for age, sex, GP, and calendar time) were identified, 2004–2014. Outcomes were hospitalisations with 10 common conditions as the primary admission diagnosis: heart failure; urinary tract infection; pneumonia; acute kidney injury (AKI); myocardial infarction; cerebral infarction; gastrointestinal bleeding; hip fracture; venous thromboembolism; and intracranial bleeding. A difference in the incidence rate of first hospitalisation for each condition was estimated between matched patients with and without CKD. Multivariable Cox regression was used to estimate a relative risk for each outcome. Results In a cohort of 242 349 pairs of patients, with and without CKD, the rate difference was largest for heart failure at 6.6/1000 person-years (9.7/1000 versus 3.1/1000 person-years in patients with and without CKD, respectively), followed by urinary tract infection at 5.2, pneumonia at 4.4, and AKI at 4.1/1000 person-years. The relative risk was highest for AKI with a fully adjusted hazard ratio of 4.90, 95% confidence interval (CI) = 4.47 to 5.38, followed by heart failure with 1.66, 95% CI = 1.59 to 1.75. Conclusion Hospitalisations for heart failure, infection, and AKI showed strong associations with CKD in absolute and(or) relative terms, suggesting targets for improved preventive care.
Patients With a Prolonged Intensive Care Unit Length of Stay Have Decreased Health-Related Quality of Life After Cardiac Surgery.

Cardiac surgery patients with a prolonged ICU length of stay (prICULOS) have lower rates of functional survival following their procedure, however detailed information on their health related quality of life (HRQoL) is lacking. We sought to investigate the potential need for intervention in these high-risk patients through comprehensive HRQoL assessments in the months to year following their surgery. A prospective, observational pilot study was undertaken and cardiac surgery patients with a prICULOS (ICU length of stay of ≥5 days) were recruited. A control group was obtained through recruitment of cardiac surgery patients with an ICU length of stay of <5 days. In-person clinical or telephone survey HRQoL assessments were completed at 3-6 months and 1-year time points after their procedure. The standardized mean difference (SMD) was calculated for all study variable comparisons to quantify the standardized effect size observed between non-prICULOS and prICULOS patients. 789 cardiac procedures were performed during the study period and 89 patients experienced a prICULOS (10.7%). Of these 89 patients, 35 prICULOS patients were recruited along with 35 controls. 29 out of 35 prICULOS patients completed the study (83%). At the 3-6 month follow up the prICULOS patients had higher levels of weight loss, fear of falling, and driving deficits. At 1-year, prICULOS patients had persistent difficulties with activities of daily living and required more family and external support. This study demonstrates the need for closer follow up and intervention for cardiac surgery patients with a prICULOS who were found to have poorer mid and long-term HRQoL.
The Basic Principles of Super-Regenerative Reception

By means of cathode-ray oscillograms and mathematical analyses the principal phenomena occurring in superregenerative receivers are explained. The results verify an earlier theory that in the separately quenched detector the received signal merely causes the detector to oscillate at maximum output for a longer period during each quench cycle, without increasing the maximum amplitude of the oscillations. It is also shown that in the self-quenched detector the signal merely produces an increase in the quench frequency, without increasing the maximum amplitude reached by the oscillations. The sensitivity, selectivity, and characteristic noise of superregenerative receivers are discussed.
The Association between Epidermal Growth Factor Receptor (EGFR) Gene Polymorphisms and Lung Cancer Risk

Lung cancer is the leading cause of cancer death globally. The epidermal growth factor receptor (EGFR) plays an important role in cell proliferation and signaling. In this study, we examined the association between EGFR gene polymorphisms and lung cancer risk among the Jordanian population. A total of 129 patients with primary lung cancer and 129 matched healthy controls were recruited into this study. EGFR rs712829, rs712830, rs2072454, and rs11543848 single nucleotide polymorphisms (SNPs) were genotyped to test for their association with lung cancer risk. A significant association was observed between the rs712829 SNP and lung cancer risk (p < 0.05) where the GG + GT genotypes were higher in lung cancer patients when compared to controls. In addition, no association was detected between rs712830, rs2072454, and rs11543848 SNPs and lung cancer risk. When patients were stratified according to the lung cancer type, a significant association was detected between both rs712829 and rs2072454 and adenocarcinoma lung cancer (p < 0.05). Haplotype analysis of all four SNPs showed a significant association between the TCCG haplotype and both lung cancer and the adenocarcinoma subtype (p < 0.001). In conclusion, EGFR rs712829, rs2072454 SNPs, and TCCG haplotypes are associated with a risk of lung cancer among Jordanians. Since genetic associations are affected by the genetic background of populations, more studies in other Arab populations are required to confirm the present findings.
Experiences of Donating Personal Data to Mental Health Research: An Explorative Anthropological Study

Technological developments, such as the advent of social networking sites, apps, and tracking ‘cookies’, enable the generation and collection of unprecedented quantities of rich personal and behavioural data, opening up a vast new resource for mental health research. Despite these non-traditional health-related data already forming a vital foundation of many new research avenues, little analysis has been done focusing on the experiences, motivations, and concerns of the individuals already engaged in data sharing and donation practices. This explorative study aims to investigate the experiences of individuals voluntarily donating their data to mental health research, specifically through the open data initiative OurDataHelps.org, which aims to develop effective suicide prevention tools. Qualitative semi-structured interviews and participant observation were used on a small sample of participants, yielding 3 key findings: (1) The relationship between participants and their data traces fluctuated between unconscious agency and hyper awareness through curatorship. (2) Despite having concerns about privacy and surveillance, participants were driven by altruistic motivations to engage with health researchers valued by their community, in the hope that their personal information could be of some benefit to future avenues of research. (3) In most cases represented in this sample group, motivation was found to stem from personal experiences with mental health, suicide, and loss. In the suicide survivor community, the experience of data donation is often valued as a method for emotional processing of a loss, connecting with the experiences of others, or as a way of regaining a sense of ‘purpose’. By understanding the motivations of individual participants, future projects can ensure that data donation processes are a positive experience and ultimately, increase and sustain the huge potential resources for health researchers worldwide.
Oxidative stress in electrohypersensitivity self-reporting patients: Results of a prospective in vivo investigation with comprehensive molecular analysis

A total of 32 electrohypersensitivity (EHS) self-reporting patients were serially included in the present prospective study for oxidative stress and antioxidative stress response assessment. All thiobarbituric acid-reactive substances (TBARs) were measured in the plasma, particularly malondialdehyde (MDA) for lipid peroxidation; additional measurements included total thiol group molecules, reduced glutathione (GSH), oxidized glutathione (GSSG) for oxidative stress assessment and nitrotyrosine, a marker of peroxynitrite-induced oxidative/nitrosative stress. In addition, the activity of Cu-Zn superoxide dismutase (SOD1) was measured in red blood cells (RBCs) and glutathione reductase (GR) and glutathione peroxidase (GPx) in RBCs and plasma. Depending of the biomarker considered, 30–50% of EHS self-reporting patients presented statistically significantly increased TBARs, MDA, GSSG and NTT mean plasmatic level values in comparison with normal values obtained in healthy controls (P<0.0001). By contrast, there were no plasmatic level values above the upper normal limits for GSH, GSH/GSSG ratio, total glutathione (GluT) and GSH/GluT ratio, and values for these GSH-associated biomarkers were statistically significantly decreased in 20–40% of the patients (P<0.0001). Furthermore, in RBCs, mean SOD1 and GPx activities were observed to be statistically significantly increased in ~60% and 19% (P<0.0001) of the patients, respectively, while increased GR activity in RBCs was observed in only 6% of the patients. The present study reports for the first time, to the best of our knowledge, that overall ~80% of EHS self-reporting patients present with one, two or three detectable oxidative stress biomarkers in their peripheral blood, meaning that these patients-as is the case for cancer, Alzheimer's disease or other pathological conditions-present with a true objective new pathological disorder.
Maintenance of Kidney Metabolic Homeostasis by PPAR Gamma

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that control the transcription of specific genes by binding to regulatory DNA sequences. Among the three subtypes of PPARs, PPARγ modulates a broad range of physiopathological processes, including lipid metabolism, insulin sensitization, cellular differentiation, and cancer. Although predominantly expressed in adipose tissue, PPARγ expression is also found in different regions of the kidney and, upon activation, can redirect metabolism. Recent studies have highlighted important roles for PPARγ in kidney metabolism, such as lipid and glucose metabolism and renal mineral control. PPARγ is also implicated in the renin-angiotensin-aldosterone system and, consequently, in the control of systemic blood pressure. Accordingly, synthetic agonists of PPARγ have reno-protective effects both in diabetic and nondiabetic patients. This review focuses on the role of PPARγ in renal metabolism as a likely key factor in the maintenance of systemic homeostasis.
A New Mathematical Formulation for Strapdown Inertial Navigation

A differential equation is developed for the orientation vector relating the body frame to a chosen reference frame. The time derivative of this vector is the sum of the inertially measurable angular velocity vector and of the inertially nonmeasurable noncommutativity rate vector. It is precisely this noncommutativity rate vector that causes the computational problems when numerically integrating the direction cosine matrix. The orientation vector formulation allows the noncommutativity contribution to be isolated and, therefore, treated separately and advantageously. An orientation vector mechanization is presented for a strap down inertial system. Further, an example is given of the applica tion of this formulation to a typical rigid body rotation problem.
The Conorfamide RPRFa Stabilizes the Open Conformation of Acid-Sensing Ion Channel 3 via the Nonproton Ligand–Sensing Domain

Acid-sensing ion channel 3 (ASIC3) is a proton-gated Na+ channel with important roles in pain. ASIC3 quickly desensitizes in less than a second, limiting its capacity to sense sustained acidosis during pain. RFamide neuropeptides are modulators of ASIC3 that slow its desensitization and induce a variable sustained current. The molecular mechanism of slowed desensitization and the RFamide binding site on ASIC3 are unknown. RPRFamide, a RFamide from the venom of a cone snail, has a comparatively high affinity for ASIC3 and strongly slows its desensitization. Here we show that covalent binding of a UV-sensitive RPRFamide variant to ASIC3 prevents desensitization, suggesting that RPRFamide has to unbind from ASIC3 before it can desensitize. Moreover, we show by in silico docking to a homology model of ASIC3 that a cavity in the lower palm domain, which is also known as the nonproton ligand–sensing domain, is a potential binding site of RPRFamide. Finally, using extensive mutagenesis of residues lining the nonproton ligand–sensing domain, we confirm that this domain is essential for RPRFamide modulation of ASIC3. As comparative analysis of ASIC crystal structures in the open and in the desensitized conformation suggests that the lower palm domain contracts during desensitization, our results collectively suggest that RPRFamide, and probably also other RFamide neuropeptides, bind to the nonproton ligand–sensing domain to stabilize the open conformation of ASIC3.
Post pancreatitis/cholecystectomy gluten intolerance

This case report describes the journey of a patient who suffered from life-limiting gastrointestinal symptoms after an acute bout of pancreatitis following ERCP for cholelithiasis bile following a ductal stone, and subsequent cholecystectomy. She was diagnosed and treated for IBS with medication without significant improvement. On implementation of a simple gluten and lactose exclusion diet she recovered to her premorbid state, and trials of gluten challenge triggered flares of symptoms. This case report will go on to discuss current evidence for use of gluten and lactose exclusion diets in some gluten sensitive patients misdiagnosed with IBS.
A fundamental factor controlling the unit dielectric strength of oil [includes discussion]

The theory is offered that the primary factor which determines the unit dielectric strength of commercial oil of controlled quality around electrodes of different geometries is the volume of that oil under stress. The reason is basically statistical. For small volumes of oil, such as test cups, statistical variations are large and unit dielectric strengths are high. For large volumes at high spacings, such as in large power equipment, lower unit dielectric strengths must be recognized, but statistical reliability and reproducibility are greatly improved. In calculations, statistical extrapolations can be eliminated by computing an equivalent volume of oil under stress and obtaining the dielectric strength from test data on a sphere gap with the same equivalent volume. Ignoring everything but the change in dielectric strength with volume, the calculation method checks the fundamental curves in Peek's 1915 empirical data with surprisingly good accuracy. Included are changes in dielectric strength with: 1. the radii of spheres, 2. the separation of spheres, and 3. the changed geometry from spheres to cylinders.
Catastrophizing, pain, and functional outcomes for children with chronic pain: a meta-analytic review

Abstract Pediatric chronic pain is associated with numerous negative outcomes including increased physical disability, increased rates of depression and anxiety, and decreased quality of life (QOL). Pain catastrophizing–broadly conceptualized as including rumination, magnification, and helplessness cognitions surrounding one's pain–has been linked with poor functional outcomes in children with chronic pain. Pain catastrophizing in pediatric chronic pain is often considered a key factor on which to focus treatment efforts. However, absent a systematic review that integrates the relevant literature, this call for routine assessment and targeted treatment may be premature. This study aimed to: (1) meta-analytically quantify the relationship between catastrophizing and pain and functional/psychosocial outcomes (functional disability/physical functioning, anxiety, depression, and QOL) in children with chronic pain, and (2) examine potential moderators of these relationships. Using a random-effects model, a total of 111 effect sizes from 38 studies were analyzed. Effect sizes ranged from medium to large, with anxiety, depression, and QOL demonstrating a strong association with catastrophizing. Pain intensity and physical disability had a moderate association with catastrophizing. These relationships were robust, minimizing potential publication bias. None of the examined moderators were significant. The strong relationships found between catastrophizing and anxiety, depression, and QOL suggest that successfully intervening on catastrophizing could have far reaching implications in improving pain outcomes in pediatric chronic pain.
Language as an engineering tool — Front preparation to results

In an analysis of the use of language as an engineering tool, the writing problem is divided into three phases: the preparation, the act of writing, and the results achieved. Questions of empathy for the reader, writing style for effective expression, and organization for clarity are discussed. Some criteria are given for mature, professional prose and for measuring the effectiveness of engineering literature.
Health Information on Firefighter Websites: Structured Analysis

Background Owing to the fact that firefighters have unique health risks, access to firefighter-specific internet-based health information is a potential mechanism for achieving better health and work outcomes. Objective The objective of our study was to identify the amount and nature of health information resources available on Canadian firefighter-specific websites and the extent to which resources are consistent across websites as a surrogate indicator of diffusion of information. Methods A search of health resources on firefighter websites (union and employer) for all Canadian provinces, major cities and a subset of smaller cities, and the International Association of Fire Fighters (IAFF) website was conducted on Google (July 2017). Content was identified and classified based on the type of resource, health focus, and location. The quantity and nature of the resources were summarized using descriptive statistics. Results Among all (N=313) websites reviewed, 41 websites had health information with a cumulative total of 128 resources that addressed firefighter mental (59/128, 46.1%), physical (43/128, 33.6%), and work health (26/128, 20.3%). The highest density of information was found on international and national websites (13 resources per website) and the least on local websites (1 resource per 7 websites). Three provinces (Ontario, Québec, and British Columbia) hosted 81% (65/80) of the provincial, territorial and local resources. General mental health (20/59, 34%), posttraumatic stress disorder (14/59, 24%), and suicide (14/59, 24%) were the most prevalent topics within the mental health resources, whereas half (21/43, 49%) of all physical health resources were on cancer. No resources from Northern Canada were found. Musculoskeletal health was not mentioned in any of the resources identified. There was minimal cross-linking of resources across sites (only 4 resources were duplicated across sites), and there was no clear indication of how the content was vetted or evaluated for quality. Conclusions There was wide variation in the amount and type of information available on different firefighter websites with limited diffusion of information across jurisdictions. Quality evaluation and coordination of resources should be considered to enhance firefighters’ access to quality health information to meet their specific needs. Mental health and cancer information aligned with high rates of these health problems in firefighters, whereas the lack of information on musculoskeletal health was discordant with their high rate of work injury claims for these problems.