Miracle-dz/UniFAR-FTUs huggingface dataset:
Low-Dose Dextromethorphan for the Treatment of Fibromyalgia Pain: Results from a Longitudinal, Single-Blind, Placebo-Controlled Pilot Trial

Objective Fibromyalgia (FM) is a debilitating chronic pain condition with few treatment options. Central sensitization and neuroinflammation have been forwarded as models of FM pathophysiology, both of which indicate dextromethorphan (DXM) as a potential treatment. DXM is an NMDA-receptor antagonist and microglial modulator with anti-neuroinflammatory properties at low doses. It is available for clinical use but has not been tested as a treatment for FM at low dosages. This study evaluated the effectiveness of DXM in treating FM-associated symptoms. Methods In a single-blind, placebo-controlled trial, 14 women meeting the 2010 American College of Rheumatology criteria for FM received a placebo for five weeks, followed by 20 mg DXM for ten weeks, while providing daily symptom reports on a 0–100 scale. Pain and physical activity were the primary and secondary outcomes, respectively. Daily symptom ratings during the last four weeks of placebo were contrasted with ratings during the last four weeks of the active treatment using generalized estimating equations (GEE). Results DXM was well tolerated, and treatment adherence was high. Baseline pain was reduced by at least 20% in six participants. Self-reported daily pain and physical activity in the entire cohort were not significantly different between the placebo and DXM conditions, and the primary hypotheses were not supported. Exploratory analyses using the entire placebo and DXM data showed that pain was significantly lower in the DXM condition than in the placebo condition (b=−9.933, p=0.013). Discussion A strong clinical effect of DXM was not observed at the 20mg/day dosage.
A Case of Esmolol-Induced False-Positive Amphetamine Urine Drug Test

False-positive urine drug screens can occur and lead to implicit bias. Confirmatory testing with gas chromatography/mass spectrometry can be performed. A morbidly obese patient with newly diagnosed atrial fibrillation spent multiple days in the cardiac intensive care unit (ICU) due to a false-positive test for methamphetamine. The patient was planned to undergo direct cardioversion with conscious-sedation anesthesia. His care was delayed because anesthesia was not comfortable administering sedatives in the setting of a positive urine drug screen for presumed methamphetamine use. Knowing that esmolol can cause a false positive on urine drug screen is imperative for delivering the best patient-centered care.
Thoracoabdominal flap reconstruction after resection of superficial soft-tissue sarcomas in the chest wall

Abstract The thoracoabdominal flap is a rotation flap, and is well known for reconstruction of defects following resections for breast cancer, but the flap is not well known for reconstructing defects following resections of soft-tissue sarcomas involving the chest wall. Here we present two patients with superficial chest wall sarcomas consisting of a dermatofibrosarcoma protuberans in a 42-year-old man and a recurrent myxofibrosarcoma in a 76-year-old man. The tumors were resected with the surrounding tissue. The defect was reconstructed with a thoracoabdominal flap elevated from the ipsilateral thorax (medially-based flap). Neither case developed necrosis of the flap or reduced shoulder range of motion. The chest wall presents few options for a donor vessel. The thoracoabdominal flap has an axial blood supply and does not require a microsurgical procedure. A thoracoabdominal flap is a suitable reconstruction option for a defect after the resection of a superficial soft-tissue sarcoma in the chest wall.
Development of a New Equation for the Prediction of Resting Metabolic Rate in Sri Lankan Adults

Resting metabolic rate (RMR) is the key determinant of the energy requirement of an individual. Measurement of RMR by indirect calorimetry is not feasible in field settings and therefore equation-based calculations are used. Since a valid equation is not available for Sri Lankans, it is important to develop a new population-specific equation for field use. The study objective was to develop a new equation for the prediction of RMR in healthy Sri Lankans using a reference method, indirect calorimetry. RMR data were collected from fifty-seven (male 27) adults aged 19 to 60 years. They were randomly assigned to validation (n = 28) and cross-validation (n = 19) groups using the statistical package R (version 3.6.3). Height, weight, and RMR were measured. Multivariable fractional polynomials (MFP) were used to determine explanatory variables and their functional forms for the model. A variable shrinkage method was used to find the best fit predictor coefficients of the equation. The developed equation was cross-validated on an independent group. Weight and sex code (male = 1; female = 0) were identified as reliable independent variables. The new equation developed was RMR (kcal/day) = 284.5 + (13.2 x weight) + (133.0 x sex code). Independent variables of the prediction equation were able to predict 88.5% of the variance. Root mean square error (RMSE) of the prediction equation in validation and cross-validation was 88.11 kcal/day and 79.03 kcal/day, respectively. The equation developed in this study is suitable for predicting RMR in Sri Lankan adults.
Factors Affecting the Decontamination Process in Hospitals in Saudi Arabia

Introduction Hospitals face various types of disasters that require either decontamination or disinfection interventions. These contaminants can be chemical, biological, radioactive, or infectious, such as COVID-19. Further, there are few studies in the literature on factors affecting decontamination in hospitals in Saudi Arabia. Methods Approximately 157 healthcare providers (doctors, nurses, and other specialists) participated in this study. Principle component analysis was used to explore three factors in Saudi Arabia that affect the ability of healthcare providers to decontaminate appropriately. Results Three factors were extracted: (1) having adequate skills to perform decontamination, (2) being adequately prepared for decontamination before a disaster occurs, and (3) organizational barriers to decontamination. There was a positive correlation between the skills and preparedness and a negative correlation between barriers and both skills and preparedness. Discussion It is essential to prepare for decontamination during disasters more effectively and to ensure that all healthcare providers have the requisite skills. Moreover, barriers to decontamination must be investigated thoroughly to improve implementation.
A novel approach to size separation of gold nanoparticles by capillary electrophoresis–evaporative light scattering detection

A simple and rapid methodology to separate and characterize gold nanoparticles (AuNPs) in aqueous medium by capillary electrophoresis–evaporative light scattering detection (CE–ELSD) is presented. First, a controlled synthesis procedure to obtain water-soluble AuNPs, by varying the trisodium citrate concentration was described. These free AuNPs were separated by capillary zone electrophoresis (CZE) based on the differences in the charge-to-mass ratio of the AuNPs–citrate in a mixed buffer of ammonium acetate (20 mM), containing tris(hydroxymethyl)-aminomethane (Tris, 20 mM) and 3-(cyclohexylamino)-1-propanesulfonic acid (CAPS; 10 mM) at pH 8.5. Under optimal working conditions, three small different-sized AuNPs were successfully separated whose average sizes were 3.5, 6.5 and 10.5 nm. The average diameter was lower than 1.2 nm for all of them (calculated by high-resolution transmission electron microscopy, TEM). Thus, this CE-based method was able to separate AuNPs that differ by only 3 nm in diameter. It can be a valuable methodology for the rapid and cost-effective characterization of other nanomaterials in the future in aqueous solutions.
COVID-19 and Diabetic Ketoacidosis: A Single Center Experience

Background and objectives: To describe the clinical characteristics and outcomes of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetic ketoacidosis (DKA) -- a single center tertiary hospital experience. Materials and Methods: A retrospective study was conducted among patients admitted to our hospital in the United States between March 1st and June 15th, 2020 with DKA and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection known as COVID-19. We compared the baseline characteristics, laboratory data, and clinical course between survivors and nonsurvivors to identify the risk factors associated with mortality in the patients with DKA. Results: A total number of 43 patients were included in this study. The median age was 52 years. Thirty-three (76.7%) patients were male. Median value of initial glucose on presentation was 553 mg/dL (300.0-1927.0 mg/dL). On admission, 33 (76.7%) patients had glycated hemoglobin (HbA1c) ≥ 8% (64 mmol/mol) and HbA1c was not obtained in 10 (23.3%) patients. Acute kidney injury (AKI) was seen in 37 (86.0%) patients, 6 (14%) patients required renal replacement therapy and 22 (51.2%) required mechanical ventilation. Among the 43 patients, 25 (58.1%) died. Out of 25 patients who died 15 (60.0%) were Hispanics, 6 (24.0%) were White, 3 (12.0%) were African American, 1 (4%) was Arabic, and 1 (4%) was Asian. The patients who died were older in age than who survived (mean age 58 ± 6.13 vs 46 ± 9.39; p = 0.023). Some 95% of the patients requiring mechanical ventilation died (odds ratio [OR]: 89.25; 95% confidence interval [CI]: 9.10-874.96); p = 0.001). Compared to survivors, nonsurvivors had significantly higher d-dimer (13.00 ± 3.20 mcg/mL vs 6.15 ± 3.66 mcg/mL; p< 0.006) and peak ferritin values (2763.66 ± 1105.32 ng/mL vs 835.16 ± 257.07 ng/mL; p= 0.016). Conclusion: Our retrospective study shows COVID-19 infection may present as DKA in patients with diabetes mellitus (DM). Older age, mechanical ventilation, elevated d-dimer, and ferritin are associated with poor prognosis in these patients. Our study shows that COVID-19 is associated with substantial mortality in DKA patients and adds to the limited literature available regarding poor risk factors associated with mortality in these patients.
Optimization of the Extraction Process of Phenolic Antioxidant from Polyalthia Longifolia (Sonn.) Thawaites

Article history: Received on: 04/02/2013 Revised on: 17/02/2013 Accepted on: 22/02/2013 Available online: 28/02/2013 The research was carried out to optimize the extraction conditions of phenolic antioxidant from the leaves of Polyalthia longifolia. It was optimized by using L16 orthogonal design of experiment. The effect of single factors such as shaking speed, extraction time, modifier concentration and material ratio on the extraction of the phenolic antioxidant was investigated. The maximum phenolic antioxidant content was obtained under optimum conditions of shaking speed at 200 rpm, shaking time 10 min with material ratio of 1:10 and 80% of ethanol.
Alpha‐lipoic acid may ameliorate testicular damage by targeting dox‐induced altered antioxidant parameters, mitofusin‐2 and apoptotic gene expression

In the study, the ameliorating effects of alfa lipoic acid (ALA) against doxorubicin‐induced testicular apoptosis, oxidative stress and disrupted mitochondrial fusion were investigated in male rats. Rats were divided into four groups as control, doxorubicin (DOX), DOX + ALA and ALA. A single dose of 15 mg/kg DOX was administered i.p to the DOX and DOX + ALA groups. 50 mg/kg ALA was given to the DOX + ALA and ALA groups by oral gavage every other day. After 28 days, rat testes and serum samples were collected and analysed. Administration of DOX alone caused a decrease in body and relative testicular weights, seminiferous tubule diameter and germinal epithelium thickness, Johnsen's score and serum testosterone levels. DOX treatment led to severe testicular damage such as tubular degeneration, and atrophic tubules. Also, the activities of superoxide dismutase and glutathione peroxidase were reduced, while the level of malondialdehyde was increased in the testis. The mRNA levels of apoptotic‐related genes (CASP3, TP53, BAX, BCL2) and apoptotic index were increased, while mitofusin‐2 decreased. DOX caused an increase in CASP3 and a decrease in mitofusin‐2 immunoreactivities. Treatment with ALA markedly improved all of DOX‐induced biochemical, histochemical and molecular alterations in rat testis. Consequently, ALA has a therapeutic role in ameliorating DOX‐induced testicular damage in rats.
Drosophila uses a tripod gait across all walking speeds, and the geometry of the tripod is important for speed control

Changes in walking speed are characterized by changes in both the animal’s gait and the mechanics of its interaction with the ground. Here we study these changes in walking Drosophila. We measured the fly’s center of mass movement with high spatial resolution and the position of its footprints. Flies predominantly employ a modified tripod gait that only changes marginally with speed. The mechanics of a tripod gait can be approximated with a simple model – angular and radial spring-loaded inverted pendulum (ARSLIP) – which is characterized by two springs of an effective leg that become stiffer as the speed increases. Surprisingly, the change in the stiffness of the spring is mediated by the change in tripod shape rather than a change in stiffness of individual legs. The effect of tripod shape on mechanics can also explain the large variation in kinematics among insects, and ARSLIP can model these variations.
Immunodeficiency and Cancer in 3.5 Million People Living with Human Immunodeficiency Virus: the South African HIV Cancer Match Study.

BACKGROUND We analysed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with the human immunodeficiency virus (HIV) in South Africa. METHODS We used data from the South African HIV Cancer Match study built on HIV-related laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry. We evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models. We reported adjusted hazard ratios (aHR) over a grid of CD4 values and estimated the aHR per 100 CD4 cells/µl decrease. RESULTS Of 3,532,266 people living with HIV (PLWH), 15,078 developed cancer. The most common cancers were cervical cancer (4,150 cases), Kaposi sarcoma (2,262 cases), and non-Hodgkin lymphoma (1,060 cases). The association between lower CD4 cell count and higher cancer incidence rates was strongest for conjunctival cancer (aHR per 100 CD4 cells/µl decrease: 1.46, 95% confidence interval [CI] 1.38-1.54), Kaposi sarcoma (aHR 1.23, 95% CI 1.20-1.26), and non-Hodgkin lymphoma (aHR 1.18, 95% CI 1.14-1.22). Among infection-unrelated cancers, lower CD4 cell counts were associated with higher incidence rates of oesophageal cancer (aHR 1.06, 95 CI 1.00-1.11), but not breast, lung, or prostate cancer. CONCLUSIONS Lower CD4 cell counts were associated with an increased risk of developing various infection-related cancers among PLWH. Reducing HIV-induced immunodeficiency may be a potent cancer prevention strategy among PLWH in sub-Saharan Africa, a region heavily burdened by cancers attributable to infections.
The Impact of Environment on Gait Assessment: Considerations from Real-World Gait Analysis in Dementia Subtypes

Laboratory-based gait assessments are indicative of clinical outcomes (e.g., disease identification). Real-world gait may be more sensitive to clinical outcomes, as impairments may be exaggerated in complex environments. This study aims to investigate how different environments (e.g., lab, real world) impact gait. Different walking bout lengths in the real world will be considered proxy measures of context. Data collected in different dementia disease subtypes will be analysed as disease-specific gait impairments are reported between these groups. Thirty-two people with cognitive impairment due to Alzheimer’s disease (AD), 28 due to dementia with Lewy bodies (DLB) and 25 controls were recruited. Participants wore a tri-axial accelerometer for six 10 m walks in lab settings, and continuously for seven days in the real world. Fourteen gait characteristics across five domains were measured (i.e., pace, variability, rhythm, asymmetry, postural control). In the lab, the DLB group showed greater step length variability (p = 0.008) compared to AD. Both subtypes demonstrated significant gait impairments (p < 0.01) compared to controls. In the real world, only very short walking bouts (<10 s) demonstrated different gait impairments between subtypes. The context where walking occurs impacts signatures of gait impairment in dementia subtypes. To develop real-world gait assessment as a clinical tool, algorithms and metrics must accommodate for changes in context.
Effect of Humanizing Mutations on the Stability of the Llama Single-Domain Variable Region

In vivo clinical applications of nanobodies (VHHs) require molecules that induce minimal immunoresponse and therefore possess sequences as similar as possible to the human VH domain. Although the relative sequence variability in llama nanobodies has been used to identify scaffolds with partially humanized signature, the transformation of the Camelidae hallmarks in the framework2 still represents a major problem. We assessed a set of mutants in silico and experimentally to elucidate what is the contribution of single residues to the VHH stability and how their combinations affect the mutant nanobody stability. We described at molecular level how the interaction among residues belonging to different structural elements enabled a model llama nanobody (C8WT, isolated from a naïve library) to be functional and maintain its stability, despite the analysis of its primary sequence would classify it as aggregation-prone. Five chimeras formed by grafting CDRs isolated from different nanobodies into C8WT scaffold were successfully expressed as soluble proteins and both tested clones preserved their antigen binding specificity. We identified a nanobody with human hallmarks that seems suitable for humanizing selected camelid VHHs by grafting heterologous CDRs in its scaffold and could serve for the preparation of a synthetic library of human-like single domains.
Collecting duct-specific knockout of sphingosine-1-phosphate receptor 1 aggravates DOCA-salt hypertension in mice

Objective: We have previously reported that renal medullary sphingosine-1-phosphate (S1P) regulates sodium excretion via the S1P type-1 receptor (S1PR1). As S1PR1 is predominantly expressed in collecting ducts (CD), the present study tested the hypothesis that the CD-S1PR1 pathway plays a critical role in sodium excretion and contributes to salt-sensitive hypertension. Methods: CD-specific S1PR1 knockout mice were generated by crossing aquaporin-2-Cre mice with S1PR1-floxed mice. Renal sodium excretion and arterial pressure were compared between wild type and KO mice in response to high-salt challenges and treatment of deoxycorticosterone acetate (DOCA) salt. Results: Protein levels of renal medullary S1PR1 were increased by 100% after high-salt intake, whereas DOCA treatment with high-salt intake blocked the increase of S1PR1 levels. Urinary sodium excretions in knockout mice were decreased by 60% compared with wild type mice after acute intravenous sodium loading (0.84 ± 0.16 vs. 2.22 ± 0.62 μmole/min per g kwt). The pressure natriuresis was impaired in knockout mice compared with wild type mice (4.32 ± 1.04 vs. 8.73 ± 0.19 μmole/min per g kwt). The chronic high-salt intake-induced positive sodium balance was enhanced in knockout mice compared with wild type mice (5.27 ± 0.39 vs. 2.38 ± 1.04 mmol/100 g BW per 24 h). After 10-day DOCA-salt treatment, knockout mice developed more severe hypertension than wild type mice (SBP 142 ± 8 vs. 115 ± 4 mmHg). Conclusion: The deletion of CD-S1PR1 reduced sodium excretion, promoted sodium retention, and accelerated DOCA-salt-induced salt-sensitive hypertension, suggesting that the CD-S1PR1 signaling is an important antihypertensive pathway by promoting sodium excretion and that impairment of renal medullary S1PR1 may represent a novel mechanism for salt-sensitive hypertension.
Charge Interactions in a Highly Charge-depleted Protein

Interactions between charged residues are difficult to study because of the complex network of interactions found in most proteins. We have designed a purposely simple system to investigate this problem by systematically introducing individual and pairs of charged and titratable residues in a protein otherwise free of such residues. We used constant pH molecular dynamics simulations, NMR spectroscopy, and thermodynamic double mutant cycles to probe the structure and energetics of the interaction between the charged residues. We found that the partial burial of surface charges contributes to a shift in pKa value, causing an aspartate to titrate in the neutral pH range. Additionally, the interaction between pairs of residues was found to be highly context dependent, with some pairs having no apparent preferential interaction, while other pairs would engage in coupled titration forming a highly stabilized salt bridge. We find good agreement between experiments and simulations, and use the simulations to rationalize our observations and to provide a detailed mechanistic understanding of the electrostatic interactions. Significance Electrostatic forces are important for protein folding and are favored targets of protein engineering. However, despite the many advances in the field of protein electrostatics, the prediction of changes in protein structure and function upon introduction or removal of titratable residues is still complicated. In order to provide a basic understanding of protein electrostatics we here characterize a highly charge-depleted protein and its titratable variants by a combination of NMR spectroscopy and constant pH molecular dynamics simulations. Our investigations reveal how strongly interacting residues engaged in salt bridging, can be characterized. Furthermore, our study may also enrich and facilitate the understanding of dehydration of salt-bridges and its potential effect on protein stability.
Evaluation of pubertal and pathological gynaecomastia in children: A single‐center experience

Gynaecomastia in adolescents is a benign glandular proliferation of the male breast. Secondary causes of gynaecomastia in adolescents are relatively rare and may result from a wide variety of rare pathological conditions. Among these, klinefelter syndrome, complete androgen resistance, adrenal tumours and oestrogen‐secreting testicular tumours, hypogonadism, hyperthyroidism, kidney disease and medications play a role in aetiology. The aim of our study is to review the demographic characteristics, hormone profile, aetiological characteristics of paediatric gynaecomastia patients admitted to a single center and to determine the frequency of pathological gynaecomastia. Forty‐three male patients with gynaecomastia who applied to the paediatric endocrinology outpatient clinic were included in our study. Demographic characteristics, physical examination findings, hormone profile, breast ultrasonography and karyotype results of the patients were recorded. There were 43 male patients in our study. Thirty‐six (83.7%) of the patients were pubertal gynaecomastia, 7 (16.2%) were pathological gynaecomastia. Three of the patients with pathological gynaecomastia were prepubertal gynaecomastia, 2 had klinefelter syndrome, 1 had hypergonadotropic hypogonadism after acute lymphoblastic leukaemia treatment and 1 had gynaecomastia after spirololactone use. Careful evaluation of patients with gynaecomastia is especially important in detecting pathological types. We reported the rare prepubertal gynaecomastia and klinefelter frequency in our study.