Miracle-dz/UniFAR-FTUs huggingface dataset:
High Plasma Glucagon Levels Correlate with Waist-to-Hip Ratio, Suprailiac Skinfold Thickness, and Deep Subcutaneous Abdominal and Intraperitoneal Adipose Tissue Depots in Nonobese Asian Indian Males with Type 2 Diabetes in North India

We aimed to correlate plasma glucagon levels with anthropometric measures and abdominal adipose tissue depots. Nonobese males (n = 81; BMI < 25 kg/m2) with T2DM of less than one-year duration and nonobese males without diabetes (n = 30) were evaluated for the following: anthropometry (BMI, waist circumference, W-HR, and truncal skinfolds), whole-body DEXA (for body fat and fat-free mass), and MRI scan (for volumes of subcutaneous abdominal adipose tissue (SCAT) including superficial and deep, intra-abdominal visceral adipose tissue (including intraperitoneal adipose tissue (IPAT), retroperitoneal adipose tissue, liver span and fatty liver, and pancreatic volume)). Plasma glucose and glucagon, serum insulin, hepatic transaminases, and lipid profile were measured. Significantly higher levels of fasting and postprandial glucagon (p < 0.001) and fasting and postprandial insulin (p < 0.001) were seen in patients with T2DM. The mean values of fasting and postprandial plasma glucagon levels were higher in T2DM patients with NAFLD (n = 37) as compared to T2DM patients without NAFLD (n = 44). Four independent predictors were derived for fasting glucagon levels in patients with T2DM, namely, W-HR, suprailiac skinfold thickness, IPAT, and deep SCAT (p < 0.05; r2 = 0.84). These observations in Asian Indians may have significance for diabetes therapies which impact glucagon levels.
High-precision measurement of the x-ray Cu Kα spectrum

The structure of the x-ray emission lines of the Cu K α complex has been remeasured on a newly commissioned instrument, in a manner directly traceable to the Système Internationale definition of the meter. In this measurement, the region from 8000 to 8100 eV has been covered with a highly precise angular scale, and well-defined system efficiency, providing accurate wavelengths and relative intensities. This measurement updates the standard multi-Lorentzian-fit parameters from Härtwig, Hölzer, et al, and is in modest disagreement with their results for the wavelength of the K α 1 line when compared via quadratic fitting of the peak top; the intensity ratio of K α 1 to K α 2 agrees within the combined error bounds. However, the position of the fitted top of K α 1 is very sensitive to the fit parameters, so it is not believed to be a robust value to quote without further qualification. We also provide accurate intensity and wavelength information for the so-called K α 3,4 ‘satellite’ complex. Supplementary data, available online at stacks.iop. org/JPB/50/115004/mmedia, is provided which gives the entire shape of the spectrum in this region, allowing it to be used directly in cases where simplified, multi-Lorentzian fits to it are not sufficiently accurate.
Measurement of the distribution of ventilation-perfusion ratios in the human lung with proton MRI: comparison with the multiple inert-gas elimination technique.

We have developed a novel functional proton magnetic resonance imaging (MRI) technique to measure regional ventilation-perfusion (V̇A/Q̇) ratio in the lung. We conducted a comparison study of this technique in healthy subjects (n = 7, age = 42 ± 16 yr, Forced expiratory volume in 1 s = 94% predicted), by comparing data measured using MRI to that obtained from the multiple inert gas elimination technique (MIGET). Regional ventilation measured in a sagittal lung slice using Specific Ventilation Imaging was combined with proton density measured using a fast gradient-echo sequence to calculate regional alveolar ventilation, registered with perfusion images acquired using arterial spin labeling, and divided on a voxel-by-voxel basis to obtain regional V̇A/Q̇ ratio. LogSDV̇ and LogSDQ̇, measures of heterogeneity derived from the standard deviation (log scale) of the ventilation and perfusion vs. V̇A/Q̇ ratio histograms respectively, were calculated. On a separate day, subjects underwent study with MIGET and LogSDV̇ and LogSDQ̇ were calculated from MIGET data using the 50-compartment model. MIGET LogSDV̇ and LogSDQ̇ were normal in all subjects. LogSDQ̇ was highly correlated between MRI and MIGET (R = 0.89, P = 0.007); the intercept was not significantly different from zero (-0.062, P = 0.65) and the slope did not significantly differ from identity (1.29, P = 0.34). MIGET and MRI measures of LogSDV̇ were well correlated (R = 0.83, P = 0.02); the intercept differed from zero (0.20, P = 0.04) and the slope deviated from the line of identity (0.52, P = 0.01). We conclude that in normal subjects, there is a reasonable agreement between MIGET measures of heterogeneity and those from proton MRI measured in a single slice of lung.NEW & NOTEWORTHY We report a comparison of a new proton MRI technique to measure regional V̇A/Q̇ ratio against the multiple inert gas elimination technique (MIGET). The study reports good relationships between measures of heterogeneity derived from MIGET and those derived from MRI. Although currently limited to a single slice acquisition, these data suggest that single sagittal slice measures of V̇A/Q̇ ratio provide an adequate means to assess heterogeneity in the normal lung.
Transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin-treated Sprague-Dawley rats with type 2 diabetes mellitus

The main actions of metformin are as follows: To reduce hyperglycemia via the suppression of gluconeogenesis, improve glucose uptake and insulin sensitivity, and stimulate activation of adenosine monophosphate-activated protein kinase during the treatment of diabetes mellitus. It is well known that metformin acts via complex mechanisms, including multitarget and multipathway mechanisms; however, the multi-targeted antidiabetic genes of metformin remain obscure. The present study aimed to perform transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin-treated Sprague-Dawley rats with type 2 diabetes mellitus. The type 2 diabetes rat model was established using streptozotocin. Fasting blood glucose, hemoglobin A1c, serum insulin and biological parameters were subsequently measured. Differentially expressed genes (DEGs) and proteins were identified in the rat livers by expression profile analysis and isobaric tags for relative and absolute quantitation (iTRAQ). A 1.5-fold alteration in gene expression, as determined using chip-based expression profile analysis, and a 1.2-fold alteration in protein expression, as determined using iTRAQ, were considered physiologically significant benchmarks, which were used to identify DEGS in metformin-treated rats with type 2 diabetes mellitus. The DEGs were verified using quantitative polymerase chain reaction (qPCR) and western blot analysis. Numerous hepatic genes involved in various metabolic pathways were affected by metformin; in particular, genes associated with lipid metabolism were markedly affected. Expression profile analysis and iTRAQ analysis suggested that carboxylesterase 1C subunit (Ces1C) and cholesterol 7α-hydroxylyase (Cyp7a1) may serve as important DEGs, which were validated by qPCR and western blot analysis. Ces1C and Cyp7a1 are the main enzymes in cholesterol metabolism, yet the result of western blotting was not consistent with qPCR. The present study demonstrated that metformin may affect the expression of numerous hepatic genes involved in metabolic pathways, particularly the lipid and cholesterol metabolic pathways. Ces1C and Cyp7a1 may be considered novel therapeutic target genes in the liver, which are involved in the antidiabetic effects of metformin.
Detailed Echocardiographic Phenotyping in Breast Cancer Patients: Associations With Ejection Fraction Decline, Recovery, and Heart Failure Symptoms Over 3 Years of Follow-Up.

BACKGROUND Cardiovascular disease in patients with breast cancer is of growing concern. The longitudinal effects of commonly used therapies, including doxorubicin and trastuzumab, on cardiac remodeling and function remain unknown in this population. We aimed to define the changes in echocardiographic parameters of structure, function, and ventricular-arterial coupling, and their associations with left ventricular ejection fraction (LVEF) and heart failure symptoms. METHODS In a longitudinal prospective cohort study of 277 breast cancer participants receiving doxorubicin (Dox), trastuzumab (Tras), or both (Dox+Tras), we obtained 1249 echocardiograms over a median follow-up of 2.0 (interquartile range, 1.0-3.0) years. Left ventricular structure, diastolic and contractile function, and ventricular-arterial coupling measures were quantified in a core laboratory blinded to participant characteristics. We evaluated changes in echocardiographic parameters over time, and used repeated-measures regression models to define their association with LVEF decline and recovery. Linear regression models defined the association between early changes in these parameters and subsequent changes in LVEF and heart failure symptoms. RESULTS Overall, 177 (64%) received Dox, 51 (18%) received Tras, and 49 (18%) received Dox+Tras. With Dox, there was a sustained, modest decrease in LVEF over the follow-up duration (1-year change in LVEF -3.6%; 95% confidence interval [CI], -4.4% to -2.8%; 3-year change -3.8%; 95% CI, -5.1% to -2.5%). With Tras, a similar LVEF decline was observed at 1 year (-4.5%; 95% CI, -6.0% to -2.9%) and 3 years (-2.8%; 95%CI, -5.3 to -0.4%). Participants receiving Dox+Tras demonstrated the greatest declines at 1 year (-6.6%; 95% CI, -8.2 to -5.0%), with partial recovery at 3 years (-2.8%; 95% CI, -4.8 to -0.8%). LVEF declines and recovery were associated primarily with changes in systolic volumes, longitudinal and circumferential strain, and ventricular-arterial coupling indices, effective arterial elastance (Ea) and the coupling ratio Ea/Eessb, without evidence for effect modification across therapies. Early changes in volumes, strain, and Ea/Eessb at 4 to 6 months were associated with 1- and 2-year LVEF changes. Similarly, early changes in strain and Ea were associated with worsening heart failure symptoms at 1 year. CONCLUSIONS Doxorubicin and trastuzumab resulted in modest, persistent declines in LVEF at 3 years. Changes in volumes, strain, and ventricular-arterial coupling were consistently associated with concurrent and subsequent LVEF declines and recovery across therapies.
Lexical decision performance in developmental surface dysgraphia: Evidence for a unitary orthographic system that is used in both reading and spelling

ABSTRACT The relationship between spelling, written word recognition, and picture naming is investigated in a study of seven bilingual adults who have developmental surface dysgraphia in both Greek (their first language) and English (their second language). Four of the cases also performed poorly at orthographic lexical decision in both languages. This finding is consistent with similar results in Italian that have been taken as evidence of a developmental impairment to a single orthographic system that is used for both reading and spelling. The remaining three participants performed well at orthographic lexical decision. At first sight, preserved lexical decision in surface dysgraphia is less easy to explain in terms of a shared orthographic system. However, the results of subsequent experiments showed clear parallels between the nature of the reading and spelling difficulties that these three individuals experienced, consistent with the existence of a single orthographic system. The different patterns that were observed were consistent with the claims of Friedmann and Lukov (2008. Developmental surface dyslexias. Cortex, 44, 1146–1160) that several distinct sub-types of developmental surface dyslexia exist. We show that individual differences in spelling in surface dysgraphia are also consistent with these sub-types; there are different developmental deficits that can give rise, in an individual, to a combination of surface dyslexia and dysgraphia. Finally, we compare the theoretical framework used by Friedmann and her colleagues that is based upon the architecture of the DRC model with an account that relies instead upon the Triangle model of reading].
TRMT1-Catalyzed tRNA Modifications Are Required for Redox Homeostasis To Ensure Proper Cellular Proliferation and Oxidative Stress Survival

ABSTRACT Mutations in the tRNA methyltransferase 1 (TRMT1) gene have been identified as the cause of certain forms of autosomal-recessive intellectual disability (ID). However, the molecular pathology underlying ID-associated TRMT1 mutations is unknown, since the biological role of the encoded TRMT1 protein remains to be determined. Here, we have elucidated the molecular targets and function of TRMT1 to uncover the cellular effects of ID-causing TRMT1 mutations. Using human cells that have been rendered deficient in TRMT1, we show that TRMT1 is responsible for catalyzing the dimethylguanosine (m2,2G) base modification in both nucleus- and mitochondrion-encoded tRNAs. TRMT1-deficient cells exhibit decreased proliferation rates, alterations in global protein synthesis, and perturbations in redox homeostasis, including increased endogenous ROS levels and hypersensitivity to oxidizing agents. Notably, ID-causing TRMT1 variants are unable to catalyze the formation of m2,2G due to defects in RNA binding and cannot rescue oxidative stress sensitivity. Our results uncover a biological role for TRMT1-catalyzed tRNA modification in redox metabolism and show that individuals with TRMT1-associated ID are likely to have major perturbations in cellular homeostasis due to the lack of m2,2G modifications.
A simple process for dry spinning of regenerated silk fibroin aqueous solution

The conventional process for preparing dry spinnable regenerated silk fibroin (RSF) aqueous solution needs not only an addition of Ca^2+ but also an adjustment of pH value. In this work, an RSF dry spinning dope was prepared by using a simplified method with solely adding Ca^2+. Compared with the conventional RSF solution, the simply prepared aqueous solution showed similar content of β-sheet conformation and diameter of RSF aggregates but lower viscosity. Furthermore, the posttreated RSF fiber dry-spun from this simply prepared solution showed higher crystallinity and crystalline orientation, smaller crystallite size, and better mechanical properties. It could be concluded that Ca^2+ played a much more important role than pH value in improving the structures and properties of RSF spinning solution and fibers. Therefore, the step of adjusting pH value could be excluded in the process of preparing high performance RSF fibers.
Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic features

Objective To assess the clinicopathological and therapeutic features of patients with low (≥1000 to <10 000 Bühlmann Titre Units) (BTU), medium (10 000–70 000) or high (≥70 000) anti-myelin-associated glycoprotein (anti-MAG) antibody titres. Methods We retrospectively and prospectively analysed standardised report forms and medical records of 202 patients from 14 neuromuscular centres. Results Mean age at onset and mean time between symptom onset to last follow-up were respectively 62.6 years (25–91.4) and 8.4 years (0.3–33.3). Anti-MAG antibody titres at diagnosis were low, medium or high in 11%, 51% and 38% of patients. Patients presented with monoclonal gammopathy of undetermined significance in 68% of cases. About 17% of patients presented with ‘atypical’ clinical phenotype independently of anti-MAG titres, including acute or chronic sensorimotor polyradiculoneuropathies (12.4%), and asymmetric or multifocal neuropathy (3%). At the most severe disease stage, 22.4% of patients were significantly disabled. Seventy-eight per cent of patients received immunotherapies. Transient clinical worsening was observed in 12% of patients treated with rituximab (11/92). Stabilisation after rituximab treatment during the 7–12-month follow-up period was observed in 29% of patients. Clinical response to rituximab during the 6-month and/or 7–12-month follow-up period was observed in 31.5% of patients and correlated with anti-MAG titre ≥10 000 BTU. Conclusion Our study highlights the extended clinical spectrum of patients with anti-MAG neuropathy, which appears unrelated to antibody titre. Besides, it may also suggest beneficial use of rituximab in the early phase of anti-MAG neuropathy.
Levels and Determinants of DDT and DDE Exposure in the VHEMBE Cohort

Background: Although indoor residual spraying (IRS) is an effective tool for malaria control, its use contributes to high insecticide exposure in sprayed communities and raises concerns about possible unintended health effects. Objective: The Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort study initiated in 2012 to characterize prenatal exposure to IRS insecticides and exposures’ impacts on child health and development in rural South Africa. Methods: In this report, we describe the VHEMBE cohort and dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) serum concentrations measured in VHEMBE mothers when they presented for delivery. In addition, we applied a causal inference framework to estimate the potential reduction in population-level p,p′-DDT and p,p′-DDE serum concentrations under five hypothetical interventions. A total of 751 mothers were enrolled. Results: Serum concentrations of p,p′ isomers of DDT and DDE were above the limit of detection (LOD) in ≥98% of the samples, whereas the o,p′ isomers were above the LOD in at least 80% of the samples. Median (interquartile range) p,p′-DDT and p,p′-DDE serum concentrations for VHEMBE cohort participants were 55.3 (19.0–259.3) and 242.2 (91.8–878.7) ng/g-lipid, respectively. Mothers reporting to have lived in a home sprayed with DDT for malaria control had ∼5–7 times higher p,p′-DDT and p,p′-DDE serum concentrations than those who never lived in a home sprayed with DDT. Of the five potential interventions tested, we found increasing access to water significantly reduced p,p′-DDT exposure and increasing the frequency of household wet mopping significantly reduced p,p′-DDT and p,p′-DDE exposure. Conclusion: Our findings suggest that several intervention approaches may reduce DDT/DDE exposure in pregnant women living in IRS communities. https://doi.org/10.1289/EHP353
The Metalloprotease Mpl Supports Listeria monocytogenes Dissemination through Resolution of Membrane Protrusions into Vacuoles

ABSTRACT Listeria monocytogenes is an intracellular pathogen that disseminates within the intestinal epithelium through acquisition of actin-based motility and formation of plasma membrane protrusions that project into adjacent cells. The resolution of membrane protrusions into vacuoles from which the pathogen escapes results in bacterial spread from cell to cell. This dissemination process relies on the mlp-actA-plcB operon, which encodes ActA, a bacterial nucleation-promoting factor that mediates actin-based motility, and PlcB, a phospholipase that mediates vacuole escape. Here we investigated the role of the metalloprotease Mpl in the dissemination process. In agreement with previous findings showing that Mpl is required for PlcB activation, infection of epithelial cells with the ΔplcB or Δmpl strains resulted in the formation of small infection foci. As expected, the ΔplcB strain displayed a strong defect in vacuole escape. However, the Δmpl strain showed an unexpected defect in the resolution of protrusions into vacuoles, in addition to the expected but mild defect in vacuole escape. The Δmpl strain displayed increased levels of ActA on the bacterial surface in protrusions. We mapped an Mpl-dependent processing site in ActA between amino acid residues 207 to 238. Similar to the Δmpl strain, the ΔactA207–238 strain displayed increased levels of ActA on the bacterial surface in protrusions. Although the ΔactA207–238 strain displayed wild-type actin-based motility, it formed small infection foci and failed to resolve protrusions into vacuoles. We propose that, in addition to its role in PlcB processing and vacuole escape, the metalloprotease Mpl is required for ActA processing and protrusion resolution.
A case report of neuromyelitis optica spectrum disorder with peripheral neuropathy as the first episode

Rationale: Neuromyelitis optica spectrum disorders (NMOSDs) represent recurrent autoimmune diseases, generally beginning with optic nerve neuritis or acute transverse myelitis. Patient concerns: A 57-year-old male with long-term alcohol intake was hospitalized because of limb numbness. EMG examination showed the peripheral sensory nerve was in demyelination and an axonal injury was found. His symptoms could not be improved by vitamin B injection but were later significantly attenuated by dexamethasone treatment. Four months later, symptoms of optic neuritis in the left eye appeared, and 6 months later he exhibited peripheral neuropathy with acute myelitis. Diagnoses: He was diagnosed NMOSD. Outcomes: Immunotherapy improved his peripheral neuropathy and myelitis symptoms. Lessons: NMOSD patients could represent peripheral neuropathy as the first episode.
Performance Testing Of Selected Types of Electronic Personal Dosimeters in X- and Gamma Radiation Fields

Abstract Electronic personal dosimeters (EPDs) are increasingly being used alongside conventional thermoluminescent dosimeters to measure the dose of legal record in terms of personal dose equivalent. Therefore, it is of great importance to execute performance tests of these dosimeters in photon fields of various energies and at various angles of incidence. This testing is done in order to simulate the behavior of these dosimeters in realistic multidirectional polyenergetic ionizing radiation fields. Tests of accuracy, linearity, energy response, and angular response have been performed on 10 EPDs from multiple manufacturers. Various radiation qualities have been used in the energy range from 33 keV to 1.33 MeV and for angles of incidence 0° to 80°. This research proves that many of the EPDs tested performed according to the manufacturer’s specifications and the requirements of the international standards regarding personal dosimetry.