Miracle-dz/UniFAR-FTUs huggingface dataset:
Types and frequency of pre-analytical errors at University of Gondar hospital laboratory

Background: As many as 93% of errors encountered in the diagnostic process are largely due to lack of standardized procedures in the pre-analytical phase of quality assurance. Hence, the aim of this study was to assess the types and frequency of pre-analytical errors in University of Gondar hospital. Methods: This was a cross sectional study that involved prospective evaluation of request papers and samples sent to the hospital laboratory for hematological and clinical chemistry analysis. Data was collected by laboratory professionals and summarized into different categories of pre-analytical quality indicators. Results: A total of 1533 (750 for hematology and 783 for clinical chemistry) samples with their respective request papers were evaluated in this study. In general, none of the request papers contained all the information that they were supposed to contain. One or more of patient identification parameters were missing in 8.7% of the request papers. Name of the requesting physician and address of the sender were missing from 44.5% and 6.5% of the request papers. Clinical information of the patients was missing in about 98% of the requests. Examination of the samples showed that 1.02%, 2.8% and 0.98% of the samples were hemolyzed, insufficient for analysis and clotted respectively. Conclusion: This study showed the existence of different pre-analytical errors in the laboratory studied. The laboratory can evaluate itself based on some of the pre-analytical quality indicators and should strive for improving its quality for maximum patient benefit.
Effects of 12 Months of Caloric Restriction on Muscle Mitochondrial Function in Healthy Individuals

Context The effects of caloric restriction (CR) on in vivo muscle mitochondrial function in humans are controversial. Objective We evaluated muscle mitochondrial function and associated transcriptional profiles in nonobese humans after 12 months of CR. Design Individuals from an ancillary study of the CALERIE 2 randomized controlled trial were assessed at baseline and 12 months after a 25% CR or ad libitum (control) diet. Setting The study was performed at Pennington Biomedical Research Center in Baton Rouge, LA. Participants Study participants included 51 (34 female subjects, 25 to 50 years of age) healthy nonobese individuals randomized to 1 of 2 groups (CR or control). Intervention This study included 12 months of a 25% CR or ad libitum (control) diet. Main Outcomes In vivo mitochondrial function [maximal ATP synthesis rate (ATPmax), ATPflux/O2 (P/O)] was determined by 31P-magnetic resonance spectroscopy and optical spectroscopy, and body composition was determined by dual-energy X-ray absorptiometry. In a subset of individuals, a muscle biopsy was performed for transcriptional profiling via quantitative reverse transcription polymerase chain reaction and microarrays. Results Weight, body mass index (BMI), fat, and fat-free mass (P < 0.001 for all) significantly decreased at month 12 after CR vs control. In vivo ATPmax and P/O were unaffected by 12 months of CR. Targeted transcriptional profiling showed no effects on pathways involved in mitochondrial biogenesis, function, or oxidative stress. A subgroup analysis according to baseline P/O demonstrated that a higher (vs lower) P/O was associated with notable improvements in ATPmax and P/O after CR. Conclusions In healthy nonobese humans, CR has no effect on muscle mitochondrial function; however, having a "more coupled" (versus "less coupled") phenotype enables CR-induced improvements in muscle mitochondrial function.
Meningothelial cells as part of the central nervous system host defence

Meningothelial cells (MECs) are the cellular components of the meninges protecting the brain and as such provide important barrier function for the central nervous system building the interface between neuronal tissue and the cerebrospinal fluid (CSF). MECs were previously shown to be involved in the clearance of waste products from the CSF and in maintaining the optic nerve microenvironment. In addition, MECs are involved in immunological processes in the brain by secretion of pro‐inflammatory cytokines in response to various pathologically relevant stress conditions.
Consumo alimentar e ecologia de populações ribeirinhas em dois ecossistemas amazônicos: um estudo comparativo

OBJECTIVE: This article analyses and compares data on household food intake of two Amazonian riverine populations settled in different rain forest ecosystems: terra firme (land not subject to annual flooding) forest and floodplain. METHODS: Food surveys were carried out in 11 households at the floodplain area (Ituqui Island), located in the Municipality of Santarem, and in 17 households at the terra firme area (Caxiuana National Forest), located in the Municipalities of Melgaco and Portel. Household food consumption data were collected using the 24-hour food recall method. Data analysis was run in Statistical Package for Social Sciences, version 12.0. RESULTS: The results confirm, in both ecosystems, the central roles of fish and manioc in the local diet. Nevertheless, other secondary food items, e.g. acai (in Caxiuana) and milk (in Ituqui) are also important. In addition, sugar stands out as a reliable household energy source to cope with the extreme seasonality of rain forest natural resources. In addition, there seems to be a greater caloric contribution of fish in Ituqui's diet, probably due to the higher productivity of lakes and rivers in Ituqui varzea (low and flat land alongside a watercourse). Finally, Ituqui has shown greater dependency over purchased items, whereas Caxiuana has still a strong reliance on agricultural activities and on local social and economic exchange networks. CONCLUSION: Besides confirming the importance of fish and manioc, results have also shown that industrialized products, such as sugar, play an important role in local diets, and may point towards new tendencies in food consumption related to the current nutritional transition and to the erosion of local subsistence systems.
Gender differences in whole-body fat oxidation kinetics during exercise.

Discrepancies appear in studies comparing fat oxidation between men and women. Therefore, this study aimed to quantitatively describe and compare whole-body fat oxidation kinetics between genders during exercise, using a sinusoidal (SIN) model. Twelve men and 11 women matched for age, body mass index, and aerobic fitness (maximal oxygen uptake and maximal power output per kilogram of fat-free mass (FFM)) performed submaximal incremental tests (Incr) with 5-min stages and a 7.5% maximal power output increment on a cycle ergometer. Fat oxidation rates were determined using indirect calorimetry, and plotted as a function of exercise intensity. The SIN model, which includes 3 independent variables (dilatation, symmetry, translation) that account for the main quantitative characteristics of kinetics, was used to mathematically describe fat oxidation kinetics and to determine the intensity (Fatmax) eliciting the maximal fat oxidation (MFO). During Incr, women exhibited greater fat oxidation rates from 35% to 85% maximal oxygen uptake, MFO (6.6 ± 0.9 vs. 4.5 ± 0.3 mg·kg FFM-1·min-1), and Fatmax (58.1% ± 1.9% vs. 50.0% ± 2.7% maximal oxygen uptake) than men (p < 0.05). While men and women showed similar global shapes of fat oxidation kinetics in terms of dilatation and symmetry (p > 0.05), the fat oxidation curve tended to be shifted toward higher exercise intensities in women (rightward translation, p = 0.08). These results support the idea that women have a greater reliance on fat oxidation than men during submaximal exercise, but also indicate that this greater fat oxidation is shifted toward higher exercise intensities in women than in men.
The Solitary Pulmonary Nodule – Is It Malignant or Benign? Diagnostic Performance of 99mTc-Depreotide SPECT

Background: The diagnosis of malignancy may be difficult to establish in solitary pulmonary nodules (SPNs). Objectives: It was the aim of this study to assess diagnostic performances of technetium-99m (99mTc)-depreotide in differentiating benign from malignant SPNs and compare its diagnostic accuracy with fluor-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) in a subgroup of patients. Methods: One hundred and eighteen patients presenting with an SPN ≤3 cm suspected of malignancy on CT were included in a prospective, open-label, European multicentre trial. Single photon emission computed tomography (SPECT) images were acquired 1.1–4.5 h after injection of 459–770 MBq of 99mTc-depreotide. A subset of 29 patients also underwent FDG-PET imaging. Images were interpreted blindly and correlated with histopathology. Results:99mTc-depreotide was positive in 65 of 73 patients with a malignant lesion and negative in 30 of 45 patients with a benign lesion, resulting in a sensitivity, specificity and diagnostic accuracy of 89, 67 and 81%, respectively. In 40 patients with SPN ≤1.5 cm, diagnostic accuracy was 88, sensitivity 75 and specificity 96%. In the subset of 29 patients who underwent both 99mTc-depreotide SPECT and FDG-PET imaging, sensitivity, specificity and diagnostic accuracy were identical for both modalities, i.e. 90, 67 and 83%, respectively. Conclusions: The diagnostic accuracy of 99mTc-depreotide SPECT is good and comparable with FDG-PET imaging in SPN of indeterminate origin.
Mechanics of blastocyst morphogenesis

During pre‐implantation development, the mammalian zygote transforms into the blastocyst, the structure that will implant the embryo in the maternal uterus. Consisting of a squamous epithelium enveloping a fluid‐filled cavity and the inner cell mass, the blastocyst is sculpted by a succession of morphogenetic events. These deformations result from the changes in the forces and mechanical properties of the tissue composing the embryo. Here, I review the recent studies, which, for the first time, informed us on the mechanics of blastocyst morphogenesis.
Efficacy and Safety of Pubertal Induction Using 17&bgr;-Estradiol in Transgirls

Context Puberty suppression using gonadotropin-releasing hormone agonists, followed by induction of the desired sex characteristics using sex steroids, has been recommended by the current guidelines as the treatment of choice for gender dysphoric adolescents, although little evidence is available. Aim To evaluate the efficacy and safety of estrogen treatment for pubertal induction in transgirls (female-identifying adolescents assigned male at birth). Methods Twenty-eight adolescents treated with oral estrogen for ≥1 year were included. The Tanner stage, anthropometry, laboratory parameters, bone age, and body composition were evaluated. Results Breast development started within 3 months in 83% of adolescents, and after 3 years, 86% had Tanner breast stage 4 to 5. The hip circumference increased and the waist/hip ratio decreased. The median serum estradiol was 100 pmol/L (range, 24 to 380) at the standard adult dose of 2 mg of 17β-estradiol. The adult height standard deviation score was +1.9 (for females). The body mass index standard deviation score, lean body mass percentage, fat percentage, and blood pressure did not change. No abnormalities of creatinine or liver enzymes were detected, and the hematocrit and hemoglobin A1c did not change. One individual developed hyperprolactinemia during high-dose ethinylestradiol treatment to limit growth. Conclusions Pubertal induction using estradiol is effective; however, an adult dose of 2 mg does not always result in appropriate serum estradiol levels. Monitoring renal function, liver enzymes, hematocrit, and hemoglobin A1c during pubertal induction with estradiol is not necessary. Further studies are needed to establish effective and safe methods to limit growth.
Water Effects on the First-Order Transition in a Model of Earthquakes

The study of 1D spring-block model of earthquake dynamics with consideration of water effects in preexisting fault deals with new forms of frictional force. An analytical study of the equation of motion enables us to establish that motion of geological fault is accelerated by water pressure. In the same setting the critical value of frictional velocity for which appears the discontinuous (first-order) transition from a stick-slip behavior to a creep motion strongly depends on water pressure. The investigation also displays the magnitude and probability of events as a function of water pressure; these two quantities decrease and increase, respectively, with the variation of water pressure.
The Effect of PCSK9 Loss‐of‐Function Variants on the Postprandial Lipid and ApoB‐Lipoprotein Response

Context: Proprotein convertase subtilisin kexin 9 (PCSK9) mediates degradation of the low‐density lipoprotein receptor (LDLR), thereby increasing plasma low‐density lipoprotein cholesterol (LDL‐C). Variations in the PCSK9 gene associated with loss of function (LOF) of PCSK9 result in greater expression of hepatic LDLR, lower concentrations of LDL‐C, and protection from cardiovascular disease (CVD). Apolipoprotein‐B (apoB) remnants also contribute to CVD risk and are similarly cleared by the LDLR. We hypothesized that PCSK9‐LOF carriers would have lower fasting and postprandial remnant lipoproteins on top of lower LDL‐C. Objective: To compare fasting and postprandial concentrations of triglycerides (TGs), total apoB, and apoB48 as indicators of remnant lipoprotein metabolism in PCSK9‐LOF carriers with those with no PCSK9 variants. Design: Case‐control, metabolic study. Setting: Clinical Research Center of The Ottawa Hospital. Participants: Persons with one or more copies of the L10ins/A53V and/or I474V and/or R46L PCSK9 variant and persons with no PCSK9 variants. Intervention: Oral fat tolerance test. Main Outcomes Measures: Fasting and postprandial plasma TG, apoB48, total apoB, total cholesterol, and PCSK9 were measured at 0, 2, 4, and 6 hours after an oral fat load. Results: Participants with PCSK9‐LOF variants (n = 22) had reduced fasting LDL‐C (‐14%) as well as lower fasting TG (‐21%) compared with noncarrier controls (n = 23). LOF variants also had reduced postprandial total apoB (‐17%), apoB48 (‐23%), and TG (‐18%). Postprandial PCSK9 declined in both groups (‐24% vs ‐16%, respectively). Conclusions: Participants carrying PCSK9‐LOF variants had attenuated levels of fasting and postprandial TG, apoB48, and total apoB. This may confer protection from CVD and further validate the use of PCSK9 inhibitors to lower CVD risk.
Prenatal Nicotine Exposure Selectively Affects Nicotinic Receptor Expression in Primary and Associative Visual Cortices of the Fetal Baboon

Exposure to nicotine during pregnancy via maternal cigarette smoking is associated with visual deficits in children. This is possibly due to the activation of nicotinic acetylcholine receptors (nAChRs) in the occipital cortex, which are important in the development of visual mapping. Using a baboon model, we explored the effects of prenatal nicotine on parameters in the primary and associated visual cortices. Pregnant baboons were infused with nicotine (0.5 mg/h, intravenous) or saline from 86 days gestation. At 161 days gestation, fetal brains were collected (n = 5 per group) and the occipital lobe assessed for nAChRs and markers of the serotonergic and catecholaminergic systems using tissue autoradiography and/or high‐performance liquid chromatography. Neuronal nAChRs and serotonergic markers were expressed in a region‐ and subunit‐dependent manner. Prenatal nicotine exposure was associated with increased binding for 3H‐epibatidine sensitive nAChRs in the primary visual cortex [Brodmann areas (BA) 17] and BA 18, but not BA 19, of the associative visual cortex (P < 0.05). Markers of the serotonergic or catecholaminergic systems were not significantly altered. Thus, prenatal nicotine exposure is associated with alterations in the cholinergic system in the occipital lobe, which may aid in the explanation of the appearance of visual deficits in children from mothers who smoke during pregnancy.
CDC73-Related Disorders: Clinical Manifestations and Case Detection in Primary Hyperparathyroidism

Context Heterozygous pathogenic germline variants in CDC73 predispose to the development of primary hyperparathyroidism (pHPT) and, less frequently, ossifying fibroma of the jaw and renal and uterine tumors. Clinical information on CDC73-related disorders has so far been limited to small case series. Objective To assess the clinical manifestations and penetrance in CDC73-related disorders and to improve case detection in pHPT. Design Nationwide retrospective Dutch cohort study. Setting Tertiary referral center. Patients We studied 89 patients with pHPT referred for germline CDC73 analysis and 43 subsequently tested relatives who proved to be mutation carriers. Investigation Germline CDC73 mutation analysis. Mean Outcome CDC73 mutation detection yield, referral rate, and CDC73-related disease penetrance. Results Pathogenic germline CDC73 variants were identified in 11 of the 89 referred pHPT patients (12.4%), with (suspected) hyperparathyroidism-jaw tumor (HPT-JT) syndrome (n = 3), familial isolated pHPT (n = 5), apparently sporadic parathyroid carcinoma (n = 2), and apparently sporadic parathyroid adenoma (n = 1). The estimated penetrance of CDC73-related disorders was 65% at age 50 years (95% confidence interval, 48% to 82%) in 43 nonindex mutation carriers. Conclusions Germline CDC73 analysis is recommended in individuals with (suspected) HPT-JT syndrome, familial isolated pHPT, atypical or malignant parathyroid histology, and young individuals with pHPT. These criteria would increase germline CDC73 mutation detection, enabling optimal clinical management of pHPT as well as genetic counseling and surveillance for family members at risk for developing CDC73-related disorders.
2‐Hydoxyglutarate: D/Riving Pathology in gLiomaS

Common pathways and mechanisms can be found in both cancers and inborn errors of metabolism. 2‐Hydroxyglutarate (2‐HG) acidurias and isocitrate dehydrogenase (IDH) 1/2 mutant tumors are examples of this phenomenon. 2‐HG can exist in two chiral forms, D(R)‐2‐HG and L(S)‐2‐HG, which are elevated in D‐ and L‐acidurias, respectively. D‐2‐HG was subsequently discovered to be synthesized in IDH 1/2 mutant tumors including ∼70% of intermediate‐grade gliomas and secondary glioblastomas (GBM). Recent studies have revealed that L‐2‐HG is generated in hypoxia in IDH wild‐type tumors. Both 2‐HG enantiomers have similar structures as α‐ketoglutarate (α‐KG) and can competitively inhibit α‐KG‐dependent enzymes. This inhibition modulates numerous cellular processes, including histone and DNA methylation, and can ultimately impact oncogenesis. D‐2‐HG can be detected in vivo in glioma patients and animal models using advanced imaging modalities. Finally, pharmacologic inhibitors of mutant IDH 1/2 attenuate the production of D‐2‐HG and show great promise as therapeutic agents.
Benign Thyroid Diseases and Risk of Thyroid Cancer: A Nationwide Cohort Study

Context Thyroid nodules, adenomas, and goiter have consistently been associated with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction and thyroid autoimmunity influence this risk. Objective To examine thyroid cancer risk after diagnoses of a wide range of benign thyroid conditions. Design Hospital and cancer registry linkage cohort study for the years 1978 to 2013. Setting Nationwide (Denmark). Participants Patients diagnosed with hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n = 12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582), other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807 residents of Denmark during the study period. Main Outcome Measures We computed standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding the first 12 months of follow-up after benign thyroid disease diagnosis. Results SIRs were significantly elevated for all benign thyroid diseases apart from hypothyroidism. SIRs were higher for men than women and in the earlier follow-up periods. Elevated SIRs were observed for localized and regional/distant thyroid cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27 thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92], nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to 11.5) remained positively associated with thyroid cancer risk. Conclusions We found an unexpected increased risk of differentiated thyroid cancer, including regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis that could not be solely attributed to increased medical surveillance. Hypothyroidism was less clearly associated with thyroid cancer risk.
Hydrocortisone Affects Fatigue and Physical Functioning Through Metabolism of Tryptophan: A Randomized Controlled Trial

Context Hydrocortisone (HC) treatment influences health-related quality of life (HRQOL) in secondary adrenal insufficiency (AI). Glucocorticoids regulate tryptophan metabolism through the kynurenine pathway, which modulates mood and energy homeostasis. Objective This study investigated whether tryptophan metabolism mediated the effect of HC dose on HRQOL in patients with secondary AI. Design, Setting, and Patients Forty-seven patients with secondary AI participated in this double-blind randomized controlled cross-over trial in the University Medical Center Groningen. Intervention Patients were treated for two 10-week periods with a daily HC dose of 0.2 to 0.3 mg/kg and 0.4 to 0.6 mg/kg body weight, respectively. Main Outcome Measures Diary data and questionnaires were used to assess HRQOL. Tryptophan, kynurenine and 3-hydroxykynurenine were measured in serum and dialyzed plasma and the kynurenine-to-tryptophan ratio (Kyn/Trp ratio) ratio was calculated. Results A higher dose HC was associated with increased levels of tryptophan (95% CI for mean difference 0.37 to 12.5, P = 0.038), reduced levels of kynurenine (95% CI, -0.49 to -0.10, P = 0.004) and 3-hydroxykynurenine (95% CI, -10.6 to -2.35, P = 0.003), and a reduced Kyn/Trp ratio (95% CI, -0.84 to -0.50, P < 0.001). The Kyn/Trp ratio mediated the effect of a higher dose HC on fatigue (P = 0.041) and physical functioning (P = 0.005). Conclusion Metabolism of tryptophan through the kynurenine pathway is reduced after a 10-week treatment with a higher dose HC and plays a role in the effect of HC on fatigue and physical functioning in patients with secondary AI.