Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergism of malnutrition and infection. Evidence from field studies in Guatemala.

Knowledge of human disease is acquired in three main ways: bedside study of the sick individual, laboratory experiment, and the epidemiological approach through observation of disease as it occurs in whole populations. All three, although first applied to infectious diseases, are equally applicable to nutritional disorders. In its simplest form the epidemiological method deals with the incidence and prevalence of a disease in various fractions of a population. The next step is to use these data to identify the multiple causative factors involved. This may be followed by the design and execution of field studies to test hypotheses of origin, and ultimately to evaluate suggested measures for prevention and control.1 The epidemiological method requires an understanding of the ecology of a disease process as determined not only by a specific agent but also by environmental and host factors which usually play the larger role in determining occurrence and severity.
Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women

What is the central question of this study? Does a clinically relevant intravenous dose of erythropoeitin affect the hypoxic ventilatory response and/or hypoxic pulmonary vasoconstriction in healthy humans? What is the main finding and its importance? Erythropoeitin does not influence the ventilatory and pulmonary vascular responses to acute hypoxia in men or women.
Engineered Ferritin for Magnetogenetic Manipulation of Proteins and Organelles Inside Living Cells

Magnetogenetics is emerging as a novel approach for remote‐controlled manipulation of cellular functions in tissues and organisms with high spatial and temporal resolution. A critical, still challenging issue for these techniques is to conjugate target proteins with magnetic probes that can satisfy multiple colloidal and biofunctional constraints. Here, semisynthetic magnetic nanoparticles are tailored based on human ferritin coupled to monomeric enhanced green fluorescent protein (mEGFP) for magnetic manipulation of proteins inside living cells. This study demonstrates efficient delivery, intracellular stealth properties, and rapid subcellular targeting of those magnetic nanoparticles via GFP–nanobody interactions. By means of magnetic field gradients, rapid spatial reorganization in the cytosol of proteins captured to the nanoparticle surface is achieved. Moreover, exploiting efficient nanoparticle targeting to intracellular membranes, remote‐controlled arrest of mitochondrial dynamics using magnetic fields is demonstrated. The studies establish subcellular control of proteins and organelles with unprecedented spatial and temporal resolution, thus opening new prospects for magnetogenetic applications in fundamental cell biology and nanomedicine.
Surgery and radioablation therapy combined: introducing a 1-week-condensed procedure bonding total thyroidectomy and radioablation therapy with recombinant human TSH.

OBJECTIVE The objective of this study was to determine whether the use of recombinant human TSH (rhTSH) to stimulate radioiodine uptake after thyroidectomy is as efficacious as a period of withholding thyroid hormones, while at the same time avoiding hypothyroidism, reducing sick leave time and shortening the hospital stay. DESIGN Our aim was to compare the standard procedure of differentiated thyroid cancer treatment, which consists of thyroidectomy followed by 4 weeks of hypothyroidism and a conclusive ablative activity of (131)iodine, with a new shortened treatment in which l-thyroxine (T(4)) medication is initiated a day after thyroidectomy, followed by application of rhTSH stimulation and subsequent ablation a few days after surgery. We presumed our treatment to represent the most sophisticated strategy for the reduction in sick leave days overall without any reduction in safety or the efficacy of ablative therapy. METHODS Patients (n=25) were randomized either for surgery and rhTSH stimulation or surgery and l-T(4) abstinence before the first application of radioiodine. Ablation success was determined by neck ultrasound and serum thyroglobulin during follow-up. RhTSH receivers were monitored for an average of 635 days (s.d.+/-289) and patients in l-T(4) abstinence for an average of 624 days (s.d.+/-205). Both groups were statistically compared for significant differences in treatment efficacy, safety and overall time of sick leave. RESULTS AND CONCLUSIONS Our shortened treatment proved to be equally efficacious and safe in comparison with the conventional therapy regimen. At the same time, it showed economic advantages through the reduction in average sick leave time from approximately 29 days (l-T(4) abstinence) down to approximately 6 days (rhTSH stimulation) as well as sustaining the patient's quality of life by the complete avoidance of hypothyroidism.
Investigation of microcytosis: a comprehensive approach

Abstract: Microcytosis is a highly prevalent finding during blood examination. This study investigates the causes of microcytosis (defined as mean corpuscular volume (MCV)<82 fl) in 466 patients referred to our laboratory for suspected hemoglobinopathy. The following data were obtained: Hb, MCV, serum iron, transferrin, ferritin, HbA2, HbF, isoelectric focusing of the Hb, gene mapping of chromosome 16 with Xba I and Bgl II and hybridization with an α‐ and a ζ‐probe, inflammatory status. Results show that iron deficiency remains the first cause of microcytosis (35.2% of our patients), even in a selected population such as ours. Deletional α‐thalassemia, probably the most frequent hemoglobinopathy throughout the world, represents the second most frequent cause of microcytosis (31.1%), followed by β‐thalassemia heterozygous state (18.9%). Of our patients, 1.3% had microcytosis due to the presence of an abnormal hemoglobin (HbC, Hb S/C, HbE). Three cases (0.6%) had other possible causes of microcytosis. Of the remaining 60 cases, 28 had an inflammatory state. Finally, 32 cases (6.9%) remain unexplained; taking into consideration the origin of these cases, their hematological parameters and their family history, we postulate that these cases are at high risk for non‐deletional α‐thalassemia.
Audit Failure of New Zealand Finance Companies – An Exploratory Investigation

Purpose The setting of private finance companies that failed in New Zealand during 2006-2012 was characterized by weaker corporate governance and enforcement of securities law. This paper aims to explore audit failure in this setting and examine whether auditors erred in their audits of the failed finance companies and whether the audit failure rate of Big N auditors was different from that of non-Big N auditors. Design/methodology/approach This paper adopts the archival research method and uses three sets of evidence to assess audit failure – the frequency of going concern opinion (GCO) prior to failure, misstatements in the last audited financial statements, and the violation of the Code of Ethics. Findings The study finds that only 41 per cent of the sample companies received the GCO in their last audit prior to failure and provides evidence of material misstatements in the financial statements of a number of failed finance companies that received clean audit opinions prior to failure and breaches of the Code of Ethics by a number of auditors. These results strongly indicate audit failure for a number of failed finance companies. The audit failure rate, however, appears less for Big N auditors than for non-Big N auditors. Practical implications The study draws attention of the stock market regulator and the accounting profession to an area, the audit of private finance companies, that needs better quality audits. Originality/value This paper provides systematic evidence of audit failure in failed finance companies in New Zealand. It also furnishes preliminary evidence of Big N auditors compensating for weaker corporate governance.
Lipid lipoprotein profile alterations in Greek infertile women with polycystic ovaries: influence of adipocytokines levels.

AIM To correlate serum and follicular fluid (FF) leptin and visfatin levels with lipid lipoprotein levels in women with and without polycystic ovary syndrome (PCOS) undergoing ovarian stimulation. MATERIALS AND METHODS We studied 90 PCOS women and 94 age- and weight-matched controls, enrolled in the In Vitro Fertilization (IVF) program. RESULTS Total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, apolipoprotein B and lipoprotein(a) levels were significantly elevated, while high-density lipoprotein (HDL)-cholesterol and apolipoprotein A1, lower in PCOS subjects. Serum and FF visfatin levels were increased in PCOS women and correlated positively with body-mass index (BMI), lipoprotein(a) and triglycerides, and negatively with apolipoprotein A1. Leptin levels were comparable between groups and positively correlated with BMI and LDL-cholesterol, and negatively with apolipoprotein B. CONCLUSION Lipid lipoprotein alterations are common in reproductive-age PCOS women increasing the risk for cardiovascular diseases later in life. Leptin and visfatin play significant roles in lipid metabolism and further research is required in this area.
Attributes of Environments Supporting Walking

Purpose. This study established a framework to audit environments supporting walking in neighborhoods. Design. Cross-sectional analysis using a telephone survey and 200 objective environmental variables. Setting. Urbanized King County, WA. Subjects. 608 randomly sampled adults. Measures. Walking measures constructed from survey questions; objective environmental measures taken from parcel-level databases in Geographic Information Systems. Analysis. Multinomial models estimated the odds of people engaging in moderate walking (< 149 min/wk) and in walking sufficiently to meet recommendations for health (150+min/wk), relative to not walking; and in walking sufficiently, relative to walking moderately. A base model consisted of survey variables, and final models incorporated both survey and environmental variables. Results. Survey variables strongly associated with walking sufficiently to enhance health included household income, not having difficulty walking, using transit, perceiving social support for walking, walking outside of the neighborhood, and having a dog (p < .01). The models isolated 14 environmental variables associated with walking sufficiently (pseudo R2 up to 0.46). Measures of distance to neighborhood destinations dominated the results: shorter distances to grocery stores/markets, restaurants, and retail stores, but longer distances to offices or mixed-use buildings (p < .01 or .05). The density of the respondent's parcel was also strongly associated with walking sufficiently (p < .01). Conclusions. The study offered valid environmental measures of neighborhood walkability.
Synapses of Amphids Defective (SAD-A) Kinase Promotes Glucose-stimulated Insulin Secretion through Activation of p21-activated Kinase (PAK1) in Pancreatic β-Cells*

Background: PAK1 is phosphorylated at Thr-423, which is required for glucose-stimulated insulin secretion, but the kinase regulator remains elusive. Results: We identified SAD-A as the kinase that phosphorylates PAK1 at Thr-423 in islet β-cells. Conclusion: SAD-A is required for insulin secretion through activation of PAK1. Significance: These data provide a key insight for biological function of SAD-A in islet β-cells. The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet β-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP-activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD-A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet β-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet β-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis.
Rosacea under the microscope: characteristic histological findings

Rosacea is a common facial dermatosis that is seldom biopsied; thus, histological aspects have not been well described. Biopsies are generally performed in the presence of atypical symptoms (e.g. granulomas). Differential diagnosis with sarcoidosis, lupus miliaris or lupus erythematosus is another indication for biopsy. There are few published studies addressing the microscopic aspects of rosacea and describing the histological and immunohistochemical features of this disease. While some textbooks consider the microscopic signs of rosacea to be non‐diagnostic, experienced dermatopathologists are generally able to make the diagnosis via histology. This article discusses the specific combinations of histological features that are highly suggestive of rosacea.
Evolutionary diversification of retinoic acid receptor ligand-binding pocket structure by molecular tinkering

Whole genome duplications (WGDs) have been classically associated with the origin of evolutionary novelties and the so-called duplication–degeneration–complementation model describes the possible fates of genes after duplication. However, how sequence divergence effectively allows functional changes between gene duplicates is still unclear. In the vertebrate lineage, two rounds of WGDs took place, giving rise to paralogous gene copies observed for many gene families. For the retinoic acid receptors (RARs), for example, which are members of the nuclear hormone receptor (NR) superfamily, a unique ancestral gene has been duplicated resulting in three vertebrate paralogues: RARα, RARβ and RARγ. It has previously been shown that this single ancestral RAR was neofunctionalized to give rise to a larger substrate specificity range in the RARs of extant jawed vertebrates (also called gnathostomes). To understand RAR diversification, the members of the cyclostomes (lamprey and hagfish), jawless vertebrates representing the extant sister group of gnathostomes, provide an intermediate situation and thus allow the characterization of the evolutionary steps that shaped RAR ligand-binding properties following the WGDs. In this study, we assessed the ligand-binding specificity of cyclostome RARs and found that their ligand-binding pockets resemble those of gnathostome RARα and RARβ. In contrast, none of the cyclostome receptors studied showed any RARγ-like specificity. Together, our results suggest that cyclostome RARs cover only a portion of the specificity repertoire of the ancestral gnathostome RARs and indicate that the establishment of ligand-binding specificity was a stepwise event. This iterative process thus provides a rare example for the diversification of receptor–ligand interactions of NRs following WGDs.
Managing Nausea and Vomiting of Pregnancy with Pharmacological and Nonpharmacological Treatments

Nausea and vomiting of pregnancy (NVP) affects approximately 80% of pregnant women; however, this condition is not always addressed, let alone treated appropriately. NVP can be physically debilitating and can also interfere with the socioeconomic aspects of a woman's life. Some women and healthcare providers are unaware of the various NVP treatments and means of management. Lack of treatment may result from misinformation or misperception regarding NVP treatments and its safety during pregnancy. However, several studies have shown that there are effective pharmacological options that do not cause adverse effects in the mother or her unborn baby. The potential consequences of untreated NVP include substantial maternal weight loss, dehydration, hospitalization, low birthweight and depression. The following review provides a detailed description of NVP and how it can adversely affect a woman's life, as well as evidence-based information on treatment strategies.
Inhibitory control of plateau properties in dorsal horn neurones in the turtle spinal cord in vitro

1 The role of inhibition in control of plateau‐generating neurones in the dorsal horn was studied in an in vitro preparation of the spinal cord of the turtle. Ionotropic and metabotropic inhibition was found to condition the expression of plateau potentials. 2 Blockade of γ‐aminobutyric acid (GABAA) and glycine receptors by their selective antagonists bicuculline (10‐50 μM) and strychnine (5‐20 μM) enhanced the excitatory response to stimulation of the dorsal root and facilitated the expression of plateau potentials. 3 Bicuculline and strychnine also facilitated the generation of plateau potentials in response to depolarizing current pulses, suggesting the presence of tonic ionotropic inhibitory mechanisms in turtle spinal cord slices. 4 Activation of GABAB receptors also inhibited plateau‐generating neurones. The selective agonist baclofen (5‐50 μM) inhibited wind‐up of the response to repeated depolarizations induced synaptically or by intracellular current pulses. 5 Baclofen reduced afferent synaptic input. This effect was not affected by bicuculline or strychnine and was blocked by the selective GABAB receptor antagonist 2‐hydroxysaclofen (2‐OH‐saclofen, 100‐400 μM). 6 Postsynaptically, baclofen inhibited plateau properties. Activation of GABAB receptors produced a hyperpolarization (7.0 ± 0.5 mV, mean ± s.e.m., n= 29) with an associated decrease in input resistance (22.7 ± 3.1 %, n= 24). These effects were blocked by extracellular Ba2+ (1‐2 mM). 7 When the baclofen‐induced hyperpolarization and shunt were compensated for by adjusting the bias current and the strength of the stimulus, baclofen still inhibited generation of plateau potentials. Wind‐up and after‐discharges were also inhibited by baclofen. These effects remained in the presence of tetrodotoxin (1 μM) and were antagonized by 2‐OH‐saclofen. 8 The inhibition of plateau properties was observed even when the baclofen‐induced hyperpolarization and shunt were blocked by Ba2+ and when potassium channels were blocked by Ba2+ (3 mM), tetraethylammonium (TEA, 15 mM) and apamin (0.25‐0.5 μM). The baclofen‐sensitive component of the plateau potential was reduced by nifedipine (10 μM), suggesting a modulation of postsynaptic L‐type Ca2+ channels. 9 We suggest that inhibitory regulation of plateau properties plays a role in somatosensory processing in the dorsal horn. The inhibitory control of wind‐up and after‐discharges may be particularly significant in physiological and therapeutic control of central sensitization to pain.
IAS 39, income smoothing, and pro-cyclicality: evidence from Hong Kong banks

Purpose - The purpose of this study is to investigate the impact of International Accounting Standard 39 (IAS 39) on income-smoothing activities and pro-cyclical behavior through loan loss provisions using a sample of Hong Kong banks. Design/methodology/approach - Fixed effects estimator is used, and the analysis covers the period from 2000 to 2009. Findings - The results suggest that Hong Kong banks engage less in income-smoothing activity after they comply with the IAS 39. No evidence supports loan loss provisions of Hong Kong banks exhibiting more pro-cyclical behavior after IAS 39 adoption. Research limitations/implications - Compliance with IAS 39 should improve the quality of bank financial reporting. The reduction in income-smoothing activities among Hong Kong banks after IAS 39 adoption fairly supports the effectiveness of International Financial Reporting Standard (IFRS) and countries that have yet to comply with IFRS may take action to apply the standards. Bank regulators should take pro-active action in addressing the issue of pro-cyclicality of loan loss provisions, as IAS 39 focuses more on improving the financial information quality, while pro-cyclicality is associated with the economic cycles. Originality/value - Hong Kong banking industry is unique, as it was among the first IFRS adopters in the East Asia region and it has its own legal framework for developing accounting standards. The results of this study are expected to shed some light on the effects of IAS 39 adoption on income smoothing and pro-cyclicality of banks in the East Asia region, where the accounting cultural value dimensions and institutional structures are different than that of European countries.
Methionine supplementation influences melanin-based plumage colouration in Eurasian kestrel, Falco tinnunculus, nestlings

SUMMARY The extent to which the expression of melanin-based plumage colouration in birds is genetically or environmentally determined is controversial. Here, we performed a between-nest design supplementation with either the sulphur amino acid dl-methionine or with water to investigate the importance of the non-genetic component of melanin-based plumage colouration in the Eurasian kestrel, Falco tinnunculus. Methionine affects growth and immunity, thus we aimed to modify nestling growth and immunity before feather development. Then, we measured the effect of the experiment on colouration of two melanin-based plumage patches of nestling kestrels. We found that methionine slowed down nestling growth through treatment administration and that nestlings compensated by speeding up their growth later. We did not find any effects of methionine on nestling immunity (i.e. lymphocyte counts, natural antibody levels or complement-mediated immunity). Effects on growth seemed to be mirrored by changes in nestling colouration in the two sexes: methionine-nestlings showed less intense brown plumage on their backs compared with control nestlings. These results provide support for a non-genetic determination of a melanin-based plumage patch in the two sexes of nestling kestrels.
Networks involved in olfaction and their dynamics using independent component analysis and unified structural equation modeling

The study of human olfaction is complicated by the myriad of processing demands in conscious perceptual and emotional experiences of odors. Combining functional magnetic resonance imaging with convergent multivariate network analyses, we examined the spatiotemporal behavior of olfactory‐generated blood‐oxygenated‐level‐dependent signal in healthy adults. The experimental functional magnetic resonance imaging (fMRI) paradigm was found to offset the limitations of olfactory habituation effects and permitted the identification of five functional networks. Analysis delineated separable neuronal circuits that were spatially centered in the primary olfactory cortex, striatum, dorsolateral prefrontal cortex, rostral prefrontal cortex/anterior cingulate, and parietal‐occipital junction. We hypothesize that these functional networks subserve primary perceptual, affective/motivational, and higher order olfactory‐related cognitive processes. Results provided direct evidence for the existence of parallel networks with top‐down modulation for olfactory processing and clearly distinguished brain activations that were sniffing‐related versus odor‐related. A comprehensive neurocognitive model for olfaction is presented that may be applied to broader translational studies of olfactory function, aging, and neurological disease. Hum Brain Mapp 35:2055–2072, 2014. © 2013 Wiley Periodicals, Inc.