Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of Epithelial and Mesenchymal Differentiation Markers in the Early Human Gonadal Development

Expressions of cytokeratin 8 (CK8), vimentin, nestin, and alpha‐smooth‐muscle‐actin (alpha‐SMA) were analyzed in the developing gonads of 12, 5–9 week old (W) human conceptuses by immunohistochemistry and immunofluorescence. During the investigated period, the number of CK8 positive cells increased from 56% to 92% in the gonadal surface epithelium, from 50% to 60% in the stroma, and from 23% to 42% in the medulla. In the early fetal period, the cell expression of CK8 increased in all gonadal parts, whereas primordial germ cells (PGC) remained negative. The expression of vimentin increased in the gonad stroma (gs) from 73% to 88%, and in the surface epithelium from 18% to 97% until ninth W. The medulla had the highest expression of vimentin in the seventh to eighth W (93%). Vimentin and CK8 colocalized in the somatic cells, while some PGCs showed vimentin expression only. Initially, nestin was positive in the gonad surface epithelium (8%) and stroma (52%), however during further development it decreased to 1% and 33%, respectively. In the early fetal period, the nestin positive cells decreased from 44% to 31% in the gonad medulla. Alpha‐SMA was positive only in the blood vessels and mesonephros. The described pattern of expression of intermediate filaments (IF) in developing human gonads suggests their role in the control of PGC apoptosis, early differentiation of gs cells and cell migration. Both epithelial and mesenchymal origins of follicular cells and possible epithelial‐to‐mesenchymal transition of somatic cells is proposed. Lastly, IF intensity expression varies depending on the cell type and developmental period analyzed. Anat Rec, 300:1315–1326, 2017. © 2017 Wiley Periodicals, Inc.
Accuracy of self-reported hypertension: a systematic review and meta-analysis

Objective: To estimate the sensitivity and specificity of self-reported hypertension (HTN) as compared with the clinical diagnosis in epidemiological studies. Methods: We searched MEDLINE, Embase, Scopus, Web of Science, LILACS, Google Scholar, and ProQuest Dissertations & Theses Global: Health & Medicine databases. In addition, we screened the references’ lists of relevant reports to identify potentially eligible articles. There were no date or language restrictions. Studies were selected by two independent reviewers, who also extracted data and assessed methodological quality using the Quality Assessment of Diagnostic Accuracy Studies criteria. A meta-analysis was performed to summarize sensitivity and specificity across studies and estimate heterogeneity. Results: Out of 2304 records, 22 were included, corresponding to a population of 112 517 adults (55% women). There was substantial variation in sensitivity and specificity across countries and age groups. Several different techniques, devices, and reference ranges were used to diagnose HTN, and self-reporting underestimated its prevalence in the majority of studies. The sensitivity was 42.1% (95% confidence interval 30.9–54.2) and the specificity was 89.5% (95% confidence interval 84.0–93.3), with high heterogeneity (I2 > 99%). Conclusion: Less than half of patients with HTN would not be identified by self-reporting in epidemiological studies. Self-reported HTN has important limitations and may represent an important source of bias in research depending on regional, socioeconomic, and cultural differences.
Pharmacological inhibition of Src kinase protects against acute kidney injury in a murine model of renal ischemia/reperfusion

Activation of Src kinase has been implicated in the pathogenesis of acute brain, liver, and lung injury. However, the role of Src in acute kidney injury (AKI) remains unestablished. To address this, we evaluated the effects of Src inhibition on renal dysfunction and pathological changes in a murine model of AKI induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in increased Src phosphorylation at tyrosine 416 (activation). Administration of PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved renal function and ameliorated renal pathological damage. PP1 treatment also suppressed renal expression of neutrophil gelatinase-associated lipocalin and reduced apoptosis in the injured kidney. Moreover, Src inhibition prevented downregulation of several adherens and tight junction proteins, including E-cadherin, ZO-1, and claudins-1/−4 in the kidney after I/R injury as well as in cultured renal proximal tubular cells following oxidative stress. Finally, PP1 inhibited I/R–induced renal expression of matrix metalloproteinase-2 and -9, phosphorylation of extracellular signal–regulated kinases1/2, signal transducer and activator of transcription-3, and nuclear factor-κB, and the infiltration of macrophages into the kidney. These data indicate that Src is a pivotal mediator of renal epithelial injury and that its inhibition may have a therapeutic potential to treat AKI.
Meta-analysis of thirty-two case–control and two ecological radon studies of lung cancer

Abstract A re-analysis has been carried out of thirty-two case–control and two ecological studies concerning the influence of radon, a radioactive gas, on the risk of lung cancer. Three mathematically simplest dose–response relationships (models) were tested: constant (zero health effect), linear, and parabolic (linear–quadratic). Health effect end-points reported in the analysed studies are odds ratios or relative risk ratios, related either to morbidity or mortality. In our preliminary analysis, we show that the results of dose–response fitting are qualitatively (within uncertainties, given as error bars) the same, whichever of these health effect end-points are applied. Therefore, we deemed it reasonable to aggregate all response data into the so-called Relative Health Factor and jointly analysed such mixed data, to obtain better statistical power. In the second part of our analysis, robust Bayesian and classical methods of analysis were applied to this combined dataset. In this part of our analysis, we selected different subranges of radon concentrations. In view of substantial differences between the methodology used by the authors of case–control and ecological studies, the mathematical relationships (models) were applied mainly to the thirty-two case–control studies. The degree to which the two ecological studies, analysed separately, affect the overall results when combined with the thirty-two case–control studies, has also been evaluated. In all, as a result of our meta-analysis of the combined cohort, we conclude that the analysed data concerning radon concentrations below ~1000 Bq/m3 (~20 mSv/year of effective dose to the whole body) do not support the thesis that radon may be a cause of any statistically significant increase in lung cancer incidence.
Distributing Power: Public Service Provision to the Poor in India

How do governments distribute basic public services when budget constraints necessitate their rationing? This paper examines variations in the distribution of scarce electrical power in northern India over the last two decades. Drawing on a novel set of satellite imagery of the earth at night that avoids the biases and missing data problems affecting traditional measures, I construct annual indicators of electrification for all 98,000 villages in Uttar Pradesh. By observing temporal variations in nighttime light output at the village level over three election cycles, I use matching and multilevel models to show that representation by a low-Caste party increases electrification rates in India’s villages.
The Psoriatic Arthritis Impact of Disease 12-item questionnaire: equivalence, reliability, validity, and feasibility of the touch-screen administration versus the paper-and-pencil version

Background Over the last few years, there has been a shift toward a more patient-centered perspective of the disease by adopting patient-reported outcomes. Touch-screen formats are increasingly being used for data collection in routine care and research. Objectives The aim of this study is to examine the equivalence, reliability, validity and respondent preference for a computerized touch-screen version of the Psoriatic Arthritis Impact of Disease 12-item (PsAID-12) questionnaire in comparison with the original paper-and-pencil version, in a cohort of patients with psoriatic arthritis (PsA). Methods One hundred and fifty-nine patients with PsA completed both the touch screen- and the conventional paper-and-pencil administered PsAID-12 questionnaire. Agreement between formats was assessed by intraclass correlation coefficients. Spearman’s rho correlation coefficient was used to test convergent validity of the touch screen format of PsAID-12, while receiver operating characteristic curve analysis was performed to test discriminant validity. In order to assess the patient’s preference, the participants filled in an additional questionnaire. The time taken to complete both formats was measured. Results A high concordance between the responses to the two modes of the PsAID-12 tested was found, with no significant mean differences. Intraclass correlation coefficients between data obtained for touch-screen and paper versions ranged from 0.801 to 0.962. There was a very high degree of correlation between the touch-screen format of PsAID-12 and composite disease activity indices (all at a P level <0.0001), Health Assessment Questionnaire, and Physician Assessment of disease activity. The discriminatory power of the touch-screen format of PsAID-12, assessed using the minimal disease activity – Outcome Measurements in Rheumatology Clinical Trials criteria, was very good, with an area under the receiver operating characteristic curve of 0.937 and a resulting cutoff value of 2.5. The touch-screen questionnaire was readily accepted and preferred. The mean time spent for completing the questionnaire on touch screen was 2 minutes and on paper was 2.7 minutes. Conclusion The touch-screen mode of administration of PsAID-12 can be a feasible and suitable alternative to the paper-and-pencil mode for the assessment of patients with PsA.
Functional and Molecular Characterization of Rod-like Cells from Retinal Stem Cells Derived from the Adult Ciliary Epithelium

In vitro generation of photoreceptors from stem cells is of great interest for the development of regenerative medicine approaches for patients affected by retinal degeneration and for high throughput drug screens for these diseases. In this study, we show unprecedented high percentages of rod-fated cells from retinal stem cells of the adult ciliary epithelium. Molecular characterization of rod-like cells demonstrates that they lose ciliary epithelial characteristics but acquire photoreceptor features. Rod maturation was evaluated at two levels: gene expression and electrophysiological functionality. Here we present a strong correlation between phototransduction protein expression and functionality of the cells in vitro. We demonstrate that in vitro generated rod-like cells express cGMP-gated channels that are gated by endogenous cGMP. We also identified voltage-gated channels necessary for rod maturation and viability. This level of analysis for the first time provides evidence that adult retinal stem cells can generate highly homogeneous rod-fated cells.
Changes in brain activation during sedation induced by dexmedetomidine

Objective Dexmedetomidine (DEX) has been widely used as a sedative, acting as an α2-adrenergic agonist on autoreceptors, presynaptic receptors and postsynaptic receptors without risk of respiratory depression. Although consciousness impairment is closely related to disturbances of brain function in different frequency bands, the time-varying DEX effects on cortical activity in specific frequency bands has not yet been studied. Methods We used electroencephalography (EEG) to analyse differences in cerebral cortex activity between the awake and sedated states, using electromagnetic tomography (standardized low resolution electromagnetic tomography (sLORETA)) to localize multiple channel scalp recordings of cerebral electric activity to specific brain regions. Results The results revealed increased activity in the cuneus at delta-band frequencies, and in the posterior cingulate cortex at theta frequencies, during awake and sedated states induced by DEX at specific frequency bands. Differences in standardized low resolution cingulate gyrus were found in beta1 frequencies (13–18 Hz), and in the cuneus at gamma frequencies. Conclusion Cerebral cortical activity was significantly altered in various brain areas during DEX sedation, including parts of the default mode network and common midline core in different frequency ranges. These alterations may elucidate the mechanisms underlying DEX sedation.
Nordic Walking improves trunk stability and gait spatial-temporal characteristics in people with Parkinson disease.

BACKGROUND This study aimed to assess the effect of walking with Nordic Walking (NW) poles on postural stability and gait spatial-temporal characteristics in individuals with PD and to determine the cognitive load associated operating the poles. METHODS Twelve individuals with PD (age: 61.6±11.7) were asked to perform four 90 s walking trials; with/without poles and with/without verbal fluency task (category fluency) after a 6-week independent NW training. We assessed gait spatial-temporal characteristics, and trunk postural stability using the APDM accelerometry system. RESULTS Trunk frontal range of motion and peak velocity were smaller in NW compared to normal walking with and without the cognitive task (p < 0.01). Cadence, gait speed and stride length decreased in both pole conditions when performed with the cognitive task (p < 0.05). However stride length was longer with poles compared to without poles. CONCLUSIONS The reduced range of motion and velocity of the trunk in the frontal plane of motion suggest that NW can improve postural stability independently of the addition of a cognitive task. Compared to normal walking, spatial-temporal characteristics did not further decline when the cognitive task was combined to NW. This suggests that NW is a suitable practice for gait rehabilitation protocols in PD.
A computational approach for inferring the cell wall properties that govern guard cell dynamics

Summary Guard cells dynamically adjust their shape in order to regulate photosynthetic gas exchange, respiration rates and defend against pathogen entry. Cell shape changes are determined by the interplay of cell wall material properties and turgor pressure. To investigate this relationship between turgor pressure, cell wall properties and cell shape, we focused on kidney‐shaped stomata and developed a biomechanical model of a guard cell pair. Treating the cell wall as a composite of the pectin‐rich cell wall matrix embedded with cellulose microfibrils, we show that strong, circumferentially oriented fibres are critical for opening. We find that the opening dynamics are dictated by the mechanical stress response of the cell wall matrix, and as the turgor rises, the pectinaceous matrix stiffens. We validate these predictions with stomatal opening experiments in selected Arabidopsis cell wall mutants. Thus, using a computational framework that combines a 3D biomechanical model with parameter optimization, we demonstrate how to exploit subtle shape changes to infer cell wall material properties. Our findings reveal that proper stomatal dynamics are built on two key properties of the cell wall, namely anisotropy in the form of hoop reinforcement and strain stiffening.
Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid β (Aβ1‐40) administration in mice

Ghrelin is a metabolic hormone that has neuroprotective actions in a number of neurological conditions, including Parkinson's disease (PD), stroke and traumatic brain injury. Acyl ghrelin treatment in vivo and in vitro also shows protective capacity in Alzheimer's disease (AD). In the present study, we used ghrelin knockout (KO) and their wild‐type littermates to test whether or not endogenous ghrelin is protective in a mouse model of AD, in which human amyloid β peptide 1‐40 (Aβ1‐40) was injected into the lateral ventricles i.c. v. Recognition memory, using the novel object recognition task, was significantly impaired in ghrelin KO mice and after i.c. v. Aβ1‐40 treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Spatial orientation, as assessed by the Y‐maze task, was also significantly impaired in ghrelin KO mice and after i.c. v. Aβ1‐40 treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Ghrelin KO mice had deficits in olfactory discrimination; however, neither i.c. v. Aβ1‐40 treatment, nor acyl ghrelin injections affected olfactory discrimination. We used stereology to show that ghrelin KO and Aβ1‐40 increased the total number of glial fibrillary acidic protein expressing astrocytes and ionised calcium‐binding adapter expressing microglial in the rostral hippocampus. Finally, Aβ1‐40 blocked long‐term potentiation induced by high‐frequency stimulation and this effect could be acutely blocked with co‐administration of acyl ghrelin. Collectively, our studies demonstrate that ghrelin deletion affects memory performance and also that acyl ghrelin treatment may delay the onset of early events of AD. This supports the idea that acyl ghrelin treatment may be therapeutically beneficial with respect to restricting disease progression in AD.
Effect Modification of Hormonal Therapy by p53 Status in Invasive Breast Cancer

Purpose We aimed to confirm the prognostic and predictive value of p53 expression, particularly in invasive breast cancer patients, according to immunohistochemical hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Methods Immunohistochemical data for p53, estrogen receptor, progesterone receptor, and HER2 expression from a total of 15,598 patients were retrospectively retrieved from the web-based database of the Korean Breast Cancer Society. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated and compared using the Kaplan-Meier method and log-rank test, respectively. Multivariate analyses were performed using a stratified Cox proportional hazard regression model. A model evaluating interactions between p53 expression and both hormonal therapy and chemotherapy was used to determine the treatment benefit from both modalities. Results The prognostic value of p53 for OS and BCSS was most significant in the HR+/HER2- subgroup, with hazard ratios of 1.44 (95% confidence interval [CI], 1.08-1.93) and 1.47 (95% CI, 1.09-1.99), respectively. The p53 overexpression hazard ratios were of borderline significance for the HR+/HER2+ subgroup and were not significant for the HR-/HER2+ and HR-/HER2- subgroups. The model with interaction terms revealed that hormonal therapy significantly interacts with p53 status (p=0.002 and p=0.007 for OS and BCSS, respectively), suggesting an insignificant prognostic value for p53 status (p=0.268 and p=0.296 for OS and BCSS, respectively). An interaction between chemotherapy and p53 status was not found in this model. Conclusion p53 overexpression has independent prognostic value, particularly in cases of HR+/HER2- invasive breast cancer, which may be due to effect modification of hormonal therapy dependent on p53 status.
Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise.

We examined the relationship between tricarboxylic acid (TCA) cycle intermediate (TCAI) pool size, TCA cycle flux (calculated from leg O2uptake), and pyruvate dehydrogenase activity (PDHa) in human skeletal muscle. Six males performed moderate leg extensor exercise for 10 min, followed immediately by intense exercise until exhaustion (3.8 ± 0.5 min). The sum of seven measured TCAI (ΣTCAI) increased ( P ≤ 0.05) from 1.39 ± 0.11 at rest to 2.88 ± 0.31 after 10 min and to 5.38 ± 0.31 mmol/kg dry wt at exhaustion. TCA cycle flux increased ∼70-fold during submaximal exercise and was ∼100-fold higher than rest at exhaustion. PDHa corresponded to 77 and 90% of TCA cycle flux during submaximal and maximal exercise, respectively. The present data demonstrate that a tremendous increase in TCA cycle flux can occur in skeletal muscle despite a relatively small change in TCAI pool size. It is suggested that the increase in ΣTCAI during exercise may primarily reflect an imbalance between the rate of pyruvate production and its rate of oxidation in the TCA cycle.
Dynamic In Vivo Profiling of DNA Damage and Repair after Radiotherapy Using Canine Patients as a Model

Time resolved data of DNA damage and repair after radiotherapy elucidates the relation between damage, repair, and cell survival. While well characterized in vitro, little is known about the time-course of DNA damage response in tumors sampled from individual patients. Kinetics of DNA damage after radiotherapy was assessed in eight dogs using repeated in vivo samples of tumor and co-irradiated normal tissue analyzed with comet assay and phosphorylated H2AX (γH2AX) immunohistochemistry. In vivo results were then compared (in silico) with a dynamic mathematical model for DNA damage formation and repair. Maximum %DNA in tail was observed at 15–60 min after irradiation, with a rapid decrease. Time-courses of γH2AX-foci paralleled these findings with a small time delay and were not influenced by covariates. The evolutionary parameter search based on %DNA in tail revealed a good fit of the DNA repair model to in vivo data for pooled sarcoma time-courses, but fits for individual sarcoma time-courses suffer from the heterogeneous nature of the in vivo data. It was possible to follow dynamics of comet tail intensity and γH2AX-foci during a course of radiation using a minimally invasive approach. DNA repair can be quantitatively investigated as time-courses of individual patients by integrating this resulting data into a dynamic mathematical model.
Downregulation of caveolin by chronic β-adrenergic receptor stimulation in mice.

Caveolae, flask-shaped invaginations of cell membranes, are believed to play pivotal roles in transmembrane transportation of molecules and cellular signaling. Caveolin, a structural component of caveolae, interacts directly with G proteins and regulates their function. We investigated the effect of chronic β-adrenergic receptor stimulation on the expression of caveolin subtypes in mouse hearts by immunoblotting and Northern blotting. Caveolin-1 and -3 were abundantly expressed in the heart and skeletal muscles, but not in the brain. Continuous (-)-isoproterenol, but not (+)-isoproterenol, infusion via osmotic minipump (30 μg ⋅ g-1 ⋅ day-1) for 13 days significantly downregulated both caveolin subtypes in the heart. The expression of caveolin-1 was reduced by 48 ± 6.1% and that of caveolin-3 by 28 ± 4.0% ( P < 0.01, n = 8 for each). The subcellular distribution of caveolin subtypes in ventricular myocardium was not altered as determined by sucrose gradient fractionation. In contrast, the expression of both caveolin subtypes in skeletal muscles was not significantly changed. Our data suggest that the expression of caveolin subtypes is regulated by β-adrenergic receptor stimulation in the heart.