Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality of life and other outcomes in children treated for Cushing syndrome.

CONTEXT Cushing syndrome (CS) in children is associated with residual impairment in measures of health-related quality of life, even after successful resolution of hypercortisolemia, highlighting the need for early identification of morbidities and improvements in long-term management of these patients. EVIDENCE ACQUISITION AND SYNTHESIS A PubMed, Scopus, and Web of Science search of articles from 1900 onward identified available studies related to quality of life and complications of pediatric CS as well as important historical articles. This review summarizes studies through November 2012 and highlights recent developments. CONCLUSIONS A review of the literature identifies significant morbidities associated with CS of pediatric onset, which must not be treated in isolation. CS affects children and adolescents in many ways that are different than adults. Post-treatment challenges for the child or adolescent treated for CS include: optimize growth and pubertal development, normalize body composition, and promote psychological health and cognitive maturation. All these factors impact health-related quality of life, which is an important outcome measure to assess the burden of disease as well as the effect of treatment. Future research efforts are needed to improve management of the physical, psychological, and emotional aspects of this disease in order to diminish the residual impairments experienced by the pediatric CS patient population.
Effect of capacitive coupled electrical stimulation on regenerate bone

An in vivo study was carried out to determine if capacitive coupled electrical stimulation increased the rate of recovery of strength of regenerate bone produced as a result of lengthening by the Ilizarov technique. Thirty‐four adult male beagles underwent a right tibial mid‐diaphyseal corticotomy, followed by a 5‐day delay, and then 21 days of lengthening (1 mm/day). At the start of the post‐distraction period (day 27), stimulation (3–6.3 V peak to peak, 5–10 mA root‐mean‐square at 60 kHz) was applied for 28 days to one group. The nonstimulated group (n = 17) underwent a 28‐day period with no stimulation. From each group, four tibiae were prepared for histology; both ends of the remaining bones were embedded in polymethylmethacrylate and tested in torsion (internal rotation at 4.7°/sec) until failure. Statistically significant changes included a 37% lower maximum torque capacity and a 40% decrease in strain energy to failure in the stimulated group compared with the nonstimulated group. The findings are supported by measured trends to a lower modulus of rigidity (37% decrease) and a smaller percentage of active osteoid perimeter (20% decrease) for the stimulated group. The experimental data suggest that when this dose of capacitive coupled electrical stimulation is applied to the regenerating bone created during distraction osteogenesis, it delays the recovery of bone strength compared with an untreated control.
Dose-response Relationship in Differentiated Thyroid Cancer Patients Undergoing Radioiodine Treatment Assessed by Means of 124 I PET/CT

The dose-response relationship in a fixed-activity approach generally applied in the treatment of differentiated thyroid cancer is assessed using 124 I PET/CT. Methods: Pre-therapeutic 124 I PET/CT images of 47 patients scheduled for radioiodine therapy were retrospectively analyzed. 124 I PET/CT images were acquired 24 and 96 hours after oral administration of approximately 28 MBq 124 I-sodium iodide. Lesions were identified as thyroid remnants or metastases (lymph node, lung, bone). After applying a neoteric segmentation technique allowing accurate volume estimation down to the 124 I PET spatial resolution of 0.15 mL, lesions were divided in a known-volume group and a small-volume group. For the known-volume group, average lesion absorbed dose (AD) values were calculated, whereas for the small-volume group a minimum lesion AD was estimated. Lesion response was determined based on 124 I PET/CT and 131 I single photon emission computed tomography(/computed tomography) (SPECT/CT) follow-up images. A lesion not detectable on any of the follow-up images was considered a completely responding lesion. Differences in lesion AD estimations between completely and incompletely responding lesions were evaluated by Mann-Whitney U test. Moreover, receiver-operator-characteristics (ROC) curves were used to test the performance of pretherapeutic 124 I PET/CT lesion AD for prediction of complete lesion response. Results: In the approach of fixed radioiodine activity (3.0 ± 1.0 GBq), 89% of thyroid remnants and 69% of metastases responded completely. Except for the small-volume groups, the lesion AD of completely responding lesions was significantly higher compared to that of incompletely responding lesions. Using ROC curve analysis, it was shown that for the known-volume group, pre-therapeutic 124 I PET/CT lesion dosimetry can be used as a prognostic tool to predict lesion-based 131 I therapy response with an area under the curve of 0.76 for remnants and 0.97 for metastases. The corresponding lesion AD threshold value maximizing correct complete response prediction was 90 Gy for remnants and 40 Gy for metastases. Conclusion: In a fixed-activity approach, a statistically significant dose-response relationship for both thyroid remnants and metastases using pretherapeutic 124 I PET/CT lesion dosimetry was found. The findings may be useful in patient management.
Why is it Difficult to Detect Sudden and Unexpected Epidemic Outbreaks in Twitter?

Social media services such as Twitter are a valuable source of information for decision support systems. Many studies have shown that this also holds for the medical domain, where Twitter is considered a viable tool for public health officials to sift through relevant information for the early detection, management, and control of epidemic outbreaks. This is possible due to the inherent capability of social media services to transmit information faster than traditional channels. However, the majority of current studies have limited their scope to the detection of common and seasonal health recurring events (e.g., Influenza-like Illness), partially due to the noisy nature of Twitter data, which makes outbreak detection and management very challenging. Within the European project M-Eco, we developed a Twitter-based Epidemic Intelligence (EI) system, which is designed to also handle a more general class of unexpected and aperiodic outbreaks. In particular, we faced three main research challenges in this endeavor: 1) dynamic classification to manage terminology evolution of Twitter messages, 2) alert generation to produce reliable outbreak alerts analyzing the (noisy) tweet time series, and 3) ranking and recommendation to support domain experts for better assessment of the generated alerts. In this paper, we empirically evaluate our proposed approach to these challenges using real-world outbreak datasets and a large collection of tweets. We validate our solution with domain experts, describe our experiences, and give a more realistic view on the benefits and issues of analyzing social media for public health.
PimF, a Mannosyltransferase of Mycobacteria, Is Involved in the Biosynthesis of Phosphatidylinositol Mannosides and Lipoarabinomannan*

Phosphatidylinositol mannosides (PIMs) and their related molecules lipomannan (LM) and lipoarabinomannan (LAM) are important components of the mycobacterial cell wall. These molecules mediate host-pathogen interactions and exhibit immunomodulatory activities. The biosynthesis of these lipoglycans is not fully understood. In this study, we have identified a mycobacterial gene (Rv1500) that is involved in the synthesis of PIMs. We have named this gene pimF. Transposon mutagenesis of pimF of Mycobacterium marinum resulted in multiple phenotypes, including altered colony morphology, disappearance of tetracyl-PIM7, and accumulation of tetraacyl-PIM5. The syntheses of LAM and LM were also affected. In addition, the pimF mutant exhibited a defect during infection of cultured macrophage cells. Although the mutant was able to replicate and persist within macrophages, the initial cell entry step was inefficient. Transformation of the M. marinum mutant with the pimF homolog of Mycobacterium tuberculosis complemented all of the above mentioned phenotypes. These results provide evidence that PimF is a mannosyltransferase. However, sequence analysis indicates that PimF is distinct from mannosyltransferases involved in the early steps of PIM synthesis. PimF catalyzes the formation of high molecular weight PIMs, which are precursors for the synthesis of LAM and LM. As such, this work marks the first analysis of a mannosyltransferase involved in the later stages of PIM synthesis.
Inhibitors of the V0 subunit of the vacuolar H+-ATPase prevent segregation of lysosomal- and secretory-pathway proteins

The vacuolar H+-ATPase (V-ATPase) establishes pH gradients along secretory and endocytic pathways. Progressive acidification is essential for proteolytic processing of prohormones and aggregation of soluble content proteins. The V-ATPase V0 subunit is thought to have a separate role in budding and fusion events. Prolonged treatment of professional secretory cells with selective V-ATPase inhibitors (bafilomycin A1, concanamycin A) was used to investigate its role in secretory-granule biogenesis. As expected, these inhibitors eliminated regulated secretion and blocked prohormone processing. Drug treatment caused the formation of large, mixed organelles, with components of immature granules and lysosomes and some markers of autophagy. Markers of the trans-Golgi network and earlier secretory pathway were unaffected. Ammonium chloride and methylamine treatment blocked acidification to a similar extent as the V-ATPase inhibitors without producing mixed organelles. Newly synthesized granule content proteins appeared in mixed organelles, whereas mature secretory granules were spared. Following concanamycin treatment, selected membrane proteins enter tubulovesicular structures budding into the interior of mixed organelles. shRNA-mediated knockdown of the proteolipid subunit of V0 also caused vesiculation of immature granules. Thus, V-ATPase has a role in protein sorting in immature granules that is distinct from its role in acidification.
Vitamin D Deficiency in Patients with Central Retinal Vein Occlusion: A Case Control Study

ABSTRACT Purpose: Central retinal vein occlusion (CRVO) has been shown to occur more often in winter/spring season. We aimed to evaluate if patients with CRVO have more vitamin D deficiency compared to matched controls. Methods: Prospective match controlled study of 72 patients with CRVO and 144 matched controls. All new CRVO cases presenting at St. Erik Eye Hospital, Stockholm, Sweden during the study period were approached to participate. Statistics Sweden provided randomly selected controls matched for age, gender, and season. The first 18 cases of CRVO and 36 controls for each of the four seasons were included and blood was drawn for 25-OH vitamin D analysis (25(OH)D). Results: About half of the patients (51.4%) in the CRVO group had vitamin D deficiency [25(OH)D < 50 nmol/l] as compared to 39.3% in the control group [odds ratio 1.64, 95% confidence interval (CI) 0.91–2.94]. The mean concentrations of serum 25(OH)D were 55.3 nmol/l (95% CI 48.4–62.2) in the study group and 59.8 nmol/l (95% CI 55.4–64.2) in the control group (p = 0.28). In stratified analysis, the CRVO patients under 75 years had significantly lower 25(OH)D levels than the matched controls (47.8 nmol/l vs. 59.0 nmol/l, p = 0.02). Conclusions: Vitamin D deficiency is common in patients with CRVO. No significant differences in vitamin deficiency or 25(OH)D levels were found in comparison to the control group. However, the CRVO patients under 75 years had significantly lower 25(OH)D levels as compared to the control group.
A Note On Side-Channels Resulting From Dynamic Compilation

Dynamic compilation systems are of fundamental importance to high performance execution of interpreted languages such as Java. These systems analyse the performance of an application at runtime and aggressively re-compile and optimise code which is deemed critical to performance. However, the premise that the code executed is not the same code as written by the programmer raises a number of important security concerns. In this paper we examine the specific problem that dynamic compilation, through transformation of the code, may introduce side-channel vulnerabilities where before there were none.
RADIATION RESISTANCE WITH AGE IN NORMAL AND IRRADIATED POPULATIONS OF MICE.

These considerations also apply to the problem of estimating residual radiation injury in irradiated populations at long times after the initial exposure. In this context, residual radiation injury refers to that component of irreparable injury that can be detected as an increased sensitivity to the acute lethal effects of further radiation exposure at times beyond the phase of acute injury and recovery after the initial exposure (6-11). The extent of this injury is usually measured by the classical "split-dose" technique (6). On the basis of the assumptions and definitions utilized in this technique, residual injury usually amounts to about 5 to 10% of the total injury sustained after the initial exposure (90 to 95% of the injury is repaired). It is often assumed that the level of residual injury remains constant throughout the remaining life of the animal, but experimental data are not entirely adequate to support this assumption. The derived impulse lethality function of Sacher and Grahn (12) suggests an ever more slowly decreasing level of injury throughout life after a single exposure. This function is based on data obtained by
FUNCTION ALGEBRAS AND THE LATTICE OF COMPACTIFICATIONS

We provide some conditions as to when K(X) _ K(Y) for two locally compact spaces X and Y (where K(X) is the lattice of all Hausdorff compactifications of X). More specifically, we prove that K(X) C K(Y) if and only if C*(X)/Co(X) C*(Y)/Co(Y). Using this result, we prove several extensions to the case where K(X) is embedded as a sub-lattice of K(Y) and to where X and Y are not locally compact. One major contribution is in the use of function algebra techniques. The use of these techniques makes the extensions simple and clean and brings new tools to the subject.
Functional Coupling between Sulfonylurea Receptor Type 1 and a Nonselective Cation Channel in Reactive Astrocytes from Adult Rat Brain

We previously identified a novel, nonselective cation channel in native reactive (type R1) astrocytes (NR1As) from injured rat brain that is regulated by cytoplasmic Ca2+ and ATP (NCCa-ATP) and exhibits sensitivity to block by adenine nucleotides similar to that of sulfonylurea receptor type 1 (SUR1). Here we show that SUR1 is involved in regulation of this channel. NR1As within the site of injury and after isolation exhibited specific binding of FITC-tagged glibenclamide and were immunolabeled with anti-SUR1 antibody, but not with anti-SUR2, anti-Kir6.1 or anti-Kir6.2 antibodies, indicating absence of ATP-sensitive K+ (KATP) channels. RT-PCR confirmed transcription of mRNA for SUR1 but not SUR2. Several properties previously associated exclusively with SUR1-regulated KATP channels were observed in patch-clamp experiments using Cs+ as the charge carrier: (1) the sulfonylureas, glibenclamide and tolbutamide, inhibited NCCa-ATP channels with EC50 values of 48 nm and 16.1 μm, respectively; (2) inhibition by sulfonylureas was lost after exposure of the intracellular face to trypsin or anti-SUR1 antibody; (3) channel inhibition was caused by a change in kinetics of channel closing, with no change in channel amplitude or open-channel dwell times; and (4) the SUR activator (“KATP channel opener”), diazoxide, activated the NCCa-ATP channel, whereas pinacidil and cromakalin did not. Also, glibenclamide prevented cell blebbing after ATP depletion, whereas blebbing was produced by exposure to diazoxide. Our data indicate that SUR1 is functionally coupled to the pore-forming portion of the NCCa-ATP channel, providing the first demonstration of promiscuity of SUR1 outside of the K+ inward rectifier family of channels.
The Association between Stress Level in Daily Life and Age at Natural Menopause in Korean Women: Outcomes of the Korean National Health and Nutrition Examination Survey in 2010-2012

Background Although several risk factors associated with reduced age at natural menopause (ANM) have been investigated, the results are inconsistent. Excessive stress, which leads to elevation of stress hormones, can also negatively affect reproductive ability, including by accelerating menopause. However, a direct association between stress level and ANM has not yet been demonstrated. Therefore, the object of this study was to investigate the association between stress level and ANM in Korean women. Methods Study participants were Korean women between 40 and 70 years old who were in natural menopause during the 5th Korean National Health and Nutrition Examination Survey (n=3,176). The level of stress in daily life was estimated based on data from the mental health topics of the survey. We used the t-test and one-way analysis of variance to analyze the correlation between stress level and ANM. Regression (β) coefficients calculated by multiple regression analysis were used to estimate various factors affecting ANM. Results Women who experienced a high level of stress in daily life had a lower mean ANM than women with a low stress level (50.17±3.7 and 50.58±3.5 years, respectively), with a statistically significant correlation (P<0.05). This correlation was still observed after adjusting for age, body mass index, menstrual regularity, and personal income (P<0.05 for variables). Conclusion In Korean women between 40 and 70 years of age who are in natural menopause, there is a statistically significant correlation between stress level and ANM. In particular, women who experience a high level of stress in daily life have reduced ANM.
Taxonomic and functional diversity of the co‐flowering community differentially affect Cakile edentula pollination at different spatial scales

The number of co‐flowering species, floral density and floral trait diversity can be major determinants of pollinator‐mediated plant–plant interactions in a community. However, evaluation of how each one of these co‐flowering components affects the pollination success of a single focal plant species, and how these effects vary at different spatial scales, is lacking. Here, we evaluated the effects of functional diversity (flower morphology and colour), taxonomic diversity (reflecting potential sampling effects) and flower density (conspecific and heterospecific), on the pollinator environment (i.e. visitation rate and pollinator diversity) and pollination success (i.e. pollen load size and number of pollen tubes per style) of Cakile edentula (Brassicaceae). We applied structural equation models (SEMs) at the floral‐neighbourhood (plot level) and community‐wide scales to uncover the factors that mediate co‐flowering community effects on C. edentula pollination success. We found that co‐flowering community effects at the community level are more important than fine‐scale floral‐neighbourhood differences in mediating plant pollination success in our study species. Increasing plant functional diversity decreased pollinator visitation rate but increased the diversity of pollinator functional groups visiting C. edentula flowers. Taxonomic diversity negatively affected pollinator diversity suggesting that other unmeasured floral traits may be relevant or that single‐species effects (sampling effects) may be important. Overall, our results suggest that functional floral trait diversity in a community may be the most important factor influencing pollination success of species in a community. We also found evidence for intra‐ and interspecific pollinator competition mediated by flower density, but none of these effects seemed to have a significant impact on pollination success. This study is an important step towards understanding the complexity of co‐flowering community effects on the pollination success of individual plant species at multiple spatial scales. This study further reveals the potential importance of plant functional diversity in a community in helping predict competitive and facilitative interactions in co‐flowering communities. Synthesis. Floral density and taxonomic and functional co‐flowering diversity are important drivers of pollination success in flowering plants. The effects of the co‐flowering diversity on the pollination success of plant species can largely depend on the spatial scale being studied. Only evaluating the outcomes of pollinator‐mediated plant–plant interactions at multiple stages of the pollination process can lead to a complete understanding of their ecological consequences in nature.
Breast Cancer Cells Can Evade Apoptosis-Mediated Selective Killing by a Novel Small Molecule Inhibitor of Bcl-2

Proteins of the Bcl-2 family are key regulators of caspase activation and apoptosis. Some members of this family, notably Bcl-2 and Bcl-xL, are overexpressed in cancer cells, which have been associated with chemoresistance. We have designed and synthesized a small molecule inhibitor of Bcl-2, named YC137, and studied its role in cancer cells. In vitro studies showed that YC137 inhibits the binding of the Bid BH3 peptide to Bcl-2, thus disrupting an interaction essential for the antiapoptotic activity of Bcl-2. This inhibitor induces apoptosis of hematopoietic progenitors overexpressing Bcl-2 but not Bcl-xL and breast cancer cells that express high levels of Bcl-2. On the contrary, a variety of normal primary cells, including CD34+ progenitors, myoblasts, and peripheral blood mononuclear cells, do not respond to the inhibitor. A breast cancer cell line resistant to YC137 was generated. Analysis of resistant cells revealed a reduced expression of Bcl-2, which correlated with low activation of signal transducer and activator of transcription-3 (Stat3) and reduced expression of the human epidermal growth factor receptor-2 (HER2). Of note, YC137-resistant cells were more sensitive to apoptosis induced by chemotherapy. Because HER2 has not been linked previously to the Stat3-Bcl-2 transcriptional pathway, we additionally confirmed that specific blockade of HER2 in breast cancer cells resulted in down-regulation of Stat3 activity and reduced levels of Bcl-2. Consistently, HER2 blockade led to YC137 resistance. These data provide evidence for the selective killing of tumor cells by YC137 and represent the first example of in vitro selection of cancer cells refractory to a Bcl-2 inhibitor.