Miracle-dz/UniFAR-FTUs huggingface dataset:
PRACTICE VARIATION IN THE MANAGEMENT OF GIRLS AND BOYS WITH DELAYED PUBERTY.

Objective: Delayed puberty is a common condition, and typical management includes "watchful waiting" and/or sex-steroid therapy. We sought to characterize treatment practices and to assess provider comfort with the management of delayed puberty in girls and boys. Methods: A national survey of pediatric endocrine providers assessed definitions of delayed puberty, practices around sex-steroid therapy, reasons for treatment, and comfort in managing delayed puberty in girls and boys. Results: Of 184 respondents (12% participation rate), 64% and 71% used the traditional age cutoffs for defining delayed puberty of 13 years for girls and 14 years for boys, respectively. Nearly half (45%) of providers would treat boys relatively earlier than girls, compared to 18% who would treat girls relatively earlier (p<0.0001). Providers were more likely to cite bone density as a reason to treat girls and alleviating patient and parental distress, accelerating growth, and "jump starting" puberty as reasons to treat boys. Greater experience in endocrine practice was associated with greater comfort managing delayed puberty in both boys and girls. Approximately 80% of providers agreed that clinical guidelines are needed for management of delayed puberty. Conclusion: There is a high degree of variability in the clinical management of delayed puberty, and our results suggest that providers are more hesitant to treat girls compared to boys and have different reasons for treating each. It remains to be determined if these discrepancies in treatment are justified by biological differences between girls and boys or represent non-evidence-based disparities in care.
Inflammation both increases and causes resistance to FGF23 in normal and uremic rats.

Fibroblast growth factor 23 (FGF23) increases phosphorus excretion and decreases calcitriol levels. FGF23 increases from early stages of renal failure. We evaluated whether strict control of phosphorus intake in renal failure prevents the increase in FGF23 and to what extent inflammation impairs regulation of FGF23. The study was performed in 5/6 nephrectomized (Nx) Wistar rats fed diets containing 0.2 to 1.2% phosphorus for 3 or 15 days. FGF23 levels significantly increased in all Nx groups in the short-term (3-day) experiment. However, at 15 days, FGF23 increased in all Nx rats except in those fed 0.2% phosphorus. In a second experiment, Nx rats fed low phosphorus diets (0.2 and 0.4%) for 15 days received daily intraperitoneal lipopolysaccharide (LPS) injections to induce inflammation. In these rats, FGF23 increased despite the low phosphorus diets. Thus, higher FGF23 levels were needed to maintain phosphaturia and normal serum phosphorus values. Renal Klotho expression was preserved in Nx rats on a 0.2% phosphorus diet, reduced on a 0.4% phosphorus diet, and markedly reduced in Nx rats receiving LPS. In ex vivo experiments, high phosphorus and LPS increased nuclear b-catenin and p65-NFkB and decreased Klotho. Inhibition of inflammation and Wnt signalling activation resulted in decreased FGF23 levels and increased renal Klotho. In conclusion, strict control of phosphorus intake prevented the increase in FGF23 in renal failure, whereas inflammation independently increased FGF23 values. Decreased Klotho may explain the renal resistance to FGF23 in inflammation. These effects are likely mediated by the activation of NFkB and Wnt/b-catenin signalling.
Virtual non-contrast for evaluation of liver parenchyma and vessels: results from 25 patients using multi-phase spectral-detector CT

Background In abdominal imaging, contrast-enhanced computed tomography (CT) examinations are most commonly applied; however, unenhanced examinations are still needed for several clinical questions but require additional scanning and radiation exposure. Purpose To evaluate accuracy of virtual non-contrast (VNC) from arterial and venous phase spectral-detector CT (SDCT) scans compared to true-unenhanced (TNC) images for the evaluation of liver parenchyma and vessels. Material and Methods A total of 25 patients undergoing triphasic SDCT examinations were included. VNC was reconstructed from arterial and venous phases and compared to TNC images. Quantitative image analysis was performed by region of interest (ROI)-based assessment of mean and SD of attenuation (HU) in each liver segment, spleen, portal vein, common hepatic artery, and abdominal aorta. Subjectively, iodine subtraction and diagnostic assessment were rated on 5-point Likert scales. Results Attenuation and image noise measured in the liver from VNC were not significantly different from TNC (TNC: 54.6 ± 10.8 HU, VNC arterial phase: 55.7 ± 10.8 HU; VNC venous phase: 58.3 ± 10.0 HU; P > 0.05). VNC also showed accurate results regarding attenuation and image noise for spleen, portal vein, and abdominal aorta. Only iodine subtraction in the common hepatic artery in the arterial phase was insufficient which was confirmed by the subjective reading. Apart from that, subjective reading showed accurate iodine subtraction and comparable diagnostic assessment. Conclusion VNC from the arterial and venous phases were very similar to TNC yielding mostly negligible differences in attenuation, image noise, and diagnostic utility. Inadequate iodine subtraction occurred in hepatic arteries in the arterial phase.
Activation of alpha‐2 adrenergic receptors stimulates GABA release by astrocytes

Norepinephrine is one of the key neurotransmitters in the hippocampus, but its role in the functioning of the neuroglial networks remains unclear. Here we show that norepinephrine suppresses NH4Cl‐induced oscillations of the intracellular Ca2+ concentration ([Ca2+]i) in hippocampal neurons. We found that the inhibitory effect of norepinephrine against ammonium‐induced [Ca2+]i oscillations is mediated by activation of alpha‐2 adrenergic receptors. Furthermore, UK 14,304, an agonist of alpha‐2 adrenergic receptors, evokes a biphasic [Ca2+]i elevation in a minor population of astrocytes. This elevation consists of an initial fast, peak‐shaped [Ca2+]i rise, mediated by Giβγ subunit and subsequent PLC‐induced mobilization of Ca2+ from internal stores, and a plateau phase, mediated by a Ca2+ influx from the extracellular medium through store‐operated and TRPC3 channels. We show the correlation between the Ca2+ response in astrocytes and suppression of [Ca2+]i oscillations in neurons. The inhibitory effect of UK 14,304 is abolished in the presence of gallein, an inhibitor of Gβγ‐signaling. In turn, application of the agonist in the presence of the PLC inhibitor decreases the frequency and amplitude of [Ca2+]i oscillations in neurons but does not suppress them. The same effect is observed in the presence of bicuculline, a GABA(A) receptor antagonist. We demonstrate that UK 14,304 application increases the frequency and amplitude of slow outward chloride currents in neurons, indicating the release of GABA by astrocytes. Thus, our findings indicate that the activation of astrocytic alpha‐2 adrenergic receptors stimulates GABA release from astrocytes via Giβγ subunit‐associated signaling pathway, contributing to the suppression of neuronal activity.
Candidates for photic entrainment pathways to the circadian clock via optic lobe neuropils in the Madeira cockroach

The compound eye of cockroaches is obligatory for entrainment of the Madeira cockroach's circadian clock, but the cellular nature of its entrainment pathways is enigmatic. Employing multiple‐label immunocytochemistry, histochemistry, and backfills, we searched for photic entrainment pathways to the accessory medulla (AME), the circadian clock of the Madeira cockroach. We wanted to know whether photoreceptor terminals could directly contact pigment‐dispersing factor‐immunoreactive (PDF‐ir) circadian pacemaker neurons with somata in the lamina (PDFLAs) or somata next to the AME (PDFMEs). Short green‐sensitive photoreceptor neurons of the compound eye terminated in lamina layers LA1 and LA2, adjacent to PDFLAs and PDFMEs that branched in LA3. Long UV‐sensitive compound eye photoreceptor neurons terminated in medulla layer ME2 without direct contact to ipsilateral PDFMEs that arborized in ME4. Multiple neuropeptide‐ir interneurons branched in ME4, connecting the AME to ME2. Before, extraocular photoreceptors of the lamina organ were suggested to send terminals to accessory laminae. There, they overlapped with PDFLAs that mostly colocalized PDF, FMRFamide, and 5‐HT immunoreactivities, and with terminals of ipsi‐ and contralateral PDFMEs. We hypothesize that during the day cholinergic activation of the largest PDFME via lamina organ photoreceptors maintains PDF release orchestrating phases of sleep–wake cycles. As ipsilateral PDFMEs express excitatory and contralateral PDFMEs inhibitory PDF autoreceptors, diurnal PDF release keeps both PDF‐dependent clock circuits in antiphase. Future experiments will test whether ipsilateral PDFMEs are sleep‐promoting morning cells, while contralateral PDFMEs are activity‐promoting evening cells, maintaining stable antiphase via the largest PDFME entrained by extraocular photoreceptors of the lamina organ.
Study of biofilm formation in bacterial isolates from contact lens wearers

Purpose: To detect biofilm forming capacity of bacterial isolates obtained from the conjunctiva, contact lens and accessories of contact lens wearers using phenotypic and genotypic methods. Methods: Bacterial strains were collected from the conjunctiva, contact lens and lens storage cases of contact lens wearers. The phenotypic detection of biofilm production was done using the tube method and congo red agar method. The biofilm-forming related genes, icaA, of Coagulase negative Staphylococcus (CONS) and Staphylococcus aureus, and pslA, of P. aeruginosa, were detected using PCR. Results: A total of 265 bacterial isolates which included S. aureus, CONS, Pseudomonas, Nil-fermenter Gram-negative bacilli (NFGNB), Bacillus spp, Diphtheroids, Micrococci, Klebsiella pneumonia, Klebsiella oxytoca, E. coli, Proteus mirabilis, Proteus vulgaris, Citrobacter koseri, Citrobacter freundii, Enterobacter cloacae, Moraxella were obtained. Of the 265 isolates, 53.5% were moderately positive, 33.2% strongly positive and 13.2% negative for biofilm production by tube method and 36.6% were moderately positive, 40% strongly positive and 23.3% negative for biofilm production by congo red agar method. Of the four S. aureus isolates, two (50%) showed the presence of icaA gene. Of the 23 CONS isolates, three (13%) showed the presence of icaA gene. All the Pseudomonas isolates were negative for presence pslA (1119 bp) gene though most of them were phenotypically positive for biofilm formation. Conclusion: Most of the bacterial isolates obtained from contact lens wearers had the potential to produce biofilms. Tube method and Congo red agar method exhibited significant statistical correlation (P-value = 0.006) and picked up a good number of biofilm-forming isolates, hence may be used for detection of biofilm production. The absence of biofilm-forming gene did not rule out the possibility for phenotypic biofilm production by bacteria.
Living with ulcerative colitis in Germany: a retrospective analysis of dose escalation, concomitant treatment use and healthcare costs

Abstract Aims: To investigate treatment of moderate-to-severe ulcerative colitis (UC) using real-world German health insurance claims data. Materials and methods: A retrospective, longitudinal cohort study was conducted from a German statutory health insurance database for adult patients with UC indexed on biologic therapy initiation (2013–2015). Anonymized data were evaluated for 12 months prior to (baseline) through 24 months after (follow-up) indexing. Biologic dose escalations, steroid and immunosuppressant use, healthcare resource utilization (HCRU) and direct healthcare costs were evaluated, with significant differences assessed across and between index biologics. Descriptive statistics, chi-square or Fisher’s exact tests, and analysis of variance were performed. Results: The analysis included 304 patients (adalimumab, n = 125; golimumab, n = 47; infliximab, n = 114; vedolizumab, n = 18). Demographic and clinical characteristics were similar across biologics. Dose escalations occurred in 58% of patients (73% of patients receiving adalimumab), with 41% receiving subsequent de-escalation. Steroids were used during follow-up by 74% of patients; 25% received steroids >14 weeks after indexing. Overall, 41% of patients received an immunosuppressant during follow-up. Steroid and immunosuppressant use were similar across biologics. Total direct healthcare costs were higher during follow-up than baseline and differed significantly across treatments (p < .05), with highest costs for golimumab. Biologic costs contributed to a major portion of follow-up costs. HCRU and costs for most resources were higher in the first 12-month follow-up period than baseline. All resource use except gastroenterology visits returned to, or below, baseline levels 13–24 months post-index date. Limitations: There was potential for inappropriate inclusion/exclusion due to miscoding. Patients may have received biologics >12 months prior to the index date. Biologic originators and biosimilars could not be differentiated. Conclusions: These data suggest that control with current biologics is suboptimal. Further treatment options that provide sustained steroid-free remission for this patient population without the need for dose escalations or concomitant therapies may be warranted.
Long-term outcome of patients with non-operated prosthetic valve infective endocarditis: is relapse the main issue?

In non-operated prosthetic valve endocarditis (PVE), long term outcome is largely unknown. We report the follow-up of 129 non-operated patients with PVE alive at discharge. At one year, the mortality rate was 24%, relapses and reinfection were rare (5% each). Enterococcal PVE was associated with a higher risk of relapse.
Gait characteristics of post-stroke hemiparetic patients with different walking speeds

Hemiparesis resulting from stroke presents characteristic spatiotemporal gait patterns. This study aimed to clarify the spatiotemporal gait characteristics of hemiparetic patients by comparing them with height-, speed-, and age-matched controls while walking at various speeds. The data on spatiotemporal gait parameters of stroke patients and that of matched controls were extracted from a hospital gait analysis database. In total, 130 pairs of data were selected for analysis. Patients and controls were compared for spatiotemporal gait parameters and the raw value (RSI) and absolute value (ASI) of symmetry index and coefficient of variation (CV) of these parameters. Stroke patients presented with prolonged nonparetic stance (patients vs. controls: 1.01 ± 0.41 vs. 0.83 ± 0.25) and paretic swing time (0.45 ± 0.12 vs. 0.39 ± 0.07), shortened nonparetic swing phase (0.35 ± 0.07 vs. 0.39 ± 0.07), and prolonged paretic and nonparetic double stance phases [0.27 ± 0.13 (paretic)/0.27 ± 0.17 (nonparetic) vs. 0.22 ± 0.10]. These changes are especially seen in low-gait speed groups (<3.4 km/h). High RSIs of stance and swing times were also observed (–9.62 ± 10.32 vs. –0.79 ± 2.93, 24.24 ± 25.75 vs. 1.76 ± 6.43, respectively). High ASIs and CVs were more generally observed, including the groups with gait speed of ≥3.5 km/h. ASI increase of the swing phase (25.79 ± 22.69 vs. 4.83 ± 4.88) and CV of the step length [7.7 ± 4.9 (paretic)/7.6 ± 5.0 (nonparetic) vs. 5.3 ± 3.0] were observed in all gait speed groups. Our data suggest that abnormalities in the spatiotemporal parameters of hemiparetic gait should be interpreted in relation to gait speed. ASIs and CVs could be highly sensitive indices for detecting gait abnormalities.
Development of a topical tissue cross-linking solution using sodium hydroxymethylglycinate (SMG): viscosity effect

Abstract Hyperviscosity agents are commonly used in ophthalmic formulations for improving corneal drug penetration by increasing tissue contact time. One such viscosity agent is hydroxypropyl methylcellulose (HPMC). HPMC has been used in riboflavin solutions for photochemical UVA cross-linking (CXL). Sodium hydroxymethylglycinate (SMG) is a small molecule formaldehyde releaser that can function as a therapeutic tissue cross-linker for corneal and scleral applications. The present study was undertaken in order to study formulation factors using HPMC and SMG that could positively influence the cross-linking effect in these ocular tissues. Formulations containing 10 mM SMG and 100 mM sodium bicarbonate were prepared with varying HPMC concentrations from 0 to 4.4%. Their cross-linking effects on porcine and rabbit eyes were measured using differential scanning calorimetry (DSC), expressed as the change/difference in melting temperature (ΔTm) compared with the control. SMG in 4.4% HPMC solution resulted in ΔTm of 6.3 ± 1.21, while other concentration showed no differences in Tm shift on porcine cornea. In ex vivo rabbit cornea, there was a trend toward an increasing cross-linking effect with higher viscosity albeit mild differences. While a significant Tm shift was observed in porcine and rabbit sclera, there was no difference in effect of cross-linking between four HPMC concentrations. Increasing the HPMC concentration does not negatively affect the cross-linking efficacy attributed by SMG and could still be a positive cross-linking enhancer by virtue of increasing tissue contact time in a dynamic biological system. This information will be useful for planning further animal and human studies.
The role of ethylene in metabolic acclimations to low oxygen

Summary Submerged plants ultimately suffer from shortage in cellular oxygen availability (hypoxia) as a result of impaired gas diffusion underwater. The gaseous plant hormone ethylene is rapidly entrapped in submerged plant tissues and is an established regulator of morphological and anatomical flood‐adaptive responses. Multiple recent discoveries suggest that ethylene also plays a crucial role in hypoxia anticipation and metabolic acclimation during plant submergence. Ethylene was shown to accelerate and enhance the hypoxic response through enhanced stability of specific transcription factors (group VII ethylene response factors). Moreover, we suggest that ethylene could play an important role in the induction of autophagy and promote reactive oxygen species amelioration, thereby contributing to enhanced survival during flooding, hypoxia, and reoxygenation stress.
Novel ultrawide field fundus fluorescein angiographic findings in a patient of Takayasu arteritis on immunosuppression

A 35-year-old male, a case of Takayasu arteritis on treatment with oral prednisolone and methotrexate, revealed novel ultrawide field fluorescein angiographic features in bilateral eyes. The typical features of delayed arm-retina circulation time, lobulated areas of nonperfusion in choroid, cattle trucking of red blood cells in veins, and delayed arteriovenous transit time were nicely captured. Additionally, we noted peripheral perivascular hyperfluorescence and disc hyperfluorescence. We believe these findings could possibly be used as markers of disease activity. Lack of marked capillary nonperfusion areas and marked perivascular leakage probably signifies modulation of disease activity by the immunosuppressants.
iMIRAGE: an R package to impute microRNA expression using protein-coding genes

SUMMARY MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression. Due to challenges in accurate profiling of small RNAs, a vast majority of public transcriptome datasets lack reliable miRNA profiles. However, the biological consequence of miRNA activity in the form of altered protein-coding gene (PCG) expression can be captured using machine-learning algorithms. Here we present iMIRAGE (imputed miRNA activity from gene expression), a convenient tool to predict miRNA expression using PCG expression of the test datasets. The iMIRAGE package provides an integrated workflow for normalization and transformation of miRNA and PCG expression data, along with the option to utilize predicted miRNA targets to impute miRNA activity from independent test PCG datasets. AVAILABILITY The iMIRAGE package for R, along with package documentation and vignette, is available at https://aritronath.github. io/iMIRAGE/index.html. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Efficient Microchannel Cooling of Multiple Power Devices With Compact Flow Distribution for High Power-Density Converters

In this article, we describe a new approach for the compact and energy-efficient cooling of converters where multiple miniaturized microfluidic cold plates are attached to transistors providing local heat extraction. The high pressure drop associated with microchannels was minimized by connecting these cold plates in parallel using a compact three-dimensional-printed flow distribution manifold. We present the modeling, design, fabrication, and experimental evaluation of this microfluidic cooling system and provide a design strategy for achieving energy-efficient cooling with minimized pumping power. An integrated cooling system is experimentally demonstrated on a 2.5-kW switched-capacitor dc–dc converter, cooling down 20 GaN transistors. A thermal resistance of 0.2 K/W was measured at a flow rate of 1.2 mL/s and a pressure drop of 20 mbar, enabling the cooling of a total of 300 W of losses in the converter using several milliwatt of pumping power, which can be realized with small micropumps. Experimental results show a tenfold increase in power density compared with the conventional cooling, potentially up to 30 kW/L. This proposed cooling approach offers a new way of coengineering the cooling and the electronics together to achieve more compact and efficient power converters.
Narcissism, Body-Esteem and Selfie-taking behaviour among Teens and Adolescents

Background: One of the latest trends among the millennial is taking selfie which is the way of self presentation. It is thus imperative to probe the knowledge, attitude and perception of the groups toward this phenomenon. Objective: The present empirical research was done to investigate whether narcissism and body-esteem difference exist among selfie-taker teens and adolescents and to explore the inter relationship between narcissism and body-esteem. Methods & Material: This field study examined the narcissism and body-esteem of teens and adolescents who take 3-5 Selfies per day, chosen purposively. The study was conducted on 100 participants, 50 teens (25 girls & 25 boys) and 50 adolescents (25 girls & 25 boys). To measure the variables, Body-Esteem Scale by Franzoi & Shields (1984) and Narcissistic Personality Inventory by Raskin & Hall (1979) were applied. ‘t’-test was used to analyse the significant difference between the samples and correlation was employed to find out the association between the variables. Result: The findings on narcissism has shown that there was statistically significant difference between selfie -taker teens and adolescents and difference was also found between male’s and female’s selfie tendency. The data on body esteem has revealed that though there was no difference between selfie-taker teens and adolescents but significant difference was observed between male’s and female’s selfie-related behaviour. The result on correlation between narcissism and body-esteem among millennial (teens & adolescents) has shown positive interrelationship with each other. Conclusion: On the basis of research finding it can be concluded that level of narcissism and body-esteem may affect the selfie behaviour of teens and adolescents which in extreme case may lead to Body Dysmorphic Disorder, Eating Disorder, and Depression etc.