Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic Profiling of Glycerophospholipid Synthesis in Fibroblasts Loaded with Free Cholesterol and Modified Low Density Lipoproteins*

Currently, the detailed regulation of major pathways of glycerophospholipid synthesis upon cholesterol loading is largely unknown. Therefore, a detailed lipid metabolic profiling using stable isotope-labeled choline, ethanolamine, and serine was performed by quantitative electrospray ionization tandem mass spectrometry (ESI-MS/MS) in free cholesterol (FC), oxidized (Ox-LDL) and enzymatically modified LDL (E-LDL)-loaded primary human skin fibroblasts. As previously described, an adaptive induction of phosphatidylcholine (PC) synthesis via CDP-choline was found upon FC loading. In contrast to PC, CDP-ethanolamine-mediated phosphatidylethanolamine (PE) synthesis was inhibited by FC incubation. Furthermore, FC induced a shift toward polyunsaturated PE and PC species, which was mediated primarily by PE biosynthesis but not PE remodeling, whereas PC species were shifted mainly by fatty acid (FA) remodeling of existing PC. Modified lipoprotein incubation revealed rather different effects on glycerophospholipid synthesis. E-LDL greatly enhanced PC synthesis, whereas Ox-LDL did not change PC synthesis. Addition of different free FAs (FFA) with and without FC coincubation, as major components of E-LDL, clearly indicated an incorporation of FFA into newly synthesized PC and PE species as well as FFA as important driving force for PC synthesis. Because FC and FFA are known to affect lipid membrane properties including membrane curvature, these data support that CTP:phosphocholine cytidylyl-transferase activity and consequently PC synthesis are regulated by modulation of membrane characteristics at the cellular level. In conclusion, the application of high throughput metabolic profiling of major glycerophospholipid pathways by ESI-MS/MS is a powerful tool to unravel mechanisms underlying the regulation of cellular lipid metabolism.
Two‐photon molecular excitation provides intrinsic 3‐dimensional resolution for laser‐based microscopy and microphotochemistry

With the development of sensitive and specific fluorescent indicators, modern laser scanning microscopies enable visualization and measurement of submicron, dynamic processes inside living cells and tissues. Here we describe the working principles of new, nonlinear laser microscopies based on two‐photon molecular excitation. In these techniques, a pulsed laser produces peak photon densities high enough that when focused into an appropriate medium, excitation by photon energy combinations can occur. For example, two red photons interacting simultaneously with a fluorescent molecule can excite within it a UV electronic transition, one corresponding to twice the energy of each single photon. Because the amount of two‐photon excitation depends on the square of the local illumination intensity, this process exhibits a unique localization to the diffraction‐limited spot of the beam focus. Elsewhere along the beam, excitation of background and photodamage is virtually nonexistent. Focal point localization of two‐photon excitation lends to all visualization, measurement, and photopharmacology studies an intrinsic, three‐dimensional resolution. We describe some preliminary biological applications, specifically, imaging of vital DNA stains in developing cells and embryos, imaging of cellular metabolic activity from NADH autofluorescence, spatially resolved measurements of cytoplasmic calcium ion activity, and optically induced micropharmacology using caged bioeffector molecules. —Williams, R. M. , Piston, D. W. , Webb, W. W. Two‐photon molecular excitation provides intrinsic three‐dimensional resolution for laser‐based microscopy and microphotochemistry. FASEB J. 8: 804‐813; 1994.
Online Discussions With Pregnant and Parenting Adolescents: Perspectives and Possibilities

The Internet is an innovative strategy to increase public participation. It is important to include pregnant and parenting teens' perspectives when planning programs to meet their needs. This qualitative study explored online discussions as a strategy to enhance participation by this population. Findings showed that online communication was preferred over face-to-face group discussions. Being anonymous online encouraged open and honest feedback. Participants experienced various forms of social support, however, there was an overall lack of teen involvement online. Strategies to engage adolescents in online discussions and reduce barriers are discussed. Strategies included the use of teen moderators, home computer access, technical support, and engagement in naturally flowing online discussions to meet social support needs. Blending researchers' with teens' needs for social support in an online environment is encouraged. With careful planning and design, online communications can result in mutual benefits for researchers, service providers, and pregnant and parenting adolescents.
CHARACTERISTICS AND OUTCOMES OF METASTATIC SDHB AND SPORADIC PHEOCHROMOCYTOMA/PARAGANGLIOMA: AN NATIONAL INSTITUTES OF HEALTH STUDY.

OBJECTIVE Overall about 10 to 20% of pheochromocytomas/paragangliomas (PHEOs/PGLs) are metastatic, with higher metastatic potential observed in succinate dehydrogenase subunit B/fumarate hydratase (SDHB/FH)-related tumors. Due to the improved availability of biochemical and genetic testing and the frequent use of anatomical/functional imaging, there is currently a higher detection rate of metastatic PHEO/PGL. METHODS A retrospective analysis of 132 patients (27 children, 105 adults) with metastatic PHEO/PGL diagnosed and treated from 2000 to 2014 was conducted. RESULTS Seventy-seven (58%) males and 55 (42%) females were included; 39 (30%) have died, with no sex preference. Seventy-three (55%) patients had SDHB mutations; 59 (45%) patients had apparently sporadic tumors (AST). SDHB patients had an average age at primary tumor diagnosis of 31 ± 16 years compared to 40 ± 15 years in AST patients (P<.001). The average metastatic interval (MI) decreased with increasing age in both SDHB and AST patients (P = .013 for both). Only 16% of all primary tumors were smaller than 4.5 cm. Eleven percent of patients had biochemically silent disease, more with SDHB. Of SDHB patients, 23% had metastatic tumors at first diagnosis, compared to 15% of AST patients. Five- and 10-year survival rates were significantly better for metastatic AST than SDHB patients (P = .01). Overall survival was significantly different between children and adults (P = .037); this was mostly attributed to the SDHB patients, in whom children had statistically significantly longer survival than adults (P = .006). The deceased patients all died due to the PHEO/PGL and mainly had noradrenergic phenotypes. CONCLUSION In children, metastatic PHEOs/PGLs are mainly due to SDHB mutations; in adults they are equally distributed between in SDHB mutations and AST, with better 5- and 10-year survival rates for ASTs. In SDHB patients, children survive longer than adults. Primary metastatic tumors, most presenting as noradrenergic PGLs, are larger than 4.5 cm in >80% of patients. The frequency of metastatic tumors from primary AST increases with age, including a decreased MI compared to SDHB tumors. These results support several recommendations that are summarized in the Discussion.
Reducing concussion symptoms among teenage youth: Evaluation of a mobile health app

ABSTRACT Objective: To evaluate whether a mobile health application that employs elements of social game design could compliment medical care for unresolved concussion symptoms. Design: Phase I and Phase II (open-label, non-randomized, ecological momentary assessment methodology). Setting: Outpatient concussion clinic. Participants: Youth, aged 13–18 years, with concussion symptoms 3+ weeks after injury; Phase I: n = 20; Phase II: n = 19. Interventions: Participants received standard of care for concussion. The experimental group also used a mobile health application as a gamified symptoms journal. Outcome measures: Phase I: feasibility and satisfaction with intervention (7-point Likert scale, 1 high). Phase II: change in SCAT-3 concussion symptoms (primary), depression and optimism. Results: Phase 1: A plurality of participants completed the intervention (14 of 20) with high use (110 +/− 18% play) and satisfaction (median +/− interquartile range (IQR) = 2.0+/− 0.0). Phase II: Groups were equivalent on baseline symptoms, intervention duration, gender distribution, days since injury and medication prescription. Symptoms and optimism improved more for the experimental than for the active control cohort (U = 18.5, p = 0.028, effect size r = 0.50 and U = 18.5, p = 0.028, effect size r = 0.51, respectively). Conclusions: Mobile apps incorporating social game mechanics and a heroic narrative may promote health management among teenagers with unresolved concussion symptoms.
Synergism between ethanol and carbon tetrachloride in the generation of liver fibrosis

In this study, alcohol‐induced histological lesions in a short‐term experimental rat model were compared with those characteristic of human alcoholic liver disease. In the rat model used, pretreatment with carbon tetrachloride (CCl4) for 6 weeks was employed possibly to sensitize the liver for the effects of alcohol and shorten the time of induction of alcoholic liver disease. After 6 weeks of CCl4 treatment, subsequent maintenance on drinking water containing up to 10 per cent alcohol for 7 weeks potentiated liver fibroplasia as compared with non‐alcohol‐treated rats. However, steatosis and alcoholic hepatitis, as histological evidence for alcoholic liver disease as seen in humans, were not observed. In non‐CCl4‐pretreated control animals, alcohol administration had no effect on liver histology.
Distinguishing the medicinal herb Oldenlandia diffusa from similar species of the same genus using fluorescence microscopy

The light microscope is routinely used for microscopic identification of Chinese Materia Medica (CMM). However, the fluorescence microscope has not been used for this purpose until now. The CMM, Baihuasheshecao, mostly used as a component of herb tea, is a well known folk‐medicine in China. According to the Chinese Pharmacopoeia, its source is the species Oldenlandia diffusa (Willd.) Roxb. Two other species of the same genus, namely O. corymbosa (L.) Lam and O. tenelliflora Bl. , had been found in use as Baihuasheshecao. To find a quick and easy method to distinguish O. diffusa from these similar species of the same genus, the fluorescence microscope was used to investigate the fluorescence emission characteristics of the three tissues, which were compared with light microscopy images of the same material. The results showed that some tissues of the three herbs emit autofluorescence. Specially, the wall of endoderm cells of O. diffusa and O. tenelliflora emit autofluorescence, while similar tissue of O. corymbosa does not. Hence, fluorescence microscopy can be helpful in the identification of CMM. Microsc. Res. Tech. 69:277–282, 2006. © 2006 Wiley‐Liss, Inc.
Harnessing the gut to treat diabetes

Abstract: The gut contains one of the largest stem cell populations in the body, yet has been largely overlooked as a source of potentially therapeutic cells. The stem cells reside in the crypts located at the base of the protruding villi, reproduce themselves, and repopulate the gut lining as differentiated cells are sloughed off into the lumen. Some studies have demonstrated that gut stem cells can be isolated and maintained in culture, but the field is currently hampered by the lack of clear markers for these cells. Nevertheless, the relative accessibility of the cells and the similar pathways of differentiation of both intestinal and pancreatic endocrine cells make the gut an attractive potential source of cells to treat diabetes. In particular, it may be possible to recapitulate islet development by the introduction of specific factors to gut stem cells. Alternatively, gut endocrine cells might be coaxed to produce insulin and secrete it into the blood in a meal‐responsive manner. Several investigations support the feasibility of both approaches as novel potential therapies for diabetes. Utilizing a patient's own gut cells to re‐establish endogenous meal‐regulated insulin secretion could represent an attractive approach to ultimately cure diabetes.
Hippocampal volume in children with temporal lobe epilepsy compared to healthy children: a magnetic resonance imaging study.

CONTEXT There are currently few published studies that compare hippocampal volume (HCV) in children with temporal lobe epilepsy (TLE). Aims : T0 o compare HCVs in children with TLE and in relation to normal controls (NC), and to analyze HCV change in the acute phase in pediatric subjects using magnetic resonance imaging (MRI). Setting and Design : T0 he case group (n=24) was matched in gender and age range with NC subjects (n=24). Subjects were divided into three groups according to age: 2-5.9 years, 6-8.9 years and 9-13 years. MATERIALS AND METHODS M0 anual measurements were used to obtain HCVs on oblique coronary MRI images obtained by three-dimensional magnetization-prepared rapid gradient-echo (3D-MPRAGE) sequence. Statistical Analyses : T0 he HCV was calculated and normalized. Paired t-tests were used to compare the right and left HCVs within each study group. Analysis of covariance (ANCOVA) was used to consider the impact of age and gender on HCVs. RESULTS T0 wenty-two patients were diagnosed with definite/probable TLE, and two were non-syndromic focal epilepsy which was distributed in the 2-5.9 years group. The range of left to right mean HCVs of the case and NC group aged 2-13 years was 2014.14 ± 54.32 mm 3 to 2165.31 ± 80.99 mm 3 and 2015.46 ± 26.97 mm 3 to 2100.93 ± 57.33 mm 3 respectively. There were age-related differences in left and right HCV, but no effect of gender. Relative to NC subjects, cases group aged 2-5.9 years had significantly different HCVs, while no significant difference was found in the other two groups. There was significant difference in the right to left HCVs in the case subjects aged 2-5.9 years, but not in the other age groups. CONCLUSIONS T0 he heterogeneity in the 2-5.9 years age cohort may relate to the increased HCVs. The HCV data from NC subjects may be used as a reference to assess hippocampal abnormalities in clinical practice.
Reevaluation of epidemiological data demonstrates that it is consistent with cross-immunity among human papillomavirus types.

BACKGROUND The degree of cross-immunity between human papillomavirus (HPV) types is fundamental both to the epidemiological dynamics of HPV and to the impact of HPV vaccination. Epidemiological data on HPV infections has been repeatedly interpreted as inconsistent with cross-immunity. METHODS We reevaluate the epidemiological data using a model to determine the odds ratios of multiple to single infections expected in the presence or absence of cross-immunity. We simulate a virtual longitudinal survey to determine the effect cross-immunity has on the prevalence of multiple infections. We calibrate our model to epidemiological data and estimate the extent of type replacement following vaccination against specific HPV types. RESULTS We find that cross-immunity can produce odds ratios of infection comparable with epidemiological observations. We show that the sample sizes underlying existing surveys have been insufficient to identify even intense cross-immunity. We also find that the removal of HPV type 16, type 18, and types 6 and 11 would increase the prevalence of nontargeted types by 50%, 29%, and 183%, respectively. CONCLUSIONS Cross-immunity between HPV types is consistent with epidemiological data, contrary to previous interpretations. Cross-immunity may cause significant type replacement following vaccination, and therefore should be considered in future vaccine studies and epidemiological models.
Bridging the gap in 1st year dental material curriculum: A 3 year randomized cross over trial

Background: Case-oriented small group discussions (COSGDs) can help students to correlate and integrate the basic science of dental materials into clinical application. We used COSGDs along with didactic lectures in dental material curriculum and hypothesized that case-oriented group discussions would be more effective than traditional lecture alone in terms of performance of students, student perception on the above two teaching methodologies and the feasibility in classes of 2010, 2011 and 2012. Methods: A total of 170 students were taught using both COSGD and didactic lecture in a randomized controlled crossover trial design. Their performance was assessed through multiple-choice questions (MCQs) as part of the formative assessment, and their perception was assessed through Likert scale questionnaire. Results: The mean difference in the scores between case-oriented group discussions with lecture and didactic lecture showed significant difference only in few topics. Around 94-96% of students perceived COSGD with didactic lecture help them understand theory better; 76-92% of students feel more comfortable asking questions in a group discussion; 89-98% of students feel such discussions motivate them and 91-100% of students agree that discussions make the subject interesting in the respective years of 2010, 2011 and 2012. Conclusion: Effectiveness of COSGD in terms of scores through MCQs is comparable to traditional lecture. However, most of the students perceive COSGD help them understand the theory better; co-relate clinically; more motivating and interesting than a traditional lecture. Feasibility in institution needs more time and resources to conduct COSGD within the dental material curriculum.
10 Tb/s scale optical interconnection system using high-density optical wiring

The bandwidth of information and communication technology (ICT) systems is increasing and is predicted to reach 10 Tb/s and over. However, an electrical interconnect cannot achieve such bandwidth because of its density limits. To solve this problem, we propose a high-density optical backplane, which consists of a fiber cassette and eleven optical backplane connectors. The fiber cassette accommodates 768 optical fibers. The backplane connector housing can mount eight 48-fiber mechanically transferable (MT)-ferrules. Optical backplane is 89 mm wide and 13 mm thick; therefore, equipment can secure a sufficient area for cooling while achieving a 9.6-Tb/s aggregate bandwidth. It also eases assembly and testing. The insertion loss of the backplane including the two connectors results in 1 dB or less. We demonstrated an optical interconnection system using the optical backplane, which exhibited error-free transmission between boards up to 25.8 Gb/s. We also propose an optical connector using lensed ferrules instead of MT-ferrules. Due to the introduction of the lensed ferrules, the spring force of the connector can be reduced to 1/5 that with an MT-ferrule. The optical connector can be mounted in the front panel of ICT system equipment. These optical wiring components enable the development of ICT systems with bandwidth exceeding 10 Tb/s.
Intermediate acting versus long acting insulin for type 1 diabetes mellitus.

BACKGROUND Diabetes mellitus type 1 is a chronic disease with short and long term complications. Its goals of therapy are to eliminate the symptoms of hyperglycaemia, reduce the long term microvascular and macrovascular complications and allow the patients to achieve a normal life-style. Basal insulin replacement for insulin dependent patients can be achieved with either intermediate or long acting insulin preparations. OBJECTIVES To assess the effects of intermediate acting versus long acting insulin preparations for basal insulin replacement in type 1 diabetic patients. SEARCH STRATEGY We searched MEDLINE, EMBASE and The Cochrane Library, as well as reference lists, databases of ongoing trials, and requests from authors of included trials. SELECTION CRITERIA Randomised controlled trials, assessing long acting insulin preparations compared to intermediate acting insulin preparations, in type 1 diabetic patients. DATA COLLECTION AND ANALYSIS Two reviewers independently scanned the titles. Data were extracted and analysed accordingly. MAIN RESULTS Twenty-three randomised controlled trials were identified. A total of 3872 and 2915 participants in the intervention and in the control group, respectively, were analysed. The weighted mean difference (WMD) for the level of glycosylated haemoglobin was -0.08 (95% confidence interval (CI) -0.12 to -0.04) in favour of the long acting insulin arm. The WMD between the groups in fasting plasma and blood glucose levels was -0.63 (95% CI -0.86 to -0.40) and -0.86 (95% CI -1.00 to -0.72) in favour of the long acting insulins. The odds ratio for a patient on long acting insulin to develop any type of hypoglycaemia was 0.93 (95% CI 0.8 to 1.08) compared to that of a patient on intermediate acting insulins. The OR for severe hypoglycaemic episodes was 0.73 (95% CI 0.61 to 0.87), and 0.70 (95% CI of 0.63 to 0.79) for nocturnal episodes. The WMD between the long and intermediate insulin groups for hypoglycaemic events per 100 patient follow up days was -0.77 (95% CI -0.89 to -0.65), -0.0 (95% CI -0.02 to 0.02) and -0.40 (95% CI -0.45 to -0.34) for overall, severe, and nocturnal hypoglycaemic episodes. Weight gain was more prominent in the control group. No difference was noted in the quantity or quality of severe adverse events or deaths. AUTHORS' CONCLUSIONS Long acting insulin preparations seem to exert a beneficial effect on nocturnal glucose levels. Their effect on the overall diabetes control is clinically unremarkable. Their use as a basal insulin regimen for type 1 diabetes mellitus warrants further substantiation.
Adaptive IMRT using a multiobjective evolutionary algorithm integrated with a diffusion–invasion model of glioblastoma

We demonstrate a patient-specific method of adaptive IMRT treatment for glioblastoma using a multiobjective evolutionary algorithm (MOEA). The MOEA generates spatially optimized dose distributions using an iterative dialogue between the MOEA and a mathematical model of tumor cell proliferation, diffusion and response. Dose distributions optimized on a weekly basis using biological metrics have the potential to substantially improve and individualize treatment outcomes. Optimized dose distributions were generated using three different decision criteria for the tumor and compared with plans utilizing standard dose of 1.8 Gy/fraction to the CTV (T2-visible MRI region plus a 2.5 cm margin). The sets of optimal dose distributions generated using the MOEA approach the Pareto Front (the set of IMRT plans that delineate optimal tradeoffs amongst the clinical goals of tumor control and normal tissue sparing). MOEA optimized doses demonstrated superior performance as judged by three biological metrics according to simulated results. The predicted number of reproductively viable cells 12 weeks after treatment was found to be the best target objective for use in the MOEA.