Miracle-dz/UniFAR-FTUs huggingface dataset:
Optical microscopy of the pediatric vocal fold.

OBJECTIVES To compare and contrast 4 optical imaging techniques for evaluating the developing microstructure of the pediatric vocal fold and to identify the optimal strategy for in vivo imaging. DESIGN Prospective study. SETTING Academic medical center. PATIENTS A total of 6 laryngeal specimens: 5 pediatric (ages 10 months to 16 years) (4 from cadavers and 1 from a living patient immediately after laryngectomy) and 1 cadaveric young adult specimen (age, 23 years). INTERVENTION Sequential noninvasive optical imaging of pediatric vocal fold specimens using optical frequency domain imaging (OFDI), angle-resolved OFDI (AR-OFDI), spectrally encoded confocal microscopy (SECM), and full-field optical coherence microscopy (FF-OCM), followed by fixation, sectioning, and histologic analysis of the same specimen for comparison. MAIN OUTCOME MEASURE Correlation between the microstructure observed using the 4 noninvasive optical imaging techniques and with the results of histopathologic analysis for the same specimen. RESULTS A successful in vivo imaging technique for developmental assessment of the pediatric vocal fold would include visualization of distinct layers (epithelium, lamina propria, and muscularis mucosa) and allow for identification of the individual cells composing the layers. The OFDI and AR-OFDI techniques provide a global assessment of the microstructure of the pediatric vocal fold to a depth of 1200 mum but lack the ability to distinguish cellular and subcellular structures. The FF-OCM technique allows for visualization with improved cellular detail (1-mum resolution), but the image acquisition speed is too slow for clinical use. The SECM technique has a faster acquisition rate and shows good cellular and subcellular detail to a depth of 250 mum. CONCLUSIONS The OFDI and SECM techniques were identified as promising and complementary candidates for in vivo cellular and subcellular imaging of the epithelium, basement membrane, and lamina propria of the pediatric vocal fold. To further validate the clinical potential of these techniques, a handheld SECM probe has been developed and demonstrated for in vivo evaluation of the pediatric vocal fold.
The effect of combination anti-endothelial growth factor receptor and anti-vascular endothelial growth factor receptor 2 targeted therapy on lymph node metastasis: a study in an orthotopic nude mouse model of squamous cell carcinoma of the oral tongue.

OBJECTIVE To evaluate the therapeutic effect of treatment with a combination of the monoclonal antibodies to the vascular endothelial growth factor receptor (DC101) and the epidermal growth factor receptor (cetuximab) in an orthotopic nude mouse model of metastatic squamous cell carcinoma of the oral tongue (SCCOT). DESIGN In vivo study. SETTING A translational research laboratory at a comprehensive cancer center. SUBJECTS Male athymic nude mice aged 8 to 12 weeks. INTERVENTION To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or luciferase (Luc)-expressing OSC-19-Luc and JMAR-Luc cells were injected into the tongues of nude mice. Animals were randomly divided into 4 groups: DC101 alone, cetuximab alone, DC101 plus cetuximab, or placebo, and all treatments were administered twice per week for 4 weeks. The in vivo antitumor activity was monitored noninvasively by bioluminescence imaging. Tumors were resected at necropsy, and immunohistochemical and immunofluorescent staining were performed. MAIN OUTCOME MEASURES Tumor size, bioluminescence, animal survival, and percentage of animals with lymph node metastasis. RESULTS At the conclusion of the treatment period, the mean tumor volumes in the cetuximab alone and the DC101 plus cetuximab groups had decreased significantly compared with those that received the placebo control (68% [P = .002] and 84% [P < .001], respectively). Significant effects of the treatment were also observed in bioluminescence imaging. Mice treated with DC101 plus cetuximab also lived longer and had a lower incidence of neck lymph node metastases compared with the control group (P = .003). CONCLUSIONS Treatment with DC101 plus cetuximab inhibited the growth of SCCOT and decreased the incidence of the neck lymph node metastases in vivo. These results suggest that this combination treatment may be an effective strategy against metastatic SCCOT and warrants further preclinical trials.
Salafisme in Nederland: aard, omvang en dreiging

De beschikbare informatie over het salafisme in Nederland is vooral dreigingsgerelateerd. Over de wijze waarop salafisten hun dagelijkse leven invullen en de consequenties voor hun deelname aan de Nederlandse samenleving is maar weinig bekend. Ook over de omvang van het aantal salafisten in Nederland is vrijwel niks bekend. De centrale onderzoeksvraag is: Wat is de aard, omvang en dreiging van het salafisme in Nederland. Daarbij komen drie aandachtsvelden aan de orde: (a) de ideologie die de organisaties uitdragen, (b) de praktijk van de ideologie onder de gelovigen, (c) de relatie tussen salafisme en democratie, met name de mate van dreiging die uitgaat van het salafisme.
Plaque disruption by coronary computed tomographic angiography in stable patients vs. acute coronary syndrome: a feasibility study.

AIMS This study was designed to determine whether coronary CT angiography (CTA) can detect features of plaque disruption in clinically stable patients and to compare lesion prevalence and features between stable patients and those with acute coronary syndrome (ACS). METHODS We retrospectively identified patients undergoing CTA, followed by invasive coronary angiography (ICA) within 60 days. Quantitative 3-vessel CTA lesion analysis was performed on all plaques ≥25% stenosis to assess total plaque volume, low attenuation plaque (LAP, <50 HU) volume, and remodelling index. Plaques were qualitatively assessed for CTA features of disruption, including ulceration and intra-plaque dye penetration (IDP). ICA was employed as a reference standard for disruption. A total of 145 (94 ACS and 51 stable) patients were identified. By CTA, plaque disruption was evident in 77.7% of ACS cases. Although more common among those with ACS, CTA also detected plaque disruption in 37.3% of clinically stable patients (P < 0.0001). CONCLUSIONS Clinically stable patients commonly manifest plaques with features of disruption as determined by CTA. Though the prevalence of plaque disruption is less than patients with ACS, these findings support the concept that some clinically stable patients may harbour 'silent' disrupted plaques. These findings may have implications for detection of 'at risk' plaques and patients.
Nutrition Across the Life Span

I: Foundations: Introduction to Nutrition Across the Life Span. Application 1: Assessing and Interpreting Nutrition. Nutrition Assessment. Application 2: A Case for Nutrition Assessment. Nutrition: Communication and Counselling. Application 3: A Case for Nutrition Counselling. II: Growth and Development: Nutrition During Infancy. Application 4: Food for Infants: the Supermarket. The High Risk Infant. Application 5: Inborn Errors of Metabolism. Nutrition During Growth: Preschool and School Years. Application 6: Lunch at School. Nutrition During Adolescence. Application 7: Substance Use During Adolescence. III: Reproduction: Reproduction: Pregnancy. Application 8: Nutrition Care for Pregnant Women. High Risk Pregnancy. Application 9: Health Care and Nutrition Resources for Pregnant Women and Their Offspring. Lactation and Breast-Feeding. Application 10: Counselling for Breast-Feeding Success. IV: The Adult Years: Adulthood. Application 11: Foods, Supplements, Herbs. Aging and Older Adults. Application 12: Program for Older Adults. V: Special Concerns Across the Lifespan. Eating Disturbances: Dietary Restraint, Binging, Purging, And Excessive Consumption. Application 13: Is It Weight, Fat or Health? Nutrition and Physical Activity. Application 14: Are Ergogenic Aids Enhancers of Sports Performance? Nutrition of Persons with Developmental Delays and Disabilities. Application 15: A Case for Nutrition Intervention.
Evaluation of patient adherence to artemether-lumefantrine obtained from public and private drug outlets in Tanzania

Adherence to artemisinin-based combination therapies (ACTs) for malaria is important for effective treatment. This thesis compares adherence to ACTs obtained in the public and private retail sectors, describes an intervention to improve dispenser knowledge and patient adherence, and addresses challenges of measuring patient adherence to ACTs. A cluster randomised trial of a text message intervention targeted at dispensers in Accredited Drug Dispensing Outlets (ADDOs) was conducted in Tanzania to improve provision of advice on artemether-lumefantrine (AL) and as a result patient adherence. An observational study was also conducted among patients obtaining AL from public health facilities. In a third study, smart blister packs that recorded when pills were removed were used to assess the validity of self-report. Adherence was measured as completion of all doses (“completed treatment”) and completion of each dose at the correct time (“timely completion”). The intervention improved dispenser knowledge, but had no effect on patient completion of treatment (intervention 68.3%, control 69.8%, p [adjusted] = 0.6), or timely completion (intervention 33.1%, control 32.6%, p [adjusted] = 0.9). ADDO patients were wealthier, more educated, older, sought care later in the day, and were less likely to test positive for malaria than health facility patients. The adjusted odds of completed treatment and of timely completion for ADDO patients were 0.65 (95% CI: 0.43, 1.00) and 0.69 (95% CI: 0.47, 1.01) times that of health facility patients. Timely completion, but not completed treatment, was lower by smart blister packs than by self-report (37% vs. 24%, p<0.0001). Adherence to AL in both sectors was suboptimal. As the private sector continues to be important for malaria treatment, better understanding is needed of which aspects of patient care are most important to maximise adherence and how methods of assessing adherence can be improved.
Absence of PMS2 mutations in colon‐CFR participants whose colorectal cancers demonstrate unexplained loss of MLH1 expression

To the Editor: Lynch syndrome (LS) (MIM#120435) is a cancer predisposition condition resulting from mutations within the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2). In a suspected LS family, tumors are assessed for microsatellite instability (MSI) and/or immunohistochemical (IHC) absence of MMR proteins, both of which are hallmarks of LS. To enable appropriate diagnosis, counseling and surveillance, the gene indicated by the IHC profile is screened for mutations via techniques such as denaturing high pressure liquid chromatography (DHPLC), sequencing and multiplex ligation-dependent probe amplification (MLPA). Using these approaches, mutations are identified in the majority of cases suspected of LS; however, there remains a substantial proportion of families for which mutations cannot be identified.
Short-term high-fat diet compromises myocardial function: a radial strain rate imaging study

Aim Long-term high-fat diet (HFD) induces both cardiac remodelling and myocardial dysfunction in murine models. The aim was to assess the time course and mechanisms of metabolic and cardiac modifications induced by short-term HFD in wild-type (WT) mice. Methods and results Thirty-three WT mice were subjected to HFD (60% fat, n = 16) and chow diet (CD, 13% fat, n = 17). Metabolic and echocardiographic data were collected at baseline and every 5 weeks for 20 weeks. Invasive haemodynamic data and myocardial samples were collected at 5 and 20 weeks. Echocardiographic data included left ventricular (LV) diameters and thickness, and systolic function using radial strain rate (SR). Histological assessment of cardiomyocyte and adipocyte sizes, interstitial fibrosis, and apoptosis index were performed. During follow-up, body weight, and glycaemia levels were higher in HFD than in CD mice, in association with an early adipose tissue remodelling. Despite no difference between both groups in blood pressure and LV mass at 5 weeks, an early LV dysfunction was observed in HFD mice as assessed by radial SR (21 ± 0.8 vs. 27 ± 0.8 unit/s, P < 0.001) and haemodynamic assessment. During follow-up, both groups demonstrated a progressive systolic and diastolic LV dysfunction and remodelling including dilatation and hypertrophy, which were more severe in HFD mice. Compared with CD mice, the early LV impairment in HFD mice was coupled with a higher cardiomyocyte apoptosis level (0.95 vs. 0.02%, P < 0.05) associated with an interstitial fibrosis process (2.3 vs. 0.2%, P < 0.05), which worsen during follow-up. Conclusion The HFD promoted early metabolic and cardiac dysfunctions, and adipose and myocardial tissues remodelling.
A Meta-Analysis on the Information Technology Application in Patients’ Knowledge and Anxiety in Taiwan

The application of information technology in health education plan in Taiwan had gone for a long time. This study was performed to synthesize existing research comparing the effects of information technology application versus traditional instruction in health education plan on patients’ knowledge and anxiety in Taiwan. In spite of claims regarding the potential benefits of using information technology in health education plan, research results comparing the effects of information technology application and traditional instruction in Taiwan were conflicting. Some studies all reported significant gains for information technology application over traditional instruction. However, some studies had found no significant differences between information technology application and traditional instruction. Meta-analysis was a statistical process whereby the findings of several studies, focusing on a common problem or topic, are pooled in an effort to draw inferences as to the meaning of a collective body of research. In an effort to lend data to this debate, this study provides the meta-analysis of information technology application verse traditional instruction in Taiwanese hospital. The results from this study suggest information technology application with health education is positive with patients’ knowledge, and information technology application with health education is negative with patients’ anxiety.
How to Improve Complex Drug Development? A Critical Review of FDA Advisory Meetings

Background: Food and Drug Administration (FDA) advisory committees are essential in the process to market new drugs or authorize a new indication for an approved drug. Methods: This review of 2004 FDA advisory committee meetings analyzes questions posed to panel experts, results of experts votes, and regulatory actions taken by the agency. Results: Thirteen proposed indications concerning 10 new drugs were reviewed. Oncologic drugs covered six indications. While efficacy questions were the most frequent, safety questions were the most challenging. Beyond a statistical significance, sponsors were regularly asked to demonstrate the clinical relevance of study results. This sometimes proved unsuccessful for oncology indications. An identified safety signal could be problematic if the risk of the adverse reaction for an individual patient is not properly defined or if the adverse reaction cannot be minimized. Potential safety concerns are frequently raised but are difficult to address within the current regulatory guidance as such a risk cannot be objectively defined or prevented. The risk benefit analysis of advisory panels frequently contradicted sponsors analysis. Only 4 of the 13 proposed indications presented were later approved by the FDA. Conclusion: A better understanding of the conflicting opinions between advisory experts and sponsors will improve the conduct and review of clinical programs aiming at new indications.
Histopathological changes after coblation inferior turbinate reduction.

OBJECTIVE To assess the medium- to long-term histopathological changes after coblation (cold ablation) inferior turbinate (IT) reduction (CITR) surgery for refractory IT hypertrophy. DESIGN Two-center, prospective, nonrandomized, controlled histological study. SETTING University-affiliated hospitals. PATIENTS The coblation-treated group included 22 samples from 16 men with IT hypertrophy in whom CITR had failed and who underwent endoscopically guided mucotomy. The control group included 18 samples from 14 men who had nasal obstruction due to refractory IT hypertrophy and who had undergone inferior turbinectomy. MAIN OUTCOME MEASURES After processing the samples of both groups, we assessed the general histopathological features, the area fraction of various soft-tissue constituents, and the epithelial integrity. RESULTS Qualitative analysis showed marked fibrosis and depletion of submucosal glands and venous sinusoids in the lamina propria after CITR. Compared with the control group, the coblation-treated group showed a significantly increased area fraction of connective tissue and a significantly decreased area fraction of submucosal glands and venous sinusoids (P < .001 for all 3 comparisons). A significantly decreased relative proportion of intact epithelium and a significantly increased relative proportion of partial epithelial shedding were also found in the coblation-treated group (P = .03 and P = .04, respectively). CONCLUSIONS The long-term histological effects of CITR were significant fibrosis, glandular and venous sinusoid depletion, and partial epithelial shedding. The latter probably resulted from vascular damage, causing a reduction in epithelial perfusion. Questions remain concerning the long-term implications of the histopathological changes of CITR on nasal physiology.
Prolonged QT interval corrected for heart rate during diabetic ketoacidosis in children.

OBJECTIVE To evaluate the effect of diabetic ketoacidosis (DKA) on the QT interval corrected for heart rate (QTc) in children. Ketosis occurs in several conditions, including DKA and alcoholic ketoacidosis, and during use of very low-carbohydrate diets. Prolongation of the QTc has been described in a few children receiving ketogenic diets, but cardiac effects of ketosis have not otherwise been investigated. DESIGN For this observational study, we performed electrocardiography during DKA and after recovery. We measured QTc as the QT interval divided by the square root of the R-R interval and correlated QTc with clinical variables. SETTING The pediatric emergency department and intensive care unit of an academic medical center. PATIENTS Thirty children with type 1 diabetes mellitus and DKA. MAIN OUTCOME MEASURE The QTc during DKA. RESULTS The mean (SD) QTc during DKA was 450 (38) milliseconds (range, 378-539 milliseconds). After recovery from DKA, the mean (SD) QTc decreased to 407 (36) milliseconds (range, 302-485 milliseconds; difference, 43 milliseconds; 95% confidence interval, 23-63 milliseconds) (P < .001). Fourteen of the 30 children (47%) had prolonged QTc during DKA (range, 450-539 milliseconds). After recovery from DKA, only 4 children (13%) had persistent QTc prolongation (range, 451-485 milliseconds). The anion gap was significantly associated with QTc prolongation (correlation coefficient, 0.49; P = .006). Most patients had no electrolyte abnormalities or hypoglycemia to account for QTc prolongation. CONCLUSIONS Prolonged QTc occurs frequently during DKA and is correlated with ketosis. Current guidelines regarding cardiac monitoring of children during DKA should be strictly followed, and electrocardiographic screening of patients with other ketotic conditions should be considered.
Patterns of dose incurred by workers on the National Radiological Protection Board's dose record keeping service I. Annual doses

The paper presents data on the externally received doses for radiation workers who used the NRPB's personal monitoring and dose record keeping service throughout 1980. Distributions of annual dose by occupational category and age of worker are given and some models which can be used to describe the data are discussed. There are significant departures from the log-normal distribution which is sometimes assumed.
Improving evidence-based care in cystic fibrosis through quality improvement.

OBJECTIVE To increase clinician adherence to prescribing guidelines for pulmonary medications in children with cystic fibrosis (CF). DESIGN Quality improvement project with multiple time series design. SETTING The CF center at a tertiary care pediatric hospital in the United States. PATIENTS Children with CF who were eligible to receive oral azithromycin, nebulized dornase alfa, or inhaled tobramycin sulfate based on prescribing guidelines for CF lung disease. INTERVENTION Evidence-based prescribing guidelines were designed by a local committee to reflect consensus recommendations from the CF Foundation. Clinicians and families were educated about guidelines. Adherence to prescribing guidelines was tracked using a local CF database and record reviews. Weekly meetings were used to highlight adherence failures and promote clinician accountability. MAIN OUTCOME MEASURE The rate of clinician adherence to prescribing guidelines. RESULTS One hundred seventy patients with CF were included. At the start of the project, the rate of clinician adherence to prescribing guidelines was 62%. After 3 months of the project, the rate of clinician adherence to prescribing guidelines was 87% (odds ratio = 4.6; 95% confidence interval, 3.0-7.0). The improvements in adherence to prescribing guidelines were sustained for 21 months of follow-up. CONCLUSIONS Educating clinicians about prescribing guidelines, sharing guidelines with families, and monitoring clinician adherence improve prescribing adherence to evidence-based recommendations.
Has invasive management for acute coronary syndromes become more ‘risk-appropriate’: pooled results of five Australian registries

Background Despite being recommended in acute coronary syndrome (ACS) guidelines, the use of invasive management within specific risk groups continues to be debated. This study examines the change in the use of invasive management in ACS by patient risk and the associated change in mortality within Australia over the last 17 years. Methods Pooled cohorts derived from five ACS registries (ACACIA, CONCORDANCE, GRACE, Snapshot-ACS, and Predict) spanned from 1999 to 2015. After excluding patients without a final diagnosis of ACS (n = 4460), enrolled outside Australia (n = 1477) and without an enrolling year (n = 4), 15 912 patients were analysed. Data was stratified across three time periods (1999-2004, 2005-2009, and 2010-2015) using clinical risk characteristics (age, ACS diagnosis, biomarker elevation, and GRACE score) to monitor change in practice. Results Over the 17-year period, the use of invasive management increased (4073/6863 (59.3%) cases [1999-2009] vs. 6670/8706 (76.6%) cases [2010-2015]). Invasive management accounted for improvements in mortality in intermediate- and high-risk groups (intermediate risk: 14% (95% CI 1-66%) [1999-2009] vs. 49% (95% CI 2-59%) [2010-2015]; high risk: 24% (95% CI 6-42%) [1999-2009] vs. 48% (95% CI 19-76%) [2010-2015]). Patients receiving no angiography compared with interventional management had worse outcomes (1999-2004 1.55 HR [95% CI 1.36-1.80], P < 0.0001 vs. 2010-2015 1.90 HR [95% CI 1.45-2.51], P < 0.0001). Conclusions Clinical practice in ACS has changed over the last 17 years with positive outcomes seen with invasive management among high-risk patients. Unfortunately, a considerable burden of mortality remains in patients managed medically, highlighting a need for more focused strategies that improve care and outcomes in this group.