Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment patterns and economic burden of metastatic and recurrent locally-advanced head and neck cancer patients

Abstract Objective: To characterize treatment patterns and measure the economic burden associated with metastatic (mHNC) and recurrent, locally-advanced head and neck cancer (rHNC). Methods: Administrative claims from Medicare- and privately-insured individuals during 2004–2008 were used in this retrospective database study of patients with advanced HNC. Patients diagnosed with HNC were matched 1:1 to cancer-free controls to measure the incremental economic burden of HNC. Outcomes of interest were measured during the 6 months following the date of a secondary tumor diagnosis for metastatic patients or the date of a diagnosis indicating rHNC. To assess treatment patterns, HNC patients were evaluated for the use frequency of treatments (radiotherapy, chemotherapy and surgery). Costs were reported in 2008 US$ from a third-party payer perspective and were analyzed using generalized linear models and two-part regression models adjusting for differences in age and baseline Charlson Comorbidity Index (excluding cancer diagnoses) between the HNC and control cohorts. Components of cost included inpatient, outpatient and other medical services as well as pharmacy costs. Results: The mHNC cohort consisted of 1042 patients and the rHNC cohort included 324 patients. The most common treatments for mHNC patients were supportive care (90.2%), radiation therapy (48.5%), surgery (41.9%) and chemotherapy (38.3%). Patients with rHNC frequently received HNC-related supportive care (71.0%), radiation therapy (67.9%) and chemotherapy (27.2%); HNC-related surgery was infrequent (12.7%) during the study period. The 6-month incremental adjusted total costs were $60,414 per patient for mHNC and $21,141 per patient for rHNC (p < 0.0001). Approximately 46–58% of the incremental cost was attributable to outpatient visits, 27–37% to inpatient costs and 11–13% to pharmacy, depending on the HNC cohort. Limitations: The identification of mHNC/rHNC was based on diagnosis codes and treatment patterns with the limitation of the claims database. Conclusions: Metastatic and recurrent, locally-advanced HNC patients frequently receive cancer-related treatments and incur substantial economic burden.
Tocilizumab for Rheumatoid Arthritis: A Cochrane Systematic Review

Objective. To compare the benefit and safety of tocilizumab to placebo in patients with rheumatoid arthritis (RA). Methods. We searched multiple databases for published randomized or controlled clinical trials comparing benefit and safety of tocilizumab to placebo, disease-modifying antirheumatic drugs (DMARD), or other biologics. For dichotomous outcomes, we calculated the relative risk, and for continuous outcomes, the mean difference. Results. Eight randomized controlled trials were included in this systematic review, with 3334 participants, 2233 treated with tocilizumab and 1101 controls. The US and Canadian approved dose of tocilizumab, 8 mg/kg every 4 weeks, was given to 1561 participants. In patients taking concomitant methotrexate, compared to placebo, patients treated with approved dose of tocilizumab were substantially and statistically significantly more likely than placebo to achieve the American College of Rheumatology 50 (absolute percentage, 38.8% vs 9.6%, respectively; RR 3.2, 95% CI 2.7, 3.7); Disease Activity Score remission (30.5% vs 2.7%; RR 8.7, 95% CI 6.3, 11.8); and a clinically meaningful decrease in Health Assessment Questionnaire (HAQ)/Modified HAQ scores (60.5% vs 34%; RR 1.8, 95% CI 1.6, 1.9). There were no substantive statistically significant differences in serious adverse effects (0.8% vs 0.7%; RR 1.2, 95% CI 0.8, 1.6) or withdrawals due to adverse events (4.9% vs 3.7%; RR 1.4, 95% CI 0.9, 2.1); however, tocilizumab-treated patients were significantly more likely to have any adverse event (74% vs 65%; RR 1.05, 95% CI 1.03, 1.07); elevation in the ratio of low-density lipoprotein to high-density lipoprotein cholesterol (HDL; 20% vs 12%; RR 1.7, 95% CI 1.2, 2.2); and increase in the ratio of total to HDL cholesterol (12% vs 7%; RR 1.7, 95% CI 1.2, 2.6); and they were less likely to withdraw from treatment for any reason (8.1% vs 14.9%; RR 0.6, 95% CI 0.5, 0.8). Conclusion. At the approved dose of 8 mg/kg every 4 weeks, tocilizumab in combination with methotrexate/DMARD is beneficial in decreasing RA disease activity and improving function. Tocilizumab treatment was associated with a significant increase in cholesterol levels and occurrence of any adverse event, but not serious adverse events. Larger safety studies are needed to address these safety concerns.
Race and sex differences in asleep blood pressure: The Coronary Artery Risk Development in Young Adults (CARDIA) study

Nocturnal hypertension and non‐dipping blood pressure are each associated with increased risk of cardiovascular disease. We determined differences in nocturnal hypertension and non‐dipping systolic/diastolic blood pressure among black and white men and women who underwent 24‐hour ambulatory blood pressure monitoring at the Coronary Artery Risk Development in Young Adults study Year 30 Exam in 2015‐2016. Asleep and awake periods were determined from actigraphy complemented by sleep diaries. Nocturnal hypertension was defined as mean asleep systolic/diastolic blood pressure ≥ 120/70 mm Hg. Non‐dipping systolic and diastolic blood pressure, separately, were defined as a decline in awake‐to‐asleep blood pressure < 10%. Among 767 participants, the prevalence of nocturnal hypertension was 18.4% and 44.4% in white and black women, respectively, and 36.4% and 59.9% in white and black men, respectively. After multivariable adjustment and compared with white women, the prevalence ratio (95% confidence interval) for nocturnal hypertension was 1.65 (1.18‐2.32) for black women, 1.63 (1.14‐2.33) for white men, and 2.01 (1.43‐2.82) for black men. The prevalence of non‐dipping systolic blood pressure was 21.5% and 41.0% in white and black women, respectively, and 20.2% and 37.9% in white and black men, respectively. Compared with white women, the multivariable‐adjusted prevalence ratio (95% confidence interval) for non‐dipping systolic blood pressure was 1.66 (1.18‐2.32), 0.91 (0.58‐1.42) and 1.66 (1.15‐2.39) among black women, white men, and black men, respectively. Non‐dipping diastolic blood pressure did not differ by race‐sex groups following multivariable adjustment. In conclusion, black women and men have a high prevalence of nocturnal hypertension and non‐dipping systolic blood pressure.
MANAGEMENT OF ENDOCRINE DISEASE: Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency; a position statement of the European Calcified Tissue Society.

Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) < 50 nmol/l or 20 ng/ml), is common in Europe and the Middle East. It occurs in < 20 % of the population in Northern Europe, in 30-60% in Western, Southern and Eastern Europe and up to 80 % in Middle East countries. Severe deficiency (serum 25(OH)D < 30 nmol/l or 12 ng/ml) is found in > 10 % of Europeans. The ECTS advises that the measurement of serum 25(OH)D be standardized e.g. by the Vitamin D Standardization Program. Risk groups include young children, adolescents, pregnant women, older people, especially the institutionalized, and non-western immigrants. Consequences of vitamin D deficiency include mineralization defects and lower bone mineral density causing fractures. Extra-skeletal consequences may be muscle weakness, falls and acute respiratory infection, and are the subject of large ongoing clinical trials. The ECTS advises to improve vitamin D status by food fortification and the use of vitamin D supplements in risk groups. Fortification of foods by adding vitamin D to dairy products, bread and cereals can improve the vitamin D status of the whole population, but quality assurance monitoring is needed to prevent intoxication. Specific risk groups such as infants and children up to 3 years, pregnant women, older persons and non-western immigrants should routinely receive vitamin D supplements. Future research should include genetic studies to better define individual vulnerability for vitamin D deficiency, and Mendelian randomization studies to address the effect of vitamin D deficiency on long term non-skeletal outcomes such as cancer.
A Heuristic Model for Supporting Users' Decision-Making in Privacy Disclosure for Recommendation

Privacy issues have become a major concern in the web of resource sharing, and users often have difficulty managing their information disclosure in the context of high-quality experiences from social media and Internet of Things. Recent studies have shown that users’ disclosure decisions may be influenced by heuristics from the crowds, leading to inconsistency in the disclosure volumes and reduction of the prediction accuracy. Therefore, an analysis of why this influence occurs and how to optimize the user experience is highly important. We propose a novel heuristic model that defines the data structures of items and participants in social media, utilizes a modified decision-tree classifier that can predict participants’ disclosures, and puts forward a correlation analysis for detecting disclosure inconsistences. The heuristic model is applied to real-time dataset to evaluate the behavioral effects. Decision-tree classifier and correlation analysis indeed prove that some participants’ behaviors in information disclosures became decreasingly correlated during item requesting. Participants can be “persuaded” to change their disclosure behaviors, and the users’ answers to the mildly sensitive items tend to be more variable and less predictable. Using this approach, recommender systems in social media can thus know the users better and provide service with higher prediction accuracy.
Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group.

PURPOSE To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). PATIENTS AND METHODS We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. RESULTS In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). CONCLUSION Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis.
Effects of salinity and flooding on post-hurricane regeneration potential in coastal wetland vegetation.

PREMISE OF THE STUDY The nature of regeneration dynamics after hurricane flooding and salinity intrusion may play an important role in shaping coastal vegetation patterns. METHODS The regeneration potentials of coastal species, types and gradients (wetland types from seaward to landward) were studied on the Delmarva Peninsula after Hurricane Sandy using seed bank assays to examine responses to various water regimes (unflooded and flooded to 8 cm) and salinity levels (0, 1, and 5 ppt). Seed bank responses to treatments were compared using a generalized linear models approach. Species relationships to treatment and geographical variables were explored using nonmetric multidimensional scaling. KEY RESULTS Flooding and salinity treatments affected species richness even at low salinity levels (1 and 5 ppt). Maritime forest was especially intolerant of salinity intrusion so that species richness was much higher in unflooded and low salinity conditions, despite the proximity of maritime forest to saltmarsh along the coastal gradient. Other vegetation types were also affected, with potential regeneration of these species affected in various ways by flooding and salinity, suggesting relationships to post-hurricane environment and geographic position. CONCLUSIONS Seed germination and subsequent seedling growth in coastal wetlands may in some cases be affected by salinity intrusion events even at low salinity levels (1 and 5 ppt). These results indicate that the potential is great for hurricanes to shift vegetation type in sensitive wetland types (e.g., maritime forest) if post-hurricane environments do not support the regeneration of extent vegetation.
Suppression of arbuscular mycorrhizal fungal activity in a diverse collection of non‐cultivated soils

&NA; Most plants form symbiotic associations with arbuscular mycorrhizal fungi (AMF). AMF increase the uptake of plant nutrients by extending their extra‐radical mycelium (ERM) in the soil where other groups of microorganisms may suppress the activity of the ERM. However, little is known about such suppression in natural soils. This work aimed to investigate the incidence of AMF suppression among soils sampled from highly variable natural ecosystems, and used 33P uptake by the ERM to evaluate AMF activity. A second aim was to identify factors behind the observed AMF‐suppression. We found that AMF‐suppressiveness varied markedly among natural soils and occurred more frequently in low pH than in high pH soils. A previous study for cultivated soils revealed a strong biological component of suppressiveness against AMF, and in accordance we found that the composition of both fungal and bacterial communities differed significantly between AMF‐suppressive and non‐suppressive natural soils. Acidobacteria, Acidothermus, Xanthomonadaceae, Archaeorhizomyces sp. , Mortierella humilis and some Mycena spp. were significantly more abundant in AMF‐suppressive soils and may therefore be direct antagonists of AMF. This implies that the functioning of AMF in natural ecosystems is strongly modulated by specific soil microbes. &NA; Graphical Abstract Figure. Arbuscular mycorrhizal fungal activity measure as transfer of phosphorus is suppressed by different bacterial and fungal taxa in natural terrestrial ecosystems.
CD4+ tissue-resident memory T-cells expand and are a major source of mucosal tumor necrosis factor α in active Crohn's Disease.

Background and Aims Tumor necrosis factor (TNF)α and IL-17A producing T-cells are implicated in Crohn's disease (CD). Tissue-resident memory T (TRM) cells are tissue-restricted T-cells that are regulated by PR zinc finger domain 1 (PRDM1), which has been implicated in pathogenic Th17 cell responses. TRM cells provide host defense but their role in CD is unknown. We thus examined CD4+ TRM cells in CD. Methods Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterize CD4+ TRM cells. Results CD4+ TRM cells are the most abundant memory T-cell population and are the major T-cell source of mucosal TNFα in CD. CD4+ TRM cells are expanded in CD and more avidly produce IL-17A and TNFα relative to control cells. There was a unique population of TNFα+IL-17A+ CD4+ TRM cells in CD that are largely absent in controls. PRDM1 was highly expressed by CD4+ TRM cells but not by other effector T-cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4+ TRM cells. Conclusion CD4+ TRM cells are expanded in CD and are a major source of TNFα, suggesting they are important in CD. PRDM1 is expressed by TRM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4+ TRM cells over the disease course.
Advanced fibrosis in nonalcoholic fatty liver disease: noninvasive assessment with MR elastography.

PURPOSE To evaluate the diagnostic accuracy of magnetic resonance (MR) elastography as a method to help diagnose clinically substantial fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and, by using MR elastography as a reference standard, to compare various laboratory marker panels in the identification of patients with NAFLD and advanced fibrosis. MATERIALS AND METHODS This retrospective study was institutional review board approved and HIPAA complaint. Informed consent was waived. This study was conducted in patients with NAFLD, who were identified by imaging characteristics consistent with steatosis in a prospective database that tracks all MR elastographic examinations. Six laboratory-based models of fibrosis were compared with MR elastographic results as well as fibrosis stage from liver biopsy results. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of each data set were compared. RESULTS Among 325 patients with NAFLD with MR elastographic data, there were 142 patients who underwent liver biopsy within 1 year of MR elastography. When comparing MR elastography results with liver biopsy results, the best cutoff for advanced fibrosis (stage F3-F4, 46 [32.4%] of 142) was 4.15 kPa (AUROC = 0.954, sensitivity = 0.85, specificity = 0.929). This cutoff value identified 104 patients with advanced fibrosis (32.0% of 325 patients). The FIB-4 score (AUROC = 0.827) and NAFLD fibrosis score (AUROC = 0.821) had the best diagnostic accuracy for advanced fibrosis, with high negative predictive values (NAFLD fibrosis score = 0.90 and FIB-4 score = 0.899). CONCLUSION MR elastography is a useful diagnostic tool for detecting advanced fibrosis in NAFLD. Of the laboratory-based methods, the NAFLD fibrosis and FIB-4 scores can most reliably detect advanced fibrosis.
Effects of Intermittent Hypoxia on Cognitive Performance and Quality of Life in Elderly Adults: A Pilot Study

Background: Physical exercise has a positive effect on cognitive performance and quality of life (QoL). One reason for this is the upregulation of brain-derived neurotrophic factor, which improves brain plasticity. Intermittent hypoxia promotes first the proliferation of endogenous neuroprogenitors which leads to an increased number of newborn neurons and second the expression of brain-derived neurotrophic factor in the adult hippocampus. Intermittent hypoxia may, therefore, support synaptic plasticity, the process of learning and provoke antidepressant-like effects. Hence, intermittent hypoxia might also lead to improved cognitive functioning and QoL. Objective: This study aims to evaluate to what extent physical activity with preceded intermittent hypoxic training is more effective than solely strength-endurance training on cognitive performance and QoL. Methods: 34 retired people aged between 60 and 70 years were randomly assigned to a control group or intervention group. Contrarily to the control group, which was supplied with a placebo air mixture, the intervention group was supplied with an intermittent hypoxic training prior to a strength-endurance exercise program. The cognitive performance of individuals was examined using the d2 test and the Number Combination Test (ZVT) both before and after the exercise program. We assessed QoL with the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-12) and Pittsburgh Sleep Quality Index (PSQI) and the strength-endurance capacity using the Spring test. Results: Regarding the d2 test, a time × group effect was observed. Speed of cognitive performance in seconds was measured using ZVT. Here, no interaction effect was discovered. An interaction effect was not found in the Physical Component Summary scores (SF-12). Regarding the Mental Component Summary, an interaction effect just failed to become statistically significant. Furthermore, we determined sleep quality with the PSQI. Here, an interaction effect was observed. The analysis of the strength-endurance test revealed no interaction effects. Conclusion: The data of the current study suggest that an additional intermittent hypoxic training combined with physical exercise augments the positive effects of exercise on cognitive performance and QoL in elderly humans.
Metronidazole-loaded nanostructured lipid carriers to improve skin deposition and retention in the treatment of rosacea

Abstract The objective of the present investigation was to improve the skin deposition and retention of metronidazole (MTZ) in rosacea therapy by incorporating it into nanostructured lipid carriers (NLCs). The main challenge in this endeavor was the partial hydrophilicity of MTZ, which mandated careful selection of excipients, including solid and liquid lipids, surfactants, and their ratios in combination. NLCs were produced by the phase inversion temperature method and finally converted into a gel for topical application. The prepared nanoparticles were evaluated for their particle size, zeta potential, entrapment efficiency, solid-state characteristics, surface morphology, in vitro drug release, and permeation through excised skin. The gel was additionally characterized for its pH, drug content, viscosity, and spreadability. The prepared nanoparticles were spherical in shape and of size less than 300 nm. Incorporation of judiciously chosen excipients made possible a relatively high entrapment efficiency of almost 40%. The drug release was found to be biphasic, with an initial burst release followed by sustained release up to 8 hours. In comparison to the plain drug gel, which had a tissue deposition of 11.23%, the NLC gel showed a much superior and desirable deposition of 26.41%. The lipophilic nature of the carrier, its size, and property of occlusion enabled greater amounts of drug to enter and be retained in the skin, simultaneously minimizing permeation through the skin, i.e. systemic exposure. The results of the study suggest that NLCs of anti-rosacea drugs have the potential to be used in the therapy of rosacea.
Sex differences in mouse models of fear inhibition: Fear extinction, safety learning, and fear–safety discrimination

Women are overrepresented in post‐traumatic stress disorder (PTSD), a mental disorder characterised by ineffective inhibition of fear. The use of male animals dominates preclinical studies, which may contribute to a lack of understanding as to why this disparity exists. Thus, the current study explores sex differences in three mouse models of fear inhibition.