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Purpose: This study was to investigate the work experience of newly recruited male nurses during the COVID-19 pandemic. Methods: With a phenomenological approach, this qualitative study was adopted semistructured interviews by phone or video calls. A total of 9 male nurses newly recruited for the COVID-19 wards in Chinese hospitals were interviewed for this study. And Colaizzi's method was applied for evaluation in the data analysis. Results: Based on our findings, three themes were extracted. First, the newly recruited male nurses showed negative emotions at the beginning of COVID-19 epidemic, which was caused by changes in working conditions and content, but also prompted the nurses to change the way of coping with the crisis. Second, they gradually mastered the working skills and psychological training to cope with COVID-19 and developed a positive attitude toward life and a high sense of professional responsibility. Finally, we learned about their needs to respond to public health emergencies such as the COVID-19 pandemic. Conclusion: COVID-19 is a disaster for all of humanity. The newly recruited male nurses are an important force in emergency rescue. Although they suffered from short-term negative emotions, they quickly adapted to the crisis. In order to better prepare for future emergencies, the disaster response capacity of newly recruited male nurses needs to be further improved. In addition, newly recruited male nurses have a strong demand for timely and personalized career development guidance.

Background The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data. Methods A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups. Results A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group. Conclusion The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.

Several lines of clinical research support the efficacy of Cognitive behavioral therapy (CBT) with a large number of population and various disease conditions, however, the true effects of CBT interventions on Quality of Life of breast cancer patients remain unknown. The aim of the study was to evaluate the effect of Cognitive Behavioral Therapy on the Quality of Life of breast cancer patients. A systematic review of articles published using Web of Science (1950–January 2020); Medline via EBSCO (1992–January 2020); Science direct via ELSEVIER (1996–January 2020); SCOPUS (2004–January 2020); and PubMed (1946–January 2020 excluding Medline from 1992–January 2020) were included. Additional studies were included after checking reference lists of all relevant studies; searching ongoing trials and research registers and manual search. Data extraction was conducted by two independent authors and a third independent author checked the data extraction. The PRISMA statement was adopted. Eleven Randomized controlled trials (RCT) with 1690 breast cancer patients were included in this review. The overall effect size of cognitive behavioral therapy on QoL of breast cancer patients was medium 0.39 (95% CI 0.12–0.66, P

Background Return to work following myocardial infarction (MI) represents an important indicator of recovery. However, MI can cause patients to feel pressure, loneliness and inferiority during work and even detachment from employment after returning to work, which may affect their quality of life. The aims of this study were to identify the influencing factors of Health-related quality of life (HRQoL) in patients with MI after returning to work and explore the correlations between these factors and HRQoL. Method This was a cross-sectional study. All participants were recruited from tertiary hospitals in China from October 2017 to March 2018. The general data questionnaire, Short-Form Health Survey-8 (SF-8), Health Promoting Lifestyle ProfileII (HPLPII), Medical Coping Modes Questionnaire (MCMQ) and Social Supporting Rating Scale (SSRS) were used to assess 326 patients with myocardial infarction returned to work after discharge. Multiple linear regression analysis was performed to explore factors related to HRQoL in patients with MI after returning to work. Results The sample consisted of 326 patients. The mean total score of quality of life was 28.03 ± 2.554. According to the multiple linear regression analysis, next factors were associated with better HRQoL: younger age (B = − 0.354, P = 0.039), higher income (B = 0.513, P = 0.000), less co-morbidity (B = − 0.440, P = 0.000), the longer time taken to return to work (B = 0.235, P = 0.003), fewer stents installed (B = − 0.359, P = 0.003), participation in cardiac rehabilitation (CR) (B = − 1.777, P = 0.000), complete CR (B = − 1.409, P = 0.000), better health behaviors such as more health responsibility (B = 0.172, P = 0.000) and exercise (B = 0.165, P = 0.000), better nutrition (B = 0.178, P = 0.000) and self-realization (B = 0.165, P = 0.000), stress response (B = 0.172, P = 0.000), more social support such as more objective support (B = 0.175, P = 0.000), subjective support (B = 0.167, P = 0.000) and better utilization of social support (B = 0.189, P = 0.028), positive copping strategies such as more coping (B = 0.133, P = 0.000) and less yield (B = − 0.165, P = 0.000). Conclusions HRQoL of MI patients after returning to work is not satisfactory. Health behavior, coping strategies, social support are factors which can affect HRQoL. A comprehensive and targeted guide may be a way to improve HRQoL and to assist patients’ successful return to society.

The objective of this study was to predict the droplet size and the spraying angle during the process of binder atomization in pharmaceutical fluidized bed granulation using an empirical model. The effects of the binder viscosity, the atomization pressure, and the spray rate on the droplet size and the spraying angle were investigated using a response surface central composite design and analysis of variance. Prediction models for droplet size and spraying angle were then established using stepwise regression analysis and were validated by comparing the measured and predicted values. The results showed that the droplet size model and the spraying angle model were well established, with an

Background Older cancer survivors are at risk of the development or worsening of both age- and treatment-related morbidity. Sedentary behavior increases the risk of or exacerbates these chronic conditions. Light-intensity physical activity (LPA) is more common in older adults and is associated with better health and well-being. Thus, replacing sedentary time with LPA may provide a more successful strategy to reduce sedentary time and increase physical activity. Objective This study primarily aims to evaluate the feasibility, acceptability, and preliminary efficacy of a home-based mobile health (mHealth) intervention to interrupt and replace sedentary time with LPA (standing and stepping). The secondary objective of this study is to examine changes in objective measures of physical activity, physical performance, and self-reported quality of life. Methods Overall, 54 cancer survivors (aged 60-84 years) were randomized in a 1:1:1 allocation to the tech support intervention group, tech support plus health coaching intervention group, or waitlist control group. Intervention participants received a Jawbone UP2 activity monitor for use with their smartphone app for 13 weeks. Tech support and health coaching were provided via 5 telephone calls during the 13-week intervention. Sedentary behavior and physical activity were objectively measured using an activPAL monitor for 7 days before and after the intervention. Results Participants included survivors of breast cancer (21/54, 39%), prostate cancer (16/54, 30%), and a variety of other cancer types; a mean of 4.4 years (SD 1.6) had passed since their cancer diagnosis. Participants, on average, were 70 years old (SD 4.8), 55% (30/54) female, 24% (13/54) Hispanic, and 81% (44/54) overweight or obese. Malfunction of the Jawbone trackers occurred in one-third of the intervention group, resulting in enrollment stopping at 54 rather than the initial goal of 60 participants. Despite these technical issues, the retention in the intervention was high (47/54, 87%). Adherence was high for wearing the tracker (29/29, 100%) and checking the app daily (28/29, 96%) but low for specific aspects related to the sedentary features of the tracker and app (21%-25%). The acceptability of the intervention was moderately high (81%). There were no significant between-group differences in total sedentary time, number of breaks, or number of prolonged sedentary bouts. There were no significant between-group differences in physical activity. The only significant within-group change occurred within the health coaching group, which increased by 1675 daily steps (95% CI 444-2906; P=.009). This increase was caused by moderate-intensity stepping rather than light-intensity stepping (+15.2 minutes per day; 95% CI 4.1-26.2; P=.008). Conclusions A home-based mHealth program to disrupt and replace sedentary time with stepping was feasible among and acceptable to older cancer survivors. Future studies are needed to evaluate the optimal approach for replacing sedentary behavior with standing and/or physical activity in this population. Trial Registration ClinicalTrials.gov NCT03632694; https://clinicaltrials.gov/ct2/show/NCT03632694

Introduction: Digital breast tomosynthesis (DBT) may decrease recall rates (RRs) and improve positive predictive values (PPVs) and cancer detection rates (CDRs) versus full-field digital mammography (FFDM). The value of DBT has not been assessed in New Mexico's rural and minority population. Objectives of this study were to compare RRs, CDRs, and PPVs using FFDM+DBT versus FFDM in screening mammograms at the University of New Mexico between 2013 and 2016 and to qualitatively evaluate patient decision-making regarding DBT. Materials and Methods: RRs, CDRs, and PPVs with 95% confidence intervals and relative risk were calculated from 35,147 mammograms. The association between relative risk and mammography approach was tested using Pearson's chi-square test. Twenty women undergoing screening were interviewed for qualitative evaluation of decision-making. Results: From 2013 to 2016, RRs were 8.4% and 11.1% for FFDM+DBT and FFDM, respectively. The difference in RRs became more pronounced with time. No significant difference was observed in PPVs or CDRs. Qualitative interviews revealed that the majority had limited prior knowledge of DBT and relied on provider recommendations. Conclusion: In New Mexico women undergoing screening mammography, a 30% relative risk reduction in RRs was observed with FFDM+DBT. Qualitative interviews suggest that women are aware of and receptive to DBT, assuming adequate educational support. Clinical Trials.gov ID: NCT03979729.

OBJECTIVE This study explored the mediating role of dyadic coping between self-efficacy, psychological distress and marital quality among young and middle-aged couples facing lymphoma. METHODS A total of 243 couples in which the patients were lymphoma were recruited to complete Dyadic Coping Inventory, Locke-Wallace Marital Adjustment Scale for both. And Strategies Used by People to Promote Health, Fear of Progression Questionnaire-Short Form for patients; General Self-Efficacy Scale and Hospital Anxiety and Depression Scale for spouses. We used the statistical programs SPSS 20.0 and SPSS Amos 20.0 for data analysis. RESULTS There were significant correlations between patient-spouse's dyadic coping and marriage quality scores. The patients' dyadic coping scores were significantly associated with their self-efficacy, fear of cancer recurrence scores, marriage quality, their spouse's self-efficacy, and marriage quality. The spouses' dyadic coping scores were significantly associated with their self-efficacy, anxiety, and marriage quality. The actor-partner interdependence mediation model analysis mediator effect of dyadic coping in the relationship between self-efficacy, psychological distress, and marriage quality had a good fit, with χ2 /df = 17.106, p = 0.194; root mean square error of approximation = 0.036; GFI = 0.992; CN = 243. CONCLUSIONS For both patient and spouses, dyadic coping mediated impact of self-efficacy on marriage quality of themselves and their spouses, and individuals' dyadic coping mediated impact their psychological distress on marriage quality of themselves and spouses. The study highlighted the need for couple-based interventions and including strategies combined with individual and dyadic therapy for both partners.

The aim of this work was to increase the solubility and oral bioavailability of isorhamnetin, kaempferol, and quercetin in the total flavones of Hippophae rhamnoides L. (TFH) by preparing their nanosuspensions (NSs) and an inclusion complex. Based on the particle size and zeta potential, P407, Soluplus, SDS, PEG-6000, and HP-β-CD were selected as stabilizers. TFH NSs and a TFH/HP-β-CD inclusion complex were prepared, and their morphology, crystallinity, molecular interactions, and cytotoxicity were investigated. Furthermore, the saturation solubility, dissolution, and pharmacokinetics of the three flavonoids in the TFH, TFH NSs, and TFH/HP-β-CD inclusion complex were compared. The five obtained TFH NSs were physically stable, and their particle sizes were all below 200 nm. The solubility and dissolution of the three active components were obviously enhanced by the formation of the TFH NSs and TFH/HP-β-CD inclusion complex. Correspondingly, the oral bioavailability of isorhamnetin, kaempferol, and quercetin increased up to 4.11-, 3.85-, and 6.73-fold, respectively, in the TFH NSs and 2.89-, 3.71-, and 9.51-fold, respectively, in the TFH/HP-β-CD inclusion complexes compared to those in the raw TFH. In brief, both NSs and inclusion complexes can improve the oral bioavailability of the three flavonoids in TFH. Taking the drug loading and the stable ratio of the multiple components into consideration, the NSs is a more promising strategy than the inclusion complex for increasing the oral bioavailability of multiple water-insoluble components in herbal extracts. Graphical abstract.

For Parkinson's disease (PD), the regulatory mechanism of α-synuclein (α-syn) aggregation remains to be clarified. Ubiquitination modification is crucial for α-syn aggregation, with implications for Lewy body formation. Besides, ubiquitin ligase absentia homolog (siAH) is involved in the ubiquitination of α-syn. We investigated whether the p75 receptor can act as a potential regulator of α-syn accumulation through ubiquitination. Western blot, immunoprecipitation, gene transfection, and RNA interference technology were employed to detect the effect of p75 in in vivo and in vitro models. In a rotenone-based stereotactic (ST) infusion in vivo model of PD, p75 receptor and siAH expression was increased significantly compared with the control group. In cellular models of rotenone-mediated neurotoxicity, the interactions between p75 and siAH were revealed by immunoprecipitation; the colocalization of p75 with α-syn was observed in the cytoplasm; p75 promoted nuclear expression of NF-κB (p65), which might interact with the promoter of the siAH gene. Moreover, siRNA-mediated p75 depletion reduced the upregulation of α-syn and nuclear expression of p65 and protected against cell apoptosis induced by rotenone. Thus, aberrant expression of p75 may regulate the increased expression of α-syn, which is related to siAH-mediated ubiquitination and nuclear expression of p65.

Contamination of soil and water by waste from abandoned uranium mines has led to chronic exposures to metal mixtures in Native American communities. Our previous work demonstrated that community exposures to mine waste increase the likelihood of developing cardiovascular disease, as well as the likelihood of developing multiple chronic diseases including diabetes, hypertension and kidney disease. Exposure to various environmental metals is associated with elevated oxidative stress, which is considered a contributor to these and other chronic disease states. The purpose of the current research was to assess potential associations between exposure to uranium and arsenic and evidence for increased oxidative stress as measured by urinary F2 -isoprostanes in pregnant women enrolled in the Navajo Birth Cohort Study. The current study also included an analysis of zinc as a potential mediator of oxidative stress in the study population. Urinary arsenic and uranium, serum zinc and urinary F2 -isoprostanes were measured for each study participant at enrollment. Study participants were pregnant women with median age of 26.8; 18.9% were enrolled in the 1st trimester, 44.7% were enrolled in the 2nd trimester, and 36.4% were enrolled in the 3rd trimester. Median urinary metal levels were 5.5 and 0.016 µg/g creatinine for arsenic and uranium, respectively. Multivariable regression analysis indicated a significant association between arsenic exposure and the lipid peroxidation product 8-iso-prostaglandin F2α, controlling for zinc and trimester. No associations were detected with uranium despite evidence that levels were in the Navajo Birth Cohort samples were 2.3 times the median reported for women in the National Health and Nutrition Examination Survey (2011-12). Zinc was not found to have any causal mediation of the effects of the other metals on oxidative stress. The current work is consistent with other studies that have detected an association between arsenic and elevated oxidative stress. In contrast to arsenic, uranium did not appear to increase oxidative stress response in this study population. These findings are relevant to assessing the potential human impact of chronic exposure to mixed metal waste from abandoned uranium mines.

By sequence homology search, the list of all the functions found and the counts of reads being aligned to them present the functional profile of a metagenomic sample. However, a significant obstacle has been observed in this approach due to the short read length associated with many next generation sequencing technologies. This includes artificial families, cross-annotations, length bias and conservation bias. The widely applied cutoff methods, such as BLAST E-value, are not able to solve the problems. Following the published successful procedures on the artificial families and the cross-annotation issue, we propose in this paper to use zero-truncated Poisson and Binomial (ZTP-Bin) hierarchical modelling to correct the length bias and the conservation bias. Goodness-of-fit of the modelling and cross-validation for the prediction using a bioinformatic simulated sample show the validity of this approach. Evaluated on an in vitro-simulated data set, the proposed modelling method outperforms other traditional methods. All three steps were then sequentially applied on real-life metagenomic samples to show that the proposed framework will lead to a more accurate functional profile of a short read metagenomic sample.

Hederagenin (HG) is a pentacyclic triterpenoid that exists in many plants in the form(s) of sapogenin or saponins. This review highlights the pharmacokinetics, pharmacological activities, mechanisms of action, and safety of HG using literature and patents from the last 50 years to collate information on this compound as a promising medicinal agent. This review also looks at the development of related derivatives of HG with increased efficacy and lower toxicity. HG is quickly absorbed in the gastrointestinal tract with a short elimination half-life, and can cross the blood-brain barrier and rapidly distribute into cerebrospinal fluid. HG has been shown to possess a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, anti-depressant, anti-neurodegenerative, anti-hyperlipidemia, anti-diabetic, anti-leishmanial, and anti-viral activity. In particular, the extensive anti-tumor activity indicates that HG has the potential to be a highly effective chemotherapy agent. Recently, in the search for more active compounds as potential pharmaceuticals, structural modification of the triterpene scaffold of HG at the C-3, C-12, C-13, C-23, and C-28 positions, has resulted in compounds that exhibited greater potency than HG itself. However, the low bioavailability and moderate hemolysis effect of HG may limit its clinical application. The cause of the observed toxic effects in some animals, including dogs, cats, cattle, goats, and horses also needs to be explained. Future studies of HG focusing on extending the half-life, improving bioavailability, enhancing pharmacological activity, as well as decreasing or avoiding hemolysis by structural modification or formulation design could potentially accelerate HG from the preclinical to clinical research phase.

Summary Default differentiation of human pluripotent stem cells has been promoted as a model of cortical development. In this study, a developmental transcriptome analysis of default-differentiated hPSNs revealed a gene expression program resembling in vivo CGE/LGE subpallial domains and GABAergic signaling. A combination of bioinformatic, functional, and immunocytochemical analysis further revealed that hPSNs consist of both cortical glutamatergic and CGE-like GABAergic neurons. This study provides a comprehensive characterization of the heterogeneous group of neurons produced by default differentiation and insight into future directed differentiation strategies., Highlights • Multiple time point transcriptome analysis of default hPSC differentiation • Resultant neurons resemble a pan-cortical population with multiple layer markers • CGE/LGE-specific transcripts are expressed to near exclusion of MGE markers • Immunocytochemistry reveals CGE markers in hPSN subpopulation, Default differentiation of human pluripotent stem cell-derived neurons (hPSNs) is thought to be a model of cortical differentiation. The authors performed transcriptome, time-course analysis of developing and mature hPSNs. In addition to cortical glutamatergic neurons, default differentiation led to significant CGE/LGE-specific GABAergic patterning. This work comprehensively characterizes the heterogeneity of neurons produced by default differentiation.

Proper nutrition during pregnancy is vital to maternal health and fetal development and may be challenging for Navajo Nation residents because access to affordable and healthy foods is limited. It has been several decades since reported diet quality during pregnancy was examined on Navajo Nation. We present the first study to estimate iodine intake and use the Healthy Eating Index (HEI‐2015) to assess maternal diet quality among pregnant women in the Navajo Birth Cohort Study (NBCS). Based on dietary intake data derived from food frequency questionnaires, overall estimated micronutrient intake has remained similar since the last assessment in 1981, with potential improvements evident for folate and niacin. A high proportion of women (>50%) had micronutrient intakes from dietary sources below the Estimated Average Requirements during pregnancy. The median urinary iodine concentration for NBCS women (90.8 μg/L; 95% CI [80, 103.5]) was less than adequate and lower than concentrations reported for pregnant women that participated in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014. Overall, average diet quality of NBCS women estimated using the HEI‐2015 (62.4; 95% CI [60.7, 64.0]) was similar to that reported for women of child‐bearing age and pregnant women in NHANES. Although, NBCS women had diets high in added sugar, with sugar‐sweetened beverages as the primary contributors. Our study provides updated insights on maternal diet quality that can inform health and nutrition initiatives in Navajo communities emphasizing nutrition education and access to prenatal vitamins and calcium, iodine, and vitamin E dense foods.

Background The Ages and Stages Questionnaires-Third Edition (ASQ-3) is a parent-completed screening to identify young children at-risk for developmental delays in the United States and internationally. Federal programs operating on Navajo Nation use the ASQ-3 to determine the need for early intervention services, even though the ASQ-3 national sample used to establish cutoff scores for referral included only 1% Native American children. Objectives The current study aimed to compare the ASQ-3 results from a sample of Navajo infants to those from a representative national U.S. sample and to examine the specificity and sensitivity of the ASQ-3 in Navajo population. Methods The sample included 530 Navajo infants (47.3% males) aged between 1 and 13 months who lived in remote and rural areas across the Navajo Nation. Children's development was assessed during home visits at 2-, 6-, 9-, and 12-month assessment windows. Results Results showed that after 6 months, Navajo children had lower mean scores and higher percentages of children at-risk for developmental delays than those from the national sample. The sensitivities and specificities, estimated using a Bayesian diagnostic approach under both conservative and nonconservative prior range choices, suggested a comparable validity performance to that from other ASQ-3 studies. Discussion The results of this study along with our ongoing comprehensive assessments at 4 years of age inform current programs working with Navajo children to improve early identification of developmental delays.

The purpose of this investigation was to improve the solubility and oral bioavailability of daidzein via preparing nanosuspensions (NS) with steric stabilizers, electrostatic stabilizers, or a combination of both. Based on particle size and zeta potential, daidzein NS stabilized by HP-β-CD, soy lecithin, HP-β-CD + soy lecithin, TPGS, TPGS + SBE-β-CD, SDS, or HPMC E5 + SDS were generated and characterized by scanning electron microscopy, powder X-ray diffraction, and Fourier transform-infrared spectroscopy. In addition, the stability, cytotoxicity, solubility, dissolution, and pharmacokinetics of NS were evaluated. The resulting daidzein NS were physically stable and biocompatible and presented as regular shapes with homogenous particle sizes of 360–600 nm and decreased crystallinity. Due to the increased solubility and dissolution rate, the oral bioavailability of daidzein NS in rats was 1.63–2.19 times greater than that of crude daidzein. In particular, among the investigated seven daidzein NS formulations, daidzein NS prepared with the costabilizers HPMC E5 + SDS is an optimal formulation for increased daidzein bioavailability. The present study proposes that the combined usage of steric and electrostatic stabilizers is a promising strategy for improving the bioavailability of water-insoluble flavonoid compounds by an NS approach.

Aims and objectives To describe nurses' attitudes, beliefs, and practices regarding sexuality care for patients with cardiovascular disease. Background Limited sexual activity is common among patients with cardiovascular disease, yet assessment of sexuality and counselling is frequently not undertaken by nurses. Design Cross-sectional study. Methods This study recruited 268 cardiac nurses from seven tertiary hospitals in five cities of Henan province. The Sexual Attitudes and Beliefs Survey, along with investigator-developed questions regarding practices and perceived barriers, was administered to the nurses. The STROBE checklist was used to ensure quality reporting during this observational study (see Supporting Information Data S1). Results The average age of nurses who participated was 31.81 years (SD = 7.41). The average score of Sexual Attitudes and Beliefs Survey was 47.72 (SD = 7.40), indicating moderate attitudinal barriers for nurses to discuss sexual activities with patients. Most nurses (91%) perceived that sexuality was too private to discuss with patients. Only 20% of nurses expressed that they would provide time to discuss sexual concerns with patients. Eighty per cent of nurses revealed that they felt uncomfortable discussing sexuality; moreover, they believed that hospitalised patients were too sick to be engaged in these types of conversations. Additionally, almost 85% of nurses conveyed that they have never conducted discussions regarding sexuality care in patients with cardiovascular disease. The most frequently reported perceived barriers preventing nurses from discussing sexual concerns included fear of offending patients (77.2%), uncertainty of how to communicate with patients (69.4%), feelings of embarrassment (67.5%), lack of safe and private environments (61.9%) and lack of knowledge (54.9%). Conclusion Nurses in this cross-sectional sample rarely discussed sexual concerns with their patients. There were several key barriers identified by nurses regarding providing sexuality care, including personal attitudes and beliefs, limited skills and knowledge, culture and organizational-related barriers. Relevance to clinical practice Targeted training for nurses and creating a culturally safe environment is recommended to improve management of sexuality in patients with CVD.

Previous studies on the association between thyroid hormones and prognosis of acute ischemic stroke (AIS) reported conflicting results. We conducted a meta-analysis to assess the prognostic value of thyroid hormones in AIS. The PubMed, EMBASE, and Cochrane library databases were searched through May 12, 2017 to identify eligible studies on this subject. Out of 2,181 studies retrieved, 11 studies were finally included with a total number of 3,936 acute stroke patients for analysis. Odds ratio (OR) for predicting poor outcome or standardized mean difference (SMD) of thyroid hormone levels with 95% confidence intervals (95% CI) obtained from the studies were pooled using Review Manager 5.3. From the results, in AIS, patients with a poor outcome had lower levels of triiodothyronine (T3) and higher thyroxine (T4). Pooled OR confirmed the same association. Our study provides statistical evidence supporting the utility of thyroid hormone levels in prognosis of acute stroke.

Background: In recent years, metagenomics, as a combination of research techniques without the process of cultivation, has become more and more popular in studying the genomic/genetic variation of microbes in environmental or clinical samples. Though generated from similar sequencing technologies, there is increasing evidence that metagenomic sequence data may not be treated as another variant of RNA-Seq count data, especially due to its compositional characteristics. While it is often of primary interest to compare taxonomic or functional profiles of microbial communities between conditions, normalization for library size is usually an inevitable step prior to a typical differential abundance analysis. Some methods have been proposed for such normalization. But the existing performance evaluation of normalization methods for metagenomic sequence data does not adequately consider the compositional characteristics.

Previous studies on the association between thyroid hormones and prognosis of acute ischemic stroke (AIS) reported conflicting results. We conducted a meta-analysis to assess the prognostic value of thyroid hormones in AIS. The PubMed, EMBASE, and Cochrane library databases were searched through May 12, 2017 to identify eligible studies on this subject. Out of 2,181 studies retrieved, 11 studies were finally included with a total number of 3,936 acute stroke patients for analysis. Odds ratio (OR) for predicting poor outcome or standardized mean difference (SMD) of thyroid hormone levels with 95% confidence intervals (95% CI) obtained from the studies were pooled using Review Manager 5.3. From the results, in AIS, patients with a poor outcome had lower levels of triiodothyronine (T3) and higher thyroxine (T4). Pooled OR confirmed the same association. Our study provides statistical evidence supporting the utility of thyroid hormone levels in prognosis of acute stroke.

Background: This study evaluates predictors of BRCA1/2 testing among breast and ovarian cancer survivors who received genetic counseling as part of a randomized trial and evaluates moderators of counseling mode on testing uptake. Methods: Predictors of BRCA1/2 testing within one year postcounseling were evaluated using multivariable logistic regression in a population-based sample of breast and ovarian cancer survivors at increased hereditary risk randomly assigned to in-person counseling (IPC; n = 379) versus telephone counseling (TC; n = 402). Variables that moderated the association between counseling mode and testing were identified by subgroup analysis. Results: Testing uptake was associated with higher perceived comparative mutation risk [OR = 1.32; 95% confidence interval (CI), 1.11–1.57] in the adjusted analysis. Those without cost barriers had higher testing uptake (OR = 18.73; 95% CI, 7.09–49.46). Psychologic distress and perceived comparative mutation risk moderated the effect of counseling and testing. Uptake between IPC versus TC did not differ at low levels of distress and risk, but differed at high distress (26.3% TC vs. 44.3% IPC) and high perceived comparative risk (33.9% TC vs. 50.5% IPC). Conclusions: Cost concerns are a strong determinant of testing. Differences in testing uptake by counseling mode may depend on precounseling distress and risk perceptions. Impact: Cost concerns may contribute to low testing in population-based samples of at-risk cancer survivors. Precounseling psychosocial characteristics should be considered when offering in-person versus telephone counseling. Cancer Epidemiol Biomarkers Prev; 26(12); 1772–80. ©2017 AACR.

Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease‐control rate (DCR), complete response (CR) + partial response (PR)+ stable disease (SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0.2 and 0.4, respectively) were set as undesirable (null) and desirable results. 26 HCC and 7 BDC patients were accrued. In HCC, 1 PR, 10 SD, and 9 PDs were seen. DCR in HCC was 42%. Among seven (7) patients with BDC, one patient was not evaluable; one achieved a long lasting PR, and five patients had SD and DCR was 86%. Median overall survival (OS) times and progression‐free survivals (PFS) were 196 and 149 days in HCC and 238 days and not reached in BDC. PFS at 26 weeks in HCC was 41% and at 21 weeks in BDC was 60%. Grade 3 toxicities in >5% of patients were fatigue (12.9%), neutropenia (9.6%), thrombocytopenia (9.6%), and diarrhea (6.4%). G+O+E exceeded both preset P0a and P1 of the primary objective with a PFS of 41% at 26 weeks for HCC and preliminary BDC data may warrant further investigations.

Various modeling techniques were used to understand fluidized bed granulation using a two-step approach. First, Plackett-Burman design (PBD) was used to identify the high-risk factors. Then, Box-Behnken design (BBD) was used to analyze and optimize those high-risk factors. The relationship between the high-risk input variables (inlet air temperature X1, binder solution rate X3, and binder-to-powder ratio X5) and quality attributes (flowability Y1, temperature Y2, moisture content Y3, aggregation index Y4, and compactability Y5) of the process was investigated using response surface model (RSM), partial least squares method (PLS) and artificial neural network of multilayer perceptron (MLP). The morphological study of the granules was also investigated using a scanning electron microscope. The results showed that X1, X3, and X5 significantly affected the properties of granule. The RSM, PLS and MLP models were found to be useful statistical analysis tools for a better mechanistic understanding of granulation. The statistical analysis results showed that the RSM model had a better ability to fit the quality attributes of granules compared to the PLS and MLP models. Understanding the effect of process parameters on granule properties provides the basis for modulating the granulation parameters and optimizing the product performance at the early development stage of pharmaceutical products.

Background To assess whether the ultrasound (US) is a reliable approach in detecting lower-limb deep-vein thrombosis (DVT) in patients without symptoms of DVT. Methods The research team performed a systematic search in PubMed, Ovid, Cochrane, and Web of Science without language or date restrictions. Full-text reports on prospective diagnostic studies involve the detection of lower-limb proximal and distal DVT in patients without symptoms of DVT using US and venography. A meta-analysis was performed using Meta-DiSc (version 1.4), providing the pooled sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios of the detection accuracy of US. There were 4 different classes of subgroup analysis-the class of patients stratified by location of US exam (proximal, distal, whole leg), the class stratified by technique (color/doppler, compression, both modalities), the class stratified by kind of surgery (orthopedic, otherwise hospitalized) and the class stratified by era of publishing (1980s, 1990s, 2000s). The study quality and the risk of bias were evaluated using QUADAS-2, with heterogeneity was assessed and quantified by the Q score and I statistics, respectively. Results The meta-analysis included 26 articles containing 41 individual studies with a total of 3951 patients without symptoms of DVT. Using venography as the gold standard, US for proximal DVT had a pooled sensitivity of 59% (95% confidence interval (CI) = 51%-66%) and a pooled specificity of 98% (95% CI = 97%-98%), US for distal DVT had a poor sensitivity of 43% (95% CI = 38%-48%) and a pooled specificity of 95% (95% CI = 94%-96%), US for whole-leg DVT had a pooled sensitivity of 59% (95% CI = 54%-64%) and a pooled specificity of 95% (95% CI = 94%-96%), US for post-major orthopedic surgery patients had a pooled sensitivity of 52% (95% CI = 49%-55%), and US for other types of patients had a pooled sensitivity of 58% (95% CI = 43%-72%). Pure compression technique for DVT had a poor sensitivity of 43% (95% CI = 39%-48%), pure color/doppler technique for DVT had a pooled sensitivity of 58% (95% CI = 53%-63%), compression and color/doppler technique for DVT had a pooled sensitivity of 61% (95% CI = 48%-74%). Conclusion US could be a useful tool for diagnosing DVT, but it has a lower positive rate and a higher false negative rate. The rate of missed diagnosis of lower-limb DVT by US amounts to 50% or so in the patients without symptoms of DVT. The negative results do not preclude the possibility of DVT and if appropriate heightened surveillance and continued monitoring or try a more accurate inspection method is warranted. The whole leg evaluation and color/doppler technique should be the preferred approach.

Purpose The ongoing integration of cancer genomic testing into routine clinical care has led to increased demand for cancer genetic services. To meet this demand, there is an urgent need to enhance the accessibility and reach of such services, while ensuring comparable care delivery outcomes. This randomized trial compared 1-year outcomes for telephone genetic counseling with in-person counseling among women at risk of hereditary breast and/or ovarian cancer living in geographically diverse areas. Patients and Methods Using population-based sampling, women at increased risk of hereditary breast and/or ovarian cancer were randomly assigned to in-person (n = 495) or telephone genetic counseling (n = 493). One-sided 97.5% CIs were used to estimate the noninferiority effects of telephone counseling on 1-year psychosocial, decision-making, and quality-of-life outcomes. Differences in test-uptake proportions for determining equivalency of a 10% prespecified margin were evaluated by 95% CIs. Results At the 1-year follow-up, telephone counseling was noninferior to in-person counseling for all psychosocial and informed decision-making outcomes: anxiety (difference [d], 0.08; upper bound 97.5% CI, 0.45), cancer-specific distress (d, 0.66; upper bound 97.5% CI, 2.28), perceived personal control (d, −0.01; lower bound 97.5% CI, −0.06), and decisional conflict (d, −0.12; upper bound 97.5% CI, 2.03). Test uptake was lower for telephone counseling (27.9%) than in-person counseling (37.3%), with the difference of 9.4% (95% CI, 2.2% to 16.8%). Uptake was appreciably higher for rural compared with urban dwellers in both counseling arms. Conclusion Although telephone counseling led to lower testing uptake, our findings suggest that telephone counseling can be effectively used to increase reach and access without long-term adverse psychosocial consequences. Further work is needed to determine long-term adherence to risk management guidelines and effective strategies to boost utilization of primary and secondary preventive strategies.

Importance A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. Objective To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. Design, Setting, and Participants The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. Main Outcome Measures Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). Results From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], −9.0; 95% CI, −12.0 to −5.8; P P = .03), and from 240.2 to 0 for CIN3 (APC, −41.3; 95% CI, −65.7 to 0.3; P = .05). Reductions in the CIN2 incidence were also significant for women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, −6.3; 95% CI, −10.9 to −1.4; P = .02). Conclusions and Relevance Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination.

The count of the nucleotides in a cloned, short genomic sequence has become an important criterion to annotate such a sequence as a miRNA molecule. While the majority of human mature miRNA sequences consist of 22 nucleotides, there exists discrepancy in the characteristic lengths of the miRNA sequences. There is also a lack of systematic studies on such length distribution and on the biological factors that are related to or may affect this length. In this paper, we intend to fill this gap by investigating the sequence structure of human miRNA molecules using statistics tools. We demonstrate that the traditional discrete probability distributions do not model the length distribution of the human mature miRNAs well, and we obtain the statistical distribution model with a decent fit. We observe that the four nucleotide bases in a miRNA sequence are not randomly distributed, implying that possible structural patterns such as dinucleotide (trinucleotide or higher order) may exist. Furthermore, we study the relationships of this length distribution to multiple important factors such as evolutionary conservation, tumorigenesis, the length of precursor loop structures, and the number of predicted targets. The association between the miRNA sequence length and the distributions of target site counts in corresponding predicted genes is also presented. This study results in several novel findings worthy of further investigation that include: (1) rapid evolution introduces variation to the miRNA sequence length distribution; (2) miRNAs with extreme sequence lengths are unlikely to be cancer-related; and (3) the miRNA sequence length is positively correlated to the precursor length and the number of predicted target genes.

Gene set analysis is widely used to facilitate biological interpretations in the analyses of differential expression from high throughput profiling data. Wilcoxon Rank-Sum (WRS) test is one of the commonly used methods in gene set enrichment analysis. It compares the ranks of genes in a gene set against those of genes outside the gene set. This method is easy to implement and it eliminates the dichotomization of genes into significant and non-significant in a competitive hypothesis testing. Due to the large number of genes being examined, it is impractical to calculate the exact null distribution for the WRS test. Therefore, the normal distribution is commonly used as an approximation. However, as we demonstrate in this paper, the normal approximation is problematic when a gene set with relative small number of genes is tested against the large number of genes in the complementary set. In this situation, a uniform approximation is substantially more powerful, more accurate, and less intensive in computation. We demonstrate the advantage of the uniform approximations in Gene Ontology (GO) term analysis using simulations and real data sets.

In functional metagenomics, BLAST homology search is a common method to classify metagenomic reads into protein/domain sequence families such as Clusters of Orthologous Groups of proteins (COGs) in order to quantify the abundance of each COG in the community. The resulting functional profile of the community is then used in downstream analysis to correlate the change in abundance to environmental perturbation, clinical variation, and so on. However, the short read length coupled with next-generation sequencing technologies poses a barrier in this approach, essentially because similarity significance cannot be discerned by searching with short reads. Consequently, artificial functional families are produced, in which those with a large number of reads assigned decreases the accuracy of functional profile dramatically. There is no method available to address this problem. We intended to fill this gap in this paper. We revealed that BLAST similarity scores of homologues for short reads from COG protein members coding sequences are distributed differently from the scores of those derived elsewhere. We showed that, by choosing an appropriate score cut-off, we are able to filter out most artificial families and simultaneously to preserve sufficient information in order to build the functional profile. We also showed that, by incorporated application of BLAST and RPS-BLAST, some artificial families with large read counts can be further identified after the score cutoff filtration. Evaluated on three experimental metagenomic datasets with different coverages, we found that the proposed method is robust against read coverage and consistently outperforms the other E-value cutoff methods currently used in literatures.