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Small number of clusters combined with cluster level heterogeneity poses a great challenge for the data analysis. We have published a weighted Jackknife approach to address this issue applying weighted cluster means as the basic estimators. The current study proposes a new version of the weighted delete-one-cluster Jackknife analytic framework, which employs Ordinary Least Squares or Generalized Least Squares estimators as the fundamentals. Algorithms for computing estimated variances of the study estimators have also been derived. Wald test statistics can be further obtained, and the statistical comparison in the outcome means of two conditions is determined using the cluster permutation procedure. The simulation studies show that the proposed framework produces estimates with higher precision and improved power for statistical hypothesis testing compared to other methods. [ABSTRACT FROM AUTHOR]

In a large-scale environmental health population study that is composed of subprojects, often different fractions of participants out of the total enrolled have measures of specific outcomes. It's conceptually reasonable to assume the association study would benefit from utilizing additional exposure information from those with a specific outcome not measured. Partial least squares regression is a practical approach to determine the exposure-outcome associations for mixture data. Like a typical regression approach, however, the partial least squares regression requires that each data observation must have both complete covariate and outcome for model fitting. In this paper, we propose novel adjustments to the general partial least squares regression to estimate and examine the association effects of individual environmental exposure to an outcome within a more complete context of the study population's environmental mixture exposures. The proposed framework takes advantage of the bilinear model structure. It allows information from all participants, with or without the outcome values, to contribute to the model fitting and the assessment of association effects. Using this proposed framework, incorporation of additional information will lead to smaller root mean square errors in the estimation of association effects, and improve the ability to assess the significance of the effects. [ABSTRACT FROM AUTHOR]

The rates of SMM have been steadily increasing in Arkansas, a southern rural state, which has the 5th highest maternal death rate among the US states. The aims of the study were to test the functionality of the Bateman index in association to SMM, in clustering the risks of pregnancies to SMM, and to study the predictability of SMM using the Bateman index. From the ANGELS database, 72,183 pregnancies covered by Medicaid in Arkansas between 2013 and 2016 were included in this study. The expanded CDC ICD-9/ICD-10 criteria were used to identify SMM. The Bateman comorbidity index was applied in quantifying the comorbidity burden for a pregnancy. Multivariable logistic regressions, KMeans method, and five widely used predictive models were applied respectively for each of the study aims. SMM prevalence remained persistently high among Arkansas women covered by Medicaid (195 per 10,000 deliveries) during the study period. Using the Bateman comorbidity index score, the study population was divided into four groups, with a monotonically increasing odds of SMM from a lower score group to a higher score group. The association between the index score and the occurrence of SMM is confirmed with statistical significance: relative to Bateman score falling in 0–1, adjusted Odds Ratios and 95% CIs are: 2.1 (1.78, 2.46) for score in 2–5; 5.08 (3.81, 6.79) for score in 6–9; and 8.53 (4.57, 15.92) for score ≥10. Noticeably, more than one-third of SMM cases were detected from the studied pregnancies that did not have any of the comorbid conditions identified. In the prediction analyses, we observed minimal predictability of SMM using the comorbidity index: the calculated c-statistics ranged between 62% and 67%; the Precision-Recall AUC values are <7% for internal validation and <9% for external validation procedures. The comorbidity index can be used in quantifying the risk of SMM and can help cluster the study population into risk tiers of SMM, especially in rural states where there are disproportionately higher rates of SMM; however, the predictive value of the comorbidity index for SMM is inappreciable. [ABSTRACT FROM AUTHOR]

Purpose: The status and associated factors of the health-related quality of life of non-small-cell lung cancer (NSCLC) patients under targeted anti-cancer therapy have not been investigated. Self-management and coping style have been proven to be closely related to patients' health-related quality of life. Based on these observations, this study was designed to firstly assess the status of health-related quality of life, and then explore the relationships among coping styles, self-management, and health-related quality of life of NSCLC patients with skin adverse drug reactions under targeted therapy.Methods: We performed a cross-sectional study including 536 NSCLC patients with skin adverse drug reactions under targeted therapy in cancer clinics of three hospitals in China between May 2020 and May 2021. Structured questionnaires, including the Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor 18, Cancer Patient Self-management Evaluation Scale, and Medical Coping Modes Questionnaire, were used to collect data. Relationships among coping style, self-management, and health-related quality of life were identified by Pearson correlation analysis and a multiple linear regression algorithm.Results: The total score of health-related quality of life was 46 ± 12.84 in 536 NSCLC patients with skin adverse drug reactions undergoing targeted therapy. Health-related quality of life was positively correlated with self-management (r = 0.785, P < 0.01) and facing (r = 0.807, P < 0.01) and negatively correlated with yield (r =  - 0.718, P < 0.01), avoidance (r =  - 0.711, P < 0.01), and the severity of skin adverse reactions (r =  - 0.722, P = 0.000). Via multiple linear regression analysis, we identified some significant factors associated with health-related quality of life, including age, education level, combination of medicine, Charlson Comorbidity Index, stages of disease, facing, yield, symptom management, daily activity management, psychological and emotional management, self-efficacy, and self-management (P < 0.05).Conclusions: NSCLC patients with skin adverse drug reactions undergoing targeted therapy generally had a compromised health-related quality of life. The critical factors that were associated with the status of health-related quality of life were age, education level, comorbidity, the combinatorial application of drugs, stage of disease, self-management, and coping styles. [ABSTRACT FROM AUTHOR]

Background: High medication literacy is the basis of rational medication application and is essential for the management of severe adverse drug reactions. The objective of the present study was to assess the level of medication literacy and determine the association between medication literacy and skin adverse drug reactions in non-small-cell lung cancer (NSCLC) patients undergoing targeted epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy.Methods: This is a cross-sectional study conducted from May to September 2020. In total, 296 NSCLC patients undergoing targeted EGFR-TKI therapy were recruited from hospitals in Henan, China. Structured questionnaires were used to evaluate skin adverse drug reactions and medication literacy. Pearson correlation analysis and binary logistic regression analysis were carried out to identify the correlations between medication literacy and the severity of skin adverse drug reactions in the recruited patients.Results: The research sample consisted of 296 patients with a response rate of 92.5%. The mean score of skin adverse drug reactions and the mean score of medication literacy were 1.83 ± 0.91 and 6.54 ± 2.78, respectively. In total, 188 patients (63.5%) were considered to have moderate medication literacy. According to the binary logistic regression analysis, the following factors were associated with severe skin adverse drug reactions: age (B =  - 3.929, P = 0.000), sex (B = -4.062, P = 0.000), educational level (B = 2.712, P = 0.002), comorbidity (B = 3.297, P = 0.001), eczema history (B = 2.996, P = 0.001), nutritional status (B = -4.891, P = 0.000), blood interleukin-6 level (B = -2.143, P = 0.013), blood high-sensitivity C-reactive protein level (B = -4.015, P = 0.000), combination of drugs (B = -3.183, P = 0.048) and medication literacy (B =  - 1.503, P = 0.000). Subgroup analysis showed that in addition to medication literacy, some other factors including education level, comorbidity, nutritional status, blood interleukin-6 level and combined drug application were common factors that contributed to various adverse skin drug reactions in NSCLC patients under targeted EGFR-TKI therapy.Conclusion: The low medication literacy of the investigated NSCLC patients undergoing targeted EGFR-TKI therapy was correlated with a high proportion of severe skin adverse drug reactions. In addition, factors other than medication literacy including education level, comorbidity, nutritional status, blood interleukin-6 level and the combinatorial application of drugs were also related to the severity of various adverse skin drug reactions. A comprehensive and targeted intervention may be beneficial to improve medication literacy and control severe skin adverse drug reactions in NSCLC patients. [ABSTRACT FROM AUTHOR]

The change of chemical composition of aged asphalt mixture is significant to determine the mechanism of asphalt aging and obtain the direction to produce an advisable asphalt rejuvenator for the specified aged asphalt. For this purpose, this article aims to determine the change of asphaltene after the asphalt aging by centrifugal separation combined with an air stripping method. The result indicates that the content of asphaltene in aged asphalt is approximately 25%, while the content of asphaltene in base asphaltene is about 20%. In addition, compared with traditional distillation-extraction method, the new approach has the advantages of simplicity, rapidity, accuracy and a reduction in pollution to the environment. Furthermore, the analytical result could be provided for preparation and application of asphalt rejuvenators. [ABSTRACT FROM AUTHOR]

Background: High medication literacy is the basis of rational medication application and is essential for the management of severe adverse drug reactions. The objective of the present study was to assess the level of medication literacy and determine the association between medication literacy and skin adverse drug reactions in non-small-cell lung cancer (NSCLC) patients undergoing targeted epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Methods: This is a cross-sectional study conducted from May to September 2020. In total, 296 NSCLC patients undergoing targeted EGFR-TKI therapy were recruited from hospitals in Henan, China. Structured questionnaires were used to evaluate skin adverse drug reactions and medication literacy. Pearson correlation analysis and binary logistic regression analysis were carried out to identify the correlations between medication literacy and the severity of skin adverse drug reactions in the recruited patients. Results: The research sample consisted of 296 patients with a response rate of 92.5%. The mean score of skin adverse drug reactions and the mean score of medication literacy were 1.83 ± 0.91 and 6.54 ± 2.78, respectively. In total, 188 patients (63.5%) were considered to have moderate medication literacy. According to the binary logistic regression analysis, the following factors were associated with severe skin adverse drug reactions: age (B = − 3.929, P = 0.000), sex (B = -4.062, P = 0.000), educational level (B = 2.712, P = 0.002), comorbidity (B = 3.297, P = 0.001), eczema history (B = 2.996, P = 0.001), nutritional status (B = -4.891, P = 0.000), blood interleukin-6 level (B = -2.143, P = 0.013), blood high-sensitivity C-reactive protein level (B = -4.015, P = 0.000), combination of drugs (B = -3.183, P = 0.048) and medication literacy (B = − 1.503, P = 0.000). Subgroup analysis showed that in addition to medication literacy, some other factors including education level, comorbidity, nutritional status, blood interleukin-6 level and combined drug application were common factors that contributed to various adverse skin drug reactions in NSCLC patients under targeted EGFR-TKI therapy. Conclusion: The low medication literacy of the investigated NSCLC patients undergoing targeted EGFR-TKI therapy was correlated with a high proportion of severe skin adverse drug reactions. In addition, factors other than medication literacy including education level, comorbidity, nutritional status, blood interleukin-6 level and the combinatorial application of drugs were also related to the severity of various adverse skin drug reactions. A comprehensive and targeted intervention may be beneficial to improve medication literacy and control severe skin adverse drug reactions in NSCLC patients. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) testing for cervical screening has been shown to increase the yield of precancerous disease and reduce the incidence of cervical cancer more than cytology alone. Here we document the state-wide uptake of co-testing with HPV and cytology in women aged 30–64 years as recommended by national and international bodies. Registry-based study of all screening cytology and HPV tests in New Mexico from 2008 to 2019 among women aged 21–64 years, with a focus on cytology negative tests to distinguish co-testing from reflex HPV testing to triage equivocal or mildly abnormal cytology. A total of 1,704,055 cervical screening tests from 681,440 women aged 21–64 years in the state of New Mexico were identified. The proportion of screening tests which were co-tests rose from 5.6% in 2008 to 84.3% in 2019 among women aged 30–64 years with a marked change from the near exclusive use of the Hybrid Capture II HPV test, (a signal amplified test method) to the use of target amplified HPV tests. The largest increases were seen between 2013 and 2015, reflecting the introduction and adoption of new clinical guidelines. Increases in co-testing were also seen in younger women. Co-testing is now well established in women aged 30–64 years, but smaller increases have also been seen at younger ages, although this is not currently recommended. The impact of co-testing on cervical disease outcomes and number of colposcopies and biopsies in routine population settings remain important, especially in young women. • Cervical cancer screening by co-testing increased from 5.6% in 2008 to 84.3% in 2019 among women ages 30–64 years. • Smaller increases in co-test usage were observed in women of younger ages, although not currently recommended. • The median screening interval increased from 15 to 39 months as screening guideline recommendations were adopted. • The near exclusive use of the Hybrid Capture II HPV test has changed to the use of target amplified HPV tests. [ABSTRACT FROM AUTHOR]

Recent advances in virtual reality cameras have contributed to a phenomenal growth of 360$^{\circ }$∘ videos. Estimating regions likely to attract user attention is critical for efficiently streaming and rendering 360$^{\circ }$∘ videos. In this article, we present a simple, novel, GPU-driven pipeline for saliency computation and virtual cinematography in 360$^{\circ }$∘ videos using spherical harmonics (SH). We efficiently compute the 360$^{\circ }$∘ video saliency through the spectral residual of the SH coefficients between multiple bands at over 60FPS for 4K resolution videos. Further, our interactive computation of spherical saliency can be used for saliency-guided virtual cinematography in 360$^{\circ }$∘ videos. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We propose a weighted delete-one-cluster Jackknife based framework for few clusters with severe cluster-level heterogeneity. The proposed method estimates the mean for a condition by a weighted sum of estimates from each of the Jackknife procedures. Influence from a heterogeneous cluster can be weighted appropriately, and the conditional mean can be estimated with higher precision. An algorithm for estimating the variance of the proposed estimator is also provided, followed by the cluster permutation test for the condition effect assessment. Our simulation studies demonstrate that the proposed framework has good operating characteristics. [ABSTRACT FROM AUTHOR]

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 cut-off 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Lymphoma has become 1 of the 10 most common cancers with increased prevalence in young- and middle-aged adults in China. This poses a tremendous burden on patients and their families and brings great challenges to maintaining the balance of family functioning in young- and middle-aged patients. Objective This cross-sectional study aimed to analyse the influence of resourcefulness on the family functioning of Chinese young- and middle-aged lymphoma patients. Methods A total of 172 Chinese young- and middle-aged patients with lymphoma were recruited from the oncology departments of two tertiary hospitals in Zhengzhou, Henan, China. They were invited to complete a survey that included a demographic questionnaire, the Resourcefulness Scale and the Chinese Version Family Adaptability and Cohesion Scale II. Multiple linear regression was used to analyse the related factors for family functioning. Results The multiple regression analysis revealed that the main influencing factors of family cohesion were resourcefulness (β  = 0.338, 95% CI (0.072, 0.173)), spouse caregiver (β  = 0.376, 95% CI (1.938, 10.395)), and cancer stage (β  = –0.274, 95% CI (–3.219, –1.047)). Resourcefulness (β  = 0.438, 95% CI (0.096, 0.181)), spouse caregiver (β  = 0.340, 95% CI (1.348, 8.363)), and family per capita monthly income (β  = 0.157, 95% CI (0.066, 2.243)) were the influencing factors of family adaptability. Conclusions Healthcare professionals and family scholars should value young- and middle-aged lymphoma patients' family functioning throughout the cancer treatment process, and family interventions should be designed by healthcare providers based on patients' resourcefulness. Moreover, healthcare providers need to pay attention to the risk factors of patients' family cohesion and adaptability, such as low family per capita monthly income, and consider employing corresponding measures to help them. [ABSTRACT FROM AUTHOR]

• Platelet glycoprotein Ibα (GPIbα) dysfunction enhances radiation lethality in mice. • GPIbα dysfunction reduces platelet–leukocyte aggregation before/after irradiation. • GPIbα dysfunction increases monocyte activation and gut damage following radiation. • GPIbα dysfunction increases serum cytokine levels following radiation. Platelet membrane glycoprotein Ibα (GPIbα), the major ligand-binding subunit of the GPIb-IX–V complex, binds to a number of ligands contributing to hemostasis, thrombosis, and inflammation. Binding to von Willebrand factor (VWF) initiates the process of hemostasis/thrombosis, while binding to the leukocyte receptor Macrophage-1 antigen (Mac-1) has been implicated in modulating the inflammatory response. Thus as GPIbα resides at the nexus of thrombosis and inflammation, we investigated the impact of GPIbα on radiation injury outcomes as this injury triggers both the thrombotic and inflammatory pathways. We used wild-type (WT) C57BL/6J mice and a dysfunctional GPIbα mouse model, in which endogenous GPIbα is replaced with a non-functional α-subunit (hIL-4R/Ibα), to determine whether the impairment of platelet GPIbα alters radiation response. Following exposure to 8.5 Gy total body irradiation (TBI), a series of parameters including radiation lethality, platelet–neutrophil/monocyte interactions, neutrophil/monocyte activation, serum cytokine levels and intestinal injury, were compared between the strains. The lack of functional GPIbα resulted in higher radiation lethality, greater monocyte activation, increased levels of serum pro-inflammatory cytokines, heightened intestinal damage, and a reduction of intestinal neutrophil recovery. These data suggest that loss of platelet GPIbα enhances radiation toxicity and that GPIbα-mediated interactions may play a crucial role in limiting radiation damage. Thus, a mechanistic understanding of the biological impact of GPIbα following TBI could provide crucial insights for improving the safety of radiotherapy and minimizing the deleterious effects of accidental or occupational exposure to high-dose radiation. [ABSTRACT FROM AUTHOR]

To assess the level of supportive care needs of caregivers of colorectal cancer patients and explore the related key influencing factors. Totaling 283 caregivers of patients with colorectal cancer were investigated in this study. Firstly, caregivers were invited to complete a set of questionnaires, including the general information questionnaire, the Supportive Care Needs Survey-Partners and the Caregivers of cancer patients, the Caregiver Preparedness Scale, the Benefit Finding Scale, and the Comprehensive Score for Financial Toxicity. Univariate and multivariate linear regression were performed to investigate the associated factors of supportive care needs. The caregivers of patients with colorectal cancer have a moderate level of needs, scored at 2.71 ± 0.42. Caregiver preparedness, benefit finding, and financial toxicity were significantly negatively associated with the supportive care needs of caregivers (r = − 0.555, P < 0.001; r = − 0.534, P < 0.001; and r = − 0.615, P < 0.001, respectively). Our multivariate regression analysis identified some factors that directly affected the supportive care needs of caregivers, including the duration of illness, tumor stage, the age and educational level of caregivers, caregiver preparedness, benefit finding, and financial toxicity (R2 = 0.574, F = 23.337, P < 0.001). Supportive care needs are common among caregivers of colorectal cancer patients. Higher caregiver preparedness, benefit finding, and financial toxicity tend to ease these needs. Healthcare workers should have an in-depth understanding of the needs of caregivers of colorectal cancer patients and actively provide targeted financial/informational/technical/emotional support to promote nursing skills and reduce caregivers’ burdens. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

DNA ligase I (LigI), the predominant enzyme that joins Okazaki fragments, interacts with PCNA and Pol δ. LigI also interacts with UHRF1, linking Okazaki fragment joining with DNA maintenance methylation. Okazaki fragments can also be joined by a relatively poorly characterized DNA ligase IIIα (LigIIIα)-dependent backup pathway. Here we examined the effect of LigI-deficiency on proteins at the replication fork. Notably, LigI-deficiency did not alter the kinetics of association of the PCNA clamp, the leading strand polymerase Pol ε, DNA maintenance methylation proteins and core histones with newly synthesized DNA. While the absence of major changes in replication and methylation proteins is consistent with the similar proliferation rate and DNA methylation levels of the LIG1 null cells compared with the parental cells, the increased levels of LigIIIα/XRCC1 and Pol δ at the replication fork and in bulk chromatin indicate that there are subtle replication defects in the absence of LigI. Interestingly, the non-replicative histone H1 variant, H1.0, is enriched in the chromatin of LigI-deficient mouse CH12F3 and human 46BR.1G1 cells. This alteration was not corrected by expression of wild type LigI, suggesting that it is a relatively stable epigenetic change that may contribute to the immunodeficiencies linked with inherited LigI-deficiency syndrome. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore plant-derived peptides as carrier material with the function of anti-hot-melt stickiness of traditional Chinese herbal extracts during spray drying. Crataegi fructus extract (CFE) with a severe hot-melt stickiness problem was used as a model drug, and soy peptides (SPT) were screened as the most effective and suitable carrier material among seven plant-derived proteins and peptides which include soy protein isolate, walnut protein and five kinds of peptides (corn peptides, wheat peptides, walnut peptides, rice peptides and SPT). The addition of 15% SPT also exhibited a strong anti-stickiness effect in other four hot-melt sticky herbal extracts from Chinese herbs (Lycii fructus, Corni fructus, Chaenomelis fructus and Mume fructus) since the obtained powder increased from completely sticking to the wall to more than 50% powder yield. The dynamic surface tensions (DST) of CFE decreased consistently with the increase of SPT from 5% to 20%, and DST1000ms had consistent reduction with the addition of SPT from zero to 20%. Meanwhile, the adhesive force of the single droplet at 28 min decreased below 18.5 N. The softening point of the spray-dried powder of CFE added 15% SPT increased by about 40 °C, and the addition of 15% SPT improved the stability which might be similar with the addition of 50% MD based on scanning electron microscope analysis but more efficiently. These findings confirmed that SPT plant-derived could serve as effective and stable carrier material with good anti-stickiness ability during spray drying. [ABSTRACT FROM AUTHOR]

Arthritis is a general term for various types of inflammatory joint diseases. The most common clinical conditions are mainly represented by rheumatoid arthritis and osteoarthritis, which affect more than 4% of people worldwide and seriously limit their mobility. Arthritis medication generally requires long-term application, while conventional administrations by oral delivery or injections may cause gastrointestinal side effects and are inconvenient for patients during long-term application. Emerging microneedle (MN) technology in recent years has created new avenues of transdermal delivery for arthritis drugs due to its advantages of painless skin perforation and efficient local delivery. This review summarizes various types of arthritis and current therapeutic agents. The current development of MNs in the delivery of arthritis drugs is highlighted, demonstrating their capabilities in achieving different drug release profiles through different self-enhancement methods or the incorporation of nanocarriers. Furthermore, the challenges of translating MNs from laboratory studies to the clinical practice and the marketplace are discussed. This promising technology provides a new approach to the current drug delivery paradigm in treating arthritis in transdermal delivery. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seroprevalence studies largely focus on adults, but little is known about spread in children. We determined SARS-CoV-2 seroprevalence in children and adolescents from Arkansas over the first year of the coronavirus disease of 2019 (COVID-19) pandemic. Methods We tested remnant serum samples from children ages 1-18 years who visited Arkansas hospitals or clinics for non-COVID-19-related reasons from April 2020 through April 2021 for SARS-CoV-2 antibodies. We used univariable and multivariable regression models to determine the association between seropositivity and participant characteristics. Results Among 2357 participants, seroprevalence rose from 7.9% in April/May 2020 (95% CI, 4.9-10.9) to 25.0% in April 2021 (95% CI, 21.5-28.5). Hispanic and black children had a higher association with antibody positivity than non-Hispanic and white children, respectively, in multiple sampling periods. Conclusions By spring 2021, most children in Arkansas were not infected with SARS-CoV-2. With the emergence of SARS-CoV-2 variants, recognition of long-term effects of COVID-19, and the lack of an authorized pediatric SARS-CoV-2 vaccine at the time, these results highlight the importance of including children in SARS-CoV-2 public health, clinical care, and research strategies. [ABSTRACT FROM AUTHOR]

The purpose of this cross-sectional study was to estimate the proportion of Arkansas residents who were infected with the SARS-CoV-2 virus between May and December 2020 and to assess the determinants of infection. To estimate seroprevalence, a state-wide population-based random-digit dial sample of non-institutionalized adults in Arkansas was surveyed. Exposures were age, sex, race/ethnicity, education, occupation, contact with infected persons, comorbidities, height, and weight. The outcome was past COVID-19 infection measured by serum antibody test. We found a prevalence of 15.1% (95% CI: 11.1%, 20.2%) by December 2020. Seropositivity was significantly elevated among participants who were non-Hispanic Black, Hispanic (prevalence ratio [PRs]:1.4 [95% CI: 0.8, 2.4] and 2.3 [95% CI: 1.3, 4.0], respectively), worked in high-demand essential services (PR: 2.5 [95% CI: 1.5, 4.1]), did not have a college degree (PR: 1.6 [95% CI: 1.0, 2.4]), had an infected household or extra-household contact (PRs: 4.7 [95% CI: 2.1, 10.1] and 2.6 [95% CI: 1.2, 5.7], respectively), and were contacted in November or December (PR: 3.6 [95% CI: 1.9, 6.9]). Our results indicate that by December 2020, one out six persons in Arkansas had a past SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

High shear wet granulation (HSWG) is considered a complicated and multivariate pharmaceutical process that is influenced by a large number of variables derived from equipment, formulations, and processes. A better understanding and effective control of the granulation process are required to achieve the desired attributes of the final target products and to improve the efficiency of product development. This review provides a comprehensive introduction to the improvement of HSWG-based product development, including the granulation mechanism, factors affecting the granulation process, in-line monitoring technologies, and modeling methods for HSWG process. We also discuss the application of quality by design in process control, especially its two important tools, risk management and design of experience. Additionally, some potential problems and challenges in current research are analyzed and highlighted. The main purpose is to provide comprehensive guidance for formulation scientists to better understand and control the HSWG process and then improve the product development. Unlabelled Image [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• A classification method was established based on the functional parameters of powder; • w , a , k G , y 0 , k a , k b , b , k FES , k E3 are considered as key functional parameters; • The properties of each category of powder were analyzed in detail; • b is considered the most critical functional parameter affecting tablet quality; • In addition, w , k a , k G , and a related parameter affect the qualities of the tablet. Direct compaction (DC) is the ideal method for tablet production. However, DC requires the highest quality powder functional properties, such as good flowability, compressibility, compactibility, and appropriate elasticity. In the present study, 24 types of natural plant product (NPP) powders, prepared using three commonly used methods, and 18 types of fillers were evaluated for their fundamental and functional properties. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to classify the powders and analyze the characteristics of each category of powder, based on functional properties. Partial least squares (PLS) regression models were established to predict the tensile strength (TS), ejection force (EF), disintegration time (DT), and solid fraction (SF) based on the powder's functional properties. The results show that: (i) Except for the direct pulverization powder, the fundamental properties among the NPP powders were similar; however, the functional properties were quite different; (ii) The powders could be classified well based on their functional parameters (w , a , k G , y 0 , k a , k b , b , k FES , k E3). The order of powders suitable for DC is Group 4 > Group 5 > Group 2 > Group 3 > Group 1; (iii) The compressibility and compactibility of the powder are beneficial to the TS and EF of the tablet. The compressibility of the powders correlated negatively with DT; nevertheless, the compactibility correlated positively with DT and SF. The true density (ρ true), median particle size (D 0.5) of the powders correlated negatively with SF. Overall, this study systematically evaluated the properties of commonly used NPP powders and fillers and found the key properties that affect the quality of tablets. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Result: 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 < 0.00001, I2 = 83%). Five studies had shown statistically significant improvement in functional and symptoms scales in the treatment group than the control group. Conclusion: CBT is effective in improving the Quality of Life of breast cancer patients. In future research, further randomized controlled trials with adequate randomization, allocation concealment, and appropriate blinding may be needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Highlights • P75 regulated α-syn expression. • Dysregulation of siAH interacted with p75. • P75 controlled nuclear expression of p65. 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. [ABSTRACT FROM AUTHOR]

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 F 2 -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 F 2 -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 3 rd 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 F 2α, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Motivation: With the advance of new sequencing technologies producing massive short reads data, metagenomics is rapidly growing, especially in the fields of environmental biology and medical science. The metagenomic data are not only high dimensional with large number of features and limited number of samples but also complex with a large number of zeros and skewed distribution. Efficient computational and statistical tools are needed to deal with these unique characteristics of metagenomic sequencing data. In metagenomic studies, one main objective is to assess whether and how multiple microbial communities differ under various environmental conditions.Results: We propose a two-stage statistical procedure for selecting informative features and identifying differentially abundant features between two or more groups of microbial communities. In the functional analysis of metagenomes, the features may refer to the pathways, subsystems, functional roles and so on. In the first stage of the proposed procedure, the informative features are selected using elastic net as reducing the dimension of metagenomic data. In the second stage, the differentially abundant features are detected using generalized linear models with a negative binomial distribution. Compared with other available methods, the proposed approach demonstrates better performance for most of the comprehensive simulation studies. The new method is also applied to two real metagenomic datasets related to human health. Our findings are consistent with those in previous reports.Availability: R code and two example datasets are available at http://cals.arizona.edu/∼anling/software.htmContact: anling@email.arizona.eduSupplementary information: Supplementary file is available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

A new parameter named Strain/Stress Max was found to be highly relevant to tablet friability. A design space was developed to achieve <1% tablet friability at various combinations of Strain/Stress Max and tensile strength. [Display omitted] • The tablet quality attributes and texture performances of five excipients were studied systematically. • A new parameter highly relevant to tablet friability, named Strain/Stress Max, was discovered. • Strain/Stress Max was directly obtained from the diametrical breaking test. • Tablet friability values of binary mixtures were satisfactorily predicted through the constructed correlation model. • A design space of <1% tablet friability was constructed based on Strain/Stress Max and tensile strength. In this paper, a new parameter highly relevant to tablet friability is proposed based on a systematical study of the tablet quality attributes and texture performances of five different direct compression excipients, including microcrystalline cellulose, starch, lactose, mannitol, and dicalcium phosphate anhydrous. The new parameter, named Strain/Stress Max, could indicate the tablet's ability against external force to maintain integrity. It was directly obtained from the diametrical breaking test which is extensively used to assess tablet mechanical strength, and thus no extra work is required. The values varied significantly among the tablets formed by materials with different mechanical properties under the same compression pressure. A design space was developed to achieve <1% tablet friability at various combinations of Strain/Stress Max and tensile strength. Additionally, data from binary mixture tablets validated the availability of the constructed design space. And the upper limit of Strain/Stress Max value was advisable for 1.5 MPa−1 for pharmaceutical tablets. In conclusion, the new parameter and design space are available for fast identification of the tablets with acceptable friability to facilitate the development of tablet formulation using as few active pharmaceutic ingredients as possible. [ABSTRACT FROM AUTHOR]

[Display omitted] • A high-dose, high-hydrophobicity API was used for HSWG. • Failure Modes and Effect Analysis was used to evaluate CPPs and CQAs in detail. • Evaluated the influence of process variables on granule and tablet properties. • Combination of QbD and MVA provides a paradigm for HSWG–based product development. High shear wet granulation (HSWG), as a widely used granulation technology, has been studied extensively. However, for the HSWG of formulations containing hydrophobic components, the influence of process variables on the properties of granules and tablets has not been reported. In the present study, based on a combination of quality by design and multivariate analysis (MVA) approaches, quercetin with high-dose and high-hydrophobicity was used to study the relationship between process variables, granule properties, and tablet properties in HSWG systematically. Control and response variables were determined using risk assessment. The optimal fitting empirical models established by Box-Behnken design showed that the liquid to solid ratio and impeller speed were the most important factors, which affected all product properties except Carr's index and yield pressure. Instead, the influence of wet massing time was relatively small (only the effects on yield, granule size, granule hardness, and compression ratio were significant). Then, the process design space was obtained by limiting the related critical quality attributes, which was verified effectively. Scanning electron microscope images showed that smooth granules were produced using higher process parameters, whereas rough and porous granules resulted at lower process parameters. Furthermore, the MVA results demonstrated that increasing the granule hardness led to an increase in the compression ratio and a decrease in tensile strength of the tablets. Tablet fragility and disintegration time were mainly affected by granule density and bulk density, respectively, and both were negatively correlated. The established research paradigm is not only conducive to the successful development of quercetin products, but also provides valuable guidance for improving HSWG–based product development with such formulation characteristics. [ABSTRACT FROM AUTHOR]