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Background: Unmet social needs (SNs) often coexist in distinct patterns within specific population subgroups, yet these patterns are understudied. Objective: To identify patterns of social needs (PSNs) and characterize their associations with health-related quality-of-life (HRQoL) and healthcare utilization (HCU). Design: Observational study using data on SNs screening, HRQoL (i.e., low mental and physical health), and 90-day HCU (i.e., emergency visits and hospital admission). Among patients with any SNs, latent class analysis was conducted to identify unique PSNs. For all patients and by race and age subgroups, compared with no SNs, we calculated the risks of poor HRQoL and time to first HCU following SNs screening for each PSN. Patients: Adult patients undergoing SNs screening at the Mass General Brigham healthcare system in Massachusetts, United States, between March 2018 and January 2023. Main Measures: SNs included: education, employment, family care, food, housing, medication, transportation, and ability to pay for household utilities. HRQoL was assessed using the Patient-Reported Outcomes Measurement Information System Global-10. Key Results: Six unique PSNs were identified: "high number of social needs," "food and utility access," "employment needs," "interested in education," "housing instability," and "transportation barriers." In 14,230 patients with HRQoL data, PSNs increased the risks of poor mental health, with risk ratios ranging from 1.07(95%CI:1.01–1.13) to 1.80(95%CI:1.74–1.86). Analysis of poor physical health yielded similar findings, except that the "interested in education" showed a mild protective effect (0.97[95%CI:0.94–1.00]). In 105,110 patients, PSNs increased the risk of 90-day HCU, with hazard ratios ranging from 1.09(95%CI:0.99–1.21) to 1.70(95%CI:1.52–1.90). Findings were generally consistent in subgroup analyses by race and age. Conclusions: Certain SNs coexist in distinct patterns and result in poorer HRQoL and more HCU. Understanding PSNs allows policymakers, public health practitioners, and social workers to identify at-risk patients and implement integrated, system-wide, and community-based interventions. [ABSTRACT FROM AUTHOR]

Objective: To understand how diabetes mellitus (DM) diagnosed at different ages of adulthood are associated with various incident subsequent non-communicable diseases (NCDs). Methods: We performed a nationwide population-based analysis comparing 212 participants first diagnosed with DM at 20–39, 40–49, 50–59, or 60–69 years of age, with 17,541 participants without DM history, using data from the Indonesian Family Life Survey. Subsequent NCDs that were examined included hypertension, lung diseases, heart diseases, arthritis, liver diseases, kidney diseases, and digestive diseases. We estimated weighted risk ratios and 95% confidence intervals using Poisson regression, adjusting for age, sex, urbanicity, and tobacco use history. Results: Those diagnosed with DM in all age groups had significantly higher risk of hypertension, compared with those without DM history. Compared with those without DM history, younger individuals with DM diagnosed at 20–39 years of age had significantly higher risks of lung diseases and arthritis, and those with DM diagnosed at 20–49 years of age had significantly higher risk of digestive diseases. Older individuals with DM diagnosed at 40–69 years of age had significantly higher risk of liver diseases, and those with DM diagnosed at 40–59 years of age had significantly higher risk of heart diseases, compared with those without DM history. Participants with DM were diagnosed with subsequent NCDs at younger ages compared with those without DM history. Conclusion: Our findings contribute to health surveillance and may promote beneficial lifestyle changes in those with early-onset and later-onset DM, which can help prevent subsequent NCDs and improve public health. [ABSTRACT FROM AUTHOR]

Purpose: Early-onset breast cancer incidence has been increasing globally and in Taiwan. However, previous studies have not comprehensively examined how clinical and lifestyle characteristics influence the 5-year survival of breast cancer diagnosed at different stages of adulthood. Methods: We analyzed the Taiwan National Cancer Registry and Cause of Death datasets to understand how clinical factors (including tumor and treatment characteristics) and lifestyle factors (including body mass index, cigarette smoking, and alcohol consumption) were associated with the 5-year survival of 8471 young, 57,695 middle-aged, and 14,074 elderly female adult invasive breast cancer patients respectively diagnosed at age 20–39, 40–64, and ≥ 65 years between 2002 and 2015, with mortality follow-up to 2020. Poisson regression was used for obtaining the crude and adjusted 5-year survival risk ratios. Results: Clinical and lifestyle characteristics were distributed differently but had mostly similar direction of association with 5-year survival for the three age groups. Receiving any treatment was associated with better survival, especially for elderly patients. Being underweight at initial cancer treatment was associated with worse survival than having normal weight, especially for elderly patients. Current smokers had worse survival than never smokers for middle-aged and elderly patients. The 5-year breast cancer-specific survival was not significantly higher for those of age 45–49 years than 40–44 years, despite the recommended starting screening age is 45 years in Taiwan. Conclusion: Our findings contribute to the understanding of early-onset and later-onset female breast cancer characteristics and prognosis, which may inform surveillance and treatment strategies to achieve better breast cancer prognosis. [ABSTRACT FROM AUTHOR]

A dataset may exhibit multiple class labels for each observation; sometimes, these class labels manifest in a hierarchical structure. A textbook analogy would be that a book can be labelled as statistics as well as the encompassing label of non-fiction. To capture this behaviour in a model-based clustering context, we describe a model formulation and estimation procedure for performing clustering with nested Gaussian clusters in orthogonal intrinsic variable subspaces. We elucidate a two-stage clustering model, whereby the observed manifest variables are assumed to be a rotation of intrinsic primary and secondary clustering subspaces with additional noise subspaces. In a hierarchical sense, secondary clusters are presumed to be subclusters of primary clusters and so share Gaussian cluster parameters in the primary cluster subspace. An estimation procedure using the expectation-maximization algorithm is provided, with model selection via Bayesian information criterion. Real-world datasets are evaluated under the proposed model. [ABSTRACT FROM AUTHOR]

Purpose: Cancer is the second leading cause of death globally and in the U.S., but screening can reduce cancer-related deaths. We analyzed data from a nationwide survey to compare how sociodemographic factors were associated with never or not timely screening for multiple types of cancer, and the use of different colorectal cancer screening procedures. Methods: We analyzed data from the 2019 U.S. National Health Interview Survey. To understand breast, cervical, and colorectal cancer screening participation among those recommended to screen, we respectively analyzed 8,110 women 45 to 74 years of age, 9,583 women 21 to 65 years of age, and 13,497 individuals 50 to 75 years of age at survey. Weighted Poisson regression was used to estimate the unadjusted and confounding-adjusted prevalence ratio and 95% confidence intervals. Results: In our analysis populations, 6.9% never had a mammogram, 14.6% never screened for cervical cancer, and 26.8% never screened for colorectal cancer; the prevalence respectively increased to 24.7%, 23.8%, and 32.3% for not timely screening according to national guidelines. The prevalence of never screening was 81.9% for non-invasive colorectal cancer tests, compared with 32.5% for colonoscopy or sigmoidoscopy. Individuals with lower education level, with no health insurance, or in poverty had higher prevalence of never screening for all three cancers. There was low sociodemographic disparity for the use of non-invasive colorectal cancer screening tests. Conclusion: Socioeconomically disadvantaged individuals have higher prevalence of never or not timely screening. The utilization of non-invasive colorectal cancer screening procedures remains low across sociodemographic groups. [ABSTRACT FROM AUTHOR]

Generalized linear models are a popular analytics tool with interpretable results and broad applicability, but require iterative estimation procedures that impose data transfer and computational costs that can be problematic under some infrastructure constraints. We propose a doubly-sketched approximation of the iteratively re-weighted least squares algorithm to estimate generalized linear model parameters using a sequence of surrogate datasets. The procedure sketches once to reduce data transfer costs, and sketches again to reduce data computation costs, yielding wall-clock time savings. Regression coefficients and standard errors are produced, with comparison against literature methods. Asymptotic properties of the proposed procedure are shown, with empirical results from simulated and real-world datasets. The efficacy of the proposed method is investigated across a variety of commodity computational infrastructure configurations accessible to practitioners. A highlight of the present work is the estimation of a Poisson-log generalized linear model across almost 1.7 billion observations on a personal computer in 25 min. [ABSTRACT FROM AUTHOR]

Complex fibrillar networks mediate liquid–liquid phase separation of biomolecular condensates within the cell. Mechanical interactions between these condensates and the surrounding networks are increasingly implicated in the physiology of the condensates and yet, the physical principles underlying phase separation within intracellular media remain poorly understood. Here, we elucidate the dynamics and mechanics of liquid–liquid phase separation within fibrillar networks by condensing oil droplets within biopolymer gels. We find that condensates constrained within the network pore space grow in abrupt temporal bursts. The subsequent restructuring of condensates and concomitant network deformation is contingent on the fracture of network fibrils, which is determined by a competition between condensate capillarity and network strength. As a synthetic analog to intracellular phase separation, these results further our understanding of the mechanical interactions between biomolecular condensates and fibrillar networks in the cell.Liquid–liquid phase separation is known in cell biology as an underlying mechanism of intracellular organization. The authors study a complex interplay between phase separation, network mechanics, and condensate capillarity, providing explanation for the phenomena in complex environments like the cellular interior. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to improve the understanding of the interrelationships between sociodemographic factors, pregnancy intention, and antenatal care by: (1) identifying sociodemographic predictors of unintended pregnancy; (2) examining associations between unintended pregnancy types and antenatal care (ANC) inadequacy; (3) examining how the association between unintended pregnancy and ANC inadequacy is modified by maternal characteristics; and (4) identifying sociodemographic predictors of ANC inadequacy by pregnancy intention status. Methods: We analyzed women 15–49 years of age who participated in the nationwide cross-sectional Vietnam Multiple Indicator Cluster Survey. Pregnancy intention and ANC adequacy were assessed for the most recent live birth within two years preceding survey completion. Weighted Poisson regression was used to estimate risk ratios. Results: Of the 1,474 study participants, 17.8% had unintended pregnancy and 29.0% had inadequate ANC. There was no significant confounding-adjusted association between unintended pregnancy and ANC inadequacy, except in those currently not working. Women with intended pregnancy or unintended pregnancy had significantly higher ANC inadequacy risk if they lived in rural areas, were less educated, and had no media exposure, lower wealth status, or more than two children. Younger age, ever given birth, having child loss, and positive attitude towards partner violence were significant predictors of ANC inadequacy only in women with intended pregnancy. Conclusions for Practice: ANC inadequacy was more strongly predicted by sociodemographic characteristics rather than pregnancy intention, and the sociodemographic variables' prediction of ANC inadequacy was stronger in women with intended pregnancy than unintended pregnancy. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms of the small bowel are a diverse group of tumors with a broad spectrum of imaging findings and clinical implications. Most tumors originate in close proximity to the ileocecal valve and most commonly metastasize to the mesentery and liver. This review will highlight the imaging findings of primary and metastatic small bowel neuroendocrine neoplasm that are most relevant to the surgical team. [ABSTRACT FROM AUTHOR]

Background: Liver metastasis from duodenopancreatic neuroendocrine neoplasms (DP-NENs) is a major cause of mortality in multiple endocrine neoplasia type 1 (MEN1) patients, yet much of their natural history is unknown. Methods: This longitudinal, retrospective cohort study analyzed all MEN1 patients with imageable functional (F) and nonfunctional (NF) DP-NENs (1990–2021) for liver metastasis-free survival (LMFS) and overall survival (OS). Results: Of 138 patients, 85 (61.6%) had imageable DP-NENs (28 F, 57 NF), and the mean largest tumor size was 1.8 ± 1.4 cm. Multifocality was present in 32 patients (37.7%). Surgery was performed for 49 patients (57.7%). During an 11-year median follow-up period (IQR, 6–17 years), 23 (27.1%) of the patients had liver metastasis, and 19 (22.4%) patients died. Death was attributed to liver metastasis in 60% of cases. The patients with F-DP-NENs versus NF-DP-NENs more often had liver metastasis (46.4% vs. 15.8%; p = 0.002) but had similar 10-year LMFS (80.9 vs. 87.0%; p = 0.44) and OS (82.7 vs. 94.3%; p = 0.69). The patients with NF-DP-NENs had surgery when their tumors were larger (p < 0.001). Tumor size was not associated with liver metastasis (p = 0.89). The average growth rate was 0.04 cm/year (SE, 0.02 cm/year; p = 0.01) during active surveillance for NF-DP-NENs (n = 38). Liver metastasis developed in four patients with tumors smaller than 2 cm. The risk of liver metastasis was independent of surgery (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.21–2.93; p = 0.72) and death (HR, 0.51; 95% CI, 0.08–3.06; p = 0.46). Conclusions: Although the observed outcomes in this study were better than historical data, small NF-DP-NENs still developed liver metastasis and liver metastasis remains a major cause of death. These results suggest that size as a sole criterion for surgery may be insufficient to predict tumor behavior. [ABSTRACT FROM AUTHOR]

Insulin therapy often increases body weight and leads to visceral fat accumulation. Progression in diabetes is also associated with accelerated loss of muscle mass. Little is known about body composition changes in type 2 diabetes mellitus (T2DM) patients on insulin therapy who use sodium–glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors. This study examined the effect of 25 mg of empagliflozin compared with 5 mg of linagliptin for 24 weeks on body weight and body composition in patients with T2DM on premixed insulin. Body composition was assessed with bioelectrical impedance analysis. The mean difference between the linagliptin and empagliflozin groups in terms of mean body weight change from baseline to 24 weeks was − 1.80 kg (95% CI − 2.57, − 1.03). Empagliflozin also significantly reduced muscle mass (− 1.39 kg, 95% CI − 2.49, − 0.29) and total body water (− 1.07 kg, 95% CI − 1.88, − 0.27) compared with linagliptin. Compared to linagliptin, empagliflozin decreased body fat mass more from baseline to week 24, but this was not significant (− 0.31 kg, 95% CI − 1.51, 0.90). Further research on insulin-treated T2DM patients is necessary to investigate the long-term effects of SGLT2 and DPP4 inhibitors on body composition, as well as their effects on muscle strength and physical function. Trial registration: ClinicalTrials.gov no. NCT03458715, registration date: March 8, 2018. [ABSTRACT FROM AUTHOR]

In the era of single-cell sequencing, there is a growing need to extract insights from data with clustering methods. Here, we introduce Forest Fire Clustering, an efficient and interpretable method for cell-type discovery from single-cell data. Forest Fire Clustering makes minimal prior assumptions and, different from current approaches, calculates a non-parametric posterior probability that each cell is assigned a cell-type label. These posterior distributions allow for the evaluation of a label confidence for each cell and enable the computation of "label entropies", highlighting transitions along developmental trajectories. Furthermore, we show that Forest Fire Clustering can make robust, inductive inferences in an online-learning context and can readily scale to millions of cells. Finally, we demonstrate that our method outperforms state-of-the-art clustering approaches on diverse benchmarks of simulated and experimental data. Overall, Forest Fire Clustering is a useful tool for rare cell type discovery in large-scale single-cell analysis. In the era of single-cell sequencing, there is a growing need to extract insights from data with clustering methods. Here, inspired by forest fire dynamics, the authors devise an algorithm that can cluster single-cell data with minimal prior assumptions and can compute a non-parametric posterior probability for each data point. [ABSTRACT FROM AUTHOR]

Hybrid species tend to exhibit a mixture of parent characteristics; we propose chimeral clusters as exhibiting a mixture of parent parameters, a type of intercluster structure. Morphometric measurements in the iris dataset describe the hybrid Iris versicolor as intermediate to those of parent species Iris setosa and Iris virginica, which motivates our extension of Gaussian mixture models to allow mixing in the parameter space. We propose a mixing mechanism whereby chimeral clusters are parameterized by a convex combination of fully varying prototype cluster parameters and characterize the identifiability of the postulated mixture model. Estimation of chimeral clustering models is described using variations of the expectation-maximization algorithm and the solution to the continuous-time algebraic Riccati equation. The efficacy of chimeral clustering is demonstrated using morphometric datasets describing iris, Cooper's hawks, and water striders, with comparisons to typical Gaussian mixture models. We evaluate parameter recovery on a synthetic dataset and demonstrate that parsimonious covariance matrices and chimeral clustering capture different kinds of intercluster structure. [ABSTRACT FROM AUTHOR]

RNA-seq has matured and become an important tool for studying RNA biology. Here we compared two RNA-seq (MGI DNBSEQ and Illumina NextSeq 500) and two microarray platforms (GeneChip Human Transcriptome Array 2.0 and Illumina Expression BeadChip) in healthy individuals administered recombinant human erythropoietin for transcriptome-wide quantification of differential gene expression. The results show that total RNA DNB-seq generated a multitude of target genes compared to other platforms. Pathway enrichment analyses revealed genes correlate to not only erythropoiesis and oxygen transport but also a wide range of other functions, such as tissue protection and immune regulation. This study provides a knowledge base of genes relevant to EPO biology through cross-platform comparisons and validation. [ABSTRACT FROM AUTHOR]

Introduction: Cancer patients are increasingly incorporating medical marijuana into the management of treatment-related side effects. Currently however, data is limited regarding the risks and benefits of therapeutic cannabis for cancer patients. We sought to characterize radiation oncologists' practices and opinions regarding therapeutic cannabis via a nationwide survey. Materials and methods: An anonymous survey was distributed via email to 873 radiation oncologists in the American Society for Radiation Oncology member database. Radiation oncologists were asked their opinions and practices regarding the use of therapeutic cannabis for their patients. Bivariate analyses of potential predictors for responses were conducted using standard statistical techniques. Results: One hundred seven radiation oncologists completed the survey. According to the survey, 36% of respondents would recommend therapeutic cannabis to their patients to mitigate treatment toxicity. Physicians practicing in states where medical marijuana is legal were more likely to recommend it compared to physicians working in states that have not legalized medical marijuana (OR = 3.79, 1.19–12.1, p = 0.01). Seventy-one percent of respondents reported therapeutic cannabis as being effective at least some of the time for managing treatment-related toxicities. Fifty-eight percent of physicians reported lacking sufficient knowledge to advise patients regarding therapeutic cannabis, while 86% of respondents were interested in learning more about therapeutic cannabis for cancer patients. Conclusions: Although a majority of radiation oncologists believe there are benefits to therapeutic cannabis, many are hesitant to recommend for or against its use. Radiation oncologists appear to be interested in learning more about how therapeutic cannabis may play a role in their patients' care. [ABSTRACT FROM AUTHOR]

Accesses Per Cycle (APC), Concurrent Average Memory Access Time (C-AMAT), and Layered Performance Matching (LPM) are three memory performance models that consider both data locality and memory assess concurrency. The APC model measures the throughput of a memory architecture and therefore reflects the quality of service (QoS) of a memory system. The C-AMAT model provides a recursive expression for the memory access delay and therefore can be used for identifying the potential bottlenecks in a memory hierarchy. The LPM method transforms a global memory system optimization into localized optimizations at each memory layer by matching the data access demands of the applications with the underlying memory system design. These three models have been proposed separately through prior efforts. This paper reexamines the three models under one coherent mathematical framework. More specifically, we present a new memory- centric view of data accesses. We divide the memory cycles at each memory layer into four distinct categories and use them to recursively define the memory access latency and concurrency along the memory hierarchy. This new perspective offers new insights with a clear formulation of the memory performance considering both locality and concurrency. Consequently, the performance model can be easily understood and applied in engineering practices. As such, the memory-centric approach helps establish a unified mathematical foundation for model-driven performance analysis and optimization of contemporary and future memory systems. [ABSTRACT FROM AUTHOR]

Background: Understanding variation and heterogeneity in practice patterns allows programs to develop effective strategies to improve patient outcomes. Cytoreductive surgery is a potentially highly morbid operation that could benefit from systematic assessments directed towards quality improvement. We describe the hospital-level variation and benchmarks for programs performing cytoreductive surgery. Patients and Methods: Cytoreductive and tumor debulking operations with or without hyperthermic intraperitoneal chemotherapy performed for cancer between January 1, 2013 and June 30, 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program registry. Risk-adjusted hospital-level variation in 30-day death, serious morbidity, reoperation, readmission, and a composite of death or serious morbidity (DSM) were evaluated using hierarchical models. National Cancer Institute (NCI)-designated cancer center (NCI-CC) status was also explored. Results: A total of 6203 operations across 589 hospitals were included, of which 56 were at NCI-CCs. Unadjusted rates of death, serious morbidity, reoperation, readmission, and DSM were 1.4%, 12.9%, 3.6%, 8.6%, and 13.4%, respectively. The coefficients of variation for hospital-level performance were 4.7%, 2.1%, 4.6%, 14.4%, and 1.0% for DSM, death, serious morbidity, unplanned reoperation, and unplanned readmissions, respectively. When compared with other hospitals, NCI-CCs had better risk-adjusted 30-day mortality (median odds ratio 0.984 versus 0.998, p < 0.001), but not for the other outcomes studied. Conclusions: Hospital-level variation was modestly detected using the usual measures of perioperative outcomes. Given the increasing interest in cytoreductive surgery, we demonstrate a clear opportunity to not only improve the quality of our care but to also better improve the way quality is measured for these patients. [ABSTRACT FROM AUTHOR]

The embryonic stem cell-specific cell cycle-regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGF?-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions. [ABSTRACT FROM AUTHOR]

The regulation of energy homeostasis integrates diverse biological processes ranging from behavior to metabolism and is linked fundamentally to numerous disease states. To identify new molecules that can bypass homeostatic compensatory mechanisms of energy balance in intact animals, we screened for small-molecule modulators of Caenorhabditis elegans fat content. We report on several molecules that modulate fat storage without obvious deleterious effects on feeding, growth and reproduction. A subset of these compounds also altered fat storage in mammalian and insect cell culture. We found that one of the newly identified compounds exerts its effects in C. elegans through a pathway that requires previously undescribed functions of an AMP-activated kinase catalytic subunit and a transcription factor previously unassociated with fat regulation. Thus, our strategy identifies small molecules that are effective within the context of intact animals and reveals relationships between new pathways that operate across phyla to influence energy homeostasis. [ABSTRACT FROM AUTHOR]

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 × 10−19) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3. [ABSTRACT FROM AUTHOR]

Cultural identity is central to health. Acculturation may be formulated with a bicultural model, assessing in parallel the degree of identification with both the original and the host culture. The Cortes, Rogler and Malgady Bicultural Scale (CRM-BS) is composed of two subscales: “original” culture and “mainstream-United States” (US) culture. It was modified into three ethnic versions: Latino, Korean and Chinese. Validation of the CRM-BS was conducted using health professionals and psychiatric patients from the above three ethnic groups and a control sample of mainstream-US (main-US) health professionals in New York City ( n = 394). Mean time of completion was 3.7 min and 73% judged it to be easy to use. Strong test–retest reliability correlation coefficients were found (original culture, 0.78; mainstream-US, 0.82). The internal consistency was documented by high Cronbach’s alpha values (original culture, 0.88; mainstream-US, 0.80). Factorial analysis revealed two factors, the first one involving all the items of the original culture and the second all of the mainstream-US items. Concerning its discriminant validity, non-main-US subjects scored significantly higher than main-US subjects on the original culture subscale, and vice versa. Construct validity was assessed comparing intergenerational mean scores on both subscales; as generations become older, mean scores for the original culture decreased, while those for the “host” culture increased. Results for each specific ethnic version are also presented. Cutoff scores were calculated to categorize the involvement with the original culture or the host culture, both of them, or neither. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM. [ABSTRACT FROM AUTHOR]

This study documents the validation study of the Multicultural Quality of Life Index, Chinese version (MQLI-Ch). This self-rated instrument is composed of ten items that correspond to multiple dimensions of the concept of quality of life. Each item is rated on a scale from 1 to 10, according to the subject’s culture-informed understanding of the concept. The MQLI-Ch was tested on 144 Chinese subjects (124 psychiatric patients and 20 professionals). It was found to be quite efficient (about 3 min to be completed) and easy to use. A Cronbach’s α of 0.94 demonstrated its internal consistency. The factor analysis of the ten items yielded one single factor, which accounted for 65.19% of the variance. The test–retest reliability correlation coefficient was 0.80. Its discriminant validity was documented by a highly significant difference ( P < 0.001) between the mean scores of the two samples with presumed differences in quality of life. Thus, the MQLI-Ch showed high feasibility, internal structure, reliability and discriminant validity. [ABSTRACT FROM AUTHOR]

Our research team of multilingual and multicultural members designed comprehensive, yet efficient, culture-informed, and self-rated Multicultural Quality of Life Indexes for both English-speaking individuals and for growing immigrant groups in the United States. A Korean version of the Multicultural Quality of Life Index (MQLI-Kr) was developed as part of this multilingual project. The team tested the MQLI-Kr on 130 Koreans (100 psychiatric patients and 30 professionals). MQLI-Kr was quite efficient and easy to use. The internal consistency attained a Cronbach’s α of 0.97 for the combined sample. A factor analysis yielded one single factor, which accounted for 81.5% of the items’ variance. The test–retest reliability correlation coefficient of the MQLI-Kr was 0.85. Significant differences in the mean MQLI-Kr scores were observed between the patients’ group and the professionals’ group ( p < 0.001). Thus the results of this study showed high feasibility, internal consistency, reliability, and discriminant validity for the MQLI-Kr. [ABSTRACT FROM AUTHOR]

Foregut malformations (oesophageal atresia, tracheo-oesophageal fistula, lung anomalies and congenital stenosis of the oesophagus and trachea) are relatively common anomalies occurring in 1 in 2,000-5,000 live births, although their aetiology is poorly understood. The secreted glycoprotein Sonic hedgehog (Shh) has been suggested to act as an endodermal signal that controls hindgut patterning and lung growth. In mice, three zinc-finger transcription factors, Gli1, Gli2 and Gli3, have been implicated in the transduction of Shh signal. We report here that mutant mice lacking Gli2 function exhibit foregut defects, including stenosis of the oesophagus and trachea, as well as hypoplasia and lobulation defects of the lung. A reduction of 50% in the gene dosage of Gli3 in a Gli2?/? background resulted in oesophageal atresia with tracheo-oesophageal fistula and a severe lung phenotype. Mutant mice lacking both Gli2 and Gli3 function did not form oesophagus, trachea and lung. These results indicate that Gli2 and Gli3 possess specific and overlapping functions in Shh signalling during foregut development, and suggest that mutations in GLI genes may be involved in human foregut malformations. [ABSTRACT FROM AUTHOR]

Chronic inflammation underlies many autoimmune diseases, including hypothyroidism, hyperthyroidism, and rheumatoid arthritis, also type-2 diabetes and osteoarthritis. Associations have been suggested of high-dose ionising radiation exposure with type-2 diabetes and elevated levels of C-reactive protein, a marker of chronic inflammation. In this analysis we used a proportional hazards model to assess effects of radiotherapy on risks of subsequent inflammatory disease morbidity in 110,368 US radiologic technologists followed from a baseline survey (1983-1989/1994-1998) through 2008. We used a linear model to assess log-transformed C-reactive protein concentration following radiotherapy in 1326 technologists. Relative risk of diabetes increased following radiotherapy (p < 0.001), and there was a borderline significant increasing trend per treatment (p = 0.092). For osteoarthritis there was increased relative risk associated with prior radiotherapy on all questionnaires (p = 0.005), and a significant increasing trend per previous treatment (p = 0.024). No consistent increases were observed for other types of inflammatory disease (hypothyroidism, hyperthyroidism, rheumatoid arthritis) associated with radiotherapy. There was a borderline significant (p = 0.059) increasing trend with dose for C-reactive protein with numbers of prior radiotherapy treatments. Our results suggest that radiotherapy is associated with subsequent increased risk of certain inflammatory conditions, which is reinforced by our finding of elevated levels of C-reactive protein. [ABSTRACT FROM AUTHOR]