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Despite advances in treating newly diagnosed multiple myeloma (NDMM), a biomarker-driven personalized approach remains an unmet need. A combination of lenalidomide and dexamethasone (RD) is a widely available chemotherapeutic option for NDMM. We aimed to find a circulating immune cell-based biomarker to predict prognosis following RD in patients with NDMM. Clinical data and peripheral blood samples of 71 consecutive NDMM patients treated with RD were retrospectively analyzed. Peripheral blood samples were taken at the time of diagnosis. Immune cell populations, including natural killer (NK) cells, T cells, and their subpopulations, were identified by flow cytometry. In univariable analysis, four variables, including low expression (third or lower quartile) of NK cells, high expression (first or greater quartile) of regulatory T (Treg) cells, female sex, and lambda light chain type, could be plausible factors in predicting poor progression-free survival (PFS). With use of the ratio of NK cells to Treg cells (NK/Treg) as a biomarker, the median PFS of patients with low NK/Treg (less than first quartile, n = 18) was significantly inferior to that of patients with high NK/Treg (first or greater quartile, n = 53): 19.8 months versus 57.3 months, p = 0.047. In multivariable analysis, low NK/Treg was significantly associated with poor PFS (hazard ratio: 2.877, 95% confidence interval: 0.001-1.009, p = 0.048), even after adjusting for other confounding factors. NK/Treg at the time of diagnosis might be a useful immune cell biomarker for clinical decision-making for the use of RD in NDMM. Further investigations are needed to improve outcomes of NDMM patients based on the understanding of the role of NK/Treg.

Supplementary figure S1. Differential sensitivity of human AML LSCs to JQ1. Supplementary figure S2. Relative levels of the autophagy pathway effectors LC3-II, beclin-1, and pULK1 (S555). Supplementary figure S3. Autophagy induction in KG1 and KG1a cells and effects of autophagy inhibition on JQ1-induced apoptosis in LSCs. Supplementary figure S4. JQ1-induced apoptosis through intrinsic apoptosis pathway in JQ1-sensitive LSCs. Supplementary figure S5. Diagram illustrating the potential effects of the BET inhibitor JQ1 in JQ1-resistant LSCs.

Purpose: Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSC) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1.Experimental Design: We evaluated the levels of apoptosis and autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34+CD38− leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations.Results: JQ1 effectively induced apoptosis in a concentration-dependent manner in JQ1-sensitive AML cells. However, in JQ1-resistant AML LSCs, JQ1 induced little apoptosis and led to upregulation of beclin-1, increased LC3-II lipidation, formation of autophagosomes, and downregulation of p62/SQSTM1. Inhibition of autophagy by pharmacologic inhibitors or knockdown of beclin-1 using specific siRNA enhanced JQ1-induced apoptosis in resistant cells, indicating that prosurvival autophagy occurred in these cells. Independent of mTOR signaling, activation of the AMPK (pThr172)/ULK1 (pSer555) pathway was found to be associated with JQ1-induced autophagy in resistant cells. AMPK inhibition using the pharmacologic inhibitor compound C or by knockdown of AMPKα suppressed autophagy and promoted JQ1-induced apoptosis in AML LSCs.Conclusions: These findings revealed that prosurvival autophagy was one of the mechanisms involved in the resistance AML LSCs to JQ1. Targeting the AMPK/ULK1 pathway or inhibition of autophagy could be an effective therapeutic strategy for combating resistance to BET inhibitors in AML and other types of cancer. Clin Cancer Res; 23(11); 2781–94. ©2016 AACR.

Patient characteristics according to JQ1 sensitivity in primary acute myeloid leukemia blasts

BACKGROUND: Antisocial personality disorder (ASPD) incurs a high cost to society due to the high risk of violent and nonviolent offenses associated with this personality disorder, thus making the examination of the etiology and the onset of ASPD an important public health concern. METHOD: The present study consisted of five waves of data collection of the Harlem Longitudinal Development Study (N=674). In the Cox proportional hazard model, latent multiple substance use trajectories from mid-adolescence to emerging adulthood (mean age 14 to mean age 24) were used as a predictor for the onset of ASPD during emerging adulthood to the mid-thirties (mean age 24 to mean age 36). The control variables were gender, ethnicity, problem behaviors, and victimization. RESULTS: In the multiple Cox proportional hazard model, the high (HR = 2.74, p

Over the past few decades, DNA has been recognized as a powerful self-assembling material capable of crafting supramolecular nanoarchitectures with quasi-angstrom precision, which promises various applications in the fields of materials science, nanoengineering, and biomedical science. Notable structural features include biocompatibility, biodegradability, high digital encodability by Watson-Crick base pairing, nanoscale dimension, and surface addressability. Bottom-up fabrication of complex DNA nanostructures relies on the design of fundamental DNA motifs, including parallel (PX) and antiparallel (AX) crossovers. However, paranemic or PX motifs have not been thoroughly explored for the construction of DNA-based nanostructures compared to AX motifs. In this review, we summarize the developments of PX-based DNA nanostructures, highlight the advantages as well as challenges of PX-based assemblies, and give an overview of the structural and chemical features that lend their utilization in a variety of applications. The works presented cover PX-based DNA nanostructures in biological systems, dynamic systems, and biomedical contexts. The possible future advances of PX structures and applications are also summarized, discussed, and postulated.

This study aimed to investigate predictors of male sexual partner risk among Latinas and Black women in their late thirties. We used multiple regression analysis to examine factors associated with male sexual partner risk among 296 women who participated in two waves of the Harlem Longitudinal Development Study (New York, 2011-2013 and 2014-2016). Women who experienced childhood sexual abuse had higher risk partners than those who did not [b = 0.16, 95% confidence interval (CI) = 0.06, 0.28]. Earlier marijuana use was a risk factor for partner risk in the late thirties (b = 0.12, 95% CI = 0.04, 0.27). Higher levels of ethnic/racial identity commitment mitigated this risk (b = - 0.15, 95% CI = - 0.26, - 0.04). Ethnic/racial identity commitment can be protective against male sexual partner risk among Latina and Black women who use marijuana. Further research should explore the protective role of different dimensions of ethnic/racial identity against sexually transmitted infections, including HIV.

Schwarz’s Bayesian information criterion (BIC) is one of the most popular criteria for model selection, that was derived under the assumption of independent and identical distribution. For correlated data in longitudinal studies, Jones (Statistics in Medicine, 30, 3050–3056, 2011) modified the BIC to select the best linear mixed effects model based on the effective sample size where the number of parameters in covariance structure was not considered. In this paper, we propose an extended Jones’ modified BIC by considering covariance parameters. We conducted simulation studies under a variety of parameter configurations for linear mixed effects models. Our simulation study indicates that our proposed BIC performs better in model selection than Schwarz’s BIC and Jones’ modified BIC do in most scenarios. We also illustrate an example of smoking data using a longitudinal cohort of cancer patients.

Although MYC and BCL2 co-expression in diffuse large B cell lymphoma (DLBCL) is associated with inferior prognosis, it remains uncertain whether upfront autologous hematopoietic stem cell transplantation (ASCT) is beneficial in this lymphoma. This study aimed to investigate whether ASCT consolidation could have a positive role for patients with MYC and BCL2 co-expression (double-expressor lymphoma, DEL). We retrospectively evaluated 67 DLBCL patients who underwent upfront ASCT following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) were 82.3% and 79.2%, respectively. There were 23 (34.3%) patients with DEL and 51 (76.1%) patients with non-germinal center B cell (GCB) subtype. The 5-year OS and PFS of patients with DEL were not different from those with non-DEL (P = 0.429 and P = 0.614, respectively). No survival difference for OS and PFS was also observed between GCB and non-GCB subtypes (P = 0.950 and P = 0.901, respectively). The OS and PFS were comparable for patients with DEL and non-DEL and both GCB and non-GCB subtypes. In conclusion, MYC and BCL2 co-expression did not have a poor prognostic impact among high-risk patients with DLBCL treated with upfront ASCT regardless of molecular classification. This preliminary study suggested that the role of consolidative ASCT is needed to be evaluated in a prospective randomized clinical trial.

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Background: The adverse consequences of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) affect a significant portion of the US population every year (i.e., 15 million for MDD; 8 million for PTSD) and are of public health concern. The current study examines tobacco, alcohol, and marijuana use as possible longitudinal predictors of MDD and/or PTSD. Methods: A community sample of 674 participants (53% African Americans and 47% Puerto Ricans; 405 females and 269 males) were recruited from the Harlem Longitudinal Development Study. We used M plus software to obtain the triple trajectories of tobacco, alcohol, and marijuana use from mean age 14 to 36. Logistic regression analyses were then conducted to examine the associations between those triple trajectory groups and a single diagnosis of MDD or PTSD as well as a dual diagnosis of MDD with PTSD at age 36. Results: The observed percentages of MDD, PTSD, and the comorbidity of MDD and PTSD were 17%, 8%, and 5%, respectively. The heavy use of all 3 substances group was associated with an increased likelihood of having MDD (adjusted odds ratio [AOR] = 3.14, P

In New York City, over 90% of women newly diagnosed with human immunodeficiency virus (HIV) are Black and Latina; a quarter of these infections occur among 30-39 year-olds. A survey was administered to 343 Black and Puerto Rican women (2014-2016) to examine two HIV infection risk factors: relationship exclusivity and having experienced childhood sexual abuse (CSA). A majority of male partners (69.7%) had at least one risk for HIV transmission. Women in non-exclusive sexual relationships (nESRs) had higher-risk partners, but engaged in safer sex practices than those in ESRs. Two-thirds of women in ESRs (64.8%) reported unprotected vaginal intercourse, although 33.5% had partners with a history of concurrent relationships. Among women in nESRs, having experienced CSA was a strong risk factor for HIV infection. Black and Latina women's vulnerability to HIV infection is significant, even when in exclusive relationships. Safer sex counseling should be integrated in primary care.

Approximately 9% of adults report the symptoms of insomnia, and there are a number of adverse consequences of insomnia. This could be a public health concern. The current study seeks plausible longitudinal predictors of insomnia for prevention purposes. A community sample of 674 participants (53% African Americans and 47% Puerto Ricans; 60% were females) were recruited from the Harlem Longitudinal Development Study. We applied a growth mixture model to obtain the triple trajectories of alcohol, cigarette, and marijuana use. Logistic regression analyses were then conducted to examine the associations between the triple trajectory groups from mean age 14 to 36 and insomnia at age 36. The estimated prevalence of insomnia is 7.1%. A five-group triple trajectory model was selected: A) Increasing use of all three substances (18%); B) Moderate use of alcohol and marijuana, and high use of cigarette (11%); C) Moderate use of alcohol and cigarette, and experimental use of marijuana (3%); D) Moderate use of all three substances (5%); and E) No or low use of all three substances (63%). Among the five trajectory groups, the increasing use of all three substances group (AOR = 2.71, p-value = .011) was associated with an increased likelihood of having insomnia as compared to the no or low use of all three substances group. Treatment programs to quit or reduce the use of alcohol, cigarette, and marijuana may help decrease the prevalence of insomnia. This could lead to improvements in individualized treatments for patients who have symptoms of insomnia and who also use substances.

Objectives As the rate of cannabis use increases, it is expected that more individuals will develop a Cannabis Use Disorder (CUD). Relatively little is known, however, about the psychosocial correlates of CUDs among racial/ethnic minority women. This study, therefore, examined correlates of CUDs among a cohort of adult African American and Puerto Rican women. Methods The sample consisted of African American and Puerto Rican female participants (N = 343), who have been followed by the Harlem Longitudinal Development Study from mean age 14 to mean age 39 years. The bivariate and multivariate associations between CUDs at age 39 and variables from 5 domains - demographics, earlier cannabis use, childhood abuse, the relationship with the spouse/partner, and media exposure - were assessed using logistic regression analyses. Results The results showed that, with the exception of demographic factors, variables from each of the domains (e.g., sexual abuse in childhood, arguments with spouse/partner, and hours of visual media exposure) were related to CUDs at age 39. Conclusions Findings suggest that in addition to treating CUDs, couples therapy may be indicated to strengthen the spousal/partner relationship, enlist the spouse/partner's support for cannabis use cessation. Furthermore, frequency of visual media exposure may need to be reduced.

Influenza viruses can result in significant lung injury with significant morbidity and mortality. In this study, we evaluated the impact of cigarette smoke (CS) exposure on the pulmonary fibroblastic response after influenza infection. We used a murine model in which animals were exposed to CS or room air and subsequently infected with H1N1 influenza virus. Inflammatory and fibrotic responses were measured at different time points after influenza infection. Primary fibroblasts were isolated from the lungs of mice and their characteristics were evaluated. Exposure to CS significantly increased the amount of collagen in the lungs of mice infected with influenza virus compared with the nonsmoking group at 30 days after infection. Furthermore, the presence of fibroblast-specific protein–positive cells increased in the lungs of influenza-infected mice that were exposed to CS compared with the infection-alone group. The smoking group also showed delays in weight recovery and higher cell counts in BAL fluid after infection. Active transforming growth factor β1 levels in BAL fluid increased in both groups; however, CS-exposed mice had a later surge in active transforming growth factor β1 (Day 24). Ex vivo cultures of lung-derived fibroblasts from CS-exposed mice with influenza infection showed rapid proliferation, increased expression of α-smooth muscle actin–stained stress fibers, and higher expression of growth factors compared with fibroblasts from room air–exposed lungs after infection. These results suggest that CS exposure changes the fibroblastic potential, leading to increased fibrosis after influenza infection.

Hyun Lee,1,* Byung Woo Jhun,1,* Juhee Cho,2–4 Kwang Ha Yoo,5 Jin Hwa Lee,6 Deog Kyeom Kim,7 Jong Deog Lee,8 Ki-Suck Jung,9 Jung Yeon Lee,10 Hye Yun Park1 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 2Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 4Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea; 6Division of Pulmonary and Critical Care Medicine, School of Medicine, Ewha Womans University, Seoul, South Korea; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, South Korea; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungju Hospital, Konkuk University School of Medicine, Chungju, South Korea *These authors contributed equally to this work Background: Patients with chronic obstructive pulmonary disease (COPD) often have poor health-related quality of life (HRQoL) that is disproportionate to their degree of airflow limitation. This study evaluated the association between St George’s Respiratory Questionnaire for COPD (SGRQ-C) score and forced expiratory volume in one second and investigated the factors responsible for high SGRQ-C score according to severity of airflow limitation.Methods: Data from 1,264 COPD patients were obtained from the Korean COPD Subgroup Study (KOCOSS) cohort. Patients were categorized into two groups according to severity of airflow limitation: mild-to-moderate and severe-to-very severe COPD groups. We evaluated the clinical factors associated with high SGRQ-C score (≥25) in each COPD patient group.Results: Of the 1,264 COPD patients, 902 (71.4%) had mild-to-moderate airflow limitation and 362 (28.6%) had severe-to-very severe airflow limitation. Of the mild-to-moderate COPD patients, 59.2% (534/902) had high SGRQ-C score, while 80.4% (291/362) of the severe-to-very severe COPD patients had high SGRQ-C score. The association between SGRQ-C score and post-bronchodilator forced expiratory volume in one second (% predicted) was very weak in the mild-to-moderate COPD patients (r=–0.103, p=0.002) and weak in the severe-to-very severe COPD patients (r=–0.219, p

A quarter of people living with human immunodeficiency virus (HIV) infection in the United States are women. Furthermore, African American and Hispanic/Latina women continue to be disproportionately affected by HIV, compared with women of other races/ethnicities. Cannabis use prior to intercourse may be associated with increased risky sexual behaviors which are highly related to HIV. The ultimate goal of this research is to better understand the relationships between unconventional personal attributes (e.g., risk-taking behaviors) in the late 20s, substance use (e.g., alcohol) in the mid 30s, and cannabis use prior to intercourse in the late 30s using a community sample; such an understanding may inform interventions. This study employing data from the Harlem Longitudinal Development Study includes 343 female participants (50% African Americans, 50% Puerto Ricans). Structural equation modeling indicated that unconventional personal attributes in the late 20s were associated with substance use in the mid 30s (β=0.32, p

Purpose: Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSC) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. Experimental Design: We evaluated the levels of apoptosis and autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34+CD38− leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations. Results: JQ1 effectively induced apoptosis in a concentration-dependent manner in JQ1-sensitive AML cells. However, in JQ1-resistant AML LSCs, JQ1 induced little apoptosis and led to upregulation of beclin-1, increased LC3-II lipidation, formation of autophagosomes, and downregulation of p62/SQSTM1. Inhibition of autophagy by pharmacologic inhibitors or knockdown of beclin-1 using specific siRNA enhanced JQ1-induced apoptosis in resistant cells, indicating that prosurvival autophagy occurred in these cells. Independent of mTOR signaling, activation of the AMPK (pThr172)/ULK1 (pSer555) pathway was found to be associated with JQ1-induced autophagy in resistant cells. AMPK inhibition using the pharmacologic inhibitor compound C or by knockdown of AMPKα suppressed autophagy and promoted JQ1-induced apoptosis in AML LSCs. Conclusions: These findings revealed that prosurvival autophagy was one of the mechanisms involved in the resistance AML LSCs to JQ1. Targeting the AMPK/ULK1 pathway or inhibition of autophagy could be an effective therapeutic strategy for combating resistance to BET inhibitors in AML and other types of cancer. Clin Cancer Res; 23(11); 2781–94. ©2016 AACR.

The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P

Millions of people are living with the human immunodeficiency virus (HIV). African American and Hispanic/Latino communities suffer the most severe burden of HIV in the US. The ultimate goal of this study was to better understand risk factors for this infection: Do impulsivity and self control operate independently or synergistically with respect to HIV sexual risk behaviors in women? An enhanced understanding of these risk factors may better inform future interventions. Among the total of 343 female participants, half were African American and the other half were Latina. Data in this study were collected in the area of New York City during 2014–2016, when the mean age of the participants was 39 years. Linear regression analyses were used to examine the associations of impulsivity and self control with HIV sexual risk behaviors. Impulsivity and self control were independently associated with most of the HIV sexual risk behaviors examined. In addition, the interaction terms between impulsivity and low self control were all significantly associated with each of the sexual risk behaviors. Prevention programs should consider incorporating the roles of impulsivity and self control simultaneously as related to HIV risk behaviors., Highlights • Impulsivity was positively associated with the HIV sexual risk behaviors. • Self control was negatively associated with the HIV sexual risk behaviors. • Interaction effect of impulsivity and low self control was related to HIV risks.

Objective To examine the effect of long-term violent victimization from late adolescence to the mid-30s on posttraumatic stress disorder (PTSD) and comorbid psychiatric disorders in adulthood among urban African Americans and Puerto Ricans. Method Data were collected from a large urban community sample (N = 674) at 4 time points associated with mean ages of 19, 24, 29, and 36 years. Trajectories of violent victimization were extracted using growth mixture modeling and used to predict psychiatric disorders and comorbidities in adulthood. Results The sample was 52.8% African American and 47.2% Puerto Rican, with 60% females. Three trajectory groups of violent victimization were identified: high, intermediate, and low. Over half of the sample reported relatively high- and intermediate-level violent victimization experiences from adolescence to adulthood. Group comparisons showed that participants belonging to the relatively high-victimization group had greater odds of having PTSD, major depressive episode (MDE), and substance use disorder (SUD) separately, as well as comorbid PTSD-SUD and PTSD-MDE, compared with those classified as having relatively low levels of victimization. Having intermediate-level victimization experiences, compared with low-level victimization experiences, over time was associated with higher odds of PTSD and MDE separately and comorbid PTSD-MDE. Conclusions Long-term exposure to relatively high levels of violent victimization during emerging and young adulthood is associated with PTSD and comorbid psychiatric disorders in the 30s. Social, structural, and interpersonal factors underlying the differential patterns of violent victimization in urban African American and LatinX youth need to be identified to adequately inform prevention efforts. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

OBJECTIVES: Since the number of individuals who use substances in the United States has markedly increased every year, substance use is a significant public health concern. The current study examines the possible risk and protective factors associated with triple comorbid trajectories of longitudinal alcohol, tobacco, and cannabis use from age 14 to 36. METHODS: A community sample of 674 participants (53% African Americans and 47% Puerto Ricans; 60% females) were recruited from the Harlem Longitudinal Development Study. Multinomial logistic regression analyses were conducted to examine the associations between the risk (low self-control, peer drug use) and protective (parent-child attachment, family church attendance) factors at age 14 and membership in the triple trajectory groups derived from a multivariate growth mixture model. RESULTS: Low self-control and peer drug use were associated with an increased likelihood of being a member in the triple comorbid trajectory groups compared to the reference group (i.e., low alcohol, no tobacco, and no cannabis use). On the other hand, parent-child attachment and family church attendance were associated with a decreased likelihood of being a member in the triple comorbid trajectory groups compared to the reference group. CONCLUSIONS: Treatment programs for adolescents who use substances may be more helpful if their parents and/or friends could also participate together with the adolescent, rather than only the adolescent participates in the treatment programs. Further research is needed to gain a greater understanding of the conceptual nature of the relationship between earlier risk and protective factors and later substance use patterns.

Human's direct supervision on robot's erroneous behavior is crucial to enhance a robot intelligence for a ‘flawless’ human-robot interaction. Motivating humans to engage more actively for this purpose is however difficult. To alleviate such strain, this research proposes a novel approach, a growth and regression metaphoric interaction design inspired from human's communicative, intellectual, social competence aspect of developmental stages. We implemented the interaction design principle unto a conversational agent combined with a set of synthetic sensors. Within this context, we aim to show that the agent successfully encourages the online labeling activity in response to the faulty behavior of robots as a supervision process. The field study is going to be conducted to evaluate the efficacy of our proposal by measuring the annotation performance of real-time activity events in the wild. We expect to provide a more effective and practical means to supervise robot by real-time data labeling process for long-term usage in the human-robot interaction.

Background and Objectives The excessive consumption of alcohol is a major issue in the United States and elsewhere. It is associated with a number of adverse health consequences, as well as difficulty in relationships and employment. Therefore, the present longitudinal study investigates the direct and indirect adolescent predictors of alcohol use in adulthood. Methods Among the 674 participants (53% African Americans, 47% Puerto Ricans), 60% were females (n = 405). Mplus software was used to perform structural equation modeling. Results Parental problems with alcohol use in the participants’ late adolescence were related to low parent-child attachment in late adolescence, which in turn, was related to self delinquency in late adolescence. This was related to peer delinquency in emerging adulthood, which in turn, was associated with alcohol use in emerging adulthood and in adulthood. Low parent-child attachment in late adolescence was also related to low satisfaction with school in late adolescence, which in turn, was related to self delinquency in late adolescence. This was associated with alcohol use in emerging adulthood, which in turn, was associated with alcohol use in adulthood. Conclusions and Scientific Significance One of the key implications of this study is that an impaired low parent-child attachment relationship is a determinant of children's engagement in delinquent behavior and ultimately the use of alcohol in adult life. Implications for social interventions from the findings of the current study were also discussed. (Am J Addict 2016;25:549–556)

We conducted a retrospective study to evaluate the clinical impact of an early recovery of posttransplant absolute lymphocyte count (ALC) on the outcome of frontline autologous stem cell transplantation (ASCT) for diffuse large B-cell lymphoma (DLBCL). We reviewed 65 DLBCL patients who underwent frontline ASCT after primary chemotherapy based on cyclophosphamide, doxorubicin, vincristine, and prednisone. A receiver operating characteristic analysis was performed to determine the optimal cut point (0.4 × 109 /L) for an ALC at 15 days after ASCT (ALC-15). Both event-free survival and overall survival rates of the higher-ALC-15 group were significantly better than those of the lower-ALC-15 group (event-free survival, P = .008; overall survival, P = .013). The infused CD34+ cell count was significantly associated with the recovery of ALC-15 (>0.4 × 109 /L) after ASCT (P = .028). A multivariate analysis confirmed that a higher infused CD34+ cell dose (>5.0 × 106 cells/kg) was an independent factor affecting an early recovery of ALC after ASCT (odds ratio, 4.145; 95% confidence interval, 1.106-15.528; P = .035). In conclusion, an early recovery of ALC after ASCT can be regarded as a good prognostic marker in patients with DLBCL who have undergone frontline ASCT. We found that the infused CD34+ cell dose for ASCT was associated with the recovery of ALC.

Purpose Primary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma (NHL). Absolute lymphocyte count (ALC) has been suggested to have a prognostic value in several subtypes of NHL. We evaluated the prognostic significance of clinical factors, including ALC, in patients with PCNSL to develop a new prognostic model. Methods We analysed prognostic factors, including ALC, at diagnosis in 81 PCNSL patients receiving high-dose methotrexate-based therapy. Results The median ALC at diagnosis was 1210 × 106/L (range, 210–3610), with lymphopenia (≤875 × 106/L) being detected in 27 (33.3%) patients. In the multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) >1 (hazard ratio [HR] 3.18, P = 0.003), age >50 years (HR 4.23, P = 0.012), and lymphopenia at diagnosis (HR 2.83, P = 0.008) remained independent prognostic factors for low overall survival (OS). Lymphopenia was also a significant prognostic factor for progression-free survival (HR 3.17, P = 0.001). By means of a new three-factor prognostic model using ECOG PS >1, age >50 years, and presence of lymphopenia, with 1 point assigned to each factor, we successfully classified the patients into three risk groups: low (0 and 1), intermediate (2), and high (3). The 5-year OS rates of the patients in the low-, intermediate-, and high-risk groups were 74.3%, 21.7%, and 12.5%, respectively (P Conclusions Low ALC is a useful indicator of poor prognosis in patients with PCNSL. The proposed three-factor model should be validated in large-scale studies.

Upfront autologous stem cell transplantation (ASCT) has shown favourable outcome in patients with primary central nervous system lymphoma (PCNSL), but the role of risk-adapted upfront ASCT consolidation has not been evaluated in PCNSL. As PCNSL patients with the International Extranodal Lymphoma Study Group (IELSG) prognostic score ≥2 or those who did not achieve complete response after two courses of induction chemotherapy (non-CR1) have shown inferior outcomes, we retrospectively analysed the role of upfront ASCT in 66 high-risk (IELSG ≥2 and/or non-CR1) younger (age

Insomnia is increasingly recognized as a public health concern in modern society. Insomnia diagnoses appear to be increasing and are associated with poor health outcomes. They may cost $100 billion annually in health services.Given the adverse consequences of insomnia such as cardiovascular disease, diabetes, and depression, the present study was designed to examine the relationship of the trajectories of earlier cigarette smoking and later insomnia. The ultimate goal is to reduce the prevalence of insomnia.674 participants (53% African Americans, 47% Puerto Ricans, 60% females) were surveyed at 6 points in time. We employed the growth mixture model to obtain the trajectories of cigarette smoking from age 14 to 32. We used logistic regression analyses to examine the associations between the trajectories of smoking and insomnia.Males were less likely to have insomnia than females (Adjusted odds ratio: AOR = 0.34, p.05). A higher Bayesian posterior probability (BPP) for the chronic smoking trajectory group (AOR = 2.69, p.05) and for the moderate smoking trajectory group (AOR = 5.33, p.01) was associated with an increased likelihood of having insomnia at age 36 compared with the BPP of the no or low smoking trajectory group.Prevention and treatment programs for individuals who suffer from insomnia should be implemented in parallel with programs for smoking cessation. From a public health perspective, our longitudinal study that examined the association between earlier smoking trajectories and later insomnia suggests that treatments designed to reduce or cease smoking may lessen the occurrence of symptoms of insomnia.

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies., Graphical Abstract

Danger signals, or damage-associated molecular patterns (DAMPs), instigate mitochondrial innate immune responses wherein mitochondrial antiviral signaling protein (MAVS) functions as a key platform molecule to mediate them. The role of MAVS in the pathogenesis of idiopathic pulmonary fibrosis (IPF), however, has not yet been identified. Whether MAVS signalling can be modulated by currently existing drugs has also not been explored.We used an established model of pulmonary fibrosis to demonstrate that MAVS is a critical mediator of multiple DAMP signalling pathways and the consequent lung fibrosis after bleomycin-induced injuryin vivo.After bleomycin injury, MAVS expression was mainly observed in macrophages. Multimeric MAVS aggregation, a key event of MAVS signalling activation, was significantly increased and persisted in bleomycin-injured lungs. A proapoptotic BH3 mimetic, ABT-263, attenuated the expression of MAVS and its signalling and, consequently, the development of experimental pulmonary fibrosis. In contrast, the therapeutic effects of nintedanib and pirfenidone, two drugs approved for IPF treatment, were not related to the modulation of MAVS or its signalling. Multimeric MAVS aggregation was significantly increased in lungs from IPF patients as well.MAVS may play an important role in the development of pulmonary fibrosis, and targeting MAVS with BH3 mimetics may provide a novel and much needed therapeutic strategy for IPF.

Despite the development of molecular targeted therapies, few advances have been made in the treatment of lung squamous cell carcinoma (SCC). SOX2 amplification is one of the most common genetic alterations in SCC. Here, we investigated the effects of THZ1, a potent cyclin-dependent kinase 7 (CDK7) inhibitor that plays a key role in gene transcription, in SCC. Lung SCC-derived cell viabilities were assessed using a CCK-8 assay. SOX2 expression and RNAPII-CTD phosphorylation levels after THZ1 treatment were determined by Western blotting. The effect of SOX2 suppression using shRNA was assessed by flow cytometry. Gene expression patterns after THZ1 treatment of lung SCC-derived cells were identified using microarray-based mRNA profiling. We found that THZ1 treatment led to suppression of cell growth and apoptotic cell death in SOX2-amplified SCC-derived cells only, whereas the modest growth-inhibitory effect of cisplatin did not differ according to SOX2 amplification status. We also found that THZ1 decreased the phosphorylation of the carboxyl-terminal domain of RNA polymerase II and the expression of several genes. Specifically, we found that the expression of transcription-associated genes, including SOX2, was down-regulated by THZ1 in SOX2-amplified SCC cells. This inhibition of SOX2 expression resulted in suppression of the growth of these cells. From our data, we conclude that THZ1 may effectively control the proliferation and survival of SOX2-amplified SCC cells through a decrease in global transcriptional activity, suggesting that CDK7 inhibition leading to transcription suppression may be a promising therapeutic option for lung SCC with a SOX2 amplification.

Purpose:Multiparity might increase general mortality for women, but has inconclusive in patients with breast cancer. Here, we aim to discover their effect in terms of the breast cancer development hypothesis: from ductal carcinoma in situ to invasive carcinoma.Methods:We included 37 947 patients from the web-based breast cancer registration program of the Korean Breast Cancer Society and analyzed survivals using multivariate Cox regression analysis and whether the associations of these factors displayed linear trends. They were divided into the following groups: (1) pure ductal carcinoma in situ (DCIS), (2) invasive ductal carcinoma (IDC) mixed with intraductal component (DCIS-IDC), and (3) node negative pure IDC.Results:The mean age was 48.9 ± 9.9 years including premenopausal women was 61.8%. Although patients with parities of 1-3 had better prognosis compared with patients with nulliparous women, high parity (⩾4) increased the hazard ratio (HR) of overall survival (OS) (DCIS: HR, 1.52; 95% confidence interval [CI] 0.62-3.78; IDC: HR, 1.43, 95% CI 0.89-2.31; and DCIS-IDC: HR, 1.44, 95% CI 0.45-4.59) during 84.2 (±10.7) months. For breast cancer specific survival (BCSS), the HR of the IDC group ( P-value for trend = .04) increased along with increasing parity and was worse than nulliparous patients, and the HR of the DCIS-IDC group increased but was better than nulliparous patients ( P-value for trend = .02). Compared with nulliparous patients, any age at first birth (AFB) decreased HR of OS in the DCIS and IDC groups (DCIS: P = .01; IDC: P = .04).Conclusions:Parity show dual effects on OS of women with all ductal typed breast cancer but show different effects on BCSS in Korea.