NSCLC Digital PCR Panel Returns Low-Input Sample Results Where Sequencing Fails.

Molecular diagnostics has drastically improved the survival rate of patients diagnosed with non-small cell lung cancer (NSCLC) over the last 10 years. Despite advancements in molecular testing, targeted therapies, and national guideline recommendations, more than half of NSCLC patients in the United States either never receive testing or patient care is not informed via molecular testing. Here, we sought to explore the relationship between DNA/RNA input, the molecular testing method, and test success rates. On a shared set of low-input reference test materials (n = 3), we ran both a hybrid capture-based, next-generation sequencing (NGS) assay and a multiplexed digital PCR (dPCR) panel. The dPCR panel was highly sensitive and specific for low-input samples in dilution studies ranging from 40 to 1 ng DNA and from 20 to 2.5 ng RNA, while NGS had up to an 86% loss in sensitivity as contrived sample inputs were serially diluted. The dPCR panel also demonstrated a high PPA (>95%) at diluted inputs as low as 15/7.5 ng DNA/RNA on 23 banked clinical samples with the same NGS hybrid capture assay at a high input. These data suggest that digital PCR is an accurate and effective way of identifying clinically relevant NSCLC mutations at low nucleotide input and quality.

Experiences of interpersonal violence among a diverse sample of male sex workers.

A notable portion of men who have sex with men engage in exchange sex-i.e. the trading of sex for money, drugs, shelter or other material goods. Despite the risks for physical and sexual violence, threatening behaviour and robbery that male sex workers confront, very little is known about their experiences of such actions by clients. To gain more insight into male sex workers' experiences of interpersonal violence, we analysed qualitative interview data from 180 men who have sex with men from 8 US cities who engaged in sex work with clients they had met primarily through dating/hookup websites and apps. Participants discussed their experiences of a range of untoward behaviours by clients including physical violence, sexual violence, threats and robbery. Healthcare and social services providers can play a significant role in violence prevention among male sex workers. The decriminalisation of sex work could also potentially reduce the risks many sex workers face by facilitating their reporting of harms suffered.

Condomless Anal Sex Between Male Sex Workers and Clients in the Age of Hookup Apps.

Among men who have sex with men (MSM), those who also engage in the exchange of sex for money, drugs, shelter or other material goods (i.e., male sex workers-MSWs) have been found to have higher rates of condomless anal sex (CAS), HIV, and STIs than MSM who do not engage in exchange sex. To gain a better understanding of the factors that influence MSWs' engagement in CAS with male clients, we analyzed qualitative interview data from a diverse sample of 141 MSWs from 8 U.S. cities who met clients primarily through hookup or dating apps/websites and who reported having condomless anal sex with at least one of their exchange sex partners in the prior three months. While high client demand and financial incentives were the most frequently mentioned reasons for engaging in CAS with clients, other factors including drug and alcohol use, attraction to the client, the heat of the moment, concerns about sexual performance, and reliance on pre-exposure prophylaxis (PrEP) were also important. Participants who engaged in CAS generally felt that due to client characteristics or mitigating steps they had taken themselves, their chance of acquiring HIV/STIs was acceptably low. Hookup or dating apps/websites have provided an additional and increasingly popular venue for exchange sex to be arranged. These platforms also offer an opportunity for HIV/STI prevention through interventions and tailored messages delivered through these venues that address the motivations, misconceptions and/or situational factors that may lead to CAS.

RESUMEN: Entre los hombres que tienen relaciones sexuales con hombres (HSH), se ha encontrado que aquellos que también participan en el intercambio de sexo por dinero, drogas, vivienda u otros bienes materiales (es decir, hombres trabajadores sexuales-HTS) tienen tasas más altas de sexo anal sin condón (SASC), VIH y ETS que los HSH que no participan en relaciones sexuales de intercambio. Para obtener una mejor comprensión de los factores que influyen en la participación de los HTS en SASC con clientes masculinos, analizamos los datos de entrevistas cualitativas de una muestra diversa de 141 HTS de 8 ciudades de EE. UU. que conocieron a los clientes principalmente a través de aplicaciones/sitios web de conexión o citas y que informaron haber tenido sexo anal sin condón con al menos una de sus parejas sexuales de intercambio en los tres meses anteriores. Mientras la alta demanda de los clientes y los incentivos financieros fueron las razones mencionadas con mayor frecuencia para participar en SASC con los clientes, otros factores como el uso de drogas y alcohol, la atracción hacia el cliente, la seducción del momento, las preocupaciones sobre el desempeño sexual y la dependencia de la profilaxis preexposición (PrEP) también fueron importantes. Los participantes que tomaron parte en SASC generalmente sintieron que debido a las características del cliente o a los pasos de mitigación que habían tomado ellos mismos, su probabilidad de contraer VIH / ETS era aceptablemente baja. Las aplicaciones/sitios web de conexión o citas han proporcionado un lugar adicional y cada vez más popular para organizar el intercambio de sexo. Estas plataformas también ofrecen una oportunidad para la prevención del VIH/ETS a través de intervenciones y mensajes personalizados que se transmiten a través de estos lugares y que abordan las motivaciones, los conceptos erróneos y/o los factores situacionales que pueden conducir a SASC.

"I Want to Be Really Clear": What Male Sex Workers Want to Clarify With Prospective Clients Before Agreeing to Meet for Sex.

Men who have sex with men (MSM) and engage in sex work (MSW) frequently meet clients through dating/hookup apps. This provides an opportunity to discuss the parameters of the exchange prior to meeting and to learn things about the prospective client and the risks he might pose. Limited research has examined the specific issues or topics MSWs discuss with clients before agreeing to meet. We analyzed interview data from a sample of 180 MSWs from eight U.S. cities who engaged in exchange sex with clients they had primarily met through dating/hookup apps and websites. Participants typically asked about clients' sexual interests and expectations regarding what will transpire when they meet to make sure they were compatible with their own boundaries and limitations. Most participants inquired about clients' sexual health and often discussed condom use. Assertiveness and communication skills training might help MSWs negotiate encounters with clients that promote health and safety.

Analytical Performance and Concordance with Next-Generation Sequencing of a Rapid, Multiplexed dPCR Panel for the Detection of DNA and RNA Biomarkers in Non-Small-Cell Lung Cancer.

FDA approval of targeted therapies for lung cancer has significantly improved patient survival rates. Despite these improvements, barriers to timely access to biomarker information, such as nucleic acid input, still exist. Here, we report the analytical performance and concordance with next-generation sequencing (NGS) of a highly multiplexed research-use-only (RUO) panel using digital PCR (dPCR). The panel's analytical sensitivity and reactivity were determined using contrived DNA and RNA mixes. The limit of blank was established by testing FFPE curls classified as negative by pathology. Concordance was established on 77 FFPE samples previously characterized using the Oncomine Precision Assay®, and any discordant results were resolved with Archer Fusionplex® and Variantplex® panels. The analytical sensitivity, reported as the estimated mutant allele fraction (MAF), for DNA targets ranged from 0.1 to 0.9%. For RNA targets (ALK, RET, ROS, NTRK 1/2/3 Fusions, and MET Exon 14 skipping alteration), the analytical sensitivity ranged from 23 to 101 detected counts with 5 ng of total RNA input. The population prevalence-based coverage ranged from 89.2% to 100.0% across targets and exceeded 99.0% in aggregate. The assay demonstrated >97% concordance with respect to the comparator method.

Purpose in life: A resolution on the definition, conceptual model, and optimal measurement.

Theoretically, purpose serves as a basic dimension of healthy psychological functioning and an important protective factor from psychopathology. Theory alone, however, is insufficient to answer critical questions about human behavior and functioning; we require empirical evidence that explores the parameters of purpose with respect to measurement, prediction, and modification. Here, we provide empirically supported insights about how purpose can operate as a beneficial outcome (e.g., marker of well-being), a predictor or mechanism that accounts for benefits that a person derives (such as from an intervention), or a moderator that offers insight into when benefits arise. Advancing the study of purpose requires careful consideration of how purpose is conceptualized, manipulated, and measured across the lifespan. Our aim is to help scientists understand, specify, and conduct high-quality studies of purpose in life. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Social anxiety and interpersonal risk for suicidal ideation: A longitudinal daily diary analysis.

INTRODUCTION: Social anxiety is associated with elevated suicidal ideation (SI). One potential explanation is that socially anxious persons experience frequent interpersonal stressors that elicit SI. Longitudinal designs with temporal ordering are needed to adequately test this hypothesis. Therefore, this study leveraged a longitudinal design combining trait and daily reports. METHODS: Two hundred eleven community adult participants with elevated levels of depression and/or social anxiety completed social anxiety and SI measures at baseline and again at a 1.5-month follow-up. Between these assessments, participants completed a 14-day diary study that assessed three forms of interpersonal distress: unfavorable social comparisons, perceived barriers to seeking social support, and loneliness. RESULTS: As predicted, simple mediation models revealed that baseline social anxiety had a significant indirect effect on SI severity at 1.5 months postbaseline via unfavorable social comparisons (indirect effect: ß = 0.07, p < 0.05) and barriers to seeking support (indirect effect: ß = 0.08, p < 0.05); however, social anxiety did not have a significant indirect effect on SI severity through loneliness. CONCLUSION: Study results are consistent with the proposition that increases in interpersonal distress may explain socially anxious persons' vulnerability to SI. Implications of these findings for the research, assessment, and treatment of suicidality in social anxiety are discussed.

Male Sex Workers' Strategies to Manage Client-Related Risks of Violence.

A substantial minority of men who have sex with men (MSM) engage in the exchange of sex for money, drugs, shelter, or material goods. This work carries risks for violence, sexual assault, and other kinds of harm such as robbery and threatening behavior by clients. Yet limited research has focused on the strategies that male sex workers (MSWs) use to prevent or manage these risks. To gain more insights into this matter, we analyzed qualitative interview data from 180 MSM recruited from eight U.S. cities who engaged in sex work with clients they had primarily met through dating/hookup websites and apps. Participants described the strategies they used to manage risks of interpersonal violence, both prior to meeting their clients and at the time of their encounters. Many of the strategies used ahead of the encounter relied upon information and communication technologies, such as negotiating the parameters of the exchange encounter, screening clients, sharing information about the client and meeting place with others, identifying safe meeting locations, and gathering information from social networks about problematic clients. Strategies employed during the encounter included: receiving payment up front; being prepared to protect oneself with a weapon or self-defense techniques; staying alert and sober; and planning an exit route from the location. Technology-based interventions through dating/hookup apps could play an important role in providing resources and skill building for MSWs to help them protect themselves during sex work.

Multicolor plate reader fluorescence calibration.

Plate readers are commonly used to measure cell growth and fluorescence, yet the utility and reproducibility of plate reader data is limited by the fact that it is typically reported in arbitrary or relative units. We have previously established a robust serial dilution protocol for calibration of plate reader measurements of absorbance to estimated bacterial cell count and for green fluorescence from proteins expressed in bacterial cells to molecules of equivalent fluorescein. We now extend these protocols to calibration of red fluorescence to the sulforhodamine-101 fluorescent dye and blue fluorescence to Cascade Blue. Evaluating calibration efficacy via an interlaboratory study, we find that these calibrants do indeed provide comparable precision to the prior calibrants and that they enable effective cross-laboratory comparison of measurements of red and blue fluorescence from proteins expressed in bacterial cells.

Long term survival after a first transient ischaemic attack in England: A retrospective matched cohort study.

OBJECTIVE: Transient ischaemic attacks (TIA) serve as warning signs for future stroke, and the impact of TIA on long term survival is uncertain. We assessed the long-term hazards of all-cause mortality following a first episode of a transient ischaemic attack (TIA). DESIGN: Retrospective matched cohort study. METHODS: Cohort study using electronic primary health care records from The Health Improvement Network (THIN) database in the United Kingdom. Cases born in or before 1960, resident in England, with a first diagnosis of TIA between January 1986 and January 2017 were matched to three controls on age, sex and general practice. The primary outcome was all-cause mortality. The hazards of all-cause mortality were estimated using a time-varying Double-Cox Weibull survival model with a random frailty effect of general practice, while adjusting for different socio-demographic factors, medical therapies, and comorbidities. RESULTS: 20,633 cases and 58,634 controls were included. During the study period, 24,176 participants died comprising of 7,745 (37.5%) cases and 16,431(28.0%) controls. In terms of hazards of mortality, cases aged 39 to 60 years at the first TIA event had the highest hazard ratio (HR) of mortality compared to their 39-60 years matched controls (HR = 3.04 (2.91 - 3.18)). The HR for cases aged 61-70 years, 71-76 years and 77+ years were 1.98 (1.55 - 2.30), 1.79 (1.20 - 2.07) and 1.52 (1.15 - 1.97) compared to their same-aged matched controls. Cases aged 39-60 at TIA onset who were prescribed aspirin were associated with reduced HR of 0.93 (0.84 - 1.01), 0.90 (0.82 - 0.98) and 0.88 (0.80 - 0.96) at 5, 10 and 15 years respectively, compared to the same aged cases who were not prescribed any antiplatelet. Statistically significant reductions in hazard ratios were observed with aspirin at 10 and 15 years in all age groups. Hazard ratio point estimates for other antiplatelets (dipyridamole or clopidogrel) and dual antiplatelet therapy were very similar to aspirin at 5, 10 and 15 years but with wider confidence intervals that included 1. There was no survival benefit associated with antiplatelet prescription in controls. CONCLUSIONS: The overall risk of death was considerably elevated in all age groups after a first-ever TIA event. Aspirin prescription was associated with a reduced risk. These findings support the use of aspirin in secondary prevention for people with a TIA. The results do not support the use of antiplatelet medication in people without TIA.

Psychological well-being in US veterans with non-fatal suicide attempts: A multi-cohort population-based study.

BACKGROUND: Most people who survive suicide attempts neither re-attempt suicide nor die by suicide. Research on suicide attempt survivors has primarily focused on negative endpoints (e.g., increased suicide risk) rather than positive outcomes. One important outcome is psychological well-being (PWB), defined as positive functioning across emotional, intrapersonal, and interpersonal domains. We compared PWB among US military veterans with (i.e., attempt survivors) and without (i.e., non-attempters) a history of suicide attempt(s) using data from three nationally representative cohorts. METHODS: Each US veteran cohort (Cohort1: N = 3148; Cohort2: N = 1474; Cohort3: N = 4042) completed measures of suicidality (e.g., attempt history), character strengths (e.g., curiosity, optimism), psychological symptoms (e.g., depression), and indicators of PWB (e.g., happiness). t-Tests were conducted to examine group differences in PWB; hierarchical regressions were conducted to examine suicide attempt status as a predictor of PWB controlling for symptoms and demographics. Multivariable regressions were conducted to identify predictors of PWB among attempt survivors. RESULTS: In each cohort, reported PWB was markedly lower among suicide attempt survivors than non-attempters (ds = 0.9-1.2), even after adjusting for mental health symptoms. Individual differences in PWB were observed, with a subset of suicide attempt survivors reporting higher PWB levels than non-attempters (1.4-7.4 %). Curiosity and optimism were positively associated with PWB among suicide attempt survivors (rs = 0.60-0.78). LIMITATIONS: Data were cross-sectional, limiting inferences about causation and directionality of associations. CONCLUSIONS: Findings highlight diminished PWB as an important and understudied concern among veteran attempt survivors. Collectively, our findings underscore the importance of considering PWB in the research, assessment, and treatment of suicidality.

Motives and Consequences of Alcohol Use in People With Social Anxiety Disorder: A Daily Diary Study.

People with social anxiety disorder (SAD) are at increased risk for alcohol-related problems. Most research exploring social anxiety and alcohol use has examined negative drinking consequences, with less consideration of positive consequences-namely positive social experiences-that may reinforce alcohol use. In this daily diary study, we examined how adults diagnosed with SAD (N = 26) and a psychologically healthy control group (N = 28) experienced positive drinking consequences in naturally occurring drinking episodes during the study period. For 14 consecutive days, participants answered questions about alcohol use, motives for drinking, and positive consequences of drinking. On days when participants drank, those with SAD were more likely than healthy controls to perceive a reduction in anxiety, but the two groups did not differ in their likelihood of experiencing positive social drinking consequences. For both groups, on days when they were more motivated to drink to enhance social experiences (affiliation motives) or cope with distress (coping motives), they were more likely to obtain positive consequences from drinking. Compared to controls, participants with SAD endorsed stronger trait and daily coping motives (anxiety-coping, social anxiety-coping, and depression-coping). Results are discussed in the context of reinforcement mechanisms that may maintain social anxiety and alcohol use.

Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development.

Introduction: We sought to explore biomarkers of coronary atherosclerosis in an unbiased fashion. Methods: We analyzed 665 patients (mean ± SD age, 56 ± 11 years; 47% male) from the GLOBAL clinical study (NCT01738828). Cases were defined by the presence of any discernable atherosclerotic plaque based on comprehensive cardiac computed tomography (CT). De novo Bayesian networks built out of 37,000 molecular measurements and 99 conventional biomarkers per patient examined the potential causality of specific biomarkers. Results: Most highly ranked biomarkers by gradient boosting were interleukin-6, symmetric dimethylarginine, LDL-triglycerides [LDL-TG], apolipoprotein B48, palmitoleic acid, small dense LDL, alkaline phosphatase, and asymmetric dimethylarginine. In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis. Discussion: Triglyceride-rich LDL particles, which can now be routinely measured with a direct homogenous assay, may play an important role in atherosclerosis development. Clinical trial registration: GLOBAL clinical study (Genetic Loci and the Burden of Atherosclerotic Lesions); [https://clinicaltrials.gov/ct2/show/NCT01738828?term=NCT01738828&rank=1], identifier [NCT01738828].

Toward Full-Stack In Silico Synthetic Biology: Integrating Model Specification, Simulation, Verification, and Biological Compilation.

We present the Infobiotics Workbench (IBW), a user-friendly, scalable, and integrated computational environment for the computer-aided design of synthetic biological systems. It supports an iterative workflow that begins with specification of the desired synthetic system, followed by simulation and verification of the system in high-performance environments and ending with the eventual compilation of the system specification into suitable genetic constructs. IBW integrates modeling, simulation, verification, and biocompilation features into a single software suite. This integration is achieved through a new domain-specific biological programming language, the Infobiotics Language (IBL), which tightly combines these different aspects of in silico synthetic biology into a full-stack integrated development environment. Unlike existing synthetic biology modeling or specification languages, IBL uniquely blends modeling, verification, and biocompilation statements into a single file. This allows biologists to incorporate design constraints within the specification file rather than using decoupled and independent formalisms for different in silico analyses. This novel approach offers seamless interoperability across different tools as well as compatibility with SBOL and SBML frameworks and removes the burden of doing manual translations for standalone applications. We demonstrate the features, usability, and effectiveness of IBW and IBL using well-established synthetic biological circuits.

Adolescent depressed mood and difficulties with emotion regulation: Concurrent trajectories of change.

INTRODUCTION: Adolescent depression is a significant mental health concern. Emotion regulation difficulties have been associated with subsequent depressive symptoms, though different facets of emotion regulation are rarely compared. This study examined the degree to which trajectories of change in different facets of emotion regulation (goal-directed behavior, impulse control, and regulation strategies) and depressive symptoms were associated across twelve months in a clinical adolescent sample. METHODS: Participants included 110 adolescents from the US who were enrolled in a randomized trial that tested a cognitive-behavioral treatment for youth with co-occurring mental health and substance use concerns (Mage = 15.71 years; 57.3% male). Assessments were conducted at baseline, 3-, 6-, and 12-month follow-ups. Three separate bivariate latent basis growth curve analyses were conducted. Correlations between latent intercepts and latent slopes, as well as overall model fit, were examined. RESULTS: Impulse control and goal-directed behavior were each associated with depressive symptoms at baseline. Additionally, change in impulse control over time was significantly associated with change in depressive symptoms. However, the same was not true for goal-directed behavior. Overall fit indices for models of emotion regulation strategies were below acceptable levels and thus could not be interpreted. CONCLUSIONS: Findings from the present study indicate that adolescents' depressive symptoms appear to improve as their perceived ability to control impulses improves. These results suggest that addressing impulse control difficulties may be an important step in treating adolescent depression and co-occurring disorders.

Does negative emotion differentiation influence how people choose to regulate their distress after stressful events? A four-year daily diary study.

Much is known about the types of strategies people use to regulate emotions. Less is known about individual differences that influence emotion regulation strategy selection. In this study, we tested the moderating role of negative emotion differentiation (NED; i.e., the ability to label and describe subtle differences among negative emotions) on the relationship between the intensity of stressful daily events and the strategies used to regulate distress arising from these events. Prior research shows that NED is associated with low endorsement of disengagement emotion regulation (e.g., substance use), but less is known about the link to engagement regulation (e.g., problem-solving, seeking social support). Participants were college students (N = 502) completing a 30-day daily diary survey for each of four college years. We preregistered hypotheses that 1) the intensity of each day's most stressful event would be associated with greater use of disengagement and engagement regulation strategies, and 2) people higher in NED would be less likely to use disengagement and more likely to use engagement strategies when highly stressed. Results suggest that higher stress intensity is associated with greater use of all regulation strategies. Greater NED is associated with less use of disengagement regulation strategies, whereas NED was unrelated to engagement regulation strategies and did not moderate the relationship between stress and engagement strategies. The majority of hypothesized moderation effects of NED were nonsignificant, prompting a reconsideration of whether, when, and how NED plays a role in stress responding. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Phase I dose-escalation, safety, and CNS pharmacokinetic study of dexanabinol in patients with brain cancer.

BACKGROUND: Dexanabinol is a synthetic analogue of tetrahydrocannabinol identified as a potential anti-cancer therapeutic by e-Therapeutics PLC. Dexanabinol was selected for further investigation based on its preclinical tumoricidal activity. This phase I dose-escalation trial examined the safety, drug penetration into the central nervous system (CNS), preliminary antitumor activity, and recommended phase II dose. METHODS: Dexanabinol formulated in cremophor/ethanol was administered once weekly via 3-hour intravenous infusion to patients with brain cancer. RESULTS: A total of 26 patients were dosed once weekly at 2, 4, 8, 16, 24, 28, and 36 mg/kg. Two patients at 36 mg/kg were nonevaluable for dose level confirmation, having withdrawn early for reasons unrelated to study treatment. A recommended phase II dose of dexanabinol was established at 28 mg/kg due to related, reversible adverse events at higher dose levels that required medications for symptomatic relief. The most common drug-related toxicities were the depressed level of consciousness and lightheadedness, diarrhea, itching, fatigue, chest discomfort, and tingling in the mouth. Systemic exposure to dexanabinol (AUC0-t and C max) increased from 2 to 36 mg/kg, with dose nonproportionality apparent at the highest dose; dexanabinol was present in appreciable levels in the cerebrospinal fluid (CSF), which implies the possibility of exposure of intracranial tumors to drug. Five of 24 efficacy-evaluable patients (21%) experienced stable disease with a median duration of 2 cycles (28-day cycle) as the best response. CONCLUSIONS: Dexanabinol administered weekly by intravenous infusion was safe and well-tolerated up to 28 mg/kg in brain cancer patients, but has limited antitumor activity in patients with brain cancer.

The Biology of Casmara subagronoma (Lepidoptera: Oecophoridae), a Stem-Boring Moth of Rhodomyrtus tomentosa (Myrtaceae): Descriptions of the Previously Unknown Adult Female and Immature Stages, and Its Potential as a Biological Control Candidate.

Rhodomyrtus tomentosa is a perennial shrub native to Southeast Asia and is invasive in South Florida and Hawai'i, USA. During surveys of R. tomentosa in Hong Kong from 2013-2018 for potential biological control agents, we collected larvae of the stem borer, Casmara subagronoma. Larvae were shipped in stems to a USDA-ARS quarantine facility where they were reared and subjected to biology studies and preliminary host range examinations. Casmara subagronoma is the most recent Casmara species to be described from males collected in Vietnam and Indonesia. Because the original species description was based on only two male specimens, we also provide a detailed description of the female, egg, larva, and pupa. Finally, we conducted preliminary host range trials utilizing Myrtus communis, Myrcianthes fragrans, and Camellia sinensis. Casmara subagronoma emerged from M. fragrans, a Florida-native shrub, and larvae were able to survive in non-target stems for over a year (>400 days). Based on these findings and difficulty in rearing, we do not believe C. subagronoma is a suitable insect for biological control of R. tomentosa at this time, but may warrant further study. This investigation also illustrates the importance of host surveys for conservation and taxonomic purposes.

Capturing Multicellular System Designs Using Synthetic Biology Open Language (SBOL).

Synthetic biology aims to develop novel biological systems and increase their reproducibility using engineering principles such as standardization and modularization. It is important that these systems can be represented and shared in a standard way to ensure they can be easily understood, reproduced, and utilized by other researchers. The Synthetic Biology Open Language (SBOL) is a data standard for sharing biological designs and information about their implementation and characterization. Previously, this standard has only been used to represent designs in systems where the same design is implemented in every cell; however, there is also much interest in multicellular systems, in which designs involve a mixture of different types of cells with differing genotype and phenotype. Here, we show how the SBOL standard can be used to represent multicellular systems, and, hence, how researchers can better share designs with the community and reliably document intended system functionality.

REPLATINUM Phase III randomized study: RRx-001 + platinum doublet versus platinum doublet in third-line small cell lung cancer.

RRx-001 is a cysteine-directed anticancer alkylating agent with activity in a Phase II study in platinum refractory small cell lung cancer. Here, we describe the design of REPLATINUM, an open-label, Phase III trial. 120 patients with previously platinum-treated small cell lung cancer in third line will be randomized 1:1 to receive RRx-001 followed by four cycles of a platinum doublet, and then alternating cycles of RRx-001 and single agent platinum until progression versus four cycles of a platinum doublet. At radiologic progression on the platinum doublet, patients may cross over to the RRx-001 arm. Primary objective: to demonstrate superior progression-free survival in the RRx-001 population. Secondary objectives: to demonstrate superiority for overall survival and objective response rate. Clinical Trial registration: NCT03699956.