Managing Opioid Withdrawal Symptoms During the Fentanyl Crisis: A Review.

Illicitly manufactured fentanyl (IMF) is a significant contributor to the increasing rates of overdose-related deaths. Its high potency and lipophilicity can complicate opioid withdrawal syndromes (OWS) and the subsequent management of opioid use disorder (OUD). This scoping review aimed to collate the current OWS management of study populations seeking treatment for OWS and/or OUD directly from an unregulated opioid supply, such as IMF. Therefore, the focus was on therapeutic interventions published between January 2010 and November 2023, overlapping with the period of increasing IMF exposure. A health science librarian conducted a systematic search on November 13, 2023. A total of 426 studies were screened, and 173 studies were reviewed at the full-text level. Forty-nine studies met the inclusion criteria. Buprenorphine and naltrexone were included in most studies with the goal of transitioning to a long-acting injectable version. Various augmenting agents were tested (buspirone, memantine, suvorexant, gabapentin, and pregabalin); however, the liberal use of adjunctive medication and shortened timelines to initiation had the most consistently positive results. Outside of FDA-approved medications for OUD, lofexidine, gabapentin, and suvorexant have limited evidence for augmenting opioid agonist initiation. Trials often have low retention rates, particularly when opioid agonist washout is required. Neurostimulation strategies were promising; however, they were developed and studied early. Precipitated withdrawal is a concern; however, the rates were low and adequately mitigated or managed with low- or high-dose buprenorphine induction. Maintenance treatment continues to be superior to detoxification without continued management. Shorter induction protocols allow patients to initiate evidence-based treatment more quickly, reducing the use of illicit or non-prescribed substances.

Transitioning Virtual-Only Group Therapy for Substance Use Disorder Patients to a Hybrid Model.

Purpose: Telehealth is associated with a myriad of benefits; however, little is known regarding substance use disorder (SUD) treatment outcomes when participants join group therapy sessions in a combination in-person and virtual setting (hybrid model). We sought to determine if treatment completion rates differed. Patients and Methods: Policy changes caused by the COVID-19 pandemic created a naturalistic, observational cohort study at seven intensive outpatient (IOP) programs in rural Minnesota. Virtual-only delivery occurred 6/1/2020-6/30/2021, while hybrid groups occurred 7/1/2021-7/31/2022. Data was evaluated retrospectively for participants who initiated and discharged treatment during the study period. Participants were IOP group members 18 years and older who had a SUD diagnosis that both entered and discharged treatment during the 26-month period. A consecutive sample of 1502 participants (181-255 per site) was available, with 644 removed: 576 discharged after the study conclusion, 49 were missing either enrollment or discharge data, 14 transferred sites during treatment, and 5 initiated treatment before the study initiation. Helmert contrasts evaluated the impact of hybrid group exposure. Results: A total of 858 individuals were included. Data was not from the medical chart and was deidentified preventing specific demographics; however, the overall IOP sample for 2020-2022, from which the sample was derived, was 29.8% female, and 64.1% were 18-40 years of age. For completed treatment, hybrid group exposure relative to virtual-only had a univariate odds ratio of 1.88 (95% CI: 1.50-2.41, p < 0.001). No significant difference was seen across IOP sites. Conclusion: These results describe a novel hybrid group approach to virtual care for SUDs with outcome data not previously documented in the literature. While virtual treatment delivery can increase access, these results suggest a benefit is derived from including an in-person option. Further research is needed to identify how an in-person component may change dynamics and if it can be replicated in virtual-only models.

Systematic review and meta-analysis: Combining transcranial magnetic stimulation or direct current stimulation with pharmacotherapy for treatment of substance use disorders.

BACKGROUND AND OBJECTIVES: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have evidence for their potential in the treatment of substance use disorders (SUD). Medication for addiction treatment (MAT) is underutilized and not always effective. We identified randomized controlled trials (RCTs) and case studies that evaluated the effectiveness of TMS or tDCS used concurrently with MAT in SUD treatment. METHODS: A systematic review of published literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on 6/1/2023 by a medical librarian. Craving-related scales were extracted for an effect size calculation. The Physiotherapy Evidence Database (PEDro) scale assessed study quality. RESULTS: Eight studies (7 RCT, 1 case) including 253 individuals were published from 2015 to 2022, 5 of which had available data for meta-analysis. TMS or tDCS combined with MAT significantly reduced craving-related measures relative to sham stimulation (Hedges' g = -0.42, confidence interval: -0.73 to -0.11, p < .01). Opioid use disorder, methadone, and the dorsolateral prefrontal cortex were the most commonly studied SUD, MAT, and target region. DISCUSSION AND CONCLUSIONS: Our results show a significant effect; however, is limited by a small number of studies with heterogeneous methodology across intervention methods and SUDs. Additional trials are needed to fully assess the clinical impact and mechanisms of combined brain stimulation and pharmacotherapy. We discuss a possible mechanism for synergism from these treatment combinations. SCIENTIFIC SIGNIFICANCE: Adds the first systematic review of combination treatment with TMS or tDCS and MAT in SUD patients to the literature and estimates its overall effect size.

Evidence of "Repeated Admission Bias" Among Those Who Use Injection Drugs Across 2 Decades of US Treatment Admissions: 2000-2020.

OBJECTIVES: Encounter-based datasets like the Treatment Episode Dataset-Admissions (TEDS-A) are used for substance use-related research. Although TEDS-A reports the number of previous treatment admissions, a limitation is this reflects encounters, not people. We sought to quantify the methodologic bias incorporated by using all encounters versus initial encounters and assess if this risk is evenly distributed across all routes of drug administration. METHODS: TEDS-A 2000-2020 dataset with nonmissing primary substance data was used. Of the data, 3.17% were missing the usual administration route, and 11.9% were missing prior admission data. Prior admissions are documented as 0 through 4, then binned for 5 or greater (5+). Risk of admission bias was defined as odds ratio (OR RAB ): odds of total admissions relative to the odds of the first admission. Bootstrap confidence intervals were generated (5000 iterations) across administration routes and demographics; however, their widths were <0.0055 and not reported. RESULTS: There were 38,238,586 admissions over the 21 years, with 13,865,517 (41.2%) first admissions. Of all admissions, 15.7% indicated injection drug use (IDU); 26.3% of encounters reporting IDU were in the 5+ group. This resulted in an OR RAB of 1.77. White enrollees had an elevated OR RAB (1.05), whereas among Latinos, OR RAB was low (0.74). CONCLUSIONS: Using encounter-based datasets can introduce bias when including all admissions versus exclusively initial treatment episodes. This report is the first to quantify this bias and shows that individuals with IDU are at highest risk for returning to treatment, thereby over-representing this method of use when all encounters are used.

Mortality in Treatment-seeking Older Adults Receiving Medications for Opioid Use Disorder.

OBJECTIVES: Older adults (OAs; age 55+ years) are increasingly seeking specialty treatment of opioid use disorder. Previous analyses of the Treatment Episode Data Set-Discharges (TEDS-D) database have reported higher rates of in-treatment mortality for those receiving medications for opioid use disorder (MOUD). We evaluate current trends in mortality for treatment-seeking OAs. METHODS: Using the 2020 TEDS-D, logistic regression predicted in-treatment mortality for OAs from planned MOUD, service level, and interaction terms. RESULTS: Of the 26,993 OA treatment discharges, 679 people were discharged due to death (2.52%). OAs with MOUD (3.65%, 95% confidence interval [CI], 3.37%-3.95%) were significantly more likely to discharge due to death than those without MOUD (0.82%; 95% CI, 0.66%-1.01%). Most records were for nonintensive outpatient (83.7%; n = 22,588), which had the highest mortality (2.89%; 95% CI, 2.68%-3.11%); intensive services (n = 4405) had a mortality rate of 0.61% (95% CI, 0.42%-0.89%). Among OAs, planned MOUD with nonintensive outpatient services had a mortality rate of 4.17% (95% CI, 3.56%-4.9%). CONCLUSIONS: This TEDS-D analysis extends previous literature highlighting a significant interaction between planned MOUD and service intensity on in-treatment mortality for OAs. Additional research is needed to address the causal mechanisms behind these interactions and inform the delivery of safe effective care in the growing OA population.

Evidence of telescoping in females across two decades of US treatment admissions for injection drug use: 2000-2020.

Background: People who inject drugs (PWID) have an increased risk of soft tissue infection, drug overdose and death. Females may be particularly vulnerable due to barriers to substance use disorder (SUD) treatment entry, stigma, and telescoping, or the greater severity in substance use-related comorbidity and consequences despite a shorter history of use. We set out to identify sex differences in United States injection drug use (IDU). Methods: The Treatment Episode Dataset-Admission (2000-2020) provided data to identify PWID undergoing their initial SUD treatment admission. Mann-Whitney U test, chi-square, and Spearman correlations were used for ordinal variables, categorical variables, and to assess similarity of male/female trends over the 21 years, respectively. The probabilistic index (PI) and Cramer's V provided effect sizes for Mann-Whitney U tests and chi-square tests, respectively. Results: A total of 13,612,978 records existed for cases entering their initial treatment. Mapping to a history of IDU left 1,458,695 (561,793 females). Females had a higher prevalence among PWID across all 21 years; IDU trends were essentially identical between males and females (r = 0.97). Females endorsed beginning their primary substance later in life (PI = 0.47, p < 0.0001) and entered treatment after a shorter period of substance use (PI = 0.57, p < 0.0001). Conclusions: We saw evidence of telescoping among PWID with a SUD entering their initial episode of treatment. Interventions should be implemented prior to the transition to IDU, and this window of opportunity is shortened in females. Utilizing gender-responsive treatment options may be a way to increase treatment-seeking earlier in the disease course.

Recovery Capital Correlates With Less Methamphetamine Use and Crime in the Community.

OBJECTIVES: Reentry postcorrectional involvement is a high-risk time for patients with a history of addiction. We investigated whether participation in an addiction medicine clinic with active case management led to improvements in patients' recovery capital and whether there were associated changes in criminal activity and co-occurring methamphetamine or alcohol use. METHODS: Participants (n = 136) were patients with an opioid or stimulant use disorder who had Department of Corrections involvement in the preceding year, who completed the Assessment of Recovery Capital (ARC) and reported criminal activity and days of methamphetamine or alcohol use twice over a 6-month study. Three logistic regression models were used to assess changes in total ARC with criminal activity, alcohol use, and methamphetamine use over the previous 30 days. RESULTS: Baseline mean (SD) ARC scores were 34.1 (11.1) and increased to a mean (SD) score of 40.3 (9.4) at study end. A 1-SD shift in ARC was significantly protective across outcomes, with adjusted odds ratios of 0.32, 0.18, and 0.34 for any past 30-day criminal activity, alcohol use, or methamphetamine use. There was no significant difference in baseline ARC, crimes committed, days of alcohol use, or days of methamphetamine use for study completers versus noncompleters; however, unmeasured confounders may have had a differential impact on retention. CONCLUSIONS: Recovery capital provides an additional framework to help address patients' substance use and criminal activity in a multifaceted way, which is especially important in the postincarceration community. Recovery capital is dynamic and has multiple areas to target psychosocial interventions.

Recovery Capital Gains May Precede Craving Reduction in Opioid Use Disorder.

Purpose: Cravings for drugs and alcohol have been significantly associated with worse treatment outcomes. We investigated if improvements in recovery capital (RC) (eg, a measure of social capital/network, financial resources, education, and cultural factors) over time were associated with decreased reported cravings. Patients and Methods: The original cohort consisted of 133 participants (63 females) with opioid use disorder seeking outpatient treatment, who completed the Assessment of Recovery Capital (ARC) (range 0 to 50) and the Brief Addiction Monitor (BAM) thrice over the 6-month study. Intervention was medication and case management. Analysis included one-way mixed models testing change over time for ARC total scores and single question craving rating (5-point Likert scale). Cross-lagged panel estimates used structural equation models with variables z-scored, allowing for path coefficient evaluation as standard deviations (sd). Results: Total ARC significantly increased over the study (χ2 = 33.77, df = 2, p < 0.0001), with baseline of 36.6 (n = 114, sd = 11.1) and 6-month of 41.2 (n = 107, sd = 9.5). Craving also changed significantly (χ2 = 8.51, df = 2, p < 0.015), with baseline of 1.1 (n = 101, sd = 1.2) and 6-month of 0.9 (n = 107, sd = 1.1). The cross-lag from baseline RC to 3-month craving was significant (ß = -0.28, SE = 0.11, z = -2.53, p < 0.011). The converse was not true; baseline craving did not affect later RC. Results were similarly significant when comparing 3-month to 6-month. The majority of sample was on buprenorphine. Conclusion: As RC improves, the reported cravings at both 3- and 6-month study time points are significantly reduced. When evaluated inversely, there was not a significant association with baseline cravings and follow-up RC. Significant path coefficients provide an estimation of a directional effect from increased RC towards craving reduction.

Sex Differences in Recovery Capital Gains Post-Incarceration.

BACKGROUND: People with substance use disorders are highly prevalent in the carceral system. Recovery capital (RC) is the resources available to an individual to initiate or maintain substance use cessation. Sex differences have been identified in RC during both active substance use and recovery in the general population, however, less is known about these sex differences in the post-incarceration population. METHODS: Participants (n = 136) were those with an opioid or stimulant use disorder with past year involvement with the Iowa criminal justice system (USA), who completed the Assessment of Recovery Capital (ARC) twice over a six-month cohort study. Participants were involved in an addiction clinic that utilized active case management. Analysis of covariance evaluated changes in ARC during the study. Separate models compared total ARC and individual ARC domains, with sex as the independent variable of interest. Model means were generated for interpretation based on sex, comparing baseline and study endpoint ARC scores. RESULTS: There were no baseline sex differences in total ARC. ARC increased significantly for the group, however, males showed disproportionate growth. Females ended the study with a mean ARC of 37.8 (SD= 9.3) and males finished at 41.6 (SD= 9.3), which was a significant difference (p = 0.044); this significant difference was driven by ARC subdomains of 'Psychological Health' and 'Physical Health.' CONCLUSIONS: People post-incarceration are at high risk for return to substance use. Treatment that is informed by sex-based differences may have the potential to decrease the differing rates of growth in RC between sexes.

Improvements in recovery capital are associated with decreased alcohol use in a primary opioid use disorder treatment-seeking cohort.

BACKGROUND AND OBJECTIVES: Comorbid substance use can negatively impact multiple aspects of treatment for patients with an opioid use disorder (OUD). We investigated if treatment for OUD led to improvements in patients' recovery capital (RC) overtime, and whether there were associated changes in co-occurring alcohol use. METHODS: Participants (n = 133) were patients with OUD seeking outpatient treatment, who completed the Assessment of Recovery Capital (ARC) and reported drinking days per 30-day period thrice over the 6-month study. No specific treatments targeting alcohol were used. Two different models were employed to assess changes in total ARC score and adjusted odds ratio (aOR) for past 30-day abstinence. RESULTS: Baseline mean ARC scores were 36.6 and significantly increased to mean score of 41.2 at study end. Ninety-one participants (68.4%) reported no alcohol use at baseline, and 97 (78.9%) reported no use in the previous 30 days at study endpoint. For each increase in ARC, there was an aOR 1.07 (confidence interval [CI]: 1.02-1.13) for past 30-day abstinence. Considering ARC standard deviation of 10.33 over all measurements, this equates to an aOR of 2.10 (CI: 1.22-3.62) for past 30-day abstinence. DISCUSSION AND CONCLUSIONS: We saw significantly increased aOR for past 30-day abstinence as RC improved in an OUD treatment-seeking population. This difference was not caused by differences in ARC between study completers and noncompleters. SCIENTIFIC SIGNIFICANCE: Showcases how RC growth may be protective of past 30-day alcohol use in an OUD cohort and adds specific aOR for abstinence per ARC increase.

Perceived risk of LSD varies with age and race: evidence from 2019 United States cross-sectional data.

PURPOSE: Psychedelics are being explored for their potential therapeutic benefits across a wide range of psychiatric diagnoses and may usher in a new age in psychiatric treatment. There is stigma associated with these currently illegal substances, and use varies by race and age. We hypothesized that minoritized racial and ethnic populations, relative to White respondents, would perceive psychedelic use as riskier. METHODS: Using 2019 cross-sectional data from the National Survey of Drug Use and Health, we conducted a secondary analysis of 41,679 respondents. Perceived risk of heroin was used as a surrogate for overall risk of illegal substance use; heroin and lysergic acid diethylamide were the only substances queried this way in the sample. RESULTS: A majority regarded lysergic acid diethylamide (66.7%) and heroin (87.3%) as a great risk if used once or twice. There were clear differences by race, with White respondents and those indicating more than one race having significantly lower perceived risk of lysergic acid diethylamide than respondents from other groups. Perceived risk of use also significantly increased with age. CONCLUSION: Perceived risk of lysergic acid diethylamide is unevenly distributed across the population. Stigma and racial disparities in drug-related crimes likely contribute to this. As research into potential therapeutic indications for psychedelics continues, perceived risk of use may change.

Case Report: Buprenorphine-precipitated fentanyl withdrawal treated with high-dose buprenorphine.

Background: Buprenorphine, a partial agonist of the mu-opioid receptor, is an increasingly prescribed medication for maintenance treatment of opioid use disorder. When this medication is taken in the context of active opioid use, precipitated withdrawal can occur, leading to acute onset of opioid withdrawal symptoms. Fentanyl complicates use of buprenorphine, as it slowly releases from body stores and can lead to higher risk of precipitated withdrawal. Objectives: Describe the successful management of buprenorphine precipitated opioid withdrawal from fentanyl with high doses of buprenorphine. We seek to highlight how no adverse effects occurred in this patient and illustrate his stable transition to outpatient treatment. Case report: We present the case of a patient with severe opioid use disorder who presented in moderately severe opioid withdrawal after taking non-prescribed buprenorphine-naloxone which precipitated opioid withdrawal from daily fentanyl use. He was treated with high doses of buprenorphine, 148 mg over the first 48 hours, averaging 63 mg per day over four days. The patient reported rapid improvement in withdrawal symptoms without noted side effects and was able to successfully taper to 16 mg twice daily by discharge. Conclusions: This case demonstrates the safety and effectiveness of buprenorphine at high doses for treatment of precipitated withdrawal. While other options include symptomatic withdrawal management, initiating methadone or less researched options like ketamine, utilizing buprenorphine can preserve or re-establish confidence in this life-saving medication. This case also increases the previously documented upper boundary on buprenorphine dosing for withdrawal and should provide additional confidence in its use.

Developing Precision Invasive Neuromodulation for Psychiatry.

Psychiatric conditions are common and often disabling. Although great strides have been made in alleviating symptoms with pharmacotherapy and psychotherapeutic approaches, many patients continue to have severe disease burden despite the best therapies available. One of the pervasive challenges to improving treatment is that present diagnostic and therapeutic strategies lag behind our modern conceptualization of the pathophysiology of these disorders. Psychiatric symptoms manifest through activity in specific neural circuits; thus, therapies capable of modulating these circuits are attractive. The investigators reviewed recent advances that facilitate treating medically refractory psychiatric disorders with intracranial neuromodulation in a way that intervenes more directly with the underlying pathophysiology. Specifically, they reviewed the prospects for using intracranial multielectrode arrays to record brain activity with high spatiotemporal resolution and identify circuit-level electrophysiological correlates of symptoms. A causal relationship of circuit electrophysiology to symptoms could then be established by modulating the circuits to disrupt the symptoms. Personalized therapeutic neuromodulation strategies can then proceed in a rational manner with stimulation protocols informed by the underlying circuit-based pathophysiology of the most bothersome symptoms. This strategy would enhance current methods in neurotherapeutics by identifying individualized anatomical targets with symptom-specific precision, circumventing many of the limitations inherent in modern psychiatric nosology and treatment.

scRepertoire: An R-based toolkit for single-cell immune receptor analysis.

Single-cell sequencing is an emerging technology in the field of immunology and oncology that allows researchers to couple RNA quantification and other modalities, like immune cell receptor profiling at the level of an individual cell. A number of workflows and software packages have been created to process and analyze single-cell transcriptomic data. These packages allow users to take the vast dimensionality of the data generated in single-cell-based experiments and distill the data into novel insights. Unlike the transcriptomic field, there is a lack of options for software that allow for single-cell immune receptor profiling. Enabling users to easily combine mRNA and immune profiling, scRepertoire was built to process data derived from 10x Genomics Chromium Immune Profiling for both T-cell receptor (TCR) and immunoglobulin (Ig) enrichment workflows and subsequently interacts with the popular Seurat R package. The scRepertoire R package and processed data are open source and available on GitHub and provides in-depth tutorials on the capability of the package.

A transcriptomic map of murine and human alopecia areata.

Alopecia areata (AA) is a common autoimmune condition, presenting initially with loss of hair without other overt skin changes. The unremarkable appearance of the skin surface contrasts with the complex immune activity occurring at the hair follicle. AA pathogenesis is due to the loss of immune privilege of the hair follicle, leading to autoimmune attack. Although the literature has focused on CD8+ T cells, vital roles for CD4+ T cells and antigen-presenting cells have been suggested. Here, we use single-cell sequencing to reveal distinct expression profiles of immune cells in murine AA. We found clonal expansions of both CD4+ and CD8+ T cells, with shared clonotypes across varied transcriptional states. The murine AA data were used to generate highly predictive models of human AA disease. Finally, single-cell sequencing of T cells in human AA recapitulated the clonotypic findings and the gene expression of the predictive models.

Identification of Patients With High Mortality Risk and Prediction of Outcomes in Delirium by Bispectral EEG.

BACKGROUND: Delirium is common and dangerous, yet underdetected and undertreated. Current screening questionnaires are subjective and ineffectively implemented in busy hospital workflows. Electroencephalography (EEG) can objectively detect the diffuse slowing characteristic of delirium, but it is not suitable for high-throughput screening due to size, cost, and the expertise required for lead placement and interpretation. This study hypothesized that an efficient and reliable point-of-care EEG device for high-throughput screening could be developed. METHODS: This prospective study, which measured bispectral EEG (BSEEG) from elderly inpatients to assess their outcomes, was conducted at the University of Iowa Hospitals and Clinics from January 2016 to October 2017. A BSEEG score was defined based on the distribution of 2,938 EEG recordings from the 428 subjects who were assessed for delirium; primary outcomes measured were hospital length of stay, discharge disposition, and mortality. RESULTS: A total of 274 patients had BSEEG score data available for analysis. Delirium and BSEEG score had a significant association (P < .001). Higher BSEEG scores were significantly correlated with length of stay (P < .001 unadjusted, P = .001 adjusted for age, sex, and Charlson Comorbidity Index [CCI] score) as well as with discharge not to home (P < .01). Hazard ratio for survival controlling for age, sex, CCI score, and delirium status was 1.35 (95% CI,1.04 to 1.76; P = .025). CONCLUSIONS: In BSEEG, an efficient and reliable device that provides an objective measurement of delirium status was developed. The BSEEG score is significantly associated with pertinent clinical outcomes of mortality, hospital length of stay, and discharge disposition. The BSEEG score better predicts mortality than does clinical delirium status. This study identified a previously unrecognized subpopulation of patients without clinical features of delirium who are at increased mortality risk.

Religiosity and Chance Beliefs in Persons with DSM-IV Pathological Gambling Enrolled in a Longitudinal Follow-Up Study.

This study investigates the association of public, private and intrinsic religiosity and chance beliefs (superstition, illusion of control) with gambling behavior in a longitudinal follow-up study of younger and older adult subjects with DSM-IV pathological gambling (PG) and an older adult comparison group without PG. One-hundred sixty-three subjects were enrolled including 60 younger adults with PG (≥ 18/< 40 years), 53 older adults with PG (≥ 60 years), and 50 older adults without PG (≥ 60). Subjects were assessed at baseline and every 6 months thereafter. The Duke University Religion Index for Religious Assessment and the Drake Beliefs About Chance scales were administered at baseline. Follow-up was a mean (SD) of 2.6 (1.4) years. Older adults with PG scored lower on measures of public and intrinsic aspects of religiosity than older adults without PG, and scored higher on superstition and illusion of control. Older adults with PG also scored higher than younger adults with PG on private and intrinsic religiosity, but not public religiosity. Superstition predicted intrinsic, but not other aspects of religiosity. Importantly, during follow-up, higher levels of public and intrinsic religiosity were protective against problematic (levels 2, 3) gambling; were protective against chronic PG; and were predictive of PG remission status. Lower illusion of control ratings were protective against problematic gambling and chronic PG; lower superstition ratings were predictive of remission. We conclude that higher levels of public and intrinsic religiosity and lower levels of chance beliefs are associated with a more benign PG course.

TRGAted: A web tool for survival analysis using protein data in the Cancer Genome Atlas.

Reverse-phase protein arrays (RPPAs) are a highthroughput approach to protein quantification utilizing antibody-based micro-to-nano scale dot blot. Within the Cancer Genome Atlas (TCGA), RPPAs were used to quantify over 200 proteins in 8,167 tumor and metastatic samples. Protein-level data has particular advantages in assessing putative prognostic or therapeutic targets in tumors. However, many of the available pipelines do not allow for the partitioning of clinical and RPPA information to make meaningful conclusions. We developed a cloud-based application, TRGAted to enable researchers to better examine patient survival based on single or multiple proteins across 31 cancer types in the TCGA. TRGAted contains up-to-date overall survival, disease-specific survival, disease-free interval and progression-free interval information. Furthermore, survival information for primary tumor samples can be stratified based on gender, age, tumor stage, histological type, and subtype, allowing for highly adaptive and intuitive user experience. The code and processed data are open sourced and available on github and contains a tutorial built into the application for assisting users.

The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity.

Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity (AHR). As a comparison, we also used previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating AHR; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.

Geometry-assisted three-dimensional superlocalization imaging of single-molecule catalysis on modular multilayer nanocatalysts.

To establish the structure-catalytic property relationships of heterogeneous catalysts, a detailed characterization of the three-dimensional (3D) distribution of active sites on a single catalyst is essential. Single-particle catalysis of a modular multilayer catalytic platform that consists of a solid silica core, a mesoporous silica shell, and uniformly distributed Pt nanoparticles sandwiched in between these layers is presented. The first 3D high-resolution super-localization imaging of single fluorescent molecules produced at active sites on the core-shell model nanocatalysts is demonstrated. The 3D mapping is aided by the well-defined geometry and a correlation study in scanning electron microscopy and total internal reflection fluorescence and scattering microscopy. This approach can be generalized to study other nano- and mesoscale structures.