The spectrum of movement disorders in young children with ARX-related epilepsy-dyskinesia syndrome.

Children with developmental and epileptic encephalopathies often present with co-occurring dyskinesias. Pathogenic variants in ARX cause a pleomorphic syndrome that includes infantile epilepsy with a variety of movement disorders ranging from focal hand dystonia to generalized dystonia with frequent status dystonicus. In this report, we present three patients with severe movement disorders as part of ARX-associated epilepsy-dyskinesia syndrome, including a patient with a novel pathogenic missense variant (p.R371G). These cases illustrate diagnostic and management challenges of ARX-related disorder and shed light on broader challenges concerning epilepsy-dyskinesia syndromes.

Simulation-based medical education in Canadian anesthesiology academic institutions: a national survey.

PURPOSE: Simulation-based medical education (SBME) is provided by all anesthesiology residency programs in Canada. The purpose of this study was to characterize SBME in Canadian anesthesiology residency training programs. METHODS: We administered a 21-question survey to the simulation director/coordinator for all 17 Canadian academic departments of anesthesiology from October 2019 to January 2020. The survey consisted of questions pertaining to the characteristics of the simulation centres, their faculty, learners, curriculum, and assessment processes. RESULTS: All 17 residency training programs participated in the survey and reported large variability in the number and formal training of simulation faculty and in content delivery. Five programs (29%) did not provide faculty recognition for curriculum design and running simulation sessions. Most programs offered one to four simulation sessions per academic year for each year of residency. All programs offered mannequin-based and part-task trainers for teaching technical and nontechnical skills. Fourteen programs (82%) offered interprofessional and interdisciplinary simulation sessions, and ten programs (59%) did not include in situ simulation training. Commonly reported barriers to faculty involvement were lack of protected time (12 programs, 71%), lack of financial compensation (ten programs, 59%), and lack of appreciation for SBME (seven programs, 41%). CONCLUSION: Large variability exists in the delivery of SBME in Canadian anesthesiology residency simulation programs, in part because of differences in financial/human resources and educational content. Future studies should explore whether training and patient outcomes differ between SBME programs and, if so, whether additional standardization is warranted.

RéSUMé: OBJECTIF: La formation médicale par simulation est offerte par tous les programmes de résidence en anesthésiologie au Canada. L'objectif de cette étude était de déterminer l'état actuel de la formation médicale par simulation dans les programmes canadiens de résidence en anesthésiologie. MéTHODE: D'octobre 2019 à janvier 2020, nous avons administré un sondage comportant 21 questions aux directions et équipes de coordination de la simulation des 17 départements universitaires d'anesthésiologie canadiens. L'enquête comportait des questions portant sur les caractéristiques des centres de simulation, le corps professoral, les apprenants et apprenantes, le programme d'études et les processus d'évaluation. RéSULTATS: Les 17 programmes de résidence ont tous participé à l'enquête et ont fait état d'une grande variabilité dans le nombre et la formation officielle du corps professoral en simulation ainsi que dans la prestation de contenu. Cinq programmes (29 %) n'ont pas reconnu le corps professoral en charge de la conception des programmes d'études et de l'organisation des séances de simulation. La plupart des programmes offraient une à quatre séances de simulation par année universitaire à chaque année de résidence. Tous les programmes disposaient de simulateurs d'entraînement pour tâches partielles et de mannequins pour enseigner des compétences techniques et non techniques. Quatorze programmes (82 %) offraient des séances de simulation interprofessionnelles et interdisciplinaires, et dix programmes (59 %) ne comportaient pas de formation par simulation in situ. Les obstacles les plus fréquemment signalés à la participation du corps professoral étaient le manque de temps protégé (12 programmes, 71 %), le manque de compensation financière (dix programmes, 59 %) et le manque d'appréciation de la formation médicale par simulation (sept programmes, 41 %). CONCLUSION: Il existe une grande variabilité dans la prestation de formation médicale par simulation dans les programmes de simulation pendant la résidence en anesthésiologie au Canada, causée en partie par des différences dans les ressources financières et humaines et par le contenu de la formation. Des études futures devraient déterminer si la formation et les issues pour les patient·es diffèrent d'un programme de formation médicale par simulation à l'autre et, dans l'affirmative, si une normalisation supplémentaire est justifiée.

Timed material self-assembly controlled by circadian clock proteins.

Active biological molecules present a powerful, yet largely untapped, opportunity to impart autonomous regulation to materials. Because these systems can function robustly to regulate when and where chemical reactions occur, they have the ability to bring complex, life-like behavior to synthetic materials. Here, we achieve this design feat by using functionalized circadian clock proteins, KaiB and KaiC, to engineer time-dependent crosslinking of colloids. The resulting material self-assembles with programmable kinetics, producing macroscopic changes in material properties, via molecular assembly of KaiB-KaiC complexes. We show that colloid crosslinking depends strictly on the phosphorylation state of KaiC, with kinetics that are synced with KaiB-KaiC complexing. Our microscopic image analyses and computational models indicate that the stability of colloidal super-structures depends sensitively on the number of Kai complexes per colloid connection. Consistent with our model predictions, a high concentration stabilizes the material against dissolution after a robust self-assembly phase, while a low concentration allows circadian oscillation of material structure. This work introduces the concept of harnessing biological timers to control synthetic materials; and, more generally, opens the door to using protein-based reaction networks to endow synthetic systems with life-like functional properties.

Somatic Mosaicism in PIK3CA Variant Correlates With Stereoelectroencephalography-Derived Electrophysiology.

Objectives: Brain-limited pathogenic somatic variants are associated with focal pediatric epilepsy, but reliance on resected brain tissue samples has limited our ability to correlate epileptiform activity with abnormal molecular pathology. We aimed to identify the pathogenic variant and map variant allele fractions (VAFs) across an abnormal region of epileptogenic brain in a patient who underwent stereoelectroencephalography (sEEG) and subsequent motor-sparing left frontal disconnection. Methods: We extracted genomic DNA from peripheral blood, brain tissue resected from peri-sEEG electrode regions, and microbulk brain tissue adherent to sEEG electrodes. Samples were mapped based on an anatomic relationship with the presumed seizure onset zone (SOZ). We performed deep panel sequencing of amplified and unamplified DNA to identify pathogenic variants with subsequent orthogonal validation. Results: We detect a pathogenic somatic PIK3CA variant, c.1624G>A (p.E542K), in the brain tissue samples, with VAF inversely correlated with distance from the SOZ. In addition, we identify this variant in amplified electrode-derived samples, albeit with lower VAFs. Discussion: We demonstrate regional mosaicism across epileptogenic tissue, suggesting a correlation between variant burden and SOZ. We also validate a pathogenic variant from individual amplified sEEG electrode-derived brain specimens, although further optimization of techniques is required.

Use of Voice-Based Conversational Artificial Intelligence for Basal Insulin Prescription Management Among Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Optimizing insulin therapy for patients with type 2 diabetes can be challenging given the need for frequent dose adjustments. Most patients receive suboptimal doses and do not achieve glycemic control. Objective: To examine whether a voice-based conversational artificial intelligence (AI) application can help patients with type 2 diabetes titrate basal insulin at home to achieve rapid glycemic control. Design, Setting, and Participants: In this randomized clinical trial conducted at 4 primary care clinics at an academic medical center from March 1, 2021, to December 31, 2022, 32 adults with type 2 diabetes requiring initiation or adjustment of once-daily basal insulin were followed up for 8 weeks. Statistical analysis was performed from January to February 2023. Interventions: Participants were randomized in a 1:1 ratio to receive basal insulin management with a voice-based conversational AI application or standard of care. Main Outcomes and Measures: Primary outcomes were time to optimal insulin dose (number of days needed to achieve glycemic control), insulin adherence, and change in composite survey scores measuring diabetes-related emotional distress and attitudes toward health technology and medication adherence. Secondary outcomes were glycemic control and glycemic improvement. Analysis was performed on an intent-to-treat basis. Results: The study population included 32 patients (mean [SD] age, 55.1 [12.7] years; 19 women [59.4%]). Participants in the voice-based conversational AI group more quickly achieved optimal insulin dosing compared with the standard of care group (median, 15 days [IQR, 6-27 days] vs >56 days [IQR, >29.5 to >56 days]; a significant difference in time-to-event curves; P = .006) and had better insulin adherence (mean [SD], 82.9% [20.6%] vs 50.2% [43.0%]; difference, 32.7% [95% CI, 8.0%-57.4%]; P = .01). Participants in the voice-based conversational AI group were also more likely than those in the standard of care group to achieve glycemic control (13 of 16 [81.3%; 95% CI, 53.7%-95.0%] vs 4 of 16 [25.0%; 95% CI, 8.3%-52.6%]; difference, 56.3% [95% CI, 21.4%-91.1%]; P = .005) and glycemic improvement, as measured by change in mean (SD) fasting blood glucose level (-45.9 [45.9] mg/dL [95% CI, -70.4 to -21.5 mg/dL] vs 23.0 [54.7] mg/dL [95% CI, -8.6 to 54.6 mg/dL]; difference, -68.9 mg/dL [95% CI, -107.1 to -30.7 mg/dL]; P = .001). There was a significant difference between the voice-based conversational AI group and the standard of care group in change in composite survey scores measuring diabetes-related emotional distress (-1.9 points vs 1.7 points; difference, -3.6 points [95% CI, -6.8 to -0.4 points]; P = .03). Conclusions and Relevance: In this randomized clinical trial of a voice-based conversational AI application that provided autonomous basal insulin management for adults with type 2 diabetes, participants in the AI group had significantly improved time to optimal insulin dose, insulin adherence, glycemic control, and diabetes-related emotional distress compared with those in the standard of care group. These findings suggest that voice-based digital health solutions can be useful for medication titration. Trial Registration: ClinicalTrials.gov Identifier: NCT05081011.

Detecting nuance in conspiracy discourse: Advancing methods in infodemiology and communication science with machine learning and qualitative content coding.

The spread of misinformation and conspiracies has been an ongoing issue since the early stages of the internet era, resulting in the emergence of the field of infodemiology (i.e., information epidemiology), which investigates the transmission of health-related information. Due to the high volume of online misinformation in recent years, there is a need to continue advancing methodologies in order to effectively identify narratives and themes. While machine learning models can be used to detect misinformation and conspiracies, these models are limited in their generalizability to other datasets and misinformation phenomenon, and are often unable to detect implicit meanings in text that require contextual knowledge. To rapidly detect evolving conspiracist narratives within high volume online discourse while identifying nuanced themes requiring the comprehension of subtext, this study describes a hybrid methodology that combines natural language processing (i.e., topic modeling and sentiment analysis) with qualitative content coding approaches to characterize conspiracy discourse related to 5G wireless technology and COVID-19 on Twitter (currently known as 'X'). Discourse that focused on correcting 5G conspiracies was also analyzed for comparison. Sentiment analysis shows that conspiracy-related discourse was more likely to use language that was analytic, combative, past-oriented, referenced social status, and expressed negative emotions. Corrections discourse was more likely to use words reflecting cognitive processes, prosocial relations, health-related consequences, and future-oriented language. Inductive coding characterized conspiracist narratives related to global elites, anti-vax sentiment, medical authorities, religious figures, and false correlations between technology advancements and disease outbreaks. Further, the corrections discourse did not address many of the narratives prevalent in conspiracy conversations. This paper aims to further bridge the gap between computational and qualitative methodologies by demonstrating how both approaches can be used in tandem to emphasize the positive aspects of each methodology while minimizing their respective drawbacks.

Outcomes of Orchiectomy for Gender-affirming Surgery: A National Surgical Quality Improvement Program Study.

OBJECTIVE: To identify perioperative outcomes of transgender orchiectomy (TGO) and to broadly compare outcomes of TGO to cisgender orchiectomy (CGO) for nononcologic indications. METHODS: Using the National Surgical Quality Improvement Program (NSQIP) database from 2010 to 2020, a retrospective study was performed on patients with ICD-9/10 codes for gender dysphoria, testicular torsion, and testicular pain who underwent simple orchiectomy. Demographics and surgical outcomes were summarized. Welch two-sample t test and chi-square test were used for group analysis. A trend analysis was performed for temporal trends of these surgeries. RESULTS: 246 patients underwent TGO and 997 patients underwent CGO (607 testicular torsion, 390 testicular pain). Overall complication rates between TGO and CGO did not differ for testicular torsion (3.7% vs 4.4%, P = .6) or testicular pain (3.7% vs 5.9%, P = .2). No differences in patient characteristics were seen within the TGO group when comparing those who experienced complications to those who didn't. From 2015 to 2020, TGO cases significantly increased by, on average, 9.5 cases per year (95% CI: 6.3-12.7, P = .001), while CGO had showed no significant temporal change. CONCLUSION: Standalone TGO can be performed safely in an outpatient setting with an acceptable complication profile in medically diverse patients.

Exploring the Study of Simulation as a Continuing Professional Development Strategy for Physicians.

INTRODUCTION: Practicing physicians have the responsibility to engage in lifelong learning. Although simulation is an effective experiential educational strategy, physicians seldom select it for continuing professional development (CPD) for reasons that are poorly understood. The objective of this study was to explore existing evidence on simulation-based CPD and the factors influencing physicians' engagement in simulation-based CPD. METHODS: A scoping review of the literature on simulation-based CPD included MEDLINE, Embase, and CINAHL databases. Studies involving the use of simulation for practicing physicians' CPD were included. Information related to motivations for participating in simulation-based CPD, study objectives, research question(s), rationale(s), reasons for using simulation, and simulation features was abstracted. RESULTS: The search yielded 8609 articles, with 6906 articles undergoing title and abstract screening after duplicate removal. Six hundred sixty-one articles underwent full-text screening. Two hundred twenty-five studies (1993-2021) were reviewed for data abstraction. Only four studies explored physicians' motivations directly, while 31 studies described incentives or strategies used to enroll physicians in studies on simulation-based CPD. Most studies focused on leveraging or demonstrating the utility of simulation for CPD. Limited evidence suggests that psychological safety, direct relevance to clinical practice, and familiarity with simulation may promote future engagement. DISCUSSION: Although simulation is an effective experiential educational method, factors explaining its uptake by physicians as a CPD strategy are unclear. Additional evidence of simulation effectiveness may fail to convince physicians to participate in simulation-based CPD unless personal, social, educational, or contextual factors that shape physicians' motivations and choices to engage in simulation-based CPD are explored.

Crystal lattice defects in nanocrystalline metacinnabar in contaminated streambank soils suggest a role for biogenic sulfides in the formation of mercury sulfide phases.

At mercury (Hg)-contaminated sites, streambank erosion can act as a main mobilizer of Hg into nearby waterbodies. Once deposited into the waters, mercury from these soils can be transformed to MeHg by microorganisms. It is therefore important to understand the solid-phase speciation of Hg in streambanks as differences in Hg speciation will have implications for Hg transport and bioavailability. In this study, we characterized Hg solid phases in Hg-contaminated soils (100-1100 mg per kg Hg) collected from the incised bank of the East Fork Poplar Creek (EFPC) in Oak Ridge, TN (USA). The analysis of the soil samples by scanning electron microscopy-energy dispersive spectroscopy indicated numerous microenvironments where Hg and sulfur (S) are co-located. According to bulk soil analyses by extended X-ray absorption fine structure spectroscopy (EXAFS), the near-neighbor Hg molecular coordination in the soils closely resembled freshly precipitated Hg sulfide (metacinnabar, HgS); however, EXAFS fits indicated the Hg in the HgS structure was undercoordinated with respect to crystalline metacinnabar. This undercoordination of Hg-S observed by spectroscopy is consistent with transmission electron microspy images showing the presence of nanocrystallites with structural defects (twinning, stacking faults, dislocations) in individual HgS-bearing particles. Although the soils were collected from exposed parts of the stream bank (i.e., open to the atmosphere), the presence of reduced forms of S and sulfate-reducing microbes suggests that biogenic sulfides promote the formation of HgS nanoparticles in these soils. Altogether, these data demonstrate the predominance of nanoparticulate HgS with crystal lattice defects in the bank soils of an industrially impacted stream. Efforts to predict the mobilization and bioavailability of Hg associated with nano-HgS forms should consider the impact of nanocrystalline lattice defects on particle surface reactivity, including Hg dissolution rates and bioavailability on Hg fate and transformations.

Patient-reported outcome measurement implementation in cancer survivors: a systematic review.

PURPOSE: Patient-reported outcome measurements (PROMs) are increasingly used for cancer patients receiving active treatment, but little is known about the implementation and usefulness of PROMs in cancer survivorship care. This systematic review evaluates how cancer survivors and healthcare providers (HCPs) perceive PROM implementation in survivorship care, and how PROM implementation impacts cancer survivors' health outcomes. METHODS: We systematically searched PubMed/MEDLINE, Embase, CINAHL, Web of Science, and Cochrane Database of Systematic Reviews from database inception to February 2022 to identify randomized and nonrandomized studies of PROM implementation in cancer survivors. RESULTS: Based on prespecified eligibility criteria, we included 29 studies that reported on 26 unique PROMs. The studies were heterogeneous in study design, PROM instrument, patient demographics, and outcomes. Several studies found that cancer survivors and HCPs had favorable impressions of the utility of PROMs, and a few studies demonstrated that PROM implementation led to improvements in patient quality of life (QoL), with small to moderate effect sizes. CONCLUSIONS: We found implementation of PROMs in cancer survivorship care improved health outcomes for select patient populations. Future research is needed to assess the real-world utility of PROM integration into clinical workflows and the impact of PROMs on measurable health outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors accepted PROMs. When successfully implemented, PROMs can improve health outcomes after completion of active treatment. We identify multiple avenues to strengthen PROM implementation to support cancer survivors.

ARDS With Pneumothorax in a Young Adult.

CASE PRESENTATION: A 19-year-old, previously healthy man presented with 3 days of cough, high-grade fevers (40 °C), and dyspnea. Apart from a resolved history of seizures not requiring medications, he had no medical or surgical history. He had no known drug allergies. He took montelukast for allergies and trimethoprim-sulfamethoxazole (TMP-SMX) for 2 weeks before admission for acne, but no other medications, including over-the-counter medications and supplements. He had animal exposures to a new puppy and a friend's bird. He had no history of smoking, vaping, or recreational drug use. His paternal grandmother had rheumatoid arthritis.

Dissection and Immunostaining of Larval Salivary Glands from Anopheles gambiae Mosquitoes.

Mosquito salivary glands (SGs) are a requisite gateway organ for the transmission of insect-borne pathogens. Disease-causing agents, including viruses and the Plasmodium parasites that cause malaria, accumulate in the secretory cavities of SG cells. Here, they are poised for transmission to their vertebrate hosts during a subsequent blood meal. As adult glands form as an elaboration of larval SG duct bud remnants that persist beyond early pupal SG histolysis, the larval SG is an ideal target for interventions that limit disease transmission. Understanding larval SG development can help develop a better understanding of its morphology and functional adaptations and aid in the assessment of new interventions that target this organ. This video protocol demonstrates an efficient technique for isolating, fixing, and staining larval SGs from Anopheles gambiae mosquitoes. Glands dissected from larvae in a 25% ethanol solution are fixed in a methanol-glacial acetic acid mixture, followed by a cold acetone wash. After a few rinses in phosphate-buffered saline (PBS), SGs can be stained with a broad array of marker dyes and/or antisera against SG-expressed proteins. This method for larval SG isolation could also be used to collect tissue for in situ hybridization analysis, other transcriptomic applications, and proteomic studies.

Influence of Polarity Change and Photophysical Effects on Photosurfactant-Driven Wetting.

Photosurfactants have shown considerable promise for enabling stimuli-responsive control of the properties and motion of fluid interfaces. Recently, a number of photoswitch chemistries have emerged to tailor the photoresponsive properties of photosurfactants. However, systematic studies investigating how photoresponsive surfactant behavior depends on the photochemical and photophysical properties of the switch remain scarce. In this work, we develop synthetic schemes and surfactant designs to produce a well-controlled library of photosurfactants to comparatively assess the behavior of photoswitch chemistry on interfacial behavior. We employ photoinduced spreading of droplets at fluid interfaces as a model for such studies. We show that although photosurfactant response is largely guided by expected trends with changes in polarity of the photoswitch, interfacial behavior also depends nontrivially and sometimes counter-intuitively on the kinetics and mechanisms of photoswitching, particularly at the interface of two solvents, as well as on complex interactions with other surfactants. Understanding these complexities enables the design of new photosurfactant systems and their optimization toward responsive functions including triggered spreading, dewetting, and destabilization of droplets on solid and fluid surfaces.

Seizure action plans in the pediatric population with epilepsy: Uptake, determinants, and parental interest in a mobile application.

BACKGROUND: Status epilepticus (SE) is a common pediatric neurological emergency that requires timely treatment to minimize morbidity and mortality, yet administration of rescue medications is often delayed and underdosed. Seizure action plans (SAPs) outline the steps that should be taken by parents and caregivers in case of SE in order to optimize patient outcomes. Our study determined the uptake of SAPs in a pediatric population with epilepsy and assessed parental interest in a SAP mobile application. METHODS: A survey was distributed to parents of patients with epilepsy aged 1 month to 19 years at British Columbia Children's Hospital. Following chart review, univariate and multivariate analyses were performed to identify variables that predict whether patients have SAPs. A systematic search of available mobile applications for epilepsy management was conducted. RESULTS: Of 192 participants, 62% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82% of patients with SAPs. 83% of parents were interested in a SAP mobile application. There are currently 40 mobile applications available for epilepsy management, but only 15% of respondents reported using them. CONCLUSIONS: There is a need to increase the percentage of patients with epilepsy with SAPs, particularly in those at greater risk of SE. Most parents would find a SAP mobile application valuable in their child's epilepsy management. There is a gap between the high parental interest in mobile applications for epilepsy management and their current use of such applications.

Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses.

OBJECTIVES: As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical. STUDY DESIGN: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified. RESULTS: A total of 192 children (mean age, 10.2 ± 7.0 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met the criteria for MIS-C. Only 25 children (51%) with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were nonspecific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower angiotensin-converting enzyme 2 expression (P = .004). Immunoglobulin M (IgM) and Immunoglobulin G (IgG) to the receptor binding domain of the SARS-CoV-2 spike protein were increased in severe MIS-C (P < .001), with dysregulated humoral responses observed. CONCLUSIONS: This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic despite having milder disease or a lack of symptoms; immune dysregulation is implicated in severe postinfectious MIS-C.

A detailed smoking history and determination of MYC status predict response to checkpoint inhibitors in advanced non-small cell lung cancer.

BACKGROUND: Although many studies have determined that PD-L1 expression by immunohistochemistry can be somewhat predictive of a response to checkpoint inhibitor the impact of specific genomic changes and smoking history in the context of PD-L1 expression is limited. This single-center study examined clinical and genomic factors beyond STK11 and EGFR in patients with advanced non-small cell lung cancer (NSCLC) to determine which patients benefit from therapy with immune checkpoint inhibitors (ICIs). METHODS: Clinical and genomic features of patients with NSCLC treated with immunotherapy were compiled into a database. Genomic information collected included gene mutations via next generation sequencing, tumor mutation burden (TMB), and PD-L1 tumor proportional scores. RESULTS: A total of 131 patients with advanced NSCLC treated with ICIs were examined. Race was not associated with response. A positive response to immunotherapy was associated with smoke year increase (P=0.042). KRAS mutation and MYC amplification were associated with a positive response to immunotherapy while EGFR, RB1, and NF1 mutations were associated with a lack of response. KRAS mutation (P=0.007) and high TMB (P=0.070) were positively associated with smoking history. EGFR mutation was negatively associated with smoking history (P=0.002) . In multivariate analysis controlling for age and smoking history, MYC amplification continued to be the only predictive genomic marker with a trend toward response to therapy (P=0.092) beyond the smoking history. CONCLUSIONS: Among the clinical and genomic factors examined in this study, smoking status is the most predictive of response to ICIs. Only MYC amplification continued to predict a trend toward response to immunotherapy when controlling for smoking history. Other genomic predictors such as EGFR and KRAS simply reflect their association with smoking. Detailed smoking history and MYC amplification alone can predict response to ICI.

Attention and cardiac phase boost judgments of trust.

Fluctuations in mental and bodily states have both been shown to be associated with negative affective experience. Here we examined how momentary fluctuations in attentional and cardiac states combine to regulate the perception of positive social value. Faces varying in trustworthiness were presented during a go/no-go letter target discrimination task synchronized with systolic or diastolic cardiac phase. Go trials lead to an attentional boosting of perceived trust on high trust and ambiguous neutral faces, suggesting attention both boosted existing and generated positive social value. Cardiac phase during face presentation interacted with attentional boosting of trust, enhancing high trust faces specifically during relaxed diastolic cardiac states. Confidence judgments revealed that attentional trust boosting, and its cardiac modulation, did not reflect altered perceptual or response fluency. These results provide evidence for how moment-to moment fluctuations in top-down mental and bottom-up bodily inputs combine to enhance a priori and generate de novo positive social value.