Cerebellar volume measures may differentiate multiple sclerosis fallers from non-fallers.

Introduction: The cerebellum is a common lesion site in persons with multiple sclerosis (PwMS). Physiologic and anatomic studies have identified a topographic organization of the cerebellum including functionally distinct motor and cognitive areas. This study implemented a recent parcellation algorithm developed by Han et al., 2020 to a sample of PwMS and healthy controls to examine relationships among specific cerebellar regions, fall status, and common clinical measures of motor and cognitive functions. Methods: Thirty-one PwMS and 29 age and sex-matched controls underwent an MRI scan and motor and cognitive testing. The parcellation algorithm was applied to all images and divided the cerebellum into 28 regions. Mann-Whitney U tests were used to compare cerebellar volumes among PwMS and controls, and MS fallers and MS non-fallers. Relationships between cerebellar volumes and motor and cognitive function was evaluated using Spearman correlations. Results: PwMS performed significantly worse on functional measures compared to controls. We found significant differences in volumetric measures between PwMS and controls in the corpus medullare, lobules I-III, and lobule V. Volumetric differences seen between PwMS and controls were primarily driven by the MS fallers. Finally, functional performance on motor and cognitive tasks was associated with cerebellar volumes. Conclusions: Using the parcellation tool, our results showed that volumes of motor and cognitive lobules impact both motor and cognitive performance, and that functional performance and cerebellar volumes distinguishes MS fallers from non-fallers. Future studies should explore the potential of cerebellar imaging to predict falls in PwMS.

Point mutation in a virus-like capsid drives symmetry reduction to form tetrahedral cages.

Protein capsids are a widespread form of compartmentalization in nature. Icosahedral symmetry is ubiquitous in capsids derived from spherical viruses, as this geometry maximizes the internal volume that can be enclosed within. Despite the strong preference for icosahedral symmetry, we show that simple point mutations in a virus-like capsid can drive the assembly of unique symmetry-reduced structures. Starting with the encapsulin from Myxococcus xanthus, a 180-mer bacterial capsid that adopts the well-studied viral HK97 fold, we use mass photometry and native charge detection mass spectrometry to identify a triple histidine point mutant that forms smaller dimorphic assemblies. Using cryoelectron microscopy, we determine the structures of a precedented 60-mer icosahedral assembly and an unexpected 36-mer tetrahedron that features significant geometric rearrangements around a new interaction surface between capsid protomers. We subsequently find that the tetrahedral assembly can be generated by triple-point mutation to various amino acids and that even a single histidine point mutation is sufficient to form tetrahedra. These findings represent a unique example of tetrahedral geometry when surveying all characterized encapsulins, HK97-like capsids, or indeed any virus-derived capsids reported in the Protein Data Bank, revealing the surprising plasticity of capsid self-assembly that can be accessed through minimal changes in the protein sequence.

Is Seeing Believing? Hallmark Movie Viewership and Relationship Beliefs.

The Hallmark Channel, a highly watched cable network, is known for its consistently idealistic portrayals of romantic relationships. Despite its popularity, no research has examined whether increased viewership of Hallmark movies covaries with endorsement of relationship beliefs. According to cultivation theory, what we watch impacts our beliefs and perceptions of reality. Additionally, the Differential Susceptibility to Media Effects Model (DSMM) proposes that certain variables, such as developmental (i.e., age, relationship length) and dispositional factors (e.g., attachment style, gender), may make certain viewers more or less susceptible to the effects of media viewership. Based on this grounding, the main purpose of this study was to determine if watching more Hallmark movies is associated with endorsing certain beliefs about romantic relationships and opposite-sex friendships when controlling for several susceptibility factors. A nationwide sample of heterosexual, married participants (N = 279) completed measures of Romantic Beliefs, Implicit Theories of Relationships, and beliefs about opposite-sex friendships and reported on their media consumption. More frequent Hallmark movie viewership was associated with increased endorsement of several relationship beliefs, above and beyond susceptibility factors (e.g., attachment, relationship length) and daily television consumption. Specifically, greater Hallmark movie viewership was positively associated with greater endorsement of multiple unrealistic relationship beliefs, destiny beliefs, and believing that opposite-sex friendships are problematic. The findings of the current study provide further support for cultivation theory and DSMM.

Assessment of salivary cortisol dynamics in an infantry training exercise: a pilot study.

INTRODUCTION: Measuring cortisol during military training offers insights into physiological responses to stress. We attempted precisely timed, cortisol awakening response (CAR) and pre-sleep cortisol (PSC), and diurnal slope (peak morning minus evening cortisol), during a British Army exercise. We aimed to understand cortisol dynamics and evaluate the feasibility of CAR and PSC in this environment. METHOD: Setting: high-intensity, 10-day infantry exercise. Participants: regular infantry soldiers exercising (EX, n=25) or headquarters-based (HQ, n=6). Participants undertook PSC and WAKE and WAKE+30 min samples after 1-2 days, 5-6 days and 9-10 days. Wrist-worn GENEActiv accelerometers were used to assess sleep duration in EX only. Samples taken ±15 min from prespecified time points were deemed adherent. Validated questionnaires were used to measure resilience and perceived stress. Cortisol and cortisone were measured simultaneously by liquid chromatography tandem mass spectrometry. RESULTS: From adherent participants' samples, CAR was positive and tended to decrease as the exercise progressed. From all available data, HQ demonstrated greater diurnal slope than EX (F=7.68, p=0.02), reflecting higher morning cortisol (F=4.72, p=0.038) and lower PSC (p=0.04). No differences were seen in cortisol:cortisone ratio. 26.1% of CAR samples were adherent, with moderately strong associations between adherence and stress (r=0.41, p=0.009) but no association between adherence and day of exercise (χ2=0.27, p=0.8), sleep duration (r=-0.112, p=0.43) or resilience (r=-0.79, p=0.75). Test-retest reliability ratings for CAR were Cronbach's α of 0.48, -11.7 and 0.34 for the beginning, middle and end of the exercise, respectively. CONCLUSIONS: We observed a reduction in morning cortisol and decreased diurnal slope during a high-intensity military exercise, compared with the HQ comparator cohort in whom diurnal slope was preserved. A carefully timed CAR was not feasible in this setting.

Perceptions of an acceptance-based weight management treatment among adults living in rural areas.

Obesity and obesity-related comorbidities disproportionately affect rural communities. Research has emerged in support of a novel acceptance-based behavioural weight management treatment (ABT) that integrates the principles and procedures of acceptance-commitment therapy (ACT) with traditional components of standard behavioural treatment (SBT). The current study assessed the perceptions of community stakeholders in rural areas to session materials of a commercially available ABT program. Surveys and focus groups were used to solicit feedback from three former interventionists with experience delivering SBTs in rural counties and from 17 former participants in these programs. Qualitative responses encompassed four overarching themes: (1) recommendations to support participant engagement, (2) comments about preferences for specific ABT and SBT strategies, (3) concerns about specific aspects of treatment delivery, and (4) requests for aesthetic changes to session materials to enhance clarity and engagement. Overall, participants viewed ABT materials and concepts favourably but believed it would be important to begin the intervention with rapport building and training in traditional SBT strategies prior to delving into ACT strategies. Future studies should investigate the efficacy of ABT for weight loss in adults with obesity living in rural communities and continue to solicit feedback from rural community stakeholders.

Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC): a prospective cohort study protocol.

INTRODUCTION: Radical chemoradiotherapy represents the gold standard for locally advanced cervical cancer. However, despite significant progress in improving local tumour control, distant relapse continues to impact overall survival. The development of predictive and prognostic biomarkers is consequently important to risk-stratify patients and identify populations at higher risk of poorer treatment response and survival outcomes. Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC) is a prospective exploratory cohort study, which aims to investigate the role of multiparametric functional MRI (fMRI) using diffusion-weighed imaging (DWI), dynamic contrast-enhanced (DCE) and blood oxygen level-dependent imaging (BOLD) MRI to assess treatment response and predict outcomes in patients undergoing radical chemoradiotherapy for cervical cancer. METHODS AND ANALYSIS: The study aims to recruit 40 patients across a single-centre over 2 years. Patients undergo multiparametric fMRI (DWI, DCE and BOLD-MRI) at three time points: before, during and at the completion of external beam radiotherapy. Tissue and liquid biopsies are collected at diagnosis and post-treatment to identify potential biomarker correlates against fMRI. The primary outcome is to evaluate sensitivity and specificity of quantitative parameters derived from fMRI as predictors of progression-free survival at 2 years following radical chemoradiotherapy for cervical cancer. The secondary outcome is to investigate the roles of fMRI as predictors of overall survival at 2 years and tumour volume reduction across treatment. Statistical analyses using regression models and survival analyses are employed to evaluate the relationships between the derived parameters, treatment response and clinical outcomes. ETHICS AND DISSEMINATION: The EMPIRIC study received ethical approval from the NHS Health Research Authority (HRA) on 14 February 2022 (protocol number RD2021-29). Confidentiality and data protection measures are strictly adhered to throughout the study. The findings of this study will be disseminated through peer-reviewed publications and scientific conferences, aiming to contribute to the growing body of evidence on the use of multiparametric MRI in cervical cancer management. TRIAL REGISTRATION NUMBER: NCT05532930.

Development and validation of a pulmonary function test data extraction tool for the US department of veterans affairs electronic health record.

OBJECTIVE: Pulmonary function test (PFT) results are recorded variably across hospitals in the Department of Veterans Affairs (VA) electronic health record (EHR), using both unstructured and semi-structured notes. We developed and validated a hospital-specific code to extract pre-bronchodilator measures of obstruction (ratio of forced expiratory volume in one second [FEV1] to forced vital capacity [FVC]) and severity of obstruction (percent predicted of FEV1). RESULTS: Among 36 VA facilities with the most PFTs completed between 2018 and 2022 from a parent cohort of veterans receiving long-acting controller inhalers, 12 had a consistent syntactical convention or template for reporting PFT data in the EHR. Of the 42,718 PFTs identified from these 12 facilities, the hospital-specific text processing pipeline yielded 24,860 values for the FEV1:FVC ratio and 23,729 values for FEV1. A ratio of FEV1:FVC less than 0.7 was identified in 17,615 of 24,922 studies (70.7%); 8864 of 24,922 (35.6%) had a severe or very severe reduction in FEV1 (< 50% of the predicted value). Among 100 randomly selected PFT reports reviewed by two pulmonary physicians, the coding solution correctly identified the presence of obstruction in 99 out of 100 studies and the degree of obstruction in 96 out of 100 studies.

Tissue oxygen saturation is positively correlated with oxygen delivery and cardiac output in a canine hemorrhagic shock and resuscitation model.

OBJECTIVE: To determine if tissue oxygen saturation (StO2) correlates with oxygen delivery (DO2) and/or cardiac output (CO) in a canine hemorrhagic shock model. ANIMALS: 8 healthy purpose-bred dogs. METHODS: Dogs were anesthetized, and hemorrhagic shock was induced by withdrawing up to 60% of total blood volume, targeting a mean arterial pressure (MAP) of 40 mm Hg. The withdrawn blood was returned to the patient in 2 equal aliquots. Data was collected at 4 time points: 10 minutes after MAP was stabilized under anesthesia (time point [TP]-1), 10 minutes after up to 60% of blood volume was removed to target a MAP of 40 mm Hg (TP2), 10 minutes after the return of 50% of shed blood (TP3), and 10 minutes after the return of the remaining 50% of shed blood (TP4). Total blood volume withdrawn, StO2, CO, heart rate, and MAP were recorded, and DO2 was calculated at each TP. RESULTS: Mean StO2 significantly decreased between TP1 (77.8% [± 9.54]) and TP2 (44.8% [± 19.5]; P < .001 vs TP1). Mean StO2 increased to 63.1% (± 9.85) at TP3, but remained significantly lower compared to TP1 (P = .002). There was no difference between mean StO2 at TP4 (82.5% [± 12.6]) versus TP1 (P = .466). StO2 has a strong, positive correlation to both CO (r = 0.80; P < .001) and DO2 (r = 0.75; P < .001). CLINICAL RELEVANCE: A decrease in StO2 may be used in conjunction with physical examination findings and diagnostic parameters to support a diagnosis of shock. The return of shed blood was correlated with increases in StO2, DO2, and CO, suggesting that StO2 may be used as a marker of adequate resuscitation.

The thermoneutral zone in women takes an "arctic" shift compared to men.

Conventionally, women are perceived to feel colder than men, but controlled comparisons are sparse. We measured the response of healthy, lean, young women and men to a range of ambient temperatures typical of the daily environment (17 to 31 °C). The Scholander model of thermoregulation defines the lower critical temperature as threshold of the thermoneutral zone, below which additional heat production is required to defend core body temperature. This parameter can be used to characterize the thermoregulatory phenotypes of endotherms on a spectrum from "arctic" to "tropical." We found that women had a cooler lower critical temperature (mean ± SD: 21.9 ± 1.3 °C vs. 22.9 ± 1.2 °C, P = 0.047), resembling an "arctic" shift compared to men. The more arctic profile of women was predominantly driven by higher insulation associated with more body fat compared to men, countering the lower basal metabolic rate associated with their smaller body size, which typically favors a "tropical" shift. We did not detect sex-based differences in secondary measures of thermoregulation including brown adipose tissue glucose uptake, muscle electrical activity, skin temperatures, cold-induced thermogenesis, or self-reported thermal comfort. In conclusion, the principal contributors to individual differences in human thermoregulation are physical attributes, including body size and composition, which may be partly mediated by sex.

On the Move: Correlation of Impaired Mobility with Spatial Navigation Ability in Persons with Multiple Sclerosis.

Spatial navigation ability is essential for independent living, and it relies on complex cognitive and motor processes that are vulnerable to decline in persons with multiple sclerosis (pwMS). The role of mobility in the physical act of navigation has been well documented; however, its association with cognitive processing that supports efficient navigation and recall of the environment is unknown. This study examined the relation between clinical mobility function and spatial navigation ability in pwMS. In a clinical sample of 43 individuals with relapsing-remitting MS (MPDDS = 2; age 25-67 years), we assessed spatial navigation ability in a virtual Morris water maze that allowed for active search by controlling a joystick while seated at a computer, and subsequent free recall of environment details. Individuals with worse mobility (measured by slower forward and backward walking) traveled less efficient virtual navigation routes to the goal location and recalled fewer accurate details of the environment. A stratified analysis by disability revealed moderate-strong correlations for those with a low level of disability, and effects were attenuated in individuals with a high level of disability. Given that the virtual navigation task was performed while seated, evidence of any correlation with mobility suggests differences in navigation ability that cannot be ascribed to general walking impairment, and instead suggests a role for mobility impairment to modify cognitive processing supporting navigation in pwMS.

Contraceptive Risk Events among Family Planning Specialists: a Cross Sectional Study.

Background: Proponents of abortion restriction cite advancements in contraceptive technology as a reason against the need for abortion care today, most recently through oral arguments in the Supreme Court of the United States case, Dobbs v. Jackson Women's Health. However, consistent and correct use of contraception requires reproductive health literacy. Our objectives were to quantify contraceptive risk events and assess contraceptive history and preferences among a population well-equipped to evade contraceptive risks, family planning specialists following initiation of their medical training. "Risk events" are defined as reported episodes of contraceptive failure, emergency contraception use and/or unprotected or underprotected intercourse. Methods: This was a cross-sectional study among current members of a professional organization of family planning specialists. Inclusion criteria included: status as a current or retired clinician, consensual penile-vaginal intercourse since the start of medical training, and personal or partner capacity to become pregnant. Descriptive statistics were performed. This study was IRB exempt. Results: Among 229 respondents, 157 (69%) reported experiencing a contraceptive risk event since training. Twenty-nine (13%) respondents reported an occurrence within the last year. By category, 47% (108/229; 3 reported unknown) reported under- or unprotected intercourse, 35% (81/229) reported emergency contraception use, and 52% of participants (117/227; 2 unknown) reported known or suspected contraceptive failure. The mean number of contraceptive methods used was 3.7 (SD 1.7) out of the 13 methods listed. Almost all (97%) participants reported at least one method was not an acceptable option, with a mean of 5.6 (SD 2.7) of the 13 listed methods. Conclusions: The majority of family planning specialists have experienced contraceptive risk events during times of active pregnancy prevention since their medical training. Contraceptive method change is common and most respondents were limited in the number of methods that were personally acceptable to them. Dialogue idealizing the role of contraception in minimizing or eliminating abortion need is simplistic and inaccurately represents the lived realities of pregnancy-capable individuals and their partners, including among those with exceptional contraceptive literacy and access.

Awareness and Support of Responsive Bottle Feeding Among WIC Counselors and Caregivers: A Formative Qualitative Study.

OBJECTIVE: To understand the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) counselor experiences discussing responsive bottle feeding during counseling and WIC participants' knowledge, understanding, and use of responsive bottle feeding. METHODS: Qualitative descriptive, semistructured interviews with 23 participants (8 WIC counselors and 15 WIC participants) were conducted online via Zoom. The WIC counselors and mothers of WIC-enrolled bottle-fed infants were recruited through a network of WIC clinics in North Carolina. Interviews were recorded, transcribed, and collaboratively analyzed using content analysis. RESULTS: The WIC participants received responsive infant feeding support from WIC counselors but often in the context of breastfeeding. WIC counselors provided valuable support for families but were challenged by limited training on responsive bottle feeding, balancing promoting breastfeeding with supporting mothers' feeding decisions, and time constraints. CONCLUSIONS AND IMPLICATIONS: Findings provide preliminary support for the need to develop and pilot an intervention focused on promoting responsive feeding for parents of bottle-fed infants.

Higher interleukin-6 is associated with greater momentary social connection in close relationships in daily life.

Recent evidence has documented associations between higher levels of inflammation and social approach behaviors toward close others in laboratory-based tasks. Yet it is unknown if this translates to interactions with close others in daily life. Given that momentary experiences of social connection have both relational and health consequences, this is a critical gap in our knowledge. To address the association between inflammation and momentary social connection experiences in close relationships, 55 participants provided blood samples on two consecutive days, which were assayed for circulating levels of the inflammatory marker interleukin-6 (IL-6). After providing the first blood sample, participants received the annual influenza vaccine as a mild inflammatory challenge. Participants also reported on cognitive, affective, and behavioral indicators of social connection with a specific close other multiple times across the two study days. Results indicated that levels of IL-6 were positively associated with temporally-proximal indicators of momentary social connection with a close other. Specifically, higher levels of IL-6 were associated with greater feelings of comfort from the close other, greater desire to be near them, and higher reported relationship quality. Greater IL-6 reactivity to the vaccine was only associated with increased reported relationship quality. These data add to the existing literature suggesting that higher levels of IL-6 may motivate social approach toward a close other, extending evidence to now include momentary social connection experiences in daily life.

Positive emotions co-experienced with strangers and acquaintances predict COVID-19 vaccination intentions through prosocial tendencies.

BACKGROUND: The efficacy of vaccination depends on its widespread adoption, making vaccine uptake not just a personal health behavior but also a prosocial one. Previous research has shown that everyday moments of co-experienced positive emotions (positivity resonance) are associated with higher prosocial tendencies, and these moments, in turn, prospectively predict people's pandemic hygiene behaviors. Yet, limited research has explored how moments of positivity resonance may have predicted greater COVID-19 vaccine intentions during the early months of the pandemic. METHODS: We longitudinally surveyed a national U.S. sample across four weeks during the fall of 2020. We tested the hypothesis that positivity resonance with strangers and acquaintances indirectly predicts COVID-19 vaccine intentions, as statistically mediated by prosocial tendencies. We also aimed to replicate the indirect effects of positivity resonance on hygiene behaviors (such as mask wearing and hand washing), effects that have been demonstrated in previous research. RESULTS: In a pre-registered structural equation model, we found that perceived positivity resonance experienced with strangers and acquaintances prospectively predicted prosocial tendencies, which in turn amplified people's COVID-19 vaccine intentions (ß = 0.053) and hygiene behaviors - i.e., social distancing (ß = 0.032), mask wearing (ß = 0.027), hand washing (ß = 0.049). CONCLUSIONS: Understanding the effects of high-quality social interactions with strangers and acquaintances on vaccine intentions and hygiene behaviors is critical, particularly given the likelihood of emerging pandemics and novel vaccines. We discuss theoretical and practical implications related to perceived positivity resonance, prosocial tendencies, and vaccination uptake for novel vaccines.

COVID-19 Vaccine Hesitancy in the Perinatal Period: A Survey Among Residents of Hawaii.

Introduction: This study describes the vaccination status among people in Hawaii who are attempting pregnancy, currently pregnant, recently delivered (<6 months), and/or breastfeeding and documents common concerns and information sources associated with vaccine decision making. Methods: We conducted a cross-sectional online survey between April and September 2022 throughout Hawaii. The anonymous surveys were disseminated through flyers and online links posted by physician offices and community partners throughout Hawaii. Results: Final analyses included 165 responses. Almost half of the respondents (n=75, 45%) were unvaccinated, 38% (n=62) were fully vaccinated, and 17% (n=28) were partially vaccinated. The most influential sources for vaccine decision making for vaccinated respondents were their healthcare providers (n=28, 45%) and official healthcare organizations (n=22, 36%), whereas unvaccinated respondents reported friends/family (n=28, 37%) and their healthcare providers (n=26, 35%) as their most influential sources. Top COVID-19 vaccine concerns for unvaccinated individuals were reactions to vaccine (n=78, 76%) and concerns for safety of the vaccine (n=75, 73%). Conclusions: Efforts should be made to increase and expand vaccine education about the benefits and safety of vaccines during pregnancy beyond the pregnant person to create more supportive social norms for COVID-19 vaccination in the perinatal period. Consistent and unequivocal support across medical specialties, including obstetrics, pediatrics, and family medicine, is also crucial for encouraging the uptake of the vaccine during pregnancy or when breastfeeding.

Functional genomics in inborn errors of immunity.

Inborn errors of immunity (IEI) comprise a diverse spectrum of 485 disorders as recognized by the International Union of Immunological Societies Committee on Inborn Error of Immunity in 2022. While IEI are monogenic by definition, they illuminate various pathways involved in the pathogenesis of polygenic immune dysregulation as in autoimmune or autoinflammatory syndromes, or in more common infectious diseases that may not have a significant genetic basis. Rapid improvement in genomic technologies has been the main driver of the accelerated rate of discovery of IEI and has led to the development of innovative treatment strategies. In this review, we will explore various facets of IEI, delving into the distinctions between PIDD and PIRD. We will examine how Mendelian inheritance patterns contribute to these disorders and discuss advancements in functional genomics that aid in characterizing new IEI. Additionally, we will explore how emerging genomic tools help to characterize new IEI as well as how they are paving the way for innovative treatment approaches for managing and potentially curing these complex immune conditions.

Predicting Phase Stability at Interfaces.

We present the RAFFLE methodology for structural prediction of the interface between two materials and demonstrate its effectiveness by applying it to MgO encapsulated by two layers of graphene. To address the challenge of interface structure prediction, our methodology combines physical insights derived from morphological features observed in related systems with an iterative machine learning technique. This employs physical-based methods, including void-filling and n-body distribution functions to predict interface structures. For the carbon-MgO encapsulated system, we have shown the rocksalt and hexagonal phases of MgO to be the two most energetically stable in the few-layer regime. We demonstrate that monolayer rocksalt is heavily stabilized by interfacing with graphene, becoming more energetically favorable than the graphenelike monolayer hexagonal MgO. The RAFFLE methodology provides valuable insights into interface behavior, and a route to finding new materials at interfaces.

Point mutation in a virus-like capsid drives symmetry reduction to form tetrahedral cages.

Protein capsids are a widespread form of compartmentalisation in nature. Icosahedral symmetry is ubiquitous in capsids derived from spherical viruses, as this geometry maximises the internal volume that can be enclosed within. Despite the strong preference for icosahedral symmetry, we show that simple point mutations in a virus-like capsid can drive the assembly of novel symmetry-reduced structures. Starting with the encapsulin from Myxococcus xanthus, a 180-mer bacterial capsid that adopts the well-studied viral HK97 fold, we use mass photometry and native charge detection mass spectrometry to identify a triple histidine point mutant that forms smaller dimorphic assemblies. Using cryo-EM, we determine the structures of a precedented 60-mer icosahedral assembly and an unprecedented 36-mer tetrahedron that features significant geometric rearrangements around a novel interaction surface between capsid protomers. We subsequently find that the tetrahedral assembly can be generated by triple point mutation to various amino acids, and that even a single histidine point mutation is sufficient to form tetrahedra. These findings represent the first example of tetrahedral geometry across all characterised encapsulins, HK97-like capsids, or indeed any virus-derived capsids reported in the Protein Data Bank, revealing the surprising plasticity of capsid self-assembly that can be accessed through minimal changes in protein sequence.

Understanding the role of antibiotic-associated adverse events in influencing antibiotic decision-making.

Objective: To (1) understand the role of antibiotic-associated adverse events (ABX-AEs) on antibiotic decision-making, (2) understand clinician preferences for ABX-AE feedback, and (3) identify ABX-AEs of greatest clinical concern. Design: Focus groups. Setting: Academic medical center. Participants: Medical and surgical house staff, attending physicians, and advanced practice practitioners. Methods: Focus groups were conducted from May 2022 to December 2022. Participants discussed the role of ABX-AEs in antibiotic decision-making and feedback preferences and evaluated the prespecified categorization of ABX-AEs based on degree of clinical concern. Thematic analysis was conducted using inductive coding. Results: Four focus groups were conducted (n = 15). Six themes were identified. (1) ABX-AE risks during initial prescribing influence the antibiotic prescribed rather than the decision of whether to prescribe. (2) The occurrence of an ABX-AE leads to reassessment of the clinical indication for antibiotic therapy. (3) The impact of an ABX-AE on other management decisions is as important as the direct harm of the ABX-AE. (4) ABX-AEs may be overlooked because of limited feedback regarding the occurrence of ABX-AEs. (5) Clinicians are receptive to feedback regarding ABX-AEs but are concerned about it being punitive. (6) Feedback must be curated to prevent clinicians from being overwhelmed with data. Clinicians generally agreed with the prespecified categorizations of ABX-AEs by degree of clinical concern. Conclusions: The themes identified and assessment of ABX-AEs of greatest clinical concern may inform antibiotic stewardship initiatives that incorporate reporting of ABX-AEs as a strategy to reduce unnecessary antibiotic use.

Valence and Intensity of Emotional Expression in Autistic and Non-Autistic Toddlers.

PURPOSE: Differences in emotional experience and expression have long been recognized as common in the presentation of autism, yet research examining emotional expression in early childhood is limited, with mixed findings. Understanding emotional reactivity and expression in autism in early life is an essential step towards uncovering the mechanisms of these risks and identifying targets for intervention. METHODS: The present study examined emotional expression in autistic (N = 17) and non-autistic (N = 20) toddlers (mean age = 25.27; SD = 1.88) during emotion elicitation tasks aimed at eliciting joy, frustration, and unease. Video recorded tasks were coded in ten second intervals for emotional valence and intensity, and the following variables were computed: proportion of time in positive, neutral, and negative affect; maximum intensity of positive and negative affect; and range of affect (i.e., most negative to most positive intensity). RESULTS: Autistic toddlers spent more time in neutral facial expressions, less time displaying positive affect, and had somewhat less intense positive emotional expression than non-autistic peers. Small differences were apparent in intensity of negative affect expression, while no differences emerged in duration of time spent in negative affect. CONCLUSION: Findings emphasize that differences may be more apparent in duration, rather than intensity of emotional expression, and that it may be particularly important to examine periods of "neutral" affect in young autistic children. Future research should consider the best ways to understand emotional reactivity in this population considering their unique interests, challenges, and communication styles.