Young Adult Cancer Survivors' Perspectives on Cancer's Impact on Different Life Areas Post-Treatment: A Qualitative Study.

Purpose: Young adult cancer survivors experience disruptions in various life domains (e.g., relationships, academic/career) during and after treatment. This study examined life disruptions and related supports to update interventions to improve psychological outcomes. Methods: In April-July 2023, young adult survivors (n = 23) were recruited (via clinics, support groups, nonprofit organizations, etc.) to complete semi-structured interviews assessing cancer's impact across life domains, how they coped with related disruptions, and facilitators to improved psychosocial well-being. We used a dual deductive-inductive approach to develop a codebook and then coded transcripts in Dedoose. Results: This sample was on average 33.7 years old (standard deviation [SD] = 4.4), 78.3% female, 73.9% non-Hispanic White, 47.8% married/cohabitating, 2.4 (SD = 1.0) years post-diagnosis, 1.4 years (SD = 0.9) post-treatment, and largely diagnosed with breast cancer (52.1%) or leukemia/lymphoma (34.7%). The most salient themes related to disruptions included mental health, feelings of isolation during survivorship, and disruptions to career and relationships with family or partners. Participants reported challenges navigating these feelings and disruptions, and difficulty understanding and conveying their needs. Many experienced limited support for navigating cancer-related trauma and life disruptions as a survivor. Participants also reported some positive impacts, like reevaluating their values and goals or feeling resilient, and emphasized the need to identify supports, accept that life had changed because of cancer, and have their needs and continued struggles validated by others during survivorship. Conclusions: Young adults experience ongoing disruptions across multiple life domains, underscoring the need for integrated, longer-term psychosocial supports to help them navigate these disruptions and reevaluate their goals.

A protocol to determine the acceptability and feasibility of a pilot intervention emergency department virtual observation unit fall prevention program.

BACKGROUND: As a third of all community dwellers aged 65+ fall each year, falls are common reasons for older adults to present to an Emergency Department (ED). Although EDs should assess patients' multifactorial fall risks to prevent future fall-related injuries, this frequently does not occur. We describe our protocol to determine the feasibility, acceptability, and safety of a pilot ED Virtual Observation Unit (VOU) Falls program. METHODS: To ensure standardized conduct and reporting, the Standard Protocol Items for Intervention Trials (SPIRIT) guidelines will be used. The VOU is a program where patients are sent home from the ED but are part of a virtual observation unit in that they can call on-call ED physicians while they are being treated for conditions such as cellulitis, congestive heart failure, or pneumonia. A paramedic conducts daily visits with the patient and facilitates a telemedicine consult with an ED physician. VOU nursing staff conduct daily assessments of patients via telemedicine. The ED VOU Falls program is one of the VOU pathways and is a multi-component fall prevention program for fall patients who present after an ED visit. The paramedic conducts a home safety evaluation, a Timed Up and Go Test (TUG). During the VOU visit, the ED physician conducts a telemedicine visit, while the paramedic is visiting the home, to review patients' fall-risk-increasing drugs and their TUG test. We will determine feasibility by calculating rates of patient enrollment refusal, and adherence to fall-risk prevention recommendations using information from 3-month follow-up telephone calls, as well as qualitative interviews with the paramedics. We will determine the acceptability of the ED VOU Falls program based on patient and provider surveys using a Likert scale. We will ask VOU nursing staff to report any safety issues encountered while the patient is in the ED VOU Falls program (e.g., tripping hazards). We will use the chi-square test or Fisher's exact test for categorical variables, Student's t-test for continuous variables, and Mann-Whitney for nonparametric data. We will review interview transcripts and generate codes. Codes will then be extracted and organized into concepts to generate an overall theme following grounded theory methods. This is a pilot study; hence, results cannot be extrapolated. However, a definite trial would be the next step in the future to determine if such a program could be implemented as part of fall prevention interventions. DISCUSSION: This study will provide insights into the feasibility and acceptability of a novel ED VOU Falls program with the aim of ultimately decreasing falls. In the future, such a program could be implemented as part of fall prevention interventions.

Patient Perceptions of Emergency Department Observation Care at Home.

Introduction: The Virtual Observation Unit (VOU) utilizes telehealth and community paramedicine to provide observation-level care in patients' homes. Patients' experience of this novel program has not been reported. Methods: A phone-based patient experience survey was administered to the patients who were admitted to the VOU at an urban, academic Emergency Department in the Northeast United States. The survey asked about patient's perception of the program's quality of care (0 = worst care possible, 10 = best care possible). t Tests with a Bonferroni adjustment assessed for differences between patient demographic groups. Results: The survey response rate was 40% (124/307). Overall mean scores for perceived quality of care were very high (9.51 ± 1.19). There were no significant differences in patient's perception of quality of care between demographic cohorts of age, gender, race, or ethnicity. Conclusions: Patient experience with a novel VOU program was very positive and did not differ significantly by demographic cohort. Further research is warranted.

Hox gene-specific cellular targeting using split intein Trojan exons.

The Trojan exon method, which makes use of intronically inserted T2A-Gal4 cassettes, has been widely used in Drosophila to create thousands of gene-specific Gal4 driver lines. These dual-purpose lines provide genetic access to specific cell types based on their expression of a native gene while simultaneously mutating one allele of the gene to enable loss-of-function analysis in homozygous animals. While this dual use is often an advantage, the truncation mutations produced by Trojan exons are sometimes deleterious in heterozygotes, perhaps by creating translation products with dominant negative effects. Such mutagenic effects can cause developmental lethality as has been observed with genes encoding essential transcription factors. Given the importance of transcription factors in specifying cell type, alternative techniques for generating specific Gal4 lines that target them are required. Here, we introduce a modified Trojan exon method that retains the targeting fidelity and plug-and-play modularity of the original method but mitigates its mutagenic effects by exploiting the self-splicing capabilities of split inteins. "Split Intein Trojan exons" (siTrojans) ensure that the two truncation products generated from the interrupted allele of the native gene are trans-spliced to create a full-length native protein. We demonstrate the efficacy of siTrojans by generating a comprehensive toolkit of Gal4 and Split Gal4 lines for the segmentally expressed Hox transcription factors and illustrate their use in neural circuit mapping by targeting neurons according to their position along the anterior-posterior axis. Both the method and the Hox gene-specific toolkit introduced here should be broadly useful.

The impact of COVID-19 on school nursing: A qualitative survey of stressors faced by school nurses.

BACKGROUND: As students returned to school, school nurses were responsible for infection control, communication, and the preparation of supplies and facilities. School nurses in the Pacific Northwest US demonstrated a higher prevalence of mental health symptoms in the years since the pandemic began, suggesting that their experience may have been unique. OBJECTIVE: This study aimed to explore the stressors of school nurses in the Pacific Northwest at two time points. DESIGN: This study is a qualitative, descriptive analysis of anonymous survey responses collected in June of 2021 (n = 333) and between October and December 2021 (n = 284). SAMPLE: Self-identifying school nurses working in K-12 schools in Washington State were invited to participate. MEASUREMENTS: Participants completed open-ended survey questions designed to elicit their experiences during the pandemic. RESULTS: Four themes emerged from the data: (1) isolation from administration and the school community, (2) COVID-19-related workload, (3) disorganized and inconsistent communication, and (4) concern for students, themselves, and others. CONCLUSIONS: School nurses played a vital public health role during the pandemic. However, their effectiveness may not have been fully utilized and sometimes undermined. Lastly, our findings highlight the difficulties encountered in implementing the changing scientific and public health guidance during the pandemic.

The Value of an Emergency Medicine Virtual Observation Unit.

STUDY OBJECTIVE: We implemented a virtual observation unit in which emergency department (ED) patients receive observation-level care at home. Our primary aim was to compare this new care model to in-person observation care in terms of brick-and-mortar ED length of stay (inclusive of ED observation unit time) as well as secondarily on inpatient admission and 72-hour return visits (overall and with admission). METHODS: In a retrospective analysis of electronic health record data on ED observation patients from January 1, 2022 to December 29, 2022 from an academic urban ED, we used propensity matching to compare virtual to in-person observation patients on outcomes of interest. Patients were matched 1:1 based on age, sex, Charlson Comorbidity Index, and reason for observation. We also conducted real-time review of all virtual observation cases for potential safety concerns. RESULTS: Of 8,218 observation stays, 361 virtual observation patients were matched with 361 in-person observation patients. Virtual observation patients experienced lower median brick-and-mortar ED + EDOU LOS [14.6 (IQR 10.2, 18.9) versus 33.3 (IQR 28.1, 38.1) hours] and lower inpatient admission rates (10.2% [SD 5.0] versus 24.7% [SD 11.3]). The 72-hour return rate was higher for virtual observation patients (3.6% [SD 3.0] versus 2.5% [SD 3.0]). Among those with return visits, the rate of inpatient admission was higher among virtual observation patients (53.8% [SD 3.2] versus 11.1% [13.0]). There were no significant patient safety events recorded. CONCLUSION: Virtual observation unit patients used fewer hours in ED and ED observation relative to on-site observation patients. This new care delivery model warrants further study because it has the potential to positively impact ED capacity.

Institutional Variability in Respiratory Support Use for Pediatric Critical Asthma: A Multicenter Retrospective Study.

Rationale: Over 20,000 children are hospitalized in the United States for asthma every year. Although initial treatment guidelines are well established, there is a lack of high-quality evidence regarding the optimal respiratory support devices for these patients.Objectives: The objective of this study was to evaluate institutional and temporal variability in the use of respiratory support modalities for pediatric critical asthma.Methods: We conducted a retrospective cohort study using data from the Virtual Pediatrics Systems database. Our study population included children older than 2 years old admitted to a VPS contributing pediatric intensive care unit from January 2012 to December 2021 with a primary diagnosis of asthma or status asthmaticus. We evaluated the percentage of encounters using a high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive bilevel positive pressure ventilation (NIV), and invasive mechanical ventilation (IMV) for all institutions, then divided institutions into quintiles based on the volume of patients. We created logistic regression models to determine the influence of institutional volume and year of admission on respiratory support modality use. We also conducted time-series analyses using Kendall's tau.Results: Our population included 77,115 patient encounters from 163 separate institutions. Institutional use of respiratory modalities had significant variation in HFNC (28.3%, interquartile range [IQR], 11.0-49.0%; P < 0.01), CPAP (1.4%; IQR, 0.3-4.3%; P < 0.01), NIV (8.6%; IQR, 3.5-16.1%; P < 0.01), and IMV (5.1%; IQR, 3.1-8.2%; P < 0.01). Increased institutional patient volume was associated with significantly increased use of NIV (odds ratio [OR], 1.33; 1.29-1.36; P < 0.01) and CPAP (OR, 1.20; 1.15-1.25; P < 0.01), and significantly decreased use of HFNC (OR, 0.80; 0.79-0.81; P < 0.01) and IMV (OR, 0.82; 0.79-0.86; P < 0.01). Time was also associated with a significant increase in the use of HFNC (11.0-52.3%; P < 0.01), CPAP (1.6-5.4%; P < 0.01), and NIV (3.7-21.2%; P < 0.01), whereas there was no significant change in IMV use (6.1-4.0%; P = 0.11).Conclusions: Higher-volume centers are using noninvasive positive pressure ventilation more frequently for pediatric critical asthma and lower frequencies of HFNC and IMV. Treatment with HFNC, CPAP, and NIV for this population is increasing in the last decade.

Wide Institutional Variability in the Treatment of Pediatric Critical Asthma: A Multicenter Retrospective Study.

OBJECTIVES: Children with status asthmaticus refractory to first-line therapies of systemic corticosteroids and inhaled beta-agonists often receive additional treatments. Because there are no national guidelines on the use of asthma therapies in the PICU, we sought to evaluate institutional variability in the use of adjunctive asthma treatments and associations with length of stay (LOS) and PICU use. DESIGN: Multicenter retrospective cohort study. SETTING: Administrative data from the Pediatric Health Information Systems (PHIS) database. PATIENTS: All inpatients 2-18 years old were admitted to a PHIS hospital between 2013 and 2021 with a diagnostic code for asthma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study included 213,506 inpatient encounters for asthma, of which 29,026 patient encounters included care in a PICU from 39 institutions. Among these PICU encounters, large variability was seen across institutions in both the number of adjunctive asthma therapies used per encounter (min: 0.6, median: 1.7, max: 2.5, p < 0.01) and types of adjunctive asthma therapies (aminophylline, ipratropium, magnesium, epinephrine, and terbutaline) used. The center-level median hospital LOS ranged from 1 (interquartile range [IQR]: 1, 3) to 4 (3, 6) days. Among all the 213,506 inpatient encounters for asthma, the range of asthma admissions that resulted in PICU admission varied between centers from 5.2% to 47.3%. The average number of adjunctive therapies used per institution was not significantly associated with hospital LOS ( p = 0.81) nor the percentage of encounters with PICU admission ( p = 0.47). CONCLUSIONS: Use of adjunctive therapies for status asthmaticus varies widely among large children's hospitals and was not associated with hospital LOS or the percentage of encounters with PICU admission. Wide variance presents an opportunity for standardizing care with evidence-based guidelines to optimize outcomes and decrease adverse treatment effects and hospital costs.

An Electronic Medical Record Intervention to Increase Pharmacologic Prophylaxis for Venous Thromboembolism in Emergency Department Observation Patients.

STUDY OBJECTIVE: The role of venous thromboembolism (VTE) prophylaxis among patients receiving emergency department (ED) observation unit care is unclear. We investigated an electronic health record-based clinical decision support tool aimed at increasing pharmacologic VTE prophylaxis use among at-risk patients placed in ED observation units. METHODS: We conducted an interrupted time-series study of an Epic-based best practice advisory implemented in May 2019 at a health care system comprising 2 academic medical centers and 4 community hospitals with dedicated ED observation units. The best practice advisory alerted staff at 24 hours to conduct a risk assessment and linked to a VTE prophylaxis order set. We used an interrupted time series, Bayesian structured time series, and a multivariable mixed-effect regression model to estimate the intervention effect. RESULTS: Prior to the best practice advisory implementation, there were 8,895 ED observation unit patients with a length of stay more than or equal to 24 hours, and 0.9% received pharmacologic VTE prophylaxis. Afterward, there were 12,664 ED observation unit patients with a length of stay more than or equal to 24 hours, and 4.8% received pharmacologic VTE prophylaxis. The interrupted time series and causal impact analysis showed a statistically significant increase in VTE prophylaxis (eg, absolute percent difference 3.8%, 95% confidence interval 3.5 to 4.1). In a multivariable model, only the intervention was significantly associated with receiving VTE prophylaxis (odds ratio 4.56, 95% confidence interval 2.22 to 9.37). CONCLUSION: An electronic health record-based alert helped to prompt staff caring for ED observation unit patients at risk for VTE with prolonged visits to order recommended pharmacologic prophylaxis. The best risk assessment model to use and the true incidence of VTE events in this population are unclear.

Chromatin priming elements direct tissue-specific gene activity before hematopoietic specification.

Tissue-specific gene regulation during development involves the interplay between transcription factors and epigenetic regulators binding to enhancer and promoter elements. The pattern of active enhancers defines the cellular differentiation state. However, developmental gene activation involves a previous step called chromatin priming which is not fully understood. We recently developed a genome-wide functional assay that allowed us to functionally identify enhancer elements integrated in chromatin regulating five stages spanning the in vitro differentiation of embryonic stem cells to blood. We also measured global chromatin accessibility, histone modifications, and transcription factor binding. The integration of these data identified and characterised cis-regulatory elements which become activated before the onset of gene expression, some of which are primed in a signalling-dependent fashion. Deletion of such a priming element leads to a delay in the up-regulation of its associated gene in development. Our work uncovers the details of a complex network of regulatory interactions with the dynamics of early chromatin opening being at the heart of dynamic tissue-specific gene expression control.

Transcriptional reprogramming by mutated IRF4 in lymphoma.

Disease-causing mutations in genes encoding transcription factors (TFs) can affect TF interactions with their cognate DNA-binding motifs. Whether and how TF mutations impact upon the binding to TF composite elements (CE) and the interaction with other TFs is unclear. Here, we report a distinct mechanism of TF alteration in human lymphomas with perturbed B cell identity, in particular classic Hodgkin lymphoma. It is caused by a recurrent somatic missense mutation c.295 T > C (p.Cys99Arg; p.C99R) targeting the center of the DNA-binding domain of Interferon Regulatory Factor 4 (IRF4), a key TF in immune cells. IRF4-C99R fundamentally alters IRF4 DNA-binding, with loss-of-binding to canonical IRF motifs and neomorphic gain-of-binding to canonical and non-canonical IRF CEs. IRF4-C99R thoroughly modifies IRF4 function by blocking IRF4-dependent plasma cell induction, and up-regulates disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single mutation causes a complex switch of TF specificity and gene regulation and open the perspective to specifically block the neomorphic DNA-binding activities of a mutant TF.

The Resilience of Pediatric Nurses in Context: A Mixed Methods Study.

BACKGROUND: Resilience, an individual's ability to cope with and recover from stressors, is supported by contextually specific factors. Factors in the work environment may support or hinder nurses' resilience to the specific stressors present in pediatric nursing, an understudied population. OBJECTIVE: We aimed to explore the contextual factors in the work environment of pediatric nurses with varying levels of resilience, including social support, the work environment, and opportunities for coping from an individual approach. METHODS: This study is a secondary mixed-methods analysis using ordinal logistic regression and a meta-matrix of survey responses and semi-structured interview transcripts from 30 pediatric nurses. RESULTS: 5 themes, 3 supporting and 2 hindering resilience, emerged from the interviews. Nurses described their resilience as supported by sharing the burden, support from administration, and taking a break. Participants described resilience as hindered when they found it challenging to provide quality nursing care and when they felt unappreciated or undervalued. No theme significantly changed the odds of having higher resilience. CONCLUSIONS: Our findings suggest that nurses recognize resources and conditions within their work environment as influencing their resilience. However, workplace resources and conditions are only one contributor to pediatric nurse resilience. Encouraging breaks and informal opportunities for nurses to support each other may support resilience in pediatric nurses. In addition, nursing leaders can support pediatric nurse resilience by regularly spending time connecting with nurses. Finally, health care organizations should consider how changes in the work environment may hinder nurse resilience by adding stress or changing access to supportive factors.

Factors Associated with the Digital Patient Experience of Virtual Care Across Specialties.

Background: We aimed to characterize patient experience with virtual care across medical specialties using validated survey data. Primary objective: to determine whether experience varied by visit modality (virtual vs. in-person) and whether relationships persisted after adjusting for patient and provider characteristics. Secondarily, among physicians with sufficient data, we compared virtual versus in-person patient experience scores at the physician level and identified characteristics associated with better experience scores for virtual care. Methods: This was a retrospective analysis of administrative databases from a large New England health care system, including all ambulatory visits from October 1, 2020 to September 30, 2021 with patient experience scores recorded. We compared experience between virtual and in-person at the visit level (score: 0-10) and the physician level for likelihood of recommending the physician to friends or family. We used a series of cross-classified hierarchical models with visits grouped by patient and by physician to decompose sources of variation. Among physicians with sufficient data, we compared physicians with higher virtual versus higher in-person net promoter score (NPS). Results: Of 378,472 visits performed by 3368 physicians, 86,878 (23%) were conducted virtually. Most scored ≥9 for either modality, with a small preference for virtual versus in-person care (9.6 vs. 9.5, p < 0.001). We found that more variation in scores was explained by patient than by physician (22.9% vs. 3%). Visit modality was of minimal explanatory value. Most physicians' virtual and in-person NPS were similar, and virtual visit volume was not associated. Conclusions: We found robust evidence for the parity of patient experience between virtual and in-person modalities across specialties.

Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak.

Importance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, Setting, and Participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure: Respiratory syncytial virus. Main Outcomes and Measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and Relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

The impact of multiple-behavior HIV interventions as a function of regional disadvantages: An analysis of syndemics.

OBJECTIVE: Disadvantaged populations, including inhabitants of developing countries as well as racial/ethnic and sexual minorities in the United States, are disproportionally burdened by human immunodeficiency virus (HIV) infection, delayed HIV diagnosis, and unfavorable HIV-treatment outcomes. HIV interventions targeting single behaviors (e.g., testing) in these populations have shown to be efficacious at producing behavioral and clinical change but have been unable to eliminate the social health disparities associated with syndemics (i.e., a set of connected risks, interacting synergistically, and contributing to excess burden of disease in a population). METHOD: This meta-analysis of 331 reports (clusters; number of effect sizes [k] = 1,364) assessed whether multiple-behavior interventions that target clusters of syndemic risks are more efficacious for those in disadvantaged regions and social groups. RESULTS: Across the board, multiple-behavior interventions were more efficacious than single-behavior ones as well as passive control groups among samples from countries with lower log gross domestic product (GDP), lower Human Development Index (HDI), and lower Healthcare Access and Quality (HAQ) Index. CONCLUSIONS: Within the United States, the efficacy of multiple-behavior interventions was similar across different levels of representation of racial/ethnic and sexual minorities. The analyses used robust variance estimation with small-sample corrections to assess the differential effects of multiple-behavior interventions and Egger Sandwich test with the multilevel meta-analysis approach to detect selection biases. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of serotonin inhibition within the treatment of carcinoid syndrome.

Carcinoid syndrome is the most frequent hormonal complication associated with neuroendocrine neoplasms. It was first reported in 1954, and the classical symptoms are diarrhoea, flushing and abdominal pain. It is caused by the secretion of several vasoactive substances, the most prominent being serotonin, which play a pathophysiological role in the clinical symptoms which characterise carcinoid syndrome. Therefore, the focus of carcinoid syndrome treatment is to reduce serotonin production and hence improve the patient's quality of life. There are a variety of management options for carcinoid syndrome including medical, surgical and loco-regional interventional radiological procedures. The most widely used are somatostatin analogues with three clinically approved drugs: lanreotide and octreotide (first-generation) and pasireotide (second-generation). Both everolimus and interferon used in combination with octreotide have shown significant reduction in urinary 5-hydroxyindoleacetic acid compared to octreotide alone. Telotristat ethyl has been increasingly utilised for patients with symptoms despite taking somatostatin analogues. It has also been shown to have a significant improvement in bowel movement frequency which was associated with a significant improvement in quality of life. Peptide receptor radionuclide therapy has proven symptomatic improvement in patients with uncontrolled symptoms. Chemotherapy is primarily reserved for patients with high proliferation tumours, with limited research on the efficacy in reducing symptoms. Surgical resection remains the optimal treatment due to being the only one that can achieve a cure. Liver-directed therapies are considered in patients where curative resection is not possible. There are therefore numerous different therapies. This paper describes the pathophysiology and therapy of carcinoid syndrome.

split-intein Gal4 provides intersectional genetic labeling that is repressible by Gal80.

The split-Gal4 system allows for intersectional genetic labeling of highly specific cell types and tissues in Drosophila. However, the existing split-Gal4 system, unlike the standard Gal4 system, cannot be repressed by Gal80, and therefore cannot be controlled temporally. This lack of temporal control precludes split-Gal4 experiments in which a genetic manipulation must be restricted to specific timepoints. Here, we describe a split-Gal4 system based on a self-excising split-intein, which drives transgene expression as strongly as the current split-Gal4 system and Gal4 reagents, yet which is repressible by Gal80. We demonstrate the potent inducibility of "split-intein Gal4" in vivo using both fluorescent reporters and via reversible tumor induction in the gut. Further, we show that our split-intein Gal4 can be extended to the drug-inducible GeneSwitch system, providing an independent method for intersectional labeling with inducible control. We also show that the split-intein Gal4 system can be used to generate highly cell type-specific genetic drivers based on in silico predictions generated by single-cell RNAseq (scRNAseq) datasets, and we describe an algorithm ("Two Against Background" or TAB) to predict cluster-specific gene pairs across multiple tissue-specific scRNA datasets. We provide a plasmid toolkit to efficiently create split-intein Gal4 drivers based on either CRISPR knock-ins to target genes or using enhancer fragments. Altogether, the split-intein Gal4 system allows for the creation of highly specific intersectional genetic drivers that are inducible/repressible.

Can tablet video-based telehealth assessment of the abdomen safely determine the need for abdominal imaging? A pilot study.

Objective: There is limited evidence on the reliability of video-based physical examinations. We aimed to evaluate the safety of a remote physician-directed abdominal examination using tablet-based video. Methods: This was a prospective observational pilot study of patients >19 years old presenting with abdominal pain to an academic emergency department July 9, 2021-December 21, 2021. In addition to usual care, patients had a tablet video-based telehealth history and examination by an emergency physician who was otherwise not involved in the visit. Both telehealth and in-person clinicians were asked about the patient's need for abdominal imaging (yes/no). Thirty-day chart review searched for subsequent ED visits, hospitalizations, and procedures. Our primary outcome was agreement between telehealth and in-person clinicians on imaging need. Our secondary outcome was potentially missed imaging by the telehealth physicians leading to morbidity or mortality. We used descriptive and bivariate analyses to examine characteristics associated with disagreement on imaging needs. Results: Fifty-six patients were enrolled; the median age was 43 years (interquartile range: 27-59), 31 (55%) were female. The telehealth and in-person clinicians agreed on the need for imaging in 42 (75%) of the patients (95% confidence interval [CI]: 62%-86%), with moderate agreement with Cohen's kappa ((k = 0.41, 95% CI: 0.15-0.67). For study patients who had a procedure within 24 hours of ED arrival (n = 3, 5.4%, 95% CI: 1.1%-14.9%) or within 30 days (n = 7, 12.5%, 95% CI: 5.2%-24.1%), neither telehealth physicians nor in-person clinicians missed timely imaging. Conclusion: In this pilot study, telehealth physicians and in-person clinicians agreed on the need for imaging for the majority of patients with abdominal pain. Importantly, telehealth physicians did not miss the identification of imaging needs for patients requiring urgent or emergent surgery.

Gradient nanostructured steel with superior tensile plasticity.

Nanostructured metallic materials with abundant high-angle grain boundaries exhibit high strength and good radiation resistance. While the nanoscale grains induce high strength, they also degrade tensile ductility. We show that a gradient nanostructured ferritic steel exhibits simultaneous improvement in yield strength by 36% and uniform elongation by 50% compared to the homogenously structured counterpart. In situ tension studies coupled with electron backscattered diffraction analyses reveal intricate coordinated deformation mechanisms in the gradient structures. The outermost nanolaminate grains sustain a substantial plastic strain via a profound deformation mechanism involving prominent grain reorientation. This synergistic plastic co-deformation process alters the rupture mode in the post-necking regime, thus delaying the onset of fracture. The present discovery highlights the intrinsic plasticity of nanolaminate grains and their significance in simultaneous improvement of strength and tensile ductility of structural metallic materials.