Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

BACKGROUND: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. METHODS: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. RESULTS: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). CONCLUSION: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.

The microbiota and T cells non-genetically modulate inherited phenotypes transgenerationally.

The host-microbiota relationship has evolved to shape mammalian physiology, including immunity, metabolism, and development. Germ-free models are widely used to study microbial effects on host processes such as immunity. Here, we find that both germ-free and T cell-deficient mice exhibit a robust sebum secretion defect persisting across multiple generations despite microbial colonization and T cell repletion. These phenotypes are inherited by progeny conceived during in vitro fertilization using germ-free sperm and eggs, demonstrating that non-genetic information in the gametes is required for microbial-dependent phenotypic transmission. Accordingly, gene expression in early embryos derived from gametes from germ-free or T cell-deficient mice is strikingly and similarly altered. Our findings demonstrate that microbial- and immune-dependent regulation of non-genetic information in the gametes can transmit inherited phenotypes transgenerationally in mice. This mechanism could rapidly generate phenotypic diversity to enhance host adaptation to environmental perturbations.

Altered COVID-19 immunity in children with asthma by atopic status.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a spectrum of clinical outcomes that may be complicated by severe asthma. Antiviral immunity is often compromised in patients with asthma; however, whether this is true for SARS-CoV-2 immunity and children is unknown. Objective: We aimed to evaluate SARS-CoV-2 immunity in children with asthma on the basis of infection or vaccination history and compared to respiratory syncytial viral or allergen (eg, cockroach, dust mite)-specific immunity. Methods: Fifty-three children from an urban asthma study were evaluated for medical history, lung function, and virus- or allergen-specific immunity using antibody or T-cell assays. Results: Polyclonal antibody responses to spike were observed in most children from infection and/or vaccination history. Children with atopic asthma or high allergen-specific IgE, particularly to dust mites, exhibited reduced seroconversion, antibody magnitude, and SARS-CoV-2 virus neutralization after SARS-CoV-2 infection or vaccination. TH1 responses to SARS-CoV-2 and respiratory syncytial virus correlated with antigen-respective IgG. Cockroach-specific T-cell activation as well as IL-17A and IL-21 cytokines negatively correlated with SARS-CoV-2 antibodies and effector functions, distinct from total and dust mite IgE. Allergen-specific IgE and lack of vaccination were associated with recent health care utilization. Reduced lung function (forced expiratory volume in 1 second ≤ 80%) was independently associated with (SARS-CoV-2) peptide-induced cytokines, including IL-31, whereas poor asthma control was associated with cockroach-specific cytokine responses. Conclusion: Mechanisms underpinning atopic and nonatopic asthma may complicate the development of memory to SARS-CoV-2 infection or vaccination and lead to a higher risk of repeated infection in these children.

Hidden in Plain Sight: A Case Series of Inflammatory Bowel Disease With Dermatologic Lesions As Initial or Concurrent Manifestations.

Pyoderma gangrenosum (PG) and erythema nodosum (EN) are rare skin conditions associated with inflammatory bowel disease (IBD), with increasing incidence as the disease progresses. We describe three cases of newly diagnosed IBD with cutaneous extraintestinal manifestations (EIMs) at the time of diagnosis. Three previously healthy patients presented with bloody diarrhea and concomitant nodular and ulcerating skin lesions at the onset of diarrhea. Dermatopathology showed PG and EN with endoscopic confirmation of ulcerative colitis. Clinical improvement was achieved with steroids and biological agents. These cases display the importance of a proper review of symptoms and a detailed workup of dermatological lesions prior to assuming infectious etiology.

Perioperative Estrogen Hormonal Therapy Does Not Increase Venous Thromboembolism Risk In Facial Feminization Surgery.

BACKGROUND: Conflicting data exist regarding increased perioperative VTE risk while on feminizing hormone therapy. The effect has been poorly studied within the transgender population. Acute perioperative cessation of feminizing hormone therapy often leads to unpleasant side effects and exacerbates gender dysphoria in the perioperative period. We seek to identify the VTE incidence in patients undergoing facial feminization while continuing HRT throughout the time of surgery. METHODS: A 38-year retrospective cohort study within a two-surgeon practice (D.K.O. and J.C.D.) was designed to evaluate postoperative VTE in patients continuing hormone therapy. The primary outcome variable was identified as suffering a VTE postoperatively. RESULTS: 1,715 patients underwent facial feminization surgery within our search window. 953 patients met final inclusion criteria. 1 patient (0.10%) was diagnosed with a VTE postoperatively, comparable to reported literature rates for similar cosmetic and orthognathic procedures. The average Caprini score of all patients was 3.1±1.0 and the average case length was 491.9±111.0 minutes. Subgroup analysis of patients before and after internal practice changes identified 714 (77.7%) patients continuing full dose hormonal therapy perioperatively, 197 (20.7%) patients undergoing hormonal dose reduction to 25-50% perioperatively, and 8 patients who were either not taking hormonal therapy or stopped in the perioperative period. There was no significant difference in VTE incidence between the 3 subgroups (p > 0.99). CONCLUSIONS: Perioperative use of feminizing hormonal therapy does not increase risk for perioperative VTE in patients undergoing facial feminization surgery. Therefore, it is reasonable to continue these medications through the time of surgery.

Giant Colonic Diverticulum: A Rare Type of Diverticular Disease.

Giant colonic diverticulum (GCD) is a well-recognized but infrequently encountered disease in clinical practice. GCD is its own unique entity and differs from commonly seen diverticular disease in both size and management. Initial clinical presentation is typically associated with diverticulitis and symptoms such as abdominal pain, fever, nausea, vomiting, rectal bleeding, or even a palpable abdominal mass. Surgery is the recommended treatment option largely due to the risk of associated complications including colonic perforation. We describe the case of a 56-year-old female diagnosed with a sigmoid GCD that was successfully stabilized medically and definitively treated surgically.

A Case of Postoperative Biliary Leak in a Patient With Duplicated Cystic Ducts.

Duplicated cystic ducts are a rare congenital malformation with less than 20 reported cases before 2019. This malformation is important to identify to reduce the risk of intraoperative complications such as bile duct injuries that can increase postoperative morbidity and mortality. We present the case of a 62-year-old male with duplicated cystic ducts that were ligated during laparoscopic cholecystectomy and subsequently complicated by postoperative biloma formation. Treatment options for biliary leak include endoscopic retrograde cholangiopancreatography (ERCP) with stenting, percutaneous drainage, and duct embolization. Each carries the risk of complications such as infection, duct perforation, and stent/drain displacement. Roux-en-Y hepaticojejunostomy (RHYJ) tends to be the last resort when other minimally invasive procedures fail. It is imperative to identify postoperative complications related to cystic duct anomalies and the various treatment options available should these complications occur.

Distinct functional neutrophil phenotypes in sepsis patients correlate with disease severity.

Purpose: Sepsis is a clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a highly heterogeneous syndrome with distinct phenotypes that impact immune function and response to infection. To develop targeted therapeutics, immunophenotyping is needed to identify distinct functional phenotypes of immune cells. In this study, we utilized our Organ-on-Chip assay to categorize sepsis patients into distinct phenotypes using patient data, neutrophil functional analysis, and proteomics. Methods: Following informed consent, neutrophils and plasma were isolated from sepsis patients in the Temple University Hospital ICU (n=45) and healthy control donors (n=7). Human lung microvascular endothelial cells (HLMVEC) were cultured in the Organ-on-Chip and treated with buffer or cytomix ((TNF/IL-1ß/IFNγ). Neutrophil adhesion and migration across HLMVEC in the Organ-on-Chip were used to categorize functional neutrophil phenotypes. Quantitative label-free global proteomics was performed on neutrophils to identify differentially expressed proteins. Plasma levels of sepsis biomarkers and neutrophil extracellular traps (NETs) were determined by ELISA. Results: We identified three functional phenotypes in critically ill ICU sepsis patients based on ex vivo neutrophil adhesion and migration patterns. The phenotypes were classified as: Hyperimmune characterized by enhanced neutrophil adhesion and migration, Hypoimmune that was unresponsive to stimulation, and Hybrid with increased adhesion but blunted migration. These functional phenotypes were associated with distinct proteomic signatures and differentiated sepsis patients by important clinical parameters related to disease severity. The Hyperimmune group demonstrated higher oxygen requirements, increased mechanical ventilation, and longer ICU length of stay compared to the Hypoimmune and Hybrid groups. Patients with the Hyperimmune neutrophil phenotype had significantly increased circulating neutrophils and elevated plasma levels NETs. Conclusion: Neutrophils and NETs play a critical role in vascular barrier dysfunction in sepsis and elevated NETs may be a key biomarker identifying the Hyperimmune group. Our results establish significant associations between specific neutrophil functional phenotypes and disease severity and identify important functional parameters in sepsis pathophysiology that may provide a new approach to classify sepsis patients for specific therapeutic interventions.

A review on the impact of single-stranded library preparation on plasma cell-free diversity for cancer detection.

In clinical oncology, cell-free DNA (cfDNA) has shown immense potential in its ability to noninvasively detect cancer at various stages and monitor the progression of therapy. Despite the rapid improvements in cfDNA liquid biopsy approaches, achieving the required sensitivity to detect rare tumor-derived cfDNA still remains a challenge. For next-generation sequencing, the perceived presentation of cfDNA is strongly linked to the extraction and library preparation protocols. Conventional double-stranded DNA library preparation (dsDNA-LP) focuses on assessing ~167bp double-stranded mononucleosomal (mncfDNA) and its other oligonucleosomal cell-free DNA counterparts in plasma. However, dsDNA-LP methods fail to include short, single-stranded, or nicked DNA in the final library preparation, biasing the representation of the actual cfDNA populations in plasma. The emergence of single-stranded library preparation (ssDNA-LP) strategies over the past decade has now allowed these other populations of cfDNA to be studied from plasma. With the use of ssDNA-LP, single-stranded, nicked, and ultrashort cfDNA can be comprehensively assessed for its molecular characteristics and clinical potential. In this review, we overview the current literature on applications of ssDNA-LP on plasma cfDNA from a potential cancer liquid biopsy perspective. To this end, we discuss the molecular principles of single-stranded DNA adapter ligation, how library preparation contributes to the understanding of native cfDNA characteristics, and the potential for ssDNA-LP to improve the sensitivity of circulating tumor DNA detection. Additionally, we review the current literature on the newly reported species of plasma ultrashort single-stranded cell-free DNA plasma, which appear biologically distinct from mncfDNA. We conclude with a discussion of future perspectives of ssDNA-LP for liquid biopsy endeavors.

Differential effects of community involvement on eating disorder prevention outcomes in sexual minority men.

Prior research has been conflicted on whether gay community involvement serves as a risk or protective factor for body image and eating disorders (EDs) in sexual minority men (SMM), perhaps given that prior research has examined community involvement unidimensionally. The present study examined whether non-appearance-based ("social activism") and appearance-based ("going out/nightlife") community involvement differentially predicted ED prevention outcomes in SMM. SMM (N = 73) enrolled in a randomized controlled trial of an ED prevention program completed measures of community involvement, drive for muscularity, body dissatisfaction, and bulimic symptoms at pre-intervention, post-intervention, and 1-month follow-up. "Social activism" community involvement moderated intervention effects for drive for muscularity and body dissatisfaction scores, but not bulimic symptoms, such that those who placed higher importance on social activism demonstrated expected improvements, while those who placed lower importance on social activism did not exhibit expected improvements. "Going out/nightlife" community involvement did not moderate intervention outcomes; however, greater importance of going out/nightlife was associated with increased body dissatisfaction. Findings support that the impact of community involvement on body image and ED risk for SMM may be nuanced. Encouraging community involvement through activism could help enhance ED prevention efforts for SMM.

Universal pictures: A lithophane codex helps teenagers with blindness visualize nanoscopic systems.

People with blindness have limited access to the high-resolution graphical data and imagery of science. Here, a lithophane codex is reported. Its pages display tactile and optical readouts for universal visualization of data by persons with or without eyesight. Prototype codices illustrated microscopy of butterfly chitin-from N-acetylglucosamine monomer to fibril, scale, and whole insect-and were given to high schoolers from the Texas School for the Blind and Visually Impaired. Lithophane graphics of Fischer-Spier esterification reactions and electron micrographs of biological cells were also 3D-printed, along with x-ray structures of proteins (as millimeter-scale 3D models). Students with blindness could visualize (describe, recall, distinguish) these systems-for the first time-at the same resolution as sighted peers (average accuracy = 88%). Tactile visualization occurred alongside laboratory training, synthesis, and mentoring by chemists with blindness, resulting in increased student interest and sense of belonging in science.

Is trait rumination associated with affective reactivity to the menstrual cycle? A prospective analysis.

BACKGROUND: A minority of naturally cycling individuals experience clinically significant affective changes across the menstrual cycle. However, few studies have examined cognitive and behavioral constructs that may maintain or worsen these changes. Several small studies link rumination with premenstrual negative affect, with authors concluding that a tendency to ruminate amplifies and perpetuates hormone-sensitive affective symptoms. Replication in larger samples is needed to confirm the validity of rumination as a treatment target. METHOD: 190 cycling individuals (M = 30.82 years; 61.1% Caucasian) were recruited for moderate perceived stress, a risk factor for cyclical symptoms. They completed the Rumination Response Scale at baseline, then reported daily affective and physical symptoms across 1-6 cycles. Multilevel growth models tested trait rumination as a predictor of baseline levels, luteal increases, and follicular decreases in symptoms. RESULTS: The degree of affective cyclicity was normally distributed across a substantial range, supporting feasibility of hypothesis tests and validating the concept of dimensional hormone sensitivity. Contrary to prediction, higher brooding did not predict levels or cyclical changes of any symptom. In a subsample selected for luteal increases in negative affect, brooding predicted higher baseline negative affect but still did not predict affective cyclicity. CONCLUSIONS: An individual's trait-like propensity to engage in rumination may not be a valid treatment target in premenstrual mood disorders. State-like changes in rumination should still be further explored, and well-powered prospective studies should explore other cognitive and behavioral factors to inform development of targeted psychological treatments for patients with cyclical affective symptoms.

Directed evolution of enzymatic silicon-carbon bond cleavage in siloxanes.

Volatile methylsiloxanes (VMS) are man-made, nonbiodegradable chemicals produced at a megaton-per-year scale, which leads to concern over their potential for environmental persistence, long-range transport, and bioaccumulation. We used directed evolution to engineer a variant of bacterial cytochrome P450BM3 to break silicon-carbon bonds in linear and cyclic VMS. To accomplish silicon-carbon bond cleavage, the enzyme catalyzes two tandem oxidations of a siloxane methyl group, which is followed by putative [1,2]-Brook rearrangement and hydrolysis. Discovery of this so-called siloxane oxidase opens possibilities for the eventual biodegradation of VMS.

METTL17 is an Fe-S cluster checkpoint for mitochondrial translation.

Friedreich's ataxia (FA) is a debilitating, multisystemic disease caused by the depletion of frataxin (FXN), a mitochondrial iron-sulfur (Fe-S) cluster biogenesis factor. To understand the cellular pathogenesis of FA, we performed quantitative proteomics in FXN-deficient human cells. Nearly every annotated Fe-S cluster-containing protein was depleted, indicating that as a rule, cluster binding confers stability to Fe-S proteins. We also observed depletion of a small mitoribosomal assembly factor METTL17 and evidence of impaired mitochondrial translation. Using comparative sequence analysis, mutagenesis, biochemistry, and cryoelectron microscopy, we show that METTL17 binds to the mitoribosomal small subunit during late assembly and harbors a previously unrecognized [Fe4S4]2+ cluster required for its stability. METTL17 overexpression rescued the mitochondrial translation and bioenergetic defects, but not the cellular growth, of FXN-depleted cells. These findings suggest that METTL17 acts as an Fe-S cluster checkpoint, promoting translation of Fe-S cluster-rich oxidative phosphorylation (OXPHOS) proteins only when Fe-S cofactors are replete.

Cochlear-Implant Simulated Signal Degradation Exacerbates Listening Effort in Older Listeners.

OBJECTIVES: Individuals with cochlear implants (CIs) often report that listening requires high levels of effort. Listening effort can increase with decreasing spectral resolution, which occurs when listening with a CI, and can also increase with age. What is not clear is whether these factors interact; older CI listeners potentially experience even higher listening effort with greater signal degradation than younger CI listeners. This study used pupillometry as a physiological index of listening effort to examine whether age, spectral resolution, and their interaction affect listening effort in a simulation of CI listening. DESIGN: Fifteen younger normal-hearing listeners (ages 18 to 31 years) and 15 older normal-hearing listeners (ages 65 to 75 years) participated in this experiment; they had normal hearing thresholds from 0.25 to 4 kHz. Participants repeated sentences presented in quiet that were either unprocessed or vocoded, simulating CI listening. Stimuli frequency spectra were limited to below 4 kHz (to control for effects of age-related high-frequency hearing loss), and spectral resolution was decreased by decreasing the number of vocoder channels, with 32-, 16-, and 8-channel conditions. Behavioral speech recognition scores and pupil dilation were recorded during this task. In addition, cognitive measures of working memory and processing speed were obtained to examine if individual differences in these measures predicted changes in pupil dilation. RESULTS: For trials where the sentence was recalled correctly, there was a significant interaction between age and spectral resolution, with significantly greater pupil dilation in the older normal-hearing listeners for the 8- and 32-channel vocoded conditions. Cognitive measures did not predict pupil dilation. CONCLUSIONS: There was a significant interaction between age and spectral resolution, such that older listeners appear to exert relatively higher listening effort than younger listeners when the signal is highly degraded, with the largest effects observed in the eight-channel condition. The clinical implication is that older listeners may be at higher risk for increased listening effort with a CI.

1-Year Comparative Effectiveness of Tofacitinib vs Ustekinumab for Patients With Ulcerative Colitis and Prior Antitumor Necrosis Factor Failure.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Real-world data comparing the effectiveness of tofacitinib to ustekinumab are limited. We compared 52-week outcomes of tofacitinib vs ustekinumab for UC after antitumor necrosis factor (anti-TNF) failure. METHODS: In this retrospective cohort study, adults initiated tofacitinib or ustekinumab for UC after anti-TNF failure May 1, 2018 to April 1, 2021, at a US academic medical center. The primary outcome was steroid-free clinical remission (SFCR) at 12 and 52 weeks. The secondary outcome was drug survival (ie, time to drug discontinuation due to nonresponse). Adverse events (AEs) were also assessed. RESULTS: Sixty-nine patients initiated tofacitinib, and 97 patients initiated ustekinumab with median follow-up of 88.0 and 62.0 weeks, respectively. After inverse probability of treatment-weighted logistic and Cox regression, there was no association of tofacitinib vs ustekinumab with SFCR at 12 weeks (odds ratio, 1.65; 95% CI, 0.79-3.41), SFCR at 52 weeks (odds ratio, 1.14; 95% CI, 0.55-2.34), or drug survival (hazard ratio, 1.37; 95% CI, 0.78-2.37). Kaplan-Meier analysis demonstrated no separation in drug survival curves. Regression results were similar after excluding patients with prior tofacitinib or ustekinumab exposure. During available follow-up, 17 AEs were reported for tofacitinib (most commonly shingles, n = 4), and 10 AEs were reported for ustekinumab (most commonly arthralgia and rash, each n = 2). Two patients discontinued treatment due to AEs (1 tofacitinib for elevated liver enzymes, 1 ustekinumab for arthralgia). CONCLUSIONS: In a real-world UC cohort, tofacitinib and ustekinumab demonstrated similar effectiveness at 52 weeks. Adverse events were consistent with the known safety profiles of these agents.

In this real-world cohort of anti-TNF-exposed patients with ulcerative colitis, tofacitinib and ustekinumab demonstrated similar effectiveness in achieving steroid-free clinical remission at 12 and 52 weeks. Adverse events were consistent with the known safety profiles of these agents.

Predicting Acute Changes in Suicidal Ideation and Planning: A Longitudinal Study of Symptom Mediators and the Role of the Menstrual Cycle in Female Psychiatric Outpatients With Suicidality.

OBJECTIVE: Cross-sectional and preliminary longitudinal findings suggest that cyclical ovarian hormone fluctuations influence acute suicide risk. The authors provide the first analyses in females with suicidality to investigate which daily symptoms covary with suicidal ideation and planning thoughts, the role of the menstrual cycle in daily symptom variation, how daily fluctuations in symptoms mediate the menstrual cycle-suicidality relationship, and how these associations vary across individuals. METHODS: Naturally cycling psychiatric outpatients (N=119) with past-month suicidal ideation provided daily ratings of psychiatric symptoms (depression, hopelessness, anxiety, feeling overwhelmed, agitation, anhedonia, worthlessness, rejection sensitivity, anger, perceived burdensomeness, and interpersonal conflict), suicidal ideation, and suicidal planning across at least one menstrual cycle. Symptom ratings were decomposed into trait (person-centered mean) and state (daily person-centered mean deviation) components. Five cycle phases were identified in relation to menses onset and ovulation (surge in urine luteinizing hormone level). Hypotheses were tested in multilevel structural equation models. RESULTS: Nearly all psychiatric symptoms covaried with fluctuations in daily suicidal ideation, and a limited set of symptoms (depression, hopelessness, rejection sensitivity, and perceived burdensomeness) predicted within-person increases in suicidal planning. Many patients demonstrated perimenstrual worsening of psychiatric symptoms, suicidal ideation, and suicidal planning. Depressive symptoms (depression, hopelessness, perceived burdensomeness, and anhedonia) were the most robust statistical mediators predicting perimenstrual exacerbation of suicidality. CONCLUSIONS: Research on the menstrual cycle and suicide has been limited historically by small, cross-sectional samples. This study provides the first evidence that measuring day-to-day correlates of suicidality in a large transdiagnostic sample of females with suicidal ideation can contribute to understanding the pathways by which the menstrual cycle influences acute suicide risk.

Examining the association of structural stigmas with body image-related outcomes among sexual minority individuals.

Sexual minority individuals display heightened body image disturbance, which is associated with negative health outcomes. Structural stigmas are associated with negative health outcomes among sexual minority individuals, but the association between structural stigmas and body image is not understood. Using a linear regression approach, we examined how U.S. state-level structural racism and structural sexual minority stigma were associated with body image-related outcomes including eating pathology, appearance and/or performance-enhancing drug (APED) misuse, and dysmorphic concern. Participants were 942 cisgender sexual minority individuals ages 18-30, with approximately equal representation among non-Hispanic/Latinx White, Black, Asian, and Hispanic/Latinx individuals. There was not a significant main effect of state-level structural sexual minority stigma on body image-related outcomes. In states with higher structural racism, Hispanic/Latinx participants endorsed higher APED misuse, and this interaction was not significant among non-Hispanic/Latinx White individuals. This pattern was not found among Black or Asian participants, nor was it replicated for dysmorphic concern or eating pathology. Findings suggest that reducing exposure to structural racism could reduce APED misuse among Hispanic/Latinx individuals.

Under Disguise: A Concealed Case of Acute Hepatitis A Infection.

Acute hepatitis A virus infection is routinely identified through a thorough patient history in conjunction with liver chemistries and viral serologies. The diagnosis has the potential to be delayed when the clinical picture is obscured with another, seemingly more urgent presenting pathology with overlapping features. Here, we describe the case of a young female who presented with acute calculous cholecystitis with concurrent acute hepatitis A virus infection.

Integrating Youth Readiness Intervention and Entrepreneurship in Sierra Leone: A Hybrid Type II Cluster Randomized Trial.

OBJECTIVE: Conflict-affected youth are at risk for poor psychological and social outcomes, yet few receive mental health services. Strategies to expand access and sustain evidence-based interventions (EBIs) across novel delivery platforms must be tested. The present study was a hybrid type II implementation-effectiveness trial using a cluster randomized design. The primary goal was to evaluate feasibility and impact of using the collaborative team approach to deliver the Youth Readiness Intervention (YRI), an EBI, integrated into a youth entrepreneurship program (ENTR) with quality control in post-conflict Sierra Leone. METHOD: Youth were screened and randomly assigned to control, ENTR, or combined YRI and ENTR (YRI+ENTR). Implementation outcomes were dissemination and implementation indicators, competence, and fidelity. Effectiveness outcomes were emotion regulation, psychological distress, and interpersonal functioning. Secondary outcomes were third-party reporter assessments of youth functioning and behavior. RESULTS: Data were collected and analyzed from 1,151 youth participants and 528 third-party reporters. Scores on implementation constructs, competence, and fidelity demonstrated acceptable intervention response and quality. YRI+ENTR participants showed overall improvements in depression (ß = -.081, 95% CI -0.124 to -0.038, d = -0.154) and anxiety (ß = -.043, 95% CI -0.091 to -0.005, d = 0.082) symptoms compared with control participants. Community leaders indicated that YRI+ENTR participants demonstrated improvements in overall work or training performance compared with control participants (ß = -.114, 95% CI 0.004 to 0.232, d = 0.374). CONCLUSION: Integration of EBIs such as the YRI into youth employment programs has the potential to address limited reach of EBIs in conflict and post-conflict settings. A collaborative team implementation approach can facilitate integration and fidelity. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. One or more of the authors of this paper received support from a program designed to increase minority representation in science. CLINICAL TRIAL REGISTRATION INFORMATION: Youth FORWARD Phase 2 YRI and EPP Study; https://clinicaltrials.gov/; NCT03542500.