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Report of the Higgs working group for the Workshop `Physics at TeVColliders', Les Houches, France, 21 May - 1 June 2001. It contains 7 separatesections: A. Theoretical Developments B. Higgs Searches at the Tevatron C.Experimental Observation of an invisible Higgs Boson at LHC D. Search for theStandard Model Higgs Boson using Vector Boson Fusion at the LHC E. Study of theMSSM channel $A/H \to \tau \tau$ at the LHC F. Searching for Higgs Bosons in$t\bar t H$ Production G. Studies of Charged Higgs Boson Signals for theTevatron and the LHC

Background. The purpose of this study was to determine the numeracy information included in three prominent breast cancer Web sites. Methods. A content analysis was performed, grouping numeracy items into 15 categories. Interrater reliability was high. Results. Of the 3,206 items identified, 14.3% were numbers, 33.9% were descriptive measures (e.g., many, lower), 27.3% were statistical terms (e.g., predictive, risk), and 12.4% were temporal terms (e.g., before, always). Conclusions. Findings suggest that there is an abundance of numeric information presented in breast cancer Web sites, much of which may be conceptually too advanced for the intended audience. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this project was to gather preliminary data on preferred content for text reminders sent to low-income parents. METHODS: A brief, IRB-approved survey was administered to 200 consecutive English-speaking parents of children under 6 years old at a Pediatric Residency clinic. Because text messages can hold only limited content, parents were given three example texts ranging from very basic to very specific information and asked to select the information they would wish to receive. RESULTS: Of the 190 parents (95%) who responded, 22.1% (42) were Hispanic and 76.3% (145) were non-Hispanic. Over 80% (153) received Medicaid. Of the 79.5% (151) of respondents interested in receiving text messages who responded to the question regarding content, nearly 50% (74) preferred Option 2, with the remaining respondents divided between Option 1 (43) and Option 3 (35). Results differed significantly between Hispanic and non-Hispanic respondents ([chi](2)(2)=6.36, p=0.042). CONCLUSION: The majority of parents preferred a message containing the child's name, specific immunization information and physician information. However, Hispanic respondents were significantly more likely to endorse an option that included additional information. PRACTICE IMPLICATIONS: Text messaging may be an optimal vehicle for provider-patient communication, however cultural differences should be considered when developing messages. [ABSTRACT FROM AUTHOR]

Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4 + T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics., Competing Interests: Declaration of interests G.R.H. has consulted for Generon Corporation, NapaJen Pharma, iTeos Therapeutics, and Neoleukin Therapeutics and has received unrelated research funding from Compass Therapeutics, Syndax Pharmaceuticals, Applied Molecular Transport, Serplus Technology, Heat Biologics, Laevoroc Oncology, iTeos Therapeutics, Genentech, and CSL Behring., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Calcineurin inhibitors (CNIs) constitute the backbone of modern acute graft-versus-host disease (aGVHD) prophylaxis regimens but have limited efficacy in the prevention and treatment of chronic GVHD (cGVHD). We investigated the effect of CNIs on immune tolerance after stem cell transplantation with discovery-based single-cell gene expression and T cell receptor (TCR) assays of clonal immunity in tandem with traditional protein-based approaches and preclinical modeling. While cyclosporin and tacrolimus suppressed the clonal expansion of CD8+ T cells during GVHD, alloreactive CD4+ T cell clusters were preferentially expanded. Moreover, CNIs mediated reversible dose-dependent suppression of T cell activation and all stages of donor T cell exhaustion. Critically, CNIs promoted the expansion of both polyclonal and TCR-specific alloreactive central memory CD4+ T cells (TCM) with high self-renewal capacity that mediated cGVHD following drug withdrawal. In contrast to posttransplant cyclophosphamide (PT-Cy), CSA was ineffective in eliminating IL-17A-secreting alloreactive T cell clones that play an important role in the pathogenesis of cGVHD. Collectively, we have shown that, although CNIs attenuate aGVHD, they paradoxically rescue alloantigen-specific TCM, especially within the CD4+ compartment in lymphoid and GVHD target tissues, thus predisposing patients to cGVHD. These data provide further evidence to caution against CNI-based immune suppression without concurrent approaches that eliminate alloreactive T cell clones.

Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (T PHEX ), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with BATF expression and motif accessibility. IFN-γ + T PHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ + T PHEX . We also observed IFN-γ + T PHEX within CD19-targeted chimeric antigen receptor T cells, which killed CD19 + leukemia cells. An IFN-γ + T PHEX gene signature was recapitulated in T EX cells from human cancers, including myeloma and lymphoma. Here, we characterize a T EX subset in hematological malignancies that paradoxically retains function and is distinct from dysfunctional T EX found in chronic viral infections. Thus, IFN-γ + T PHEX represent a potential target for immunotherapy of blood cancers.

Abstract: Autologous stem cell transplantation (ASCT) is the standard of care consolidation therapy for eligible patients with myeloma but most patients eventually progress, an event associated with features of immune escape. Novel approaches to enhance antimyeloma immunity after ASCT represent a major unmet need. Here, we demonstrate that patient-mobilized stem cell grafts contain high numbers of effector CD8 T cells and immunosuppressive regulatory T cells (Tregs). We showed that bone marrow (BM)-residing T cells are efficiently mobilized during stem cell mobilization (SCM) and hypothesized that mobilized and highly suppressive BM-derived Tregs might limit antimyeloma immunity during SCM. Thus, we performed ASCT in a preclinical myeloma model with or without stringent Treg depletion during SCM. Treg depletion generated SCM grafts containing polyfunctional CD8 T effector memory cells, which dramatically enhanced myeloma control after ASCT. Thus, we explored clinically tractable translational approaches to mimic this scenario. Antibody-based approaches resulted in only partial Treg depletion and were inadequate to recapitulate this effect. In contrast, a synthetic interleukin-2 (IL-2)/IL-15 mimetic that stimulates the IL-2 receptor on CD8 T cells without binding to the high-affinity IL-2Ra used by Tregs efficiently expanded polyfunctional CD8 T cells in mobilized grafts and protected recipients from myeloma progression after ASCT. We confirmed that Treg depletion during stem cell mobilization can mitigate constraints on tumor immunity and result in profound myeloma control after ASCT. Direct and selective cytokine signaling of CD8 T cells can recapitulate this effect and represent a clinically testable strategy to improve responses after ASCT., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-γ in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-γ-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy.

Introduction: Sudden unexpected infant death (SUID) is the leading cause of death among U.S. infants aged 28 days to 1 year. In Kansas, Hispanic infant mortality is nearly 50% higher than non-Hispanic White. Further, the SUID rate did not change between 2005-2018, while rates for non-Hispanic Black and White infants decreased significantly. This study sought to identify characteristics and behaviors of Hispanic birthing persons related to SUID., Methods: Linked Kansas birth/death vital statistics data (2005-2018) identified Hispanic birthing persons with a singleton birth who experienced SUID. To reduce confounding effects, greedy nearest neighbor matching paired each SUID case sequentially with the four nearest controls based on age, race, payor source and parity. Matching procedures, likelihood-ratio χ2, Fisher exact test and multiple logistic regression model with Firth's penalized maximum likelihood estimation were computed., Results: Of 86,052 Hispanic singleton births, 66 involved SUID and were matched with 264 controls. No differences were related to marital status, population density of residence, education level, language spoken, prenatal BMI, weight gained during pregnancy, adequacy of prenatal care, enrollment in WIC, or state immunization registry participation (all p>0.05). However, tobacco use during pregnancy contributed to a three times greater risk of SUID (OR=3.208; 95% CI=1.438 to 7.154). Multivariable models for behavioral variables revealed low predictive accuracy with area under the ROC curve=0.6303., Conclusion: This study suggests SUID deaths to rural Hispanic families are likely multifaceted. Study results inform educational programs on the importance of addressing tobacco cessation in SUID risk reduction interventions for Hispanic families., (© 2023. W. Montague Cobb-NMA Health Institute.)

Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic stem cell transplantation (SCT), and severe intestinal manifestation is the major cause of early mortality. Intestinal microbiota control MHC class II (MHC-II) expression by ileal intestinal epithelial cells (IECs) that promote GVHD. Here, we demonstrated that genetically identical mice of differing vendor origins had markedly different intestinal microbiota and ileal MHC-II expression, resulting in discordant GVHD severity. We utilized cohousing and antibiotic treatment to characterize the bacterial taxa positively and negatively associated with MHC-II expression. A large proportion of bacterial MHC-II inducers were vancomycin sensitive, and peri-transplant oral vancomycin administration attenuated CD4 + T cell-mediated GVHD. We identified a similar relationship between pre-transplant microbes, HLA class II expression, and both GVHD and mortality in a large clinical SCT cohort. These data highlight therapeutically tractable mechanisms by which pre-transplant microbial taxa contribute to GVHD independently of genetic disparity., Competing Interests: Declaration of interests W.M.G. is a scientific advisory board member for Freenome, Guardant Health, and SEngine and consultant for DiaCarta, Natera, Guidepoint, and GLG. He is an investigator in a clinical trial sponsored by Janssen Pharmaceuticals and receives research support from Tempus and LucidDx. M.R.M.v.d.B. has received research support and stock options from Seres Therapeutics and stock options from Notch Therapeutics and Pluto Therapeutics; he has received royalties from Wolters Kluwer; has consulted, received honorarium from or participated in advisory boards for Seres Therapeutics, Vor Biopharma, Rheos Medicines, Frazier Healthcare Partners, Nektar Therapeutics, Notch Therapeutics, Ceramedix, Lygenesis, Pluto Therapeutics, GlaskoSmithKline, Da Volterra, Thymofox, Garuda, Novartis (Spouse), Synthekine (Spouse), Beigene (Spouse), and Kite (Spouse); has IP Licensing with Seres Therapeutics and Juno Therapeutics; and holds a fiduciary role on the Foundation Board of DKMS (a nonprofit organization). Memorial Sloan Kettering has institutional financial interests relative to Seres Therapeutics. K.A.M. serves in an advisory role and holds stock in PostBiotics Plus Research and has consulted for Incyte. D.N.F. and T.L.F. have financial relationships with BD for licensure of molecular diagnosis of bacterial vaginosis, unrelated to the research presented in this article. G.R.H. has consulted for Generon Corporation, NapaJen Pharma, iTeos Therapeutics, and Neoleukin Therapeutics and receives research funding from Compass Therapeutics, Syndax Pharmaceuticals, Applied Molecular Transport, Serplus Technology, Heat Biologics, Laevoroc Oncology,iTeos Pharmaceuticals, and Genentech., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This retrospective study compared knowledge, intention, and satisfaction outcomes between pregnant women who attended prenatal education in person ( n = 202; 55%) prior to the COVID-19 pandemic or virtually ( n = 166; 45%) during the pandemic. Results identified increases in knowledge and intention for a healthy pregnancy and safe infant care for both groups. Virtual participants were less likely to endorse developing a birth plan ( p = 0.035), knowledge of breastfeeding resources ( p = 0.006), confidence in the ability to breastfeed ( p = 0.033), and plans to use only a safe infant sleep location ( p = 0.045). Important education was provided by continuing Baby Talk during the pandemic. However, topics with activities/demonstrations during in-person learning that were discontinued for virtual learning had significantly lower increases for virtual participants. Virtual education should incorporate more demonstrations/activities., Competing Interests: The authors have no relevant financial interest or affiliations with any commercial interests related to the subjects discussed within this article., (© Copyright 2023 Lamaze International.)

Background/objectives: Although understudied, risk of venous thromboembolism (VTE) appears to be increased during acute pancreatitis (AP). We aimed to further characterize a hypercoagulable state associated with AP utilizing thromboelastography (TEG), a readily available, point of care test., Methods: AP was induced in C57/Bl6 mice using l-arginine and caerulein. TEG was performed with citrated native samples. The maximum amplitude (MA) and coagulation index (CI), a composite marker of coagulability, were evaluated. Platelet aggregation was assessed using whole blood collagen-activated platelet impedance aggregometry. Circulating tissue factor (TF), the initiator of extrinsic coagulation, was measured with ELISA. A VTE model using IVC ligation followed by measurement of clot size and weight was evaluated. After IRB approval and consent, blood samples from patients hospitalized with a diagnosis of AP were evaluated by TEG., Results: Mice with AP displayed a significant increase in MA and CI, consistent with hypercoagulability. Hypercoagulability peaked at 24 h after induction of pancreatitis, then returned to baseline by 72 h. AP resulted in significantly increased platelet aggregation and elevated circulating TF. Increased clot formation with AP was observed in an in vivo model of deep vein thrombosis. In a proof of concept, correlative study, over two thirds of patients with AP demonstrated an elevated MA and CI compared to the normal range, consistent with hypercoagulability., Conclusions: Murine acute pancreatitis results in a transient hypercoagulable state that can be assessed by TEG. Correlative evidence for hypercoagulability was also demonstrated in human pancreatitis. Further study to correlate coagulation measures to incidence of VTE in AP is warranted., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Autologous stem cell transplantation (ASCT) with subsequent lenalidomide maintenance is standard consolidation therapy for multiple myeloma, and a subset of patients achieve durable progression-free survival that is suggestive of long-term immune control. Nonetheless, most patients ultimately relapse, suggesting immune escape. TIGIT appears to be a potent inhibitor of myeloma-specific immunity and represents a promising new checkpoint target. Here we demonstrate high expression of TIGIT on activated CD8+ T cells in mobilized peripheral blood stem cell grafts from patients with myeloma. To guide clinical application of TIGIT inhibition, we evaluated identical anti-TIGIT antibodies that do or do not engage FcγR and demonstrated that anti-TIGIT activity is dependent on FcγR binding. We subsequently used CRBN mice to investigate the efficacy of anti-TIGIT in combination with lenalidomide maintenance after transplantation. Notably, the combination of anti-TIGIT with lenalidomide provided synergistic, CD8+ T cell-dependent, antimyeloma efficacy. Analysis of bone marrow (BM) CD8+ T cells demonstrated that combination therapy suppressed T cell exhaustion, enhanced effector function, and expanded central memory subsets. Importantly, these immune phenotypes were specific to the BM tumor microenvironment. Collectively, these data provide a logical rationale for combining TIGIT inhibition with immunomodulatory drugs to prevent myeloma progression after ASCT.

People who read and dismiss distracting notifications while performing academic or professional tasks may pay a high cognitive price. Multimedia interruptions clearly impair comprehension and memory; however, their impact may depend on the individual's cognitive abilities and experiences. In a pilot study and two experiments, we explored the effects of three levels of distraction from cellphone notifications (no notifications, dismiss notifications and read notifications) on memory for categorised word lists. Individual differences in working memory capacity, attachment to and dependence on cellphones, and media multitasking, texting, video gaming and musical experience were assessed. Memory impairment increased with the level of distraction irrespective of participant scores on the individual difference measures. Dismissing notifications disrupted relational processing more than individual-item processing, whereas reading notifications disrupted both types of processing. Heavy texters demonstrated particularly poor memory performance, whereas individuals with high working memory capacity and high reliance on their cellphones performed relatively well. These results were interpreted in terms of recent multitasking theories and suggest that no one is immune from the disruptive effects of cellphone notifications while performing academic or professional tasks.

Some hematological malignancies such as multiple myeloma are inherently resistant to immune-mediated antitumor responses, the cause of which remains unknown. Allogeneic bone marrow transplantation (alloBMT) is the only curative immunotherapy for hematological malignancies due to profound graft-versus-tumor (GVT) effects, but relapse remains the major cause of death. We developed murine models of alloBMT where the hematological malignancy is either sensitive [acute myeloid leukemia (AML)] or resistant (myeloma) to GVT effects. We found that CD8 + T cell exhaustion in bone marrow was primarily alloantigen-driven, with expression of inhibitory ligands present on myeloma but not AML. Because of this tumor-independent exhaustion signature, immune checkpoint inhibition (ICI) in myeloma exacerbated graft-versus-host disease (GVHD) without promoting GVT effects. Administration of post-transplant cyclophosphamide (PT-Cy) depleted donor T cells with an exhausted phenotype and spared T cells displaying a stem-like memory phenotype with chromatin accessibility present in cytokine signaling genes, including the interleukin-18 (IL-18) receptor. Whereas ICI with anti-PD-1 or anti-TIM-3 remained ineffective after PT-Cy, administration of a decoy-resistant IL-18 (DR-18) strongly enhanced GVT effects in both myeloma and leukemia models, without exacerbation of GVHD. We thus defined mechanisms of resistance to T cell-mediated antitumor effects after alloBMT and described an immunotherapy approach targeting stem-like memory T cells to enhance antitumor immunity.

Background: Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared to cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes., Methods: Targeted metabolomics, that included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer (n=10/group, equally divided by sex). Additional patient samples were analyzed (total n=95) and Receiver Operating Characteristic (ROC) analyses were performed to establish if any metabolite could effectively serve as a biomarker of cachexia., Results: Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only altered in cachectic males., Conclusions: Our findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia., Competing Interests: Competing Interests JMC, MED, CRS, PVR, TMW, and EET declare that they have no conflicts of interest. DCE declares that he has received research support and has a speaking and consulting agreement with Abbott Laboratories. DCG declares that he receives research support from Pfizer and consults for Immuneering and Catabasis.

Introduction: Clinical trials are the gold standard for assessing the effectiveness and safety of treatments. The objective of this study was to assess provider opinions regarding implementing pediatric clinical trials in various practice settings across Kansas., Methods: The study was completed within the Sunflower Pediatric Clinical Trials Research Extension (SPeCTRE), an affiliate of the IDeA States Pediatric Clinical Trials Network (ISPCTN). A cross-sectional, 36-item survey was administered to a state-wide convenience sample targeting health care providers and clinic staff., Results: A total of 115 health care providers and clinic staff completed surveys; 31% were physicians. Physicians were more likely than other clinic staff to have experience with clinical trials (correlation coefficient [CC] = 0.270, p = 0.004). When compared to urban respondents, rural providers were less supportive of recruitment for clinical trials in their practices (CC = -0.251, p = 0.008) and more likely to feel comfortable referring patients for clinical trials involving treatments that their insurance did not cover (CC = 0.302, p = 0.001)., Conclusions: A range of rural and urban health care professionals supported conducting pediatric clinical trials but identified several barriers as well. These results will support future pediatric clinical trials across the country including Kansas., (© 2022 The University of Kansas Medical Center.)

Introduction: Pediatric clinical trials are difficult to conduct, leading to off-label use of medication in children based on results of trials with adults. As a unique population, children deserve to have appropriately tested therapies. The purpose of this study was to evaluate pediatric caregivers' beliefs and perceived barriers to participation in clinical trials., Methods: The study was completed within the Sunflower Pediatric Clinical Trials Research Extension (SPeCTRE), an affiliate of the IDeA States Pediatric Clinical Trials Network (ISPCTN). This was a cross-sectional survey, adapted from the Pediatric Research Participation Questionnaire. A convenience sample of pediatric caregivers was recruited in three areas of a highly rural Midwestern state between 2017 and 2018., Results: A total of 159 caregivers completed surveys; the majority (72.3%) were previously familiar with clinical trials, but less than 20% had ever been invited to participate. Caregivers were willing to consider enrolling their child if a physician in whom they had high trust recommended the trials (H = 10.1, p = 0.04) and if there were perceived benefits, such as access to tests and medications not covered by insurance (correlation coefficient [CC] = 0.4, p < 0.01) and compensation for time and travel (CC = 0.3, p = 0.04)., Conclusions: Trust in their physician highly influences likelihood of a caregiver consenting to have their child participate in a clinical trial. Therefore, to facilitate opportunities for children to participate in clinical trials, physicians need to be trained so they can offer trials locally. In addition, trials need to offer benefits, such as increased access to tests and medications as well as appropriate compensation., (© 2022 The University of Kansas Medical Center.)

Introduction: Psychological distress affects up to 25% of pregnant women and contributes to poor birth outcomes. Screening with appropriate referral or treatment is critical, yet many women do not access services. This project aimed to identify knowledge of and barriers to mental health services in the perinatal period., Methods: Interviews with low-income pregnant or postpartum women, primary care providers (PCPs), and mental health care providers were conducted in Sedgwick County, Kansas. Interviews were transcribed, independently reviewed using grounded theory, and stratified using a social-ecological model framework., Results: Thirty-three interviews were conducted with 12 (36%) pregnant or postpartum women, 15 (45%) PCPs, and 6 (18%) mental health care providers. Barriers were categorized into three levels: individual, social, and society. Individual level barriers, including cost or lack of insurance and transportation, were consistent across groups, however, women identified barriers only at this level. Provider groups identified barriers at all levels, including lack of support, poor communication between providers, and Medicaid limitations., Conclusions: Multi-level interventions are needed to improve access to mental health care for low-income women in the perinatal period., (© 2022 The University of Kansas Medical Center.)

Background: We sought to derive and validate a prediction model of survival and recurrence among Western patients undergoing resection of gastric cancer., Methods: Patients who underwent curative-intent surgery for gastric cancer at seven US institutions and a major Italian center from 2000 to 2020 were included. Variables included in the multivariable Cox models were identified using an automated model selection procedure based on an algorithm. Best models were selected using the Bayesian information criterion (BIC). The performance of the models was internally cross-validated via the bootstrap resampling procedure. Discrimination was evaluated using the Harrell's Concordance Index and accuracy was evaluated using calibration plots. Nomograms were made available as online tools., Results: Overall, 895 patients met inclusion criteria. Age (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.17-1.84), presence of preoperative comorbidities (HR 1.66, 95% CI 1.14-2.41), lymph node ratio (LNR; HR 1.72, 95% CI 1.42-2.01), and lymphovascular invasion (HR 1.81, 95% CI 1.33-2.45) were associated with overall survival (OS; all p < 0.01), whereas tumor location (HR 1.93, 95% CI 1.23-3.02), T category (Tis-T1 vs. T3: HR 0.31, 95% CI 0.14-0.66), LNR (HR 1.82, 95% CI 1.45-2.28), and lymphovascular invasion (HR 1.49; 95% CI 1.01-2.22) were associated with disease-free survival (DFS; all p < 0.05) The models demonstrated good discrimination on internal validation relative to OS (C-index 0.70) and DFS (C-index 0.74)., Conclusions: A web-based nomograms to predict OS and DFS among gastric cancer patients following resection demonstrated good accuracy and discrimination and good performance on internal validation., (© 2021. Society of Surgical Oncology.)

Introduction: Hispanics represent the largest minority group in the United States. In Kansas, the population of Hispanics has been increasing; unfortunately, their infant mortality rate has increased as well. Baby Talk is a prenatal education program promoting maternal and infant health through risk-reduction strategies and healthy decision-making. The aim of this pilot project was to develop and evaluate a Spanish curriculum for Baby Talk., Methods: A collaborative partnership between bilingual community members and health professionals from different origins, nationalities, and Spanish dialects was formed to create a culturally and linguistically appropriate Spanish Baby Talk curriculum. This interventional pilot mixed methods research study employed quantitative and qualitative methods to evaluate participant knowledge, intentions, satisfaction, and perceptions of the new curriculum., Results: Fifteen pregnant women participated in Spanish Baby Talk. Of those, 12 participated in either phone interviews (n = 6) or a focus group (n = 6). All respondents described their experience with the Spanish Baby Talk program as "excellent". Significant increases in knowledge were seen related to topics such as benefits of full-term pregnancy and benefits of breastfeeding. Four themes were identified from the focus group and interviews: 1) lack of accessible community resources; 2) sense of community; 3) Spanish Baby Talk strengths; and 4) areas for improvements., Conclusions: Findings suggested that the Spanish Baby Talk curriculum was linguistically appropriate and resulted in increases in knowledge and intentions related to health and safety behaviors. Areas for improvement were related to marketing the program and referring to resources that provide material supports (i.e., diapers) to continue the move towards a culturally competent program., (© 2022 The University of Kansas Medical Center.)

Background: Pancreatic diseases have long been associated with impaired glucose control. This study sought to identify the incidence of new insulin-dependent diabetes mellitus (IDDM) after pancreatectomy and the predictive accuracy of hemoglobin A1c (HbA1c) or blood glucose., Methods: Patients who underwent partial pancreatectomy and had preoperative HbA1c available at two academic institutions were assessed for new IDDM on discharge in relation to complication rates and survival., Results: Of the 267 patients analyzed, 67% had abnormal HbA1c levels prior to surgery (mean 6.8%, glucose 135 mg/dL). Two hundred eight (77.9%) were not insulin-dependent prior to surgery, and 35 (16.8%) developed new IDDM after resection. On multivariable regression, increasing HbA1c and preoperative glucose were the only significant predictors for new IDDM. Optimal predictive cutoffs (HbA1c of 6.25% and glucose of 121 mg/dL) were determined in a discovery group (n = 143) and confirmed in a validation group (n = 124) with a diagnostic sensitivity of 72.7% and specificity of 84.8%. Patients with new IDDM after resection had higher rates of severe complications (OR 3.39), increased TPN at discharge (OR 4.32), and increased rates of discharge to nursing facilities (OR 2.57) (all P < 0.05). New IDDM was also associated with a decreased cancer-specific survival., Conclusion: Preoperative HbA1c ≥ 6.25% and blood glucose ≥ 121 mg/dL can accurately identify patients at increased risk of IDDM. These diagnostics may help identify patients in a preoperative setting that may benefit from interventions such as diabetes education or enhanced glucose control preoperatively., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: Safe Sleep Community Baby Showers address strategies to prevent sleep-related infant deaths. Due to the COVID-19 pandemic, these events transitioned from in-person to virtual., Objective: This study describes outcomes of transitioning Safe Sleep Community Baby Showers to a virtual format and compares outcomes to previous in-person events., Methods: Participants from four rural Kansas counties were emailed the presurvey, provided educational materials (videos, livestream, or digital documents), and completed a postsurvey. Those who completed both surveys received a portable crib and wearable blanket. Within-group comparisons were assessed between pre- and postsurveys; between-group comparisons (virtual vs in-person) were assessed by postsurveys., Results: Based on data from 145 in-person and 74 virtual participants, virtual participants were more likely to be married (P<.001) and have private insurance (P<.001), and were less likely to report tobacco use (P<.001). Both event formats significantly increased knowledge and intentions regarding safe sleep and avoidance of secondhand smoke (all P≤.001). Breastfeeding intentions did not change. Differences were observed between in-person and virtual meetings regarding confidence in the ability to avoid secondhand smoke (in-person: 121/144, 84% vs virtual: 53/74, 72%; P=.03), intention to breastfeed ≥6 months (in-person: 79/128, 62% vs virtual: 52/66, 79%; P=.008), and confidence in the ability to breastfeed ≥6 months (in-person: 58/123, 47% vs virtual: 44/69, 64%; P=.02)., Conclusions: Although both event formats demonstrated increased knowledge/intentions to follow safe sleep recommendations, virtual events may further marginalize groups who are at high risk for poor birth outcomes. Strategies to increase technology access, recruit priority populations, and ensure disparities are not exacerbated will be critical for the implementation of future virtual events., (©Carolyn R Ahlers-Schmidt, Christy Schunn, Ashley M Hervey, Maria Torres, Jill Elizabeth V Nelson. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 22.11.2021.)

Introduction: The purpose of this study was to explore healthcare provider training, comfort, and provision of internet safety counseling. Prior research has demonstrated increased parental concern regarding the pervasive access to the internet by children, including the potential impacts of risky internet behavior and adverse media exposure., Methods: A self-reported survey was provided to a convenience sample of 31 healthcare providers during a mental health training seminar. Responses were analyzed using descriptive statistics., Results: Internet safety counseling, especially regarding risky online behavior, was not a focal point of provider-patient interaction in the sample population. This finding was reinforced with more than half of the respondents indicating that they infrequently or never provide internet safety counseling (n = 17, 56%). While research has placed an emphasis on the importance of discussing the risks of exposure to violence, drugs, and sexually explicit media online, this study found that the topics most often discussed were setting time limits (77%), limiting access to media devices (67%), and supervising internet use (50%). This may be due in part to the fact that most respondents (n = 17, 57%) reported never receiving training on internet safety counseling., Conclusions: Overall, significant deficits were identified in internet safety counseling training for professionals and provision of education for families. These finding were inconsistent with the American Academy of Pediatrics recommendations around media use counseling and a point of urgent concern given the increasing time spent on media devices, particularly during the COVID pandemic., (© 2021 The University of Kansas Medical Center.)

Objectives: In the United States, sleep-related deaths are one of the primary causes of death for infants age 28 days to one year. The American Academy of Pediatrics (AAP) developed Safe Sleep Recommendations which provide risk reduction strategies for sleep-related infant deaths. Interventions such as Safe Sleep Community Baby Showers have increased knowledge and intentions to engage in these safe sleep behaviors for women who speak English. This study assessed the feasibility, acceptability and initial outcomes of Safe Sleep Community Baby Showers for women who speak Spanish., Methods: Six Spanish Safe Sleep Community Baby Showers were held in Sedgwick County, Kansas. One hundred forty-six pregnant or recently delivered women who spoke Spanish completed pre- and post-assessments. Univariate comparisons were made using McNemar's test for paired dichotomous variables., Results: Participants had a high school diploma/General Educational Diploma (GED) or less (75.3%), and were uninsured (52.1%) or had Medicaid (n = 49; 33.6%). The majority reported being very satisfied (n = 130; 89.0%) or satisfied (n = 8; 5.5%). Compared to baseline, significant increases in intentions and confidence to follow the AAP Safe Sleep Recommendations were observed following the events. The majority of participants reported intending to place their infant on the back to sleep (98.6%), use only a safe surface (crib, portable crib, bassinet; 99.3%), and only include safe items (firm mattress, fitted sheet; 93.5%) (all p < .001)., Conclusions: Study findings support both feasibility and acceptability of modifying Safe Sleep Community Baby Showers to provide culturally and linguistically appropriate education for women who speak Spanish. Initial outcomes suggest increased intentions to follow safe sleep recommendations., (Copyright © 2021 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Malignant pancreatic tumors involving the celiac artery can be resected with a distal pancreatectomy, splenectomy and celiac axis resection (DP-CAR), relying on collateral flow to the liver through the gastroduodenal artery (GDA). In the current manuscript, the technical conduct of robotic DP-CAR is outlined. The greater curve of the stomach is mobilized with care to avoid sacrificing the gastroepiploic vessels. The stomach and liver are retracted cephalad to facilitate dissection of the porta hepatis. The hepatic artery (HA) is dissected and encircled with a vessel loop. The gastroduodenal artery (GDA) is carefully preserved. The common HA is clamped and triphasic flow in the proper HA via the GDA is confirmed using intra-operative ultrasound. A retropancreatic tunnel is made over the superior mesenteric vein (SMV). The pancreas is divided with an endovascular stapler at the neck. The inferior mesenteric vein (IMV) and splenic vein are ligated. The HA is stapled proximal to the GDA. The entire specimen is retracted laterally with further dissection cephalad to expose the superior mesenteric artery (SMA). The SMA is then traced back to the aorta. The dissection continues cephalad along the aorta with the bipolar energy device used to divide the crural fibers and celiac nerve plexus. The specimen is mobilized from the patient's right to left until the origin of the celiac axis is identified and oriented towards the left. The trunk is circumferentially dissected and stapled. Additional dissection with hook cautery and the bipolar energy device fully mobilizes the pancreatic tail and spleen. The specimen is removed from the left lower quadrant extraction site and one drain is left in the resection bed. A final intra-operative ultrasound of the proper HA confirms pulsatile, triphasic flow in the artery and liver parenchyma. The stomach is inspected for evidence of ischemia. Robotic DP-CAR is safe, feasible and when used in conjunction with multi-modality therapy, offers potential for long-term survival in selected patients.

As robotic surgery has become more widespread, early exposure to the robotic platform is becoming increasingly important, not only to graduate medical education, but also for medical students pursuing surgical residency. In an effort to orient students to robotic technology and decrease the learning curve for what is likely to become an integral part of residency training, we created a formal, elective robotic surgery curriculum for senior medical students. Throughout this 2-week fourth year rotation, students completed online training modules and assessment; mastered exercises on the simulator system related to the console, camera, energy, dexterity, and suturing skills; attended didactics; utilized the dual console during one-on-one simulation lab sessions with attending robotic surgery experts; and translated new skills to biotissue anastomoses as well as bedside-assisting in the operating room. During cases, students were able to have more meaningful observation experiences, recognizing the significance of various robotic approaches employed and utilization of specific instruments. Future aims of this rotation will assess student experience as it impacts readiness for surgical residency., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Sleep-related infant deaths, including Sudden Infant Death Syndrome (SIDS), are the number one cause of death in infants between 28 days and one year of life. Nearly half of families experiencing a sleep-related infant death in Kansas were involved with the Department of Children and Families Child Protective Services (CPS), making CPS staff a priority for safe sleep training. This study assessed the impact of the two-day Kansas Infant Death and SIDS (KIDS) Network Safe Sleep Instructor (SSI) train-the-trainer program on CPS staffs' knowledge of the American Academy of Pediatrics safe sleep recommendations. Training was attended by 43 participants, 27 (63%) of whom were employed by CPS. CPS staff had significantly lower baseline knowledge on the 10-item pretest ( t = 3.33, p = 0.002), but both CPS and other attendees showed significant improvement by posttest ( t = 8.53, p < 0.001 and t = 4.44, p < 0.001, respectively). Following SSI certification, CPS SSIs provided more safe sleep training to professionals than other SSIs (1051 vs. 165, respectively), and both groups of SSIs were able to significantly increase the knowledge of their trainees. Overall, the KIDS Network SSI training was successful. The innovative partnership with CPS allowed for provision of training to a group not historically targeted for safe sleep education.

Introduction: The learning curve associated with robotic pancreatoduodenectomy (RPD) is a hurdle for new programs to achieve optimal results. Since early analysis, robotic training has recently expanded, and the RPD approach has been refined. The purpose of this study is to examine RPD outcomes for surgeons who implemented a new program after receiving formal RPD training to determine if such training reduces the learning curve., Methods: Outcomes for consecutive patients undergoing RPD at a single tertiary institution were compared to optimal RPD benchmarks from a previously reported learning curve analysis. Two surgical oncologists with formal RPD training performed all operations with one surgeon as bedside assistant and the other at the console., Results: Forty consecutive RPD operations were evaluated. Mean operative time was 354 ± 54 min, and blood loss was 300 ml. Length of stay was 7 days. Three patients (7.5%) underwent conversion to open. Pancreatic fistula affected five patients (12.5%). Operative time was stable over the study and lower than the reported benchmark. These RPD operative outcomes were similar to reported surgeon outcomes after the learning curve., Conclusion: This study suggests formal robotic training facilitates safe and efficient adoption of RPD for new programs, reducing or eliminating the learning curve., (© 2020 Wiley Periodicals LLC.)

Participants recalled low- and high-priority words varying in distinctiveness in three experiments. Word priority was established by assigning point values based on font colour or conceptual category. Word distinctiveness varied across three list structures: homogeneous lists of words (same colour or category), 50/50 lists containing words in two font colours or from two categories, and isolation lists in which a word was isolated in serial position two either by colour (Experiments 1 and 2) or category (Experiment 3). Word priority was established before list presentation in Experiment 1 and after list presentation in Experiments 2 and 3. When colour priority was established before list presentation, participants recalled high-priority words better than low-priority words across all list structures. Early isolation enhanced recall for high-priority words but impaired recall for low-priority words. When colour priority was established after list presentation, neither priority nor distinctiveness enhanced recall. When category priority was established after list presentation, participants recalled high-priority words better than low-priority words, and isolation only enhanced recall when it was combined with high priority. We concluded that priority and distinctiveness combine to produce the early isolation effect, and that encoding and retrieval processes interact to enhance memory for high-priority and distinctive events.

Purpose: To determine whether participants in the Baby Talk prenatal education program were more likely to initiate breastfeeding than nonparticipants., Design: Retrospective cohort study comparing women with a singleton pregnancy who were enrolled in Baby Talk with matched controls based on zip code, maternal age, race, language spoken, and payer source., Setting: Urban Midwest county., Sample: Baby Talk participants enrolled between November 2015 and December 2016 (n = 299) and matched controls identified through vital statistics records who were not enrolled (n = 1190)., Intervention: A 12-hour prenatal education curriculum with 2.5 hours of breastfeeding content., Measures: The primary outcome was breastfeeding at hospital discharge as reported in vital statistics., Analysis: Likelihood-ratio χ 2 and Fisher exact test were used to test the significant association between categorical variables., Results: Baby Talk participants were significantly more likely to initiate breastfeeding (93.65%) than matched nonparticipants (87.48%; P = .003). Non-Hispanic white and black Baby Talk participants were more likely to initiate breastfeeding than controls (96.15% vs 89.83%; 91.03% vs 77.02%, respectively; P < .05)., Conclusions: Prenatal education has the potential to increase breastfeeding initiation among low-income women, especially non-Hispanic white and black. This study is limited as participants were from a single community, though Baby Talk was offered at 5 separate locations, and potentially from information bias as it was reliant on the accuracy of vital statistics data.

Objective: Better understand knowledge, attitudes and practices of pregnant women and mothers of infants around coronavirus disease 2019 (COVID-19)., Methods: A 58-item electronic survey was distributed to pregnant and postpartum women (infants <12 months) who were >15 years, English-speaking and enrolled in prenatal programs. Data is summarized using central tendency, frequencies and nonparametric statistics., Results: Of 114 (51 % response rate) participants, 82.5 % reported negative changes in mental status measures (e.g. stress, anxious thoughts, changes in sleep patterns). All reported risk-reduction behavior changes (e.g. handwashing/use of sanitizer, social distancing). Significant changes were reported in employment and financial status due to the pandemic. Increases in alcohol consumption among postpartum women were also reported. Few reported changes in prenatal, infant or postpartum healthcare access., Conclusion: This study provides initial insight into the knowledge, attitudes and practices of pregnant and postpartum women during the COVID-19 pandemic. This study is limited as participants represent a single Midwest community and social desirability response bias may have impacted responses. However, results may inform future interventions to support pregnant women and mothers of infants during pandemics., Practice Implications: Providers should consider the impact of such events on mental status, access to resources and changes in behaviors., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020. Published by Elsevier B.V.)

MLL is a target of chromosomal translocations in acute leukemias with poor prognosis. The common MLL fusion partner AF9 (MLLT3) can directly bind to AF4, DOT1L, BCOR, and CBX8. To delineate the relevance of BCOR and CBX8 binding to MLL-AF9 for leukemogenesis, here we determine protein structures of AF9 complexes with CBX8 and BCOR, and show that binding of all four partners to AF9 is mutually exclusive. Using the structural analyses, we identify point mutations that selectively disrupt AF9 interactions with BCOR and CBX8. In bone marrow stem/progenitor cells expressing point mutant CBX8 or point mutant MLL-AF9, we show that disruption of direct CBX8/MLL-AF9 binding does not impact in vitro cell proliferation, whereas loss of direct BCOR/MLL-AF9 binding causes partial differentiation and increased proliferation. Strikingly, loss of MLL-AF9/BCOR binding abrogated its leukemogenic potential in a mouse model. The MLL-AF9 mutant deficient for BCOR binding reduces the expression of the EYA1 phosphatase and the protein level of c-Myc. Reduction in BCOR binding to MLL-AF9 alters a MYC-driven gene expression program, as well as altering expression of SIX-regulated genes, likely contributing to the observed reduction in the leukemia-initiating cell population., Competing Interests: Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed.

Background: To investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs)., Method: The TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined., Results: Among 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P < 0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p = 0.05; TBS vs. number of tumors, p < 0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p = 0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p = 0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p = 0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p < 0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p < 0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p = 0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS., Conclusions: TBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established., Methods: The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed., Results: Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%., Conclusions: Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.

Background & Aims: Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis., Methods: We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis., Results: The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P < .001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria., Conclusions: In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the patient safety culture among the workers of a hospital institution in southern Brazil., Method: This is a cross-sectional study, which was performed with 630 hospital workers, at Santa Rosa, Rio Grande do Sul, Brazil, through the Safety Attitudes Questionnaire tool, in the month of April 2017., Results: We found positive scores in all the safety culture domains, except for the perceived stress domain., Conclusion: Job satisfaction and teamwork spirit showed better scores for nursing and health professionals, when compared to the support team. Schooling, gender, operation time and the choice of workplace positively influenced the safe atmosphere.