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Type 2 diabetes mellitus (T2DM), characterized by insulin resistance, is closely associated with Alzheimer's disease (AD). Cerebrovascular dysfunction is manifested in both T2DM and AD, and is often considered as a pathological link between the two diseases. Insulin signaling regulates critical functions of the blood-brain barrier (BBB), and endothelial insulin resistance could lead to BBB dysfunction, aggravating AD pathology. However, insulin signaling is intrinsically dynamic and involves interactions among numerous molecular mediators. Hence, a mechanistic systems biology model is needed to understand how insulin regulates BBB physiology and the consequences of its impairment in T2DM and AD. In this study, we investigated the pharmacodynamic effect of insulin on the expression of vascular cell adhesion molecule 1 (VCAM1), a marker of cerebrovascular inflammation. Intriguingly, normal insulin concentrations selectively activated the PI3K-AKT pathway, leading to decreased VCAM1 expression. However, exposure to supraphysiological insulin levels, which is present in insulin resistance, activated both PI3K-AKT and MEK-ERK pathways, and increased VCAM1 expression. We developed a mathematical model that adequately described the dynamics of various insulin signaling nodes and VCAM1 expression. Further, the model was integrated with in vitro proteomics and transcriptomics data from AD patients to simulate VCAM1 expression under pathological conditions. This approach allowed us to establish a quantitative systems pharmacology framework to investigate BBB dysfunction in AD and metabolic syndrome, thereby offering opportunities to identify specific disruptions in molecular networks that will enable us to identify novel therapeutic targets., (© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Marginal ulcers (MUs) are potential complications following Roux-en-Y gastric bypass (RYGB) surgery. Our institution performs 3 different laparoscopic gastrojejunal anastomosis (GJA) techniques. The aim of this study was to analyze the incidence of MUs between 25-mm circular stapler (CS), linear stapler (LS), and hand-sewn (HS) GJA techniques using data collected over a 10-year period., Methods: A retrospective single-institutional review of patients who underwent upper endoscopy after RYGB was queried (2010-2019). The type of GJA performed, complications, endoscopic interventions, smoking, and nonsteroidal anti-inflammatory drug (NSAID) use were analyzed., Results: Overall, 2683 RYGBs were performed (1564 CS, 883 LS, and 236 HS) and an upper endoscopy was performed in 12.4% of these patients (15.4% of CS, 8.1% of LS, and 8.1% of HS patients). The incidence of MU was 6.7% (9.2% of CS, 3.3% of LS, 3.4% of HS patients). Rates of endoscopy were higher after CS versus LS and HS GJA, and incidence of MU was higher in the CS cohort versus LS and HS. Incidence of strictures was higher after CS GJA versus LS and HS, and revision of the GJA due to MU was higher following use of a CS versus LS and HS., Conclusion: Comparing 3 common GJA techniques for RYGB, the incidence of upper endoscopy after RYGB was higher following CS GJA, and incidence of MU, stricture, and revisional surgery for MU after RYGB were high in the CS cohort., Competing Interests: Disclosures Abdelrahman Nimeri received travel honorarium from Intuitive; Keith S. Gersin is a consultant in GI Dynamics. Keith Gersin and Timothy Kuwada WL Gore honoraria speaker and received ownership interest from Standard Bariatrics. James Feimster, Leslie Okorji, B. Amy Paul, Kyle J. Thompson, Selwan Barbat, Timothy S. Kuwada, Roc Bauman, and Iain H. Mckillop have no conflicts of interest or financial ties to disclose., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

The OmicsFootPrint framework addresses the need for advanced multi-omics data analysis methodologies by transforming data into intuitive two-dimensional circular images and facilitating the interpretation of complex diseases. Utilizing deep neural networks and incorporating the SHapley Additive exPlanations algorithm, the framework enhances model interpretability. Tested with The Cancer Genome Atlas data, OmicsFootPrint effectively classified lung and breast cancer subtypes, achieving high area under the curve (AUC) scores-0.98 ± 0.02 for lung cancer subtype differentiation and 0.83 ± 0.07 for breast cancer PAM50 subtypes, and successfully distinguished between invasive lobular and ductal carcinomas in breast cancer, showcasing its robustness. It also demonstrated notable performance in predicting drug responses in cancer cell lines, with a median AUC of 0.74, surpassing nine existing methods. Furthermore, its effectiveness persists even with reduced training sample sizes. OmicsFootPrint marks an enhancement in multi-omics research, offering a novel, efficient and interpretable approach that contributes to a deeper understanding of disease mechanisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Amyloid β (A β ) deposition and neurofibrillary tangles are widely considered the primary pathological hallmarks of familial and sporadic forms of Alzheimer disease (AD). However, cerebrovascular inflammation, which is prevalent in 70% of AD patients, is emerging as another core feature of AD pathology. In our current work, we investigated the hypothesis that A β 42 exposure drives an increase in vascular cell adhesion molecule-1 (VCAM-1) expression, a cerebrovascular inflammatory marker expressed on the blood-brain barrier (BBB) endothelium in humans and murine models. We have demonstrated that the inflammation signaling pathway is upregulated in AD patient brains, and VCAM-1 expression is increased in AD patients compared with healthy controls. Furthermore, dynamic SPEC/CT imaging in APP,PS1 transgenic mice (a mouse model that overexpresses A β 42) demonstrated VCAM-1 upregulation at the BBB. Although there is a strong association between A β 42 exposure and an increase in VCAM-1 expression, the underlying mechanisms remain partially understood. Molecular mechanisms driving VCAM-1 expression at the BBB were investigated in polarized human cerebral microvascular endothelial cell monolayers. Moreover, by employing reverse-phase protein array assays and immunocytochemistry we demonstrated that A β 42 increases VCAM-1 expression via the Src/p38/MEK signaling pathway. Therefore, targeting the Src/p38/MEK pathway may help modulate VCAM-1 expression at the BBB and help mitigate cerebrovascular inflammation in Alzheimer disease. SIGNIFICANCE STATEMENT: Although considered a core pathological feature of Alzheimer disease, molecular pathways leading to cerebrovascular inflammation remain only partially understood. Moreover, clinical diagnostic methods for detecting cerebrovascular inflammation are underdeveloped. This study demonstrated the detection of VCAM-1 using radio-iodinated VCAM-1 antibody and single-photon emission computed tomography/computed tomography imaging. Additionally, exposure to A β 42 increases VCAM-1 expression on the blood-brain barrier endothelium via the Src/p38/MEK pathway. These findings are expected to aid in the development of diagnostic and therapeutic approaches for addressing cerebrovascular inflammation in AD., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

The Dissociative Experiences Scale (DES) is the most widely used self-report measure of dissociation but lacks a validity scale. Abu-Rus et al. (2020) created the DES-V by embedding atypical and inconsistency items in the DES, ultimately concluding that atypicality demonstrated the greatest ability to differentiate honest respondents from feigners. Among their study limitations, Abu-Rus et al. noted the homogeneous nature of their clinical group (i.e., largely comprising individuals with PTSD) and the potential need to refine the existing atypicality items for a more heterogenous dissociation population. The current study aimed to refine the DES-V by enlisting dissociation experts to improve the believability of the atypical items (while simultaneously ensuring they did not betoken any actual dissociative symptomology) and by supplementing the online sample with a clinical sample that included a broad range of dissociative disorders. Data cleaning comprised eight different techniques, to better ensure the validity of the online sample. Honest and Feigning groups completed the assessments through Amazon's Mechanical Turk; the clinical dissociative disorder group completed hard copy versions. The atypicality scale discriminated the three groups well, with the Feigning group scoring significantly higher than both of the honest groups (online and clinical). The mean atypicality scores of the two honest groups did not differ significantly. In addition, the scale incremented over the original DES-V in a logistic regression predicting honest and feigning participants. These robust results suggest that the revised DES-V could provide researchers with a valuable tool for validating online samples with greater precision - an increasingly vital need in light of the growing reliance on online samples.

Background: The incidence of obesity in African Americans (AAs) is higher than in non-AA in the USA. Previous studies using large national databases report that AA patients have worse outcomes than non-AA patients., Objectives: To assess perioperative outcomes among AA patients after MBS at a center of excellence (COE) that serves a large, diverse patient population., Setting: University Hospital METHODS: A retrospective analysis was performed on patients undergoing MBS between 2010 and 2020 at our two accredited MBSAQIP (Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program) COEs where the AA population makes up over 35% of the population. Preoperative variables were compared using unpaired t-test or chi-squared test where appropriate. Thirty-day outcomes were compared following propensity score matching (exact algorithm) of demographics and comorbidities., Results: Overall, 5742 patients (AA = 2058, 36%) had Roux-en-Y gastric bypass (AA = 1028, 26%) or sleeve gastrectomy (AA = 1030, 27%). AA patients were more often female (90.2% vs. 80.2%, p < 0.001) and had higher rates of hypertension (56.3% vs. 47.8%, p < 0.001), while non-AA patients had higher rates of hyperlipidemia (27.3% vs. 20.7%, p < 0.001) and obstructive sleep apnea (41.2% vs. 37.1%, p = 0.0024). Matched data showed that AA patients had higher rates of pulmonary embolism (PE) (0.3% vs. 0.1%, p = 0.020) and more emergency department visits (7.0% vs. 5.1%, p = 0.012) but no differences in mortality, readmission, reintervention, or reoperation rates., Conclusions: In a diverse area, AA patients who underwent MBS had similar perioperative outcomes compared to non-AA patients except that they experienced higher rates of PE. They also experienced higher rates of emergency department visits but had similar readmission rates., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: African Americans (AA) are widely underrepresented in plasma biomarker studies for Alzheimer's disease (AD) and current diagnostic biomarker candidates do not reflect the heterogeneity of AD., Methods: Untargeted proteome measurements were obtained using the SomaScan 7k platform to identify novel plasma biomarkers for AD in a cohort of AA clinically diagnosed as AD dementia (n=183) or cognitively unimpaired (CU, n=145). Machine learning approaches were implemented to identify the set of plasma proteins that yields the best classification accuracy., Results: A plasma protein panel achieved an area under the curve (AUC) of 0.91 to classify AD dementia vs CU. The reproducibility of this finding was observed in the ANMerge plasma and AMP-AD Diversity brain datasets (AUC=0.83; AUC=0.94)., Discussion: This study demonstrates the potential of biomarker discovery through untargeted plasma proteomics and machine learning approaches. Our findings also highlight the potential importance of the matrisome and cerebrovascular dysfunction in AD pathophysiology., Competing Interests: Conflict of Interest Statement: LAK, CDH, BMO, and MMC report no disclosures.

Strain engineering can modulate the properties of two-dimensional (2D) semiconductors for electronic and optoelectronic applications. Recent theory and experiments have found that uniaxial tensile strain can improve the electron mobility of monolayer MoS 2 , a 2D semiconductor, but the effects of biaxial strain on charge transport are not well characterized in 2D semiconductors. Here, we use biaxial tensile strain on flexible substrates to probe electron transport in monolayer WS 2 and MoS 2 transistors. This approach experimentally achieves ∼2× higher on-state current and mobility with ∼0.3% applied biaxial strain in WS 2 , the highest mobility improvement at the lowest strain reported to date. We also examine the mechanisms behind this improvement through density functional theory simulations, concluding that the enhancement is primarily due to reduced intervalley electron-phonon scattering. These results underscore the role of strain engineering in 2D semiconductors for flexible electronics, sensors, integrated circuits, and other optoelectronic applications.

Polycyclic aromatic hydrocarbon (PAH) contamination in marine environments range from low-diffusive inputs to high loads. The influence of PAH concentration on the expression of functional genes [e.g. those encoding ring-hydroxylating dioxygenases (RHDs)] has been overlooked in PAH biodegradation studies. However, understanding marker-gene expression under different PAH loads can help to monitor and predict bioremediation efficiency. Here, we followed the expression (via RNA sequencing) of Cycloclasticus pugetii strain PS-1 in cell suspension experiments under different naphthalene (100 and 30 mg L-1) concentrations. We identified genes encoding previously uncharacterized RHD subunits, termed rhdPS1α and rhdPS1β, that were highly transcribed in response to naphthalene-degradation activity. Additionally, we identified six RHD subunit-encoding genes that responded to naphthalene exposure. By contrast, four RHD subunit genes were PAH-independently expressed and three other RHD subunit genes responded to naphthalene starvation. Cycloclasticus spp. could, therefore, use genetic redundancy in key PAH-degradation genes to react to varying PAH loads. This genetic redundancy may restrict the monitoring of environmental hydrocarbon-degradation activity using single-gene expression. For Cycloclasticus pugetii strain PS-1, however, the newly identified rhdPS1α and rhdPS1β genes might be potential target genes to monitor its environmental naphthalene-degradation activity., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

A metabotropic glutamate receptor coupled to phospholipase D (PLD-mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage to PLD activation are well established and indicate it is a highly atypical glutamate receptor. A receptor with the same pharmacology is present in spindle primary sensory terminals where its blockade can totally abolish, and its activation can double, the normal stretch-evoked firing. We report here the first identification of this PLD-mGluR protein, by capitalizing on its expression in primary mechanosensory terminals, developing an enriched source, pharmacological profiling to identify an optimal ligand, and then functionalizing it as a molecular tool. Evidence from immunofluorescence, western and far-western blotting indicates PLD-mGluR is homomeric GluK2, since GluK2 is the only glutamate receptor protein/receptor subunit present in spindle mechanosensory terminals. Its expression was also found in the lanceolate palisade ending of hair follicle, also known to contain the PLD-mGluR. Finally, in a mouse model with ionotropic function ablated in the GluK2 subunit, spindle glutamatergic responses were still present, confirming it acts purely metabotropically. We conclude the PLD-mGluR is a homomeric GluK2 kainate receptor signalling purely metabotropically and it is common to other, perhaps all, primary mechanosensory endings., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: A strong body of evidence suggests that cerebrovascular pathologies augment the onset and progression of Alzheimer's disease (AD). One distinctive aspect of this cerebrovascular dysfunction is the degeneration of brain pericytes-often overlooked supporting cells of blood-brain barrier endothelium., Objective: The current study investigates the influence of pericytes on gene and protein expressions in the blood-brain barrier endothelium, which is expected to facilitate the identification of pathophysiological pathways that are triggered by pericyte loss and lead to blood-brain barrier dysfunction in AD., Methods: Bioinformatics analysis was conducted on the RNA-Seq expression counts matrix (GSE144474), which compared solo-cultured human blood-brain barrier endothelial cells against endothelial cells co-cultured with human brain pericytes in a non-contact model. We constructed a similar cell culture model to verify protein expression using western blots., Results: The insulin resistance and ferroptosis pathways were found to be enriched. Western blots of the insulin receptor and heme oxygenase expressions were consistent with those observed in RNA-Seq data. Additionally, we observed more than 5-fold upregulation of several genes associated with neuroprotection, including insulin-like growth factor 2 and brain-derived neurotrophic factor., Conclusions: Results suggest that pericyte influence on blood-brain barrier endothelial gene expression confers protection from insulin resistance, iron accumulation, oxidative stress, and amyloid deposition. Since these are conditions associated with AD pathophysiology, they imply mechanisms by which pericyte degeneration could contribute to disease progression.

Objective: To estimate the incidence and outcomes of sepsis hospitalisations in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales. Design and participants: Prospective cohort study of residents aged 45 years and older, recruited between 2006 and 2009, and followed for hospitalisation for sepsis. Main outcome measures: Incidence and hazard ratio (HR) of sepsis hospitalisation and intensive care unit (ICU) admission identified using International Classification of Diseases (10th revision) coding on discharge data. Length of stay, readmission and mortality in those admitted for sepsis. Results: Of 264 678 participants, 1928 (0.7%) identified as Aboriginal and/or Torres Strait Islander. Sepsis hospitalisation was higher in Aboriginal and Torres Strait Islander participants (8.67 v 6.12 per 1000 person-years; age- and sex-adjusted HR, 2.35; 95% CI, 1.98-2.80) but was attenuated after adjusting for sociodemographic factors, health behaviour and comorbidities (adjusted HR, 1.56; 95% CI, 1.31-1.86). Among those hospitalised for sepsis, after adjusting for age and sex, there were no differences between the proportions of Aboriginal and Torres Strait Islander and non-Indigenous participants admitted to an ICU (18.0% v 16.1%; P = 0.42) or deceased at 1 year (36.1% v 36.8%; P = 0.92). Aboriginal and Torres Strait Islander participants had shorter lengths of hospital stay (9.98 v 11.72 days; P < 0.001) and ICU stay (4.38 v 6.35 days; P < 0.001) than non-Indigenous participants. Overall, more than 70% of participants were readmitted to hospital within 1 year. Conclusion: We found that the rate of sepsis hospitalisation in NSW was higher for Aboriginal and Torres Strait Islander adults. Culturally appropriate, community-led strategies targeting chronic disease prevention and the social determinants of health may reduce this gap. Preventing readmission following sepsis is a priority for all Australians., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Background: New treatments are needed for people with treatment-resistant depression (TRD), who do not benefit from anti-depressants and many of whom do not recover fully with psychological treatments. The Community Navigator programme was co-produced with service users and practitioners. It is a novel social intervention which aims to reduce loneliness and thus improve health outcomes for people with TRD. Participants receive up to 10 individual meetings with a Community Navigator, who helps them to map their social world and set and enact goals to enhance their social connections and reduce loneliness. Participants may also access group meet-ups with others in the programme every 2 months, and may be offered modest financial support to enable activities to support social connections., Methods: A researcher-blind, multi-site, 1:1 randomised controlled trial with N = 306 participants will test the effectiveness of the Community Navigator programme for people with TRD in secondary community mental health teams (CMHTs). Our primary hypothesis is that people who are offered the Community Navigator programme as an addition to usual CMHT care will be less depressed, assessed using the PHQ-9 self-report measure, at 8-month, end-of-treatment follow-up, compared to a control group receiving usual CMHT care and a booklet with information about local social groups and activities. We will follow participants up at end-of-treatment and at 14 months, 6 months after end-of-treatment follow-up. Secondary outcomes include the following: loneliness, anxiety, personal recovery, self-efficacy, social network, social identities. We will collect data about health-related quality of life and service use to investigate the cost-effectiveness of the Community Navigator programme., Discussion: This trial will provide definitive evidence about the effectiveness and cost-effectiveness of the Community Navigator programme and whether it can be recommended for use in practice. The trial is due to finish in August 2025., Trial Registration: Prospectively registered on 8th July 2022 at: ISRCTN13205972., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Microbial degradation of petroleum hydrocarbons is a crucial process for the clean-up of oil-contaminated environments. Cycloclasticus spp. are well-known polycyclic aromatic hydrocarbon (PAH) degraders that possess PAH-degradation marker genes including rhd3α , rhd2α , and pahE . However, it remains unknown if the expression of these genes can serve as an indicator for active PAH degradation. Here, we determined transcript-to-gene (TtG) ratios with (reverse transcription) qPCR in cultures of Cycloclasticus pugetii strain PS-1 grown with naphthalene, phenanthrene, a mixture of these PAHs, or alternate substrates (i.e., no PAHs). Mean TtG ratios of 1.99 × 10 -2 , 1.80 × 10 -3 , and 3.20 × 10 -3 for rhd3α , rhd2α , and pahE , respectively, were measured in the presence or absence of PAHs. The TtG values suggested that marker-gene expression is independent of PAH degradation. Measurement of TtG ratios in Arctic seawater microcosms amended with water-accommodated crude oil fractions, and incubated under in situ temperature conditions (i.e., 1.5°C), only detected Cycloclasticus spp. rhd2α genes and transcripts (mean TtG ratio of 4.15 × 10 -1 ). The other marker genes- rhd3α and pahE- were not detected, suggesting that not all Cycloclasticus spp. carry these genes and a broader yet-to-be-identified repertoire of PAH-degradation genes exists. The results indicate that the expression of PAH marker genes may not correlate with PAH-degradation activity, and transcription data should be interpreted cautiously., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vogel, Thompson, Straub, App, Gutierrez, Löffler and Kleindienst.)

Background: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Patients with TNBC are primarily treated with neoadjuvant chemotherapy (NAC). The response to NAC is prognostic, with reductions in overall survival and disease-free survival rates in those patients who do not achieve a pathological complete response (pCR). Based on this premise, we hypothesized that paired analysis of primary and residual TNBC tumors following NAC could identify unique biomarkers associated with post-NAC recurrence., Methods and Results: We investigated 24 samples from 12 non-LAR TNBC patients with paired pre- and post-NAC data, including four patients with recurrence shortly after surgery (< 24 months) and eight who remained recurrence-free (> 48 months). These tumors were collected from a prospective NAC breast cancer study (BEAUTY) conducted at the Mayo Clinic. Differential expression analysis of pre-NAC biopsies showed minimal gene expression differences between early recurrent and nonrecurrent TNBC tumors; however, post-NAC samples demonstrated significant alterations in expression patterns in response to intervention. Topological-level differences associated with early recurrence were implicated in 251 gene sets, and an independent assessment of microarray gene expression data from the 9 paired non-LAR samples available in the NAC I-SPY1 trial confirmed 56 gene sets. Within these 56 gene sets, 113 genes were observed to be differentially expressed in the I-SPY1 and BEAUTY post-NAC studies. An independent (n = 392) breast cancer dataset with relapse-free survival (RFS) data was used to refine our gene list to a 17-gene signature. A threefold cross-validation analysis of the gene signature with the combined BEAUTY and I-SPY1 data yielded an average AUC of 0.88 for six machine-learning models. Due to the limited number of studies with pre- and post-NAC TNBC tumor data, further validation of the signature is needed., Conclusion: Analysis of multiomics data from post-NAC TNBC chemoresistant tumors showed down regulation of mismatch repair and tubulin pathways. Additionally, we identified a 17-gene signature in TNBC associated with post-NAC recurrence enriched with down-regulated immune genes., (© 2023. The Author(s).)

Objectives: Economic evaluations of intensive care unit (ICU) interventions have specific considerations, including how to cost ICU stays and accurately measure quality of life in survivors. The aim of this article was to develop best practice recommendations for economic evaluations alongside future ICU randomised controlled trials (RCTs)., Review Methods: We collated our experience based on expert consensus across several recent economic evaluations to provide best-practice, practical recommendations for researchers conducting economic evaluations alongside RCTs in the ICU. Recommendations were structured according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) Task Force Report., Results: We discuss recommendations across the components of economic evaluations, including: types of economic evaluation, the population and sample size, study perspective, comparators, time horizon, choice of health outcomes, measurement of effectiveness, measurement and valuation of quality of life, estimating resources and costs, analytical methods, and the increment cost-effectiveness ratio. We also provide future directions for research with regard to developing more robust economic evaluations for the ICU., Conclusion: Economic evaluations should be built alongside ICU RCTs and should be designed a priori using appropriate follow-up and data collection to capture patient-relevant outcomes. Further work is needed to improve the quality of data available for linkage in Australia as well as developing costing methods for the ICU and appropriate quality of life measurements., (Copyright © 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

A major source of anthropogenic polycyclic aromatic hydrocarbon (PAH) inputs into marine environments are diffuse emissions which result in low PAH concentrations in the ocean water, posing a potential threat for the affected ecosystems. However, the remediation of low-dosage PAH contaminations through microbial processes remains largely unknown. Here, we developed a process-based numerical model to simulate batch cultures receiving repeated low-dosage naphthalene pulses compared to the conventionally used one-time high-dosage. Pulsing frequency as well as dosage concentration had a large impact on the degradation efficiency. After 10 days, 99.7%, 97.2%, 86.6%, or 83.5% of the 145 mg L -1 naphthalene was degraded when given as a one-time high-dosage or in 2, 5, or 10 repeated low-concentration dosages equally spaced throughout the experiment, respectively. If the simulation was altered, giving the system that received 10 pulses time to recover to 99.7%, pulsing patterns affected the degradation of naphthalene. When pulsing 10 days at once per day, naphthalene accumulated following each pulse and if the degradation was allowed to continue until the recovered state was reached, the incubation time was prolonged to 17 days with a generation time of 3.81 days. If a full recovery was conditional before the next pulse was added, the scenario elongated to 55 days and generation time increased to 14.15 days. This indicates that dissolution kinetics dominate biodegradation kinetics, and the biomass concentration of PAH-degrading bacteria alone is not a sufficient indicator for quantifying active biodegradation. Applying those findings to the environment, a one-time input of a high dosage is potentially degraded faster than repeated low-dosage PAH pollution and repeated low-dosage input could lead to PAH accumulation in vulnerable pristine environments. Further research on the overlooked field of chronic low-dosage PAH contamination is necessary., (© 2023. The Author(s).)

The current study assessed the reliability and validity of three measures of dissociation. Three hundred students completed the Dissociative Experiences Scale Revised (DESR), the Dissociative Experiences Scale-II (DES-II), and the Dissociative Experiences Scale Comparison (DESC); an additional 252 community adults evaluated clarity of instructions. Findings revealed that the three dissociation measures showed acceptable test-retest reliability and Cronbach's alphas. The DESR and DES-II strongly intercorrelated, but the DESC correlated only moderately with the two remaining dissociation measures, sharing less than 10% of the variance with the original scale. Additionally, the DESR and DES-II showed stronger convergent validity (correlation with measures of alexithymia and post-traumatic stress disorder) than did the DESC. The DESC was the only measure unrelated to trauma history. Participants reported substantially greater difficulty in understanding and utilizing the metric offered by the DESC. In conclusion, evidence supports the DES-II and DESR as alternate measures, but the DESC requires more investigation.

Background: Obesity rates in Hispanics and African Americans (AAs) are higher than in Caucasians in the USA, yet the rate of metabolic and bariatric surgery (MBS) for weight loss remains lower for both Hispanics and AAs., Methods: Patient demographics and outcomes of adult AA and Hispanic patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedures were analyzed using the MBSAQIP dataset [2015-2018] using unmatched and propensity-matched data., Results: In total, 173,157 patients were included, of whom 98,185 were AA [56.7%] [21,163-RYGB; 77,022-SG] and 74,972 were Hispanic [43.3%] [20,282-RYGB; 54,690-SG]). Preoperatively, the AA cohort was older, had more females, and higher BMIs with higher rates of all tracked obesity-related medical conditions except for diabetes, venous stasis, and prior foregut surgery. Intra- and postoperatively, AAs were more likely to experience major complications including unplanned ICU admission, 30-day readmission/reintervention, and mortality. After propensity matching, the differences in ED visits, treatment for dehydration, 30-day readmission, 30-day intervention, and pulmonary embolism remained for both SG and RYGB cohorts. Progressive renal insufficiency and ventilator use lost statistical significance in both cohorts. Conversely, 30-day reoperation, postoperative ventilator requirement, unplanned intubation, unplanned ICU admission, and mortality lost significance in the RYGB cohort, but not SG patients., Conclusion: Outcomes for AA patients were worse than for Hispanic patients, even after propensity matching. After matching, differences in major complications and mortality lost significance for RYGB, but not SG. These data suggest that outcomes for RYGB may be driven by the presence and severity of pre-existing patient-related factors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The aim of this study was to evaluate the impact of the COVID-19 pandemic on volume and outcomes of Acute Care Surgery patients, and we hypothesized that inpatient mortality would increase due to COVID+ and resource constraints., Methods: An American College of Surgeons verified Level I Trauma Center's trauma and operative emergency general surgery (EGS) registries were queried for all patients from Jan. 2019 to Dec. 2020. April 1st, 2020, was the demarcation date for pre- and during COVID pandemic. Primary outcome was inpatient mortality., Results: There were 14,460 trauma and 3091 EGS patients, and month-over-month volumes of both remained similar (p > 0.05). Blunt trauma decreased by 7.4% and penetrating increased by 31%, with a concomitant 25% increase in initial operative management (p < 0.001). Despite this, trauma (3.7%) and EGS (2.9-3.0%) mortality rates remained stable which was confirmed on multivariate analysis; p > 0.05. COVID + mortality was 8.8% and 3.7% in trauma and EGS patients, respectively., Conclusion: Acute Care Surgeons provided high quality care to trauma and EGS patients during the pandemic without allowing excess mortality despite many hardships and resource constraints., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fatty acid binding protein-4 ( FABP4 ) is not normally expressed in the liver but is induced in alcohol-dependent liver disease (ALD)). This study sought to identify mechanisms whereby ethanol (EtOH) metabolism alters triglyceride accumulation and FABP4 production. Human hepatoma cells which were stably transfected to express alcohol dehydrogenase (ADH) or cytochrome P4502E1 (CYP2E1) were exposed to EtOH in the absence/presence of inhibitors of ADH (4-methylpyrazole) or CYP2E1 (chlormethiazole). Cells were analyzed for free fatty acid (FFA) content and FABP4 mRNA, then culture medium assayed for FABP4 levels. Cell lysates were analyzed for AMP-activated protein kinase-α (AMPKα), Acetyl-CoA carboxylase (ACC), sterol regulatory element binding protein-1c (SREBP-1c), and Lipin-1β activity and localization in the absence/presence of EtOH and pharmacological inhibitors. CYP2E1-EtOH metabolism led to increased FABP4 mRNA/protein expression and FFA accumulation. Analysis of signaling pathway activity revealed decreased AMPKα activation and increased nuclear-SREBP-1c localization following CYP2E1-EtOH metabolism. The role of AMPKα-SREBP-1c in regulating CYP2E1-EtOH-dependent FFA accumulation and increased FABP4 was confirmed using pharmacological inhibitors and over-expression of AMPKα. Inhibition of ACC or Lipin-1β failed to prevent FFA accumulation or changes in FABP4 mRNA expression or protein secretion. These data suggest that CYP2E1-EtOH metabolism inhibits AMPKα phosphorylation to stimulate FFA accumulation and FABP4 protein secretion via an SREBP-1c dependent mechanism.

Introduction: The interaction between activated hepatic stellate cells (aHSCs) and macrophages is central to liver fibrosis development. The cargo contained within aHSC exosomes (aHSC-EXOs) and how aHSC-EXOs affect macrophage function is poorly understood., Methods: RNA from aHSC-EXOs was separated into small (<200-basepairs) and large (≥200-basepairs) RNA species, transfected into macrophages, and macrophage IL-6 and TNFα mRNA expression and protein secretion measured. Next generation sequencing was performed on EXOs from rat quiescent and aHSCs and human aHSCs. aHSCs were transfected with siRNA against ectodysplasin-A (EDA), EXOs collected, and their effect on macrophage function analyzed. Human cirrhotic liver was analyzed for EDA mRNA expression and compared to non-tumor liver (NTL)., Results: Transfection with large RNA from aHSC-EXOs stimulated macrophage IL-6 and TNFα mRNA expression and protein secretion. EDA mRNA was highly expressed in aHSCs and transfection of aHSCs with EDA-siRNA decreased aHSC-EXO EDA mRNA and blunted the effect of aHSC-EXOs on macrophage function (IL-6/TNFα expression and macrophage migration). Human cirrhotic liver exhibited high EDA mRNA compared to NTL., Conclusions: HSC activation leads to altered EXO mRNA/miRNA profiles with aHSC-EXOs mRNAs exerting a dominant role in altering macrophage function. Ectodysplasin-A mRNA is an important component in aHSC-EXOs in regulating macrophage function., Competing Interests: Declaration of competing interest The authors have no disclosures to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nonresponse is a common problem in survey sampling. Appropriate treatment can be challenging, especially when dealing with detailed breakdowns of totals. Often, the nearest neighbor imputation method is used to handle such incomplete multinomial data. In this article, we investigate the nearest neighbor ratio imputation estimator, in which auxiliary variables are used to identify the closest donor and the vector of proportions from the donor is applied to the total of the recipient to implement ratio imputation. To estimate the asymptotic variance, we first treat the nearest neighbor ratio imputation as a special case of predictive matching imputation and apply the linearization method of Yang and Kim (2020). To account for the non-negligible sampling fractions, parametric and generalized additive models are employed to incorporate the smoothness of the imputation estimator, which results in a valid variance estimator. We apply the proposed method to estimate expenditures detail items based on empirical data from the 2018 collection of the Service Annual Survey, conducted by the United States Census Bureau. Our simulation results demonstrate the validity of our proposed estimators and also confirm that the derived variance estimators have good performance even when the sampling fraction is non-negligible.

Competing Interests: The authors report no conflicts of interest.

Objective: Although many screening tools, resources, and programs for identifying victims of human trafficking exist, consensus is lacking on which tools are most useful, which have been validated, and whether they are effective. The objectives of this study were to determine what tools exist to identify or screen for victims of human trafficking in health care settings and whether these tools have been validated., Method: We conducted a scoping review of the literature on human trafficking identification in health care settings following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) protocol for scoping reviews. We searched the MEDLINE, PsycInfo, Embase, and Scopus databases without language or date limitations. Two independent reviewers screened each citation. We included human research studies in English with populations of all ages, all genders, all geographic locations, and using quantitative and/or qualitative research methods. We excluded studies that were not conducted in a health care setting, review articles, and meta-analyses. We summarized additional screening tools available online and identified through hand-searching., Results: Database searches yielded 8730 studies, of which 4806 remained after removing duplicates. We excluded 4720 articles based on title/abstract review, we reviewed 85 full-text studies for eligibility, and we included 8 articles. Hand-searching revealed 9 additional screening tools not found in the literature. Through our search for validated screening tools, only 6 had been studied for validation in health care settings., Conclusions: Few studies have evaluated screening tools for identifying victims of human trafficking in health care settings. The absence of a gold standard for human trafficking screening and lack of consensus on the definition of human trafficking make screening tool validation difficult. Further research is required for the development of safe, effective approaches to patient screening.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with low overall survival rates and high molecular heterogeneity; therefore, few targeted therapies are available. The luminal androgen receptor (LAR) is the most consistently identified TNBC subtype, but the clinical utility has yet to be established. Here, we constructed a novel genomic classifier, LAR-Sig, that distinguishes the LAR subtype from other TNBC subtypes and provide evidence that it is a clinically distinct disease. A meta-analysis of seven TNBC datasets ( n = 1086 samples) from neoadjuvant clinical trials demonstrated that LAR patients have significantly reduced response (pCR) rates than non-LAR TNBC patients (odds ratio = 2.11, 95% CI: 1.33, 2.89). Moreover, deconvolution of the tumor microenvironment confirmed an enrichment of luminal epithelium corresponding with a decrease in basal and myoepithelium in LAR TNBC tumors. Increased immunosuppression in LAR patients may lead to a decreased presence of cycling T-cells and plasma cells. While, an increased presence of myofibroblast-like cancer-associated cells may impede drug delivery and treatment. In summary, the lower levels of tumor infiltrating lymphocytes (TILs), reduced immune activity in the micro-environment, and lower pCR rates after NAC, suggest that new therapeutic strategies for the LAR TNBC subtype need to be developed., (© The Author(s) 2022. Published by Oxford University Press on behalf of NAR Cancer.)

Purpose: To examine the association of sex with hospitalisation due to sepsis and related outcomes., Methods: Prospective cohort study of 264,678 adults, average age 62.7 years at recruitment (2006-2009) in Australia. Participants were followed for sepsis hospitalisation identified using the International Classification of Diseases coding. Outcomes included sex differences in the risk of an incident sepsis hospitalisation, mortality, length of ICU and hospital stay and readmissions during the following year., Results: Over 2,070,343 years of follow-up there were 12,912 sepsis hospitalisations, 59.6% in men. Age-standardised risk of hospitalisation was higher in men versus women (10.37 vs 6.77 per 1,000 person years; age-adjusted HR 1.58; 95% CI 1.53-1.59) and did not attenuate after adjusting for sociodemographics, health behaviours and co-morbidities. Relative risks were similar for sepsis-related ICU admissions (adjusted HR 1.72; 95% CI 1.57-1.88). Death at one year was more common in men than women (39.3% vs 33.7% p<0.001). After adjusting for age, men had a longer hospital (12.0 vs 11.2 days; p<0.001) and ICU (6.5 vs 5.8 days; p<0.001) stays and were more likely to be readmitted to hospital for sepsis (22.3 vs 19.4%; p<0.001) or any reason (73.0% vs 70.7%; p<0.001) at one year., Conclusion: In older adults, compared to women, men are at an increased risk of sepsis hospitalisation, sepsis-related ICU admission, death and readmission to hospital within one year after a sepsis hospitalisation. Understanding these sex differences and their mechanisms may offer opportunities for better prevention and management and improved patient outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Hepatic steatosis is an early pathology of alcohol-associated liver disease (ALD). Fatty acid-binding protein-4 (FABP4, a FABP not normally produced in the liver) is secreted by hepatocytes in ALD and stimulates hepatoma proliferation and migration. This study sought to investigate the mechanism[s] by which hepatic ethanol metabolism regulates FABP4 and steatosis., Methods: Human hepatoma cells (HepG2/HuH7) and cells stably transfected to express cytochrome P450 2E1 (CYP2E1), were exposed to ethanol in the absence or presence of chlormethiazole (a CYP2E1-inhibitor; CMZ) and/or EX-527 (a sirtuin-1 [SIRT1] inhibitor). The culture medium was analyzed for ethanol metabolism and FABP4 protein abundance. Cells were analyzed for FABP4 mRNA expression, SIRT1 protein abundance, and neutral lipid accumulation. In parallel, cells were analyzed for forkhead box O1 [FOXO1], β-catenin, peroxisome proliferator-activated receptor-α [PPARα], and lipin-1α protein abundance in the absence or presence of ethanol and pharmacological inhibitors of the respective target proteins., Results: CYP2E1-dependent ethanol metabolism inhibited the amount of SIRT1 protein detected, concomitant with increased FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation, effects abolished by CMZ. Analysis of pathways associated with lipid oxidation revealed increased FOXO1 nuclear localization and decreased β-catenin, PPARα, and lipin-1α protein levels in CYP2E1-expressing cells in the presence of ethanol. Pharmacological inhibition of SIRT1 mimicked the effects of ethanol, while inhibition of FOXO1 abrogated the effect of ethanol on FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation in CYP2E1-expressing cells. Pharmacological inhibition of β-catenin, PPARα, or lipin-1α failed to alter the effects of ethanol on FABP4 or neutral lipid accumulation., Conclusion: CYP2E1-dependent ethanol metabolism inhibits SIRT1-FOXO1 signaling, which leads to increased FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation. These data suggest that FABP4 released from steatotic hepatocytes could play a role in promoting tumor cell expansion in the setting of ALD and represents a potential target for therapeutic intervention., (© 2022 by the Research Society on Alcoholism.)

Introduction: For patients with super obesity (BMI > 50 kg/m 2 ), biliopancreatic diversion/duodenal switch (BPD/DS) can be an effective bariatric operation. Technical challenges and patient safety concerns, however, have limited its use as a primary procedure. This study sought to assess the safety of primary versus revisional BPD/DS., Materials and Methods: The MBSAQIP database was queried for primary and revisional BPD/DS (2015-2018). Inclusion criteria were patients ≥ 18 years of age, BMI > 50 kg/m 2 , and with no concurrent procedures. Preoperative variables were compared using a chi-square test or Wilcoxon two-sample tests. Multivariate logistic or robust linear regression models were used to compare outcomes., Results: There were 3,378 primary BPD/DS and 487 revisional BPD/DS patients. Primary BPD/DS patients had higher BMI (56.5 [IQR4.4] versus 54.8 [IQR4] kg/m 2 , p < 0.0001) and had more diabetes mellitus type II (29.1% versus 17.2%, p < 0.0001). Intraoperatively, revisional BPD/DS had longer operative time (165 [IQR47] min versus 139 [IQR100] min, p < 0.0001). After adjusting for preoperative characteristics, there was no difference in 30-day readmission or ED visits (primary 12.9% versus revisional 14.6%), reoperation or reintervention (primary 5.7% versus revisional 7.8%), or mortality (primary 0.4% versus revisional 0.6%). In contrast, the revisional BPD/DS patients had higher odds of major morbidity (primary 3.4% versus revisional 5.3%, OR 1.9, CI 1.1-3.2, p = 0.019)., Conclusions: Revisional BPD/DS is associated with higher morbidity than primary BPD/DS in patients with super obesity. These patients should thus be counselled appropriately when choosing a primary or revisional bariatric procedure., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of the study was to determine whether adjunctive hydrocortisone reduced healthcare expenditure and was cost-effective compared with placebo in New Zealand patients in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial., Design: This is a health economic analysis using data linkage to New Zealand Ministry of Health databases to determine resource use, costs, and cost-effectiveness for a 24-month period., Setting: The study was conducted in New Zealand., Participants and Intervention: Patients with septic shock were randomised to receive a 7-day continuous infusion of 200 mg of hydrocortisone or placebo in the ADRENAL trial., Main Outcome Measures: Healthcare expenditure was associated with all hospital admissions, emergency department presentations, outpatient visits, and pharmacy expenditure. Effectiveness outcomes included mortality at 6 months and 24 months and quality of life at 6 months. Cost-effectiveness outcomes were assessed with reference to quality-adjusted life years gained at 6 months and life years gained at 24 months., Results: Of 3800 patients in the ADRENAL trial, 419 (11.0%) were eligible, and 405 (96.7% of those eligible) were included. The mean total costs per patient over 24 months were $143,627 ± 100,890 and $143,772 ± 97,117 for the hydrocortisone and placebo groups, respectively (p = 0.99). Intensive care unit costs for the index admission were $50,492 and $62,288 per patient for the hydrocortisone and placebo groups, respectively (p = 0.09). The mean number of quality-adjusted life years gained at 6 months and mean number of life years gained at 24 months was not significantly different by treatment group, and the probability of hydrocortisone being cost-effective was 55% at 24 months., Conclusions: In New Zealand, adjunctive hydrocortisone did not reduce total healthcare expenditure or improve outcomes compared with placebo in patients with septic shock., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Roux-en-Y gastric bypass (RYGB) is an established surgical treatment for obesity. Variations in limb length during RYGB procedures have been investigated for optimizing weight loss while minimizing nutritional deficiencies. The role of the total alimentary limb length (TALL; Roux limb plus common channel [CC]), however, is poorly defined., Objective: Compare TALL in RYGB procedures for weight loss outcomes and malnutrition., Setting: Systematic review., Methods: Ovid Medline and PubMed databases were searched for entries between 1993 and 2020. Search terms included "gastric bypass" and "TALL." Two independent reviewers screened the results., Results: A total of 21 studies measured TALL in RYGB. Of these, 4 of 6 reported a relationship between TALL and weight loss. Additionally, 11 studies reported that when TALL was ≤400 cm and CC <200 cm, 3.4% to 63.6% of patients required limb lengthening for protein malnutrition., Conclusions: The majority of studies on RYGB do not report TALL length. There is some evidence that weight loss is affected by shortening TALL, while a TALL ≤400 cm with CC<200 should be avoided due to severe protein malnutrition. More studies on the effect of TALL are needed., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Laparoscopy has enjoyed improvements over the last three decades primarily in achieving high definition, but the 70° field of view (FOV) remains unchanged. Complications related to events that take place out of the FOV continue to be reported. Additional problems leading to poor visualization are fogging and smoke accumulation. A novel laparoscopic system (SurroundScope, 270Surgical) was developed and dramatically expands the FOV from the 70° to 270° by adding side cameras at the distal tip of the laparoscope, while LED illumination eliminates fogging and improves smoke effects. This study describes the initial clinical experience with SurroundScope and its potential advantages over traditional laparoscopy., Methods: SurroundScope was studied at Bnai Zion Medical Center in Israel and the Minnesota Institute for Minimally Invasive Surgery in America. 27 laparoscopic surgeries were performed, and at the end of each procedure, evaluations were completed by all surgeons and camera holders., Results: All 27 cases were completed successfully without adverse events. No injuries occurred as a result of surgical tool manipulation outside of the central frame while 133 potentially adverse events were identified on side frames. There was no fogging across the 27 cases. The impact of smoke was negligible in all cases, as laparoscope removal or venting was never necessary. Surgeon respondents indicated that tools could be followed from the port to the site of surgery without camera manipulation. Most surgeons strongly agreed that the potential to identify bleeding was improved. Camera holders strongly agreed that the ergonomics were improved and that they moved the camera less than with a standard laparoscope., Conclusions: Initial results demonstrate numerous advantages for SurroundScope as compared to traditional laparoscopy. The important benefits of expanded FOV, complete lack of fogging, and negligible smoke may improve patient safety, reduce adverse events and the duration of surgery. Further investigation to quantify these benefits is recommended., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Marginal ulceration (MU) is a common long-term complication following Roux-en-Y gastric bypass (RYGB). The causes of MU after RYGB are multifactorial and include surgical technique of constructing the gastrojejunal anastomosis (GJA). The purpose of this study is to evaluate the relationship between gastric pouch size in RYGB and MU using CT volumetrics., Material and Methods: Patients were retrospectively identified who underwent esophagogastroduodenoscopy (EGD) following RYGB at a tertiary care teaching hospital. Measurement of gastric pouch size was performed using 3-D CT software. Standard statistical methods were used, a univariate comparison was performed between MU and non-MU patients followed by a propensity-matched comparison to control for factors known to affect MU, and a propensity-matched subgroup analysis was also performed., Results: In total, 122 patients met criteria, 57 of which had MU on EGD and 65 who did not. The MU group had more smokers and patients with PPI use than the non-MU group, and the mean time from operation to CT scan was 26.6 months (range: 0-108 months). The MU group had a larger gastric pouch size than the non-MU group (34.1 ± 11.8 versus 20.1 ± 6.8 cm 3 ). When analyzed for matched patient cohorts, this difference remained for the MU group that included smokers and PPI use. When stratified for pouch size, for each 5 cm 3 increase in pouch size, patients had 2.4 times odds increase of MU formation., Conclusions: CT volumetric analysis demonstrated that a larger gastric pouch size was associated with MU following RYGB., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Triple Negative Breast Cancer (TNBC) accounts for 15-20% of all breast cancer cases, yet is responsible for a disproportionately high percentage of breast cancer mortalities. Thus, there is an urgent need to identify novel biomarkers and therapeutic targets based on the molecular events driving TNBC pathobiology. Estrogen receptor beta (ERβ) is known to elicit anti-cancer effects in TNBC, however its mechanisms of action remain elusive. Here, we report the expression profiles of ERβ and its association with clinicopathological features and patient outcomes in the largest cohort of TNBC to date. In this cohort, ERβ was expressed in approximately 18% of TNBCs, and expression of ERβ was associated with favorable clinicopathological features, but correlated with different overall survival outcomes according to menopausal status. Mechanistically, ERβ formed a co-repressor complex involving enhancer of zeste homologue 2/polycomb repressive complex 2 (EZH2/PRC2) that functioned to suppress oncogenic NFκB/RELA (p65) activity. Importantly, p65 was shown to be required for formation of this complex and for ERβ-mediated suppression of TNBC. Our findings indicate that ERβ+ tumors exhibit different characteristics compared to ERβ- tumors and demonstrate that ERβ functions as a molecular switch for EZH2, repurposing it for tumor suppressive activities and repression of oncogenic p65 signaling., (© 2022. The Author(s).)

This paper presents a probabilistic method of record linkage, developed using the U.S. full count censuses of 1900 and 1910 but applicable to many sources of digitized historical records. The method links records using a two-step approach, first establishing high confidence matches among men by exploiting a comprehensive set of individual and contextual characteristics. The method then proceeds to link both men and women by leveraging links between households established in the first step. While only the first stage links can be directly comparable to other popular methods in research on the U.S., our method yields both considerably higher linkage rates and greater accuracy while only performing negligibly worse than other algorithms in resembling the target population., Competing Interests: Disclosure statement: No conflicts of interest to report

The capillary force can peel off a substrate-attached film if the adhesion energy ( G w ) is low. Capillary peeling has been used as a convenient, rapid, and nondestructive method for fabricating free-standing thin films. However, the critical value of G w , which leads to the transition between peeling and sticking, remains largely unknown. As a result, capillary peeling remains empirical and applicable to a limited set of materials. Here, we investigate the critical value of G w and experimentally show the critical adhesion ( G w,c ) to scale with the water-film interfacial energy (≈0.7γ fw ), which corresponds well with our theoretical prediction of G w,c = γ fw . Based on the critical adhesion, we propose quantitative thermodynamic guidelines for designing thin film interfaces that enable successful capillary peeling. The outcomes of this work present a powerful technique for thin film transfer and advanced nanofabrication in flexible photovoltaics, battery materials, biosensing, translational medicine, and stretchable bioelectronics.

Purpose: Ex vivo hepatectomy is the incorporation of liver transplant techniques in the non-transplant setting, providing opportunity for locally advanced tumors found conventionally unresectable. Because the procedure is rare and reports in the literature are limited, we sought to perform a systematic review and meta-analysis investigating technical variations of ex vivo hepatectomies., Methods: In the literature, there is a split in those performing the procedure between venovenous bypass (VVB) and temporary portacaval shunts (PCS). Of the 253 articles identified on the topic of ex vivo resection, 37 had sufficient data to be included in our review., Results: The majority of these procedures were performed for hepatic alveolar echinococcosis (69%) followed by primary and secondary hepatic malignancies. In 18 series, VVB was used, and in 18, a temporary PCS was performed. Comparing these two groups, intraoperative variables and morbidity were not statistically different, with a cumulative trend in favor of PCS. Ninety-day mortality was significantly lower in the PCS group compared to the VVB group (p=0.03)., Conclusion: In order to better elucidate these differences between technical approaches, a registry and consensus statement are needed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: Patients undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) are at risk of developing strictures of the gastrojejunal anastomosis (GJA). Several variables can affect this, one of which may be the method of anastomosis. Between 2010 and 2014, our institution utilized three different anastomotic techniques for creating the GJA (25 mm end-to-end circular-stapled (CS), linear-stapled (LS), and robotic hand sewn (HS)). Our objectives were to compare the method of GJA relative to the subsequent development of anastomotic stricture., Methods: We queried our electronic health record for all patients who underwent an upper endoscopy (EGD) after RYGB (2010-2014). Patient charts were retrospectively reviewed for type of GJA, weight loss, complications, interventions, and revisions of the GJA., Results: In total, 1112 RYGB were performed at our institute, and 17.4% of patients (194/1112) had an upper endoscopy (EGD). Overall, 3.1% (34/1112) were found to have a stricture of the GJA. Patients undergoing a CS, LS, and HS anastomosis had GJA stricture rates of 4.9%, 0.5%, and 1.2% respectively (CS to LS (p < 0.05), p = NS among CS vs. HS, and LS vs. HS). The rate of GJA revision was 1.5%, 0.5%, and 0.1% (p = NS). In patients who had an EGD, excess BMI loss was 57.4%, 64.6%, and 59.2% (p = NS). In patients symptomatic from strictures, excess BMI loss was 69.4%, 83%, and 63.5% respectively (p = NS)., Conclusion: The anastomotic technique for creating of the GJA may impact the formation of strictures. Based on our experience, gastrojejunostomies created with a 2-mm EEA-stapling technique are at higher risk of strictures., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Programmed death ligand 1 [PD-(L)1]-targeted therapies have shown modest survival benefit in triple-negative breast cancer (TNBC). PD-L1 + microenvironments in TNBC are not well characterized and may inform combinatorial immune therapies. Herein, we characterized clinicopathologic features, RNA-based immune signatures, and spatially defined protein-based tumor-immune microenvironments (TIME) in early-stage PD-L1 + and PD-L1 - TNBC., Experimental Design: From a large cohort of chemotherapy-naïve TNBC, clinicopathologic features, deconvoluted RNA immune signatures, and intraepithelial and stromal TIME (Nanostring GeoMX) were identified in subsets of PD-L1 + and PD-L1 - TNBC, as defined by FDA-approved PD-L1 companion assays., Results: 228 of 499 (46%) TNBC were PD-L1 + (SP142: ≥1% immune cells-positive). Using PD-L1 22C3, 46% had combined positive score (CPS) ≥ 1 and 16% had CPS ≥10. PD-L1 + TNBC were higher grade with higher tumor-infiltrating lymphocytes (TIL; P < 0.05). PD-L1 was not associated with improved survival following adjustment for TILs and other variables. RNA profiles of PD-L1 + TNBC had increased dendritic cell, macrophage, and T/B cell subset features; and decreased myeloid-derived suppressor cells. PD-L1+ stromal and intraepithelial TIMEs were highly enriched in IDO-1, HLA-DR, CD40, and CD163 compared with PD-L1-TIME, with spatially specific alterations in CTLA-4, Stimulator of Interferon Genes (STING), and fibronectin. Macrophage- and antigen presentation-related proteins correlated most strongly with PD-L1 protein., Conclusions: In this early-stage TNBC cohort, nearly 50% were PD-L1 + (SP142 companion assay) while 16% were PD-L1 + with the 22C3 companion assay. PD-L1 + TNBC had specific myeloid-derived and lymphoid features. Spatially defined PD-L1 + TIME were enriched in several clinically actionable immune proteins. These data may inform future studies on combinatorial immunotherapies for patients with PD-L1 + TNBC. See related commentary by Symmans, p. 5446 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: Marginal ulceration (MU) and bleeding are possible complications following laparoscopic Roux-en-Y gastric bypass (RYGB). Our institution utilizes three techniques for performing the gastrojejunal anastomosis (GJA), providing a means to compare postoperative MU and bleeding as it relates to GJA technique., Objectives: We sought to analyze the incidence of MU and bleeding between the 25-mm end-to-end anastomosis (EEA) stapler, linear stapler (LS), and robotic hand-sewn (RHS) GJA techniques., Methods: Electronic health records for all patients who had an upper endoscopy (EGD) after RYGB were queried (2010-2014). Charts were retrospectively reviewed for type of GJA, complications, endoscopic interventions, and smoking and NSAID use., Results: Out of 1112 RYGBs, the GJA was created using an EEA, LS, or RHS approach in 58.6%, 33.6%, and 7.7% of patients, respectively. 17.4% had an EGD (19.9% EEA, 13.9% LS, and 14.0% RHS). Incidence of MU was 7.3% (9.3% EEA, 4.8% LS, and 5.8% RHS). Rates of EGD and MU were significantly higher after EEA vs. LS GJA (p<0.05). The bleeding rate was 1.5%, [1.1% EEA, 2.1% LS, and 2.3% RHS (p=NS)]. MU within 90 days of RYGB occurred in 4.1%, 0.8%, and 4.7%, respectively (p<0.05 for EEA vs LS only). NSAID and cigarette use were identified in 29.3%, 38.9%, and 60% and 17.2%, 22.2%, and 20%, respectively, for the EEA, LS, and RHS GJA (p=NS)., Conclusion: The method of GJA has an impact on rate of MU formation. A GJA fashioned with a 25-mm EEA stapler tends to have higher rates of EGD and MU.

Background: The aim of this study was to investigate outcomes associated with neoadjuvant chemotherapy in patients undergoing pancreatoduodenectomy for early stage pancreatic adenocarcinoma in the era of modern chemotherapy., Methods: The National Cancer Database (2010-2016) was queried for patients with clinical stage 0-2 pancreatic adenocarcinoma who underwent pancreatoduodenectomy. Patients who underwent up-front pancreatoduodenectomy were propensity matched to patients who received neoadjuvant chemotherapy. Postoperative outcomes, pathologic outcomes, and overall survival were compared., Results: A total of 2036 patients were in each group. Neoadjuvant chemotherapy was associated with shorter length of stay, lower 30-day readmission rate, and lower 30 and 90-day mortality rates (all p < 0.05). Neoadjuvant chemotherapy was associated with lower rates of positives nodes and positive resection margins (all p < 0.0001). Neoadjuvant chemotherapy was associated with longer survival (26.8 vs. 22.1months, p < 0.0001). Patients who received neoadjuvant chemotherapy followed by surgery and adjuvant therapy had the longest OS, followed by neoadjuvant + surgery, surgery + adjuvant therapy, and surgery alone (29.8 vs. 25.6 vs. 23.9 vs. 13.1 months; p < 0.0001)., Conclusions: Neoadjuvant chemotherapy is associated with improved postoperative outcomes, oncologic outcomes, and overall survival in patients with early stage pancreatic adenocarcinoma. Neoadjuvant chemotherapy should be considered in all patients with early stage pancreatic adenocarcinoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)