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Laparoscopic surgery via a single port is an evolving technique being applied to an increasing variety of operations [1]. Multiple series over the past 3 years have shown single-incision laparoscopic cholecystectomy to be feasible and safe [2]. The ergonomic difficulties of single-port laparoscopy include a loss of instrument triangulation and operation with camera and instruments in parallel. Many different modifications of techniques and equipment have been used to compensate. Single-port techniques have been applied by a few authors to laparoscopic nephrectomy [3], splenectomy [4], and obesity surgery [5, 6]. Laparoscopic liver resection is well established and shown to be safe in multiple series [7]. The laparoscopic approach is accepted as the gold standard for resection of segments 2 and 3 [8]. To the authors' knowledge, no reports of laparoscopic liver resection via a single port have been published. They report the use of their technique for single-incision laparoscopic left lateral segmentectomy in a patient with a solitary segment 2 colorectal liver metastasis. The authors maintained strict oncologic principles and adhered to their standard laparoscopic technique as far as possible. They used a TriPort (Advanced Surgical Concepts, Wicklow, Ireland) placed via a 12-mm incision at the umbilicus. Following diagnostic laparoscopy and intraoperative liver ultrasound, hepatic attachments were divided using electrocautery. Parenchymal transection and vascular control were achieved using an ultrasonic dissector and laparoscopic staplers. Standard straight laparoscopic instruments were used. A number of technical challenges were apparent. Movement of instruments was jerky at times, either because instruments were clashing with one another other or deflecting the camera. The multiport device can be stiff, requiring copious lubrication throughout surgery. Crossing hands facilitates internal triangulation of the operating instruments to allow retraction or to apply tension, for example, during the division of hepatic attachments. Control of minor hemorrhage is possible with judicious and patient application of pressure using small pieces of surgical gauze. An articulating laparoscopic stapler is useful to achieve the ideal angle of staple deployment during transection of vascular pedicles. The specimen was extracted by extending the umbilical incision. No complications occurred. The patient was able to resume an oral diet and full mobility free of opioid analgesia on the first postoperative day. The resection margin was clear. This video demonstrates that the authors' technique is feasible and oncologically safe for selected patients requiring liver resection. [ABSTRACT FROM AUTHOR]

Introduction: For high-risk women, breast magnetic resonance (MR) is the preferred supplemental imaging option, but spatial access differences may exacerbate disparities in breast care., Methods: This was a cross-sectional study examining distance between ZIP codes and the nearest breast imaging facility (MR, mammography, ultrasound) using 2023 data from the Food and Drug Administration and the American College of Radiology. Linear regression was used to assess distance differences controlling for Area Deprivation Index (ADI), urbanicity, and population size. Analyses were conducted in 2024., Results: Among the 29,629 ZIP codes with an ADI and known urbanicity, unadjusted mean distance to breast MR was 23.2±25.1 miles (SD) compared with 8.2±8.3 for mammography and 22.2±25.0 for ultrasound. Hence, the average distance to breast MR facilities was 2.8 times further than to mammography facilities. ADI and urbanicity were associated with increased distance to the nearest breast imaging facility. The additional miles associated with the least advantaged areas compared with most advantaged areas was 12.2 (95%CI: 11.3, 13.2) for MR, 11.5 miles (95%CI: 10.6, 12.3) for ultrasound, and 2.4 (95%CI: 2.1, 2.7) for mammography. Compared with metropolitan areas, the additional miles to breast MR facilities was 23.2 (95%CI: 22.5, 24.0) for small/rural areas., Conclusions: Spatial access is substantially better for mammography sites compared with breast MR or ultrasound sites. Given these findings, consideration of options to mitigate the impact of differential access should be considered. For example, mammography sites could offer contrast-enhanced mammography. Future research should examine the feasibility and effectiveness of this and other options., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rhabdomyosarcoma (RMS) is a pediatric tumor that resembles undifferentiated muscle cells; yet the extent to which cell state heterogeneity is shared with human development has not been described. Using single-cell/nucleus RNA sequencing from patient tumors, patient-derived xenografts, primary in vitro cultures, and cell lines, we identify four dominant muscle-lineage cell states: progenitor, proliferative, differentiated, and ground cells. We stratify these RMS cells/nuclei along the continuum of human muscle development and show that they share expression patterns with fetal/embryonal myogenic precursors rather than postnatal satellite cells. Fusion-negative RMS (FN-RMS) have a discrete stem cell hierarchy that recapitulates fetal muscle development and contain therapy-resistant FN-RMS progenitors that share transcriptomic similarity with bipotent skeletal mesenchymal cells. Fusion-positive RMS have tumor-acquired cells states, including a neuronal cell state, that are not found in myogenic development. This work identifies previously underappreciated cell state heterogeneity including unique treatment-resistant and tumor-acquired cell states that differ across RMS subtypes., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that a mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need a better understanding of the relationship between patient tumor heterogeneity and preclinical models., Results: Here, we generate single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived xenograft models (PDX), and a genetically engineered mouse model (GEMM). We develop an unsupervised machine learning approach ("automatic consensus nonnegative matrix factorization" (acNMF)) to compare the gene expression programs found in preclinical models to a large cohort of patient tumors. We confirm a weakly expressed, mesenchymal-like program in otherwise adrenergic cancer cells in some pre-treated high-risk patient tumors, but this appears distinct from the presumptive drug-resistance mesenchymal programs evident in cell lines. Surprisingly, however, this weak-mesenchymal-like program is maintained in PDX and could be chemotherapy-induced in our GEMM after only 24 h, suggesting an uncharacterized therapy-escape mechanism., Conclusions: Collectively, our findings improve the understanding of how neuroblastoma patient tumor heterogeneity is reflected in preclinical models, provides a comprehensive integrated resource, and a generalizable set of computational methodologies for the joint analysis of clinical and pre-clinical single-cell RNA-seq datasets., (© 2024. The Author(s).)

Single-cell RNA sequencing (scRNA-seq) greatly advanced the understanding of intratumoral heterogeneity by identifying distinct cancer cell subpopulations. However, translating biological differences into treatment strategies is challenging due to a lack of tools to facilitate efficient drug discovery that tackles heterogeneous tumors. Developing such approaches requires accurate prediction of drug response at the single-cell level to offer therapeutic options to specific cell subpopulations. Here, we developed a transparent computational framework (nicknamed scIDUC) to predict therapeutic efficacies on an individual cell basis by integrating single-cell transcriptomic profiles with large, data-rich pan-cancer cell line screening data sets. This method achieved high accuracy in separating cells into their correct cellular drug response statuses. In three distinct prospective tests covering different diseases (rhabdomyosarcoma, pancreatic ductal adenocarcinoma, and castration-resistant prostate cancer), the predicted results using scIDUC were accurate and mirrored biological expectations. In the first two tests, the framework identified drugs for cell subpopulations that were resistant to standard-of-care (SOC) therapies due to intrinsic resistance or tumor microenvironmental effects, and the results showed high consistency with experimental findings from the original studies. In the third test using newly generated SOC therapy-resistant cell lines, scIDUC identified efficacious drugs for the resistant line, and the predictions were validated with in vitro experiments. Together, this study demonstrates the potential of scIDUC to quickly translate scRNA-seq data into drug responses for individual cells, displaying the potential as a tool to improve the treatment of heterogenous tumors., Significance: A versatile method that infers cell-level drug response in scRNA-seq data facilitates the development of therapeutic strategies to target heterogeneous subpopulations within a tumor and address issues such as treatment failure and resistance., (©2024 American Association for Cancer Research.)

Background: The risk of spinal epidural hematoma (SEH) has been described in the literature but the impact in various patient populations has not been assessed in the same study. We identified the risk factors for SEH and calculated the OR for recovery in the pediatric, adult and obstetric (OB) patients based on the degree of neurological deficit before surgery., Methods: Adult non-OB cases were categorized whether they were on anticoagulants or not; SEH was related to neuraxial or pain procedure; or whether there was adherence to the American Society of Regional Anesthesia (ASRA) guidelines. Eligible cases were identified through PubMed and Embase searches in the English literature from 1954 to July 2022., Results: A total of 940 cases were evaluated. In the pediatric cases, SEH was typically spontaneous, related to coagulopathy or athletic trauma. OB cases were spontaneous or related to neuraxial injections. Among adults on anticoagulant(s), SEH was mostly spontaneous with no related etiology or related to neuraxial procedure. SEH occurred despite adherence to the ASRA guidelines. Among non-OB adults not on anticoagulants, SEH was due to trauma, neuraxial injections, surgery or other causes. Neurological recovery was related to the degree of neurological deficit before surgery., Conclusions: Our data show a preponderance of spontaneous SEH in all patient populations. SEH developed even though the ASRA guidelines were followed, especially in patients on multiple anticoagulants. Patients with less impairment prior to surgery had a higher likelihood of complete recovery, regardless of the interval between surgery and onset of symptoms., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this meta-analysis was to assess whether treatment with ursodeoxycholic acid (UDCA) in patients who have undergone bariatric surgery reduces gallstone formation. A systematic literature search was performed using electronic databases (MEDLINE, Embase, CENTRAL, Web of Science, PROSPERO, Google Scholar and the WHO International Clinical Trials Registry platform). RCTs without restrictions on study language, year, status of publication and patient's age were used. Pooled risk ratios were calculated using a random-effects model. Subgroup analyses for drug dose, duration and procedure types were performed. Sensitivity analyses and a summary of findings table were generated to assess the robustness and the level of evidence provided, respectively. Fourteen trials were included (3619 patients, 2292 in UDCA vs 1327 in control group). Procedures included SG, RYGB, OAGB, AGB and Gastroplasty. UDCA dose ranged from 300 to 1200 mg per day. Gallstone formation occurred in 19.3% (8.3% in UDCA vs 38.1% in the control group). UDCA significantly reduced the risk of gallstone formation (14 trials, 3619 patients; RR 0.27, 95% CI 0.18-0.41; P < 0.001). UDCA significantly reduced the risk of symptomatic gallstone disease (6 trials, 2458 patients; RR 0.30, 95% CI 0.21-0.43; P < 0.001). No subgroup difference was found for different doses, duration and type of procedure performed. Oral UDCA treatment significantly reduces the risks of developing gallstones in postoperative bariatric patients from 38 to 8%. The use of 500 to 600 mg UDCA for 6 months is effective and should be implemented in all patients post-bariatric surgery., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ly-6A, a member of the Ly-6/uPAR supergene family of proteins, is a cell adhesion and cell signaling protein. Signaling through Ly-6A activates the cell-intrinsic apoptotic cell death pathway in CD4 + T cell lines, as indicated by the release of cytochrome C, and activation of caspases 9 and 3. In addition, Ly-6A induces cytokine production and growth inhibition. The mechanism underlying the distinct cellular responses that are triggered by engaging Ly-6A protein has remained unknown. To examine the relatedness of these distinct responses, we have quantified the production of pro-apoptotic, growth inhibitory and tumor suppressive cytokines, such as TNF-α, TGF-β and a related protein GDF-10, in response to Ly-6A signaling. Anti-Ly-6A monoclonal antibody-induced activation of YH16.33 CD4 + T cell line generated low levels of TGF-β and GDF-10 but elevated levels of TNF-α. Blocking the biological activity of TNF-α resulted in reduced Ly-6A-induced apoptosis in T cells. The Ly-6A-induced response in the T cell line was distinct, as signaling through the antigen receptor complex did not cause growth inhibition and apoptosis despite high levels of TGF-β and GDF-10 that were detected in these cultures. Additionally, in response to antigen receptor complex signaling, lower amount of TNF-α was detected. These results indicate the contribution of TNF-α in the observed Ly-6A-induced growth inhibition and apoptosis and provide a mechanistic explanation for the biologically distinct responses observed in CD4 + T cells after engaging Ly-6A protein. Additionally, the findings reported here will aid in the understanding of inhibitory signaling initiated by Ly-6A protein, especially in the context of its potential immune checkpoint inhibitory role in T cells., (© 2023. L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.)

Objective: Postprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery., Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429)., Results and Conclusions: Postprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Apart from the anti-GD2 antibody, immunotherapy for neuroblastoma has had limited success due to immune evasion mechanisms, coupled with an incomplete understanding of predictors of response. Here, from bulk and single-cell transcriptomic analyses, we identify a subset of neuroblastomas enriched for transcripts associated with immune activation and inhibition and show that these are predominantly characterized by gene expression signatures of the mesenchymal lineage state. By contrast, tumors expressing adrenergic lineage signatures are less immunogenic. The inherent presence or induction of the mesenchymal state through transcriptional reprogramming or therapy resistance is accompanied by innate and adaptive immune gene activation through epigenetic remodeling. Mesenchymal lineage cells promote T cell infiltration by secreting inflammatory cytokines, are efficiently targeted by cytotoxic T and natural killer cells and respond to immune checkpoint blockade. Together, we demonstrate that distinct immunogenic phenotypes define the divergent lineage states of neuroblastoma and highlight the immunogenic potential of the mesenchymal lineage., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Neuroblastoma is a leading cause of cancer-related death in children. Accumulated data suggest that differentiation arrest of the neural-crest-derived sympathoadrenal lineage contributes to neuroblastoma formation. The developmental arrest of these cell types explains many biological features of the disease, including its cellular heterogeneity, mutational spectrum, spontaneous regression, and response to drugs that induce tumor cell differentiation. In this review, we provide evidence that supports the notion that arrested neural-crest-derived progenitor cells give rise to neuroblastoma and discuss how this concept could be exploited for clinical management of the disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease recurrence. Here, we use single-cell and single-nucleus RNA sequencing to show that RMS tumors recapitulate the spectrum of embryonal myogenesis. Using matched patient samples from a clinical trial and orthotopic patient-derived xenografts (O-PDXs), we show that chemotherapy eliminates the most proliferative component with features of myoblasts within embryonal RMS; after treatment, the immature population with features of paraxial mesoderm expands to reconstitute the developmental hierarchy of the original tumor. We discovered that this paraxial mesoderm population is dependent on EGFR signaling and is sensitive to EGFR inhibitors. Taken together, these data serve as a proof of concept that targeting each developmental state in embryonal RMS is an effective strategy for improving outcomes by preventing disease recurrence., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Laparoscopic liver resection (LLR) is a highly demanding procedure with great variability. Previously published randomized trials have proven oncological safety of laparoscopic liver resection (LLR) as compared to open surgery. However, these were started after the learning curve (LC) was established. This leaves the question of whether the LC of LLR in the early laparoscopic era has affected the survival of patients with colorectal liver metastasis (CRLM)., Methods: All consecutive LLRs performed by a single surgeon between 2000 and 2019 were retrospectively analysed. A risk-adjusted cumulative sum (RA-CUSUM) chart for conversion rate and the log regression analysis of the blood loss identified two phases in the LC. This was then applied to patients with CRLM, and the two subgroups were compared for recurrence-free (RFS) and overall survival (OS). The analysis was repeated with propensity score-matched (PSM) groups., Results: A total of 286 patients were included in the LC analysis, which identified two distinct phases, the early (EP; 68 patients) and the late (LP; 218 patients) phases. The LC was applied to 192 patients with colorectal liver metastasis (EPc, 45 patients; LPc, 147 patients). For patients with CRLM, R0 resection was achieved in 93 per cent: 100 per cent in the EPc group and 90 per cent in the LPc group (P = 0.026). Median OS and RFS were 60 and 16 months, respectively. The 5-year OS and RFS were 51 per cent and 32.7 per cent, respectively. OS (hazard ratio (h.r.) 0.78, 95 per cent confidence interval (c.i.) 0.51 to 1.2; P = 0.286) and RFS (h.r. 0.94, 95 per cent c.i. 0.64 to 1.37; P = 0.760) were not compromised by the learning curve. The results were replicated after PSM., Conclusion: In our experience, the development of a laparoscopic liver resection programme can be achieved without adverse effects on the long-term survival of patients with CRLM., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Gene expression is regulated by promoters and enhancers marked by histone H3 lysine 27 acetylation (H3K27ac), which is established by the paralogous histone acetyltransferases (HAT) EP300 and CBP. These enzymes display overlapping regulatory roles in untransformed cells, but less characterized roles in cancer cells. We demonstrate that the majority of high-risk pediatric neuroblastoma (NB) depends on EP300, whereas CBP has a limited role. EP300 controls enhancer acetylation by interacting with TFAP2β, a transcription factor member of the lineage-defining transcriptional core regulatory circuitry (CRC) in NB. To disrupt EP300, we developed a proteolysis-targeting chimera (PROTAC) compound termed "JQAD1" that selectively targets EP300 for degradation. JQAD1 treatment causes loss of H3K27ac at CRC enhancers and rapid NB apoptosis, with limited toxicity to untransformed cells where CBP may compensate. Furthermore, JQAD1 activity is critically determined by cereblon (CRBN) expression across NB cells., Significance: EP300, but not CBP, controls oncogenic CRC-driven transcription in high-risk NB by binding TFAP2β. We developed JQAD1, a CRBN-dependent PROTAC degrader with preferential activity against EP300 and demonstrated its activity in NB. JQAD1 has limited toxicity to untransformed cells and is effective in vivo in a CRBN-dependent manner. This article is highlighted in the In This Issue feature, p. 587., (©2021 The Authors; Published by the American Association for Cancer Research.)

Super-enhancers are expansive regions of genomic DNA comprised of multiple putative enhancers that contribute to the dynamic gene expression patterns during development. This is particularly important in neurogenesis because many essential transcription factors have complex developmental stage- and cell-type specific expression patterns across the central nervous system. In the developing retina, Vsx2 is expressed in retinal progenitor cells and is maintained in differentiated bipolar neurons and Müller glia. A single super-enhancer controls this complex and dynamic pattern of expression. Here we show that deletion of one region disrupts retinal progenitor cell proliferation but does not affect cell fate specification. The deletion of another region has no effect on retinal progenitor cell proliferation but instead leads to a complete loss of bipolar neurons. This prototypical super-enhancer may serve as a model for dissecting the complex gene expression patterns for neurogenic transcription factors during development. Moreover, it provides a unique opportunity to alter expression of individual transcription factors in particular cell types at specific stages of development. This provides a deeper understanding of function that cannot be achieved with traditional knockout mouse approaches., (© 2022. The Author(s).)

Purpose: To assess the impact of elevated blood pressure on the rate of major hemorrhagic complication after renal transplant biopsy., Methods: Pre-procedural systolic (SBP), diastolic (SBP), and mean arterial (MAP) blood pressure for consecutive patients undergoing US-guided renal transplant biopsies from 08/01/2015 to 7/31/2017 were retrospectively recorded. Patients who had a major bleeding complication were identified. The risk of complication as a function of SBP, DBP, and MAP was statistically analyzed, with significance set at p < 0.05., Results: Of 1689 biopsies, there were 10 bleeding complications (10/1689, 0.59%). There was no statistically significant difference between biopsies with complication compared to those without complication based on SBP (p = 0.351), DBP (p = 0.088), or MAP (p = 0.132). Using risk dichotomization criteria, the odds ratio for hemorrhagic complication when the patient had SBP ≥ 180 mmHg and DBP ≥ 95 mmHg was 75.63 (95% CI 6.87-516.8, p = 0.002)., Conclusion: The rate of hemorrhagic complication from renal transplant biopsy is low, and there is no statistically significant threshold for increased biopsy risk based on SBP, DBP, or MAP alone. The risk of complication was significantly higher only when both the SBP is ≥ 180 mmHg and DBP is ≥ 95 mmHg., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nonhuman primates are frequently transported to a new location or temporarily relocated within their colony. Both transportation and relocation expose animals to new environments, causing them to undergo a stress response (before adapting). In our NHP colony, the mentioned situations are not infrequent for many reasons, including maintenance. The objective of this study was to determine whether abrupt changes consisting of relocation, housing, separation, and grouping could influence hematological and immunological parameters and thereby functional activity. The current study used squirrel monkeys as a model to investigate the stress-inducing effects of relocation within a facility, while animals acclimated to new situations (physical, housing). A detailed blood analysis revealed significant changes in lymphocytes, triglycerides, total protein, creatinine, and ALT. Flow cytometric analysis of peripheral blood showed reduction in CD3 + , CD4 + , and CD8 + T cells and monocytes, while B cells and natural killer (NK) cells changed with relocation. Simultaneously, changes in functional activity of immune cells altered proliferative responses and as shown by ELISpot (IFN γ ). Though the parameters studied are not affected as severely as those in animals transported by road or air, stress responses induced by intrafacility relocation are significant and worth consideration. Our findings indicate that squirrel monkeys mimic the features seen in humans exposed to social stressors and may serve an important model for understanding the mechanisms of stress-induced immune dysfunction in humans., Competing Interests: The authors have no conflict of interest., (Copyright © 2021 Pramod N. Nehete et al.)

Objectives: We analyzed growth rates of benign ovarian serous cystadenomas and cystadenofibromas to understand what percentage would show a volume doubling time (DT) of less than 3 years, between 3 and 5 years, or greater than 5 years., Methods: We retrospectively reviewed pathology records (January 1, 2014, to June 30, 2019) to find all surgically excised ovarian serous cystadenomas and cystadenofibromas. Imaging records were then reviewed to identify those that had been confidently identified with ultrasound imaging, magnetic resonance imaging, or computed tomography at least twice before surgical removal, with at least a 60-day interval between studies. Three orthogonal measurements were recorded on the first and last imaging studies on which the mass was detected, with volume calculations by the prolate formula (product of 3 measurements multiplied by 0.52). The volume DT was calculated and grouped into 1 of 5 categories: (1) DT of less than 1 year; (2) DT of 1 to 3 years; (3) DT of 3 to 5 years; (4) DT of 5 to 10 years; and (5) no growth (any mass with a DT >10 years or showing a decrease in volume)., Results: A total of 102 of 536 cystadenomas and 44 of 227 cystadenofibromas met inclusion criteria. Of the 146 tumors, 40 (27.4%) had a DT of less than 1 year; 38 (26.0%) had a DT of 1 to 3 years; 22 (15.1%) had a DT of 3 to 5 years; 10 (6.8%) had a DT of 5 to 10 years; and 36 (24.7%) showed no growth., Conclusions: A total of 53.4% of ovarian serous cystadenomas/cystadenofibromas have a DT of less than 3 years; 15.1% have a DT between 3 and 5 years; and 31.5% have a DT of greater than 5 years or show no growth., (© 2020 American Institute of Ultrasound in Medicine.)

Alzheimer's disease is the most common cause of dementia and the only illness among the top 10 causes of death for which there is no disease-modifying therapy. The failure rate of clinical trials is very high, in part due to the premature translation of successful results in transgenic mouse models to patients. Extensive evidence suggests that dysregulation of innate immunity and microglia/macrophages plays a key role in Alzheimer's disease pathogenesis. Activated resident microglia and peripheral macrophages can display protective or detrimental phenotypes depending on the stimulus and environment. Toll-like receptors (TLRs) are a family of innate immune regulators known to play an important role in governing the phenotypic status of microglia. We have shown in multiple transgenic Alzheimer's disease mouse models that harnessing innate immunity via TLR9 agonist CpG oligodeoxynucleotides (ODNs) modulates age-related defects associated with immune cells and safely reduces amyloid plaques, oligomeric amyloid-β, tau pathology, and cerebral amyloid angiopathy (CAA) while promoting cognitive benefits. In the current study we have used a non-human primate model of sporadic Alzheimer's disease pathology that develops extensive CAA-elderly squirrel monkeys. The major complications in current immunotherapeutic trials for Alzheimer's disease are amyloid-related imaging abnormalities, which are linked to the presence and extent of CAA; hence, the prominence of CAA in elderly squirrel monkeys makes them a valuable model for studying the safety of the CpG ODN-based concept of immunomodulation. We demonstrate that long-term use of Class B CpG ODN 2006 induces a favourable degree of innate immunity stimulation without producing excessive or sustained inflammation, resulting in efficient amelioration of both CAA and tau Alzheimer's disease-related pathologies in association with behavioural improvements and in the absence of microhaemorrhages in aged elderly squirrel monkeys. CpG ODN 2006 has been well established in numerous human trials for a variety of diseases. The present evidence together with our earlier, extensive preclinical research, validates the beneficial therapeutic outcomes and safety of this innovative immunomodulatory approach, increasing the likelihood of CpG ODN therapeutic efficacy in future clinical trials., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Women with obesity are at risk of pelvic floor dysfunction with a 3-fold increased incidence of urge urinary incontinence (UUI) and double the risk of stress urinary incontinence (SUI). The National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) recommend that women with a body mass index ≥30 kg/m 2 should consider weight loss prior to consideration for incontinence surgery. This systematic review and meta-analysis will assess this recommendation to aid in the counselling of women with obesity-related urinary incontinence (UI). Medical Literature Analysis and Retrieval System online (MEDLINE), EMBASE, Cochrane, ClinicalTrials.gov, and SCOPUS were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori and presented original, empirical data relevant to weight loss intervention in the management of urinary incontinence. Thirty-three studies and their outcomes were meta-analysed. Weight loss interventions were associated in a decreased prevalence in UI (OR 0.222, 95% CI [0.147, 0.336]), SUI (OR 0.354, 95% CI [0.256, 0.489]), UUI (OR 0.437, 95% CI [0.295, 0.649]) and improved quality of life (PFDI-20, SMD -0.774 (95% CI [-1.236, -0.312]). This systematic review and meta-analysis provide evidence that weight loss interventions are effective in reducing the prevalence of obesity-related UI symptoms in women. Bariatric surgery in particular shows greater sustained weight loss and improvements in UI prevalence. Further large scale, randomized control trials assessing the effect of bariatric surgery on women with obesity-related UI are needed to confirm this study's findings., (© 2021 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Faithful tumor mouse models are fundamental research tools to advance the field of immuno-oncology (IO). This is particularly relevant in diseases with low incidence, as in the case of pediatric malignancies, that rely on pre-clinical therapeutic development. However, conventional syngeneic and genetically engineered mouse models fail to recapitulate the tumor heterogeneity and microenvironmental complexity of human pathology that are essential determinants of cancer-directed immunity. Here, we characterize a novel mouse model that supports human natural killer (NK) cell development and engraftment of neuroblastoma orthotopic patient-derived xenograft (O-PDX) for pre-clinical antibody and cytokine testing. Using cytotoxicity assays, single-cell RNA-sequencing, and multi-color flow cytometry, we demonstrate that NK cells that develop in the humanized mice are fully licensed to execute NK cell cytotoxicity, permit human tumor engraftment, but can be therapeutically redirected to induce antibody-dependent cell-mediated cytotoxicity (ADCC). Although these cells share phenotypic and molecular features with healthy controls, we noted that they lacked an NK cell subset, termed activated NK cells, that is characterized by differentially expressed genes that are induced by cytokine activation. Because this subset of genes is also downregulated in patients with neuroblastoma compared to healthy controls, we hypothesize that this finding could be due to tumor-mediated suppressive effects. Thus, despite its technical complexity, this humanized patient-derived xenograft mouse model could serve as a faithful system for future testing of IO applications and studies of underlying immunologic processes.

OBJECTIVE. The purpose of this study was to analyze the timing of major bleeding complications after renal transplant biopsy in the context of a standardized 1-hour postprocedure observation protocol. MATERIALS AND METHODS. We retrospectively reviewed the electronic medical records for consecutive patients who underwent ultrasound-guided renal transplant biopsies between January 1, 2012, and December 31, 2017, and were observed according to a newly implemented 1-hour postprocedure observation protocol. The development of a major bleeding complication (Common Terminology Criteria for Adverse Events class 3 or higher) was recorded along with all available details regarding the time course of patient symptoms and presentation. Complications were grouped into one of four categories according to onset time after biopsy: 2 hours or less (timing category 1), more than 2 hours but 4 hours or less (timing category 2), more than 4 hours but 8 hours or less (timing category 3), and more than 8 hours (timing category 4). RESULTS. In 1824 patients (769 women, 1055 men) who underwent 4519 consecutive ultrasound-guided renal transplant biopsies during the study period, 11 class 3 complications were found (11/4519 [0.2%]). Four of the 11 patients (36.4%) had symptoms during the 1-hour observation period. Of these four patients, three (3/11 [27.3%]) had substantial symptoms related to major bleeding and were classified as timing category 1, and one (1/11 [9.1%]) had initially minor symptoms that increased in severity more than 2 hours but within 4 hours and was classified as timing category 2. Seven of the 11 patients (63.6%) did not have any symptoms at 1 hour of observation and were discharged; three (27.3%) were classified as timing category 3, and four (36.4%) were classified as category 4. CONCLUSION. Major bleeding complications following ultrasound-guided renal transplant biopsy are rare (0.2% of patients in this study). In our study, more than half were not clinically apparent within 4 hours of biopsy. A 1-hour postprocedure recovery period can be safely used after renal transplant biopsy.

Strong electrodes with good energy storage capabilities are necessary to accommodate the current needs for structural and flexible electronics. To this end, conjugated polymers such as polyaniline (PANI) have attracted much attention due to their exceptional energy storage performance. However, PANI is typically brittle and requires the use of substrates for structural support. Here, we report a strategy for developing free-standing structural supercapacitor and battery electrodes based on PANI. More specifically, aniline is polymerized in the presence of branched aramid nanofibers (BANFs) and single walled carbon nanotubes (SWCNTs). This results in a network morphology that allows for efficient load transfer and electron transport, leading to electrodes with capacity values up to 128 ± 5 mA h g-1 (vs. a theoretical capacity of 147 mA h g-1), Young's modulus of 4 ± 0.5 GPa, and tensile strength of 40 ± 4 MPa. Furthermore, the charge storage mechanism is investigated, in which both Faradaic and non-Faradaic contributions are observed. This work demonstrates an efficient strategy for designing structural electrodes based on conjugated polymers.

Obesity is an ever growing pandemic and a prevalent problem among men of reproductive age that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the precision and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and preclinical data support these findings. Clinical studies on the impact of medically induced weight loss on serum testosterone concentrations and spermatogenesis is promising but may show differential and unsustainable results. In contrast, literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in serum testosterone concentrations that is superior than that obtained with only lifestyle modifications, supporting a further metabolic benefit from surgery that may be specific to the male reproductive system. The data on sperm and semen parameters is controversial to date. Emerging evidence in the burgeoning field of genetics and epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, conveying the potential impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Healthcare professionals treating male infertility and obesity need to adapt their practice to assimilate these new findings to better counsel men about the importance of paternal preconception health and the impact of novel non-medical therapeutic interventions. Herein, we summarize the pathophysiology of obesity on the male reproductive system and emerging evidence regarding the potential role of bariatric surgery as treatment of male obesity-associated gonadal dysfunction., (Copyright © 2020 Sultan, Patel, El-Hassani, Whitelaw, Leca, Vincent, le Roux, Rubino, Aywlin and Dimitriadis.)

Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated from fresh tumors, single-nucleus RNA-Seq (snRNA-Seq) is needed to profile frozen or hard-to-dissociate tumors. Each requires customization to different tissue and tumor types, posing a barrier to adoption. Here, we have developed a systematic toolbox for profiling fresh and frozen clinical tumor samples using scRNA-Seq and snRNA-Seq, respectively. We analyzed 216,490 cells and nuclei from 40 samples across 23 specimens spanning eight tumor types of varying tissue and sample characteristics. We evaluated protocols by cell and nucleus quality, recovery rate and cellular composition. scRNA-Seq and snRNA-Seq from matched samples recovered the same cell types, but at different proportions. Our work provides guidance for studies in a broad range of tumors, including criteria for testing and selecting methods from the toolbox for other tumors, thus paving the way for charting tumor atlases.

Introduction: Ten percent of cirrhotic patients are known to have a high risk of postoperative complications. Ninety percent of bariatric patients suffer from non-alcoholic fatty liver disease (NAFLD), and 50% of them may develop non-alcoholic steatohepatitis (NASH) which can progress to cirrhosis. The aim of this study was to assess whether the presence of cirrhosis at the time of bariatric surgery is associated with an increased rate and severity of short- and long-term cirrhotic complications., Methods: A cohort of 110 bariatric patients, between May 2003 and February 2018, who had undergone liver biopsy at the time of bariatric surgery were reassessed for histological outcome and divided into two groups based on the presence (C, n = 26) or absence (NC, n = 84) of cirrhosis. The NC group consisted of NASH (n = 49), NAFLD (n = 24) and non-NAFLD (n = 11) liver histology. Medical notes were retrospectively assessed for patient characteristics, development of 30-day postoperative complications, severity of complications (Clavien-Dindo (CD) classification) and length of stay. The C group was further assessed for long-term cirrhosis-related outcomes., Results: The C group was older (52 years vs 43 years) and had lower BMI (46 kg/m 2 vs 52 kg/m 2 ) and weight (126 kg vs 145 kg) compared to the NC group (p < 0.05). The C group had significantly higher overall complication rate (10/26 vs 14/84, p < 0.05) and severity of complications (CD class ≥ III, 12% vs 7%, p < 0.05) when compared to the NC group. The length of stay was similar between the two groups (5 days vs 4 days). The C group had significant improvement in model end-stage liver disease scores (7 vs 6, p < 0.01) with median follow-up of 4.5 years (range 2-11 years). There were no long-term cirrhosis-related complications or mortality in our studied cohort (0/26)., Conclusion: Bariatric surgery in cirrhotic patients has a higher risk of immediate postoperative complications. Long-term cirrhosis-related complications or mortality was not increased in this small cohort. Preoperative identification of liver cirrhosis may be useful for risk stratification, optimisation and informed consent. Bariatric surgery in well-compensated cirrhotic patients may be used as an aid to improve long-term outcome.