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Background Single‐slice computed tomography (CT) body composition has been studied extensively for prognostication in patients with cancer. New software packages can also provide multi‐slice volumetric measurements, but the clinical utility of these remains under explored. This study aimed to evaluate the agreement between single‐ and multi‐slice body composition analyses in patients with oesophagogastric cancer and to explore the association between these measures and overall survival. Methods Consecutive patients with newly diagnosed oesophagogastric (OG) cancer were identified through the prospectively maintained regional database of the South East Scotland Cancer Network across a 2‐year study period. CT body composition analyses were undertaken using scans collected during routine clinical care. Single‐slice (cross‐sectional area at mid L3) and multi‐slice (volume between T12 and L4) measurements were compared for skeletal muscle (SKM), subcutaneous adipose (SAT), visceral adipose (VAT) and intermuscular adipose (IMAT). Agreement between sex‐stratified z‐scores was quantified using Pearson correlation coefficients and Bland–Altman analyses. Cox proportional hazard modelling was used to estimate the effect of these measures on overall survival. Results Overall, 504 patients (67.9% male, median 72 years) were newly diagnosed with OG cancer during the study period. Single‐ and multi‐slice (mean: 169 slices) measurements correlated highly for SKM (R: 0.97, p < 0.001), SAT (R: 0.98, p < 0.001), VAT (R: 0.97, p < 0.001), SKM radiodensity (R: 0.93, p < 0.001) and IMAT (R: 0.88, p < 0.001). Bias on Bland–Altman analysis was 0.00 for all tissue measurements. Limits of agreement (LoA) were narrowest for SAT (±0.43), VAT (±0.46) and SKM (±0.48), but slightly wider for SKM radiodensity (±0.73) and IMAT (±0.96). Adipose tissue ‘outliers’ (those where agreement between single‐ and multi‐slice z‐scores was outside the LoA) had a higher median weight and body mass index (BMI), suggestive of poorer agreement in patients with obesity. Sensitivity analysis, excluding those with BMI > 30, narrowed the LoA for SKM, VAT, SAT and IMAT. Direction and magnitudes of observed effect sizes for overall survival were all highly comparable, with hazard ratios for each tissue type varying by ≤ 0.04 between single‐ and multi‐slice adjusted estimates. Conclusions Single‐slice and multi‐slice CT assessments provide highly correlated tissue measurements amongst patients with OG cancer. Associations between these measurements and overall survival were also comparable across both types of body composition analysis. Agreement between single‐ and multi‐slice measurements of adiposity is worse in patients with obesity, suggesting single‐slice analyses may less accurately reflect the quantity or distribution of adipose tissue in this patient group.

Patient and public involvement (PPI) has gained increased attention in research circles. The consistency of PPI reporting has been addressed by the development of validated checklists such as GRIPP and GRIPP2. The primary aim of this study was to identify the incidence of PPI reporting in bariatric research. MEDLINE/PubMed, EMBASE, and CINAHL/Cochrane databases were searched for publications between 1st January 2018 to 31st December 2021 for “bariatric surgery” OR “weight loss surgery” OR “obesity surgery” AND “randomized controlled trials.” Ninety studies fulfilled exclusion criteria; two studies reported direct PPI involvement, one indirectly used PPI and one reported not using PPI methods. No other study made direct or indirect mention of PPI. Concluding, that GRIPP2 and PPI reporting in bariatric surgery trials is lacking.

IntroductionCONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC).MethodsThe treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic (‘COVID’ cohort, 16/03/2020-10/05/2020), with 12-month follow-up.ResultsAmong 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8–4.1) vs. 4.4 (IQR 3.6–5.2) months, p = 0.093).ConclusionPathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned.

Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2 /Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients. DNA methylation profiling of 565 meningiomas highlights three groups associated with distinct molecular, clinical and therapeutic features.

Meningiomas are associated with inactivation of NF2 /Merlin, but approximately one-third of meningiomas with favorable clinical outcomes retain Merlin expression. Biochemical mechanisms underlying Merlin-intact meningioma growth are incompletely understood, and non-invasive biomarkers that may be used to guide treatment de-escalation or imaging surveillance are lacking. Here, we use single-cell RNA sequencing, proximity-labeling proteomic mass spectrometry, mechanistic and functional approaches, and magnetic resonance imaging (MRI) across meningioma xenografts and patients to define biochemical mechanisms and an imaging biomarker that underlie Merlin-intact meningiomas. We find Merlin serine 13 (S13) dephosphorylation drives meningioma Wnt signaling and tumor growth by attenuating inhibitory interactions with β-catenin and activating the Wnt pathway. MRI analyses show Merlin-intact meningiomas with S13 phosphorylation and favorable clinical outcomes are associated with high apparent diffusion coefficient (ADC). These results define mechanisms underlying a potential imaging biomarker that could be used to guide treatment de-escalation or imaging surveillance for patients with Merlin-intact meningiomas. The molecular mechanisms underlying merlin-intact meningioma growth remain to be explored. Here, the authors show that merlin activates Wnt signalling and tumour growth through its dephosphorylation on serine 13 attenuating the inhibitory interactions with β-catenin.

Hemispheric brain asymmetry is a basic organizational principle of the human brain and has been implicated in various psychiatric conditions, including autism spectrum disorder. Brain asymmetry is not a uniquely human feature and is observed in other species such as the mouse. Yet, asymmetry patterns are generally nuanced, and substantial sample sizes are required to detect these patterns. In this pre-registered study, we use a mouse dataset from the Province of Ontario Neurodevelopmental Network, which comprises structural MRI data from over 2000 mice, including genetic models for autism spectrum disorder, to reveal the scope and magnitude of hemispheric asymmetry in the mouse. Our findings demonstrate the presence of robust hemispheric asymmetry in the mouse brain, such as larger right hemispheric volumes towards the anterior pole and larger left hemispheric volumes toward the posterior pole, opposite to what has been shown in humans. This suggests the existence of species-specific traits. Further clustering analysis identified distinct asymmetry patterns in autism spectrum disorder models, a phenomenon that is also seen in atypically developing participants. Our study shows potential for the use of mouse models to understand the biological bases of typical and atypical brain asymmetry but also warrants caution as asymmetry patterns seem to differ between humans and mice.

The objective of this study was to characterize head biomechanics of video-recorded falls involving young children in a licensed childcare setting. Children 12 to < 36 months of age were observed using video monitoring during daily activities in a childcare setting (in classrooms and outdoor playground) to capture fall events. Sensors (SIM G) incorporated into headbands worn by the children were used to obtain head accelerations and velocities during falls. The SIM G device was activated when linear acceleration was ≥ 12 g. 174 video-recorded falls activated the SIM G device; these falls involved 31 children (mean age = 21.6 months ± 5.6 SD). Fall heights ranged from 0.1 to 1.2 m. Across falls, max linear head acceleration was 50.2 g, max rotational head acceleration was 5388 rad/s 2 , max linear head velocity was 3.8 m/s and max rotational head velocity was 21.6 rad/s. Falls with head impact had significantly higher biomechanical measures. There was no correlation between head acceleration and fall height. No serious injuries resulted from falls—only 1 child had a minor injury. In conclusion, wearable sensors enabled characterization of head biomechanics during video-recorded falls involving young children in a childcare setting. Falls in this setting did not result in serious injury.

Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, the most common tumors of the peripheral nervous system. We find schwannomas are comprised of 2 molecular groups that are distinguished by activation of neural crest or nerve injury pathways that specify tumor cell states and the architecture of the tumor immune microenvironment. Moreover, we find radiotherapy is sufficient for interconversion of neural crest schwannomas to immune-enriched schwannomas through epigenetic and metabolic reprogramming. To define mechanisms underlying schwannoma groups, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of tumor evolution and establish a paradigm of epigenetic and metabolic reprograming of cancer cells that shapes the immune microenvironment in response to radiotherapy. Schwannomas are regularly treated with radiotherapy, but the molecular effects on these tumours and their microenvironment remain unclear. Here, the authors show that radiotherapy can induce epigenetic reprogramming and immune infiltration in schwannomas, and develop the snARC-seq approach to analyse the epigenomic evolution at the single-cell level.

Meningiomas are associated with inactivation of NF2/Merlin, but approximately one-third of meningiomas with favorable clinical outcomes retain Merlin expression. Biochemical mechanisms underlying Merlin-intact meningioma growth are incompletely understood, and non-invasive biomarkers that may be used to guide treatment de-escalation or imaging surveillance are lacking. Here, we use single-cell RNA sequencing, proximity-labeling proteomic mass spectrometry, mechanistic and functional approaches, and magnetic resonance imaging (MRI) across meningioma xenografts and patients to define biochemical mechanisms and an imaging biomarker that underlie Merlin-intact meningiomas. We find Merlin serine 13 (S13) dephosphorylation drives meningioma Wnt signaling and tumor growth by attenuating inhibitory interactions with β-catenin and activating the Wnt pathway. MRI analyses show Merlin-intact meningiomas with S13 phosphorylation and favorable clinical outcomes are associated with high apparent diffusion coefficient (ADC). These results define mechanisms underlying a potential imaging biomarker that could be used to guide treatment de-escalation or imaging surveillance for patients with Merlin-intact meningiomas.

What is already known about this topic? In 2015, the estimated HIV infection prevalence among persons who inject drugs (PWID) in 20 U.S. metropolitan statistical areas was 7%. What is added by this report? In 2018, estimated HIV prevalence among PWID remained unchanged, and although overall syringe service program use did not significantly change, a substantial decrease in their use occurred among Black PWID. What are the implications for public health practice? Low-barrier access is needed to comprehensive and integrated needs-based syringe service programs (where legally permissible) that include provision of sterile syringes and safe syringe disposal, HIV and hepatitis C virus testing and referrals for treatment, HIV preexposure prophylaxis, and treatment for substance use and mental health disorders for PWID.