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Background: While enrolled in Hospital at Home (HaH) programs, patients rely on their social network to provide supportive behaviors that are routinely provided by hospital staff in the inpatient setting. Objective: This study investigated how social connectedness is associated with patient outcomes in a HaH program. Design: The explanatory iterative sequential mixed methods design included an electronic health record review to collect quantitative measures to describe the severity of patient illness and healthcare utilization and then qualitative interviews to explain quantitative findings. Participants: The quantitative phase included 100 patients (18 years or older) admitted to the hospital who were subsequently enrolled in the HaH program. In the qualitative phase, 33 of the 100 patients participated in semi-structured interviews. Analysis: Qualitative data was analyzed using the Sort & Sift, Think & Shift method. Integrated analysis included merged data displays of healthcare utilization data and patient descriptions of their care and genogram-type illustrations to enable variable-oriented analysis of structural support. We then examined patient narratives by two variables: life course and care elevation, to understand differences in the trajectories of six subsets of patients as identified by the quantitative data. Key Results: Three factors prompted patients to enroll in HaH: low attention from hospital staff during hospital stay; loneliness and isolation during hospital stay; and family encouragement to enroll. After discharge, social support within the home structure facilitated recovery during HaH. Conversely, HaH patients with limited support within the home were more likely to be readmitted. Conclusions: Structural social connectedness facilitates patient recovery in HaH. Before enrolling patients in HaH, clinicians should take an in-depth social history, including questions about social/familial roles, household responsibilities, and technology acceptance. Clinicians should engage formal and informal caregivers in these conversations early and communicate a clear picture of what caregivers should do to support the patient through recovery. [ABSTRACT FROM AUTHOR]

Cellulose nitrate, commonly known as nitrocellulose (NC), is an energetic polymer with a broad function in industrial and military applications. The use of biomass waste for nitrocellulose production offers a promising solution to the growing demand for renewable and sustainable raw materials, addressing one of the most critical issues of recent decades. However, the product quality remains suboptimal, presenting one of the biggest challenges in developing NC production from biomass. Enhancing NC performance through the modification of cellulose crystal structures and allomorph is considered an excellent approach. Herein, the transformation of cellulose-I into cellulose-II was explored during the hydrolysis step to produce high-performance NC. The present study demonstrated that cellulose-II precursors effectively produced the highest-performance NC from the solid byproducts of avocado seed extraction (EAS), highlighting its promising potential for high-energy applications. [ABSTRACT FROM AUTHOR]

Background: Patients with head and neck squamous cell carcinoma (HNSCC) face several physical, emotional, and psychological challenges throughout treatment. Cisplatin-based chemoradiotherapy (CRT) is an effective but toxic treatment, with an increased risk for toxicities in patients with low skeletal muscle mass (SMM). Consequently, these patients are anticipated to experience greater treatment-related difficulties. We aimed to explore the experiences of patients with HNSCC and low SMM regarding cisplatin-based CRT. Methods: A descriptive qualitative study was conducted, interviewing seven patients 3 months after CRT using a topic guide. Thematic analysis of semi-structured interviews was conducted, to create a multi-dimensional understanding of patients’ experiences during and after cisplatin-based CRT. Results: Prior to CRT themes included pre-treatment information, expectations towards treatment and trial, psychosocial circumstances, and supporting network. During CRT themes included toxicities, psychosocial impact, and supporting network. After CRT themes included reflection on period during CRT, psychosocial circumstances, informal support from networks and healthcare workers, and ongoing toxicities. Conclusion: Most patients experience cisplatin-based CRT as a life-changing and distressing life event but cope through various strategies and supporting networks. Tailored counseling, ideally with on-demand consultations, is recommended. No differences were noted in patients’ perceptions of their cisplatin regimen. [ABSTRACT FROM AUTHOR]

There is important variation in the occurrence of Paget's disease in different regions and populations. There are though few data concerning the occurrence of clinically diagnosed disease in black and ethnic minority groups in the United Kingdom (UK). We undertook an anonymised search using an integrated primary and secondary care-based database in Greater Manchester, covering a population of over 3 million people. We looked also among those with a first positive COVID test, the influence of Paget's disease on subsequent admission to hospital within 28 days. Within our database, there were 534,571 people aged 60 years and over alive on 1 January 2020. The majority were white (84%) with 4.7% identifying as Asian or Asian British, and 1.27% Black or Black British. There were 931 with clinically diagnosed Paget's disease. Overall prevalence in the greater Manchester area was 0.174%. Prevalence was higher in men than women (0.195 vs 0.155%). Compared to the prevalence of Paget's in whites (0.179%) the prevalence was lower among those identifying as Asian or Asian British (0.048%) and higher among those identifying as Black or Black British (0.344%). Prevalence increased with increasing deprivation. Clinically diagnosed Paget's disease is uncommon affecting 0.174% of men and women aged 60 or more years. Within Greater Manchester, it was more common in those identifying as Black or Black British and less common in those identifying as Asian or Asian British. [ABSTRACT FROM AUTHOR]

Background: Survival from childhood and adolescent cancer has increased, but the chance of a livebirth in female survivors under 18 years at diagnosis may be reduced. Methods: We performed a national population-based analysis, including all female cancer survivors diagnosed in Scotland before the age of 18 years between 1981 and 2012. Scottish Cancer Registry records were linked to Scottish maternity records. Females from the exposed group with no pregnancies before cancer diagnosis (n = 2118) were compared with three general population controls matched for age and year of diagnosis. Findings: The cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33–40%) for cancer survivors at 30 years of age vs 58% (57–60%) for controls. The deficit varying by diagnosis: for lymphoid leukaemia, the cumulative incidence at 30 years was 29% (23–36%) vs 57% (52–61%) for controls with similar deficits in CNS tumours and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently. Interpretation: We have shown a reduced chance of livebirth in female survivors of cancer diagnosed before age 18. The deficit is present for all diagnoses. [ABSTRACT FROM AUTHOR]

CDK4/6 inhibition in combination with endocrine therapy is the standard of care for estrogen receptor (ER+) breast cancer, and although cytostasis is frequently observed, new treatment strategies that enhance efficacy are required. Here, we perform two independent genome-wide CRISPR screens to identify genetic determinants of CDK4/6 and endocrine therapy sensitivity. Genes involved in oxidative stress and ferroptosis modulate sensitivity, with GPX4 as the top sensitiser in both screens. Depletion or inhibition of GPX4 increases sensitivity to palbociclib and giredestrant, and their combination, in ER+ breast cancer models, with GPX4 null xenografts being highly sensitive to palbociclib. GPX4 perturbation additionally sensitises triple negative breast cancer (TNBC) models to palbociclib. Palbociclib and giredestrant induced oxidative stress and disordered lipid metabolism, leading to a ferroptosis-sensitive state. Lipid peroxidation is promoted by a peroxisome AGPAT3-dependent pathway in ER+ breast cancer models, rather than the classical ACSL4 pathway. Our data demonstrate that CDK4/6 and ER inhibition creates vulnerability to ferroptosis induction, that could be exploited through combination with GPX4 inhibitors, to enhance sensitivity to the current therapies in breast cancer.While CDK4/6 inhibitors (CDK4/6i) have improved outcomes for breast cancer patients, estrogen receptor (ER +) breast cancers often develop resistance, and triple negative breast cancer (TNBC) show poor sensitivity. Here, the authors identify a vulnerability of CDK4/6i treated ER+ and TNBC on ferroptosis and identify the combination of CDK4/6i and GPX4 inhibition as synergistic. [ABSTRACT FROM AUTHOR]

Amorphous powder cores are promising components for next-generation power electronics. However, they present inherent challenges of internal air gaps and stresses during cold compaction, which significantly deteriorate soft magnetic properties. Here, we report the formation of a local adaptive insulation structure of biconcave lens in amorphous powder cores by ultrasonic rheomolding. Consequently, compared with conventional cold-compacted powder cores, the ultrasonic rheomolded powder cores offer significant simultaneous improvements in the permeability from 31.3–32.4 to 41.8–43.3 and the direct-current bias performance from 69.4–69.7% to 87.4–87.8% (7960 A/m), thereby overcoming the trade-off between permeability and direct-current bias performance. In particular, their core losses are as low as 13.73–15.45 kW/m3, approximately one twentieth of that of the cold-compacted powder cores (282.84–304.03 kW/m3) at a magnetic field of 100 mT and 100 kHz. The biconcave-lens insulation structure can effectively buffer the impact of high mechanical stress on the magnetization of magnetic powder particles, allowing for the ultrasonic rheomolded powder cores to maintain better magnetization efficiency and consequently resulting in excellent soft magnetic properties under the cooperative effect of very low internal stresses and low porosity. The ultrasonic rheomolded powder cores can be used as alternative core components in next generation miniaturized power electronics. Amorphous powder cores with superior soft magnetic properties are promising components for next-generation power electronics. Here, authors introduce an ultrasonic rheomolding method to modulate a local adaptive insulation in amorphous powder cores, which induces low core loss and high DC bias. [ABSTRACT FROM AUTHOR]

This study investigated the dynamics of land use and land cover (LULC) modelling, mapping, and assessment in the Kegalle District of Sri Lanka, where policy decision-making is crucial in agricultural development where LULC temporal datasets are not readily available. Employing remotely sensed datasets and machine learning algorithms, the work presented here aims to compare the accuracy of three classification approaches in mapping LULC categories across the time in the study area primarily using the Google Earth Engine (GEE). Three classifiers namely random forest (RF), support vector machines (SVM), and classification and regression trees (CART) were used in LULC modelling, mapping, and change analysis. Different combinations of input features were investigated to improve classification performance. Developed models were optimised using the grid search cross-validation (CV) hyperparameter optimisation approach. It was revealed that the RF classifier constantly outstrips SVM and CART in terms of accuracy measures, highlighting its reliability in classifying the LULC. Land cover changes were examined for two periods, from 2001 to 2013 and 2013 to 2022, implying major alterations such as the conversion of rubber and coconut areas to built-up areas and barren lands. For suitable classification with higher accuracy, the study suggests utilising high spatial resolution satellite data, advanced feature selection approaches, and a combination of several spatial and spatial–temporal data sources. The study demonstrated practical applications of derived temporal LULC datasets for land management practices in agricultural development activities in developing nations. [ABSTRACT FROM AUTHOR]

Diffuse-type gastric cancer (DGC) accounts for approximately one-third of gastric cancer diagnoses but is a more clinically aggressive disease with peritoneal metastases and inferior survival compared with intestinal-type gastric cancer (IGC). The understanding of the pathogenesis of DGC has been relatively limited until recently. Multiomic studies, particularly by The Cancer Genome Atlas, have better characterized gastric adenocarcinoma into molecular subtypes. DGC has unique molecular features, including alterations in CDH1, RHOA, and CLDN18-ARHGAP26 fusions. Preclinical models of DGC characterized by these molecular alterations have generated insight into mechanisms of pathogenesis and signaling pathway abnormalities. The currently approved therapies for treatment of gastric cancer generally provide less clinical benefit in patients with DGC. Based on recent phase II/III clinical trials, there is excitement surrounding Claudin 18.2-based and FGFR2b-directed therapies, which capitalize on unique biomarkers that are enriched in the DGC populations. There are numerous therapies targeting Claudin 18.2 and FGFR2b in various stages of preclinical and clinical development. Additionally, there have been preclinical advancements in exploiting unique therapeutic vulnerabilities in several models of DGC through targeting of the focal adhesion kinase (FAK) and Hippo pathways. These preclinical and clinical advancements represent a promising future for the treatment of DGC. [ABSTRACT FROM AUTHOR]

Purpose: Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results. Methods: Postmenopausal women with HR+ BC who were 45–57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method. Results: This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85–2.81), DRFS (HR = 1.51; 95% CI 0.73–3.11), OS (HR = 1.64; 95% CI 0.75–3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84–4.63) when compared with patients without OFR. Conclusion: In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients. [ABSTRACT FROM AUTHOR]

This report is the first analysis of the coexistence and microstructure of the equilibrium phases in the Fe-Pd L10 + L12 eutectoid region. Coexistence of L10 + L12 is observed at higher temperatures (650 ∘ C ), resulting in L10 polytwin plates with internal boundaries that are decorated by L12. For higher Pd content, the L10 plates are embedded in an extended L12 matrix, but the L12 wetting layers still persist. For aging at low temperatures (525 ∘ C ), L1' + L12 coexistence is observed, but the microstructure is essentially similar, except that L10 is replaced by L1'. The two-phase region is found to be much narrower than reported in published phase diagrams, of order 0.6 to 1 at pct in extent. There may be a further re-entrant narrowing below the L1' formation temperature. This work establishes L1' as a phase distinguishable from both L10 and L12, but does not yet prove that L1' is an equilibrium phase. The preferred formation of L1' at lower temperatures may relate both to stability conferred by overall ferrimagnetic interactions, and perhaps by kinetics, where L1' should have a reduced nucleation barrier from A1 relative to L10. [ABSTRACT FROM AUTHOR]

Background: The CRC-PIPAC-II study prospectively assessed bidirectional therapy (BT) consisting of first-line palliative systemic therapy and electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC-OX) in patients with unresectable colorectal peritoneal metastases (CPM). This study describes the exploration of patient-reported outcomes (PROs). Methods: In this phase II trial, 20 patients with isolated CPM were treated with up to three cycles of BT, each cycle consisting of two to three courses of systemic therapy, followed by ePIPAC-OX (92 mg/m2). Patients were asked to complete the EuroQoL EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-CR29 questionnaires at baseline, during the first cycle of BT, and one and four weeks after each consecutive BT cycle. PRO scores were calculated and compared between baseline and each subsequent time point using linear-mixed modeling (LMM). PROs were categorized into symptom scales and function scales. Symptom scales ranged from 0 to 100, with 100 representing the maximum symptom load. Function scales ranged from 0 to 100, with 100 representing optimal functioning. Results: Twenty patients underwent a total of 52 cycles of bidirectional therapy. Most PROs (29 of 37, 78%) were not significantly affected during trial treatment. In total, only eight PROs (22%) were significantly affected during trial treatment: Six PROs (index value, global health status, emotional functioning, C30, appetite, and insomnia) showed transient improvement at different time points. Two PROs transiently deteriorated: pain initially improved during the first BT cycle [− 16, p < 0.001] yet worsened temporarily one week after the first two BT cycles (+ 20, p < 0.001; + 17, p = 0.004; respectively). Abdominal pain worsened temporarily one week after the first BT cycle (+ 16, p = 0.004), before improving again four weeks after treatment ended (− 10, p = 0.004). All significant effects on Pros were clinically significant and all deteriorations in PROs were of temporary nature. Discussion: Patients undergoing BT for unresectable CPM had significant, but reversible alterations in several PROs. Most affected PROs concerned improvements and only two PROs showed deteriorations. Both deteriorated PROs returned to baseline after trial treatment and were of a temporary nature. These outcomes help to design future studies on the role of ePIPAC in the palliative setting. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between joint structure and gait in patients with knee osteoarthritis (OA). Methods: IMI-APPROACH recruited 297 clinical knee OA patients. Gait data was collected (GaitSmart®) and OA-related joint measures determined from knee radiographs (KIDA) and MRIs (qMRI/MOAKS). Patients were divided into those with/without radiographic OA (ROA). Principal component analyses (PCA) were performed on gait parameters; linear regression models were used to evaluate whether image-based structural and demographic parameters were associated with gait principal components. Results: Two hundred seventy-one patients (age median 68.0, BMI 27.0, 77% female) could be analyzed; 149 (55%) had ROA. PCA identified two components: upper leg (primarily walking speed, stride duration, hip range of motion [ROM], thigh ROM) and lower leg (calf ROM, knee ROM in swing and stance phases). Increased age, BMI, and radiographic subchondral bone density (sclerosis), decreased radiographic varus angle deviation, and female sex were statistically significantly associated with worse lower leg gait (i.e. reduced ROM) in patients without ROA (R2 = 0.24); in ROA patients, increased BMI, radiographic osteophytes, MRI meniscal extrusion and female sex showed significantly worse lower leg gait (R2 = 0.18). Higher BMI was significantly associated with reduced upper leg function for non-ROA patients (R2 = 0.05); ROA patients with male sex, higher BMI and less MRI synovitis showed significantly worse upper leg gait (R2 = 0.12). Conclusion: Structural OA pathology was significantly associated with gait in patients with clinical knee OA, though BMI may be more important. While associations were not strong, these results provide a significant association between OA symptoms (gait) and joint structure. [ABSTRACT FROM AUTHOR]

Estuarine systems that provide valuable ecosystem services to society and important foraging and rearing habitat for fish and wildlife species continue to undergo degradation. In Puget Sound, WA, as much as 70–80% of historic estuarine habitat has been lost to anthropogenic development, and continued losses are expected through the end of the twenty-first century due to rising sea levels. To evaluate whether Puget Sound's estuarine habitats will keep pace with current and projected sea-level rise (SLR), we assessed vertical rates of elevation change from a regional network of surface elevation tables and marker horizons (SET-MH). Over the past two decades, SET-MH equipment has been installed throughout a variety of habitats in five Puget Sound estuaries: the Nisqually, Snohomish, Stillaguamish, and Skagit River estuaries, and Padilla Bay. These data provide a unique opportunity to assess elevation change and habitat resilience across a spatiotemporal and environmental gradient. We observed different rates of surface elevation change among estuaries and habitats (Nisqually = 4.64 ± 2.81 mm/year, Snohomish = 5.71 ± 5.83 mm/year, Stillaguamish = 12.82 ± 10.29 mm/year, Skagit = 16.13 ± 7.57 mm/year, Padilla = − 1.25 ± 1.58 mm/year). The highest rates were found at restoring sites with regular sediment input in the Stillaguamish and Skagit estuaries, whereas rates were consistently negative at low elevation sites in sediment starved Padilla Bay. Many sites in Puget Sound appear to be keeping pace with current rates of relative SLR, and some areas are on track to exceed projected rates through the end of the century. These findings indicate that Puget Sound's estuarine habitats can be resilient to rising tidal levels—as long as sediment delivery is maintained. [ABSTRACT FROM AUTHOR]

Coastal mangrove forests are at risk of being submerged due to sea-level rise (SLR). However, mangroves have persisted with changing sea levels due to a variety of biotic and physical feedback mechanisms that allow them to gain and maintain relative soil surface elevation. Therefore, mangrove's resilience to SLR is dependent upon their ability to build soil elevation at a rate that tracks with SLR, or well-enough to migrate inland. Anthropogenic disturbances, such as altered hydrology and eutrophication, can degrade mangrove forest health and compromise this land building process, placing mangroves at greater risk. Much of Florida's mangroves are adjacent to highly urbanized areas that produce nutrient-loaded runoff. This study assesses how experimental nutrient inputs in the eutrophic Caloosahatchee Estuary influence the soil surface elevation change (SEC) in two distinct mangrove zones. Annual rates of SEC were reduced by phosphorus additions and differed by mangrove zone, ranging from 0.67 ± 0.59 to 2.13 ± 0.61 and 4.21 ± 0.58 to 6.39 ± 0.59 mm year−1 in the fringe and basin zone, respectively. This suggests that eutrophication can reduce the maximum potential SEC response to SLR and that a mangrove forest's vulnerability to SLR is not uniform throughout forest but can differ by mangrove zone. [ABSTRACT FROM AUTHOR]

Introduction: Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve implantation, with an estimated yearly incidence of at least 0.4-1.0%. The Duke criteria and subsequent modifications have been developed as a diagnostic framework for infective endocarditis (IE) in clinical studies. However, their sensitivity and specificity are limited, especially for PVE. Furthermore, their most recent versions (ESC2015 and ESC2023) include advanced imaging modalities, e.g., cardiac CTA and [18F]FDG PET/CT as major criteria. However, despite these significant changes, the weighing system using major and minor criteria has remained unchanged. This may have introduced bias to the diagnostic set of criteria. Here, we aimed to evaluate and improve the predictive value of the modified Duke/ESC 2015 (MDE2015) criteria by using machine learning algorithms. Methods: In this proof-of-concept study, we used data of a well-defined retrospective multicentre cohort of 160 patients evaluated for suspected PVE. Four machine learning algorithms were compared to the prediction of the diagnosis according to the MDE2015 criteria: Lasso logistic regression, decision tree with gradient boosting (XGBoost), decision tree without gradient boosting, and a model combining predictions of these (ensemble learning). All models used the same features that also constitute the MDE2015 criteria. The final diagnosis of PVE, based on endocarditis team consensus using all available clinical information, including surgical findings whenever performed, and with at least 1 year follow up, was used as the composite gold standard. Results: The diagnostic performance of the MDE2015 criteria varied depending on how the category of 'possible' PVE cases were handled. Considering these cases as positive for PVE, sensitivity and specificity were 0.96 and 0.60, respectively. Whereas treating these cases as negative, sensitivity and specificity were 0.74 and 0.98, respectively. Combining the approaches of considering possible endocarditis as positive and as negative for ROC-analysis resulted in an excellent AUC of 0.917. For the machine learning models, the sensitivity and specificity were as follows: logistic regression, 0.92 and 0.85; XGBoost, 0.90 and 0.85; decision trees, 0.88 and 0.86; and ensemble learning, 0.91 and 0.85, respectively. The resulting AUCs were, in the same order: 0.938, 0.937, 0.930, and 0.941, respectively. Discussion: In this proof-of-concept study, machine learning algorithms achieved improved diagnostic performance compared to the major/minor weighing system as used in the MDE2015 criteria. Moreover, these models provide quantifiable certainty levels of the diagnosis, potentially enhancing interpretability for clinicians. Additionally, they allow for easy incorporation of new and/or refined criteria, such as the individual weight of advanced imaging modalities such as CTA or [18F]FDG PET/CT. These promising preliminary findings warrant further studies for validation, ideally in a prospective cohort encompassing the full spectrum of patients with suspected IE. [ABSTRACT FROM AUTHOR]

Background: Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival. Methods: Patients who had cT2-4aN0-3M0 esophageal cancer treated with nCRT were identified from a trial database. Metastases detected up to 14 weeks after nCRT on 18F-FDG-PET/CT or during surgery were categorized as oligometastases (≤3 lesions located in one single organ or one extra-regional lymph node station) or as non-oligometastases. The primary outcome was the proportion of patients with metastases after nCRT. The secondary outcomes were overall survival (OS) and the site and treatment of metastases. Results: Between 2013 and 2021, 973 patients received nCRT, and 10.3% had interval metastases. Of 100 patients, 30 (30%) had oligometastases, located mostly in non-regional lymph nodes (33.3%) or bones (26.7%). The median OS of this group was 13.8 months (95% confidence interval [CI] 9.2–27.1 months). Of 30 patients, 12 (40%) with oligometastases underwent potentially curative treatment, with a median OS of 22.8 months (95% CI 10.4–NA). The patients with non-oligometastases underwent mostly systemic therapy or BSC and had a median OS of 9 months (95% CI 7.4–10.9 months). Conclusions: Interval metastases were detected in about 10% of patients after nCRT, underscoring the importance of re-staging with 18F-FDG-PET/CT for those who proceed to surgery. A favorable survival might be accomplished for a subgroup of patients with oligometastases. [ABSTRACT FROM AUTHOR]

Recent advances in Rosai-Dorfman-Destombes disease (RDD), notably molecular testing, targeted therapy, and PET-CT imaging, hold promise for better recognition and improved outcomes. This study presents patients diagnosed and treated in a "real world" setting, where navigating limited resources must be considered. This retrospective single-center review includes 15 adult patients diagnosed with RDD at Vancouver General Hospital between November 2015 and October 2023. The cohort comprised five males and ten females with a median age 53 years (range 19–80 years). All 15 patients had extra-nodal disease; 11 patients exclusively had extra-nodal disease, and four patients also had lymph node involvement. Seven patients had tissue next-generation sequencing, identifying MAP2K1 mutations in four cases and a KRAS p.K117N mutation in one case that was treated with targeted therapy using trametinib. PET-CT was used for disease staging in four cases. Six patients with refractory disease tolerated lenalidomide and dexamethasone without significant toxicity; three patients achieved complete response, and three had partial response. This study highlights RDD's diverse extra-nodal manifestations. Lenalidomide combined with dexamethasone is an effective and well-tolerated treatment option for select patients, especially those with refractory disease. Broad utilization of NGS and PET-CT can positively influence management decisions. [ABSTRACT FROM AUTHOR]

The recent proliferation of large language models (LLMs) has led to divergent narratives about their environmental impacts. Some studies highlight the substantial carbon footprint of training and using LLMs, while others argue that LLMs can lead to more sustainable alternatives to current practices. We reconcile these narratives by presenting a comparative assessment of the environmental impact of LLMs vs. human labor, examining their relative efficiency across energy consumption, carbon emissions, water usage, and cost. Our findings reveal that, while LLMs have substantial environmental impacts, their relative impacts can be dramatically lower than human labor in the U.S. for the same output, with human-to-LLM ratios ranging from 40 to 150 for a typical LLM (Llama-3-70B) and from 1200 to 4400 for a lightweight LLM (Gemma-2B-it). While the human-to-LLM ratios are smaller with regard to human labor in India, these ratios are still between 3.4 and 16 for a typical LLM and between 130 and 1100 for a lightweight LLM. Despite the potential benefit of switching from humans to LLMs, economic factors may cause widespread adoption to lead to a new combination of human and LLM-driven work, rather than a simple substitution. Moreover, the growing size of LLMs may substantially increase their energy consumption and lower the human-to-LLM ratios, highlighting the need for further research to ensure the sustainability and efficiency of LLMs. [ABSTRACT FROM AUTHOR]

Background: We developed a whole transcriptome sequencing (WTS)-based Consensus Molecular Subtypes (CMS) classifier using FFPE tissue and investigated its prognostic and predictive utility in a large clinico-genomic database of CRC patients (n = 24,939). Methods: The classifier was trained against the original CMS datasets using an SVM model and validated in an independent blinded TCGA dataset (88.0% accuracy). Kaplan–Meier estimates of overall survival (OS) and time-on-treatment (TOT) were calculated for each CMS (p < 0.05 considered significant). Results: CMS2 tumors were enriched on left-side of colon and conferred the longest median OS. In RAS-wildtype mCRC, left-sided tumors and CMS2 classification were associated with longer TOT with anti-EGFR antibodies (cetuximab and panitumumab). When restricting to only CMS2, there was no significant difference in TOT between right- versus left-sided tumors. CMS1 tumors were associated with a longer median TOT with pembrolizumab relative to other CMS groups, even when analyzing only microsatellite stable (MSS) tumors. Discussion: A WTS-based CMS classifier allowed investigation of a large multi-institutional clinico-genomic mCRC cohort, suggesting anti-EGFR therapy benefit for right-sided RAS-WT CMS2 tumors and immune checkpoint inhibitor benefit for MSS CMS1. Routine CMS classification of CRC provides important treatment associations that should be further investigated. [ABSTRACT FROM AUTHOR]

Ageing impairs the ability of neural stem cells (NSCs) to transition from quiescence to proliferation in the adult mammalian brain. Functional decline of NSCs results in the decreased production of new neurons and defective regeneration following injury during ageing1–4. Several genetic interventions have been found to ameliorate old brain function5–8, but systematic functional testing of genes in old NSCs—and more generally in old cells—has not been done. Here we develop in vitro and in vivo high-throughput CRISPR–Cas9 screening platforms to systematically uncover gene knockouts that boost NSC activation in old mice. Our genome-wide screens in primary cultures of young and old NSCs uncovered more than 300 gene knockouts that specifically restore the activation of old NSCs. The top gene knockouts are involved in cilium organization and glucose import. We also establish a scalable CRISPR–Cas9 screening platform in vivo, which identified 24 gene knockouts that boost NSC activation and the production of new neurons in old brains. Notably, the knockout of Slc2a4, which encodes the GLUT4 glucose transporter, is a top intervention that improves the function of old NSCs. Glucose uptake increases in NSCs during ageing, and transient glucose starvation restores the ability of old NSCs to activate. Thus, an increase in glucose uptake may contribute to the decline in NSC activation with age. Our work provides scalable platforms to systematically identify genetic interventions that boost the function of old NSCs, including in vivo, with important implications for countering regenerative decline during ageing.CRISPR–Cas9 screens in cultures of young and old neural stem cells (NSCs) and in vivo in old mice identify gene knockouts that can boost old NSC activation and neurogenesis, with Slc2a4, which encodes the glucose transporter GLUT4, showing particular efficacy. [ABSTRACT FROM AUTHOR]

Gate-defined quantum dots are a promising candidate system for realizing scalable, coupled qubit systems and serving as a fundamental building block for quantum computers. However, present-day quantum dot devices suffer from imperfections that must be accounted for, which hinders the characterization, tuning, and operation process. Moreover, with an increasing number of quantum dot qubits, the relevant parameter space grows sufficiently to make heuristic control infeasible. Thus, it is imperative that reliable and scalable autonomous tuning approaches are developed. This meeting report outlines current challenges in automating quantum dot device tuning and operation with a particular focus on datasets, benchmarking, and standardization. We also present insights and ideas put forward by the quantum dot community on how to overcome them. We aim to provide guidance and inspiration to researchers invested in automation efforts. [ABSTRACT FROM AUTHOR]

Endolymphatic hydrops, increased endolymphatic fluid within the cochlea, is the key pathologic finding in patients with Meniere's disease, a disease of episodic vertigo, fluctuating hearing loss, tinnitus, and aural fullness. Endolymphatic hydrops also can occur after noise trauma and its presence correlates with cochlear synaptopathy, a form of hearing loss caused by reduced numbers of synapses between hair cells and auditory nerve fibers. Here we tested whether there is a mechanistic link between these two phenomena by using multimodal imaging techniques to analyze the cochleae of transgenic mice exposed to blast and osmotic challenge. In vivo cochlear imaging after blast exposure revealed dynamic increases in endolymph that involved hair cell mechanoelectrical transduction channel block but not the synaptic release of glutamate at the hair cell–auditory nerve synapse. In contrast, ex vivo and in vivo auditory nerve imaging revealed that synaptopathy requires glutamate release from hair cells but not endolymphatic hydrops. Thus, although endolymphatic hydrops and cochlear synaptopathy are both observed after noise exposure, one does not cause the other. They are simply co-existent sequelae that derive from the traumatic stimulation of hair cell stereociliary bundles. Importantly, these data argue that Meniere's disease derives from hair cell transduction channel blockade. [ABSTRACT FROM AUTHOR]

As metallic nanostructures shrink towards the size of the electronic mean free path, thermal conductivity decreases due to increased electronic scattering rates. Matthiessen's rule is commonly applied to assess changes in electron scattering rates, although this rule has not been validated experimentally at typical operating temperatures for most of the electronic systems (e.g., near room temperature). In this study, we experimentally evaluate the validity of Matthiessen's rule in determining the thermal conductivity of thin metal films by measuring the in-plane thermal conductivity and electronic scattering rates of copper (Cu) films with varying thicknesses (27 nm — 5 µm), microstructures, and grain boundary segregation. Comparing total electron scattering rates measured with infrared ellipsometry to infrared ultrafast pump-probe measurements, we find that the electron-phonon coupling factor is independent of film thickness, whereas the total electronic scattering rate increases with decreasing film thickness. Our findings provide experimental validation of Matthiessen's rule for electron transport in thin metal films at room temperature and also introduce an approach to discern critical heat transfer processes in thin metal interconnects, which holds significance for the advancement of future CMOS technology. The authors examine Matthiessen's rule for determining the thermal conductivity in thin Cu film. They attribute reductions in the thermal conductivity of Cu to electron scattering at boundaries and grain boundary segregation. [ABSTRACT FROM AUTHOR]

Background: The commonly used ('legacy') PROMs evaluating outcomes of total hip arthroplasty (THA), have several limitations regarding their measurement properties and interpretation of scores. One innovation in PROMs is the use of Computerized Adaptive Testing (CAT). The Patient-Reported Outcomes Measurement Information System (PROMIS®) is a validated system of CATs. The aim of this study was to assess the measurement properties of PROMIS and legacy instruments in patients undergoing THA. Methodology: Patients in this multicenter study filled out a questionnaire twice, including Dutch-Flemish PROMIS v1.2 Physical Function (PROMIS-PF) and v1.1 Pain Interference (PROMIS-PI) CATs and short forms, PROMIS v1.0 Pain Intensity, and legacy PROMs (Hip disability and Osteoarthritis Outcome Score (HOOS), HOOS-Physical function Shortform (HOOS-PS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Hip Score (OHS), and two numeric rating scales measuring pain). The reliability, measurement precision (Standard Error of Measurement (SEM)), smallest detectable change (SDC), and burden of PROMIS instruments were presented head-to-head to legacy PROMs. Furthermore, construct validity was assessed. Results: 208 patients were included. All instruments had a sufficient test-retest reliability (range ICC: 0.83–0.96). The SEM of PROMIS CATs and short forms ranged from 1.8 to 2.2 T-score points, the SEM of legacy instruments 2.6–11.1. The SDC of PROMIS instruments ranged from 2.1 to 7.3 T-score points, the SDC of legacy instruments 7.2–30.9. The construct validity of PROMIS CAT and short forms were found sufficient, except for the PROMIS-PI short form. The burden of PROMIS CATs was smaller than PROMIS short forms (range 4.8–5.2 versus 8–20 items, respectively). The burden of legacy instruments measuring physical functioning ranged from 5 to 40 items. Conclusions: The PROMIS-PF is less burdensome, with high measurement precision, and almost no minimal or maximal scores, and an equal reliability compared to legacy instruments measuring physical functioning in patients undergoing THA. The PROMIS Pain Intensity 1a is comparable to the legacy pain instruments in terms of burden, reliability and SDC. Measuring the construct Pain Interference may not have additional value in this population because of its high correlation with instruments measuring physical functioning. The SDC values presented in this study can be used for individual patient monitoring. [ABSTRACT FROM AUTHOR]

Background: To develop and validate a novel administration device for holmium-166 transarterial radioembolisation (TARE) with the purpose of facilitating controlled fractional microsphere administration for a more flexible and image-guided TARE procedure. Methods: A Controlled Administration Device (CAD) was developed using MR-conditional materials. The CAD contains a rotating syringe to keep the microspheres in suspension during administration. Different rotational speeds were tested ex vivo to optimise the homogeneity of microsphere fractions administered from the device. The technical performance, accuracy, and safety was validated in three patients in a clinical TARE setting by administering a standard clinical dose in 5 fractions (identifier: NCT05183776). MRI-based dosimetry was used to validate the homogeneity of the given fractions in vivo, and serious adverse device event ((S)A(D)E) reporting was performed to assess safety of the CAD. Results: A rotational speed of 30 rpm resulted in the most homogeneous microsphere fractions with a relative mean deviation of 1.1% (range: -9.1-8.0%). The first and last fraction showed the largest deviation with a mean of -26% (std. 16%) and 7% (std. 13%). respectively. In the three patient cases the homogeneity of the microsphere fractions was confirmed given that MRI-based dosimetry showed near linear increase of mean absorbed target liver dose over the given fractions with R2 values of 0.98, 0.97 and 0.99. No (S)A(D)E's could be contributed to the use of the CAD. Conclusions: The newly developed CAD facilitates safe and accurate fractional microsphere administration during TARE, and can be used for multiple applications in the current and future workflows of TARE. [ABSTRACT FROM AUTHOR]

Mozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation—follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1–9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1–9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF < 5% had SCR of 5.0 and 4.7. The district with TF ≥ 5% had a SCR of 6.0. This enhanced TIS furthered understanding of transmission in these districts and provides information on additional indicators for monitoring trachoma programs. [ABSTRACT FROM AUTHOR]

Prematurity-associated lung disease (PLD) is a long-term consequence of preterm-birth. Since the underlying mechanisms of PLD remain poorly characterised, we compared the urinary metabolome between recently described spirometry phenotypes of PLD. Preterm- and term-born children aged 7–12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) cohort, underwent spirometry and urine collection. The urinary metabolome was analysed by gas chromatography time-of-flight mass spectrometry. Preterm-born children were classified into phenotypes of prematurity-associated obstructive lung disease (POLD, Forced expiratory volume in 1 s (FEV1) < lower limit of normal (LLN), FEV1/Forced Vital Capacity (FVC) < LLN), prematurity-associated preserved ratio impaired spirometry (pPRISm, FEV1 < LLN, FEV1/FVC ≥ LLN) and Preterm/Term controls (FEV1 ≥ LLN). Metabolite set enrichment analysis was used to link significantly altered metabolites between the groups with metabolic pathways. Univariable and multivariable linear regression models examined associations between early and current life factors and significantly altered metabolites of interest. Urine from 197 preterm- and 94 term-born children was analysed. 23 and 25 were classified into POLD and pPRISm groups respectively. Of 242 identified metabolites, 49 metabolites were significantly altered in the POLD group compared with Preterm controls. Decreased capric acid (log2 fold change − 0.23; p = 0.003), caprylic acid (− 0.18; 0.003) and ceratinic acid (− 0.64; 0.014) in the POLD group, when compared to preterm controls, were linked with reduced β-oxidation of very long chain fatty acids (p = 0.004). Reduced alanine (log2 fold change − 0.21; p = 0.046), glutamic acid (− 0.24; 0.023), and pyroglutamic acid (− 0.17; 0.035) were linked with decreased glutathione metabolism (p = 0.008). These metabolites remained significantly associated with POLD in multivariable models adjusting for early/current life factors. The pPRISm urinary metabolome was minimally changed when compared with preterm-born controls. When compared to term-born subjects, alterations in tryptophan metabolism were implicated (p = 0.01). The urinary metabolome in POLD showed significantly altered β-oxidation of fatty acids and glutathione metabolism, implying alterations in cellular metabolism and oxidative stress. Similar findings have been noted in adults with chronic obstructive pulmonary disease. Given the similarity of findings between the POLD group and those reported for COPD, the POLD group should be considered at future risk of developing COPD. [ABSTRACT FROM AUTHOR]

Plants remain an important source of biologically active small molecules with high therapeutic potential. The voltage-gated potassium (Kv) channel formed by Kv7.2/3 (KCNQ2/3) heteromers is a major target for anticonvulsant drug development. Here, we screened 1444 extracts primarily from plants collected in California and the US Virgin Islands, for their ability to activate Kv7.2/3 but not inhibit Kv1.3, to select against tannic acid being the active component. We validated the 7 strongest hits, identified Thespesia populnea (miro, milo, portia tree) as the most promising, then discovered its primary active metabolite to be gentisic acid (GA). GA highly potently activated Kv7.2/3 (EC50, 2.8 nM). GA is, uniquely to our knowledge, 100% selective for Kv7.3 versus other Kv7 homomers; it requires S5 residue Kv7.3-W265 for Kv7.2/3 activation, and it ameliorates pentylenetetrazole-induced seizures in mice. Structure-activity studies revealed that the FDA-approved vasoprotective drug calcium dobesilate, a GA analog, is a previously unrecognized Kv7.2/3 channel opener. Also an active aspirin metabolite, GA provides a molecular rationale for the use of T. populnea as an anticonvulsant in Polynesian indigenous medicine and presents novel pharmacological prospects for potent, isoform-selective, therapeutic Kv7 channel activation. The voltage-gated potassium (Kv) channel formed by Kv7.2/3 heteromers is a major target for anticonvulsant drug development, however, specificity and potency are key challenges for Kv7.2/3 opener development. Here, the authors report the discovery of gentisic acid as a potent and selective Kv7.3 opener from Thespesia populnea — a plant reportedly used as an anticonvulsant in Polynesian traditional medicine. [ABSTRACT FROM AUTHOR]

Pediatric obesity rates have quadrupled in the United States, and deficits in higher-order cognition have been linked to obesity, though it remains poorly understood how deviations from normal body mass are related to the neural dynamics serving cognition in youth. Herein, we determine how age- and sex-adjusted measures of body mass index (zBMI) scale with neural activity in brain regions underlying fluid intelligence. Seventy-two youth aged 9–16 years underwent high-density magnetoencephalography while performing an abstract reasoning task. The resulting data were transformed into the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Whole-brain correlations with zBMI were subsequently conducted to quantify relationships between zBMI and neural activity serving abstract reasoning. Our results reveal that participants with higher zBMI exhibit attenuated theta (4–8 Hz) responses in both the left dorsolateral prefrontal cortex and left temporoparietal junction, and that weaker temporoparietal responses scale with slower reaction times. These findings suggest that higher zBMI values are associated with weaker theta oscillations in key brain regions and altered performance during an abstract reasoning task. Thus, future investigations should evaluate neurobehavioral function during abstract reasoning in youth with more severe obesity to identify the potential impact. Standardized indices of obesity are associated with alterations in neural oscillatory activity and functional connectivity in brain regions supporting abstract reasoning and fluid intelligence in typically developing youth. [ABSTRACT FROM AUTHOR]

We present the theory, concept and design of an efficient, megawatt coherent Cherenkov radiation source based on a two-dimensional periodic surface lattice (2D-PSL) cavity combined with a novel energy recovery system for the generation of highly efficient (> 50%) single-frequency radiation. We demonstrate the scalability of the transverse dimension of the 2D-PSL cavity of the Cherenkov source and thus the potential for efficient, continuous-wave, high-power (> 1 MW) operation; fundamental to the eventual realization of clean, fusion energy. These new sources, with the capacity to operate in the 0.1-10THz range, hold strong promise to address the long-standing "Terahertz gap". By combining a Cherenkov oscillator driven by a non-gyrating beam with an innovative four-stage depressed collector energy recovery system, the overall device efficiency can be increased to be competitive with gyrotrons in the requirements for heating and current drive in fusion plasma. In these Cherenkov devices, the frequency independence of the magnetic guide field enables advantageous frequency scaling without deployment constraints, making them especially attractive for high-impact applications in fusion science, turbulence diagnostics, non-destructive testing and biochemical spectroscopy. The novel energy recovery techniques presented in this paper have broad applicability to many electron-beam driven devices, bringing revolutionary potential to future THz source technologies. [ABSTRACT FROM AUTHOR]

In global impact modeling, there is a need to address the heterogeneous characteristics of households and individuals that drive different behavioral responses to, for example, environmental risk, socio-economic policy changes and spread of diseases. In this research, we present GLOPOP-S, the first global synthetic population dataset with 1,999,227,130 households and 7,335,881,094 individuals for the year 2015, consistent with population statistics at an administrative unit 1 level. GLOPOS-S contains the following attributes: age, education, gender, income/wealth, settlement type (urban/rural), household size, household type, and for selected countries in the Global South, ownership of agricultural land and dwelling characteristics. To generate GLOPOP-S, we use microdata from the Luxembourg Income Study (LIS) and Demographic and Health Surveys (DHS) and apply synthetic reconstruction techniques to fit national survey data to regional statistics, thereby accounting for spatial differences within and across countries. Additionally, we have developed methods to generate data for countries without available microdata. The dataset can be downloaded per region or country. GLOPOP-S is open source and can be extended with other attributes. [ABSTRACT FROM AUTHOR]

Purpose: High consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited. Methods: Fruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case–control studies. Unconditional logistic regression was used to estimate study-specific odds ratio's (ORs) with 95% confidence intervals (CIs) and combined using a random-effects model for intakes of total fruits, total vegetables, and subgroups of fruits and vegetables. Results: A total of 11 case–control studies were included, comprising 5637 BC cases and 10,504 controls. Overall, participants with the highest intakes versus the lowest intakes of fruits in total (OR 0.79; 95% CI 0.68–0.91), citrus fruits (OR 0.81; 95% CI 0.65–0.98), pome fruits (OR 0.76; 95% CI 0.65–0.87), and tropical fruits (OR 0.84; 95% CI 0.73–0.94) reduced the BC risk. Greater consumption of vegetables in total, and specifically shoot vegetables, was associated with decreased BC risk (OR 0.82; 95% CI 0.68–0.96 and OR 0.87; 95% CI 0.78–0.96, respectively). Substantial heterogeneity was observed for the associations between citrus fruits and total vegetables and BC risk. Conclusion: This comprehensive study provides compelling evidence that the consumption of fruits overall, citrus fruits, pome fruits and tropical fruits reduce the BC risk. Besides, evidence was found for an inverse association between total vegetables and shoot vegetables intake. [ABSTRACT FROM AUTHOR]

Purpose: Pelvic incidence (PI) is commonly used to determine sagittal alignment. Historically, PI was believed to be a fixed anatomic parameter. However, recent studies have suggested that there is positionally-dependent motion that occurs through the sacroiliac joint (SIJ) resulting in changes in PI. Methods: We reviewed 100 consecutive adult spinal deformity (ASD) patients seen at our academic tertiary referral center. Two reviewers measured pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and lumbar lordosis (LL) on standing radiographs and scout computed tomography scans (CT). Unilateral, bilateral, or absent SIJ vacuum sign (VS) was determined using CTs. Results: Eighty-six patients (42 M:44 F) were included with an average age of 64.1 years and BMI of 28.8 kg/m2. Standing PI was low (< 50°) in 35 patients (40.7%), average (50°-60°) in 22 (25.6%), and high (> 60°) in 29 (33.7%). Average and high PI patients had significant PI changes of 3.0° (p = 0.037) and 4.6° (p = 0.005), respectively. Bilateral SIJ VS was seen in 68 patients, unilateral VS in 9, and VS was absent in 9. The average change in PI between standing and supine was 2.1° in bilateral SIJ VS patients (p = 0.045), 2.2° in unilateral SIJ VS (p = 0.23), and − 0.1° in patients without SIJ VS (p = 0.93). The average absolute difference in PI between supine and standing was 5.5° ±5.5° (p < 0.001). Conclusion: There is a change in PI from supine to standing. In patients with high PI and bilateral VS on CT, the change from supine to standing is significant, perhaps representing instability of the SIJ. [ABSTRACT FROM AUTHOR]

Difficulties in global face processing have been associated with autism. However, autism is heterogenous, and it is not known which dimensions of autistic traits are implicated in face-processing difficulties. To address this gap in knowledge, we conducted two experiments to examine how identification of Mooney face stimuli (stylized, black-and-white images of faces without details) related to the six subscales of the Comprehensive Autistic Trait Inventory in young adults. In Experiment 1, regression analyses indicated that participants with poorer communication skills had lower task sensitivity when discriminating between face-present and face-absent images, whilst other autistic traits had no unique predictive value. Experiment 2 replicated these findings and additionally showed that autistic traits were linked to a reduced face inversion effect. Taken together, these results indicate autistic traits, especially communication difficulties, are associated with reduced configural processing of face stimuli. It follows that both reduced sensitivity for identifying upright faces amongst similar-looking distractors and reduced susceptibility to face inversion effects may be linked to relatively decreased reliance on configural processing of faces in autism. This study also reinforces the need to consider the different facets of autism independently. [ABSTRACT FROM AUTHOR]

Introduction: Combined radiotherapy and immune checkpoint inhibition is a potential treatment option for head and neck squamous cell carcinoma (HNSCC). Immunocompetent mouse models can help to successfully develop radio- immunotherapy combinations and to increase our understanding of the effects of radiotherapy on the tumor microenvironment for future clinical translation. Therefore, the aim of this study was to develop a homogeneous, reproducible HNSCC model originating from the Mouse Oral Cancer 1 (MOC1) HNSCC cell line, and to explore the radiotherapy-induced changes in its tumor microenvironment, using flow cytometry and PD-L1 microSPECT/CT imaging. Materials and Methods: In vivo growing tumors originating from the parental MOC1 line were used to generate single cell derived clones. These clones were screened in vitro for their ability to induce programmed cell death ligand 1 (PD-L1) and major histocompatibility complex class I (MHC-I) following IFNγ exposure. Clones with different IFNγ sensitivity were inoculated in C57BL/6 mice and assessed for tumor outgrowth. The composition of the tumor microenvironment of a stably growing (non)irradiated MOC1-derived clone was assessed by immunohistochemistry, flow cytometry and PD-L1 microSPECT/CT. Results: Low in vitro inducibility of MHC-I and PD-L1 by IFNγ was associated with increased tumor outgrowth of MOC1 clones in vivo. Flow cytometry analysis of cells derived from a stable in vivo growing MOC1 clone MOC1.3D5low showed expression of MHC-I and PD-L1 on several cell populations within the tumor. Upon irradiation, MHC-I and PD-L1 increased on leukocytes (CD45.2+) and cancer associated fibroblasts (CD45.2−/EpCAM−/CD90.1+). Furthermore, PD-L1 microSPECT/CT showed increased tumor uptake of radiolabeled PD-L1 antibodies with a heterogeneous spatial distribution of the radio signal, which co-localized with PD-L1+ and CD45.2+ areas. Discussion: PD-L1 and MHC-I inducibility by IFNγ in vitro is associated with tumor outgrowth of MOC1 clones in vivo. In tumors originating from a stably growing MOC1-derived clone, expression of these immune-related markers was induced by irradiation shown by flow cytometry on several cell populations within the tumor microenvironment such as immune cells and cancer associated fibroblasts. PD-L1 microSPECT/CT showed increased tumor uptake following radiotherapy, and autoradiography showed correlation of uptake with areas that are heavily infiltrated by immune cells. Knowledge of radiotherapy-induced effects on the tumor microenvironment in this model can help optimize timing and dosage for radio- immunotherapy combination strategies in future research. [ABSTRACT FROM AUTHOR]

Purpose: Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced. Methods: All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR). Results: A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only − 0.01%. The 5-year overall survival (OS) and relative survival (RS) were 24.5 and 32.4%, respectively. Relative survival did not increase over time. The addition of adjuvant radiotherapy to surgery was not associated with a higher OS and RS compared to surgery alone. Conclusion: Sinonasal mucosal melanoma is a rare disease with stable incidence rates in the Netherlands between 2001 and 2021. There has been no improvement in survival over the course of the inclusion period. The study reaffirms that adjuvant radiotherapy does not seem to improve patient outcomes. Given the generally poor outcomes for SNMM patients, novel therapeutic options ought to be considered in order to improve care. [ABSTRACT FROM AUTHOR]

Purpose: Tobacco and alcohol use influence cancer risk as well as treatment outcomes, specifically for esophageal and gastric cancer patients. Therefore, it is an important topic to discuss during consultations. This study aims to uncover medical, radiation, and surgical oncologists’ communication about substance use, i.e., tobacco and alcohol use, in simulated consultations about curative and palliative esophagogastric cancer treatment. Methods: Secondary analyses were performed on n = 40 standardized patient assessments (SPAs) collected in three Dutch clinical studies. Simulated patients with esophagogastric cancer were instructed to ask about smoking or alcohol use during treatment. The responses of the 40 medical, radiation, and surgical oncologists were transcribed verbatim, and thematic analysis was performed in MAXQDA. Results: Oncologists consistently advocated smoking cessation during curative treatment. There was more variation in their recommendations and arguments in the palliative compared to the curative setting and when addressing alcohol use instead of smoking. Overall, oncologists were less stringent regarding behavior change in the palliative than in the curative setting. Few oncologists actively inquired about the patient’s perspective on the substance use behavior, the recommended substance use change, or the support offered. Conclusion: Clear guidelines for oncologists on when and how to provide unequivocal recommendations about substance use behavior change and support to patients are needed. Oncologists might benefit from education on how to engage in a conversation about smoking or alcohol. [ABSTRACT FROM AUTHOR]

The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid factor (RF) for modern treatment outcomes remains unknown. We aimed to investigate the prognostic value of IgA-ACPA and IgA-RF for treatment outcomes in an early arthritis population. IgA-ACPA/RF isotypes were measured in baseline sera from 480 inflammatory arthritis (IA) patients, who were included in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH). The tREACH trial was a multicentre, stratified, single-blinded trial with a treat-to-target approach. The prognostic value of IgA-ACPA/RF was determined by evaluating differences in (1) quick-attained (< 6 months after diagnosis) and persistent remission rates, (2) DMARD-free remission and (3) biological use between IA patients with and without IgA-ACPA/RF over 3 years of follow-up. IgA-ACPA was present in 23% of patients and overlapped with IgG-ACPA positivity in 94%. Similarly, IgA-RF overlapped with IgM-RF in 90% of patients. IgA-ACPA positivity was associated with lower DFR rates and more biological use, but this effect was largely mediated by the presence of IgG-ACPA, since this effect disappeared after stratification for IgG-ACPA (HR 0.6, 95%CI 0.2-1.6 for DFR). No differences were observed in 'quick-attained and persistent remission' rates and for IgA-RF. Their seems to be no additional value of IgA-ACPA and IgA-RF for modern, long-term clinical outcomes. The effects of IgA-ACPA seen in our study are largely mediated by the presence of IgG-ACPA. Based on these results, there is no rationale for measuring these isotypes in daily practice. [ABSTRACT FROM AUTHOR]

The effective lifetime of the B s 0 meson in the decay B s 0 → J / ψK S 0 is measured using data collected during 2016–2018 with the CMS detector in s = 13 TeV proton-proton collisions at the LHC, corresponding to an integrated luminosity of 140 fb−1. The effective lifetime is determined by performing a two-dimensional unbinned maximum likelihood fit to the B s 0 meson invariant mass and proper decay time distributions. The resulting value of 1.59 ± 0.07(stat) ± 0.03(syst) ps is the most precise measurement to date and is in good agreement with the expected value. [ABSTRACT FROM AUTHOR]

Objectives: Previous research has demonstrated that mindfulness meditation is associated with a variety of benefits, including improved mental health. Researchers have suggested these benefits may be underpinned by differences in neural oscillations. However, previous studies measuring neural oscillations have not controlled for non-oscillatory neural activity, the power spectrum of which follows a 1/f distribution (whereby the power of neural activity at each frequency is inversely proportional to that frequency (such that as frequency increases, power decreases)) and contributes to power measurements within oscillation frequencies of interest. We applied recently developed methods to determine if past findings related to neural oscillations in meditation are present even after controlling for non-oscillatory 1/f activity. Method: Forty-eight experienced meditators and 44 demographically matched non-meditators provided resting electroencephalography (EEG) recordings. Whole-scalp EEG comparisons (topographical ANOVAs) were used to test for differences between meditators and non-meditators in the distribution or global power of activity for theta, alpha, beta, and gamma oscillations, and for the 1/f components slope and intercept using the extended Better OSCillation detection toolbox. Results: Results indicated that meditators showed differences in theta, alpha, and gamma oscillatory power compared to non-meditators (all p < 0.05). Post hoc testing suggested that the oscillatory differences were primarily driven by differences in the distribution of neural activity between meditators and non-meditators, rather than differences in the overall power across all scalp electrodes. Conclusions: Our results suggest that experience with meditation is associated with higher oscillatory power and altered distributions of theta, alpha, and gamma oscillations, even after controlling for non-oscillatory 1/f activity. Band-specific differences in oscillatory activity may be a mechanism through which meditation leads to neurophysiological benefits. Preregistration: This study was not preregistered. [ABSTRACT FROM AUTHOR]

The recovery trajectories of collegiate athletes with sport-related concussion (SRC) are well characterized in contact/collision sports but are less well understood in limited contact sports with lower risk, reducing the ability of clinicians to effectively manage the return-to-play (RTP) process. The current study investigated the time to asymptomatic and RTP across a broad range of male and female collegiate sports and sought to group sports by recovery intervals. Data from the Concussion Assessment, Research and Education (CARE) Consortium included 1049 collegiate athletes who sustained a SRC while participating in game or practice/training of their primary sport. Injury setting and subsequent clinical presentation data were obtained. Survival analysis using the Cox Proportional Hazard model estimated the median recovery times for each sport. Optimal univariate K-means clustering grouped sports into recovery categories. Across all sports, median time to asymptomatic following SRC ranged from 5.9 (female basketball) to 8.6 days (male wrestling). Median RTP protocol duration ranged from 4.9 days (female volleyball) to 6.3 days (male wrestling). Median total RTP days ranged from 11.2 days (female lacrosse) to 16.9 days (male wrestling). Sport clusters based on recovery differences in time to asymptomatic (3) and RTP protocol duration (2) were identified. The findings from this study of a large sample of more than 1000 NCAA collegiate athletes with SRC show there exists ranges in recovery trajectories. Clinicians can thus manage athletes with similar guidelines, with individualized treatment and recovery plans. [ABSTRACT FROM AUTHOR]

Background: This paper investigates the mechanical properties and failure behaviours of rivet-bonded hybrid joints composed of aluminium adherends and steel rivets under quasi-static tensile loading. Objective: The damage law of hybrid joints is studied to provide a reference for the design and manufacture of hybrid joints. Methods: Tensile tests were conducted on aluminium and steel specimens at various triaxial stress levels. The corresponding finite element model (FEM) was developed to verify the Johnson–Cook damage parameters of the studied metals. The hybrid joint considering the rivet forming process was constructed through FE modelling using the Johnson–Cook failure criterion and Cohesive Zone Model (CZM), which was then validated with the experimental results. Results: Experimental results of the hybrid joint showed that a typical two-stage failure: 1) the adhesive layer bears the majority of the load during the initial loading stage, and 2) the adhesive layer completely fails after reaching the peak load and the rivet solely bears the load subsequently. Conclusions: The riveting process did not cause damage to the adhesive layer, which ensured the reliability of the manufacturing techniques of the hybrid joint. And the yielding of rivets may buffer the immediate failure of hybrid joints. [ABSTRACT FROM AUTHOR]

Based on the two-dimensional resistive magnetohydrodynamics (MHD) model, this study explores the impact of shear flow on the resonant magnetic perturbation (RMP)-induced double tearing mode (DTM). The results indicate that the effectiveness of shear flow in suppressing the double tearing mode is primarily dependent on the flow velocity at the outer rational surface. A notable finding is that, with higher flow velocities, the double tearing mode is effectively suppressed. However, in cases of very weak flow velocities, the shear flow still exerts an influence, but with a limited suppression effect. Specifically, it can only inhibit the inner island, while the outer island continues to grow under the influence of the resonant magnetic perturbation. [ABSTRACT FROM AUTHOR]

Progressive inflammation of one hemisphere characterises Rasmussen's encephalitis (RE), but contralesional epileptiform activity has been repeatedly reported. We aimed to quantify contralesional epileptiform activity in RE and uncover its functional and structural underpinnings. We retrospectively ascertained people with RE treated between 2000 and 2018 at a tertiary centre (Centre 1) and reviewed all available EEG datasets. The temporal occurrence of preoperative contralesional epileptiform activity (interictal/ictal) was evaluated using mixed-effects logistic regression. Cases with/without contralesional epileptiform activity were compared for cognition, inflammation (ipsilesional brain biopsies), and MRI (cortical and fixel-based morphometry). EEG findings were validated in a second cohort treated at another tertiary centre (Centre 2) between 1995 and 2020. We included 127 people with RE and 687 EEG samples. Preoperatively, contralesional epileptiform activity was seen in 30/68 (44%, Centre 1) and 8/59 (14%, Centre 2). In both cohorts, this activity was associated with younger onset age (OR = 0.9; 95% CI 0.83–0.97; P = 0.006). At centre 1, contralesional epileptiform activity was associated with contralesional MRI alterations, lower intelligence (OR = 5.19; 95% CI 1.28–21.08; P = 0.021), and impaired verbal memory (OR = 10.29; 95% CI 1.97–53.85; P = 0.006). After hemispherotomy, 11/17 (65%, Centre 1) and 28/37 (76%, Centre 2) were seizure-free. Contralesional epileptiform activity was persistent postoperatively in 6/12 (50%, Centre 1) and 2/34 (6%, Centre 2). Preoperative contralesional epileptiform activity reduced the chance of postoperative seizure freedom in both cohorts (OR = 0.69; 95% CI 0.50–0.95; P = 0.029). Our findings question the concept of strict unilaterality of RE and provide the evidence of contralesional epileptiform activity as a possible EEG predictor for persisting postoperative seizures. [ABSTRACT FROM AUTHOR]

Diboson production in association with jets is studied in the fully leptonic final states, pp → (Z/γ*)(Z/γ*) + jets → 2ℓ2ℓ′ + jets, (ℓ, ℓ′ = e or μ) in proton-proton collisions at a center-of-mass energy of 13 TeV. The data sample corresponds to an integrated luminosity of 138 fb−1 collected with the CMS detector at the LHC. Differential distributions and normalized differential cross sections are measured as a function of jet multiplicity, transverse momentum pT, pseudorapidity η, invariant mass and ∆η of the highest-pT and second-highest-pT jets, and as a function of invariant mass of the four-lepton system for events with various jet multiplicities. These differential cross sections are compared with theoretical predictions that mostly agree with the experimental data. However, in a few regions we observe discrepancies between the predicted and measured values. Further improvement of the predictions is required to describe the ZZ+jets production in the whole phase space. [ABSTRACT FROM AUTHOR]