National Institute Research Articles

Establishment of Different Intraoperative Monitoring and Mapping Techniques and Their Impact on Survival, Extent of Resection, and Clinical Outcome in Patients with High-Grade Gliomas-A Series of 631 Patients in 14 Years.

The resection of brain tumors can be critical concerning localization, but is a key point in treating gliomas. Intraoperative neuromonitoring (IONM), awake craniotomy, and mapping procedures have been incorporated over the years. Using these intraoperative techniques, the resection of eloquent-area tumors without increasing postoperative morbidity became possible. This study aims to analyze short-term and particularly long-term outcomes in patients diagnosed with high-grade glioma, who underwent surgical resection under various technical intraoperative settings over 14 years. A total of 1010 patients with high-grade glioma that underwent resection between 2004 and 2018 under different monitoring or mapping procedures were screened; 631 were considered eligible for further analyses. We analyzed the type of surgery (resection vs. biopsy) and type of IONM or mapping procedures that were performed. Furthermore, the impact on short-term (The National Institute of Health Stroke Scale, NIHSS; Karnofsky Performance Scale, KPS) and long-term (progression-free survival, PFS; overall survival, OS) outcomes was analyzed. Additionally, the localization, extent of resection (EOR), residual tumor volume (RTV), IDH status, and adjuvant therapy were approached. In 481 patients, surgery, and in 150, biopsies were performed. The number of biopsies decreased significantly with the incorporation of awake surgeries with bipolar stimulation, IONM, and/or monopolar mapping (p < 0.001). PFS and OS were not significantly influenced by any intraoperative technical setting. EOR and RTV achieved under different operative techniques showed no statistical significance (p = 0.404 EOR, p = 0.186 RTV). Based on the present analysis using data from 14 years and more than 600 patients, we observed that through the implementation of various monitoring and mapping techniques, a significant decrease in biopsies and an increase in the resection of eloquent tumors was achieved. With that, the operability of eloquent tumors without a negative influence on neurological outcomes is suggested by our data. However, a statistical effect of monitoring and mapping procedures on long-term outcomes such as PFS and OS could not be shown.

Omalizumab for the Treatment of Multiple Food Allergies

BackgroundFood allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.MethodsIn this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension.ResultsOf the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group.ConclusionsIn persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.)

Measuring EQ-5D-5L utility values in parents who have experienced perinatal death.

Policymakers use clinical and cost-effectiveness evidence to support decisions about health service commissioning. In England, the National Institute for Health and Care Excellence (NICE) recommend that in cost-effectiveness analyses "effectiveness" is measured as quality-adjusted life years (QALYs), derived from health utility values. The impact of perinatal death (stillbirth/neonatal death) on parents' health utility is currently unknown. This knowledge would improve the robustness of cost-effectiveness evidence for policymakers. This study aimed to estimate the impact of perinatal death on parents' health utility. An online survey conducted with mothers and fathers in England who experienced a perinatal death. Participants reported how long ago their baby died and whether they/their partner subsequently became pregnant again. They were asked to rate their health on the EQ-5D-5L instrument (generic health measure). EQ-5D-5L responses were used to calculate health utility values. These were compared with age-matched values for the general population to estimate a utility shortfall (i.e. health loss) associated with perinatal death. There were 256 survey respondents with a median age of 40years (IQR 26-40). Median time since death was 27months (IQR 8-71). The mean utility value of the sample was 0.774 (95% CI 0.752-0.796). Utility values in the sample were 13% lower than general population values (p < 0.05). Over 10years, this equated to a loss of 1.1 QALYs. This reduction in health utility was driven by anxiety and depression. Perinatal death has important and long-lasting health impacts on parents. Mental health support following perinatal bereavement is especially important.

Increase of multidrug-resistant bacteria after the COVID-19 pandemic in a major teaching Hospital in Sicily (2018-2021)

IntroductionThe COVID-19 pandemic has further highlighted the continuing threat of antimicrobial resistance (AMR) to global health and economic development. In the last two decades, AMR has raised increasing concern, with an estimated 4.95 million deaths globally due to bacterial AMR in 2019 alone.The aim of this study was to analyse the impact of the pandemic on the spread of multidrug-resistant organisms (MDROs) using data from the Hospital “P. Giaccone” in Palermo, comparing pre-pandemic and pandemic periods. MethodsThis observational study involved adult patients who were discharged from the hospital between 01 January 2018 and 31 December 2021. Hospital Discharge Cards were linked with microbiological laboratory reports to assess MDRO isolations. SARS-CoV-2 positivity during hospitalisation was evaluated using the National Institute of Health surveillance system. ResultsA total of 58 427 hospitalisations were evaluated in this study. Half the patients were aged over 65 years (N=26 984) and most admissions were in the medical area (N=31 716). During the hospitalisation period, there were 2681 patients (5%) with MDROs isolations, and 946 patients (2%) were positive for SARS-CoV-2. Multivariable analyses showed that during 2020 and 2021, there was a significantly increased risk of isolation of Staphylococcus aureus, Acinetobacter baumannii, and Klebsiella pneumoniae. Age, weight of the Diagnosis-Related Group (DRG), wards with higher intensity of care, and length-of-stay were associated with a higher risk of MDRO isolation. ConclusionThis study provides new insights into the impact of the COVID-19 pandemic on MDRO isolation and has important implications for infection control and prevention efforts in healthcare facilities. Age, DRG-weight, and longer hospital stays further increased the risk of MDRO isolation. Thus, it is imperative to improve and follow hospital protocols to prevent healthcare-associated infections.

Impact of neurofibromatosis type 1 on quality of life using the Skindex-29 questionnaire quality of life in NF1.

Neurofibromatosis type 1 (NF1) is one of the most common RASopathies predisposing affected patients to melanic lesions and benign tumors. NF1 is associated with considerable esthetic and functional burden negatively affecting the patient's quality of life (QoL). This study aims to assess the clinical features of NF1 patients and evaluate their impact on QoL. We identified NF1 patients from a public health database of a region in Spain. All patients underwent clinical and ophthalmological evaluation for NF1 features. We measured QoL using the Spanish version of the Skindex-29. Forty patients fulfilled the NF1 National Institute of Health criteria when we recruited patients. The median age was 42.00 years (IQR 26.5 -53.75). The median total Skindex-29 score was 12.3 (IQR 5.9-22.4); (emotion: 15.0, IQR 5.0-37.5; symptoms 8.9, IQR 0.0-17.9 and functioning 8.3; IQR 0.5-18.3). Women and NF1 patients with lower educational levels were associated with poorer QoL scores. We identified itching and sleep troubles to influence NF1 patients' QoL negatively. NF1 considerably influences the psychological well-being of NF1 patients. We observed that female and low-educated patients scored higher on the emotional dimension of the Skindex-29 and could, therefore, be more at risk of depression. We also pointed out some "minor symptoms" that negatively impact NF1 patients' QoL such, as itching and sleep troubles which doctors could treat if sought by doctors.

Effects of foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain: a systematic review of randomized trials

ObjectiveTo analyze the effects of using foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain.MethodsThis systematic review was registered in the National Institute for Health Research’s prospective online registry of systematic reviews (PROSPERO) under CRD42023456841. The databases Pubmed, Medline (via Ovid), Embase, BVS, and PEDro (Physiotherapy Evidence Database) were consulted to carry out this systematic review. Notably, the records of clinical trials characterized as eligible were manually searched. The search terms were: (foam rolling OR foam rolling vibration) AND (acute musculoskeletal pain) AND (chronic musculoskeletal pain). The search was performed until August 22, 2023. For the analysis of the methodological quality, the PEDro scale was used for each of the manuscripts included in the systematic review. Due to the heterogeneity in the studies included in this systematic review, performing a meta-analysis of the analyzed variables was impossible.ResultsOnly six manuscripts were eligible for data analysis. The type of FR used was non-vibrational, being applied by a therapist in only one of the manuscripts. With an application time ranging from at least 45 s to 15 min, the non-vibrational FR was applied within a day up to six weeks. Using the PEDro scale, scores were assigned that varied between 4 and 8 points, with an average of 6 ± 1.29 points. Only two randomized clinical trials found a significant benefit in pain intensity of adding FR associated with a therapeutic exercise protocol in individuals with patellofemoral pain syndrome and chronic neck pain.ConclusionThe results of this systematic review do not elucidate or reinforce the clinical use of FR in pain intensity in individuals with chronic and acute musculoskeletal pain.

Emergency neurosurgical care for patients with acute cerebral circulation disorders

Aim. To improve the results of neurosurgical treatment of patients with acute cerebrovascular disorders.Material and Methods. An analysis of the results of neurosurgical treatment of 48 patients admitted to the Department of Neurosurgery of the State Institution National Medical Center - “Shifobakhsh” was carried out. The age of patients ranged from 30 to 75 years. In each case, patients underwent clinical and laboratory studies, including using CT and MRI, as well as using three-dimensional (3D) and four-dimensional (4D) reconstruction methods of cerebral vessels.Result and Discussion. The most common cause leading to the formation of intracranial hematomas was hypertension, found in 32 (66.6%) patients, while other causes were identified in 12 (25%) patients (including angiopathy, cerebral vascular pathologies, amyloidosis, and the use of certain medications, among others). All patients underwent neurosurgical operations. The highest frequency of recurrences (4.1%) was observed after surgical interventions performed within the first 24 hours following the hemorrhagic event.Conclusion. With early detection of intracranial hematomas and with the optimal choice of method for their treatment, good functional results are observed with a low incidence of deaths.

Environmental Management of Ecuador’s Business Sector in the Fight against Climate Change

The private sector is part of the United Nations Global Compact, which promotes the voluntary participation of organizations to implement environmental care strategies. The purpose of this article is to examine the performance of Ecuadorian companies in regard to environmental management, especially in the fight against climate change, considering the economic sectors (manufacturing, mining, commerce, construction and services). Figures from the National Institute of Statistics and the Census of Ecuador (2020) are used, including descriptive statistics and cross-tabulations with Cramer’s V index. The results show that approximately 5% of companies had the ISO 14001:2015 certification. In the seven actions against climate change considered, the proportion of companies that did not consider them to be current expenses predominated. Cramer’s V index, for associating the economic sector and the environmental spend, revealed that certain economic sectors (manufacturing and mining) are contributing significantly to environmental management spending in the areas of air, soil, wastewater and waste treatment, while no economic sector dominates the others in areas such as radiation treatment, the use of mineral or energy resources and water resources.

BlastAssist: a deep learning pipeline to measure interpretable features of human embryos.

BlastAssist: a deep learning pipeline to measure interpretable features of human embryos.

Association of maternal pre-pregnancy or first trimester body mass index with neurodevelopmental impairment or death in extremely low gestational age neonates.

To compare the rates of death or survival with severe neurodevelopmental impairment (sNDI) at 2 years among extremely preterm infants in relation to pre-pregnancy or first-trimester maternal body mass index (BMI). This retrospective cohort study included extremely preterm infants (gestational age 220/7-266/7 weeks). The study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites. The primary outcome was death or sNDI at 2 years. Data on the primary outcome were available for 1208 children. Death or sNDI was not different among the three groups: 54.9% in normal, 56.1% in overweight, and 53.4% in obese group (p = 0.39). There was no significant difference in mortality, sNDI, moderate/severe cerebral palsy, Bayley Scales of Infant Development (BSID)-III cognitive composite score <70, BSID-III language composite score <70 in adjusted models. Neurodevelopmental outcome was not significantly associated with maternal pre-pregnancy BMI among extreme preterm infants.

Highly sensitive Cu/Fe calcined layered double hydroxide sensor to detect imidacloprid, a neurotransmission blocker

Pesticides are widely used in agricultural sector, however their overutilization has significantly contaminated the environment and leads to the loss of biodiversity. Imidacloprid (IMI) is a systemic insecticide associated with the family of neonicotinoids which has a potential to affect the central nervous system and whose residues in environment are highly harmful to living organisms. To control the overutilization of such intoxicants, the National Institute for Public Health and the Environment, Netherland assigned the permissible limit of IMI in water as 0.17 µg L−1. Herein, we report on a novel material, Cu/Fe calcined layered double hydroxide (Cu/Fe CLDH), employed as a catalyst to detect the pesticide IMI via electrochemical pathway. From SEM images, the transformation of closely packed nanocages into small lumps of surface beds was observed in the novel material, which is believed to have enhanced its electro-catalytic properties. The developed electrochemical sensor has a good selectivity towards IMI with the percentage inhibition of less than 4.91% and sensitivity of 4.45 nA nM−1. The developed sensor showed good sensor merits such as a linear range between 1 and 200 nM, and the detection limit (LOD) and limit of quantification (LOQ) as 0.099 and 0.330 nM, respectively.

External validation of the modified Marsh and Schnider models for medium-chain triglyceride propofol in target-controlled infusion anesthesia

BackgroundPropofol formulated with medium- and long-chain triglycerides (MCT/LCT propofol) has rapidly replaced propofol formulated with long-chain triglycerides (LCT propofol). Despite this shift, the modified Marsh and Schnider pharmacokinetic models developed using LCT propofol are still widely used for target-controlled infusion (TCI) of propofol. This study aimed to validate the external applicability of these models by evaluating their predictive performance during TCI of MCT/LCT propofol in general anesthesia.MethodsAdult patients (n = 48) undergoing elective surgery received MCT/LCT propofol via a TCI system using either the modified Marsh or Schnider models. Blood samples were collected at various target propofol concentrations and at specific time points, including the loss of consciousness and the recovery of consciousness (13 samples per patient). The actual plasma concentration of propofol was determined using high-performance liquid chromatography. The predictive performance of each pharmacokinetic model was assessed by calculating four parameters: inaccuracy, bias, divergence, and wobble.ResultsBoth the modified Marsh and Schnider models demonstrated predictive performances within clinically acceptable ranges for MCT/LCT propofol. The inaccuracy values were 24.4% for the modified Marsh model and 26.9% for the Schnider model. Both models showed an overall positive bias, 16.4% for the modified Marsh model and 16.6% for the Schnider model. The predictive performance of MCT/LCT propofol was comparable to that of LCT propofol, suggesting formulation changes might exert only a minor impact on the reliability of the TCI system during general anesthesia. Additionally, both models exhibited higher bias and inaccuracy at target concentrations ranging from 3.5 ~ 5 ug/ml than at concentrations between 2 ~ 3 ug/ml.ConclusionsThe modified Marsh and Schnider models, initially developed for LCT propofol, remain clinically acceptable for TCI with MCT/LCT propofol.Trial registrationThis study was registered at the Clinical Research Information Service of the Korean National Institute of Health (https://cris.nih.go.kr; registration number: KCT0002191; 06/01/2017).

Test-Retest Reliability and Reliable Change on the NIH Toolbox Cognition Battery.

Researchers and practitioners can detect cognitive improvement or decline within a single examinee by applying a reliable change methodology. This study examined reliable change through test-retest data from the English-language National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) normative sample. Participants included adults (n = 138; age: M ± SD = 54.8±20.0, range: 18-85; 51.4% men; 68.1% White) who completed test-retest assessments about a week apart on five fluid cognition tests, providing raw scores, age-adjusted standard scores (SS), and demographic-adjusted T-scores (T). The Fluid Cognition Composite (SS: ICC = 0.87; T-score: ICC = 0.84) and the five fluid cognition tests had good test-retest reliability (SS: ICC range = 0.66-0.85; T-score: ICC range = 0.64-0.86). The lower and upper bounds of 70%, 80%, and 90% confidence intervals (CIs) were calculated around change scores, which serve as cutoffs for determining reliable change. Using T-scores, 90% CI, and adjustment for practice effects, 32.3% declined on one or more tests, 9.7% declined on two or more tests, 36.6% improved on one or more tests, and 5.4% improved on two or more tests. It was common for participants to show reliable change on at least one test score, but not two or more test scores. Per an 80% CI, test-retest difference scores beyond these cutoffs would indicate reliable change: Dimensional Change Card Sort (SS ≥ 14/T ≥ 10), Flanker (SS ≥ 12/T ≥ 8), List Sorting (SS ≥ 14/T ≥ 10), Picture Sequence Memory (SS ≥ 19/T ≥ 13), Pattern Comparison (SS ≥ 11/T ≥ 8), and Fluid Cognition Composite (SS ≥ 10/T ≥ 7). The reliable change cutoffs could be applied in research or practice to detect within-person change in fluid cognition at the individual level.

A large multicenter Ralstonia pickettii outbreak in critically ill patients during the COVID-19 pandemic: Epidemiological and clinical characteristics of 66 cases.

To describe a multicenter outbreak of R. pickettii that occurred in a large number of critically ill patients in a city in Colombia, during the COVID-19 pandemic. In April 2021, the National Institute for Food and Drug Surveillance (INVIMA) reported an outbreak of R. pickettii infection associated with contaminated intravenous medications. The Municipal Health Department began collecting data for all cases identified by the hospitals and the results of microbiological studies. Medical records and death certificates of included cases were reviewed. Between March and May 2021, 66 cases of R. pickettii bloodstream infections from nine hospitals were documented. The median age of the patients was 60years (IQR 51-72), and most of them had comorbidities (78.8%), mainly arterial hypertension and diabetes mellitus. At the time of the R. pickettii bloodstream infection, 89.4% had COVID-19, 86.4% were on mechanical ventilation, and 98.5% were receiving corticosteroids. The overall mortality was 81.8%. Nearly 60% of the deaths were related to R. pickettii bloodstream infections. R. pickettii was identified in the cultures from intravenous medications. This large multicenter outbreak caused by intravenous medications contaminated with R. pickettii mainly affected critically ill COVID-19 patients. Mortality was high and largely related to R. pickettii bloodstream infection.

Implementation strategies to build mental health-care capacity in Malawi: a health-economic evaluation

Depression is a major contributor to morbidity and mortality in sub-Saharan Africa. Due to low system capacity, three in four patients with depression in sub-Saharan Africa go untreated. Despite this, little attention has been paid to the cost-effectiveness of implementation strategies to scale up evidence-based depression treatment in the region. In this study, we investigate the cost-effectiveness of two different implementation strategies to integrate the Friendship Bench approach and measurement-based care in non-communicable disease clinics in Malawi. The two implementation strategies tested in this study are part of a trial, in which ten clinics were randomly assigned (1:1) to a basic implementation package consisting of an internal coordinator acting as a champion (IC-only group) or to an enhanced package that complemented the basic package with quarterly external supervision, and audit and feedback of intervention delivery (IC + ES group). We included material costs, training costs, costs related to project-wide meetings, transportation and medication costs, time costs related to internal champion activities and depression screening or treatment, and costs of external supervision visits if applicable. Outcomes included the number of patients screened with the patient health questionnaire 2 (PHQ-2), cases of remitted depression at 3 and 12 months, and disability-adjusted life-years (DALYs) averted. We compared the cost-effectiveness of both packages to the status quo (ie, no intervention) using a micro-costing-informed decision-tree model. Relative to the status quo, IC + ES would be on average US$10 387 ($1349-$17 365) more expensive than IC-only but more effective in achieving remission and averting DALYs. The cost per additional remission would also be lower with IC + ES than IC-only at 3 months ($119 vs $223) and 12 months ($210 for IC + ES; IC-only dominated by the status quo at 12 months). Neither package would be cost-effective under the willingness-to-pay threshold of $65 per DALY averted currently used by the Malawian Ministry of Health. However, the IC + ES package would be cost-effective in relation to the commonly used threshold of three times per-capita gross domestic product per DALY averted. Investing in supporting champions might be an appropriate use of resources. Although not currently cost-effective by Malawian willingness-to-pay standards compared with the status quo, the IC + ES package would probably be a cost-effective way to build mental health-care capacity in resource-constrained settings in which decision makers use higher willingness-to-pay thresholds. National Institute of Mental Health.

A Deep Learning System for Detecting Cardiomegaly Disease Based on CXR Image

The potential of technology to revolutionize healthcare is exemplified by the synergy between artificial intelligence (AI) and early detection of cardiomegaly, demonstrating the power of proactive intervention in cardiovascular health. This paper presents an innovative approach that leverages advanced AI algorithms, specifically deep learning (DL) technology, for the early detection of cardiomegaly. The methodology consists of five key steps, including data collection, image preprocessing, data augmentation, feature extraction, and classification. Utilizing chest X-ray (CXR) images from the National Institutes of Health (NIH), the study applies rigorous image preprocessing operations, including color transformation and normalization. To enhance model generalization, data augmentation is employed, paving the way for two distinct DL models, a convolutional neural network (CNN) developed from scratch and a pretrained residual network with 50 layers (ResNet50), and adapted to the problem domain. Both models are systematically evaluated with five optimizers, revealing the AdaMax optimizer’s superiority for the CNN model and AdaGrad’s efficacy for the modified ResNet50. The proposed CNN with AdaMax achieves an impressive 99.91% accuracy, outperforming recent techniques in precision, recall, and F1−score. This research underscores the transformative potential of AI in cardiovascular health diagnostics, emphasizing the significance of timely intervention.

Two implementation strategies to support the integration of depression screening and treatment into hypertension and diabetes care in Malawi (SHARP): parallel, cluster-randomised, controlled, implementation trial

Although evidence-based treatments for depression in low-resource settings are established, implementation strategies to scale up these treatments remain poorly defined. We aimed to compare two implementation strategies in achieving high-quality integration of depression care into chronic medical care and improving mental health outcomes in patients with hypertension and diabetes. We conducted a parallel, cluster-randomised, controlled, implementation trial in ten health facilities across Malawi. Facilities were randomised (1:1) by covariate-constrained randomisation to either an internal champion alone (ie, basic strategy group) or an internal champion plus external supervision with audit and feedback (ie, enhanced strategy group). Champions integrated a three-element, evidence-based intervention into clinical care: universal depression screening; peer-delivered psychosocial counselling; and algorithm-guided, non-specialist antidepressant management. External supervision involved structured facility visits by Ministry officials and clinical experts to assess quality of care and provide supportive feedback approximately every 4 months. Eligible participants were adults (aged 18-65 years) seeking hypertension and diabetes care with signs of depression (Patient Health Questionnaire-9 score ≥5). Primary implementation outcomes were depression screening fidelity, treatment initiation fidelity, and follow-up treatment fidelity over the first 3 months of treatment, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03711786, and is complete. Five (50%) facilities were randomised to the basic strategy and five (50%) to the enhanced strategy. Between Oct 1, 2019, and Nov 30, 2021, in the basic group, 587 patients were assessed for eligibility, of whom 301 were enrolled; in the enhanced group, 539 patients were assessed, of whom 288 were enrolled. All clinics integrated the evidence-based intervention and were included in the analyses. Of 60 774 screening-eligible visits, screening fidelity was moderate (58% in the enhanced group vs 53% in the basic group; probability difference 5% [95% CI -38% to 47%]; p=0·84) and treatment initiation fidelity was high (99% vs 98%; 0% [-3% to 3%]; p=0·89) in both groups. However, treatment follow-up fidelity was substantially higher in the enhanced group than in the basic group (82% vs 20%; 62% [36% to 89%]; p=0·0020). Depression remission was higher in the enhanced group than in the basic group (55% vs 36%; 19% [3% to 34%]; p=0·045). Serious adverse events were nine deaths (five in the basic group and four in the enhanced group) and 26 hospitalisations (20 in the basic group and six in the enhanced group); none were treatment-related. The enhanced implementation strategy led to an increase in fidelity in providers' follow-up treatment actions and in rates of depression remission, consistent with the literature that follow-up decisions are crucial to improving depression outcomes in integrated care models. These findings suggest that external supervision combined with an internal champion could offer an important advance in integrating depression treatment into general medical care in low-resource settings. The National Institute of Mental Health.

STING signalling compensates for low tumour mutation burden to drive anti-tumour immunity

While mutation-derived neoantigens are well recognized in generating anti-tumour T cell response, increasing evidences highlight the complex association between tumour mutation burden (TMB) and tumour infiltrating lymphocytes (TILs). The exploration of non-TMB determinants of active immune response could improve the prognosis prediction and provide guidance for current immunotherapy. The transcriptomic and whole exome sequence data in The Cancer Genome Atlas were used to examine the relationship between TMB and exhausted CD8+ T cells (Tex), as an indicator of tumour antigen-specific T cells across nine major cancer types. Computational clustering analysis was performed on 4510 tumours to identify different immune profiles. NanoString gene expression analysis and single cell RNA-seq analysis using fresh human breast cancer were performed for finding validation. TMB was found to be poorly correlated with active immune response in various cancer types. Patient clustering analysis revealed a group of tumours with abundant Tex but low TMB. In those tumours, we observed significantly higher expression of the stimulator of interferon genes (STING) signalling. Dendritic cells, particularly those of BATF3+ lineage, were also found to be essential for accumulation of Tex within tumours. Mechanistically, loss of genomic and cellular integrity, marked by decreased DNA damage repair, defective replication stress response, and increased apoptosis were shown to drive STING activation. These results highlight that TMB alone does not fully predict tumour immune profiles, with STING signalling compensating for low TMB in non-hypermutated tumours to enhance anti-tumour immunity. Translating these results, STING agonists may benefit patients with non-hypermutated tumours. STING activation may serve as an additional biomarker to predict response to immune checkpoint blockades alongside TMB. Our research also unravelled the interplay between genomic instability and STING activation, informing potential combined chemotherapy targeting the axis of genomic integrity and immunotherapy. City of Hope Christopher Family Endowed Innovation Fund for Alzheimer's Disease and Breast Cancer Research in honor of Vineta Christopher; Breast Cancer Alliance Early Career Investigator Award; National Cancer Institute of the National Institutes of Health under award number R01CA256989 and R01CA240392.

Ship- and aircraft-based XCH4 over oceans as a new tool for satellite validation

Abstract. Satellite-based estimations of dry-air column-averaged mixing ratios of methane (XCH4) contribute to a better understanding of changes in CH4 emission sources and variations in its atmospheric growth rates. High accuracy of the satellite measurements is required, and therefore, extensive validation is performed, mainly against the Total Carbon Column Observing Network (TCCON). However, validation opportunities at open-ocean areas outside the coastal regions are sparse. We propose a new approach to assess the accuracy of satellite-derived XCH4 trends and variations. We combine various ship and aircraft observations with the help of atmospheric chemistry models, mainly used for the stratospheric column, to derive observation-based XCH4 (obs. XCH4). Based on our previously developed approach for the application to XCO2, we investigated three different advancements, from a simple approach to more elaborate approaches (approaches 1, 2, and 3), to account for the higher tropospheric and stratospheric variability in CH4 as compared to CO2. Between 2014 and 2018, at 20–40° N of the western Pacific, we discuss the uncertainties in the approaches and the derived obs. XCH4 within 10° by 20° latitude–longitude boxes. Uncertainties were 22 ppb (parts per billion) for approach 1, 20 ppb for approach 2, and 16 ppb for approach 3. We analyzed the consistency with the nearest TCCON stations and found agreement of approach 3 with Saga of 1±12 ppb and -1±11 ppb with Tsukuba for the northern and southern latitude box, respectively. Furthermore, we discuss the impact of the modeled stratospheric column on the derived obs. XCH4 by applying three different models in our approaches. Depending on the models, the difference can be more than 12 ppb (0.6 %), showing the importance for the appropriate choice. We show that our obs. XCH4 dataset accurately captures seasonal variations in CH4 over the ocean. Using different retrievals of the Greenhouse Gases Observing Satellite (GOSAT) from the National Institute for Environmental Studies (NIES), the RemoTeC full-physics retrieval operated at the Netherlands Institute for Space Research (SRON), and the full-physics retrieval of the University of Leicester (UoL-OCFP), we demonstrate the applicability of the dataset for satellite evaluation. The comparison with results of approach 3 revealed that NIES showed a difference of −0.04 ± 13 ppb and strong scatter at 20–30° N, while RemoTeC and OCFP have a rather systematic negative bias of −12.1 ± 8.1 and −10.3 ± 9.6 ppb. Our new approach to derive XCH4 reference datasets over the ocean can contribute to the validation of existing and upcoming satellite missions in future.

Cesarean sections and sociodemographic disparities in Ecuador: A nationwide study from hospital registries between 2015 and 2022.

This study aimed to analyze sociodemographic factors associated with cesarean sections (c-sections) in Ecuador. Data were extracted from the Ecuadorian National Institute of Statistics and Censuses (INEC). Multivariate binary and multinomial logistic regression analyses were performed to assess sociodemographic factors associated with c-sections overall and with each type of c-section (elective or emergency c-section). This study included 1 118 842 in-hospital deliveries during 2015-2022 in Ecuador, of which 41.3% were c-sections. This exceeds the recommended levels of medical justified c-sections. Those who were older than 20-29 years showed a higher probability for c-sections overall. Regarding ethnicity, Montubios had 57% higher probability for c-sectioned with an adjusted odds ratio (aOR) of 1.57 and a 95% confidence interval (CI) of 1.45-1.71; while indigenous, black, and white individuals exhibited 73%, 29%, and 21% lower probabilities, respectively. However, this varied according to specific type of c-sections: black individuals had 11% higher probability of elective c-section but 44% lower probability of emergency c-section. Deliveries in private healthcare facilities exhibited significantly higher probabilities of c-sections overall (aOR 15.38, 95% CI 15.20-15.56). Higher probability of emergency c-section was also observed during 2020-2022. Cesarean sections in Ecuador still exceed the recommended levels of medically justified c-sections, highlighting the importance of adopting an approach to childbirth that reduces unnecessary interventions. These results suggest an important role of sociodemographic factors, which aligns with the reported need for multicomponent and locally tailored strategies for addressing c-section overuse. The increase in c-sections during the COVID-19 pandemic (2020-2022) might suggest the influence of external health crises on maternal healthcare.