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Correction to: Molecular Psychiatry, published online 2 May 2023 In this article Honami Arai, Irene Bollettini, Rosa Calvo Escalona, Ana Coelho, Federica Colombo, Leila Darwich, Martine Fontaine, Toshikazu Ikuta, Jonathan C. Ipser, Asier Juaneda-Seguí, Hitomi Kitagawa, Gerd Kvale, Mafalda Machado-Sousa, Astrid Morer, Takashi Nakamae, Jin Narumoto, Joseph O’Neill, Sho Okawa, Eva Real, Veit Roessner, Joao R. Sato, Cinto Segalàs, Roseli G. Shavitt, Dick J. Veltman, Kei Yamada were missing from the author list indexed under the ENIGMA-OCD Working Group. Additionally, there was an error regarding Tokiko Yoshida’s name, where the first name and last name were written in the wrong order. The original article has been corrected.

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohens d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohens d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

BACKGROUND: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. METHODS: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. RESULTS: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. CONCLUSIONS: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.

Sodium glucose cotransporter-2 inhibitors (SGLT2i), originally developed for type II diabetes mellitus, have recently been approved for the treatment of heart failure in both diabetic and non-diabetic patients due to their significant cardiovascular benefits. Beyond their established role in diabetes and heart failure management, current research is exploring the potential applications of SGLT2 inhibitors in the field of cardio-oncology. This interest is driven by dual possible benefits: cardioprotection against the adverse effects of antitumor therapies and inherent antitumor properties. Patients affected by cancer often face the challenge of managing cardiovascular toxicity induced by antineoplastic treatments. SGLT2 inhibitors have shown promise in mitigating toxicities, thereby enhancing the cardiovascular health of these patients. Additionally, emerging evidence suggests that SGLT2 inhibitors may possess direct antitumor effects, further contributing to their therapeutic potential in oncology. This review aims to provide a comprehensive overview of the molecular mechanisms through which SGLT2 inhibitors exert their cardioprotective and antitumor effects. Furthermore, we will examine the current body of evidence supporting the use of these inhibitors in a cardio-oncology setting.

Since the 1970s, the issue of ageing farmers and generational renewal in agriculture has consistently attracted the attention of policymakers. However, despite successive reforms of the European Union Structural Funds, efforts to encourage young people to enter the agricultural sector remain largely focused on agricultural and rural policies, specifically on the First Settlement scheme. This paper highlights the role of the European Union’s rural development policy in supporting and encouraging generational renewal in agriculture. A qualitative analysis of the Italian case examining some of the demographic changes that have occurred within the agricultural system at the regional level has been conducted. The analysis is based on the comparison of policy implementations in different programming periods. Using data from the General Censuses of Agriculture and the Italian Agricultural Payments Agency—supplemented by the Annual Implementation Reports of the Italian Rural Development Programmes—the research traces the evolution of initiatives supporting young farmers. The main findings reveal a notable decline in the number of young people in the primary sector over the last decade, together with an ageing population of agricultural farmers. Measures to support young farmers under the Common Agricultural Policy appear to be ineffective in countering the ageing trend. There is scope for integrated policies to enhance the attractiveness and profitability of rural areas and to ensure long-term sustainable generational renewal in the agricultural sector.

This study focuses on the development of a people-centred early warning system (EWS) against floods in the Sirba River basin between Niger and Burkina Faso. This densely populated area has witnessed an increase in extreme flooding events in recent years. Several flood forecasting systems in the Sahel exist, although there is no EWS that integrates the four components of people-centred EWSs, namely risk knowledge, monitoring and warning service, dissemination and communication, and response capacity. The proposed EWS, named SLAPIS, includes a risk knowledge component that involves defining four levels of vigilance. Its monitoring and alert component involves a user-friendly web application containing real-time data collected through automatic stations. The EWS communicate seamlessly with the national alert system. The response capacity is strengthened through the creation of a flood zone atlas. In this framework, the EWS integrates significant geoinformatics in preparation of local risk reduction plans and the awareness of local communities. In the SLAPIS case study, multi-temporal classifications were conducted using Sentinel-2 data and high-resolution images (approximately 10 cm) generated through Structure from Motion (SfM) techniques. Digital Terrain Model (DTM) creation for hydraulic model calibration employed a multiscale approach, incorporating GNSS survey data processed via Precise Point Positioning (PPP), HydroSHEDS (approximately 100m resolution), and commercial 10m resolution data. All information was calibrated, harmonised, and integrated into the EWS model, which is accessible via a web platform. Capacity building encompassed direct training and field implementation to streamline the primary EWS generation steps.

BackgroundThe COVID-19 outbreak played a significant psychological impact on nurses, as they coped with intense emotional and cognitive demands, in a context in which the Health System was not prepared to face the emergency. Literature showed that pandemics influenced the nurses' stress and psychosocial health due to poor rest, high work overloads, a lack of control over the patient flows, and a frequent isolation from family. Under these circumstances, nurses experienced severe psychological and mental stressors that generated mental health problems. Recent literature showed that coping strategies, especially those that were positive, promoted mental health in workers and helped them to face stressors.ObjectiveThe study aimed to investigate the relationship between vicarious traumas and the impact of traumatic events on nurses' mental health. In addition, we analyzed the role of coping strategies in moderating the effect of vicarious traumas on mental health.MethodsThe study was performed in November 2020, during the first wave of the COVID-19 pandemic. A self-reported structured questionnaire was administered via an online method to reduce face-to-face contact. Logistic regressions were conducted to analyze the relationship between both vicarious traumas and the impact of traumatic events impact and mental health. An interaction analysis with the PROCESS macro was performed to analyze the role of coping strategies in moderating the relationship between vicarious traumas and mental health.ResultsA total of 183 nurses answered to the questionnaire. A moderation analysis showed that positive coping strategies such as physical activity, reading/music, and yoga/meditation showed to be protective in reducing the effect of vicarious traumas on the nurses' mental health problems. Conversely, negative coping strategies strengthened that relationship and may compromise their quality of working life.ConclusionThese findings provide further support for considering positive coping strategies as an important resource to alleviate psychological distress, thus helping the professional to reduce the negative effects of stress.

Machine learning can be used to define subtypes of psychiatric conditions based on shared clinical and biological foundations, presenting a crucial step toward establishing biologically based subtypes of mental disorders. With the goal of identifying subtypes of disease progression in schizophrenia, here we analyzed cross-sectional brain structural magnetic resonance imaging (MRI) data from 4,291 individuals with schizophrenia (1,709 females, age=32.5 years±11.9) and 7,078 healthy controls (3,461 females, age=33.0 years±12.7) pooled across 41 international cohorts from the ENIGMA Schizophrenia Working Group, non-ENIGMA cohorts and public datasets. Using a machine learning approach known as Subtype and Stage Inference (SuStaIn), we implemented a brain imaging-driven classification that identifies two distinct neurostructural subgroups by mapping the spatial and temporal trajectory of gray matter (GM) loss in schizophrenia. Subgroup 1 (n=2,622) was characterized by an early cortical-predominant loss (ECL) with enlarged striatum, whereas subgroup 2 (n=1,600) displayed an early subcortical-predominant loss (ESL) in the hippocampus, amygdala, thalamus, brain stem and striatum. These reconstructed trajectories suggest that the GM volume reduction originates in the Broca's area/adjacent fronto-insular cortex for ECL and in the hippocampus/adjacent medial temporal structures for ESL. With longer disease duration, the ECL subtype exhibited a gradual worsening of negative symptoms and depression/anxiety, and less of a decline in positive symptoms. We confirmed the reproducibility of these imaging-based subtypes across various sample sites, independent of macroeconomic and ethnic factors that differed across these geographic locations, which include Europe, North America and East Asia. These findings underscore the presence of distinct pathobiological foundations underlying schizophrenia. This new imaging-based taxonomy holds the potential to identify a more homogeneous sub-population of individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Centromeres are epigenetically specified by the histone H3 variant CENP-A. Although mammalian centromeres are typically associated with satellite DNA, we previously demonstrated that the centromere of horse chromosome 11 (ECA11) is completely devoid of satellite DNA. We also showed that the localization of its CENP-A binding domain is not fixed but slides within an about 500 kb region in different individuals, giving rise to positional alleles. These epialleles are inherited as Mendelian traits but their position can move in one generation. It is still unknown whether centromere sliding occurs during meiosis or during development. Here, we first improve the sequence of the ECA11 centromeric region in the EquCab3.0 assembly. Then, to test whether centromere sliding may occur during development, we map the CENP-A binding domains of ECA11 using ChIP-seq in five tissues of different embryonic origin from the four horses of the equine FAANG (Functional Annotation of ANimal Genomes) consortium. Our results demonstrate that the centromere is localized in the same region in all tissues, suggesting that the position of the centromeric domain is maintained during development.

Background and Purpose: The development of Magnetic Resonance Imaging (MRI)-only Radiotherapy (RT) represents a significant advancement in the field. This study introduces a Deep Learning (DL) algorithm designed to quickly generate synthetic CT (sCT) images from low-field MR images in the brain, an area not yet explored. Methods: Fifty-six patients were divided into training (32), validation (8), and test (16) groups. A conditional Generative Adversarial Network (cGAN) was trained on pre-processed axial paired images. sCTs were validated using mean absolute error (MAE) and mean error (ME) calculated within the patient body. Intensity Modulated Radiation Therapy (IMRT) plans were optimised on simulation MRI and calculated considering sCT and original CT as electron density (ED) map. Dose distributions using sCT and CT were compared using global gamma analysis at different tolerance criteria (2 %/2mm and 3 %/3mm) and evaluating the difference in estimating different Dose Volume Histogram (DVH) parameters for target and organs at risk (OARs). Results: The network generated sCTs of each single patient in less than two minutes (mean time = 103 ± 41 s). For test patients, the MAE was 62.1 ± 17.7 HU, and the ME was −7.3 ± 13.4 HU. Dose parameters on sCTs were within 0.5 Gy of those on original CTs. Gamma passing rates 2 %/2mm, and 3 %/3mm criteria were 99.5 %±0.5 %, and 99.7 %±0.3 %, respectively. Conclusion: The proposed DL algorithm generates in less than 2 min accurate sCT images in the brain for online adaptive radiotherapy, potentially eliminating the need for CT simulation in MR-only workflows for brain treatments.

Abstract In chronic lymphocytic leukemia, the reliability of next‐generation sequencing (NGS) to detect TP53 variants ≤10% allelic frequency (low‐VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%, 94.5%, and 94.8% at 1%, 2%, and 3% VAF cut‐off, respectively. While only one false positive (FP) result was reported at >2% VAF, it was more challenging to distinguish true variants

The study aimed to characterize Salmonella and Yersinia enterocolitica detected in fattening pigs in Sardinia, examining genetic similarity and antimicrobial resistance of isolates from farms and slaughterhouses and evaluating carcass hygiene. Environmental samples were collected from six pig farms, and the same pigs were also sampled at the slaughterhouses. Palatine tonsils, mesenteric lymph nodes, colon content, and carcass surface samples were collected and tested for Salmonella and Y. enterocolitica. Antimicrobial resistance testing and whole genome sequencing were performed on all isolates. Carcass surface samples were tested for total aerobic colony count (ACC) and Enterobacteriaceae count (EBC). Y. enterocolitica was found in two farms (33%), while Salmonella was absent in environmental farm samples. At slaughterhouses, 13.1% of pigs were found positive for Salmonella (lymph nodes, colon content, and palatine tonsils samples), but Y. enterocolitica was not detected. Salmonella isolates were typed as monophasic S. Typhimurium ST34 and S. Goldcoast ST358, with few allelic differences among isolates of the same ST. Salmonella ST34 showed resistance towards ampicillin, streptomycin, sulfonamide, and tetracycline (blaTEM-1B, aph(3´´)-Ib, sul2 and tetB genes, R-type ASSuT). Y. enterocolitica isolates (biotype 2, ST853, and ST859) showed resistance to ampicillin and amoxicillin-clavulanic acid (blaA gene). Process hygiene criteria were generally met, with mean (log10 CFU/cm2 ± standard deviation) values for ACC and EBC being 2.23±0.74 and 0.75±0.81. Pigs of Sardinia are confirmed carriers of Salmonella and Y. enterocolitica, but overall hygienic status in farms and slaughterhouses in Sardinia is acceptable. Monophasic S. Typhimurium and Y. enterocolitica isolates showed typical resistance patterns. Monophasic S. Typhimurium ST34 isolates with R-type ASSuT are confirmed as epidemic clones.

Introduction Adolescent idiopathic scoliosis (AIS) affects an estimated 200 million adolescents globally and curvatures exceeding 30° at skeletal maturity are associated with increased health risks in adulthood. The International Society for the Orthopedic and Rehabilitative Treatment of Scoliosis recommends specific therapeutic exercises to prevent the progression of AIS. However, studies have questioned the effects of specific and general therapeutic exercises on the progression of AIS. This systematic review will evaluate the effectiveness of general and specific therapeutic exercises in preventing Cobb angle progression compared with other conservative interventions.Methods and analysis We will search MEDLINE (via PubMed), EMBASE, CENTRAL, PEDro and CINAHL from inception to 14 December 2023. Randomised clinical trials involving individuals aged 10 to 18 years with a Cobb angle above 10° will be considered. The effectiveness of therapeutic exercises will be compared with minimal intervention, other exercises and brace use, alone or in combination with exercise. The primary outcome is the Cobb angle measurement, with subgroup analyses assessing severity based on SOSORT classifications. The risk of bias will be assessed using the PEDro scale and Grading of Recommendations, Assessment, Development and Evaluation will be used to assess certainty of evidence. The Review Manager 5.4 software will be used for meta-analysis. The protocol follows the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines.Ethics and dissemination This is a literature-based study and ethical approval is not required. The findings will be disseminated through peer-reviewed publications.PROSPERO registration numberCRD42020156639.

Mobility as a Service (MaaS) has been tested in numerous cities and enables users to travel within an integrated system of collective and shared transport services, with a single travel package or bundle, giving them the ability to plan, book and pay for a trip using a unique technological platform. At this stage of the MaaS system experimentation, a detailed analysis on a small scale enables, through the understanding of the mechanisms governing travel choices, the planning of a MaaS service on a large scale that has the right flexibility to adapt to different territorial contexts. The paper reports the main findings of a study carried out as part of a national research project funded by the Italian Ministry of University and Research. Within this project, evaluation methodologies were developed (Technology Acceptance Model, Revealed Preferences and Intended Preference surveys), pilot surveys were conducted on samples of potential users, and the results were analysed and compared to assess the potential activation of a MaaS and to estimate its impacts on mobility.Two pilot experiments and an extended test, with a sample of almost 200 users, were carried out in different territorial contexts in Italy: the metropolitan areas of Reggio Calabria and Messina, the extra-urban area of Gioia Tauro and the urban area of the metropolitan city of Cagliari. The activities should be regarded as preliminary and indispensable stage for the design of more extensive investigations, as well as for the planning of a possible MaaS system in the areas examined.

Accurate cave surveying is crucial for understanding their genesis, current state, and potential hazards, especially in challenging environments marked by limited accessibility and poor visibility. This study applies geomatics techniques, including Terrestrial Laser Scanning (TLS), SLAM-based Mobile Mapping Systems (MMS), and digital photogrammetry, to create three-dimensional models of artificial caves in Gravina in Puglia, Apulia region, southern Italy. The research aims to assess these methodologies' accuracy, reliability, and performance for structural monitoring and hazard assessment. Despite challenges such as rough conditions, limited accessibility and poor visibility, the study reveals promising insights into the capabilities of these techniques for efficient surveying in complex underground environments. While highlighting the potential of MMS for cost-effective and rapid data acquisition, digital photogrammetry using spherical cameras also emerges as a viable alternative, offering comprehensive data collection capabilities with minimal capture time. Further research is warranted to optimize these techniques for enhanced hazard assessment and structural monitoring in challenging underground environments.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.