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This paper focuses on the perceptual, social and aesthetic dynamics at work when interacting with immersive pornographic products. The main aim of this analysis is to demonstrate that immersion in a 360° iconic environment promotes a double quasi-inter-subjective movement: that with the solid bodies and identities reproduced in the iconic space, and that with the wearable machine. The interaction of these two elements promotes a peculiar somatechnical relationship with the apparatus and the audiovisual, in line with the carnal qualities of the pornographic product from its origins. After a brief genealogy of this erotic liaison, this contribution analyses the main features of the contemporary conformation of pornography in Virtual Reality, showing how the material device in the pornographic experience is understood as a quasi-subjectivity that shares in the erotic charge of the product. Through its ergonomic conformation, VR porn promotes unprecedented forms of identity experimentation, which also heighten the medium's value in socio-political terms.

Background:Multidisciplinary care has been shown to improve the quality of life and extend survival for patients with motor neuron disease (pwMND). Several barriers to accessing care have been previously identified. Telehealth can potentially mitigate this by providing remote specialist healthcare services.Aims:Systematically review the existing literature to assess if and how telehealth can reduce barriers to access multidisciplinary team (MDT) care and improve health outcomes for pwMND.Methods:A mixed-methods, systematic literature review was conducted to identify evaluations of telehealth interventions. Telehealth interventions were evaluated using the Evaluating Digital Health Interventions Framework.Findings:A total of 293 articles were identified from the search and 16 studies met the criteria for inclusion in the review. Modes of telehealth delivery included video conferencing, app-based self-assessment and remote monitoring. Healthcare outcomes identified as being approved included accessibility, improved communication, timely interventions and satisfaction.Conclusion:Telehealth has the potential to mitigate barriers to access to specialist MDT and improve healthcare outcomes for pwMND. Patients’ preferences should always be considered in decision-making when considering available options.

AbstractBees are affected by several factors, including pathogens and pesticides, which may cause mortality and consequent population decline. Considering the ecological and economic importance of these pollinators, this study evaluated the occurrence of the microsporidia Nosema apisand Nosema ceranae, the viruses ABVP, DWV, BQCV, KBV, IAPV and CBPV and residues of the pesticides atrazine, chlorantraniliprole, deltamethrin, fipronil and glyphosate in workers from field colonies of Africanized honey bee Apis melliferaacross one year. The presence of pesticide residues was also evaluated in honey and pollen samples. All tested viruses were found in the workers, with BQCV showing the highest copy number. BQCV levels were correlated with relative humidity. Nosema ceranaewas the only microsporidian with higher intensities of infection during summer and autumn; seasons with high availability of food resources, which can act as dispersers of this pathogen. Small amounts of glyphosate and its metabolite were detected in the bees tested. These data show that honey bees are contaminated with pathogens and pesticides in the field and present correlative data for these threats.

Purpose: Hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. We investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism. Research design and methods: Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral Center. The data of both groups were compared with 54 in house-controls and 503 subjects from the 1000 Genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis. Results: The NPHPT group differed significantly at SNPs in OPG and ESR1. Also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes. Conclusions: Our NPHPT patient set harbored a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancer types globally. Due to the complex anatomy of the region, diagnosis and treatment is challenging. Early diagnosis and treatment are important, because advanced and recurrent HNSCC have a poor prognosis. Robust and precise tools are needed to help diagnose HNSCC reliably in its early stages. The aim of this study was to assess the applicability of a convolutional neural network in detecting and auto-delineating HNSCC from PET-MRI data. Methods: 2D U-net models were trained and tested on PET, MRI, PET-MRI and augmented PET-MRI data from 44 patients diagnosed with HNSCC. The scans were taken 12 weeks after chemoradiation therapy with a curative intention. A proportion of the patients had follow-up scans which were included in this study as well, giving a total of 62 PET-MRI scans. The scans yielded a total of 178 PET-MRI slices with cancer. A corresponding number of negative slices were chosen randomly yielding a total of 356 slices. The data was divided into training, validation and test sets (n= 247, n= 43 and n= 66 respectively). Dice score was used to evaluate the segmentation accuracy. In addition, the classification capabilities of the models were assessed. Results: When true positive segmentations were considered, the mean Dice scores for the test set were 0.79, 0.84 and 0.87 for PET, PET-MRI and augmented PET-MRI, respectively. Classification accuracies were 0.62, 0.71 and 0.65 for PET, PET-MRI and augmented PET-MRI, respectively. The MRI based model did not yield segmentation results. A statistically significant difference was found between the PET-MRI and PET models (p= 0.008). Conclusion: Automatic segmentation of HNSCC from the PET-MRI data with 2D U-nets was shown to give sufficiently accurate segmentations.

Graphene and graphyne electrodes are both relevant for electrochemical energy storage applications due to their unique physical, chemical, and electronic properties. Graphyne has been considered even more attractive than graphene due to its larger specific surface area, greater electronic mobility, and intrinsic band gap. The analyses presented here reveal relevant features of graphyne in an interaction with an electrolyte that can be useful for practical applications. Although there is already a considerable volume of work on graphyne, the analysis of its properties taking into account the dynamics of its network and the interaction with the condensed medium has not yet been presented. In this work, ab initio molecular dynamics simulations were performed to study the energetic, structural, spectroscopic, and electronic properties of graphene and graphyne electrodes in vacuum and in the presence of an electrolyte (EMIM-BF4). A detailed analysis of the electrode–electrolyte interaction is reported for both systems. Structural features are presented in terms of both radial and spatial distribution functions and angular orientation distributions. Power spectral analyses and molecular orbital maps provided important insights into the intermolecular interactions in graphene and graphyne systems, describing the main differences as well as revealing similarities between them.

A convolutional neural network (CNN) can be used to perform fully automatic tumor segmentation from the positron emission tomography (PET) images of head and neck cancer patients but the predictions often contain false positive segmentation caused by the high concentration of the tracer substance in the human brain. A potential solution would be a one-click annotation in which a user points the location of the tumor by clicking the image. This information can then be given either directly to a CNN or an algorithm that fixes its predictions. In this article, we compare the fully automatic segmentation to four semi-automatic approaches by using 962 transaxial slices collected from the PET images of 100 head and neck cancer patients. According to our results, a semi-automatic segmentation method with information about the center of the tumor performs the best with a median Dice score of 0.708.

Owing to the ever-present solar wind, our vast solar system is full of plasmas. The turbulent solar wind, together with sporadic solar eruptions, introduces various space plasma processes and phenomena in the solar atmosphere all the way to Earth’s ionosphere and atmosphere and outward to interact with the interstellar media to form the heliopause and termination shock. Remarkable progress has been made in space plasma physics in the last 65 years, mainly due to sophisticated in situ measurements of plasmas, plasma waves, neutral particles, energetic particles, and dust via space-borne satellite instrumentation. Additionally, high-technology ground-based instrumentation has led to new and greater knowledge of solar and auroral features. As a result, a new branch of space physics, i.e., space weather, has emerged since many of the space physics processes have a direct or indirect influence on humankind. After briefly reviewing the major space physics discoveries before rockets and satellites (Section I), we aim to review all our updated understanding on coronal holes, solar flares, and coronal mass ejections, which are central to space weather events at Earth (Section II), solar wind (Section III), storms and substorms (Section IV), magnetotail and substorms, emphasizing the role of the magnetotail in substorm dynamics (Section V), radiation belts/energetic magnetospheric particles (Section VI), structures and space weather dynamics in the ionosphere (Section VII), plasma waves, instabilities, and wave-particle interactions (Section VIII), long-period geomagnetic pulsations (Section IX), auroras (Section X), geomagnetically induced currents (GICs, Section XI), planetary magnetospheres and solar/stellar wind interactions with comets, moons and asteroids (Section XII), interplanetary discontinuities, shocks and waves (Section XIII), interplanetary dust (Section XIV), space dusty plasmas (Section XV), and solar energetic particles and shocks, including the heliospheric termination shock (Section XVI). This article is aimed to provide a panoramic view of space physics and space weather.

The US National Institute of Allergy and Infectious Diseases (NIAID) convened a virtual workshop in July 2022 to address the research landscape and identify gaps and opportunities in the understanding of durable vaccine protection.

We assess the prevalence of ducted and non‐ducted whistler propagation using burst mode data from the Van Allen Probes Electric Field and Waves instrument (EFW). We have identified burst periods containing lightning‐generated whistlers (LGWs), resulting in a data set available for future use. The entire burst data set is filtered through an analysis of the search coil magnetometer (SCM) noise, identifying signals in frequency space that exceed an adaptive noise threshold. We implement DBSCAN (Density‐Based Spatial Clustering of Applications with Noise) to identify individual whistlers and clusters of whistlers. With magnetic spectral analysis, we calculate the mean wave normal angle (WNA) for each LGW group. We use ray tracing to estimate the expected WNA distributions for non‐ducted LGWs to compare to the data and determine methods for identifying potentially ducted LGWs. The ray‐tracing results provide a clear threshold in WNA for ducted whistlers. Using this threshold, we estimate that at least 10.1%$10.1\%$of LGWs in this data set are ducted. We find that the majority of potentially ducted whistlers are below L=2$L=2$and nearly half of LGWs below L=2$L=2$and within 9–18 MLT may be ducted. Lightning‐generated whistlers (LGWs) are very‐low‐frequency waves produced when lightning‐generated radio pulses known as sferics excite whistler mode waves through the ionosphere and into the magnetosphere. LGW wave power contributes to pitch angle scattering and precipitation of trapped energetic electrons, affecting atmospheric chemistry and helping maintain the slot region between the radiation belts. Field‐aligned plasma density irregularities, or ducts, affect the propagation of LGWs. Ducting can determine where the wave energy travels, how long it persists, and which energetic particle populations are affected. We present distributions of LGW wave properties and explore methods of determining ducting of LGWs. We present a complete Van Allen Probes Electric Field & Waves whistler data set generated through density‐based clusteringMost whistlers in this data set have high wave normal angles consistent with non‐ducted propagationLikely ducted whistlers are mainly below L=2$L=2$; about half of whistlers between 9 and 18 MLT and below L=2$L=2$are likely ducted We present a complete Van Allen Probes Electric Field & Waves whistler data set generated through density‐based clustering Most whistlers in this data set have high wave normal angles consistent with non‐ducted propagation Likely ducted whistlers are mainly below L=2$L=2$; about half of whistlers between 9 and 18 MLT and below L=2$L=2$are likely ducted

Allogeneic hematopoietic stem cell transplantation (Allo-HCT) remains the only curative treatment for myelofibrosis (MF). Transplantation in patients with MF is mostly done using a reduced intensity conditioning regimen with calcineurin inhibitors for graft versus host disease (GVHD) prophylaxis. Here we sought to evaluate outcomes of patients who underwent an ex vivo CD34+ -selected allo-HCT using myeloablative conditioning (MAC). Twenty-seven patients were included in this retrospective analysis. All patients were conditioned with busulfan, melphalan and fludarabine and antithymocyte globulin to prevent graft rejection. G-CSF mobilized peripheral blood stem cell grafts were depleted of T-cells using immunomagnetic CD34+ selection by CliniMACS device. Median follow-up among survivors was 50.6 months. The estimated 3-year overall survival, relapse free survival and the combined endpoint of GVHD/relapse free survival were 88% (95% CI, 75–100%), 80% (95% CI, 66–98%) and 74% (95% CI, 59–93%), respectively. The cumulative incidence of grade II-IV acute GVHD at day 100 was 33.3% (95% CI 16.4–51.3%), and two patients suffered chronic GVHD. There were no cases of primary graft failure. However, delayed graft failure occurred in two patients. We conclude that CD34+ selected allo-HCT with a MAC resulted in high survival rates in this cohort of patients with MF.

Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication after allogeneic stem cell transplantation (allo-HCT). However, there is no uniform consensus on the optimal strategy for SOS prevention. Ursodeoxycholic acid is the most used regimen, even though its administration is challenging in recipients unable to tolerate oral medication. Defibrotide was recently studied in a phase 3 trial, but enrollment was stopped early due to futility. Low-dose unfractionated heparin (UFH) is an alternative strategy. However, its efficacy is reputed but unproven increased risk of bleeding has not been fully established. We evaluated 514 adult allo-HCT recipients who received SOS prophylaxis with low-dose UFH. Bleeding complications occurred in 12 patients 2.3% of patients of which only 2 (0.4%) had significant grade 3 bleeding. Only 14 patients were diagnosed with hepatic SOS. Univariate analysis showed that day 100 SOS was higher in recipients of unmodified grafts when compared to CD34+ selected ex vivo T-cell depleted grafts (p≤ 0.001), and patients with hepatitis B and/or C exposure pre-HCT (p= 0.028). Overall, UFH was well tolerated and associated with a low incidence of subsequent hepatic SOS. Low-dose UFH prophylaxis can be considered in select patients who cannot tolerate oral ursodiol.

A PP(O)P pincer ligand based upon a peri-substituted acenaphthyl (Ace) scaffold and a secondary phosphine oxide, (5-Ph2P-Ace-6-)2P(O)H, was prepared and fully characterized including a neutron diffraction study. The reaction with [Ni(H2O)6]Cl2and PdCl2produced ionic metal(II) complexes [κ3-P,P’,P’’((5-Ph2P-Ace-6-)2P(OH))MCl]Cl, which upon addition of Et3N gave rise to zwitterionic metal(II) complexes κ3-P,P’,P’’((5-Ph2P-Ace-6-)2P(O))MCl (M = Ni, Pd). The reaction with Ni(COD)2(COD = cyclooctadiene) provided the η3-cyclooctenyl Ni(II) complex κ3-P,P’,P’’((5-Ph2P-Ace-6-)2P(O))Ni(η3-C8H13). A detailed complementary bonding analysis of the P–H, P–O, and P–M interactions was carried out (M = Ni, Pd).

Purpose: Attention has recently been paid to Clinical Linguistics for the detection and support of clinical conditions. Many works have been published on the “linguistic profile” of various clinical populations, but very few papers have been devoted to linguistic changes in patients with eating disorders. Patients with Anorexia Nervosa (AN) share similar psychological features such as disturbances in self-perceived body image, inflexible and obsessive thinking and anxious or depressive traits. We hypothesize that these characteristics can result in altered linguistic patterns and be detected using the Natural Language Processing tools. Methods: We enrolled 51 young participants from December 2019 to February 2020 (age range: 14–18): 17 girls with a clinical diagnosis of AN, and 34 normal-weighted peers, matched by gender, age and educational level. Participants in each group were asked to produce three written texts (around 10–15 lines long). A rich set of linguistic features was extracted from the text samples and the statistical significance in pinpointing the pathological process was measured. Results: Comparison between the two groups showed several linguistics indexes as statistically significant, with syntactic reduction as the most relevant trait of AN productions. In particular, the following features emerge as statistically significant in distinguishing AN girls and their normal-weighted peers: the length of the sentences, the complexity of the noun phrase, and the global syntactic complexity. This peculiar pattern of linguistic erosion may be due to the severe metabolic impairment also affecting the central nervous system in AN. Conclusion: These preliminary data showed the existence of linguistic parameters as probable linguistic markers of AN. However, the analysis of a bigger cohort, still ongoing, is needed to consolidate this assumption. Level of evidence III: Evidence obtained from case–control analytic studies.

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2Aand transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3–50, P< 2.14 × 10−6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-d-aspartate) receptor subunit GRIN2Aand AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.

Boron–nitrogen substitutions in polycyclic aromatic hydrocarbons (PAHs) have a strong impact on the optical properties of the molecules due to a significantly more heterogeneous electron distribution. However, besides these single-molecule properties, the observed optical properties of PAHs critically depend on the degree of intermolecular interactions such as π–π-stacking, dipolar interactions, or the formation of dimers in the excited state. Pyrene is the most prominent example showing the latter as it exhibits a broadened and strongly bathochromically shifted emission band at high concentrations in solution compared to the respective monomers. In the solid state, the impact of intermolecular interactions is even higher as it determines the crystal packing crucially. In this work, a thiophene-flanked BN-pyrene (BNP) was synthesized and compared with its all-carbon analogue (CCP) in solution and in the solid state by means of crystallography, NMR spectroscopy, UV–vis spectroscopy, and photoluminescence (PL) spectroscopy. In solution, PL spectroscopy revealed the solvent-dependent presence of excimers of CCPat high concentrations. In contrast, no excimers were found in BNP. Clear differences were also observed in the single-crystal packing motifs. While CCPrevealed overlapped pyrene planes with centroid distances in the range of classical π-stacking interactions, the BNPscaffolds were displaced and significantly more spatially separated.

ObjectiveA GGGGCC repeat expansion in the C9orf72gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay.MethodsWe used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS.Results and conclusionsWe show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze–thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72repeat-containing transcripts.

This study aimed to understand the impact of the prosodic deficit in Parkinson’s disease (PD) on the communicative effectiveness of vocal expression of emotion. Fourteen patients with PD and 13 healthy control subjects (HC) uttered the phrase “non è possible, non ora” (“It is not possible, not now”) six times reading different emotional narrations. Three experts evaluated the PD subjects’ vocal production in terms of their communicative effectiveness. The PD patients were divided into two groups: PD+ (with residual effectiveness) and PD− (with impaired effectiveness). The vocal productions were administered to 30 naïve listeners. They were requested to label the emotion they recognized and to make judgments about their communicative effectiveness. The PD speakers were perceived as less effective than the HC speakers in conveying emotions (especially fear and anger). The PD− group was the most impaired in the expression of emotion, suggesting that speech disorders impact differently at the same stage of the disease with varying degrees of severity.

The post-transplant scoring system (PTSS), developed by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, is based on three independent post-transplant risk factors: grade of acute graft-versus-host disease, lack of platelet recovery before day 100, and relapse before day 100; discriminating low- (0), intermediate- (1–3), and high-risk (4–8) patients. We investigated the prognostic value of the PTSS in a cohort of patients with MDS who underwent myeloablative CD34-selected TCD transplants. From 2008 to 2018, 109 patients underwent a first TCD-HCT for MDS at our center. We used Cox proportional hazards models and different landmark analyses to evaluate the association of categorized PTSS score risk groups with overall survival (OS). Patients with an intermediate/ high risk PTSS score had decreased OS at day 180 (univariate HR 3.25 [95% CI 1.60, 6.60], p= 0.001) and at day 365 (univariate HR 5.42 [95% CI 2.21, 13.3], p< 0.001) compared to low risk PTSS scores. This association remained significant after adjusting for HCT-CI. PTSS score calculated at day 100 was not associated with OS, even after adjusting for HCT-CI subgroups. In summary, the PTSS predicted survival at day 180 and day 365 in recipients of T-cell-depleted allografts for myelodysplastic syndrome.

Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS prognostication biomarkers in 252 patients with detailed clinical phenotyping. First, we identified, in a longitudinal cohort, miRNAs whose plasma levels remain stable over the course of disease. Next, we showed that high levels of miR-181, a miRNA enriched in neurons, predicts a greater than two-fold risk of death in independent discovery and replication cohorts (126 and 122 patients, respectively). miR-181 performance is similar to neurofilament light chain (NfL), and when combined together, miR-181 + NfL establish a novel RNA–protein biomarker pair with superior prognostication capacity. Therefore, plasma miR-181 alone and a novel miRNA–protein biomarker approach, based on miR-181 + NfL, boost precision of patient stratification. miR-181-based ALS biomarkers encourage additional validation and might enhance the power of clinical trials.

Polygenic risk scores (PRS) summarize genetic liability to a disease at the individual level, and the aim is to use them as biomarkers of disease and poor outcomes in real-world clinical practice. To date, few studies have assessed the prognostic value of PRS relative to standards of care. Schizophrenia (SCZ), the archetypal psychotic illness, is an ideal test case for this because the predictive power of the SCZ PRS exceeds that of most other common diseases. Here, we analyzed clinical and genetic data from two multi-ethnic cohorts totaling 8,541 adults with SCZ and related psychotic disorders, to assess whether the SCZ PRS improves the prediction of poor outcomes relative to clinical features captured in a standard psychiatric interview. For all outcomes investigated, the SCZ PRS did not improve the performance of predictive models, an observation that was generally robust to divergent case ascertainment strategies and the ancestral background of the study participants.

Whistler‐mode hiss waves are crucial to the dynamics of Earth's radiation belts, particularly in the scattering and loss of energetic electrons and forming the slot region between the inner and outer belts. The generation of hiss waves involves multiple potential mechanisms, which are under active research. Understanding the role of hiss waves in radiation belt dynamics and their generation mechanisms requires analyzing their temporal and spatial evolutions, especially for strong hiss waves. Therefore, we developed an Imbalanced Regressive Neural Network (IR‐NN) model for predicting hiss amplitudes. This model addresses the challenge posed by the data imbalance of the hiss data set, which consists of predominantly quiet‐time background samples and fewer but significant active‐time intense hiss samples. Notably, the IR‐NN hiss model excels in predicting strong hiss waves (>100 pT). We investigate the temporal and spatial evolution of hiss wave during a geomagnetic storm on 24–27 October 2017. We show that hiss waves occur within the nominal plasmapause, and follow its dynamically evolving shape. They exhibit intensifications with 1 and 2 hr timescale similar to substorms but with a noticeable time delay. The intensifications begin near dawn and progress toward noon and afternoon. During the storm recovery phase, hiss intensifications may occur in the plume. Additionally, we observe no significant latitudinal dependence of the hiss waves within |MLAT| < 20°. In addition to describing the spatiotemporal evolution of hiss waves, this study highlights the importance of imbalanced regressive methods, given the prevalence of imbalanced data sets in space physics and other real‐world applications. Whistler‐mode hiss waves play a crucial role in understanding the dynamics of Earth's radiation belts, particularly scattering and loss of energetic electrons and the formation of the slot region. The underlying generation mechanisms of hiss wave sources remain an active area of research, which needs to quantify the global evolution of these waves, especially powerful ones. We developed an Imbalanced Regressive Neural Network (IR‐NN) model, which excels at accurately predicting strong hiss wave activity, that is of particular interest in radiation belt studies. We analyzed the evolution of hiss waves during a geomagnetically active period in October 2017. We found that these waves predominantly occur within the plasmapause boundary and exhibit dynamics that follow the plasmapause's changes. These waves strengthen on timescales similar to those of magnetospheric substorms, with a slight delay, and move to different local times during different phases of the storm. These waves maintain uniform intensity across low to mid‐latitudes. This study underlines the importance of imbalanced regressive methods in handling imbalanced data sets, a common challenge in space physics and related physical science fields. This approach is not only significant for advancing our understanding of space weather phenomena but also has broader implications in other areas. An imbalanced regressive neural network model of hiss amplitude developed that predicts quiet‐time background and active‐time intense wavesHiss waves are well organized inside the plasmapause and follow its dynamic shape, evolving from dawn toward later local time during a stormModeled hiss evolution correlates with chorus, supporting the hypothesis that hiss is generated by evolving chorus waves An imbalanced regressive neural network model of hiss amplitude developed that predicts quiet‐time background and active‐time intense waves Hiss waves are well organized inside the plasmapause and follow its dynamic shape, evolving from dawn toward later local time during a storm Modeled hiss evolution correlates with chorus, supporting the hypothesis that hiss is generated by evolving chorus waves

We use the full NASA Van Allen Probes mission (2012–2019) to extract the electron plasma density from the Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS) and Electric Field and Waves (EFW) instruments and discuss the evolution of the plasmasphere. We generate new statistics including mean and standard deviations of the plasma density with respect to L‐shell, magnetic local time (MLT), and various geomagnetic indices. These statistics are generated to be applied in radiation belt physics and space weather codes (with fits provided). The mean plasmasphere is circular around Earth with respect to MLT for Kp < 1. The mean 100 cm−3level line is above L = 5 and mean 10 cm−3level expands above the Van Allen Probes apogee for Kp < 1. The outer electron belt lies within the plasmasphere for 60% of all times. As activity increases (Kp > 2), a gradual MLT asymmetry forms with higher mean density in the afternoon sector due to plumes expanding outward. Conversely, the mean density decreases on the dawn and night sectors. The mean density is between ∼500 and ∼50 cm−3between L ∼ 4 and L ∼ 6 during quiet and moderately active times (Kp < 3), representing ∼80% of all times. Statistics in regions of high density below L = 2 are underdefined for intense activity. The highest standard deviation of density represents a factor 2.5 to 3 times the mean above L = 5 and for active times. We find the percent difference between the EFW and EMFISIS densities is bounded by ±20% for quiet and moderate activity (Kp < 5) and goes up to ±100% for extreme activity. The Earth's plasmasphere, discovered in the 1950s, is a region of cold plasma made of ions and electrons of a few electronvolts in energy, originating from upwelling ionized gas from the ionosphere and forming a rotating torus around the Earth. The radial profile of the electron cold plasma density within the plasmasphere decays from 10,000 electrons per cubic centimeter at ∼1,000 km altitude to 10s electrons per cubic centimeter at its outer edge, sometimes exceeding ∼36,000 km in altitude at the equator. The state of the plasmasphere is highly dependent on geomagnetic conditions, with geomagnetic storms and substorms eroding parts of this plasma. Here, we analyze 7 years of NASA Van Allen Probes measurements of the electron plasma density and generate statistics with respect to L‐shell, magnetic local time, and geomagnetic indices. In this way, we show statistical variations of the plasmasphere, a strong magnetic local time dependence, and erosion with increasing geomagnetic activity. New mean electron densities and their standard deviation are generated and fitted with model functions that can be incorporated into space weather codes. This is important because the electron density is a key parameter influencing the strength of wave‐particle interactions that accelerate and scatter energetic particles in the inner magnetosphere. Generation of new statistics of mean and standard deviation of the plasma density from Electric Field and Waves and Electric and Magnetic Field Instrument Suite and Integrated Science of RBSP for the whole missionEmpirical density models made of fits are provided versus L‐shell, magnetic local time (MLT), and geomagnetic indices to be used in radiation belt codesAn extensive analysis of the cold plasma statistics is provided with respect to L‐shell, MLT, and geomagnetic activity Generation of new statistics of mean and standard deviation of the plasma density from Electric Field and Waves and Electric and Magnetic Field Instrument Suite and Integrated Science of RBSP for the whole mission Empirical density models made of fits are provided versus L‐shell, magnetic local time (MLT), and geomagnetic indices to be used in radiation belt codes An extensive analysis of the cold plasma statistics is provided with respect to L‐shell, MLT, and geomagnetic activity

AGILE is a space mission launched in 2007 to study X-ray and gamma-ray phenomena through data acquired by different payload instruments. The AGILE Team developed an application called AGILEScience that allows to visualize information about the AGILE space mission from mobile devices, such as smartphones and tablets. The AGILEScience application can be downloaded freely for iOS and Android devices.

Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa).

Purpose: Pervasive refusal syndrome (PRS) is a rare psychiatric disease that affects children. It was first described by Lask in 1991 (Arch Dis Child 66:866–869, 1991). Recently, Otasowie and Collaborators reported a systematic review about PRS. Despite this, PRS has not yet been classified in DSM-5 and ICD-11 and the lack of evidence-based treatment makes this syndrome a real challenge for clinicians. The aim of this paper is to present our experience through the description of a case report and its treatment. Methods and results: The case reported is a girl aged 11 years that fits the clinical picture described in the literature of PRS. In previous reports, behavioural treatment was not used or appreciated; our case adds new knowledge regarding the PRS diagnosis and the successful behavioural treatment during hospitalization, which we describe in all its phases. Conclusion: PRS is a rare, life-threatening syndrome; it would be extremely important to have an official and evidence-based treatment guide. Level of evidence: Level V, case report.

Allogeneic hematopoietic stem cell transplantation (HSCT) may potentially cure patients with chronic lymphocytic leukemia (CLL) and Richter’s transformation (CLL-RT) or CLL without RT, but the impact of novel agents on HSCT is unclear. CLL-RT patients have a grave prognosis, and their outcomes after HSCT are uncertain. We conducted a retrospective analysis of all 58 CLL patients, including 23 CLL-RT patients, who underwent reduced intensity conditioning (RIC) HSCT at Memorial Sloan Kettering Cancer Center (New York, NY) between September 2006 and April 2017. With a median follow-up of 68 months (range, 24-147 months), 5-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 28%-56%), and overall survival (OS) was 58% (95% CI, 48%-74%). The 1-year graft-versus-host disease/relapse-free survival (GRFS) was 38% (95% CI, 25%-50%). Patients with CLL-RT and CLL patients without RT had comparable outcomes. In both cohorts, treatment-sensitive response and ≤3 previous lines of therapy produced superior PFS and OS. Outcomes were agnostic to adverse cytogenetic and molecular features. Novel agents did not have a negative impact on HSCT outcomes. Total body irradiation (TBI)-containing RIC yielded inferior PFS, OS, and GRFS. CLL-RT patients older than age 55 years who had an HSCT Comorbidity Index score of ≥2 demonstrated inferior OS. This study, which is the largest series of RIC-HSCT for patients with CLL-RT, provides evidence supporting RIC-HSCT in early remission courses for patients with CLL-RT and poor-risk CLL patients. TBI-containing RIC should be considered with caution.

Allogeneic hematopoietic stem cell transplantation (HSCT) may potentially cure patients with chronic lymphocytic leukemia (CLL) and Richter's transformation (CLL-RT) or CLL without RT, but the impact of novel agents on HSCT is unclear. CLL-RT patients have a grave prognosis, and their outcomes after HSCT are uncertain. We conducted a retrospective analysis of all 58 CLL patients, including 23 CLL-RT patients, who underwent reduced intensity conditioning (RIC) HSCT at Memorial Sloan Kettering Cancer Center (New York, NY) between September 2006 and April 2017. With a median follow-up of 68 months (range, 24-147 months), 5-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 28%-56%), and overall survival (OS) was 58% (95% CI, 48%-74%). The 1-year graft-versus-host disease/relapse-free survival (GRFS) was 38% (95% CI, 25%-50%). Patients with CLL-RT and CLL patients without RT had comparable outcomes. In both cohorts, treatment-sensitive response and ≤3 previous lines of therapy produced superior PFS and OS. Outcomes were agnostic to adverse cytogenetic and molecular features. Novel agents did not have a negative impact on HSCT outcomes. Total body irradiation (TBI)-containing RIC yielded inferior PFS, OS, and GRFS. CLL-RT patients older than age 55 years who had an HSCT Comorbidity Index score of ≥2 demonstrated inferior OS. This study, which is the largest series of RIC-HSCT for patients with CLL-RT, provides evidence supporting RIC-HSCT in early remission courses for patients with CLL-RT and poor-risk CLL patients. TBI-containing RIC should be considered with caution.

The reaction of (5-Ph2P-Ace-6-)2MeSiH with [(C2H4)2RhCl]2proceeded via elimination of ethylene and oxidative addition of the Si–H bond at rhodium and provided the rhodium(III) complex (5-Ph2P-Ace-6-)2MeSiRh(H)Cl (1) possessing a reverse agostic interaction of the type Rh–H···Si, which was characterized by Hirshfeld atom refinement (HAR) of single-crystal X-ray diffraction data. This technique allows the precise and accurate determination of hydrogen positions also for heavier transition-metal hydrides. The bonding situation in the Rh–H···Si interaction was further analyzed using a set of complementary bonding indicators, such as the compliance matrix analysis or real-space bonding indicators derived from the electron and electron pair densities. The reaction of (5-Ph2P-Ace-6-)2MeSiH with [(CO)2RhCl]2occurred via elimination of hydrogen chloride and produced the rhodium(I) complex (5-Ph2P-Ace-6-)2MeSiRh(CO)2(2).

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica­tion is prescribed, with second‐generation antipsychotics usually preferred to first‐generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidence‐based family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves “recovery‐oriented”, it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological components, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patient’s needs in terms of employment, housing, self‐care, social relationships and education, and offers a focus on identity, meaning and resilience.

L’enfasi posta da Seneca sulla tortura, che si è sinora supposta derivare da fattori stilistici (il gusto dell’epoca per il macabro) e storicopersonali (il rischio reale di essere torturati, per i membri dell’élite sotto il Principato), è spiegata in questo articolo in un modo nuovo, basato sulla massima epicurea - adottata da Seneca - secondo la quale il dolore, se acuto, è breve e, se cronico, è lieve. La tortura, infatti, infliggendo deliberatamente dolore grave e prolungato e privando la vittima della possibilità di suicidarsi, mette in crisi il quadro rassicurante della tolleranza al dolore da parte del sapiens, ponendo quest’ultimo davanti al rischio di fallimento.

ObjectiveThe clinical utility of routine genetic sequencing in amyotrophic lateral sclerosis (ALS) is uncertain. Our aim was to determine whether routine targeted sequencing of 44 ALS-relevant genes would have a significant impact on disease subclassification and clinical care.MethodsWe performed targeted sequencing of a 44-gene panel in a prospective case series of 100 patients with ALS recruited consecutively from the Sheffield Motor Neuron Disorders Clinic, UK. All participants were diagnosed with ALS by a specialist Consultant Neurologist. 7/100 patients had familial ALS, but the majority were apparently sporadic cases.Results21% of patients with ALS carried a confirmed pathogenic or likely pathogenic mutation, of whom 93% had no family history of ALS. 15% met the inclusion criteria for a current ALS genetic-therapy trial. 5/21 patients with a pathogenic mutation had an additional variant of uncertain significance (VUS). An additional 21% of patients with ALS carried a VUS in an ALS-associated gene. Overall, 13% of patients carried more than one genetic variant (pathogenic or VUS). Patients with ALS carrying two variants developed disease at a significantly earlier age compared with patients with a single variant (median age of onset=56 vs 60 years, p=0.0074).ConclusionsRoutine screening for ALS-associated pathogenic mutations in a specialised ALS referral clinic will impact clinical care in 21% of cases. An additional 21% of patients have variants in the ALS gene panel currently of unconfirmed significance after removing non-specific or predicted benign variants. Overall, variants within known ALS-linked genes are of potential clinical importance in 42% of patients.

The synthesis, characterization, biological activity, and toxicology of sila-ibuprofen, a silicon derivative of the most common nonsteroidal anti-inflammatory drug, is reported. The key improvements compared with ibuprofen are a four times higher solubility in physiological media and a lower melting enthalpy, which are attributed to the carbon–silicon switch. The improved solubility is of interest for postsurgical intravenous administration. A potential for pain relief is rationalized via inhibition experiments of cyclooxygenases I and II (COX-I and COX-II) as well as via a set of newly developed methods that combine molecular dynamics, quantum chemistry, and quantum crystallography. The binding affinity of sila-ibuprofen to COX-I and COX-II is quantified in terms of London dispersion and electrostatic interactions in the active receptor site. This study not only shows the potential of sila-ibuprofen for medicinal application but also improves our understanding of the mechanism of action of the inhibition process.

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2= 0.032; liability R2= 0.017; P< 10−52), Latino (Nagelkerke’s R2= 0.089; liability R2= 0.021; P< 10−58), and European individuals (Nagelkerke’s R2= 0.089; liability R2= 0.037; P< 10−113), further highlighting the advantages of incorporating data from diverse human populations.

Understanding magnetic anisotropy and specifically how to tailor it is crucial in the search for high-temperature single-ion magnets. Herein, we investigate the magnetic anisotropy in a six-coordinated cobalt(II) compound that has a complex geometry and distinct triaxial magnetic anisotropy from the perspective of the electronic structure, using electronic spectra, ab initio calculations, and an experimental charge density, of which the latter two provides insight into the d-orbital splitting. The analysis showed that the d-orbital splitting satisfactorily predicted the complex triaxial magnetic anisotropy exhibited by the compound. Furthermore, a novel method to directly compare the ab initio results and the d-orbital populations obtained from the experimental charge density was developed, while a topological analysis of the density provided insights into the metal–ligand bonding. This work thus further establishes the validity of using d-orbitals for predicting magnetic anisotropy in transition metal compounds while also pointing out the need for a more frequent usage of the term triaxial anisotropy in the field of single-molecule magnetism.

Normal and water-in-salt Li–bis(trifluoromethane) sulfonimide anion-based electrolytes were modeled using atomistic molecular dynamics simulations. Their acetonitrile (ACN) mixtures, in various concentrations, were also studied to evaluate the impact of a cosolvent on the structural, dynamical, and electrical properties of the electrolytes using liquid electrolyte and supercapacitor models. Our simulations for pure and ACN-based electrolytes revealed a drastic difference that exists between normal electrolytes and water-in-salt electrolytes and a systematic reduction of the diffusion of species by approximately a factor of 2 because of the ACN impact. Electrolytic cells for each electrolyte were built with graphene as the electrode. Our results for capacitance reveal an asymmetry between the electrode capacitances, with negative electrode capacitance systematically higher than those of the positive electrode. The total capacitance of the electrode exhibited negligible variations regardless of the concentration and composition of the electrolyte.

An unusually low density solar wind event was observed in December 2022 moving past both Earth and Mars. The source was traced back to a coronal hole and active region on the Sun's surface. The resulting solar wind lead to the development of a co‐rotating interaction region (CIR) and trailing rarefaction region that lasted for multiple solar rotations. Within this structure, the solar wind conditions, including density, velocity, and magnetic field magnitude and orientation drastically changed. In this study we analyze the response of the Martian ionosphere using MAVEN data to these changing solar wind conditions. The low density solar wind region associated with the December event resulted in the expansion of the Martian ionospheric boundaries. We show that the ion composition boundary (ICB) is located at extreme altitudes that are beyond previously observed locations from the MAVEN mission between 2015 and 2018. Furthermore, the boundary between shocked solar wind and the Martian ionosphere identified using electron and ion data moved together on the dayside of the planet with the changing solar wind conditions. However, at the flank region these boundaries do not move together, and we show here that the decoupling of the two boundaries may be the result of a change in the interplanetary magnetic field azimuthal angle. The Sun constantly emits fast moving charged particles into interplanetary space in what is known as the solar wind. In December 2022, a region of fast moving solar wind overtook a region of slower moving solar wind. The fast solar wind acted as a broom sweeping up and compressing the slower wind preceding it. This interaction of two solar wind speeds is observed to rotate with the Sun. Trailing this interaction region is a region of low density solar wind. In December 2022, this type of interplanetary solar wind structure interacted with Mars' electrically charged atmosphere, or ionosphere. Throughout this period, the ionosphere boundary characterized by a transition from solar wind ions to planetary ions moved up and down relative to the planet near dusk. As the rarefaction region passed through the system, the ionosphere expanded to unusually high heights as it was not compressed by the solar wind. However, the flapping of the ionospheric boundary seems to depend on the orientation that the solar wind interacts with Mars. The disappearing solar wind event observed at Mars in December 2022 was caused by a co‐rotating interaction regionMars' ionosphere expanded further than previously observed locations between 2015 through 2018The flank ion composition boundary experiences large fluctuations in altitude after a change in the interplanetary magnetic field direction The disappearing solar wind event observed at Mars in December 2022 was caused by a co‐rotating interaction region Mars' ionosphere expanded further than previously observed locations between 2015 through 2018 The flank ion composition boundary experiences large fluctuations in altitude after a change in the interplanetary magnetic field direction

This article discusses the challenges faced by Mariana, a young girl who is asked to work at a factory to help her family financially. Mariana is conflicted because she knows it is illegal for her to work at her age. However, her aunt, who had been injured and unable to work, decides to return to work, relieving Mariana of the burden. The article also includes a poem by Aadya Agarwal, a 12-year-old girl, who reflects on the balance between freedom and responsibility. [Extracted from the article]

The proboscis extension response (PER) reflex may be used to condition the pairing of an odor with sucrose, which is applied to the antennae, in experiments to induce learning, where the odor represents a conditioned stimulus, while sucrose represents an unconditioned stimulus. A series of studies have been conducted on honeybees, relating learning and memory acquisition/retrieval using the PER as a strategy for accessing their ability to exhibit an unconditioned stimulus; however, the major metabolic processes involved in the PER are not well known. Thus, the aim of this investigation is profiling the metabolome of the honeybee brain involved in the PER. In this study, a semiquantitative approach of matrix-assisted laser desorption ionization (MALDI) mass spectral imaging (MSI) was used to profile the most abundant metabolites of the honeybee brain that support the PER. It was reported that execution of the PER requires the metabolic transformations of arginine, ornithine, and lysine as substrates for the production of putrescine, cadaverine, spermine, spermidine, 1,3-diaminopropane, and γ-aminobutyric acid (GABA). Considering the global metabolome of the brain of honeybee workers, the PER requires the consumption of large amounts of cadaverine and 1,3-diaminopropane, in parallel with the biosynthesis of high amounts of spermine, spermidine, and ornithine. To exhibit the PER, the brain of honeybee workers processes the conversion of l-arginine and l-lysine through the polyamine pathway, with different regional metabolomic profiles at the individual neuropil level. The outcomes of this study using this metabolic route as a reference are indicating that the antennal lobes and the calices (medial and lateral) were the most active brain regions for supporting the PER.

AimsNeoadjuvant chemoradiotherapy (neoCRT) is recommended for locally advanced rectal cancer (RC), however, this often makes lymph node (LN) search trying. The aim of this study was to evaluate, in a large retrospective, monocentric, series of post-neoCRT-RC patients, the importance of LN number, ratio and surface area in predicting metastases, overall survival (OS) and disease free survival (DFS).Methods104 patients with RC underwent total mesorectal excision, after standard neoCRT. All resected specimens were examined according to a standardised sampling/histopathological protocol. The following data regarding LNs were collected: total numbers; number with metastases; LNratio (metastatic/total); maximum diameter; surface area.ResultsA statistically significant association was found between LN number and DFS (p=0.0473). Finding ≤9 or >20 LNs correlated with worse prognosis compared with 10–20 (p value=0.049). LNratio (>0.2) was strongly associated with shorter DFS (HR=13.36; p value <0.0001) and OS (HR=26.06; p value <0.0001). Poor outcome, for DFS (HR=2.17, p value =0.0416) and OS (HR=1.18, p value =0.0025), was associated with increasing LN surface area. LNratio was independently associated with DFS at multivariate analysis (p value <0.0001).ConclusionsLN number, LNratio and LN surface area are important prognostic factors in neoCRT-RC and in particular finding ≤9 or >20 LNs is prognostically adverse.