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The classrooms in Israel are very diverse, with students differing in learning styles, their handling of literacy tasks, personal and socioeconomic backgrounds, and more. These differences significantly impact the curriculum aimed at promoting literacy resilience, explicit teaching processes in the classroom, and imparting metacognitive strategies and actions to overcome learning difficulties. This qualitative-interpretative study reveals the pedagogical perceptions, challenges, and coping strategies of fourteen Hebrew teachers in five elementary schools in central Israel regarding integrating home literacy in language lessons and cultivating literacy resilience among their students. The research data were collected through in-depth interviews with the teachers. The analysis of the teachers' reports reveals two main perceptions regarding literacy resilience: (1) Literacy resilience is a tool for life; (2) Home literacy significantly contributes to fostering literacy resilience. Furthermore, cultivating literacy resilience presents three significant challenges for the teachers: (1) Teaching in a heterogeneous classroom, (2) Encouraging parental involvement, and (3) Fostering independent learners. To cultivate literacy resilience in a heterogeneous classroom, teachers must be sensitive to each student's unique needs and plan teaching-learning processes based on principles of self-directed learning and peer dialogue. They must establish a personal-emotional connection that is a significant anchor for the students and outlines a path for integrating and strengthening the sense of competence in handling literacy tasks. It was also found that parental involvement is a significant factor influencing the cultivation of literacy resilience, and teachers undertake various actions to increase their level of involvement. This study adds an essential layer to the body of knowledge regarding the understanding of the factors affecting the development of pedagogical literacy perceptions that promote the integration of home literacy in the classroom. These perceptions may promote the nurturing process of literacy resilience among students from various cultures, accepting and understanding them. In this way, we can attempt to address literacy and language challenges in Israel.

This series of FactFinders presents a brief summary of the evidence and outlines recommendations to minimize risks associated with cervical epidural injections. Evidence in support of the following facts is presented. Minimizing Risks with Cervical Interlaminar Epidural Steroid Injections - 1) CILESIs should be performed at C6-C7 or below, with C7-T1 as the preferred access point due to the more generous dorsal epidural space at this level compared to the more cephalad interlaminar segments. This reduces the risk of the minor complication of dural puncture and the major complication of spinal cord injury due to inadvertent needle placement. 2) LF gaps are most prevalent in the midline cervical spine. This can result in diminished tactile feedback with loss of resistance (LOR), increasing the risk for inadvertent dural puncture or spinal cord injury. Based on current evidence, needle placement in the paramedian portion of the interlaminar space is safest to avoid LF gaps. 3) An optimal AP trajectory view and the physician's ability to discern engagement in the LF and subsequent LOR are crucial. Confirmation of minimal needle insertion depth relative to the ventral margin of the lamina with either a lateral or contralateral oblique (CLO) safety view is critical to minimize the risk of inadvertently inserting the needle too ventral. 4) There have been closed claims and case reports of patients who have suffered catastrophic neurologic injuries while receiving CILESIs under deep sedation. If sedation is administered, the least amount necessary should be utilized to ensure the patient can provide verbal feedback during the procedure. 5) CILESIs are an elective procedure; therefore, necessity and likelihood of benefit must be foremost considerations. Current guidelines recommend holding ACAP therapy before CILESIs due to the potentially catastrophic complications associated with epidural hematoma (EH) formation. However, there is also a risk of severe systemic complications with ceasing ACAP in specific clinical scenarios. The treating physician is obligated to determine if the procedure is indicated and can ultimately decide to delay the intervention or not perform the procedure if the benefit does not outweigh the risks. Minimizing Risks with Cervical Transforaminal Epidural Steroid Injections - the Role of Preprocedural Review of Advanced Imaging -- Variations in vascular anatomy may warrant a modified approach to CTFESI. Preprocedural review of cross-sectional imaging can provide critical information for safe injection angle planning specific to individual patients and may help to decrease the risk of unintended vascular events with potentially catastrophic outcomes. Safety of Multi-level or Bilateral Fluoroscopically-Guided Cervical Transforaminal Epidural Steroid Injections -- Safe performance of a CTFESI procedure requires the ability to detect inadvertent arterial injection. Contrast medium placed into the epidural space and/or along the exiting spinal nerves during an initial CTFESI may obscure the detection of inadvertent cannulation of a radiculomedullary artery by a subsequent CTFESI. While no available literature directly addresses the potential risk that exists with a multi-level or bilateral CTFESI, caution is still warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Photocatalytic CO 2 reduction to CO under unassisted (unbiased) conditions was recently demonstrated using heterostructure catalysts that combine p-type GaN with plasmonic Au nanoparticles and Cu nanoparticles as cocatalysts (p-GaN/Al 2 O 3 /Au/Cu). Here, we investigate the mechanistic role of Cu in p-GaN/Al 2 O 3 /Au/Cu under unassisted photocatalytic operating conditions using Cu K-edge X-ray absorption spectroscopy and first-principles calculations. Upon exposure to gas-phase CO 2 and H 2 O vapor reaction conditions, the composition of the Cu nanoparticles is identified as a mixture of Cu I and Cu II oxide, hydroxide, and carbonate compounds without metallic Cu. These composition changes, indicating oxidative conditions, are rationalized by bulk Pourbaix thermodynamics. Under photocatalytic operating conditions with visible light excitation of the plasmonic Au nanoparticles, further oxidation of Cu I to Cu II is observed, indicating light-driven hole transfer from Au-to-Cu. This observation is supported by the calculated band alignments of the oxidized Cu compositions with plasmonic Au particles, where light-driven hole transfer from Au-to-Cu is found to be thermodynamically favored. These findings demonstrate that under unassisted (unbiased) gas-phase reaction conditions, Cu is found in carbonate-rich oxidized compositions rather than metallic Cu. These species then act as the active cocatalyst and play an oxidative rather than a reductive role in catalysis when coupled with plasmonic Au particles for light absorption, possibly opening an additional channel for water oxidation in this system.

Purpose: A number of studies suggest that older patients may have reduced or no benefit from the addition of oxaliplatin to fluoropyrimidines as adjuvant chemotherapy for stage III colon cancer (CC)., Materials and Methods: We studied the prognostic impact of age, as well as treatment adherence/toxicity patterns according to age, in patients with stage III CC who received 3 or 6 months of infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (CAPOX) on the basis of data collected from trials from the ACCENT and IDEA databases. Associations between age and time to recurrence (TTR), disease-free survival (DFS), overall survival (OS), survival after recurrence (SAR), and cancer-specific survival (CSS) were assessed by a Cox model or a competing risk model, stratified by studies and adjusted for sex, performance status, T and N stage, and year of enrollment., Results: A total of 17,909 patients were included; 24% of patients were age older than 70 years (n = 4,340). Patients age ≥70 years had higher rates of early treatment discontinuation. Rates of grade ≥3 adverse events were similar between those older and younger than 70 years, except for diarrhea and neutropenia that were more frequent in older patients treated with CAPOX (14.2% v 11.2%; P = .01 and 12.1% v 9.6%; P = .04, respectively). In multivariable analysis, TTR was not significantly different between patients <70 years and those ≥70 years, but DFS, OS, SAR, and CSS were significantly shorter in those patients ≥70 years., Conclusion: In patients ≥70 years with stage III CC fit enough to be enrolled in clinical trials, oxaliplatin-based adjuvant chemotherapy was well tolerated and led to similar TTR compared with younger patients, suggesting similar efficacy. TTR may be a more appropriate end point for efficacy in this patient population.

The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations. PHLEX was developed using imaging mass cytometry (IMC) in the TRACERx study, validated using published Co-detection by indexing (CODEX), IMC and orthogonal data and benchmarked against state-of-the-art approaches. We evaluated its use on different tissue types, tissue fixation conditions, image sizes and antibody panels. As PHLEX is an automated and containerised Nextflow pipeline, manual assessment, programming skills or pathology expertise are not essential. PHLEX offers an end-to-end solution in a growing field of highly multiplexed data and provides clinically relevant insights., (© 2024. The Author(s).)

Attachment relationships are widely recognized as influential in increasing prosocial tendencies, with existing literature indicating that human attachment can increase empathetic processes, thereby potentially facilitating prosocial behavior. Given that pets frequently fulfill the criteria for attachment figures, this study investigates whether the observed associations among human attachment, empathy, and prosocial attitudes extend to human-animal interactions (HAI). This study examines the relationship between pet attachment, animal empathy, and prosocial attitudes toward humans. The study hypothesizes that animal empathy mediates the association between pet attachment and prosocial attitudes. A cross-sectional survey was administered to 343 Filipino participants, predominantly consisting of single female young adults with college education backgrounds. Participants completed a battery of assessments including the Contemporary Companion Animal Bonding Scale (CCABS), the Animal Empathy Scale (AES), and the Prosocialness Scale for Adults (PSA). Aligned with our hypothesis, our study reveals that animal empathy plays a significant mediating role in the relationship between pet attachment and attitudes toward humans. We found that stronger pet attachment correlates positively with heightened animal empathy, subsequently leading to elevated levels of prosocial attitudes. Our findings prompt discussions on implications for understanding human-animal relationships and suggest avenues for future research exploration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Faner, Dalangin, De Leon, Francisco, Sahagun and Acoba.)

Understanding the role of the tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs in treatment-naïve early-stage lung cancer using imaging mass cytometry in the TRACERx study (n = 81 patients/198 samples/2.3 million cells). In immune-hot adenocarcinomas, spatial niches of T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for niches of plasma and B cells in immune-excluded squamous cell carcinomas (LUSC). Immune-low TMEs were associated with fibroblast barriers to immune infiltration. The fourth archetype, characterized by sparse lymphocytes and high tumor-associated neutrophil (TAN) infiltration, had tumor cells spatially separated from vasculature and exhibited low spatial intratumor heterogeneity. TAN-high LUSC had frequent PIK3CA mutations. TAN-high tumors harbored recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune, and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis., Significance: This study provides novel insights into the spatial organization of the lung cancer TME in the context of tumor immunogenicity, tumor heterogeneity, and cancer evolution. Pairing the tumor evolutionary history with the spatially resolved TME suggests mechanistic hypotheses for tumor progression and metastasis with implications for patient outcome and treatment. This article is featured in Selected Articles from This Issue, p. 897., (©2024 The Authors; Published by the American Association for Cancer Research.)

Anticounterfeiting plays an essential role in authenticating genuine documents and combating forged products. To further advance the anticounterfeiting technology, there is a strong demand to design new functional materials with unique properties that will be appropriate for making multimode complex security labels. Recently, dynamic security labels have emerged as a new type of advanced anticounterfeiting method as they can hold a much higher security level than the traditional static ones. In this work, we report that calcium zinc germanate (CZGO) clinopyroxenes doped with lead ions have several interesting optical properties, such as dynamic fluorescence, long persistent luminescence, and photochromism. We find that the concentration of lead dopants can significantly impact the reaction kinetics as well as the crystallinity and luminescence properties of CZGO phosphors. By fully utilizing these unique properties, we have successfully fabricated several security labels with multilevel information encoding and dynamic optical performance. The combination of multimode and dynamic luminescence makes these labels extremely challenging to illegally duplicate. With further optimization, this lead-doped CZGO clinopyroxene can be well-integrated into modern anticounterfeiting techniques that will generate highly secure anticounterfeiting labels to combat fake products.

Objective: Unlike randomized controlled trials, practical real-world studies can offer important information about implementation of prehospital interventions, particularly in community settings where there may be reluctance to adopt new practices. We present the results of a natural experiment that was driven by mandated COVID-19 pandemic-driven shift from endotracheal intubation (ETI) to the i-gel ® supraglottic airway (SGA) as a primary advanced airway management device in the prehospital setting to reduce emergency medical services (EMS) personnel exposure to potentially infectious secretions. The objective was to compare first-pass success and timing to successful airway placement between ETI and the i-gel ® SGA under extenuating circumstances., Methods: This pre/post study compared airway placement metrics in prehospital patients requiring advance airway management for non-trauma-related conditions. Data from EMS records were extracted over 2 years, 12 months pre-pandemic, and 12 months post-pandemic. During the pre-COVID-19 year, the EMS protocols utilized ETI as the primary advanced airway device (ETI group). Post-pandemic paramedics were mandated to utilize i-gel ® SGA as the primary advanced airway device to reduce exposure to secretions (SGA group)., Results: There were 199 adult patients, 83 (42%) in the ETI group and 116 (58%) in the SGA group. First-pass success was significantly higher with SGA 96% (92%-99%) than ETI 68% (57%-78%) with paramedics citing the inability to visualize the airway in 52% of ETI cases. Time to first-pass success was significantly shorter in the SGA group (5.9 min [5.1-6.7 min]) than in the ETI group (8.3 min [6.9-9.6 min]), as was time to overall successful placement at 6.0 min (5.1-6.8 min) versus 9.6 min (8.2-11.1 min), respectively. Multiple placement attempts were required in 26% of ETI cases and 1% of the SGA cases. There were no statistically significant differences in the number and types of complications between the cohorts. Return of spontaneous circulation (on/before emergency department [ED] arrival), mortality at 28 days, intensive care unit length of stay, or ventilator-free days between the groups were not statistically different between the groups., Conclusion: In this natural experiment, the SGA performed significantly better than ETI in first-pass airway device placement success and was significantly faster in achieving first-pass success, and overall airway placement, thus potentially reducing exposure to respiratory pathogens. Practical real-world studies can offer important information about implementation of prehospital interventions, particularly in community settings and in systems with a low frequency of tracheal intubations., Competing Interests: Steven H. Katz, Shenae Samuels, and Linda Papa had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Steven H. Katz conceived the study. Steven H. Katz and Linda Papa designed the study. Data were acquired by Steven H. Katz, Joris Hoogendoorn, Daniel Levi, Ruben Troncoso, and Scott Gunn. All authors were involved in the analysis and interpretation of the data. Linda Papa, Steven H. Katz, Shenae Samuels, Matthew Katz, Lindsay Maguire, Christine VanDillen, Susan A. Miller, and Jay L. Falk drafted the manuscript, and all authors were involved in critical revision of the manuscript for important intellectual content. Statistical analysis was conducted by Linda Papa and Shenae Samuels. Administrative, technical, or material support was provided by Steven H. Katz, Joris Hoogendoorn, Daniel Levi, Shenae Samuels, Ruben Troncoso, and Scott Gunn.The authors declare they have no conflicts of interest., (© 2024 The Authors. Journal of the American College of Emergency Physicians Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Background: Lumbar articular fusion with the facet wedge (FW) technique is gaining increasing interest among surgeons for the treatment of vertebral instability due to its limited invasiveness and ease of use. Studies on cadavers have reported biomechanical properties similar to pedicle screws. Yet, the evidence supporting their use is still limited and moreover focused only on spinal degenerative disease., Methods: 96 cases of lumbar articular fusion with the FW techniques performed at 3 different centers between 2014 and 2022 were retrospectively analyzed based on the specific surgical indications: 1) degenerative spondylolisthesis/unstable lumbar stenosis; 2) synovial cysts; 3) adjacent segment disease (ASD). Medical records were reviewed to identify rates of complications and measures of functional outcome (ODI, low back pain VAS and modified Macnab scale) were collected both at baseline and at the follow-up visits. Wilcoxon signed-rank test was adopted to test for significant functional improvements., Results: Significative clinical improvements were observed from baseline to follow-up regarding ODI and VAS scores. Overall rate of moderate and severe complications (according to Landriel-Ibañez scale) was 7.9%. Only 3.4% of patients with degenerative disease developed ASD requiring reoperations. Only one case of radicular deficit and one of device mobilization were reported. 2/4 cases of synovial cysts treated with unilateral fusions developed contralateral complications. 9 out of 16 (56.25%) patients who underwent long-term postoperative CT scans presented adequate degree of articular fusion., Conclusion: FW technique is easy, safe, and effective. Its low rate of complications justifies its use for cases of mild lumbar instability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Synthetic autotrophy is a promising avenue to sustainable bioproduction from CO 2 . Here, we use iterative laboratory evolution to generate several distinct autotrophic strains. Utilising this genetic diversity, we identify that just three mutations are sufficient for Escherichia coli to grow autotrophically, when introduced alongside non-native energy (formate dehydrogenase) and carbon-fixing (RuBisCO, phosphoribulokinase, carbonic anhydrase) modules. The mutated genes are involved in glycolysis ( pgi ), central-carbon regulation ( crp ), and RNA transcription ( rpoB ). The pgi mutation reduces the enzyme's activity, thereby stabilising the carbon-fixing cycle by capping a major branching flux. For the other two mutations, we observe down-regulation of several metabolic pathways and increased expression of native genes associated with the carbon-fixing module ( rpiB ) and the energy module ( fdoGH ), as well as an increased ratio of NADH/NAD + - the cycle's electron-donor. This study demonstrates the malleability of metabolism and its capacity to switch trophic modes using only a small number of genetic changes and could facilitate transforming other heterotrophic organisms into autotrophs., Competing Interests: RB, SG, EN, RM We declare the following provisional patent related to the manuscript, "An Engineered Autotrophic E. coli Strain for CO2 Conversion to Organic Materials."European Patent Office: EP4051695A1, EM, VP, Bd, GJ, DL, HY, NN, DE, HL No competing interests declared, (© 2023, Ben Nissan, Milshtein et al.)

Progress in malaria control has stalled in recent years. With growing resistance to existing malaria vector control insecticides and the introduction of new vector control products, national malaria control programs (NMCPs) increasingly need to make data-driven, subnational decisions to inform vector control deployment. As NMCPs are increasingly conducting subnational stratification of malaria control interventions, including malaria vector control, country-specific frameworks and platforms are increasingly needed to guide data use for vector control deployment. Integration of routine health systems data, entomological data, and vector control program data in observational longitudinal analyses offers an opportunity for NMCPs and research institutions to conduct evaluations of existing and novel vector control interventions. Drawing on the experience of implementing 22 vector control evaluations across 14 countries in sub-Saharan Africa, as well as published and gray literature on vector control impact evaluations using routine health information system data, this article provides practical guidance on the design of these evaluations, makes recommendations for key variables and data sources, and proposes methods to address challenges in data quality. Key recommendations include appropriate parameterization of impact and coverage indicators, incorporating explanatory covariates and contextual factors from multiple sources (including rapid diagnostic testing stockouts; insecticide susceptibility; vector density measures; vector control coverage, use, and durability; climate and other malaria and non-malaria health programs), and assessing data quality before the evaluation through either on-the-ground or remote data quality assessments. These recommendations may increase the frequency, rigor, and utilization of routine data sources to inform national program decision-making for vector control.

Electron energy-loss spectroscopy (EELS) can measure similar information to x-ray, UV-Vis, and IR spectroscopies but with atomic resolution and increased scattering cross-sections. Recent advances in electron monochromators have expanded EELS capabilities from chemical identification to the realms of synchrotron-level core-loss measurements and to low-loss, 10-100 meV excitations, such as phonons, excitons, and valence structures. EELS measurements are easily correlated with electron diffraction and atomic-scale real-space imaging in a transmission electron microscope (TEM) to provide detailed local pictures of quasiparticle and bonding states. This perspective provides an overview of existing high-resolution EELS (HR-EELS) capabilities while also motivating the powerful next step in the field-ultrafast EELS in a TEM. Ultrafast EELS aims to combine atomic-level, element-specific, and correlated temporal measurements to better understand spatially specific excited-state phenomena. Ultrafast EELS measurements also add to the abilities of steady-state HR-EELS by being able to image the electromagnetic field and use electrons to excite photon-forbidden and momentum-specific transitions. We discuss the technical challenges ultrafast HR-EELS currently faces, as well as how integration with in situ and cryo measurements could expand the technique to new systems of interest, especially molecular and biological samples., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: A favorable postnatal prognosis in cases of pulmonary atresia/critical stenosis with intact ventricular septum (PA/CS-IVS) is generally equated with the possibility of achieving biventricular (BV) repair. Identification of fetuses that will have postnatal univentricular (UV) circulation is key for prenatal counseling, optimization of perinatal care and decision-making regarding fetal therapy. We aimed to evaluate the accuracy of published models for predicting postnatal circulation in PA/CS-IVS using a large internationally derived validation cohort., Methods: This was a systematic review of published uni- and multiparametric models for the prediction of postnatal circulation based on echocardiographic findings at between 20 and 28 weeks of gestation. Models were externally validated using data from the International Fetal Cardiac Intervention Registry. Sensitivity, specificity, predictive values, area under the receiver-operating-characteristics curves (AUCs) and proportion of cases with true vs predicted outcome were calculated., Results: Eleven published studies that reported prognostic parameters of postnatal circulation were identified. Models varied widely in terms of the main outcome (UV (n = 3), non-BV (n = 3), BV (n = 3), right-ventricle-dependent coronary circulation (n = 1) or tricuspid valve size at birth (n = 1)) and in terms of the included predictors (single parameters only (n = 6), multiparametric score (n = 4) or both (n = 1)), and were developed on small sample sizes (range, 15-38). Nine models were validated externally given the availability of the required parameters in the validation cohort. Tricuspid valve diameter Z-score, tricuspid regurgitation, ratios between right and left cardiac structures and the presence of ventriculocoronary connections (VCC) were the most commonly evaluated parameters. Multiparametric models including up to four variables (ratios between right and left structures, right ventricular inflow duration, presence of VCC and tricuspid regurgitation) had the best performance (AUC, 0.80-0.89). Overall, the risk of UV outcome was underestimated and that of BV outcome was overestimated by most models., Conclusions: Current prenatal models for the prediction of postnatal outcome in PA/CS-IVS are heterogeneous. Multiparametric models for predicting UV and non-BV circulation perform well in identifying BV patients but have low sensitivity, underestimating the rate of fetuses that will ultimately have UV circulation. Until better discrimination can be achieved, fetal interventions may need to be limited to only those cases in which non-BV postnatal circulation is certain. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Cellular lineage tracking provides a means to observe population makeup at the clonal level, allowing exploration of heterogeneity, evolutionary and developmental processes and individual clones' relative fitness. It has thus contributed significantly to understanding microbial evolution, organ differentiation and cancer heterogeneity, among others. Its use, however, is limited because existing methods are highly specific, expensive, labour-intensive, and, critically, do not allow the repetition of experiments. To address these issues, we developed gUMI-BEAR (genomic Unique Molecular Identifier Barcoded Enriched Associated Regions), a modular, cost-effective method for tracking populations at high resolution. We first demonstrate the system's application and resolution by applying it to track tens of thousands of Saccharomyces cerevisiae lineages growing together under varying environmental conditions applied across multiple generations, revealing fitness differences and lineage-specific adaptations. Then, we demonstrate how gUMI-BEAR can be used to perform parallel screening of a huge number of randomly generated variants of the Hsp82 gene. We further show how our method allows isolation of variants, even if their frequency in the population is low, thus enabling unsupervised identification of modifications that lead to a behaviour of interest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rezenman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Amblyopia is the most common developmental vision disorder in children. The initial treatment consists of refractive correction. When insufficient, occlusion therapy may further improve visual acuity. However, the challenges and compliance issues associated with occlusion therapy may result in treatment failure and residual amblyopia. Virtual reality (VR) games developed to improve visual function have shown positive preliminary results. The aim of this study is to determine the efficacy of these games to improve vision, attention, and motor skills in patients with residual amblyopia and identify brain-related changes. We hypothesize that a VR-based training with the suggested ingredients (3D cues and rich feedback), combined with increasing the difficulty level and the use of various games in a home-based environment is crucial for treatment efficacy of vision recovery, and may be particularly effective in children., Methods: The AMBER study is a randomized, cross-over, controlled trial designed to assess the effect of binocular stimulation (VR-based stereoptic serious games) in individuals with residual amblyopia (n = 30, 6-35 years of age), compared to refractive correction on vision, selective attention and motor control skills. Additionally, they will be compared to a control group of age-matched healthy individuals (n = 30) to account for the unique benefit of VR-based serious games. All participants will play serious games 30 min per day, 5 days per week, for 8 weeks. The games are delivered with the Vivid Vision Home software. The amblyopic cohort will receive both treatments in a randomized order according to the type of amblyopia, while the control group will only receive the VR-based stereoscopic serious games. The primary outcome is visual acuity in the amblyopic eye. Secondary outcomes include stereoacuity, functional vision, cortical visual responses, selective attention, and motor control. The outcomes will be measured before and after each treatment with 8-week follow-up., Discussion: The VR-based games used in this study have been conceived to deliver binocular visual stimulation tailored to the individual visual needs of the patient, which will potentially result in improved basic and functional vision skills as well as visual attention and motor control skills., Trial Registration: This protocol is registered on ClinicalTrials.gov (identifier: NCT05114252) and in the Swiss National Clinical Trials Portal (identifier: SNCTP000005024)., (© 2023. The Author(s).)

During the first Covid-19 outbreak, the Niguarda Hospital of Milan featured two Psychiatry wards, one for SARS-CoV-2 positive patient and one for patients requiring hospitalization and negative for SARS-CoV-2. The two groups of patients were compared and were similar in distribution of psychiatric diagnosis, duration of illness and previous hospitalizations. SARS-CoV-2 positive participants had a lower severity of symptoms both at admission and discharge, a lower frequency of psychotic symptoms and substance intoxication at admission. These findings suggest that patients admitted to the COVID ward were hospitalized not only for their mental health condition but also because of the infection., Competing Interests: Declaration of Competing Interest The Authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Background: Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS)., Methods: In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes., Results: Agreement between local and central review was moderate (kappa = 0.53) for VSS and high (kappa = 0.81) for ∆SUV categories (<66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p = 0.03) and OS (p = 0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable., Conclusions: These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Prior work demonstrated that a history of episodic low back pain was highly indicative of discogenic pain. Recently, there has been more focus on vertebrogenic pain, however little is known about the clinical features of this condition., Purpose: To determine if a history of severe episodic low back pain correlates with Modic endplate changes on lumbar spine magnetic resonance imaging (MRI), presumed to be a marker of vertebrogenic pain., Study Design: /setting: Retrospective, observational, in vivo study of consecutive patients at outpatient Physical Medicine & Rehabilitation clinics at a single academic spine center., Patient Sample: Consecutive patients who received a lumbar spine MRI between January 1, 2020, and December 31, 2020., Methods: A retrospective chart review identified patients who received a lumbar spine MRI in 2020. Chart review then determined if patients had a history of episodes of low back pain lasting at least 2 days, or if they had non-episodic low back pain (pain beginning with a gradual onset or after a specific event with continuous symptoms for >3 months). Patients were excluded if they had prior lumbar spine surgery, radicular leg pain without low back pain, indeterminate presentations based on chart review, acute spine fractures, or metastatic spine lesions. For the primary analysis, the MRIs were reviewed and were dichotomized into positive (having for either type 1 or type 2 Modic changes at any level) or negative (no Modic changes at any level)., Results: A total of 111 patients were analyzed. Inter-rater reliability for determining whether a patient's low back pain was episodic was strong (kappa ​= ​0.83), as was inter-rater reliability for determining if a patient had any levels with type 1 or type 2 Modic changes (kappa ​= ​0.81). Seventy-one out of 111 patients had type 1 and/or type 2 Modic changes at one or more spinal levels. The sensitivity of the test (episodic vs non-episodic low back pain) in finding patients with Modic changes was 20% and the specificity was 70%. The diagnostic confidence odds were 1.2, with a diagnostic confidence of 55%. Subgroup analyses for type 1 Modic changes, and for type 2 Modic changes, showed similar values., Conclusions: A history of episodic low back pain is not a strong indicator for a vertebrogenic etiology., (© 2023 The Authors.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Significant pulmonary regurgitation (PR) and pulmonary stenosis are common after surgical repair of some congenital heart defects. This prospective, single-arm, multicenter trial enrolled patients who underwent transcatheter heart valve (THV) implantation with a SAPIEN 3 valve to treat dysfunctional right ventricular outflow tract (RVOT) conduits or pulmonic surgical valves (≥ moderate PR and/or mean RVOT gradient ≥35 mm Hg). The primary end point was a nonhierarchical composite of THV dysfunction at 1 year comprising RVOT reintervention, ≥ moderate total PR, and mean RVOT gradient >40 mm Hg. A performance goal of <25% of upper confidence interval (CI) was prespecified for the primary end point, using a 95% exact binomial CI. Patients (n = 58) were enrolled between July 5, 2016 and July 17, 2018, with mean age of 32 years. Prestenting was performed in 53.4%. At discharge, the device success was 98.1% (single valve without explant, < moderate PR, gradient <35 mm Hg). At 30 days, there were no major adjudicated adverse clinical events. At 1 year, the primary end point composite was 4.3% (95% CI 0.5 to 14.5). The composite components were 0% (0 of 56) RVOT reintervention, 2.1% (1 of 47) ≥ moderate PR, and 2.1% (1 of 48) mean RVOT gradient >40 mm Hg. No mortality, endocarditis, thrombosis, or stent fracture were reported at 1 year. In conclusion, the SAPIEN 3 THV was safe and effective in patients with dysfunctional RVOT conduits or previously implanted valves in the pulmonic position to 1 year. Clinical trial registration: NCT02744677; https://clinicaltrials.gov/ct2/show/NCT02744677., (Copyright © 2022. Published by Elsevier Inc.)

Background: Upper extremity radicular pain is commonly treated with a cervical transforaminal epidural steroid injection (CTFESI). Recently, a new technique, the modified approach CTFESI, has been developed with a theoretical safety advantage to avoid the neurovascular structures. This approach requires an angle measurement of the superior articular process (SAP) on MRI. The inter-rater reliability of this angle measurement among practicing physicians is yet to be investigated., Objective: The purpose of this study was to determine the inter-rater reliability of SAP angle measurements on MRI., Methods: Three raters independently measured the SAP angle on 50 cervical MRIs. A two-way, mixed effects, absolute agreement, single rater statistical model was used to determine the intraclass correlation coefficient (ICC) between all three raters, as well as between each pair of raters., Results: Inter-rater reliability among all raters showed good reliability with an ICC ​= ​0.837709 (95% CI 0.75-0.9, p ​< ​0.001). Similarly, good inter-rater reliability was found between each of the pairs of raters., Conclusion: This study demonstrates good inter-rater reliability of MRI SAP angle measurement among clinicians for use in the modified CTFESI approach., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: We herein advocate for more extensive utilization of ex vivo resection techniques for otherwise unresectable liver tumors by presenting the largest collective American experience., Background: Advanced in situ resection and vascular reconstruction techniques have made R0 resection possible for otherwise unresectable liver tumors. Ex vivo liver resection may further expand the limits of resectability but remains underutilized due to concerns about technical complexity and vascular thrombosis. However, we believe that the skillset required for ex vivo liver resection is more widespread and the complications less severe than widely assumed, making ex vivo resection a more attractive option in selected case., Methods: We retrospectively analyzed 35 cases performed by surgical teams experienced with ex vivo liver resections (at least 4 cases) between 1997 and 2021., Results: We categorized malignancies as highly aggressive (n=18), moderately aggressive (n=14), and low grade (n=3). All patients underwent total hepatectomy, vascular reconstruction and resection in hypothermia on the backtable, and partial liver autotransplantation. Overall survival was 67%/39%/28%, at 1/3/5 years, respectively, with a median survival of 710 days (range: 22-4824). Patient survival for highly aggressive, moderately aggressive, and low-grade tumors was 61%/33%/23%, 67%/40%/22%, and 100%/100%/100% at 1/3/5 years, respectively, with median survival 577 days (range: 22-3873), 444 days (range: 22-4824), and 1825 days (range: 868-3549)., Conclusions: Ex vivo resection utilizes techniques commonly practiced in partial liver transplantation, and we demonstrate relatively favorable outcomes in our large collective experience. Therefore, we propose that more liberal use of this technique may benefit selected patients in centers experienced with partial liver transplantation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Occasionally, lightning will exit the top of a thunderstorm and connect to the lower edge of space, forming a gigantic jet. Here, we report on observations of a negative gigantic jet that transferred an extraordinary amount of charge between the troposphere and ionosphere (∼300 C). It occurred in unusual circumstances, emerging from an area of weak convection. As the discharge ascended from the cloud top, tens of very high frequency (VHF) radio sources were detected from 22 to 45 km altitude, while simultaneous optical emissions (777.4 nm OI emitted from lightning leaders) remained near cloud top (15 to 20 km altitude). This implies that the high-altitude VHF sources were produced by streamers and the streamer discharge activity can extend all the way from near cloud top to the ionosphere. The simultaneous three-dimensional radio and optical data indicate that VHF lightning networks detect emissions from streamer corona rather than the leader channel, which has broad implications to lightning physics beyond that of gigantic jets.

Acute colonic pseudo-obstruction (ACPO) is a condition characterized by acute dilation of the large bowel without evidence of mechanical obstruction that occurs in a variety of hospitalized patients with many predisposing factors. Management includes supportive care and limitation of offending medications with mainstays of treatment of neostigmine administration and colonic decompression. We report the case of a critically ill patient with ACPO who experienced bradycardia and a brief episode of asystole when receiving concomitant dexmedetomidine and neostigmine infusions but who later remained hemodynamically stable when receiving propofol and neostigmine infusions. The bradycardia and associated hemodynamic instability experienced while on dexmedetomidine and neostigmine infusions were rapidly corrected with atropine and cessation of offending agents. Because ACPO is encountered frequently and the use of dexmedetomidine as a sedative agent in the ICU is increasing, practitioners should be aware of the additive risk of bradycardia and potential for asystole with the combination of neostigmine and dexmedetomidine. Electronic drug interaction databases should be updated and drug information sources should include a drug-drug interaction between dexmedetomidine and neostigmine to reduce the likelihood of concomitant administration.

Predicting not only the target but also an accurate measure of uncertainty is important for many machine learning applications, and in particular, safety-critical ones. In this work, we study the calibration of uncertainty prediction for regression tasks which often arise in real-world systems. We show that the existing definition for the calibration of regression uncertainty has severe limitations in distinguishing informative from non-informative uncertainty predictions. We propose a new definition that escapes this caveat and an evaluation method using a simple histogram-based approach. Our method clusters examples with similar uncertainty prediction and compares the prediction with the empirical uncertainty on these examples. We also propose a simple, scaling-based calibration method that preforms as well as much more complex ones. We show results on both a synthetic, controlled problem and on the object detection bounding-box regression task using the COCO and KITTI datasets.

Peripheral T-cell lymphomas (PTCL), a heterogeneous group of mature aggressive non-Hodgkin's lymphomas, carry a worse prognosis for most subtypes when compared with their B-cell counterparts. Despite recent approval of newer therapies, the outlook for patients with relapsed/refractory (RR) PTCL remains poor and new treatment strategies are clearly needed. Targeting the profoundly immunosuppressive tumor microenvironment in PTCL is one such approach. To determine whether immune checkpoint blockade targeting program death receptor 1 would be effective in PTCL, we conducted an investigator-initiated phase 2 prospective study of single-agent nivolumab for RR PTCL. We report here results of the pre-specified interim analysis., Methods: The primary objective was to assess the overall response rate (ORR). Secondary objectives were to assess safety and tolerability of nivolumab in PTCL and to assess progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Hyperprogressive disease (HPD) was defined as time-to-treatment failure of less than or equal to one month from initiation of therapy., Results: Twelve patients who received at least one cycle of nivolumab were included in this interim analysis. Half (6/12) of the patients had angioimmunoblastic T-cell lymphoma (AITL), 3/12 had PTCL, not otherwise specified. Most (11/12) were advanced stage, had extranodal disease (97.1%) and had received a prior autologous stem cell transplant (50%). The ORR was 33% (95% CI: 12.3 to 63.7%) with two complete response and two partial response. The median PFS was however short at 2.7 months (95% CI: 1.5 to NE); and the median OS was 6.7 months (95% CI: 3.4 to NE). The median DOR was also short at 3.6 months (95% CI: 1.9 to NE). HPD occurred in four patients, three of whom had AITL. Observed grade 3 and higher adverse events (AEs) were non-hematologic in 5/12 (42%), while hematologic AEs were seen in 3/12 (25%)., Conclusions: Nivolumab had modest clinical activity in R/R PTCL. Due to a high number of hyperprogression and short DOR, a decision was made to halt the study. These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases., Trial Registration Number: NCT03075553., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Israel is not isolated from the global migration process. It is required to provide a medical, educational, and socio-cultural response to the integration of tens of thousands of African asylum seekers. This qualitative-phenomenological study collected data from 15 educators as a primary source and learned about their actions to mediate health and educational issues for African asylum seekers. The findings reveal four categories: (1) a healthy lifestyle; (2) emotional-behavioral; (3) learning disabilities and special needs; (4) diseases, vaccines, and medical treatments. It seems that educators are forced to take on roles traditionally entrusted to the state, and they have become agents of socialization who mediate between parents and the Israeli health and education system through personal relationships and individual conversations. This study reveals a dual reality: on the one hand, African asylum seekers experience alienation, exclusion, and violence; on the other hand, they gain a positive point of view when parents see the educators as loyal partners and sources of knowledge who can be consulted to receive help in routine times and during the coronavirus pandemic, a time in which they lost their livelihood, health insurance, and ability to understand the new rules of the lockdowns.

Guidelines for management of Melody transcatheter pulmonary valve (TPV) infective endocarditis (IE) are lacking. We aimed to identify factors associated with surgical valve removal versus antimicrobial therapy in Melody TPV IE. Multicenter retrospective analysis of all patients receiving Melody TPV from 10/2010 to 3/2019 was performed to identify cases of IE. Surgical explants versus non-surgical cases were compared. Of the 663 Melody TPV implants, there were 66 cases of IE in 59 patients (59/663, 8.8%). 39/66 (59%) were treated with IV antimicrobials and 27/66(41%) underwent valve explantation. 26/59 patients (44%) were treated medically without explantation or recurrence with average follow-up time of 3.5 years (range:1-9). 32% of Streptococcus cases, 53% of MSSA, and all MRSA cases were explanted. 2 of the 4 deaths had MSSA. CART analysis demonstrated two important parameters associated with explantation: a peak echo gradient ≥ 47 mmHg at IE diagnosis(OR 10.6, p < 0.001) and a peak echo gradient increase of > 24 mmHg compared to baseline (OR 6.7, p = 0.01). Rates of explantation varied by institution (27 to 64%). In our multicenter experience, 44% of patients with Melody IE were successfully medically treated without valve explantation or recurrence. The degree of valve stenosis at time of IE diagnosis was strongly associated with explantation. Rates of explantation varied significantly among the institutions., (© 2021. The Author(s).)

Background: Few studies have evaluated the effect of final needle position on contrast flow patterns during the performance of cervical transforaminal epidural steroid injections (TFESIs)., Objective: To analyze fluoroscopically guided cervical TFESI contrast flow patterns based upon final needle tip position., Design: Retrospective, observational in vivo study., Setting: Outpatient private practice physical medicine and rehabilitation spine clinic., Participants: One hundred consecutive patients undergoing cervical TFESIs., Interventions: Cervical TFESIs., Main Outcome Measures: Categories of contrast flow patterns including epidural, intraforaminal, "sufficient to inject," and "predominantly epidural and/or intraforaminal," based upon final needle tip position., Results: Two independent observers reviewed images from 100 consecutive patients and classified injectate flow patterns stratified by needle tip position. The interrater reliability for all categories of interest was moderate, with kappa values from 0.61 to 0.76. More medially placed needles (middle third and lateral third of the articular pillars) resulted in higher rates of epidural contrast flow (75%; 95% confidence interval [CI]: 56%-94%; and 60%; 95% CI: 47%-73%) compared to needles placed lateral to the articular pillars (26%; 95% CI: 8%-44%), and higher rates of "predominantly epidural and/or intraforaminal" flow patterns with needles placed in the middle one third (75%; 95% CI: 56%-94%) and lateral one third of the articular pillars (47%; 95% CI: 34%-60%) compared to flow patterns when needles were placed lateral to the articular pillars (17%; 95% CI: 2%-32%). No needles were placed in the medial third of the articular pillars., Conclusions: More medially placed needle tips result in more optimal flow patterns during cervical TFESIs. The importance of this finding is unknown as clinical outcomes were not measured., (© 2021 American Academy of Physical Medicine and Rehabilitation.)

Background: Cervical transforaminal epidural steroid injections (CTFESI) are commonly used in the treatment of upper extremity radicular pain. Recently, a modification of the conventional technique has been developed and validated which has a theoretical safety advantage of less risk of needle contact of the spinal nerve and vertebral artery. The new approach involves a needle trajectory under fluoroscopic guidance which is directly based upon the specific superior articular process angle measurement on MRI., Objective: The purpose of this study was to evaluate the discontinuation rate of the modified approach CTFESI procedure in a non-sedated patient population. The study was also undertaken to confirm the safety of the procedure in an office-based setting., Methods: A retrospective review was performed of the authors' (DL, SH) practice to identify all CTFESI using the modified approach, performed between October 2018 through January 2021 through a query of the investigators' (DL and SH) electronic medical record system. Any discontinued CTFESI procedure was identified. The reason for discontinuation was determined through medical record review. In addition, any significant neurologic or cardiovascular event occurring during or immediately following any completed or discontinued CTFESI was identified. Mild vasovagal reaction was not considered a significant complication., Results: A total of 973 CTFESI procedures were performed using the modified approach during the study period. Twelve procedures, 1.2% (95% CI 0.7-2.1%) were discontinued. Nine were aborted due to vascular flow not resolved with needle repositioning. Only three, 0.3% (95% CI 0.1-0.9) were aborted due to patient intolerance. There were zero significant neurologic or cardiovascular complications., Conclusion: The performance of the modified approach CTFESI appears to be well tolerated with a very low rate, 0.3%, of discontinuation due to intolerance in non-sedated patients. The zero incidence of neurologic or cardiovascular complication contributes to the current literature on the safety of this procedure., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Transgenic expression of bacterial nitroreductase (NTR) enzymes sensitizes eukaryotic cells to prodrugs such as metronidazole (MTZ), enabling selective cell-ablation paradigms that have expanded studies of cell function and regeneration in vertebrates. However, first-generation NTRs required confoundingly toxic prodrug treatments to achieve effective cell ablation, and some cell types have proven resistant. Here we used rational engineering and cross-species screening to develop an NTR variant, NTR 2.0, which exhibits ~100-fold improvement in MTZ-mediated cell-specific ablation efficacy, eliminating the need for near-toxic prodrug treatment regimens. NTR 2.0 therefore enables sustained cell-loss paradigms and ablation of previously resistant cell types. These properties permit enhanced interrogations of cell function, extended challenges to the regenerative capacities of discrete stem cell niches, and novel modeling of chronic degenerative diseases. Accordingly, we have created a series of bipartite transgenic reporter/effector resources to facilitate dissemination of NTR 2.0 to the research community., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Transcranial magnetic stimulation (TMS) has been widely applied for evaluation of the cortical eloquence through creation of the temporary "virtual lesion" allowing assessment of the evaluated function within the targeted region, which may be also employed for management of mental symptoms or modification of the abnormal behavior. It is believed that this non-invasive neuromodulation modality has a double impact on neurons-primary modulation of electrical activity and stimulation of neuroplasticity; the latter can be facilitated by repeated administration of TMS during multiple sessions over sufficiently long periods of time to induce consolidation of treatment effects through their recall at psychological, physiological, and cellular levels. These principles were employed in our data-driven, tailored strategy based on the modifications of TMS protocol and its adaptation to newly appearing changes of the clinical situation along with administration of prolonged and/or repeated courses of therapeutic stimulation, which showed high efficacy resulting in complete relief of depressive symptoms or substance use in 75% of treated patients at 1-year follow-up. Such results justify application of repetitive TMS for management of psychiatric disorders and warrant additional evaluation of its efficacy in further clinical studies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Ex vivo hepatectomy is the incorporation of liver transplant techniques in the non-transplant setting, providing opportunity for locally advanced tumors found conventionally unresectable. Because the procedure is rare and reports in the literature are limited, we sought to perform a systematic review and meta-analysis investigating technical variations of ex vivo hepatectomies., Methods: In the literature, there is a split in those performing the procedure between venovenous bypass (VVB) and temporary portacaval shunts (PCS). Of the 253 articles identified on the topic of ex vivo resection, 37 had sufficient data to be included in our review., Results: The majority of these procedures were performed for hepatic alveolar echinococcosis (69%) followed by primary and secondary hepatic malignancies. In 18 series, VVB was used, and in 18, a temporary PCS was performed. Comparing these two groups, intraoperative variables and morbidity were not statistically different, with a cumulative trend in favor of PCS. Ninety-day mortality was significantly lower in the PCS group compared to the VVB group (p=0.03)., Conclusion: In order to better elucidate these differences between technical approaches, a registry and consensus statement are needed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues. We optimise and validate image segmentation strategies and automate the process in a Nextflow-based pipeline (imcyto) that is scalable and portable, allowing for parallelised segmentation of large multi-image datasets. With these methods we interrogate the remodelling of the TME induced by a KRAS G12C inhibitor in an immune competent mouse orthotopic lung cancer model, highlighting the infiltration and activation of antigen presenting cells and effector cells., (© 2021. The Author(s).)

Early visual deprivation is known to have profound consequences on the subsequent development of spatial visual processing. However, its impact on temporal processing is not well characterized. We have examined spatial and temporal contrast sensitivity functions following treatment for early and extended bilateral visual deprivation in fifteen children born with congenital cataracts in rural India. The results reveal a marked difference in post-treatment spatial and temporal sensitivities. Whereas spatial processing in newly sighted children is significantly impaired relative to age-matched controls, temporal processing exhibits remarkable resilience and is comparable to that in the control group. This difference in spatial and temporal outcomes is especially surprising given our computational analyses of video sequences which indicate a strong linkage between the spatial and temporal spectral content of natural visual inputs. We consider possible explanations for this discrepancy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

During emerging adulthood, individuals are primarily concerned with themselves. Community participation, however, may help one to mature, and community belonging is important for well-being. As such, the current study aimed to examine these two components among young-adult Israeli backpackers abroad. We examined the role of personal (mastery, self-esteem, and posttraumatic growth) and environmental (family and friends' support) factors in sense of belonging and community participation. A cross-sectional sample survey was distributed; data were collected from 332 Israeli backpackers abroad. The findings based on t-tests, Pearson correlations, and hierarchical regression analysis showed that mastery was associated with sense of belonging, not with community participation. Self-esteem and posttraumatic growth were positively associated with both dependent variables. Friends' support was also positively associated with both dependent variables; family support was not significantly associated with either. Personal factors had the greatest association with sense of community., (© 2021 Wiley Periodicals LLC.)

In breast cancer, humoral immune responses may contribute to clinical outcomes, especially in more immunogenic subtypes. Here, we investigated B lymphocyte subsets, immunoglobulin expression, and clonal features in breast tumors, focusing on aggressive triple-negative breast cancers (TNBC). In samples from patients with TNBC and healthy volunteers, circulating and tumor-infiltrating B lymphocytes (TIL-B) were evaluated. CD20 + CD27 + IgD - isotype-switched B lymphocytes were increased in tumors, compared with matched blood. TIL-B frequently formed stromal clusters with T lymphocytes and engaged in bidirectional functional cross-talk, consistent with gene signatures associated with lymphoid assembly, costimulation, cytokine-cytokine receptor interactions, cytotoxic T-cell activation, and T-cell-dependent B-cell activation. TIL-B-upregulated B-cell receptor (BCR) pathway molecules FOS and JUN, germinal center chemokine regulator RGS1, activation marker CD69, and TNFα signal transduction via NFκB, suggesting BCR-immune complex formation. Expression of genes associated with B lymphocyte recruitment and lymphoid assembly, including CXCL13, CXCR4, and DC-LAMP, was elevated in TNBC compared with other subtypes and normal breast. TIL-B-rich tumors showed expansion of IgG but not IgA isotypes, and IgG isotype switching positively associated with survival outcomes in TNBC. Clonal expansion was biased toward IgG, showing expansive clonal families with specific variable region gene combinations and narrow repertoires. Stronger positive selection pressure was present in the complementarity determining regions of IgG compared with their clonally related IgA in tumor samples. Overall, class-switched B lymphocyte lineage traits were conspicuous in TNBC, associated with improved clinical outcomes, and conferred IgG-biased, clonally expanded, and likely antigen-driven humoral responses. SIGNIFICANCE: Tumor-infiltrating B lymphocytes assemble in clusters, undergoing B-cell receptor-driven activation, proliferation, and isotype switching. Clonally expanded, IgG isotype-biased humoral immunity associates with favorable prognosis primarily in triple-negative breast cancers., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: Hepatectomy or transplantation can serve as curative treatment for early-stage hepatocellular carcinoma (HCC). Unfortunately, as progression remains a reality, locoregional therapies (LRT) for curative or bridging intent have become common. Efficacy on viability, outcomes, and accuracy of imaging should be defined to guide treatment., Methods: Patients with HCC who underwent minimally invasive (MIS) microwave ablation (MWA), transarterial chemoembolization (TACE), or both (MIS-MWA-TACE) prior to hepatectomy or transplantation were identified. Tumor response and preoperative computed tomography (CT) accuracy were assessed and compared to pathology. Clinical and oncologic outcomes were compared between MIS-MWA, TACE, and MIS-MWA-TACE., Results: Ninety-one patients, with tumors from all stages of the Barcelona Clinic Liver Cancer (BCLC) staging, were identified who underwent LRT prior to resection or transplant. Fourteen patients underwent MIS-MWA, 46 underwent TACE, and 31 underwent both neoadjuvantly. TACE population was older; otherwise, there were no differences in demographics. Fifty-seven percent of MIS-MWA patients had no viable tumor on pathology whereas only 13% of TACE patients and 29% of MIS-MWA-TACE patients had complete destruction (p = 0.004). The amount of remaining viable tumor in the explant was also significantly different between groups (MIS-MWA: 17.2%, TACE: 48.7%, MIS-MWA-TACE: 18.6%; p ≤ 0.0001). Compared with TACE, the MIS-MWA and MIS-MWA-TACE groups had significantly improved overall survival (MIS-MWA: 99.94 months, TACE: 75.35 months, MIS-MWA-TACE: 140 months; p = 0.017). This survival remained significant with stratification by tumor size. CT accuracy was found to be 50% sensitive and 86% specific for MIS-MWA. For TACE, CT had an 82% sensitivity and 33% specificity and for MIS-MWA-TACE, there was a 42% sensitivity and 78% specificity., Conclusion: The impact of locoregional treatments on tumor viability is distinct and superior with MIS-MWA alone and MIS-MWA-TACE offering significant advantage over TACE alone. The extent of this effect may be implicated in the improved overall survival.

Introduction: The challenging environment of prehospital casualty care demands providers to make prompt decisions and to engage in lifesaving interventions, occasionally without them being adequately experienced. Telementoring based on augmented reality (AR) devices has the potential to decrease the decision time and minimise the distance gap between an experienced consultant and the first responder. The purpose of this study was to determine whether telementoring with AR glasses would affect chest thoracotomy performance and self-confidence of inexperienced trainees., Methods: Two groups of inexperienced medical students performed a chest thoracotomy in an ex vivo pig model. While one group was mentored remotely using HoloLens AR glasses, the second performed the procedure independently. An observer assessed the trainees' performance. In addition, trainees and mentors evaluated their own performance., Results: Quality of performance was found to be superior with remote guidance, without significant prolongation of the procedure (492 s vs 496 s, p=0.943). Moreover, sense of self-confidence among participant was substantially improved in the telementoring group in which 100% of the participants believed the procedure was successful compared with 40% in the control group (p=0.035)., Conclusion: AR devices may have a role in future prehospital telementoring systems, to provide accessible consultation for first responders, and could thus positively affect the provider's confidence in decision-making, enhance procedure performance and ultimately improve patient prognosis. That being said, future studies are required to estimate full potential of this technology and additional adjustments are necessary for maximal optimisation and implementation in the field of prehospital care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM., Objectives: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics., Methods: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission., Results: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels., Conclusions: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia.

A 59-year-old male with a history of gallbladder adenocarcinoma receiving chemotherapy and on therapeutic anticoagulation for portal vein thrombosis presented to the emergency department via ambulance after being found unresponsive and in cardiac arrest. Initial workup upon return of spontaneous circulation revealed a large right atrial mass, patent foramen ovale (PFO), and bilateral acute cortical infarctions. This constellation of findings were concerning for PFO-related paradoxical embolic strokes. Given the risk of recurrent paradoxical embolic events and the absolute contraindication to thrombolysis due to recent cerebral infarction, the decision was made to proceed with percutaneous vacuum-assisted thrombectomy using the AngioVac device. To prevent intraoperative thrombus propagation, PFO-closure was performed immediately prior to thrombectomy. Aspiration thrombectomy and PFO-closure were successful with complete thrombus removal and no intraoperative thrombus propagation. This case presents a minimally invasive and rapid treatment for a complex problem. An efficient and effective interdisciplinary team-based approach allowed the patient to resume cancer treatment relatively unabated.

Burns are a major trauma source in civilian and military settings, with a huge impact on patient's well-being, health system, and operation status of the force in the military setting. The purpose of our study was to summarize characteristics of all burn cases seen by the Israel Defense Forces primary care physicians during the years 2008 to 2016. This can help understand what causes most burns, in what units, at which stages and settings and consequently will allow commanders to make decisions regarding safety rules, protective equipment and uniforms, medical education for soldiers, etc. Data were collected from the military database system. All burn-related visits were analyzed using a designated big data computerized algorithm that used keywords and phrases to retrieve data from the database. 12,799 burn injuries were found presented in 65,536 burn-related visits which were analyzed according to the demographics, burn mechanism, and military unit. It was observed that most of the burns (70.7%) occurred during routine noncombat setting and there was a gradual decrease in burn injuries during the investigated period, from 17.6% of the cases in 2008 to 2.3% in 2016. Most of the burns occurred in the Air Force (19.4%), and the leading etiology was chemical (35%). The average TBSA was 7.5%. Since most of the burns occurred in a routine setting and were occupational-related, investment in education and improving fire protection has proven itself, leading to the decrease in burn prevalence, we recommend that more emphasis should be given on proper handling of chemicals., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In March 2020, with lockdown due to the coronavirus pandemic underway, the Francis Crick Institute (the Crick) regeared its research laboratories into clinical testing facilities. Two pipelines were established, one for polymerase chain reaction and the other for Serology. This article discusses the Cricks Flow Cytometry Science Technology Platform (Flow STP) role in setting up the Serology pipeline. Pipeline here referring to the overarching processes in place to facilitate the receipt of human sera through to a SARs-CoV-2 enzyme-linked immunosorbent assay result. We examine the challenges that had to be overcome by a research laboratory to incorporate clinical diagnostics and the processes by which this was achieved. It describes the governance required to run the service, the design of the standard operating procedures (SOPs) and pipeline, the setting up of the assay, the validation required to show the robustness of the pipeline and reporting the results of the assay. Finally, as the lockdown started to ease in June 2020, it examines how this new service affects the daily running of the Flow STP. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry., (© 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.)