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Spinal muscular atrophy (SMA) is a rare, genetic neurodegenerative disorder caused by insufficient production of survival motor neuron (SMN) protein. Diminished SMN protein levels lead to motor neuron loss, causing muscle atrophy and weakness that impairs daily functioning and reduces quality of life. SMN upregulators offer clinical improvements and increased survival in SMA patients, although significant unmet needs remain. Myostatin, a TGF-β superfamily signaling molecule that binds to the activin II receptor, negatively regulates muscle growth; myostatin inhibition is a promising therapeutic strategy for enhancing muscle. Combining myostatin inhibition with SMN upregulation, a comprehensive therapeutic strategy targeting the whole motor unit, offers promise in SMA. Taldefgrobep alfa is a novel, fully human recombinant protein that selectively binds to myostatin and competitively inhibits other ligands that signal through the activin II receptor. Given a robust scientific and clinical rationale and the favorable safety profile of taldefgrobep in patients with neuromuscular disease, the RESILIENT phase 3, randomized, placebo-controlled trial is investigating taldefgrobep as an adjunct to SMN upregulators in SMA (NCT05337553). This manuscript reviews the role of myostatin in muscle, explores the preclinical and clinical development of taldefgrobep and introduces the phase 3 RESILIENT trial of taldefgrobep in SMA. [ABSTRACT FROM AUTHOR]

Introduction: The disco-vertebral junction (DVJ) of the lumbar spine contains thin structures with short T2 values, including the cartilaginous endplate (CEP) sandwiched between the bony vertebral endplate (VEP) and the nucleus pulposus (NP). We previously demonstrated that ultrashort-echo-time (UTE) MRI, compared to conventional MRI, is able to depict the tissues at the DVJ with improved contrast. In this study, we sought to further optimize UTE MRI by characterizing the contrast-to-noise ratio (CNR) of these tissues when either single echo or echo subtraction images are used and with varying echo times (TEs). Methods: In four cadaveric lumbar spines, we acquired 3D Cones (a UTE sequence) images at varying TEs from 0.032 ms to 16 ms. Additionally, spin echo T1- and T2-weighted images were acquired. The CNRs of CEP-NP and CEP-VEP were measured in all source images and 3D Cones echo subtraction images. Results: In the spin echo images, it was challenging to distinguish the CEP from the VEP, as both had low signal intensity. However, the 3D Cones source images at the shortest TE of 0.032 ms provided an excellent contrast between the CEP and the VEP. As the TE increased, the contrast decreased in the source images. In contrast, the 3D Cones echo subtraction images showed increasing CNR values as the second TE increased, reaching statistical significance when the second TE was above 10 ms (p < 0.05). Conclusions: Our study highlights the feasibility of incorporating UTE MRI for the evaluation of the DVJ and its advantages over conventional spin echo sequences for improving the contrast between the CEP and adjacent tissues. Additionally, modulation of the contrast for the target tissues can be achieved using either source images or subtraction images, as well as by varying the echo times. [ABSTRACT FROM AUTHOR]

Molten salts play an important role in various energy-related applications such as high-temperature heat transfer fluids and reaction media. However, the extreme molten salt environment causes the degradation of materials, raising safety and sustainability challenges. A fundamental understanding of material-molten salt interfacial evolution is needed. This work studies the transformation of metallic Cr in molten 50/50 mol% KCl-MgCl2 via multi-modal in situ synchrotron X-ray nano-tomography, diffraction and spectroscopy combined with density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. Notably, in addition to the dissolution of Cr in the molten salt to form porous structures, a d-A15 Cr phase was found to gradually form as a result of the metal-salt interaction. This phase change of Cr is associated with a change in the coordination environment of Cr at the interface. DFT and AIMD simulations provide a basis for understanding the enhanced stability of d-A15 Cr vs. bcc Cr, by revealing their competitive phase thermodynamics at elevated temperatures and probing the interfacial behavior of the molten salt at relevant facets. This study provides critical insights into the morphological and chemical evolution of metal-molten salt interfaces. The combination of multimodal synchrotron analysis and atomic simulation also offers an opportunity to explore a broader range of systems critical to energy applications. [ABSTRACT FROM AUTHOR]

The growing number of people aging with HIV represents a group vulnerable to the symptom burdens of HIV-associated neurocognitive disorder (HAND). Among younger groups, Mindfulness-Based Stress Reduction (MBSR) has been shown to help people living with HIV manage HIV-related and other life stress, and although there is some theoretical and empirical evidence that it may be effective among those with cognitive deficits, the approach has not been studied in older populations with HAND. Participants (n = 180) 55 years or older with HIV and cognitive impairment were randomly assigned to either an 8-week MBSR arm or a waitlist control. We assessed the impact of MBSR compared to a waitlist control on psychological outcomes [stress, anxiety, depression, and quality of life (QOL)] and cognitive metrics (e.g., speed of information processing, working memory, attention, impulsivity) measured at baseline, immediately post intervention (8 weeks) and one month later (16 weeks). Intent to treat analyses showed significant improvement in the MBSR group compared to control on symptoms of depression from baseline to 8 weeks, however, the difference was not sustained at 16 weeks. The MBSR group also showed improvement in perceived QOL from baseline to 16 weeks compared to the waitlist control group. Cognitive performance did not differ between the two treatment arms. MBSR shows promise as a tool to help alleviate the symptom burden of depression and low QOL in older individuals living with HAND and future work should address methods to better sustain the beneficial impact on depression and QOL. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of gender transfer in virtual reality on implicit gender bias. Background: Gender bias is a type of discrimination based on gender, which can lead to increased self-doubt and decreased self-esteem. Sexual harassment is a hostile form of gender bias that can cause anxiety, depression, and significant mental health issues. Virtual reality (VR) has been employed to help make people become aware of their biases and change their attitudes regarding gender, race, and age. Methods: Forty participants were embodied in avatars of different genders and experienced sexual harassment scenarios in VR. A gender Implicit Association Test (IAT) was administered before and after the experience. Results: There was a statistically significant main effect of participant gender (F (1,36) = 10.67, p =.002, partial η2 =.23) on ΔIAT, where males and females reported a decrease (M = −.12, SD =.24) and an increase (M =.10, SD =.25) in IAT scores, respectively. A statistically significant two-way interaction between gender transfer and participant gender was revealed (F (1,36) = 6.32, p =.02, partial η2 =.15). There was a significant simple effect of gender transfer for male participants (F (1,36) = 8.70, p =.006, partial η2 =.19). Conclusions: Implicit gender bias can be modified, at least temporarily, through embodiment in VR. Gender transfer through embodiment while encountering different sexual harassment scenarios helped reduce implicit gender bias. There was a tendency for individuals to increase bias for the gender of the avatar in which they embodied. Applications: The current research provided promising evidence that a virtual environment system may be used as a potential training tool to improve implicit gender bias. [ABSTRACT FROM AUTHOR]

Pediatric pial arteriovenous shunts in the brain and spine are challenging to understand because of low incidence, variable presentation, and associations with genetic syndromes. What is known about their natural history comes from reviews of small series. To better understand the natural history and role for intervention, two cases are presented followed by a review of the literature. In the first case, an infant with a prior history of intracranial hemorrhage from a ruptured pial fistula returns for elective embolization for a second pial fistula which was found to be spontaneously thrombosed 2 weeks later. In the second case, a 5-year-old with a vertebro-vertebral fistula, identified on work up for a heart murmur and documented with diagnostic angiography, is brought for elective embolization 6 weeks later where spontaneous thrombosis is identified. In reviewing the literature on pediatric single-hole fistulae of the brain and spine, the authors offer some morphologic considerations for identifying which high-flow fistulae may undergo spontaneous thrombosis to decrease the potentially unnecessary risk associated with interventions in small children. [ABSTRACT FROM AUTHOR]

This article discusses the validation of the UPMC staging system for juvenile nasopharyngeal angiofibromas (JNAs), which are benign but aggressive skull base tumors. The UPMC staging system uses residual vascularity and intracranial extension to predict blood loss and recurrence when using an endoscopic approach. The study reviewed the cases of 26 pediatric patients with JNAs and found that the UPMC staging system was effective in predicting the need for staged resection, but less effective in predicting recurrence. Further research is needed to improve the accuracy of predicting recurrence. [Extracted from the article]

The corneal endothelium, comprising densely packed corneal endothelial cells (CECs) adhering to Descemet's membrane (DM), plays a critical role in maintaining corneal transparency by regulating water and ion movement. CECs have limited regenerative capacity within the body, and globally, there is a shortage of donor corneas to replace damaged corneal endothelia. The development of a carrier for cultured CECs may address this worldwide clinical need. In this study we successfully manufactured a gelatin nanofiber membrane (gelNF membrane) using electrospinning, followed by crosslinking with glutaraldehyde (GA). The fabricated gelNF membrane exhibited approximately 80% transparency compared with glass and maintained a thickness of 20 µm. The gelNF membrane demonstrated desirable permeability and degradability for a Descemet's membrane analog. Importantly, CECs cultured on the gelNF membrane at high densities showed no cytotoxic effects, and the expression of key CEC functional biomarkers was verified. To assess the potential of this gelNF membrane as a carrier for cultured CEC transplantation, we used it to conduct Descemet's membrane endothelial keratoplasty (DMEK) on rabbit eyes. The outcomes suggest this gelNF membrane holds promise as a suitable carrier for cultured CEC transplantation, offering advantages in terms of transparency, permeability, and sufficient mechanical properties required for successful transplantation. [ABSTRACT FROM AUTHOR]

Solid‐state metal dealloying (SSMD) is a promising method for fabricating nanoscale metallic composites and nanoporous metals across a range of materials. Thin‐film SSMD is particularly attractive due to its ability to create fine features via solid‐state interfacial reactions within a thin‐film geometry, which can be integrated into devices for various applications. This work examines a new dealloying couple, namely the Nb–Al alloy with the dealloying agent Sc, as previously predicted in the machine‐learning (ML) models. Prior ML predictions aimed to guide the design of nanoarchitectured materials through dealloying, relying on intuition‐driven discovery within a large parameter space. However, this work reveals that at the nanoscale, the involvement of oxygen in thin film processing may instead drive the dealloying process, resulting in the formation of bicontinuous nanostructures similar to those formed by metal‐agent dealloying. The phase evolution, as well as chemical and morphological changes, are closely analyzed using a combination of X‐ray absorption spectroscopy, diffraction, and scanning transmission electron microscopy to understand the mechanisms behind nanostructure formation. The findings suggest a potential pathway for utilizing oxygen to drive the formation of bicontinuous metal–metal oxide nanocomposites, paving the way for further development of functional nanoporous materials in diverse fields. [ABSTRACT FROM AUTHOR]

Purpose: We examine the rate of and reasons for follow-up in an Artificial Intelligence (AI)-based workflow for diabetic retinopathy (DR) screening relative to two human-based workflows.Patients and Methods: A DR screening program initiated September 2019 between one institution and its affiliated primary care and endocrinology clinics screened 2243 adult patients with type 1 or 2 diabetes without a diagnosis of DR in the previous year in the San Francisco Bay Area. For patients who screened positive for more-than-mild-DR (MTMDR), rates of follow-up were calculated under a store-and-forward human-based DR workflow ("Human Workflow"), an AI-based workflow involving IDx-DR ("AI Workflow"), and a two-step hybrid workflow ("AI–Human Hybrid Workflow"). The AI Workflow provided results within 48 hours, whereas the other workflows took up to 7 days. Patients were surveyed by phone about follow-up decisions.Results: Under the AI Workflow, 279 patients screened positive for MTMDR. Of these, 69.2% followed up with an ophthalmologist within 90 days. Altogether 70.5% (N=48) of patients who followed up chose their location based on primary care referral. Among the subset of patients that were seen in person at the university eye institute under the Human Workflow and AI–Human Hybrid Workflow, 12.0% (N=14/117) and 11.7% (N=12/103) of patients with a referrable screening result followed up compared to 35.5% of patients under the AI Workflow (N=99/279; χ2df=2 = 36.70, p < 0.00000001).Conclusion: Ophthalmology follow-up after a positive DR screening result is approximately three-fold higher under the AI Workflow than either the Human Workflow or AI–Human Hybrid Workflow. Improved follow-up behavior may be due to the decreased time to screening result. [ABSTRACT FROM AUTHOR]

Background: Neuroimaging has evolved from anatomical imaging toward a multi-modality comprehensive anatomical and functional imaging in the past decades, important functional data like perfusion-weighted imaging, permeability imaging, diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI), tractography, metabolic imaging, connectomics, event-related functional imaging, resting state functional imaging, and much more is now being offered. Summary: Precision diagnostics has proven to be essential for precision treatment. Many minimal invasive techniques have been developed, taking advantage of digital subtraction angiography and interventional neuroradiology. Furthermore, intraoperative CT and/or MRI and more recently MR-guided focused ultrasound have complemented the diagnostic and therapeutic armamentarium. Key Messages: In the current manuscript, we discuss standard imaging sequences including advanced techniques like DWI, DTI, susceptibility-weighted imaging, and 1H magnetic resonance spectroscopy, various perfusion weighted imaging approaches including arterial spin labeling, dynamic contrast enhanced imaging, and dynamic susceptibility contrast imaging. Pre-, intra, and postoperative surgical imaging including visualize imaging will be discussed. The value of connectomics will be presented for its value in neuro-oncology. Minimal invasive therapeutic possibilities of interventional neuroradiology and image-guided laser ablation and MR-guided high-intensity-focused ultrasound will be presented for treatment of pediatric brain and spinal cord tumors. Finally, a comprehensive review of spinal cord tumors and matching neuropathology has been included. [ABSTRACT FROM AUTHOR]

With the advancement in automation, the roles of machine operators have shifted from traditional physical commitments to controlling the automation process. The operators need to understand and assess the incoming information and make decisions accordingly, which will determine the next move of the process and further affect the machine's health status/performance. Such awareness and understanding of the situation, as one of the critical prerequisites of decision-making and known as situation awareness (SA), needs to be addressed appropriately in accessing the reliability of the system with human–machine interaction (HMI). Hence, we propose the HMI system reliability model considering the machine has multiple dependent degradation processes, and each degradation process is affected by the interactions of internal machine degradation, random shocks, and SA. In addition, the impacts of SA and external factors on the system are reflected in the amount and rate of the machine degradation process. The proposed model is demonstrated by a simulated case, and the sensitivity analysis is conducted to analyze the impacts of model parameters on system reliability prediction. Finally, the performance of the proposed model is demonstrated by comparing it with the existing model. [ABSTRACT FROM AUTHOR]

Purpose: Using ultrashort echo time (UTE) MRI, we determined prevalence of abnormal cartilaginous endplate (CEP), and the relationship between CEP and disc degeneration in human lumbar spines. Materials and methods: Lumbar spines from 71 cadavers (age 14–74 years) were imaged at 3 T using sagittal UTE and spin echo T2 map sequences. On UTE images, CEP morphology was defined as "normal" with linear high signal intensity or "abnormal" with focal signal loss and/or irregularity. On spin echo images, disc grade and T2 values of the nucleus pulposus (NP) and annulus fibrosus (AF) were determined. 547 CEPs and 284 discs were analysed. Effects of age, sex, and level on CEP morphology, disc grade, and T2 values were determined. Effects of CEP abnormality on disc grade, T2 of NP, and T2 of AF were also determined. Results: Overall prevalence of CEP abnormality was 33% and it tended to increase with older ages (p = 0.08) and at lower spinal levels of L5 than L2 or L3 (p = 0.001). Disc grades were higher and T2 values of the NP were lower in older spines (p < 0.001) and at lower disc level of L4-5 (p < 0.05). We found significant association between CEP and disc degeneration; discs adjacent to abnormal CEPs had high grades (p < 0.01) and lower T2 values of the NP (p < 0.05). Conclusion: These results suggest that abnormal CEPs are frequently found, and it associates significantly with disc degeneration, suggesting an insight into pathoetiology of disc degeneration. [ABSTRACT FROM AUTHOR]

Combined synchrotron X‐ray nanotomography imaging, cryogenic electron microscopy (cryo‐EM) and modeling elucidate how potassium (K) metal‐support energetics influence electrodeposit microstructure. Three model supports are employed: O‐functionalized carbon cloth (potassiophilic, fully‐wetted), non‐functionalized cloth and Cu foil (potassiophobic, nonwetted). Nanotomography and focused ion beam (cryo‐FIB) cross‐sections yield complementary three‐dimensional (3D) maps of cycled electrodeposits. Electrodeposit on potassiophobic support is a triphasic sponge, with fibrous dendrites covered by solid electrolyte interphase (SEI) and interspersed with nanopores (sub‐10 nm to 100 nm scale). Lage cracks and voids are also a key feature. On potassiophilic support, the deposit is dense and pore‐free, with uniform surface and SEI morphology. Mesoscale modeling captures the critical role of substrate‐metal interaction on K metal film nucleation and growth, as well as the associated stress state. [ABSTRACT FROM AUTHOR]

Combined synchrotron X‐ray nanotomography imaging, cryogenic electron microscopy (cryo‐EM) and modeling elucidate how potassium (K) metal‐support energetics influence electrodeposit microstructure. Three model supports are employed: O‐functionalized carbon cloth (potassiophilic, fully‐wetted), non‐functionalized cloth and Cu foil (potassiophobic, nonwetted). Nanotomography and focused ion beam (cryo‐FIB) cross‐sections yield complementary three‐dimensional (3D) maps of cycled electrodeposits. Electrodeposit on potassiophobic support is a triphasic sponge, with fibrous dendrites covered by solid electrolyte interphase (SEI) and interspersed with nanopores (sub‐10 nm to 100 nm scale). Lage cracks and voids are also a key feature. On potassiophilic support, the deposit is dense and pore‐free, with uniform surface and SEI morphology. Mesoscale modeling captures the critical role of substrate‐metal interaction on K metal film nucleation and growth, as well as the associated stress state. [ABSTRACT FROM AUTHOR]

Ni-based superalloys are promising materials for high-temperature molten salt (MS) energy generation and storage. Studying morphological and chemical evolution of pure Ni in MS provides fundamental knowledge for MS technologies and corrosion mitigation. Here, real-time 3D morphological changes of Ni microparticles in molten KCl-MgCl2 were studied by operando synchrotron X-ray nano-tomography at 700°C. Rapid Ni particle agglomeration occurred, without significant chemical reactions, such as oxide or chloride formation. The morphological growth evolved differently from classical coarsening or sintering behaviors and occurred nonuniformly, with other regions showing slight dissolution of Ni. Ni nanoparticles were found to be dispersed in many areas of the samples, either from microparticle dissolution or other radiation-induced nanoparticle formation mechanisms. This study discusses important factors, i.e., thermal gradient, amounts of salt and metals, and radiation effect, that influence morphological changes of materials in MS, critical for fundamental understanding of material–MS interactions as well as for practical applications. [ABSTRACT FROM AUTHOR]

Key Points: Question: Can DNA sequencing of blood from adults with acute myeloid leukemia (AML) in first remission prior to allogeneic hematopoietic cell transplant identify patients at increased risk of subsequent relapse and death? Findings: In patients with AML in first complete remission who received a transplant from March 1, 2013, through December 31, 2017 (discovery, n = 371) or from January 1, 2018, through February 14, 2019 (validation, n = 451), the presence of residual FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 DNA variants before transplant were associated with significantly increased rates of relapse (validation cohort difference, 47%; 95% CI, 26% to 69%) and significantly worse survival (validation cohort difference, −24%; 95% CI, −39 to −9%) at 3 years, compared with those without these markers. Meaning: Among patients with AML in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3-ITD or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without variants detected. Importance: Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized. Objective: To determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants. Design, Setting, and Participants: In this retrospective observational study, DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at 1 of 111 treatment sites from 2013 through 2019. Clinical data were collected, through May 2022, by the Center for International Blood and Marrow Transplant Research. Exposure: Centralized DNA sequencing of banked pretransplant remission blood samples. Main Outcomes and Measures: The primary outcomes were overall survival and relapse. Day of transplant was considered day 0. Hazard ratios were reported using Cox proportional hazards regression models. Results: Of 1075 patients tested, 822 had FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 mutated AML (median age, 57.1 years, 54% female). Among 371 patients in the discovery cohort, the persistence of NPM1 and/or FLT3-ITD variants in the blood of 64 patients (17.3%) in remission before undergoing transplant was associated with worse outcomes after transplant (2013-2017). Similarly, of the 451 patients in the validation cohort who had undergone transplant in 2018-2019, 78 patients (17.3%) with residual NPM1 and/or FLT3-ITD variants had higher rates of relapse at 3 years (68% vs 21%; difference, 47% [95% CI, 26% to 69%]; HR, 4.32 [95% CI, 2.98 to 6.26]; P <.001) and decreased survival at 3 years (39% vs 63%; difference, −24% [2-sided 95% CI, −39% to −9%]; HR, 2.43 [95% CI, 1.71 to 3.45]; P <.001). Conclusions and Relevance: Among patients with acute myeloid leukemia in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without these variants. Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with acute myeloid leukemia. In this observational study, targeted deep DNA sequencing was performed to test the hypothesis that detection of specific residual AML-associated variants in the blood of patients in first remission prior to allogeneic hematopoietic cell transplant would be associated with higher rates of relapse and mortality after transplant [ABSTRACT FROM AUTHOR]

A female patient with atopic dermatitis who had recently received a tattoo presented with severe right ear pain and several vesiculopustular lesions. Over 1 week, she developed approximately 80 widely distributed lesions. Laboratory testing confirmed mpox (previously monkeypox) virus, and no further lesions developed after initiation of oral tecovirimat. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the influence of game features and practice type on human kinematic and muscular performance in a virtual reality exercise (VRE). Participants demonstrated changes in shoulder flexion angle and muscle activation under different virtual scenarios. Background: Conventional VRE studies often compared the outcomes between an experimental group that underwent exercise in VR and a real-world exercise control group, whereas comparisons between VRE programs are lacking. Besides, the attributes of VREs received little attention. Method: Thirteen able-bodied participants performed upper extremity exercise movements in immersive VR using a head-mounted display. Participants performed task-oriented and imitation-oriented movements with different game features. Shoulder muscle activity (the deltoid, supraspinatus, and infraspinatus) and shoulder motion were collected. Results: Practice type (task-oriented, imitation-oriented) significantly influenced the flexion angle of the shoulder complex (F (1,11) = 9.53, p =.01), and the muscle activity of the supraspinatus (F (1,9) = 12.61, p =.006) and the infraspinatus (F (1,9) = 12.71, p =.006). Game features did not have a statistically significant effect on shoulder flexion angle or shoulder muscles' activations. Conclusions: Compared to imitation-oriented practice, task-oriented practice elicited more intensive shoulder movements and muscular efforts but also induced greater movement variations. Substantial differences across game features levels should be further investigated to have significant effects. Applications: This research may help guide the design of future VREs. For strength training or rehabilitation where intensive practice is required, task-oriented practice should be considered; for movement learning where movement consistency is required, imitation oriented practice should be adopted. [ABSTRACT FROM AUTHOR]

Background: Addressing barriers in the environment can contribute to health and quality of life for children with disabilities and their families. The Community Health Inclusion Index (CHII) is a measurement tool developed in the United States to identify environmental barriers and facilitators to community health inclusion. The CHII adopts an adult viewpoint and aspects crucial for children may have been omitted. Aims: This study aimed to develop a comprehensive list of items that are relevant for the community inclusion of children with disabilities in the Canadian context. Methods: The relevance and priority of items generated from a review of existing guidelines and best practice recommendations for community inclusion were rated as a dichotomous response and discussed by an expert panel in relevant fields related to children with disabilities. Results: A total of 189 items from 12 instruments and best practice guidelines were identified. Expert consensus contributed to a relevant and comprehensive list of items. Expert suggestions were considered to refine and reduce the item list. Conclusion: This study highlights the importance of a child version of a community inclusion tool, as the needs of children with disabilities differ from those of adults. It can help communities improve inclusion of children with disabilities and inform health promotion initiatives for this population. [ABSTRACT FROM AUTHOR]

This work aimed to evaluate the usage of a web-based intervention (WISE: Work ability Improvement through Symptom and Ergonomic strategies) developed to improve work ability for women recently diagnosed with breast cancer. Twenty-two women undergoing adjuvant treatment for breast cancer were provided access to WISE. This website includes content pages (e.g., information on ergonomics, symptom management, and other work-related resources) and worksheets (e.g., journals to track symptoms or goals). It could be personalized based on individual work activities and symptoms. Measures assessed at 3 months included usage of the website and perceived usefulness. Thirteen of the 22 participants (60%) accessed WISE; 11 personalized their information. Content and worksheet pages had 97 and 79 visits, respectively. Most frequently visited pages were "setting goals" (i.e., prioritize and track symptoms; 45 visits) and "steps to creating your WISE plan" (i.e., incorporate symptom and ergonomic strategies; 16 visits). Median duration time was 11.05 (range 0.35–79.55) minutes. Usefulness of the content and worksheet pages assessed via a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree) was 5.08 (SD = 1.59) and 4.26 (SD = 2.03), respectively. Participants were likely to recommend WISE to other women undergoing cancer treatment (mean = 6.11; SD = 1.05). The majority of participants personalized WISE work and symptom strategies. Overall, participants agreed that WISE content pages were useful and would recommend WISE for other breast cancer survivors. Results support that majority of breast cancer survivors, undergoing treatment with curative intent, accessed a web-based intervention that provided personalized information on workplace and symptom strategies. [ABSTRACT FROM AUTHOR]

Porous materials with high specific surface area, high porosity, and high electrical conductivity are promising materials for functional applications, including catalysis, sensing, and energy storage. Molten salt dealloying was recently demonstrated in microwires as an alternative method to fabricate porous structures. The method takes advantage of the selective dissolution process introduced by impurities often observed in molten salt corrosion. This work further investigates molten salt dealloying in bulk Ni–20Cr alloy in both KCl–MgCl2 and KCl–NaCl salts at 700 ℃, using scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction (XRD), as well as synchrotron X-ray nano-tomography. Micro-sized pores with irregular shapes and sizes ranging from sub-micron to several microns and ligaments formed during the process, while the molten salt dealloying was found to progress several microns into the bulk materials within 1–16 h, a relatively short reaction time, enhancing the practicality of using the method for synthesis. The ligament size increased from ~ 0.7 μm to ~ 1.3 μm in KCl–MgCl2 from 1 to 16 h due to coarsening, while remaining ~ 0.4 μm in KCl–NaCl during 16 h of exposure. The XRD analysis shows that the corrosion occurred primarily near the surface of the bulk sample, and Cr2O3 was identified as a corrosion product when the reaction was conducted in an air environment (controlled amount sealed in capillaries); thus surface oxides are likely to slow the morphological coarsening rate by hindering the surface diffusion in the dealloyed structure. 3D-connected pores and grain boundary corrosion were visualized by synchrotron X-ray nano-tomography. This study provides insights into the morphological and chemical evolution of molten salt dealloying in bulk materials, with a connection to molten salt corrosion concerns in the design of next-generation nuclear and solar energy power plants. [ABSTRACT FROM AUTHOR]

Background Pediatric neurointervention is challenged by the appropriateness of adult catheters and devices. This multicenter report on the smallest groin access sheaths offers technical notes and clinical outcomes in the pediatric neurointerventional population. Methods All pediatric neurointerventional cases from 2019 to 2021 were reviewed for use of a 3.3F Pediavascular or a 4F Merit Prelude Ideal low profile sheath. Hospital records were reviewed for complications and technical notes and compared with arterial groin access with the 4F Terumo Pinnacle in infants less than 1 year old, before the low profile sheaths at one author's institution were introduced. Results From January 1, 2019 to March 31, 2021 there were 347 procedures performed at Boston Children's Hospital and University of Wisconsin. Forty-four procedures in 26 patients were identified in which a 3.3F (38 cases, 20 patients) or 4F (6 cases, 6 patients) sheath was used. The average age was 2.2 years (1.5 days to 18 years). Retinoblastoma intra-arterial chemotherapy infusion (18 of 44) was the most common indication. The remaining procedures comprised vein of Galen embolization (12), diagnostic cerebral angiography (13), and one preoperative tumor embolization. Morbidity included a groin hematoma and decreased pulses (4.5%). No major groin complications occurred. There was no statistically significant difference compared with the historical cohort (132 procedures), which had seven instances of decreased pulses (5.3%, p>0.05). Conclusion The 3.3F Pediavascular and 4F Merit Prelude Ideal sheaths are easily incorporated into the pediatric neurointerventionalist's armamentarium for infants and readily accommodate various microcatheters for distal embolization and catheterization. [ABSTRACT FROM AUTHOR]

While color fundus photos are used in routine clinical practice to diagnose ophthalmic conditions, evidence suggests that ocular imaging contains valuable information regarding the systemic health features of patients. These features can be identified through computer vision techniques including deep learning (DL) artificial intelligence (AI) models. We aim to construct a DL model that can predict systemic features from fundus images and to determine the optimal method of model construction for this task. Data were collected from a cohort of patients undergoing diabetic retinopathy screening between March 2020 and March 2021. Two models were created for each of 12 systemic health features based on the DenseNet201 architecture: one utilizing transfer learning with images from ImageNet and another from 35,126 fundus images. Here, 1277 fundus images were used to train the AI models. Area under the receiver operating characteristics curve (AUROC) scores were used to compare the model performance. Models utilizing the ImageNet transfer learning data were superior to those using retinal images for transfer learning (mean AUROC 0.78 vs. 0.65, p-value < 0.001). Models using ImageNet pretraining were able to predict systemic features including ethnicity (AUROC 0.93), age > 70 (AUROC 0.90), gender (AUROC 0.85), ACE inhibitor (AUROC 0.82), and ARB medication use (AUROC 0.78). We conclude that fundus images contain valuable information about the systemic characteristics of a patient. To optimize DL model performance, we recommend that even domain specific models consider using transfer learning from more generalized image sets to improve accuracy. [ABSTRACT FROM AUTHOR]

Purpose: By 2020, the US population living with metastatic breast cancer (MBC) has exceeded 165,000. A knowledge gap exists regarding the factors affecting work ability for these individuals. We sought to characterize the work status, importance of work, and work-related information needs for women living with MBC. Methods: We conducted an online survey using an MBC listserv and clinic flyers in 2014–2015. Respondents working at the time of MBC diagnosis were divided into "stably-working" and "no-longer-working" based on employment status at the time of survey. Comparisons were made with chi-square or two-tailed t test. Results: Respondents (n = 133) were predominantly non-Hispanic White (93.2%); 72 were stably-working, while 61 reported no-longer-working. Those no-longer-working were older (54.0 vs 49.5 years old, p < 0.01, Cohen's d = 0.55), further from initial diagnosis of MBC (4.6 vs 3.3 years, p < 0.01, Cohen's d = 0.36), and reported high rates of life interference due to MBC (n = 51, 83.6% vs n = 39, 54.2%, p < 0.01, Cramer's V = 0.32). Stably-working respondents considered work to be important (n = 58, 80.5% vs n = 18, 29.5%, p < 0.01, Cramer's V = 0.57); the top reasons cited were financial and/or insurance (80.4%), importance of staying busy (67.9%), and desire to support themselves and family (64.3%). The stably-working respondents more often valued information on how to talk with employers or co-workers about diagnosis (n = 38, 57.6% vs n = 16, 27.1%; p < 0.01), legal rights in workplace (n = 43, 65.2% vs n = 22, 36.7%; p < 0.01), when to think about stopping work (n = 45, 68.2% vs n = 18, 30%; p < 0.01), and applying for disability (n = 42, 63.6% vs n = 26, 42.6%; p < 0.05), when compared to no-longer-working. Conclusion: The decision to stop working may represent a subsequent event driven by cancer progression. This research highlights the ongoing need of information targeting MBC to facilitate the management of employment and financial issues early in the MBC trajectory. [ABSTRACT FROM AUTHOR]

An estimated 29 million housing units in the United States still contain deteriorated lead paint and elevated levels of lead-contaminated house dust, over forty years after the ban on residential use of lead paint. Such "legacy" lead paint in homes built before 1978 has disproportionately inflicted irreversible, life-long health harms on communities of color and poor people. The Ninth Circuit, in A Community Voice v. EPA, held that the threshold for identifying risks from lead paint must be strictly based on health-based standards, without consideration of cost. While an important win for environmental justice advocates, the decision in A Community Voice was no panacea. The scheme for lead paint regulation in the United States is a complex patchwork of federal and local regulations with significant gaps that often enable and encourage inaction. The decision addressed the risk identification aspect of lead regulation; however, the need for lead paint abatement in U.S. homes remains urgent while a robust response remains unpromised. Further, the question persists of what role cost considerations should play in regulating toxic substances such as lead, which has no safe exposure level. This Note contends that cost-benefit analysis has fundamental flaws that could cause the government to inadequately account for health outcomes when regulating toxic substances like lead. Understanding that cost considerations are entrenched in the regulatory process, however, policymakers could embrace distributional weighting tools to better account for equity concerns in cost-benefit analyses. [ABSTRACT FROM AUTHOR]

Lensless X-ray nanoimaging provides 3D views of a wide range of materials with a spatial resolution better than 10 nm. These advances are enabled in part by dramatic gains in coherent X-ray flux, but they also rely on advances in signal processing to obtain images from coherent diffraction data. We outline the scientific problems that can be addressed by X-ray nanoimaging, the various imaging approaches and their associated reconstruction methods, and highlight opportunities for future advances. [ABSTRACT FROM AUTHOR]

Background: Immune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease. Methods: Thirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication. Results: We observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events. Conclusions: This pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted. [ABSTRACT FROM AUTHOR]

HER2 amplification, which results in overexpression of the receptor tyrosine kinase HER2, has been described in a wide variety of malignancies. HER2‐targeting agents have been incorporated into the treatment paradigms for HER2‐overexpressing breast and gastric cancer. More recently, these agents have shown promise in other gastrointestinal malignancies, such as colon cancer and biliary tract tumors. This study discusses two patients with gallbladder carcinoma and a third with ampullary carcinoma who were able to achieve marked responses to HER2‐directed therapy. These cases underscore the importance of molecular analysis for HER2 amplification/HER2 overexpression, irrespective of tumor histology, and highlight a need for further investigation of HER2‐directed therapy beyond breast and gastroesophageal cancers. Key Points: Current guidelines recommend molecular assessment for HER2 overexpression exclusively in breast and gastric adenocarcinoma.The focus of this report is on three cases (two biliary tract and one ampullary carcinoma) in which amplification of HER2 or overexpression of HER2 was detected and treatment with HER2‐directed therapy resulted in robust responses.These cases exemplify responsiveness of non‐breast/gastric histologies to HER2‐directed therapies, highlighting several promising new settings for these agents.Testing for amplification of HER2 or overexpression of HER2 should be considered especially in rare diseases with limited treatment options. This article presents three unique cases, two patients with gallbladder carcinoma and one patient with ampullary carcinoma, whose tumors overexpressed HER2 and responded remarkably well to HER2‐directed therapy. [ABSTRACT FROM AUTHOR]

Three-dimensional bicontinuous porous materials formed by dealloying contribute significantly to various applications including catalysis, sensor development and energy storage. This work studies a method of molten salt dealloying via real-time in situ synchrotron three-dimensional X-ray nano-tomography. Quantification of morphological parameters determined that long-range diffusion is the rate-determining step for the dealloying process. The subsequent coarsening rate was primarily surface diffusion controlled, with Rayleigh instability leading to ligament pinch-off and creating isolated bubbles in ligaments, while bulk diffusion leads to a slight densification. Chemical environments characterized by X-ray absorption near edge structure spectroscopic imaging show that molten salt dealloying prevents surface oxidation of the metal. In this work, gaining a fundamental mechanistic understanding of the molten salt dealloying process in forming porous structures provides a nontoxic, tunable dealloying technique and has important implications for molten salt corrosion processes, which is one of the major challenges in molten salt reactors and concentrated solar power plants. Understanding how pores evolve in metals submerged in molten salts is important for nanofabrication technology and molten salt corrosion in nuclear and solar power plants. Here, the authors present an in situ X-ray 3D imaging to directly visualize and quantify the process. [ABSTRACT FROM AUTHOR]

Glass interposer substrates have attracted growing interest as an alternative to traditional organic and silicon-based interposers for 3-D integrated circuit (IC) and 2.5-D through silicon via (TSV) packages in recent years. However, while glass substrates have the advantages of excellent electrical isolation, superior RF performance, good coefficient of thermal expansion (CTE) adjustability, and the potential for large-scale fabrication, they are inherently brittle. Consequently, an appropriate choice of glass and epoxy molding compound (EMC) material is essential for minimizing the warpage of the molded wafer. To facilitate the package design process, this study, therefore, develops an ANSYS simulation model to predict the warpage of the molded glass wafer given the use of different glass and EMC materials. The validity of the simulation model is confirmed by comparing the numerical results for the warpage of an 8-in molded glass wafer with the experimental measurements obtained using an Advanced Metrology Analysis (aMA) system. Single-factor-analysis experiments are then conducted to examine the effects of five different control factors, namely, the glass substrate thickness, the glass CTE, the glass modulus, the EMC CTE, and the EMC modulus, on the warpage performance of the molded glass wafer. The simulation results provide useful guidelines for the design of robust glass substrate packages. [ABSTRACT FROM AUTHOR]

Background: Postcancer work limitations may affect a substantial proportion of patients and contribute to the "financial toxicity" of cancer treatment. The degree and nature of work limitations and employment outcomes are poorly understood for cancer patients, particularly in the immediate period of transition after active treatment. We prospectively examined employment, work ability, and work limitations during and after treatment. Methods: A total of 120 patients receiving curative therapy who were employed prior to their cancer diagnosis and who intended to work during or after end of treatment (EOT) completed surveys at baseline (pretreatment), EOT, and 3, 6, and 12 months after EOT. Surveys included measures of employment, work ability, and work limitations. Descriptive statistics (frequencies, percentages, means with standard deviations) were calculated. Results: A total of 111 participants completed the baseline survey. On average, participants were 48 years of age and were mostly white (95%) and female (82%) with a diagnosis of breast cancer (69%). Full‐time employment decreased during therapy (from 88% to 50%) and returned to near prediagnosis levels by 12‐month follow‐up (78%). Work‐related productivity loss due to health was high during treatment. Conclusions: This study is the first to report the effects of curative intent cancer therapy on employment, work ability, and work limitations both during and after treatment. Perceived work ability was generally high overall 12 months after EOT, although a minority reported persistent difficulty. A prospective analysis of factors (eg, job type, education, symptoms) most associated with work limitations is underway to assist in identifying at‐risk patients. Adjuvant therapy for cancer can have a negative effect on a patient's ability to work, but the degree of work limitation due to cancer treatment has not been captured prospectively in a longitudinal fashion. This prospective study of patients with cancer receiving adjuvant chemotherapy who worked during cancer treatment reveals that most patients eventually returned to the same level of work that they had performed before treatment. [ABSTRACT FROM AUTHOR]

Background: Significant advances have been reported recently in the genetic and mechanistic characterization of extracranial venous malformations. However, intracranial purely venous malformations (icVM) analogous to those outside the CNS have not been systematically described. Purpose: We sought to ascertain whether such an entity as icVM could in fact be identified, distinct from previously described CNS venous anomalies and analogous to extracranial venous malformations. Methods: Our prospectively collected pediatric cerebrovascular database was reviewed to identify patients with icVM; 1458 consecutive angiograms and/or angiographic interventions performed on 706 children at our institution from October, 2006 through May, 2019 were evaluated, in addition to outside imaging studies on 192 additional patients sent to our Vascular Anomalies Center for cerebrovascular review during the same time period. Thus, the cohort consisted of 898 children. Results: Nineteen of 898 patients (2.1%) were found to harbor icVM, including 9 (47.3%) with sinus pericranii, 15 (78.9%) with associated large, complex extracranial venous malformations, and 3 (15.7%) with neurocognitive delay. There was no intracranial hemorrhage or venous hypertension seen in the cohort. Asymptomatic venous thrombosis in the superior sagittal sinus was seen in three patients. Conclusion: Venous malformations, both extracranial and icVM, share many characteristics that are distinct from developmental venous anomalies. icVM were not associated with venous hypertension. The underlying genetic mutations involved in the development of icVM, germ-line or somatic, remain to be elucidated, but may very well involve shared mechanisms and pathways with extracranial venous malformations. [ABSTRACT FROM AUTHOR]

An asymmetric total synthesis of [13C4]‐anatoxin‐a ([13C4]‐1) has been developed from commercially available ethyl [13C4]‐acetoacetate ([13C4]‐15). The unique requirements associated with isotope incorporation inspired a new, robust, and highly scalable route, providing access to 0.110 g of this internal standard for use in the detection and precise quantification of anatoxin‐a in freshwater. A highlight of the synthesis is a method that leverages a cyclic iminium ion racemization to achieve dynamic kinetic resolution in an enantioselective Morita–Baylis–Hillman (MBH) cyclization. [ABSTRACT FROM AUTHOR]

An asymmetric total synthesis of [13C4]‐anatoxin‐a ([13C4]‐1) has been developed from commercially available ethyl [13C4]‐acetoacetate ([13C4]‐15). The unique requirements associated with isotope incorporation inspired a new, robust, and highly scalable route, providing access to 0.110 g of this internal standard for use in the detection and precise quantification of anatoxin‐a in freshwater. A highlight of the synthesis is a method that leverages a cyclic iminium ion racemization to achieve dynamic kinetic resolution in an enantioselective Morita–Baylis–Hillman (MBH) cyclization. [ABSTRACT FROM AUTHOR]

Titanium disulfide (TiS2) with high electric conductivity, fast rate capability, and good cycling performance is a promising candidate for electrode material in sodium (Na)-ion batteries. Despite the well-studied electrochemical behaviors of TiS2 in Li-ion batteries, the detailed reaction mechanism of TiS2 in Na-ion batteries is not yet fully understood due to a more complex multi-phase conversion process. In this work, reactions of TiS2 in Na-ion batteries are investigated via a multi-modal synchrotron approach: operando X-ray Absorption Spectroscopy (XAS) – including X-ray Absorption Near-Edge Structure (XANES) and Extended X-ray Absorption Fine Structure (EXAFS) – and ex situ X-ray Powder Diffraction (XPD), coupled with computational modeling. Operando XANES spectra indicate that the redox reactions occur in both Ti and S during the electrochemically driven phase transformation. Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) analysis of XAS suggests that different numbers of components are involved in the lithiation and sodiation of TiS2, with the sodiation including at least one intermediate phase in addition to the starting material and the final sodiation product. Ex situ XPD and Rietveld refinement further determined and quantified the unknown phases, showing that three phases, TiS2, Na0.55TiS2, and NaTiS2, participate in the sodiation of TiS2. Operando EXAFS results show the changes in the Ti–Ti coordination number and interatomic distance. This explains the coulombic efficiency decay due to the incomplete recovery of the coordination number of Ti after cycling. Overall, this work reveals the reaction mechanism occurring in Na–TiS2 batteries with a greater quantitative understanding of the structural evolution. By combining the multi-modal synchrotron approach and computational work, this study provides a framework for studying a broader range of electrochemically driven phase-transformation systems towards advanced energy storage and conversion applications. [ABSTRACT FROM AUTHOR]

Purpose: Strokes associated with cervical artery dissection have been managed primarily with antithrombotics with poor outcomes. The additive role of endovascular thrombectomy remains unclear. The objective was to perform systematic review and meta-analysis to compare endovascular thrombectomy and medical therapy for acute ischemic stroke associated with cervical artery dissection. Methods: Studies from six electronic databases included outcomes of patient cohorts with acute ischemic stroke secondary to cervical artery dissection who underwent treatment with endovascular thrombectomy. A meta-analysis of proportions was conducted with a random effects model. Modified Rankin score at 90 days (mRS 0–2) was the primary outcome. Other outcomes included proportion of patients with thrombolysis in cerebral infarction (TICI) 2b-3 flow, 90-day mortality rate, and 90-day symptomatic intracerebral hemorrhage (sICH) rate. Results: Six studies were included, comprising 193 cases that underwent thrombectomy compared with 59 cases that were managed medically. Successful recanalization with a pooled proportion of thrombolysis in cerebral infarction (TICI) 2b-3 flow in the thrombectomy group was 74%. Favorable outcome (mRS 0–2) was superior in the pooled thrombectomy group (62.9%, 95% CI 55.8–69.5%) compared with medical management (41.5%, 95% CI 29.0–55.1%, P = 0.006). The pooled rate of 90-day mortality was similar for endovascular vs medical (8.6% vs 6.3%). The pooled rate of symptomatic intracranial haemorrhage (sICH) did not significantly differ (5.9% vs 4.2%, P = 0.60). Conclusions: Current data suggest that endovascular thrombectomy may be an option in patients with acute ischemic stroke due to cervical artery dissection. This requires further confirmation in higher quality prospective studies. [ABSTRACT FROM AUTHOR]

A versatile, compact heater designed at National Synchrotron Light Source‐II for in situ X‐ray nano‐imaging in a full‐field transmission X‐ray microscope is presented. Heater design for nano‐imaging is challenging, combining tight spatial constraints with stringent design requirements for the temperature range and stability. Finite‐element modeling and analytical calculations were used to determine the heater design parameters. Performance tests demonstrated reliable and stable performance, including maintaining the exterior casing close to room temperature while the heater is operating at above 1100°C, a homogenous heating zone and small temperature fluctuations. Two scientific experiments are presented to demonstrate the heater capabilities: (i) in situ 3D nano‐tomography including a study of metal dealloying in a liquid molten salt extreme environment, and (ii) a study of pore formation in icosahedral quasicrystals. The progression of structural changes in both studies were clearly resolved in 3D, showing that the new heater enables powerful capabilities to directly visualize and quantify 3D morphological evolution of materials under real conditions by X‐ray nano‐imaging at elevated temperature during synthesis, fabrication and operation processes. This heater design concept can be applied to other applications where a precise, compact heater design is required. [ABSTRACT FROM AUTHOR]