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Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms and are even more uncommon in the pediatric patients, thus leading to a lack of clinical research on diagnosis and management in this population. The purpose of this report is to review relevant literature and discuss a rare occurrence of a non-functioning pNET in a pediatric patient. This is a report of an 11-year-old male who presented with symptomatic anemia and was found to have a 6 cm mass near the pancreatic head with erosion into the duodenum. Surgical biopsy demonstrated a non-functioning pNET. He was successfully managed with complete surgical resection via a standard pancreaticoduodenectomy without evidence of recurrence after 1 year follow up. Further multi-institutional prospective studies or meta-analyses are warranted to further explore optimal management in the pediatric population.

Hepatic mesenchymal hamartomas (HMH) are benign liver lesions that present as cystic, slow growing masses within the first few years of life. Few cases demonstrate placental abnormalities and abnormal levels of alpha-fetoprotein (AFP). We report an unusual case of a rapidly growing HMH with associated placental anomalies and elevated AFP. A 2-month-old female born prematurely due to concerning placental findings presented with a prenatally-identified liver mass. Magnetic resonance imaging (MRI) showed a marked increase in the size of the mass over a three-month period. Prior to surgery, the AFP was elevated and decreased after operative resection. Histopathology confirmed the diagnosis HMH. Rapid growth of HMH is not commonly reported and raises concerns for malignancy. Abnormal placental findings may lead to prematurity, which can affect surgical management. We identified 27 cases of prenatally diagnosed HMH since 1983. The mean gestational age for identification was 29 weeks, with the majority managed by delayed resection. The timing for surgical intervention lacks consensus, but malnutrition and perioperative complications should be considered. High AFP levels with an infantile hepatic mass may indicate a more malignant process but does not exclude HMH.

The sole nonredundant role of the thymic medulla is to induce central tolerance, a vital process that depends on promiscuous gene expression (pGE), a unique feature of medullary thymic epithelial cells (mTECs). Although pGE enhances transcription of >3,000 genes in mTECs, its impact on the regulation of protein homeostasis remains unexplored. Here, we report that, because of pGE, mature mTECs synthesize substantially more proteins than other cell types and are exquisitely sensitive to loss of immunoproteasomes (IPs). Indeed, IP deficiency causes proteotoxic stress in mTECs and leads to exhaustion of postnatal mTEC progenitors. Moreover, IP-deficient mice show accelerated thymic involution, which is characterized by a selective loss of mTECs and multiorgan autoimmune manifestations. We conclude that pGE, the quintessential feature of mTECs, is a major burden for the maintenance of proteostasis, which is alleviated by the constitutive expression of IPs in mTECs.

Spinal cord hemangiomas are rare vascular malformations that can cause neurological deficits. We report a case of a 57-year-old male who previously underwent spondylolisthesis reduction for treatment of a 30% (1 cm) anterolisthesis of L4-L5 with continued neurological deficit post-operatively. The patient still reported bilateral lower extremity weakness, and he was found to have an additional ovoid intramedullary lesion at the T2-T3 level, pathologically consistent with a hemangioma. The patient underwent a T2-T3 laminectomy, and the lesion was resected without any complications. Histopathological examination confirmed the diagnosis of hemangioma. Postoperatively, the patient showed significant improvement in his lower extremity weakness and back pain. Hemangiomas are rare lesions that account for less than 5% of all spinal cord tumors. They consist of vessels similar to those of embryonic capillaries and can cause pressure on the surrounding neural tissue, leading to neurological deficits. MRI is the imaging modality of choice for diagnosing spinal cord hemangiomas. Hemangiomas typically demonstrate mixed signal intensities on T1-weighted images, depending on the fat content of the lesion. They usually demonstrate high T2 signal intensity due to high water content, and avid contrast enhancement due to high vascularity. Surgical resection is the treatment of choice for symptomatic hemangiomas, and complete resection is associated with a good prognosis.

Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors’ needs.

Although most patients with cardiac amyloidosis are diagnosed with either light chain (AL) or transthyretin (ATTR) disease, coexisting amyloid subtypes can occur. We present three cases of coexisting AL and ATTR cardiac amyloidosis and demonstrate the importance of clinical history and endomyocardial biopsy in diagnosis of this rare entity.

Dural arteriovenous fistulas are rare intracranial vascular malformations with a propensity for hemorrhage. The Cognard classification system is the most widespread classification system wherein type IIB through V must be promptly treated to avoid the risk of hemorrhage. The case presented herein reports a 71-year-old male presenting with vague non-hemorrhagic neurologic deficits found to have a Cognard type III dural arteriovenous fistula with multiple arterial feeders. Although quite obvious in retrospect, a DAVF can be missed even by an astute radiologist. This should be considered a “never miss” diagnosis as it carries a risk of intracranial hemorrhage and death.

SUMMARY: An experiment was conducted to compare the growth performance, gizzard and relative gizzard weight (RGW) of broilers fed a mash diet, micro-pellets, or coarse and fine crumbles with or without the fines removed. A total of 300 Cobb 500 one-day-old male broiler chicks were randomly distributed into 60 battery cages with 5 broilers per cage. Cages were randomly assigned to 1 of 6 dietary treatments to provide 10 replicates per treatment in a CRD. Treatments comprised of 1) mash (M); 2) micro-pellets (MP); 3) coarse-crumbles with fines (CCF); 4) coarse-crumbles with fines removed (CCNF); 5) fine-crumbles with fines (FCF); and 6) fine-crumbles with fines removed (FCNF). Overall BW, ADG, and ADFI were increased (P < 0.001), FCR improved (P < 0.001), and RGW decreased (P < 0.001) for broilers fed MP or crumbles compared to the M diet. Broilers fed MP, CCNF, and FCNF had increased (P < 0.05) BW compared to those fed CCF and FCF. Broilers fed the CCNF had improved (P < 0.05) FCR compared to those fed all other treatments. Gizzard weight (P = 0.0007) and RGW (P < 0.0001) were higher for birds fed M, FCF, and FCNF compared to other diets. The results of this study indicated that feeding MP or crumbles to broiler chicks improved feed intake, BW, and FCR but reduced RGW. Removing the fines resulted in further improvement in BW for broilers fed crumbles. Furthermore, feeding good quality crumbles yielded similar growth performance in chicks fed micro-pellets.

Pathologists who enter the workforce must have a diverse skill set beyond that of clinical diagnostics alone. Anticipating this need, the Johns Hopkins Pathology Residency Program developed Special Expertise Tracks to enhance training in relevant subspecialty domains. Using a combination of discussions and surveys, we assessed: (1) our current resident curriculum; (2) perceived curricular strengths and needs; (3) resident career preferences and ultimate career paths; (4) perceived barriers to implementing an advanced elective curriculum; and (5) available departmental/institutional resources. Additionally, we utilized the Accreditation Council for Graduate Medical Education Pathology Milestones as a curricular guide. Six professional residency training Special Expertise Tracks were established: Education, Physician-Scientist Research, Informatics, Quality Improvement/Quality Assurance/Value-Based Care, Health Policy/Hospital Management and Global Health. After implementation in 2017, the Education track has had 4 residents complete the curriculum successfully; the Physician-Scientist Research track has had 2 residents and the Informatics and Global Health tracks have each had one resident successfully complete their respective curricula. Currently, 5 residents are pursuing the Education track, one is pursuing the Physician-Scientist Research track, one is pursuing the Informatics track, and 2 residents are pursuing the Global Health track. Five residents have completed long-term projects including developing several e-learning modules, an online free digital cytopathology atlas, peer-reviewed articles, book chapters, and books. The Johns Hopkins Pathology Resident Special Expertise Track program provides pathology residents an opportunity to gain meaningful experience and additional skills tailored to their individual career interests.

Background: The Xpert MTB/RIF (MTB/RIF) test has advanced the field of tuberculosis (TB) diagnostics; however, depending on age and HIV status, 10–85% of individuals with presumed pulmonary TB (PTB) are unable to produce sputum. Methods: The feasibility of using MTB/RIF and culture on stool and string test specimens from 13 adult patients with presumed PTB was studied. Results: The string test was well tolerated with a median Wong Baker Faces score of 2. The string test had 100% sensitivity and specificity by MTB/RIF and 87.5% sensitivity and 100% specificity by culture. In stool, Mycobacterium tuberculosis DNA was detected in all cases of culture-confirmed PTB. Conclusion: The string test and stool provide diagnostic specimens that warrant further investigation.

Recent data indicate that certain pro-inflammatory cytokines are transcriptionally upregulated in the spinal cords of G93A-SOD1 mice, a model of amyotrophic lateral sclerosis (ALS). We previously showed that the receptor for tumor necrosis factor α (TNF-R1) was notably elevated at late presymptomatic as well as symptomatic phases of disease (J. Neurochem. 82 (2002) 365). We now extend these findings by showing that message for TNFα, as well as mRNA for interferon γ (IFNγ) and transforming growth factor β1/2 (TGFβ1, TGFβ2), is simultaneously increased. Furthermore, TNFα protein is significantly increased in G93A-SOD1 mouse spinal cords, as are protein levels for interleukin-6 (IL6), IFNγ, and the chemokines RANTES (CCL5) and KC. The interaction of TNFα, IL6, and IFNγ proteins was modeled in vitro using Walker EOC-20 murine microglia with nitrite (NO2−) efflux as a quantitative index of cell response. TNFα alone caused robust NO2− flux, while IL6 had a lesser effect and neither IFNγ nor IL1β was active when applied singly. The TNFα stimulus was potently magnified in the presence of IL6 or IFNγ. When applied in combination at very low concentrations, IFNγ co-synergized with IL6 to produce a multiplicative increase in NO2− after stimulation with TNFα. Taken together, these data suggest that modest increases in multiple synergistic cytokines could produce a disproportionately severe activation of microglia within the degenerating spinal cord. Our data support a model wherein TNFα acts as a principal driver for neuroinflammation, while several co-stimulating cytokines and chemokines act to potentiate the TNFα effects.

Purpose: To provide consensus-based recommendations for use of vagus nerve stimulation (VNS) therapy in the management of pediatric epilepsy., Methods: Delphi methodology with two rounds of online survey was used to build consensus. A steering committee developed 43 statements related to pediatric epilepsy and the use of VNS therapy, which were evaluated by a panel of 12 neurologists/neurosurgeons with expertise in pediatric epilepsy, who graded their agreement with each statement on a scale of 1 ("I do not agree at all") to 5 ("I strongly agree"). For each statement, consensus was established if ≥70% of the agreement scores were 4 or 5 and <30% were 1 or 2 in the final survey., Results: Twenty-four statements regarding the need for seizure reduction in pediatric epilepsy, the recommended treatment algorithm, the benefits and safety of VNS therapy, management of side effects of VNS therapy, patient selection for VNS therapy, and the use, dosing, and titration of VNS therapy achieved consensus. VNS and other neuromodulation therapies should be considered for pediatric patients with drug-resistant epilepsy who are not candidates for resective surgery, or who do not remain seizure free after resective surgery. When VNS therapy is initiated, the target dose range should be achieved via the fastest and safest titration schedule for each patient. Scheduled programming can be helpful in dose titration., Conclusion: The expert consensus statements represent the panelists' collective opinion on the best practice use of VNS therapy to optimize outcomes in the management of pediatric epilepsy., Competing Interests: Declaration of competing interest James W. Wheless is a consultant for BioMarin, Epiwatch, Neurelis, Neuro Event Labs, Jazz, and Takeda; has received research funding from LivaNova, Jazz, Neurelis, Neuro Event Labs, Shainberg Foundation, SKLSI, TSC Alliance, and UCB; and serves on the speaker's bureau for BioMarin, Jazz, Neurelis, SKLSI, and UCB. Jeffrey S. Raskin is a clinical advisory board member for Synergia, a consultant for Blackrock Neurotech, Iota, and Brainlab, and President of SMERF, Inc 501(c)(3). Anthony L. Fine has no financial interests to disclose. Kelly Knupp has consulted for UCB, Stoke, Encoded, Epygenix, Longboard and Biocodex; has received research funding from Eisai, Stoke, and UCB; and serves on a Data and Safety Monitoring Board for Jazz and Epygenix. John Schreiber is a clinical advisory board member for Stoke Therapeutics and Longboard Pharmacueticals; a consultant for Denali Therapeutics and Neurocrine; receives research funding to his institution from UCB, Neurocrine, and Stoke Therapeutics; and serves on the speaker bureau for UCB and Marinus. Adam P. Ostendorf receives research funding from NINDS and the Nationwide Children's Hospital Foundation. Gregory W. Albert has no financial interests to disclose. Eric H. Kossoff has received consultant fees from LivaNova (not for this study), Simply Good Foods, Nutricia, Vitaflo, Cerecin, and Bloom Science. He is on the data safety monitoring board for a study from NeuroPace. Joseph R. Madsen is a consultant and scientific advisory board member for BioNaut Laboratories and Anuncia Medical. Prakash Kotagal is a consultant for Biocodex, Inc., LivaNova PLC, SK Life Sciences, and Takeda Pharmaceuticals. Adam L. Numis has no financial interests to disclose. Nisha Gadgil has no financial interests to disclose. Deborah L. Holder is a speaker for LivaNova. Elizabeth A. Thiele is a consultant for Jazz, UCB, Biocodex, LivaNova, Pyros, SKLS, Stoke Therapeutics, Takeda, Marinus, and Nobelpharma. She has received research funding from Jazz, UCB, and Biocodex. George M. Ibrahim has received research funding and consulting fees from LivaNova (not for this study). He also receives consulting and advisory fees from Medtronic Inc and Synergia Inc., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Several fully continuous probabilistic genotyping software (PGS) use Markov chain Monte Carlo algorithms (MCMC) to assign weights to different proposed genotype combinations at a locus. Replicate interpretations of the same profile in these software are expected not to produce identical weights and likelihood ratio (LR) values due to the Monte Carlo aspect. This paper reports a detailed precision study under reproducibility conditions conducted as a collaborative exercise across the National Institute of Standards and Technology (NIST), Federal Bureau of Investigation (FBI), and Institute of Environmental Science and Research (ESR). Replicate interpretations generated across the three laboratories used the same input files, software version, and settings but different random number seed and different computers. This work demonstrates that using different computers to analyze replicate interpretations does not contribute to any variations in LR values. The study quantifies the magnitude of differences in the assigned LRs that is only due to run-to-run MCMC variability and addresses the potential explanations for the observed differences., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Legionella is an opportunistic waterborne pathogen that is difficult to eradicate in colonized drinking water pipes. Legionella control is further challenged by aging water infrastructure and lack of evidence-based guidance for building treatment. This study assessed multiple premise water remediation approaches designed to reduce Legionella pneumophila within a residential building located in an aging, urban drinking water system over a two-year period. Samples (n = 745) were collected from hot and cold-water lines and quantified via most probable number culture. Building-level treatment approaches included three single heat shocks, three single chemical shocks, and continuous low-level chemical disinfection in the potable water system. The building was highly colonized with L. pneumophila with 71 % L. pneumophila positivity. Single heat shocks had a statistically significant L. pneumophila reduction one day post treatment but no significant L. pneumophila reduction at one week, two weeks, and four weeks post treatment. The first two chemical shocks resulted in statistically significant L. pneumophila reduction at two days and four weeks post treatment, but there was a significant L. pneumophila increase at four weeks following the third chemical shock. Continuous low-level chemical disinfection resulted in statistically significant L. pneumophila reduction at ten weeks post treatment implementation. This demonstrates that in a building highly colonized with L. pneumophila, sustained remediation is best achieved using continuous low-level chemical treatment., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Proliferation and invasion are two key drivers of tumor growth that are traditionally considered independent multicellular processes. However, these processes are intrinsically coupled through a maximum carrying capacity, i.e., the maximum spatial cell concentration supported by the tumor volume, total cell count, nutrient access, and mechanical properties of the tissue stroma. We explored this coupling of proliferation and invasion through in vitro and in silico methods where we modulated the mechanical properties of the tumor and the surrounding extracellular matrix. E-cadherin expression and stromal collagen concentration were manipulated in a tunable breast cancer spheroid to determine the overall impacts of these tumor variables on net tumor proliferation and continuum invasion. We integrated these results into a mixed-constitutive formulation to computationally delineate the influences of cellular and extracellular adhesion, stiffness, and mechanical properties of the extracellular matrix on net proliferation and continuum invasion. This framework integrates biological in vitro data into concise computational models of invasion and proliferation to provide more detailed physical insights into the coupling of these key tumor processes and tumor growth. STATEMENT OF SIGNIFICANCE: Tumor growth involves expansion into the collagen-rich stroma through intrinsic coupling of proliferation and invasion within the tumor continuum. These processes are regulated by a maximum carrying capacity that is determined by the total cell count, tumor volume, nutrient access, and mechanical properties of the surrounding stroma. The influences of biomechanical parameters (i.e., stiffness, cell elongation, net proliferation rate and cell-ECM friction) on tumor proliferation or invasion cannot be unraveled using experimental methods alone. By pairing a tunable spheroid system with computational modeling, we delineated the interdependencies of each system parameter on tumor proliferation and continuum invasion, and established a concise computational framework for studying tumor mechanobiology., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Strength and Vulnerability Integration (SAVI) describes age-related patterns of emotional well-being. Since its initial publication, studies have tested the model, supporting its original tenets and also identifying areas needing refinement. The current review provides an updated description of SAVI, describing how age differences in well-being vary based on the proximity to acute stressors and the proposed underlying mechanisms. SAVI also addresses questions regarding why we sometimes observe increases in distress among older adults over time. In this description, we clarify predictions of SAVI, as well as suggest places where more research is needed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Susan T. Charles reports a relationship with National Institutes of Health that includes: funding grants. Jennifer R. Piazza reports a relationship with National Institutes of Health that includes: funding grants. I have not served on the editorial board for this journal, although I have reviewed for other journals in the field in the past year., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

What makes objects alike in the human mind? Computational approaches for characterizing object similarity have largely focused on the visual forms of objects or their linguistic associations. However, intuitive notions of object similarity may depend heavily on contextual reasoning-that is, objects may be grouped together in the mind if they occur in the context of similar scenes or events. Using large-scale analyses of natural scene statistics and human behavior, we found that a computational model of the associations between objects and their scene contexts is strongly predictive of how humans spontaneously group objects by similarity. Specifically, we learned contextual prototypes for a diverse set of object categories by taking the average response of a convolutional neural network (CNN) to the scene contexts in which the objects typically occurred. In behavioral experiments, we found that contextual prototypes were strongly predictive of human similarity judgments for a large set of objects and rivaled the performance of models based on CNN representations of the objects themselves or word embeddings for their names. Together, our findings reveal the remarkable degree to which the natural statistics of context predict commonsense notions of object similarity., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Protein-protein and protein-RNA interactions are essential for cell function and survival. These interactions facilitate the formation of ribonucleoprotein complexes and biomolecular condensates via phase separation. Such assembly is involved in transcription, splicing, translation and stress response. When dysregulated, proteins and RNA can undergo irreversible aggregation which can be cytotoxic and pathogenic. Despite technical advances in investigating biomolecular condensates, achieving the necessary spatiotemporal resolution to deduce the parameters that govern their assembly and behavior has been challenging. Many laboratories have applied advanced microscopy methods for imaging condensates. For example, single molecule imaging methods have enabled the detection of RNA-protein interaction, protein-protein interaction, protein conformational dynamics, and diffusional motion of molecules that report on the intrinsic molecular interactions underlying liquid-liquid phase separation. This review will outline advances in both microscopy and spectroscopy techniques which allow single molecule detection and imaging, and how these techniques can be used to probe unique aspects of biomolecular condensates., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Research has identified many factors associated with bicycling, but little is known on their relative influence for an individual's decision to bicycle or what led to the surge in bicycling during the COVID-19 pandemic in the U.S., Methods: Our research leverages a sample of 6735 U.S. adults to identify key predictors and their relative influence on both increased bicycling during the pandemic and on whether an individual commutes by bicycle. LASSO regression models identified a reduced set of predictors for the outcomes of interest from 55 determinants included in the modeling., Results: We find individual and environmental factors have a role in explaining the shift towards bicycling-with key differences in predictors for increased overall cycling during the pandemic compared to bicycle commuting., Conclusions: Our findings add to the evidence base that policies can impact bicycling behavior. Specifically, increasing e-bike accessibility and limiting residential streets to local traffic are two policies that show promise for encouraging bicycling., Competing Interests: A conflict of interest may exist when an author or the author's institution has a financial or other relationship with other people or organizations that may inappropriately influence the author's work. A conflict can be actual or potential. At the end of the text, under a subheading ‘Disclosure Statement’, all authors must disclose any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three (3) years of beginning the work submitted that could inappropriately influence (bias) their work. Examples of potential conflicts of interest which should be disclosed include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding.

Gametogenesis produces the only cell type within a metazoan that contributes both genetic and epigenetic information to the offspring. Extensive epigenetic dynamics are required to express or repress gene expression in a precise spatiotemporal manner. On the other hand, early embryos must be extensively reprogrammed as they begin a new life cycle, involving intergenerational epigenetic inheritance. Seminal work in both Drosophila and C. elegans has elucidated the role of various regulators of epigenetic inheritance, including (1) histones, (2) histone-modifying enzymes, and (3) small RNA-dependent epigenetic regulation in the maintenance of germline identity. This review highlights recent discoveries of epigenetic regulation during the stepwise changes of transcription and chromatin structure that takes place during germline stem cell self-renewal, maintenance of germline identity, and intergenerational epigenetic inheritance. Findings from these two species provide precedence and opportunity to extend relevant studies to vertebrates., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Previous research has emphasized the unique impact of Alzheimer's Disease (AD) pathology on the medial temporal lobe (MTL), a reflection that tau pathology is particularly striking in the entorhinal and transentorhinal cortex (ERC, TEC) early in the course of disease. However, other brain regions are affected by AD pathology during its early phases. Here, we use longitudinal diffeomorphometry to measure the atrophy rate from MRI of the amygdala compared with that in the ERC and TEC in cognitively unimpaired (CU) controls, CU individuals who progressed to mild cognitive impairment (MCI), and individuals with MCI who progressed to dementia of the AD type (DAT), using a dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our results show significantly higher atrophy rates of the amygdala in both groups of 'converters' (CU→MCI, MCI→DAT) compared to controls, with rates of volume loss comparable to rates of thickness loss in the ERC and TEC. We localize atrophy within the amygdala within each of these groups using fixed effects modeling. Controlling for the familywise error rate highlights the medial regions of the amygdala as those with significantly higher atrophy in both groups of converters than in controls. Using our recently developed method, referred to as Projective LDDMM, we map measures of neurofibrillary tau tangles (NFTs) from digital pathology to MRI atlases and reconstruct dense 3D spatial distributions of NFT density within regions of the MTL. The distribution of NFTs is consistent with the spatial distribution of MR measured atrophy rates, revealing high densities (and atrophy) in the amygdala (particularly medial), ERC, and rostral third of the MTL. The similarity of the location of NFTs in AD and shape changes in a well-defined clinical population suggests that amygdalar atrophy rate, as measured through MRI may be a viable biomarker for AD., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MM and SM are co-owners of Anatomy Works and are entitled to royalty distributions from the company, with the arrangement being managed by Johns Hopkins University in accordance with its conflict of interest policies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: School-based vision programs (SBVPs) are one approach to increase access to vision care by providing vision screenings, eye examinations, and eyeglasses directly in schools. Few studies report on the perspectives of teachers and staff, who are important stakeholders, on SBVPs. We examined teacher and staff perspectives on their involvement in SBVPs., Design: Qualitative study using focus groups., Participants: Teachers and staff at Baltimore and Chicago public schools served by SBVPs between 2016 and 2018., Methods: We conducted 21 semistructured focus groups with 117 teachers and staff in 10 Baltimore and 11 Chicago public preK-12 schools that participated in SBVPs. Sessions were recorded, transcribed, and coded using inductive thematic analysis., Results: Participants identified 2 main themes regarding teacher and staff involvement in SBVPs: (i) program outreach, including using multiple communication modalities to engage parents, explaining program details to families, and helping with program consent form return and (ii) promoting vision health, including identifying vision problems in the classroom, encouraging eyeglasses wear, and supporting eyeglasses maintenance. Participants also discussed limitations in capacity to partake in these activities., Conclusion: Teachers interact with parents and students throughout the SBVP process, undertaking important roles in outreach and health promotion to ensure uptake of SBVP services. SBVPs and other school-based health programs should explore strategies to support teachers in the roles they fill to optimize program impact., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To examine associations between frailty and drug, alcohol, and tobacco use among a large diverse cohort of people with HIV (PWH) in clinical care in the current era., Methods: PWH at 7 sites across the United States completed clinical assessments of patient-reported measures and outcomes between 2016 and 2019 as part of routine care including drug and alcohol use, smoking, and other domains. Frailty was assessed using 4 of the 5 components of the Fried frailty phenotype and PWH were categorized as not frail, pre-frail, or frail. Associations of substance use with frailty were assessed with multivariate Poisson regression., Results: Among 9336 PWH, 43% were not frail, 44% were prefrail, and 13% were frail. Frailty was more prevalent among women, older PWH, and those reporting current use of drugs or cigarettes. Current methamphetamine use (1.26: 95% CI 1.07-1.48), current (1.65: 95% CI 1.39-1.97) and former (1.21:95% CI 1.06-1.36) illicit opioid use, and former cocaine/crack use (1.17: 95% CI 1.01-1.35) were associated with greater risk of being frail in adjusted analyses. Current smoking was associated with a 61% higher risk of being frail vs. not frail (1.61: 95% CI 1.41-1.85) in adjusted analyses., Conclusions: We found a high prevalence of prefrailty and frailty among a nationally distributed cohort of PWH in care. This study identified distinct risk factors that may be associated with frailty among PWH, many of which, such as cigarette smoking and drug use, are potentially modifiable., Competing Interests: Conflict of interest All authors report that they have no relevant conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier B.V.)

Background: Diabetes self-management education and support (DSMES) is an effective approach for improving diabetes self-care behaviors to achieve improved glycemic management and other health outcomes. Engaging family members may improve outcomes, both for the person with diabetes (PWD) and for the family members. However, family models of DSMES have been inconsistently defined and delivered. We operationalize Family-DSMES to be generalizable and replicable, detail our protocol for a comparative effectiveness trial comparing Standard-DSMES with Family-DSMES on outcomes for PWDs and family members, and detail our mixed-methods implementation evaluation plan., Methods: We will examine Family-DSMES relative to Standard-DSMES using a Hybrid Type 1 effectiveness-implementation design. Participants are ≥18 years old with type 2 diabetes mellitus and hemoglobin A1c ≥7.0%, recruited from rural and urban primary care clinics that are part of an academic medical center. Each participant invites a family member. Dyads are randomly assigned to Family- or Standard-DSMES, delivered in a small-group format via telehealth. Data are collected at baseline, immediately post-intervention, and 6-, 12-, and 18-months post-intervention. Outcomes include PWDs' hemoglobin A1c (primary), other biometric, behavioral, and psychosocial outcomes (secondary), and family members' diabetes-related distress, involvement in the PWD's diabetes management, self-efficacy for providing support, and biometric outcomes (exploratory). Our mixed-methods implementation evaluation will include process data collected during the trial and stakeholder interviews guided by the Consolidated Framework for Implementation Research., Conclusion: Results will fill knowledge gaps about which type of DSMES may be most effective and guide Family-DSMES implementation efforts., Registration: The trial is pre-registered at clinicaltrials.gov (#NCT04334109)., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tumor-associated macrophages (TAMs) are an abundant tumor-promoting cell type in the tumor microenvironment (TME). Most TAMs exhibit a pro-tumor M2-like phenotype supportive of tumor growth, immune evasion, and metastasis. IL-4 and IL-13 are major cytokines that polarize macrophages to an M2 subset and share a common receptor, IL-4 receptor alpha (IL-4R alpha). Treatment of human ex vivo polarized M2 macrophages and M2 macrophage precursors with IL-4R alpha antagonist antibody Dupilumab (Dupixent Ⓡ ) reduces M2 macrophage features, including a shift in cell surface marker protein expression and gene expression. In animal models of prostate cancer, both pharmacologic inhibition of IL-4R alpha and genetic deletion of IL-4R alpha utilizing an Il4ra -/- mouse model result in decreased CD206 on TAMs. These data support IL-4R alpha as a target to reduce the pro-tumor, M2-like macrophage phenotype as a novel adjunct cancer therapy., (Copyright © 2022. Published by Elsevier Inc.)

The Sm protein Hfq chaperones small non-coding RNAs (sRNAs) in bacteria, facilitating sRNA regulation of target mRNAs. Hfq acts in part by remodeling the sRNA and mRNA structures, yet the basis for this remodeling activity is not understood. To understand how Hfq remodels RNA, we used single-molecule Förster resonance energy transfer (smFRET) to monitor conformational changes in OxyS sRNA upon Hfq binding. The results show that E. coli Hfq first compacts OxyS, bringing its 5' and 3 ends together. Next, Hfq destabilizes an internal stem-loop in OxyS, allowing the RNA to adopt a more open conformation that is stabilized by a conserved arginine on the rim of Hfq. The frequency of transitions between compact and open conformations depend on interactions with Hfqs flexible C-terminal domain (CTD), being more rapid when the CTD is deleted, and slower when OxyS is bound to Caulobacter crescentus Hfq, which has a shorter and more stable CTD than E. coli Hfq. We propose that the CTDs gate transitions between OxyS conformations that are stabilized by interaction with one or more arginines. These results suggest a general model for how basic residues and intrinsically disordered regions of RNA chaperones act together to refold RNA., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Pharmacy student proficiency in direct patient interactions is an integral component of the doctor of pharmacy curriculum. Service-learning experiences offer pharmacy students valuable opportunities to develop self-efficacy and empathy while serving communities with unmet needs. The objective of this review is to evaluate the impact of service-learning experiences on the self-efficacy and empathy of pharmacy and other health professions students., Methods: A narrative literature review was conducted using PubMed, ERIC, and CINAHL databases. Articles were included if they described the relationship between any health professions student service-learning experience and changes in self-efficacy and empathy. Articles were excluded if they involved simulation experiences, standardized patients, or international experiences., Results: A total of 11 relevant articles were identified, seven examined changes in student self-efficacy and six assessed student empathy. Articles included students representing seven health professions, with one eligible article in pharmacy. All articles investigating self-efficacy reported a positive impact of service learning on student confidence. Most articles focusing on empathy found that service learning had a positive impact on student empathy, and only one article noted a negative trend. Students with limited prior direct patient care experience had the greatest improvement in clinical confidence and empathy., Implications: This review adds a new perspective to the literature by evaluating evidence-based service-learning models in pharmacy education. Offering additional structured service-learning opportunities for pharmacy students fosters self-efficacy and empathy while supporting communities with unmet needs. Future studies evaluating innovative service-learning models and methods of continuous assessment within the pharmacy curriculum are warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: During the COVID-19 pandemic, governments have experimented with a wide array of policies to further public health goals. This research offers an application of multilevel regression with post-stratification (MRP) analysis to assess state-level support for commonly implemented policies during the pandemic., Methods: We conducted a national survey of U.S. adults using The Harris Poll panel from June 17-29, 2020. Respondents reported their support for a set of measures that were being considered in jurisdictions in the U.S. at the time the survey was fielded. MRP analysis was then used to generate estimates of state-level support., Results: The research presented here suggests generally high levels of support for mask mandates and social distancing measures in June 2020-support that was consistent throughout the United States. In comparison, support for other policies, such as changes to the road environment to create safer spaces for walking and bicycling, had generally low levels of support throughout the country. This research also provides some evidence that higher support for coronavirus-related policies could be found in more populous states with large urban centers, recognizing that there was low variability across states., Conclusion: This paper provides a unique application of MRP analysis in the public health field, uncovering noteworthy state-level patterns, and offering several avenues for future research. Future research could examine policy support at a small geographic level, such as by counties, to understand the distribution of support for public policies within states.

Macrodecomposers provide important ecosystem services even in human dominated habitats including urban ecosystems, but the effect of urban land conversion on their species diversity and abundance has not been explored at global scale. Here, we present the first meta-analysis to quantify the general response of two major arthropod taxa, terrestrial isopods and millipedes to urbanization and to reveal the underlying mechanisms. Climatic (temperature, precipitation, growing season length), edaphic (pH, organic carbon, CaCO 3 and clay content of surface soils), urban (population density, city age, vegetation cover and mean actual evapotranspiration) parameters and methods of study (duration, sampling technique, replications) were used as moderators. We used a hierarchical meta-analytic approach to consider the dependence of multiple effect sizes obtained from one study. Altogether 156 paired observations were extracted from 59 urban studies conducted between 1980 and 2020. Urbanization had a negative effect on species diversity (species richness and Shannon index) of both macroarthropod taxa. However, both the direction and strength of their abundance response varied to a greater extent, resulting in a neutral effect of urban disturbance on them. The key drivers influencing the urban effects on macroarthropods were mean annual temperature and precipitation, absolute minimum temperature and length of growing season. The study also highlighted the importance of sampling methods: direct sampling (hand collecting) resulted in stronger urban effects presumably due to several sources of sampling bias. Our global synthesis highlighted that urbanization is a threat to soil arthropods, particularly to litter-dwelling detritivores, which potentially alters plant residue processing and ultimately soil biogeochemical cycles., Competing Interests: Declaration of competing interest 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., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: This study evaluated the impact of an emotional intelligence (EI) workshop as a tool to improve student pharmacists' self-awareness. The primary objectives were to assess the change in student pharmacists' self-awareness as measured by the Self-Awareness Outcomes Questionnaire (SAOQ) and identify trends in their self-reflection., Educational Activity and Setting: A four-hour EI workshop was delivered in a first-year required student pharmacist leadership course. The components of the workshop included: an EI assessment via the Emotional Quotient Inventory (EQ-i 2.0) administered to student pharmacists outside of class, active learning class time that applied the principles of EI to leadership and group dynamics, and peer-to-peer discussions. Personal results of the EQ-i 2.0 were reviewed individually and in small groups. Student pharmacists completed a self-reflection and EI action plan outside of class. The SAOQ was completed before and after the workshop and the aggregated Likert scales were analyzed by paired t-tests., Findings: After two consecutive course offerings of the workshop (N = 100), there was a significant increase in the total SAOQ score as well as a significant increase for the three positive subscales: reflective self-development, acceptance, and proactivity. There was no change in the negative subscale: emotional costs. Student pharmacists positively perceived the workshop and reported that the activities motivated students to improve their interpersonal skills and increase extracurricular involvement., Discussion: Implementing an EI workshop is an effective curricular method to improve the affective domain of student development, specifically self-awareness., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The potential airborne transmission of SARS-CoV-2 has triggered concerns as schools continue to reopen and resume in-person instruction during the current COVID-19 pandemic. It is critical to understand the risks of airborne SARS-CoV-2 transmission under different epidemiological scenarios and operation strategies for schools to make informed decisions to mitigate infection risk. Through scenario-based analysis, this study estimates the airborne infection risk of SARS-CoV-2 in 111,485 U.S. public and private schools and evaluates the impacts of different intervention strategies, including increased ventilation, air filtration, and hybrid learning. Schools in more than 90% of counties exhibit infection risk of higher than 1%, indicating the significance of implementing intervention strategies. Among the considered strategies, air filtration is found to be most effective: the school average infection risk when applying MERV 13 is over 30% less than the risk levels correlating with the use of increased ventilation and hybrid learning strategies, respectively. For most schools, it is necessary to adopt combined intervention strategies to ensure the infection risk below 1%. The results provide insights into airborne infection risk in schools under various scenarios and may guide schools and policymakers in developing effective operations strategies to maintain environmental health., Competing Interests: The authors declare no conflict of interest., (© 2021 Elsevier Ltd. All rights reserved.)

Background: Coarctation of the aorta (CoA) is associated with decreased exercise capacity despite successful repair. Altered flow patterns have been identified due to abnormal aortic arch geometry. Our previous work demonstrated aorta size mismatch to be associated with exercise intolerance in this population. In this study, we studied aortic flow patterns during simulations of exercise in repaired CoA using 4D flow cardiovascular magnetic resonance (CMR) using aortic replicas connected to an in vitro flow pump and correlated findings with exercise stress test results to identify biomarkers of exercise intolerance., Methods: Patients with CoA repair were retrospectively analyzed after CMR and exercise stress test. Each aorta was manually segmented and 3D printed. Pressure gradient measurements from ascending aorta (AAo) to descending aorta (DAo) and 4D flow CMR were performed during simulations of rest and exercise using a mock circulatory flow loop. Changes in wall shear stress (WSS) and secondary flow formation (vorticity and helicity) from rest to exercise were quantified, as well as estimated DAo Reynolds number. Parameters were correlated with percent predicted peak oxygen consumption (VO2 max ) and aorta size mismatch (D AAo /D DAo )., Results: Fifteen patients were identified (VO2 max 47 to 126% predicted). Pressure gradient did not correlate with VO2 max at rest or exercise. VO2 max correlated positively with the change in peak vorticity (R = 0.55, p = 0.03), peak helicity (R = 0.54, p = 0.04), peak WSS in the AAo (R = 0.68, p = 0.005) and negatively with peak WSS in the DAo (R = - 0.57, p = 0.03) from rest to exercise. D AAo /D DAo correlated strongly with change in vorticity (R = - 0.38, p = 0.01), helicity (R = - 0.66, p = 0.007), and WSS in the AAo (R = - 0.73, p = 0.002) and DAo (R = 0.58, p = 0.02). Estimated DAo Reynolds number negatively correlated with VO2 max for exercise (R = - 0.59, p = 0.02), but not rest (R = - 0.28, p = 0.31). Visualization of streamline patterns demonstrated more secondary flow formation in aortic arches with better exercise capacity, larger DAo, and lower Reynolds number., Conclusions: There are important associations between secondary flow characteristics and exercise capacity in repaired CoA that are not captured by traditional pressure gradient, likely due to increased turbulence and inefficient flow. These 4D flow CMR parameters are a target of investigation to identify optimal aortic arch geometry and improve long term clinical outcomes after CoA repair., (© 2021. The Author(s).)

Background: Motor imitation difficulties are pervasive in children with Autism Spectrum Disorder (ASD). Previous research demonstrated the validity and reliability of an algorithm called Computerized Assessment of Motor Imitation (CAMI) using 3D depth cameras. However, incorporating CAMI into serious games and making it accessible in clinic and home settings requires a more scalable approach that uses "off-the-shelf" 2D cameras., Method: In a brief (one-minute) task, children (23 ASD, 17 typically developing [TD]) imitated a model's dance movements while simultaneously being recorded using Kinect Xbox motion tracking technology (Kinect 3D) and a single 2D camera. Pose-estimation software (OpenPose 2D) was used on the 2D camera video to fit a skeleton to the imitating child. Motor imitation scores computed from the fully automated OpenPose 2D CAMI method were compared to scores computed from the Kinect 3D CAMI and Human Observation Coding (HOC) methods., Results: Motor imitation scores obtained from the OpenPose 2D CAMI method were significantly correlated with scores obtained from the Kinect 3D CAMI method ( r 40 = 0.82, p < 0.001) and the HOC method ( r 40 = 0.80, p < 0.001). Both 2D and 3D CAMI methods showed better discriminative ability than the HOC, with the Kinect 3D CAMI method outperforming the OpenPose 2D CAMI method (area under ROC curve (AUC): AUC HOC = 0.799, AUC 2D-CAMI = 0.876, AUC 3D-CAMI = 0.94). Finally, all motor imitation scores were significantly associated with the social-communication impairment (all p ≤ 0.003)., Conclusions: This pilot-study demonstrated that motor imitation can be automatically quantified using a single 2D camera., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest.

A universe of transcription factors (TFs), cofactors, as well as chromatin remodeling and modifying enzymes combine or compete on chromatin to control transcription. Measuring quantitatively how these proteins dynamically interact is required in order to formulate models with predictive ability to elucidate transcription control mechanisms. Single molecule tracking (SMT) provides a powerful tool towards this goal: it is a fluorescence microscopy approach that measures the location and mobility of individual TF molecules, as well as their rates of association with and dissociation from chromatin in the physiological context of the living cell. Here we review SMT principles, and discuss key TF properties uncovered by live-cell SMT, such as fast turnover (seconds), and formation of clusters that locally increase activity., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes., Methods: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis., Results: Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50 years (range, 17-70 years) and 71% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68%) patients had radiologic evidence of other nervous system involvement and 20 (39%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71%) patients (median: 14/μL; range: 1-643/μL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67%); optic nerve/sheath, 9 (18%); or other nervous system region, 8 (16%). Forty patients improved with treatment (78%), 98% receiving corticosteroids and 65% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24%) had a visual acuity of 20/200 or worse at last follow-up., Conclusions: Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To examine the impact of treatment sequences of Immune checkpoint inhibitor (ICI) and cetuximab on clinical outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: Clinicopathologic data were retrospectively collected on patients with R/M HNSCC who received ICI treatment. Association between treatment sequence and clinical outcomes were assessed., Results: A total of 113 patients with R/M HNSCC were analyzed. Patients who had cetuximab prior to ICI had worse overall (HR, 1.83) and progression-free survival (HR, 1.76) compare to those without prior cetuximab. Among patients who had subsequent therapy after ICI, cetuximab-based therapy was associated with a trend toward higher response rate and longer survival than non-cetuximab regimen., Conclusion: Our single institution analysis showed that treatment sequence of cetuximab and ICI in R/M HNSCC may affect clinical outcomes. Cetuximab prior to ICI was associated with worse outcomes while the efficacy of cetuximab may be enhanced after ICI therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The interaction of anaerobic microorganisms with carbon nanotube/polymer nanocomposites (CNT/PNC) will play a major role in determining their persistence and environmental fate at the end of consumer use when these nano-enabled materials enter landfills and encounter wastewater. Motivated by the need to understand how different parameters (i.e., polymer type, microbial phenotype, CNT characteristics) influence CNT/PNC biodegradation rates, we have used volumetric biogas measurements and kinetic modeling to study biodegradation as a function of polymer type and CNT properties. In one set of experiments, oxidized multiwall carbon nanotubes (O-MWCNTs) with a range of CNT loadings 0-5% w/w were incorporated into poly-ε-caprolactone (PCL) and polyhydroxyalkanoates (PHA) matrices and subjected to biodegradation by an anaerobic microbial community. For each CNT/PNC, complete polymer biodegradation was ultimately observed, although the rate of biodegradation was inhibited above certain critical CNT loadings dependent upon the polymer type. Higher loadings of pristine MWCNTs were needed to decrease the rate of polymer biodegradation compared to O-MWCNTs, an effect ascribed principally to differences in CNT dispersion within the polymer matrices. Above certain CNT loadings, a CNT mat of similar shape to the initial PNC was formed after polymer biodegradation, while below this threshold, CNT aggregates fragmented in the media. In situations where biodegradation was rapid, methanogen growth was disproportionately inhibited compared to the overall microbial community. Analysis of the results obtained from this study indicates that the inhibitory effect of CNTs on polymer biodegradation rate is greatest under conditions (i.e., polymer type, microbial phenotype, CNT dispersion) where biodegradation of the neat polymer is slowest. This new insight provides a means to predict the environmental fate, persistence, and transformations of CNT-enabled polymer materials., Competing Interests: Declaration of competing interest 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, is considered an excellent target for the diagnosis or treatment of prostate cancer. We previously investigated the effect of β- and γ-amino acids with (S)- or (R)-configuration in the S1 pocket on the binding affinity for PSMA. However, comprehensive studies on the effect of α-amino acid with (R)-configuration in the S1' pocket has not been reported yet. We selected ZJ-43 (1) and DCIBzL (5) as templates and synthesized their analogues with (S)- or (R)-configuration in the P1 and P1' regions. The PSMA-inhibitory activities of compounds with altered chirality in the P1' region were dropped dramatically, with their IC 50 values changing from nM to μM ranges. The compounds with (S)-configuration at both P1 and P1' regions were more potent than the others. The findings of this study may provide insights regarding the structural modification of PSMA inhibitor in the S1' binding pocket., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Study Objective: To assess whether anesthesia providers' interpretations of a difficult intubation are consistent with current guidelines and explore possible explanations for any observed discrepancy including video laryngoscopy usage., Design: A retrospective data analysis of tracheal intubation records from the electronic health record of a large healthcare system in the United States from January to June 2018., Setting: General anesthesia encounters that involved a tracheal intubation in the operating rooms and non-operating room areas, including procedural areas, medical/surgical floors, and intensive care units., Patients: Records for 30,072 adult patients (33,142 cases) were identified for analysis. Patient age ranged from 18 to 100 and ASA physical status from I to V., Interventions: None., Measurements: The magnitude and direction of disagreement regarding intubation difficulty was estimated by examining anesthesiologist documentation vs. the American Society of Anesthesiologists guideline definitions. Any explanations for disagreement provided by clinicians were also analyzed. Furthermore, the association between video laryngoscopy and odds of disagreement was assessed., Main Results: While documentation of intubation difficulty in over 95% of records was consistent with current definitions, disagreement occurred in 1.6% of cases using the number of attempts definition (N = 31,964) and in 4.6% of cases using the Cormack-Lehane grade definition (N = 25,407). Some of the most frequently identified explanations clinicians gave in these cases of disagreement included the use of video laryngoscopy (used to explain documented difficult and easy intubations), clinician experience level, and the use of airway assist devices. Video laryngoscopy use was associated with greater odds of disagreement between anesthesiologist documentation and guideline definitions., Conclusions: A review of electronic anesthesia records suggests that clinicians inconsistently interpret and document difficult intubations in light of current guideline definitions and that video laryngoscopy usage appears to be associated, albeit not necessarily independently, with a greater discrepancy between anesthesiologist documentation and guideline definitions., Competing Interests: Declaration of competing interest The authors declare the following conflicts of interest: Matthew B. Kauffman: declares no conflicts of interest Jun Liu: declares no conflicts of interest Richard D. Urman: declares unrelated research funding from Merck, Medtronic. Also consulting fees from Takeda Pharma. Kara G. Fields: declares no conflicts of interest Dongdong Yao: declares no conflicts of interest, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Submicron particles (~800 nm) of paclitaxel (SPP) contain 1-2 billion molecules of pure drug that release tumoricidal levels of paclitaxel over many weeks. This study compared two dose-levels of SPP instilled into the peritoneal cavity (IP) in 200 ml of saline post-cytoreductive surgery. Eligible patients with primary (n = 6) or recurrent (n = 4) epithelial ovarian cancer who underwent complete cytoreductive surgery were enrolled to receive a single instillation of IP SPP followed by standard IV carboplatin and paclitaxel. Endpoints were PFS and evaluation of treatment emergent adverse events. Clinical response was determined by symptoms, physical exams, CT scans, and serum CA-125 measurements. Of the 24 subjects screened, 10 were enrolled and received treatment: seven patients received 100 mg/m 2 and three received 200 mg/m 2 . Seven subjects completed the 12-month follow-up period. Six patients were evaluable due to one subject who had unevaluable scans throughout the follow-up period and was thus excluded from PFS determination. Upon completion of planned chemotherapy post-SPP instillation, the PFS at 6 months was 66% (4/6) and at 12-months 66% (4/6) using RECIST 1.1. One subject had a complete response at the end of IV treatment but died (unrelated to study treatment) before PFS evaluation. There was one case of incision dehiscence and one case of vaginal cuff leakage after surgery. This pilot study supports further evaluation of IP SPP to treat peritoneal carcinomas., Competing Interests: Sally Mullany: nothing to disclose David Scott Miller: non-financial support from US Biotest. Katina Robison: nothing to disclose Kimberly Levinson: nothing to disclose Yi-Chun Lee: nothing to disclose S. Diane Yamada: non-financial support from US Biotest. Joan Walker: nothing to disclose Maurie Markman: personal fees from NanOlogy, outside the submitted work. Gere diZerega: personal fees and non-financial support from NanOlogy and US Biotest. Alyson Marin: personal fees from US Biotest. Peter Mast: personal fees from US Biotest., (© 2020 The Author(s).)

The definition of FIRS requires systemic inflammation and elevated levels of IL-6 in fetal plasma. That definition does not specify how systemic inflammation is to be recognized, and perinatal measurement of IL-6 is not a standard procedure. FIRS has not been examined in a population-based study that included post-neonatal outcome so its incidence and natural history are not known. The overlap, and similarities and differences, of FIRS as compared with other causes of neonatal encephalopathy, and how these relate to findings in the placenta, have not been jointly examined in a generalizable sample. FIRS has chiefly been discussed in the obstetric literature because of the need for decisions about management of delivery and antibiotic use. If the term "FIRS" is to be employed in other contexts, consensus should be sought as to which clinical, placental, and laboratory findings are most appropriate for identification of perinatal inflammatory processes, infectious or sterile., (© 2020 Published by Elsevier Ltd.)

Background: Preoperative identification of knee arthroplasty is important for planning revision surgery. However, up to 10% of implants are not identified prior to surgery. The purposes of this study were to develop and test the performance of a deep learning system (DLS) for the automated radiographic 1) identification of the presence or absence of a total knee arthroplasty (TKA); 2) classification of TKA vs. unicompartmental knee arthroplasty (UKA); and 3) differentiation between two different primary TKA models., Method: We collected 237 anteroposterior (AP) knee radiographs with equal proportions of native knees, TKA, and UKA and 274 AP knee radiographs with equal proportions of two TKA models. Data augmentation was used to increase the number of images for deep convolutional neural network (DCNN) training. A DLS based on DCNNs was trained on these images. Receiver operating characteristic (ROC) curves with area under the curve (AUC) were generated. Heatmaps were created using class activation mapping (CAM) to identify image features most important for DCNN decision-making., Results: DCNNs trained to detect TKA and distinguish between TKA and UKA both achieved AUC of 1. Heatmaps demonstrated appropriate emphasis of arthroplasty components in decision-making. The DCNN trained to distinguish between the two TKA models achieved AUC of 1. Heatmaps showed emphasis of specific unique features of the TKA model designs, such as the femoral component anterior flange shape., Conclusions: DCNNs can accurately identify presence of TKA and distinguish between specific arthroplasty designs. This proof-of-concept could be applied towards identifying other prosthesis models and prosthesis-related complications., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Magnetic resonance imaging (MRI) is a flexible medical imaging modality that often lacks reproducibility between protocols and scanners. It has been shown that even when care is taken to standardize acquisitions, any changes in hardware, software, or protocol design can lead to differences in quantitative results. This greatly impacts the quantitative utility of MRI in multi-site or long-term studies, where consistency is often valued over image quality. We propose a method of contrast harmonization, called DeepHarmony, which uses a U-Net-based deep learning architecture to produce images with consistent contrast. To provide training data, a small overlap cohort (n = 8) was scanned using two different protocols. Images harmonized with DeepHarmony showed significant improvement in consistency of volume quantification between scanning protocols. A longitudinal MRI dataset of patients with multiple sclerosis was also used to evaluate the effect of a protocol change on atrophy calculations in a clinical research setting. The results show that atrophy calculations were substantially and significantly affected by protocol change, whereas such changes have a less significant effect and substantially reduced overall difference when using DeepHarmony. This establishes that DeepHarmony can be used with an overlap cohort to reduce inconsistencies in segmentation caused by changes in scanner protocol, allowing for modernization of hardware and protocol design in long-term studies without invalidating previously acquired data., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A pulsed element is proposed allowing the selective inversion of a single 1 H nucleus, without regard to the presence of other degenerate 1 H nuclei, provided that it is coupled to a heteronuclear spin with adequate chemical shift resolution in a 2D heteronuclear correlation spectrum. The approach is based on selective cross polarization, in which matched weak RF fields of specific amplitude are applied on resonance to the targeted 1 H-X spin pair. It is shown theoretically that when the RF field amplitudes are set to specific values (ie. at a magic field), transfer of coherence can be fruitfully achieved transverse to the applied RF fields in addition to the normal longitudinal transfers. This enables the construction of a pulsed element which has the characteristics of a BIRD r,X element (Uhrin et al., 1993), yet with 2D frequency selectivity. Demonstration of the pulsed element is made in the context of selective spin inversion, by which all 1 H spins are inverted except the targeted 1 H spin., (Copyright © 2019 Elsevier Inc. All rights reserved.)