Nasal and pharyngeal mucosal immunity to poliovirus in children following routine immunization with inactivated polio vaccine (IPV) in the United States of America.

BACKGROUND: Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine-induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool. METHODS: To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2 to 5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs. RESULTS: PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received four IPV doses. Across the three PV serotypes, both nasal (Spearman's rho ≥ 0.87, p≤0.0003 for all) and adenoid (Spearman's rho ≥0.57, p≤0.05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization. CONCLUSIONS: Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine-induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity.

A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: A retrospective assessment.

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation.

Paired-agent imaging as a rapid en face margin screening method in Mohs micrographic surgery.

Background: Mohs micrographic surgery is a procedure used for non-melanoma skin cancers that has 97-99% cure rates largely owing to 100% margin analysis enabled by en face sectioning with real-time, iterative histologic assessment. However, the technique is limited to small and aggressive tumors in high-risk areas because the histopathological preparation and assessment is very time intensive. To address this, paired-agent imaging (PAI) can be used to rapidly screen excised specimens and identify tumor positive margins for guided and more efficient microscopic evaluation. Methods: A mouse xenograft model of human squamous cell carcinoma (n = 8 mice, 13 tumors) underwent PAI. Targeted (ABY-029, anti-epidermal growth factor receptor (EGFR) affibody molecule) and untargeted (IRDye 680LT carboxylate) imaging agents were simultaneously injected 3-4 h prior to surgical tumor resection. Fluorescence imaging was performed on main, unprocessed excised specimens and en face margins (tissue sections tangential to the deep margin surface). Binding potential (BP) - a quantity proportional to receptor concentration - and targeted fluorescence signal were measured for each, and respective mean and maximum values were analyzed to compare diagnostic ability and contrast. The BP and targeted fluorescence of the main specimen and margin samples were also correlated with EGFR immunohistochemistry (IHC). Results: PAI consistently outperformed targeted fluorescence alone in terms of diagnostic ability and contrast-to-variance ratio (CVR). Mean and maximum measures of BP resulted in 100% accuracy, while mean and maximum targeted fluorescence signal offered 97% and 98% accuracy, respectively. Moreover, maximum BP had the greatest average CVR for both main specimen and margin samples (average 1.7 ± 0.4 times improvement over other measures). Fresh tissue margin imaging improved similarity with EGFR IHC volume estimates compared to main specimen imaging in line profile analysis; and margin BP specifically had the strongest concordance (average 3.6 ± 2.2 times improvement over other measures). Conclusions: PAI was able to reliably distinguish tumor from normal tissue in fresh en face margin samples using the single metric of maximum BP. This demonstrated the potential for PAI to act as a highly sensitive screening tool to eliminate the extra time wasted on real-time pathological assessment of low-risk margins.

A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: a retrospective assessment.

Importance: Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumor removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. Objective: To develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. Design: A retrospective cohort study was conducted using frozen cSCC section slides and adjacent tissues. Setting: This study was conducted in a tertiary care academic center. Participants: Patients undergoing Mohs micrographic surgery for cSCC between January and March 2020. Exposures: Frozen section slides were scanned and annotated, delineating benign tissue structures, inflammation, and tumor to develop an AI algorithm for real-time margin analysis. Patients were stratified by tumor differentiation status. Epithelial tissues including epidermis and hair follicles were annotated for moderate-well to well differentiated cSCC tumors. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC at 50-micron resolution. Main Outcomes and Measures: The performance of the AI algorithm in identifying cSCC at 50-micron resolution was reported using the area under the receiver operating characteristic curve. Accuracy was also reported by tumor differentiation status and by delineation of cSCC from epidermis. Model performance using histomorphological features alone was compared to architectural features (i.e., tissue context) for well-differentiated tumors. Results: The AI algorithm demonstrated proof of concept for identifying cSCC with high accuracy. Accuracy differed by differentiation status, driven by challenges in separating cSCC from epidermis using histomorphological features alone for well-differentiated tumors. Consideration of broader tissue context through architectural features improved the ability to delineate tumor from epidermis. Conclusions and Relevance: Incorporating AI into the surgical workflow may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumors/neoplasms. Further algorithmic improvement is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumors, and to map tumors to their original anatomical position/orientation. Future studies should assess the efficiency improvements and cost benefits and address other confounding pathologies such as inflammation and nuclei. Funding sources: JL is supported by NIH grants R24GM141194, P20GM104416 and P20GM130454. Support for this work was also provided by the Prouty Dartmouth Cancer Center development funds. Key Points: Question: How can the efficiency and accuracy of real-time intraoperative margin analysis for the removal of cutaneous squamous cell carcinoma (cSCC) be improved, and how can tumor differentiation be incorporated into this approach?Findings: A proof-of-concept deep learning algorithm was trained, validated, and tested on frozen section whole slide images (WSI) for a retrospective cohort of cSCC cases, demonstrating high accuracy in identifying cSCC and related pathologies. Histomorphology alone was found to be insufficient to delineate tumor from epidermis in histologic identification of well-differentiated cSCC. Incorporation of surrounding tissue architecture and shape improved the ability to delineate tumor from normal tissue.Meaning: Integrating artificial intelligence into surgical procedures has the potential to enhance the thoroughness and efficiency of intraoperative margin analysis for cSCC removal. However, accurately accounting for the epidermal tissue based on the tumor's differentiation status requires specialized algorithms that consider the surrounding tissue context. To meaningfully integrate AI algorithms into clinical practice, further algorithmic refinement is needed, as well as the mapping of tumors to their original surgical site, and evaluation of the cost and efficacy of these approaches to address existing bottlenecks.

Physical activity interventions have a moderate effect in increasing physical activity in university students-a meta-analysis.

INTRODUCTION: The transition to college is associated with changes in physical activity. This meta-analysis aims to quantify the effect of interventions on increasing physical activity in healthy university students. METHODS: We conducted a literature search (up to 2/3/2020) to identify randomized controlled trials with healthy undergraduate or graduate students enrolled in a college degree program. Moderator analyses were conducted to examine the effects of intervention modality delivery (delivered in-person or remotely) and the type of outcome measure (self-report or objective measures). RESULTS: 18 publications were included. Interventions had a medium effect on physical activity (Cohen's d = 0.52). Moderator analyses revealed no differences. CONCLUSION: Suggestions of how to improve the quality of physical activity intervention studies in college students are given. The moderate effect size of physical activity interventions in college students highlights the importance of developing and testing new interventions to promote physical activity in emerging adults.Supplemental data for this article can be accessed online at https://doi.org/10.1080/07448481.2021.1998070 .

Identification of a Suitable Untargeted Agent for the Clinical Translation of ABY-029 Paired-Agent Imaging in Fluorescence-Guided Surgery.

PURPOSE: Non-specific uptake and retention of molecular targeted agents and heterogeneous tissue optical properties diminish the ability to differentiate between tumor and normal tissues using molecular targeted fluorescent agents. Paired-agent imaging (PAI) can increase the diagnostic ability to detect tumor tissue by mitigating these non-specific effects and providing true molecular contrast by co-administration of an untargeted control imaging agent with a targeted agent. This study evaluates the suitability of available clinically translatable untargeted agents for the translation of PAI in fluorescence-guided surgery using an affibody-based targeted imaging agent (ABY-029). EXPERIMENTAL: DESIGN: Three untargeted agents that fluoresce near 700 nm and exhibit good clinical safety profiles (methylene blue, IRDye 700DX, and IRDye 680LT) were tested in combination with the clinically tested IRDye 800CW-labeled anti-epidermal growth factor receptor (EGFR) affibody molecule, ABY-029 (eIND 122,681). Properties of the untargeted agent important for human use and integrity of PAI were tested: (1) plasma protein binding; (2) fluorescence signal linearity in in vitro whole blood dilution; (3) in vivo pharmacokinetic matching to targeted agent in negative control tissue; and (4) in vivo diagnostic accuracy of PAI vs single agent imaging (SAI) of ABY-029 alone in orthotopic oral head and neck squamous cell carcinomas. RESULTS: IRDye 680LT outperformed IRDye 700DX and methylene blue with the highest signal linearity (R2 = 0.9998 ± 0.0002, 0.9995 ± 0.0004, 0.91 ± 0.02, respectively), the highest fluorescence yield in whole blood at 1 µM (104.42 ± 0.05, 103.68 ± 0.09, 101.9 ± 0.2, respectively), and the most closely matched ABY-029 pharmacokinetics in EGFR-negative tissues (binding potential error percentage = 0.31% ± 0.37%, 10.25% ± 1.30%, and 8.10% ± 5.37%, respectively). The diagnostic ability of PAI with ABY-029 and IRDye 680LT outperformed conventional SAI with an area-under-the-receiver-operating-characteristic curve (AUC) value of 0.964 vs. 0.854, and 0.978 vs. 0.925 in the Odyssey scanning system and Pearl wide field imaging system, respectively. CONCLUSION: PAI is a highly promising methodology for increasing detection of tumors in fluorescence-guided surgery. Although not yet clinically approved, IRDye 680LT demonstrates promise as an untargeted agent when paired with ABY-029. The clinical translation of PAI to maximize tumor excision, while minimizing normal tissue removal, could improve both patient survival and life quality.

Improved Discrimination of Tumors with Low and Heterogeneous EGFR Expression in Fluorescence-Guided Surgery Through Paired-Agent Protocols.

PURPOSE: The goal of fluorescence-guided surgery (FGS) in oncology is to improve the surgical therapeutic index by enhancing contrast between cancerous and healthy tissues. However, optimal discrimination between these tissues is complicated by the nonspecific uptake and retention of molecular targeted agents and the variance of fluorescence signal. Paired-agent imaging (PAI) employs co-administration of an untargeted imaging agent with a molecular targeted agent, providing a normalization factor to minimize nonspecific and varied signals. The resulting measured binding potential is quantitative and equivalent to in vivo immunohistochemistry of the target protein. This study demonstrates that PAI improves the accuracy of tumor-to-healthy tissue discrimination compared to single-agent imaging for in vivo FGS. PROCEDURES: PAI using a fluorescent anti-epidermal growth factor receptor (EGFR) affibody molecule (ABY-029, eIND 122,681) with untargeted IRDye 700DX carboxylate was compared to ABY-029 alone in an oral squamous cell carcinoma xenograft mouse model at 3 h after dye administration (n = 30). RESULTS: PAI significantly enhanced tumor discrimination, as compared to ABY-029 alone in low EGFR-expressing tumors and highly heterogeneous populations including multiple cell lines with varying expression (diagnostic accuracy: 0.908 vs. 0.854 and 0.908 vs. 0.822; and ROC curve AUC: 0.963 vs. 0.909 and 0.957 vs. 0.909, respectively) indicating a potential for universal FGS image thresholds to determine surgical margins. In addition, PAI achieved significantly higher diagnostic ability than ABY-029 alone 0.25-5-h post injection and exhibited a stronger correlation to EGFR expression heterogeneity. CONCLUSION: The quantitative receptor delineation of PAI promises to improve the surgical therapeutic index of cancer resection in a clinically relevant timeline.

Rapid and Quantitative Intraoperative Pathology-Assisted Surgery by Paired-Agent Imaging-Derived Confidence Map.

PURPOSE: In nonmetastatic head and neck cancer treatment, surgical margin status is the most important prognosticator of recurrence and patient survival. Fresh frozen sectioning (FFS) of tissue margins is the standard of care for intraoperative margin assessment. However, FFS is time intensive, and its accuracy is not consistent among institutes. Mapping the epidermal growth factor receptor (EGFR) using paired-agent imaging (PAI) has the potential to provide more consistent intraoperative margin assessment in a fraction of the time as FFS. PROCEDURES: PAI was carried out through IV injection of an anti-epidermal growth factor receptor (EGFR) affibody molecule (ABY-029, eIND 122,681) and an untargeted IRDye680LT carboxylate. Imaging was performed on 4 µm frozen sections from three oral squamous cell carcinoma xenograft mouse models (n = 24, 8 samples per cell line). The diagnostic ability and tumor contrast were compared between binding potential, targeted, and untargeted images. Confidence maps were constructed based on group histogram-derived tumor probability curves. Tumor differentiability and contrast by confidence maps were evaluated. RESULTS: PAI outperformed ABY-029 and IRDye 680LT alone, demonstrating the highest individual receiver operating characteristic (ROC) curve area under the curve (PAI AUC: 0.91, 0.90, and 0.79) and contrast-to-noise ratio (PAI CNR: 1, 1.1, and 0.6) for FaDu, Det 562, and A253. PAI confidence maps (PAI CM) maintain high tumor diagnostic ability (PAI CMAUC: 0.91, 0.90, and 0.79) while significantly enhancing tumor contrast (PAI CMCNR: 1.5, 1.3, and 0.8) in FaDu, Det 562, and A253. Additionally, the PAI confidence map allows avascular A253 to be differentiated from a healthy tissue with significantly higher contrast than PAI. Notably, PAI does not require additional staining and therefore significantly reduces the tumor delineation time in a 5 [Formula: see text] 5 mm slice from ~ 35 min to under a minute. CONCLUSION: This study demonstrated that PAI improved tumor detection in frozen sections with high diagnostic accuracy and rapid analysis times. The novel PAI confidence map improved the contrast in vascular tumors and differentiability in avascular tumors. With a larger database, the PAI confidence map promises to standardize fluorescence imaging in intraoperative pathology-assisted surgery (IPAS).

Effectiveness of chronic disease self-management education (CDSME) programs to reduce loneliness.

OBJECTIVES: With about half of older adults reporting feelings of loneliness, interventions are needed to improve connectedness among our aging population. The health benefits of Chronic Disease Self-Management Education (CDSME) programs are well documented, but workshops' ability to reduce loneliness remains unknown. METHODS: Using the Campaign to End Loneliness Measurement Tool, we examined 295 CDSME participants' loneliness changes before and after the 6-week face-to-face workshops. Statistical analyzes used generalized estimating equations (GEE). RESULTS: On average, participants were age 74.3(±8.9) years and self-reported 3.3(±2.2) chronic conditions. The majority of participants were female (83%) and attended workshops in English (77%). Significant reductions in loneliness scores were observed from baseline to post-workshop (p < 0.001). DISCUSSION: Findings expand our understanding about the benefits of small-group CDSME workshops to reduce loneliness among participants. CDSME workshops may reduce loneliness because of their highly interactive and process-driven format and ability to create bonds between participants with chronic conditions and shared experiences.

Cognitive-Behavioral Versus Supportive Psychotherapy for Intermittent Explosive Disorder: A Randomized Controlled Trial.

Few clinical trials have evaluated the efficacy of psychotherapy for Intermittent Explosive Disorder (IED). The present study tested the efficacy of a cognitive behavioral intervention (versus supportive psychotherapy) among adults with IED. In this randomized clinical trial, 44 participants with IED (22 men and 22 women) aged 20-55 years completed twelve 50-minute individual sessions of either a multi-component cognitive behavioral intervention for IED (n = 19) or a time equated supportive psychotherapy (n = 25). At baseline, posttreatment, and 3-month follow-up, all participants received the Overt Aggression Scale-Modified, which was conducted by an interviewer who was blind to the participant's study condition. During these visits, participants also completed self-report measures of relational aggression (Self-Report of Relational Aggression and Social Behavior), anger (State-Trait Anger Expression Inventory-2), cognitive biases (e.g., Social Information Processing Questionnaire Attribution and Emotional Response Questionnaire), and associated symptoms (e.g., Beck Depression Inventory). Primary study outcomes were aggressive behavior and anger. Though participants in both treatments tended to improve over time, the cognitive behavioral intervention was superior to supportive psychotherapy in decreasing aggressive behavior and relational aggression. These findings support the efficacy of a multicomponent cognitive behavioral intervention in treating aggression in IED.

The effect of dialectical behavior therapy on anger and aggressive behavior: A systematic review with meta-analysis.

Dysregulated anger, and its common behavioral urge, aggression, pose substantial costs to public health and society. Though some studies have shown DBT to be efficacious in treating aggression and anger dyscontrol, the overall effects of DBT on these outcomes are unknown. To address this limitation, a systematic review with meta-analysis was conducted on 34 studies (N = 2536) published in PsycINFO and PubMed between January 1994 and February 2022 assessing the effect of DBT on anger and/or aggression. Included studies were empirical research articles published in a peer-reviewed journal and assessed the delivery of DBT on quantitative outcome measures of anger or aggression. Included studies delivered the standard outpatient DBT program or DBT adapted for the population and treatment setting, though all studies included the core components of DBT. Risk of publication bias was assessed. Results demonstrated that DBT significantly reduced anger (Hedge's G = -0.21, 95% CI [-0.32, -0.11]) independent of study design and participant variables, though longer treatment duration was associated with greater reductions in anger. There was also a non-significant trend for DBT in reducing aggression (Hedge's G = -0.10, 95% CI [-0.21, 0.00]). Findings from this study suggest that DBT demonstrates efficacy in reducing dysregulated anger transdiagnostically.

Negative mood induction effects on problem-solving task in women with eating disorders: a multi-method examination.

BACKGROUND: The effects of negative affect on problem-solving and its psychophysiological correlates are poorly understood in eating disorder populations. METHODS: This study examined respiratory sinus arrhythmia (RSA) and skin conductance responses of women with Binge Eating Disorder (BED: n = 56), Anorexia Nervosa (AN: n = 12), Bulimia Nervosa (BN: n = 32), and 24 healthy controls (HCs) at baseline, and then during: a negative mood induction task, an adapted Means Ends Problem-Solving (MEPS) task, and recovery. The MEPS task included four interpersonal scenarios: (1) binge-eating as a solution to stress, (2) job loss, (3) rejection by friends, and (4) by a significant other. RESULTS: We found that individuals with eating disorders reported less positive mood than HCs and individuals with BN and BED reported more negative mood and greater urges to binge than HCs. After a negative mood induction, women with BED provided significantly less effective problem-solving strategies compared to HCs and women with BN for the binge-eating MEPS scenario. Relative to baseline and the negative mood induction, all participants exhibited significantly higher skin conductance measures throughout the MEPS scenarios and recovery. BED showed significantly lower respiratory sinus arrhythmia (RSA) levels than individuals with BN and HCs throughout the protocol. CONCLUSIONS: The multimethod findings suggest individuals with BED are likely to have disorder-specific problem-solving difficulties after a negative mood induction.

There is some evidence that individuals with eating disorders experience more negative mood and have challenges with social problem-solving. However, the ability to solve social problems while in a negative mood has not yet been examined while also looking at physiological changes. We measured physiological responses of women with Binge Eating Disorder (BED; n = 56), Anorexia Nervosa (AN; n = 12), Bulimia Nervosa (BN; n = 32), and healthy controls (HCs; n = 24) before and after a task designed to induce a negative mood followed by a problem-solving task. The problem-solving task asked individuals to come up with solutions to social problems related to 1) binge-eating urges, 2) job loss, 3) rejection by friends, and 4) rejection of a significant other. We found that individuals with eating disorders reported less positive mood than HCs and individuals with BN and BED reported more negative mood and greater urges to binge than HCs. Individuals with BED generated fewer effective solutions on a binge-eating problem-solving task and had consistent respiratory sinus arrhythmia differences, which may indicate emotion regulation difficulties.

High-Level Executive Functions: A Possible Role of Sex and Weight Condition in Planning and Decision-Making Performances.

Evidence indicates an association between executive functioning and increased weight, with different patterns ascribed to individual differences (sex, age, lifestyles). This study reports on the relationship between high-level executive functions and body weight. Sixty-five young adults participated in the study: 29 participants (14 males, 15 females) in the normal weight range; 36 participants (18 males, 18 females) in the overweight range. The Iowa Gambling Task (IGT) and Tower of London Task were administered to assess decision making and planning. Planning did not differ in individuals in the normal-weight and overweight groups, and no difference emerged between females and males. However, normal and overweight males and females had different patterns in decision making. On the long-term consequences index of the IGT, females reported lower scores than males. Males in the overweight range had a lower long-term consequences index on the IGT than normal-weight males, while this pattern did not emerge in females. These findings suggest that decision-making responses may differ in the overweight relative to healthy weight condition, with a different expression in males and females. This pattern should be considered in weight loss prevention strategies, possibly adopting different approaches in males and females.

Evaluation of a Refined Implantable Resonator for Deep-Tissue EPR Oximetry in the Clinic.

OBJECTIVES: (1) Summarize revisions made to the implantable resonator (IR) design and results of testing to characterize biocompatibility;(2) Demonstrate safety of implantation and feasibility of deep tissue oxygenation measurement using electron paramagnetic resonance (EPR) oximetry. STUDY DESIGN: In vitro testing of the revised IR and in vivo implantation in rabbit brain and leg tissues. METHODS: Revised IRs were fabricated with 1-4 OxyChips with a thin wire encapsulated with two biocompatible coatings. Biocompatibility and chemical characterization tests were performed. Rabbits were implanted with either an IR with 2 oxygen sensors or a biocompatible-control sample in both the brain and hind leg. The rabbits were implanted with IRs using a catheter-based, minimally invasive surgical procedure. EPR oximetry was performed for rabbits with IRs. Cohorts of rabbits were euthanized and tissues were obtained at 1 week, 3 months, and 9 months after implantation and examined for tissue reaction. RESULTS: Biocompatibility and toxicity testing of the revised IRs demonstrated no abnormal reactions. EPR oximetry from brain and leg tissues were successfully executed. Blood work and histopathological evaluations showed no significant difference between the IR and control groups. CONCLUSIONS: IRs were functional for up to 9 months after implantation and provided deep tissue oxygen measurements using EPR oximetry. Tissues surrounding the IRs showed no more tissue reaction than tissues surrounding the control samples. This pre-clinical study demonstrates that the IRs can be safely implanted in brain and leg tissues and that repeated, non-invasive, deep-tissue oxygen measurements can be obtained using in vivo EPR oximetry.

First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip.

OBJECTIVE: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the 'OxyChip', as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing. METHODS: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry. RESULTS: Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4-128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6-73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5-144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation. CONCLUSIONS: Measurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes.

Monoclonal Antibodies to S and N SARS-CoV-2 Proteins as Probes to Assess Structural and Antigenic Properties of Coronaviruses.

Antibodies targeting the spike (S) and nucleocapsid (N) proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential tools. In addition to important roles in the treatment and diagnosis of infection, the availability of high-quality specific antibodies for the S and N proteins is essential to facilitate basic research of virus replication and in the characterization of mutations responsible for variants of concern. We have developed panels of mouse and rabbit monoclonal antibodies (mAbs) to the SARS-CoV-2 spike receptor-binding domain (S-RBD) and N protein for functional and antigenic analyses. The mAbs to the S-RBD were tested for neutralization of native SARS-CoV-2, with several exhibiting neutralizing activity. The panels of mAbs to the N protein were assessed for cross-reactivity with the SARS-CoV and Middle East respiratory syndrome (MERS)-CoV N proteins and could be subdivided into sets that showed unique specificity for SARS-CoV-2 N protein, cross-reactivity between SARS-CoV-2 and SARS-CoV N proteins only, or cross-reactivity to all three coronavirus N proteins tested. Partial mapping of N-reactive mAbs were conducted using truncated fragments of the SARS-CoV-2 N protein and revealed near complete coverage of the N protein. Collectively, these sets of mouse and rabbit monoclonal antibodies can be used to examine structure/function studies for N proteins and to define the surface location of virus neutralizing epitopes on the RBD of the S protein.

Diagnosis and management of oral cavity lipoblastoma and lipoblastomatosis in an 8-month-old boy.

Lipoblastoma/lipoblastomatosis presents some unique diagnostic and therapeutic challenges when encountered in the oral cavity. In these rare cases, diagnostic confirmation with molecular testing and a conservative surgical resection can contribute to successful management.

Emotion and Psychophysiological Responses During Emotion-Eliciting Film Clips in an Eating Disorders Sample.

Background: Greater vulnerability to negative emotions appears associated with the development and maintenance of eating disorders (EDs). A systematic review of psychophysiological studies using emotion-eliciting film clips reveals that there are no studies examining the effect of standardized validated film clips on psychophysiological response across a range of EDs. Methods: Using standardized validated film clips without ED-specific content, the present study examined self-reported emotions and psychophysiological responses of women with Binge-Eating Disorder (BED; n = 57), Anorexia Nervosa (AN; n = 16), Bulimia Nervosa (BN; n = 34), and Healthy Controls (HCs; n = 26) at Baseline, during Neutral, Sad, Happy, and Fear-inducing film clips, and at Recovery. Results: Throughout the protocol, the ED groups reported significantly greater sadness and anxiety than HCs. Additionally, the AN group reported more fear, the BED group more frustration, and the BED and BN groups more tension than HCs. Compared to HCs, the BED group reported stronger urges to binge throughout the protocol, whereas BN group reported stronger urges to binge relative to the HC group only at Baseline and Recovery. The BN and BED groups experienced decreased urges to binge during all film clips compared to Baseline. Respiratory Sinus Arrhythmia levels were significantly lower in the BED group compared to HCs and the BN group throughout the protocol. Discussion: Standardized validated film clips can be used to elicit expected self-reported emotion and skin conductance responses in ED groups, although individuals with EDs compared HCs report greater negative emotions. Interestingly, film clips appeared to reduce urges to binge in binge-eating groups.

When is surgical resection alone appropriate treatment for pediatric nodular lymphocyte-predominant Hodgkin lymphoma?

The surgeon's role in the management of lymphoma is typically limited to performing biopsies for diagnosis. Most patients with lymphoma are treated with chemotherapy and/or radiation, but in rare cases, lymphoma can be primarily treated with surgery. We present a case of nodular lymphocyte-predominant Hodgkin lymphoma in a 4-year-old child with cervical adenopathy and discuss initial treatment with surgery alone. Surgery as primary treatment avoids the serious long-term sequelae of chemotherapy and radiation, and reserves those options for possible future recurrences; however, this approach should be reserved for patients with limited and low-risk disease. This case report reviews the pros and cons of treating early-stage nodular lymphocyte-predominant Hodgkin lymphoma in a pediatric patient with surgery alone.