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Claudia SP Fernandez,1 Melissa A Green,2 Cheryl C Noble,3 Kathleen Brandert,4 Katherine Donnald,5 Madison R Walker,1 Ellison Henry,1 Angela Rosenberg,5 Gaurav Dave,2 Giselle Corbie-Smith2 1Department of Maternal and Child Health, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Center for Health Equity Research, UNC School of Medicine Department of Social Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 3Private Evaluation Consultancy, Scotts Valley, CA, USA; 4Office of Public Health Practice and Department of Health Promotion, Social and Behavioral Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA; 5Inside Out Enneagram Consulting, Pittsboro, NC, USACorrespondence: Claudia SP FernandezDepartment of Maternal and Child Health, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 426 Rosenau Hall, 134 Dauer Drive, Chapel Hill, NC, 27599, USATel +1 919-843-5560Fax +1-919-966-0458Email Claudia_Fernandez@unc.eduIntroduction: Since the inception of distance-based teaching modalities, a debate has ensued over the quality of online versus in-person instruction. Due to the COVID-19 pandemic, a number of teaching environments—including leadership development trainings for post-graduate learners—have been thrust into exploring the virtual learning environment more thoroughly. One three-year leadership development program for interdisciplinary healthcare professionals transitioned three simultaneous leadership intensives from in-person to online in the spring of 2020.Methods: Documented changes in overall training length, session length, and session format are described. Further, evaluative data were collected from participants at both retreats via post-session surveys. Ninety-three participants attended the 2019 retreat, and 92 participants attended the 2020 virtual retreat. Quantitative data of three rating questions per session are reported: 1) overall session satisfaction, 2) participants’ reported knowledge gain, and 3) participants’ reported ability gain. Qualitative data were obtained via two open-ended feedback questions per session.Results: In comparing pre/post scores for knowledge and ability, participants had meaningful (and in some cases higher) self-reported gains in knowledge and ability measures in the online environment, as compared to the in-person environment. Participants reported statistically significant gains in all sessions for both knowledge and ability. Qualitative data of participant feedback identified a number of positive themes similar across the in-person and virtual settings. Negative or constructive feedback of the virtual setting included time constraint issues (eg too much content in one session, a desire for more sessions overall), technical difficulties, and the loss of social connection and networking with fellow participants as compared to in-person trainings.Discussion: While meaningful shifts in knowledge and ability ratings indicate that the transition to successful online learning is possible, several disadvantages remain. The preparation time for both faculty and participants was considerable, there is a need to reduce overall content in each session due to time restraints, and participants indicated feeling the loss of one-on-one connections with their peers in the training. Lessons learned of transitioning leadership training from in-person to an online experience are highlighted.Keywords: leadership, training, virtual, clinical scholars, pandemic, workforce development

BackgroundImmunosuppression associated with surgery may predispose to increased tumour growth or recurrence. Lymphocytes are central components of the immune network, signalling specific and non-specific responses in tumour immunosurveillance. This study was therefore designed to compare the effects of minimally invasive and conventional approaches to major thoracic surgery on lymphocyte populations and oxidative activity. Patients and methodsThe effects of conventional and minimally invasive video-assisted thoracic surgery (VATS) on the numbers and types of circulating lymphocytes and on lymphocyte oxidation were compared in a prospective randomized study of 41 patients undergoing lobectomy for peripheral bronchogenic carcinoma. Blood taken pre-operatively and on days 2 and 7 post-operatively was analysed for T (CD4, CD8), B (CD19) and natural killer (NK) (CD56, CD16) cell counts and for lymphocyte oxidative activity. Leucocyte numbers were compared with pre-surgical values and oxidative rate with healthy donor controls. ResultsLymphocyte counts fell after surgery; VATS was associated with less effect on circulating T (CD4) cells at 2 days and on NK lymphocytes at 7 days post-surgery. Lymphocyte oxidation was less suppressed in the VATS group 2 days after surgery. In general, post-surgical changes in key cells of cellular immunity were smaller in the VATS group, and recovery to normal levels was more rapid. ConclusionThe degree of invasiveness of thoracic surgery may influence the extent of immunosuppression in patients undergoing pulmonary lobectomy for pulmonary neoplasm. [ABSTRACT FROM AUTHOR]

The continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the recently circulating Omicron sub-lineages BA.2.86 and JN.1. Here, we report the isolation of broad and potent neutralizing human mAbs (HuMabs) from a healthcare worker infected with SARS-CoV-2 early in the pandemic. These include a genetically unique HuMab, named K501SP6, which can neutralize different Omicron sub-lineages, including BQ.1, XBB.1, BA.2.86 and JN.1, by targeting a highly conserved epitope on the N terminal domain, as well as an RBD-specific HuMab (K501SP3) with high potency towards earlier circulating variants that was escaped by the more recent Omicron sub-lineages through spike F486 and E484 substitutions. Characterizing SARS-CoV-2 spike-specific HuMabs, including broadly reactive non-RBD-specific HuMabs, can give insight into the immune mechanisms involved in neutralization and immune evasion, which can be a valuable addition to already existing SARS-CoV-2 therapies., (© 2024. The Author(s).)

Background: Electronic patient-reported outcome measures (ePROMs) benefit adult cancer care, but their use in pediatric cancer care is limited., Objectives: To explore the feasibility of collecting weekly ePROMs from pediatric cancer patients and/or their caregivers and to describe children's levels of symptom burden, distress, and cancer-related quality of life., Methods: A prospective and longitudinal cohort study was undertaken at one tertiary children's cancer center. Children (2-18 years)/caregivers completed ePROMs with validated measures for distress, symptom burden, and cancer-related quality of life weekly for 8 weeks., Results: Seventy children/caregivers participated in the study, and 69% completed ePROMs at all 8 weeks. Distress and cancer-related quality of life significantly improved over time. However, at week 8, almost half of the participants still reported high levels of distress. Symptom burden decreased over time, with the youngest and the oldest age groups (2-3 and 13-18 years) reporting the highest number of symptoms with severe burden., Conclusions: Weekly collection of ePROMs in pediatric cancer care is feasible. Although distress, quality of life, and symptom burden improve over time, there is a need for timely assessment and interventions to improve symptoms, high levels of distress, and issues that negatively affect quality of life., Implications for Practice: Nurses are ideally placed to intervene, assess, and monitor symptoms and to provide symptom management advice to pediatric cancer patients and caregivers. Findings from this study may inform the design of models of pediatric cancer care to improve communication with the healthcare team and patient experience of care., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: In individuals highly exposed to HCV, reinfection is common, suggesting that natural development of sterilising immunity is difficult. In those that are reinfected, some will develop a persistent infection, while a small proportion repeatedly clear the virus, suggesting natural protection is possible. The aim of this study was to characterise immune responses associated with rapid natural clearance of HCV reinfection., Methods: Broad neutralising antibodies (nAbs) and Envelope 2 (E2)-specific memory B cell (MBC) responses were examined longitudinally in 15 individuals with varied reinfection outcomes., Results: Broad nAb responses were associated with MBC recall, but not with clearance of reinfection. Strong evidence of antigen imprinting was found, and the B-cell receptor repertoire showed a high level of clonality with ongoing somatic hypermutation of many clones over subsequent reinfection events. Single-cell transcriptomic analyses showed that cleared reinfections featured an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection., Conclusions: MBC quality, but not necessarily breadth of nAb responses, is important for protection against antigenically diverse variants, which is encouraging for HCV vaccine development., Impact and Implications: HCV continues to have a major health burden globally. Limitations in the health infrastructure for diagnosis and treatment, as well as high rates of reinfection, indicate that a vaccine that can protect against chronic HCV infection will greatly complement current efforts to eliminate HCV-related disease. With alternative approaches to testing vaccines, such as controlled human inoculation trials under consideration, we desperately need to identify the correlates of immune protection. In this study, in a small but rare cohort of high-risk injecting drug users who were reinfected multiple times, breadth of neutralisation was not associated with ultimate clearance of the reinfection event. Alternatively, characteristics of the HCV-specific B-cell response associated with B-cell proliferation were. This study indicates that humoral responses are important for protection and suggests that for genetically very diverse viruses, such as HCV, it may be beneficial to look beyond just antibodies as correlates of protection., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN., Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN., Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations., Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN., Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Background: The Hmong population constitutes an independent ethnic group historically dispersed throughout Southeast Asia; fallout from the Vietnam War led to their forced migration to the United States as refugees. This study seeks to investigate characteristics of the Hmong population diagnosed with in colorectal cancer (CRC) as well as survival within this population., Methods: Cases of colon and rectal adenocarcinoma diagnosed between 2004 and 2017 were identified from the National Cancer Database (NCDB). Summary statistics of demographic, clinical, socioeconomic, and treatment variables were generated with emphasis on age and stage at the time of diagnosis. Cox-proportional hazard models were constructed for survival analysis., Results: Of 881,243 total CRC cases within the NCDB, 120 were classified as Hmong. The average age of Hmong individuals at diagnosis was 58.9 years compared 68.7 years for Non-Hispanic White (NHW) individuals (p < 0.01). The distribution of analytic stage differed between the Hmong population and the reference NHW population, with 61.8% of Hmong individuals compared to 45.8% of NHW individuals with known stage being diagnosed at stage III or IV CRC compared to 0, I, or II (p = 0.001). However, there was no difference in OS when adjusting for potential confounders (HR 1.00 [0.77-1.33]; p = 0.998)., Conclusions: Hmong individuals are nearly a decade younger at the time of diagnosis of CRC compared to the NHW individuals. However, these data do not suggest an association between Hmong ethnicity and overall survival, when compared to the NHW population., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Clinical immunity to malaria develops slowly after repeated episodes of infection and antibodies are essential in naturally acquired immunity against malaria. However, chronic exposure to malaria has been linked to perturbation in B-cell homeostasis with the accumulation of atypical memory B cells. It is unclear how perturbations in B cell subsets influence antibody breadth, avidity, and function in individuals naturally exposed to malaria. We show that individuals living in high malaria transmission regions in Ghana have higher Plasmodium falciparum merozoite antigen-specific antibodies and an increased antibody breadth score but lower antibody avidities relative to low transmission regions. The frequency of circulating atypical memory B cells is positively associated with an individual's antibody breadth. In vitro growth inhibition is independent of the ability to bind to free merozoites but associated with the breadth of antibody reactivity in an individual. Taken together, our data shows that repeated malaria episodes hamper the development of high avid antibodies which is compensated for by an increase in antibody breadth. Our results provide evidence to reinforce the idea that in regions with high malaria prevalence, repeated malaria infections lead to the broadening of antibody diversity and the continued presence of atypical memory B cell populations., (© 2024. The Author(s).)

Background: Audit and feedback (A&F) is an implementation strategy that can facilitate implementation tailoring by identifying gaps between desired and actual clinical care. While there are several theory-based propositions on which A&F components lead to better implementation outcomes, many have not been empirically investigated, and there is limited guidance for stakeholders when applying A&F in practice. The current study aims to illustrate A&F procedures in six community mental health clinics, with an emphasis on reporting A&F components that are relevant to theories of how feedback elicits behavior change., Methods: Six clinics from a larger trial using a tailored approach to implement measurement-based care (MBC) were analyzed for feedback content, delivery mechanisms, barriers to feedback, and outcomes of feedback using archival data. Pattern analysis was conducted to examine relations between A&F components and changes in MBC use., Results: Several sites utilized both aggregate and individualized data summaries, and data accuracy concerns were common. Feedback cycles featuring individual-level clinician data, data relevant to MBC barriers, and information requested by data recipients were related to patterns of increased MBC use., Conclusions: These findings support extant theory, such as Feedback Intervention Theory. Mental health professionals wishing to apply A&F should consider establishing reciprocal feedback mechanisms on the quality and amount of data being received and adopting specific roles communicating and addressing data quality concerns., Trial Registration: ClinicalTrials.gov Identifier: NCT02266134., (© 2023. BioMed Central Ltd.)

Advances in neuroimaging have permitted the non-invasive examination of the human brain in pain. However, a persisting challenge is in the objective differentiation of neuropathic facial pain subtypes, as diagnosis is based on patients' symptom descriptions. We use artificial intelligence (AI) models with neuroimaging data to distinguish subtypes of neuropathic facial pain and differentiate them from healthy controls. We conducted a retrospective analysis of diffusion tensor and T1-weighted imaging data using random forest and logistic regression AI models on 371 adults with trigeminal pain (265 classical trigeminal neuralgia (CTN), 106 trigeminal neuropathic pain (TNP)) and 108 healthy controls (HC). These models distinguished CTN from HC with up to 95% accuracy, and TNP from HC with up to 91% accuracy. Both classifiers identified gray and white matter-based predictive metrics (gray matter thickness, surface area, and volume; white matter diffusivity metrics) that significantly differed across groups. Classification of TNP and CTN did not show significant accuracy (51%) but highlighted two structures that differed between pain groups-the insula and orbitofrontal cortex. Our work demonstrates that AI models with brain imaging data alone can differentiate neuropathic facial pain subtypes from healthy data and identify regional structural indicates of pain., (© 2023. The Author(s).)

Background: The development of vaccine candidates for COVID-19, and the administration of booster vaccines, has meant a significant reduction in COVID-19 related deaths world-wide and the easing of global restrictions. However, new variants of SARS-CoV-2 have emerged with less susceptibility to vaccine induced immunity leading to breakthrough infections among vaccinated people. It is generally acknowledged that immunoglobulins play the major role in immune-protection, primarily through binding to the SARS-COV-2 receptor binding domain (RBD) and thereby inhibiting viral binding to the ACE2 receptor. However, there are limited investigations of anti-RBD isotypes (IgM, IgG, IgA) and IgG subclasses (IgG1-4) over the course of vaccination and breakthrough infection., Method: In this study, SARS-CoV-2 humoral immunity is examined in a single subject with unique longitudinal sampling. Over a two year period, the subject received three doses of vaccine, had two active breakthrough infections and 22 blood samples collected. Serological testing included anti-nucleocapsid total antibodies, anti-RBD total antibodies, IgG, IgA, IgM and IgG subclasses, neutralization and ACE2 inhibition against the wildtype (WT), Delta and Omicron variants., Results: Vaccination and breakthrough infections induced IgG, specifically IgG1 and IgG4 as well as IgM and IgA. IgG1 and IgG4 responses were cross reactive and associated with broad inhibition., Conclusion: The findings here provide novel insights into humoral immune response characteristics associated with SARS-CoV-2 breakthrough infections., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Purpose: Ongoing consultation following initial training is one of the most commonly deployed implementation strategies to facilitate uptake of evidence-based practices, such as measurement-based care (MBC). Group consultation provides an interactive experience with an expert and colleagues to get feedback on actual issues faced, yet there is little research that unpacks the questions raised in consultation and what types of issues are important to address., Methods: The current study characterized the questions and concerns raised by community mental health clinicians (N = 38 across six clinics) during group consultation sessions completed as part of an MBC implementation trial. We conducted a qualitative content analysis of consultation forms completed by clinicians before each MBC consultation session., Results: Clinicians sought MBC consultation for clients across a range of ages and levels of depression severity. Qualitative results revealed five main questions and concerns in consultation sessions: (1) how to administer the PHQ-9, (2) how to review PHQ-9 scores, (3) how to respond to PHQ-9 score, (4) the types of clients for whom MBC would be appropriate, and (5) how MBC could impact a clinician's usual care., Conclusion: Findings highlight the need for ongoing consultation and limitations of workshop training alone. Practical recommendations for addressing the common questions and concerns identified are presented to support MBC use., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Trigeminal neuralgia (TN) is an orofacial pain disorder that is more prevalent in females than males. Although an increasing number of studies point to sex differences in chronic pain, how sex impacts TN patients' journeys to care has not been previously addressed. This study sought to investigate sex differences in patients' journeys to diagnosis, referral, and treatment of TN within a large national context., Methods: Patients with classic TN (n = 100; 50 females and 50 males) were randomly selected through chart reviews at the largest surgical treatment center for TN in Canada for a cross-sectional study. Statistical tests, including Welch's t-test, the chi-square test, Pearson's correlations, and analyses of covariance, were conducted with Python., Results: Key discrepancies between sexes in access to care were identified. Females had a significantly longer referral time interval (average 53.2 months vs 20.4 months, median 27.5 months vs 11.0 months, p = 0.018) and total time interval (average 121.1 months vs 67.8 months, median 78.0 months vs 45.2 months, p = 0.018) than males, despite reporting higher pain intensity at referral. Although medically intolerant patients had a significantly shorter referral time interval than medically tolerant patients (average 13.0 months vs 41.0 months, median 6.0 months vs 17.0 months, p < 0.001), medically tolerant females had a significantly longer referral time interval than medically tolerant males (average 59.9 months vs 21.7 months, median 30.0 months vs 12.0 months, p = 0.017). No statistically significant differences were detected between the sexes for diagnostic time interval (average 63.3 months vs 43.0 months, median 24.0 months vs 24.0 months, p = 0.263) or treatment time interval (average 4.6 months vs 4.7 months, median 4.0 months vs 3.0 months, p = 0.986)., Conclusions: Critical sex differences in patients' journeys to TN surgical treatment were identified, with females enduring considerably longer referral timelines and expressing significantly greater pain intensity than males at referral. Taken together, our findings suggest the presence of unconscious bias and discrimination against females and highlight the need for expediting TN treatment referral for female TN patients.

Background: Most significant change (MSC) analysis is an evaluative method used to supplement outcome and impact program evaluations. MSC stories provide mini-narratives contextualizing the effect a program had on an individual. The Clinical Scholars program evaluation team used MSC to explore learner-centric leadership outcomes of the Clinical Scholars leadership training program., Purpose of the Research: To identify thematic outcomes of trainees during the three years of their leadership training in the Clinical Scholars program., Results: We identified three central thematic areas of most significant change: (1) leadership in practice, (2) self-awareness, and (3) equity, diversity, and inclusion. Other present themes included stakeholder engagement, effective leadership, collaboration, impact, expanded influence, innovation, networking, community engagement, evidence-based, implementation science, organizational development, hope, and advocating within organizations, teams, and the community. A total of 25 mid- and advanced-career level participants represented a diverse array of disciplines within the healthcare sector., Conclusions: MSC stories represented leaders' individual and team growth due to participating in the Clinical Scholars program. Results confirmed fidelity of program implementation to the original program goals, as outlined in the grant proposal. They highlighted three critical areas of development for this cohort of Fellows., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Measurement-based care (MBC) is an evidence-based practice that is rarely integrated into psychotherapy. The authors sought to determine whether tailored MBC implementation can improve clinician fidelity and depression outcomes compared with standardized implementation., Methods: This cluster-randomized trial enrolled 12 community behavioral health clinics to receive 5 months of implementation support. Clinics randomized to the standardized implementation received electronic health record data captured with the nine-item Patient Health Questionnaire (PHQ-9), a needs assessment, clinical training, guidelines, and group consultation in MBC fidelity. Tailored implementation support included these strategies, but the training content was tailored to clinics’ barriers to MBC, and group consultation centered on overcoming these barriers. Clinicians (N=83, tailored; N=71, standardized) delivering individual psychotherapy to 4,025 adults participated. Adult patients (N=87, tailored; N=141, standardized) contributed data for depression outcome analyses., Results: The odds of PHQ-9 completion were lower in the tailored group at baseline (odds ratio [OR]=0.28, 95% CI=0.08–0.96) but greater at 5 months (OR=3.39, 95% CI=1.00–11.48). The two implementation groups did not differ in full MBC fidelity. PHQ-9 scores decreased significantly from baseline (mean±SD=17.6±4.4) to 12 weeks (mean=12.6±5.9) (p<0.001), but neither implementation group nor MBC fidelity significantly predicted PHQ-9 scores at week 12., Conclusions: Tailored MBC implementation outperformed standardized implementation with respect to PHQ-9 completion, but discussion of PHQ-9 scores in clinician-patient sessions remained suboptimal. MBC fidelity did not predict week-12 depression severity. MBC can critically inform collaborative adjustments to session or treatment plans, but more strategic system-level implementation support or longer implementation periods may be needed.

The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern (VoCs), is needed. In this study, samples collected in Denmark early in the pandemic from paucisymptomatic subjects ( n = 165) and symptomatic subjects ( n = 57) infected with SARS-CoV-2 were used to assess IgG binding and inhibition in the form of angiotensin-converting enzyme 2 receptor (ACE2) competition against the wild-type and four SARS-CoV-2 VoCs (Alpha, Beta, Gamma, and Omicron). Antibodies induced early in the pandemic via natural infection were cross-reactive and inhibited ACE2 binding of the VoC, with reduced inhibition observed for the Omicron variant. When examined longitudinally, sustained cross-reactive inhibitory responses were found to exist in naturally infected paucisymptomatic subjects. After vaccination, receptor binding domain (RBD)-specific IgG binding increased by at least 3.5-fold and inhibition of ACE2 increased by at least 2-fold. When vaccination regimens were compared (two doses of Pfizer-BioNTech BNT162b2 ( n = 50), or one dose of Oxford-AstraZeneca ChAdOx1 nCoV-19 followed by Pfizer-BioNTech BNT162b2 (ChAd/BNT) ( n = 15)), higher levels of IgG binding and inhibition were associated with mix and match (ChAd/BNT) prime-boosting and time since vaccination. These results are particularly relevant for countries where vaccination levels are low.

Abstract: Chronic pain has widespread, detrimental effects on the human nervous system and its prevalence and burden increase with age. Machine learning techniques have been applied on brain images to produce statistical models of brain aging. Specifically, the Gaussian process regression is particularly effective at predicting chronological age from neuroimaging data which permits the calculation of a brain age gap estimate (brain-AGE). Pathological biological processes such as chronic pain can influence brain-AGE. Because chronic pain disorders can differ in etiology, severity, pain frequency, and sex-linked prevalence, we hypothesize that the expression of brain-AGE may be pain specific and differ between discrete chronic pain disorders. We built a machine learning model using T1-weighted anatomical MRI from 812 healthy controls to extract brain-AGE for 45 trigeminal neuralgia (TN), 52 osteoarthritis (OA), and 50 chronic low back pain (BP) subjects. False discovery rate corrected Welch t tests were conducted to detect significant differences in brain-AGE between each discrete pain cohort and age-matched and sex-matched controls. Trigeminal neuralgia and OA, but not BP subjects, have significantly larger brain-AGE. Across all 3 pain groups, we observed female-driven elevation in brain-AGE. Furthermore, in TN, a significantly larger brain-AGE is associated with response to Gamma Knife radiosurgery for TN pain and is inversely correlated with the age at diagnosis. As brain-AGE expression differs across distinct pain disorders with a pronounced sex effect for female subjects. Younger women with TN may therefore represent a vulnerable subpopulation requiring expedited chronic pain intervention. To this end, brain-AGE holds promise as an effective biomarker of pain treatment response., (Copyright © 2022 International Association for the Study of Pain.)

Drum-drying results in pregelatinized starch with relatively low starch fragmentation and a great ability to absorb water and swell at room temperature. However, the effect of the degree of cold particle swelling and the thickening potential of drum-dried starch on its suitability as oil replacer in low-fat oil-in-water emulsions has received little attention. In this work, the potential of three pregelatinized drum-dried starches with almost identical molecular structure (as measured by size exclusion chromatography) and Water Binding Capacity (WBC), but different swelling behavior, was investigated to replace up to 60% oil in a mayonnaise-like emulsion system. The microstructure, stability, and rheology of the oil-in-water emulsions were noticeably affected by the substitution of oil with a pregelatinized drum-dried starch paste. Specifically, reduced-fat emulsions presented smaller droplet-size, a higher consistency index and increased emulsion stability, especially against freeze-thaw cycles, compared to the control full-fat mayonnaise. Importantly, the differences in cold swelling behavior (rather than simply assessing WBC) greatly influenced the consistency index and stability of low-fat emulsions, and results showed that drum-dried starch particles with high swelling potential perform better as oil replacers.

Background: Structural remodeling in chronic systolic heart failure (HF) is associated with neurohormonal and hemodynamic perturbations among HF patients presenting with cardiogenic shock (CS) and HF. Our objective was to test the hypothesis was that atrial remodeling marked by an increased right atrial volume index (RAVI) to left atrial volume index (LAVI) ratio is associated with adverse clinical outcomes in CS., Methods: Patients in this cohort were admitted to the intensive care unit with evidence of congestion (pulmonary capillary wedge pressure > 15) and cardiogenic shock (cardiac index < 2.2, systolic blood pressure < 90 mmHg, and clinical evidence supporting CS) and had an echocardiogram at the time of admission. RAVI was measured using Simpson's method in the apical four-chamber view, while LAVI was measured using the biplane disc summation method in the four and two-chamber views by two independent observers. Cox proportional hazards regression analysis was used to assess the association of RAVI-LAVI with the combined outcome of death or left ventricular assist device (LVAD)., Results: Among 113 patients (mean age 59 ± 14.9 years, 29.2% female), median RAVI/LAVI was 0.84. During a median follow-up of 12 months, 43 patients died, and 65 patients had the combined outcomes of death or LVAD. Patients with RAVI/LAVI ratio above the median had a greater incidence of death or LVAD (Log-rank p ≤ 0.001), and increasing RAVI/LAVI was significantly associated with the outcomes of death or LVAD (HR 1.71 95% CI 1.11-2.64, chi square 5.91, p = 0.010) even after adjustment for patient characteristics, echocardiographic and hemodynamic variables., Conclusion: RAVI/LAVI is an easily assessed novel echocardiographic parameter strongly associated with the survival and or the need for mechanical circulatory support in patients with CS., (© 2021. Japanese Society of Echocardiography.)

The pathogenesis of malaria is associated with blood-stage infection and there is strong evidence that antibodies specific to parasite blood-stage antigens can control parasitemia. This provides a strong rational for applying blood-stage antigen components in a multivalent vaccine, as the induced antibodies in combination can enhance protection. The Plasmodium falciparum rhoptry-associated membrane antigen (PfRAMA) is a promising vaccine target, due to its fundamental role in merozoite invasion and low level of polymorphism. Polyclonal antibodies against PfRAMA are able to inhibit P. falciparum growth and interact synergistically when combined with antibodies against P. falciparum reticulocyte-binding protein 5 (PfRh5) or cysteine-rich protective antigen (PfCyRPA). In this study, we identified a novel PfRAMA-specific mAb with neutralizing activity, which in combination with PfRh5- or PfCyRPA-specific mAbs potentiated the neutralizing effect. By applying phage display technology, we mapped the protective epitope to be in the C-terminal region of PfRAMA. Our results confirmed previous finding of synergy between PfRAMA-, PfRh5- and PfCyRPA-specific antibodies, thereby paving the way of testing these antigens (or fragments of these antigens) in combination to improve the efficacy of blood-stage malaria vaccines. The results emphasize the importance of directing antibody responses towards protective epitopes, as the majority of anti-PfRAMA mAbs were unable to inhibit merozoite invasion of erythrocytes., (© 2022. The Author(s).)

We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. We identified a lectin, SLBR-N, which binds to O-linked α2,3 sialic acids, that was able to enrich for CSCs in vitro and in vivo. This O-glycan is expressed on CD44 and promotes its interaction with hyaluronic acid, facilitating CD44 signaling and CSC properties. In contrast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC population, and it antagonizes CSC function. Collectively, our data indicate that SLBR-N can be more efficient at enriching for CSCs than CD44 itself because its use avoids the issues of CD44 splicing and glycan status. These data also reveal how differential glycosylation influences CSC fate.

Plasmodium falciparum parasites express variable surface antigens on the infected erythrocyte surface allowing adhesion to human host receptors on the blood and endothelial cells, which can result in immune evasion. One of the most studied and key antigens in adhesion is the highly polymorphic PfEMP1. However, despite the vast variation in the PfEMP1 antigens, they are the main targets of naturally acquired immunity and are therefore promising candidates for malaria vaccine development. Generating PfEMP1-specific human monoclonal antibodies from naturally immune individuals will help to determine the best targets of protection from clinical disease. Immortalization of human B cells is one of the oldest and most efficient techniques to generate human monoclonal antibodies. Nevertheless, most protocols require flow cytometry-based cell sorting, which can be a limiting factor for many laboratories. This chapter describes an efficient protocol for the generation of PfEMP1-specific human monoclonal antibodies from malaria immune individuals that can be performed without the use of advanced cell-sorting techniques., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Observational coding is the gold standard for measuring treatment fidelity; however, the intensive training needed for reliable and valid measurement has not been carefully scrutinized. A systematic review concluded there is a lack of information in published studies on how to approach training raters, and the available content suggests widely variable approaches are taken across research teams. The quality and comparability of the data produced from these treatment fidelity measures is undermined by heterogeneous training approaches occurring both within and between coding teams. No guidance for training teams to do observational coding for fidelity is currently available. The aims of the current study were to: (a) characterize expert-informed processes for observational coding regarding training, coding, and achieving reliability, and (b) generate expert recommendations for training and conducting observational coding., Method: A semi-structured interview was used to explore international CBT expert's ( N = 11) perspectives and experiences regarding observational coding training processes. A qualitative content analysis approach was used to analyze the data., Results: Experts in the study provided information about their training, coding, and reliability processes., Conclusion: Results from this study informed recommendations on how to: (a) introduce scale items, (b) anchor ratings, and (c) drift prevention., (© Copyright 2021 Springer Publishing Company, LLC.)

The highly conserved Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) is a key target for next-generation vaccines against blood-stage malaria. PfCyRPA constitute the core of a ternary complex, including the reticulocyte binding-like homologous protein 5 (PfRh5) and the Rh5-interacting protein (PfRipr), and is fundamental for merozoite invasion of erythrocytes. In this study, we show that monoclonal antibodies (mAbs) specific to PfCyRPA neutralize the in vitro growth of Ghanaian field isolates as well as numerous laboratory-adapted parasite lines. We identified subsets of mAbs with neutralizing activity that bind to distinct sites on PfCyRPA and that in combination potentiate the neutralizing effect. As antibody responses against multiple merozoite invasion proteins are thought to improve the efficacy of blood-stage vaccines, we also demonstrated that combinations of PfCyRPA- and PfRh5 specific mAbs act synergistically to neutralize parasite growth. Yet, we identified prominent strain-dependent neutralization potencies, which our results suggest is independent of PfCyRPA expression level and polymorphism, demonstrating the importance of addressing functional converseness when evaluating blood-stage vaccine candidates. Finally, our results suggest that blood-stage vaccine efficacy can be improved by directing the antibody response towards defined protective epitopes on multiple parasite antigens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Knudsen, Björnsson, Bassi, Walker, Kok, Cristinoi, Jensen and Barfod.)

Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive targeted tissue ablation technique that can be applied to the nervous system. Diffusion weighted imaging (DWI) can visualize and evaluate nervous system microstructure. Tractography algorithms can reconstruct fiber bundles which can be used for treatment navigation and diffusion tensor imaging (DTI) metrics permit the quantitative assessment of nerve microstructure in vivo . There is a need for imaging tools to aid in the visualization and quantitative assessment of treatment-related nerve changes in MRgFUS. We present a method of peripheral nerve tract reconstruction and use DTI metrics to evaluate the MRgFUS treatment effect. Materials and Methods: MRgFUS was applied bilaterally to the sciatic nerves in 6 piglets (12 nerves total). T1-weighted and diffusion images were acquired before and after treatment. Tensor-based and constrained spherical deconvolution (CSD) tractography algorithms were used to reconstruct the nerves. DTI metrics of fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivities (RD) were measured to assess acute (<1-2 h) treatment effects. Temperature was measured in vivo via MR thermometry. Histological data was collected for lesion assessment. Results: The sciatic nerves were successfully reconstructed in all subjects. Tract disruption was observed after treatment using both CSD and tensor models. DTI metrics in the targeted nerve segments showed significantly decreased FA and increased MD, AD, and RD. Transducer output power was positively correlated with lesion volume and temperature and negatively correlated with MD, AD, and RD. No correlations were observed between FA and other measured parameters. Conclusions: DWI and tractography are effective tools for visualizing peripheral nerve segments for targeting in non-invasive surgical methods and for assessing the microstructural changes that occur following MRgFUS treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Walker, Zhong, Waspe, Piorkowska, Nguyen, Anastakis, Drake and Hodaie.)

Purpose: The most common method of total wrist arthrodesis is dorsal compression plating, which can require revision for soft tissue or tendon irritation. A locked intramedullary system was developed to reduce this complication. The goal of this study was to investigate the complication rate of total wrist arthrodesis using this system in our center., Methods: A retrospective chart review of all patients undergoing intramedullary wrist arthrodesis from January 2016 to February 2018 was performed., Results: Nine wrist arthrodeses were performed with locked intramedullary wrist fusion in 5 women and 4 men. The indications for fusion included posttraumatic arthritis in 7 and inflammatory arthritis in 2. Two patients underwent primary arthrodesis and 7 had revision from prior partial wrist fusions. Local bone graft at the radiocarpal joint was used in all cases. The mean follow-up was 27 weeks. Radiocarpal fusion was achieved in 8 patients after the initial procedure and in the ninth patient after revision. There were 6 complications in 4 patients with revision reoperation required in 3. The complications were metacarpal locking screw migration in 3, metacarpal fracture in 1, radiocarpal nonunion in 1, and symptomatic middle finger carpometacarpal nonunion in 1. The revision surgeries include distal screw removal in 1, distal screw removal with replacement in 1, and bone grafting in the radiocarpal nonunion., Conclusions: Use of the locked intramedullary wrist fusion system yields high fusion rates. However, based on the high complication rate, particularly from distal screw migration, and the high revision rate in this series, we recommend caution with the use of this system., Type of Study/level of Evidence: Therapeutic V., (Copyright © 2021 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Abstract: Neurosurgical treatments for trigeminal neuralgia (TN) can provide long-lasting pain relief; however, some patients fail to respond and undergo multiple, repeat procedures. Surgical outcomes can vary depending on the type of TN, but the reasons for this are not well understood. Neuroimaging studies of TN point to abnormalities in the brainstem trigeminal fibers; however, whether this is a common characteristic of treatment nonresponse across different subtypes of TN is unknown. Here, we used diffusion tensor imaging (DTI) to determine whether the brainstem trigeminal fiber microstructure is a common biomarker of surgical response in TN and whether the extent of these abnormalities is associated with the likelihood of response across subtypes of TN. We studied 98 patients with TN (61 classical TN, 26 TN secondary to multiple sclerosis, and 11 TN associated with a solitary pontine lesion) who underwent neurosurgical treatment and 50 healthy controls. We assessed treatment response using pain intensity measures and examined microstructural features by extracting pretreatment DTI metrics from the proximal pontine segment of the trigeminal nerves. We found that microstructural abnormalities in the affected pontine trigeminal fibers (notably, lower fractional anisotropy and higher radial diffusivity) highlight treatment nonresponders (n = 47) compared with responders (n = 51) and controls, and that the degree of abnormalities is associated with the likelihood of surgical response across subtypes of TN. These novel findings demonstrate the value of DTI as an objective, noninvasive tool for the prediction of treatment response and elucidate the features that distinguish treatment responders from nonresponders in the TN population., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)