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Background: Perineural inhibitors of tumor necrosis factor have recently generated intense interest as an alternative to epidural steroid injections for lumbosacral radiculopathy.Objective: To evaluate whether epidural steroids, etanercept, or saline better improves pain and function in adults with lumbosacral radiculopathy.Design: A multicenter, 3-group, randomized, placebo-controlled trial conducted from 2008 to 2011. Randomization was computer-generated and stratified by site. Pharmacists prepared the syringes. Patients, treating physicians, and nurses assessing outcomes were blinded to treatment assignment. (ClinicalTrials.gov registration number: NCT00733096)Setting: Military and civilian treatment centers.Patients: 84 adults with lumbosacral radiculopathy of less than 6 months' duration.Intervention: 2 epidural injections of steroids, etanercept, or saline, mixed with bupivacaine and separated by 2 weeks.Measurements: The primary outcome measure was leg pain 1 month after the second injection. All patients had 1-month follow-up visits; patients whose condition improved remained blinded for the 6-month study period.Results: The group that received epidural steroids had greater reductions in the primary outcome measure than those who received saline (mean difference, -1.26 [95% CI, -2.79 to 0.27]; P = 0.11) or etanercept (mean difference, -1.01 [CI, -2.60 to 0.58]; P = 0.21). For back pain, smaller differences favoring steroids compared with saline (mean difference, -0.52 [CI, -1.85 to 0.81]; P = 0.44) and etanercept (mean difference, -0.92 [CI,-2.28 to 0.44]; P = 0.18) were observed. The largest differences were noted for functional capacity, in which etanercept fared worse than the other treatments: steroids vs. etanercept (mean difference, -16.16 [CI, -26.05 to -6.27]; P = 0.002), steroids vs. saline (mean difference, -5.87 [CI, -15.59 to 3.85]; P = 0.23), and etanercept vs. saline (mean difference, 10.29 [CI, 0.55 to 20.04]; P = 0.04). More patients treated with epidural steroids (75%) reported 50% or greater leg pain relief and a positive global perceived effect at 1 month than those who received saline (50%) or etanercept (42%) (P = 0.09).Limitation: Short-term follow-up, small sample size, and a possibly subtherapeutic dose of etanercept.Conclusion: Epidural steroid injections may provide modest short-term pain relief for some adults with lumbosacral radiculopathy, but larger studies with longer follow-up are needed to confirm their benefits.Primary Funding Source: The John P. Murtha Neuroscience and Pain Institute, International Spinal Intervention Society, and Center for Rehabilitation Sciences Research. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Sever disease is the most common cause of heel pain in athletic children. The purpose of this case report is to describe the addition of ketoprofen gel to the physical therapy intervention of a child with Sever disease. CASE DESCRIPTION: The patient was an 8-year-old girl diagnosed with Sever disease. Physical therapy intervention consisted of 6 visits over a 3-week period with traditional interventions (including rest, discontinuation of activities that aggravate the condition, hot and cold packs, heel lifts, calf stretching, and strengthening) and the addition of ketoprofen gel to reduce local inflammation and relieve pain. OUTCOMES: The patient demonstrated improvement in all outcome measures: pain rating, the Lower Extremity Functional Scale, strength, and range of motion. DISCUSSION: The child had relief of pain and returned to activities after 18 days of intervention, which was 30 days less than reports of intervention in the literature that did not include the use of ketoprofen gel. [ABSTRACT FROM AUTHOR]

Recently approved for metastatic renal cell carcinoma, this immunotherapeutic agent may soon be showing up on your unit. [ABSTRACT FROM AUTHOR]

As biologic therapies enter the mainstream for cancer and HIV treatments, clinicians need the knowledge and expertise to safely and competently care for their patients who are undergoing these therapies. This article provides an overview of the immune system, emphasizing the elements that are affected by the biologic agent Interleukin 2 (IL-2). IL-2 has been approved for use in the treatment of metastatic renal cell carcinoma and metastatic melanoma. Clinical trials currently are being conducted to determine its use in treating other cancers. The severity of the side effects of IL-2 varies with the dose, route, and schedule of administration. The most common side effects with all methods of administration are flu-like symptoms. Because the side effects of IL-2 are relatively predictable, clinical pathways offer practical tools for anticipating and managing the toxicities associated with IL-2 administration. [ABSTRACT FROM AUTHOR]

Introduction: Gene expression profiling (GEP) of primary cutaneous melanoma aims to offer prognostic and predictive information to guide clinical care. Despite limited evidence of clinical utility, these tests are increasingly incorporated into clinical care., Methods: A panel of melanoma experts from the Society of Surgical Oncology convened to develop recommendations regarding the use of GEP to guide management of patients with melanoma. The use of currently available GEP tests were evaluated in three clinical scenarios: (1) the utility in patient selection for sentinel lymph node biopsy; (2) the utility to guide surveillance; and (3) the utility to inform adjuvant therapy. As a basis for these recommendations, the panel performed a systematic review of the literature, including articles published from January 2012 until August 2023., Results: After review of 137 articles, 50 met the inclusion criteria. These articles included evidence related to three available GEP tests: 31-GEP, CP-GEP, and 11-GEP. The consensus recommendations were finalized using a modified Delphi process. The panel found that current evidence often fails to account for known clinicopathologic risk factors and lacks high-level data. The panel recognizes that the study of GEP tests is still evolving. The integration of GEP into routine clinical practice for predicting sentinel lymph node status and patient prognosis in melanoma is therefore not currently recommended., Conclusion: At present, GEP should be considered primarily an investigational tool, ideally used in the context of clinical trials or specialized research settings., (© 2024. The Author(s).)

Both goal-directed and automatic processes shape human behavior, but these processes often conflict. Behavioral control is the decision about which process guides behavior. Despite the importance of behavioral control for adaptive decision-making, its neural mechanisms remain unclear. Critically, it is unknown if there are mechanisms for behavioral control that are distinct from those supporting the formation of goal-relevant knowledge. We performed deep phenotyping of individual dopamine system function by combining multiple PET scans, fMRI, and dopaminergic drug administration in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task, with goal-directed and automatic decision-making operationalized as model-based and model-free influences on behavior. We found a double dissociation between two aspects of ventral striatal dopamine physiology: D2/3 receptor availability and dopamine synthesis capacity. Convergent and causal evidence indicated that D2/3 receptors regulate behavioral control by enhancing model-based and blunting model-free influences on behavior but do not affect model-based knowledge formation. In contrast, dopamine synthesis capacity was linked to the formation of model-based knowledge but not behavioral control. D2/3 receptors also modulated frontostriatal functional connectivity, suggesting they regulate behavioral control by gating prefrontal inputs to the striatum. These results identify central mechanisms underlying individual and state differences in behavioral control and point to striatal D2/3 receptors as targets for interventions for improving goal-directed behavior.

Background: Young women with breast cancer (YWBC; ≤40 years) often have a poorer prognosis than older women with breast cancer (OWBC; ≥65 years). We explored molecular features of tumors from YWBC and OWBC to identify a biologic connection for these patterns., Materials and Methods: We retrospectively analyzed the molecular profiles of 1879 breast tumors. Testing included immunohistochemistry (IHC), in situ hybridization (ISH), and next-generation sequencing. Statistical analyses included Pearson's chi 2 test for comparisons, with significance defined as FDR (false discovery rate)-P < .05., Results: TP53 and BRCA1 somatic mutations were more common in YWBC tumors than in OWBC tumors (53%, 42%; P = .0001, FDR-P = .0025 and 7%, 2%; P = .0001, FDR-P = .0025; respectively). Conversely, OWBC tumors had higher androgen receptor expression (55%, 45%; P = .0002, FDR-P = .0025) higher PD-L1 expression detected by IHC (8%, 5%; P = .0476, FDR-P = .2754), and more frequent PIK3CA mutations (33%, 17%; P = < .0001, FDR-P = < .0001). Among HR+/HER2- samples, YWBC had more gene amplifications in FGF3 (27%, 10%; P = .0353, FDR-P = .2462), FGF4 (27%, 9%; P = .0218, FDR-P = .1668), FGF19 (30%, 12%; P = .034, FDR-P = .2462) and CCND1 (37%, 18%; P = .0344, FDR-P = .2462) than OWBC., Conclusions: Our data suggest distinct molecular aberrations exist between YWBC and OWBC. Exploiting these molecular changes could refine our treatment strategies in YWBC and OWBC., Competing Interests: Disclosure Arielle L. Heeke: consulting (Caris Life Sciences). Wei Sha: no relevant conflicts to disclose. Rebecca Feldman: employee (Caris Life Sciences) Julie Fisher: no relevant conflicts to disclose. Lejla Hadzikadic-Gusic: no relevant conflicts to disclose. James T. Symanowski: no relevant conflicts to disclose. Richard L. White, Jr: no relevant conflicts to disclose. Antoinette R. Tan: meeting travel and accommodations (Caris Life Sciences)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Studies have shown increases in affect after acute exercise. However, the specific aspects of an exercise experience that predict or contribute to post-exercise affect remain relatively unknown. This study aimed to determine which physical (i.e., duration and intensity), contextual (i.e., social context and time of day), and psychological factors (i.e., motivation and need satisfaction) predicted post-exercise affect., Methods: In 2021, 296 gym users self-reported affect before and immediately after exercising at a gym facility. Participants also reported situational motivation towards exercise, need satisfaction (i.e., autonomy, competence, and relatedness), who they exercised with (social interaction), and the duration and perceived intensity of their exercise session. We first conducted a paired samples t-test to identify whether affect significantly increased from before to after exercise, and then a hierarchical regression model to determine which factors predicted post-exercise affect., Results: Affect significantly increased from before to after exercise (t[291] = 8.116, p < .001). Autonomous motivation (β = .23, p = <.001), autonomy satisfaction (β = .15, p = <.05), and relatedness satisfaction (β = .19, p = <.01) significantly predicted post-exercise affect, whereas duration, perceived intensity, social interaction, and time of day did not., Conclusions: People should be encouraged to engage in activities that satisfy their need for autonomy and relatedness during leisure-time (i.e., not during the workday). SO WHAT?: This approach to physical activity promotion may lead to better affective outcomes and increased adherence compared to focusing on how long, how intense, or with whom people exercise., (© 2024 The Author(s). Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Despite the growing popularity of walking sports, little is known about who is attracted to them, and what skills, motivations, and experiences encourage ongoing participation. The aim of this study was to gain an in-depth understanding of the phenomenon of walking football in Australia. The authors first conducted semistructured interviews with 53 older adults (M = 62.37 years, 30.19% female) participating in walking football in Australia. Next, they conducted thematic analysis to develop themes that represented participant perspectives. Results indicated that walking football led to several physical benefits, but the social and mental benefits seemed to be more closely associated with continued participation. The slower pace of walking football created a valuable option to engage in physical activity among those with injuries or severe health issues, as well as older adults concerned about injuries. The slower pace also shifted the focus of walking football away from fitness and ability, and toward technique and skill development, and this focus, along with the mix in abilities, led to informal coaching and mentoring roles which were highly valued among older participants. Participant views about competition in walking football were diverse, with some expressing a mild concern. Understanding such diverse experiences of walking football helps to better understand how different aspects of the sport influence the perceived benefits and likelihood of continuing for different people. Using these findings to further develop walking sports in Australia could have large impacts on the health and well-being of older people.

Background: Physical activity is beneficial to physical, social, and emotional well-being, and schools are required to provide opportunities to engage in physical activity. While physical education and school sport have been extensively researched, little is known about the value of informal, unstructured, exercise opportunities., Methods: This study involved interviews with 19 adolescent girls who attended "extra" exercise opportunities provided by their school. The 3 opportunities were: (1) informal before-school exercise sessions at school, (2) before-school sport training, and (3) externally provided exercise sessions in a community setting during school hours., Results: Students perceived all opportunities as valuable with benefits to confidence, social well-being, and emotional well-being. The informal exercise sessions held greater benefits to confidence as confidence transferred from the physical activity context into the academic classroom more so than for those participating in sport. Social benefits were greater for those exercising before school as this opportunity created new relationships with teachers and with students from other classes and year groups., Conclusions: The opportunity to engage in informal exercise with peers before school widened social networks, increased confidence, changed the overall school climate, and increased attendance., (© 2024 The Author(s). Journal of School Health published by Wiley Periodicals LLC on behalf of American School Health Association.)

Research has shown that blue space (i.e. water-based environments) can be good for physical and mental health, with one possible reason being that people are physically active when visiting blue space environments. However, little is known about how active people are when visiting blue space. We used the System for Observing Physical Activity and Recreation in Natural Areas to systematically record whether people were active while visiting eight different blue space locations in Australia. We first calculated the proportion of people who were moderately or vigorously active at each location and then conducted a series of linear regression models to determine which demographic and environmental factors predicted higher activity levels. We identified that 44% of people visiting blue space locations were active. However, there were significant interactions between both age and gender, and type of blue space. Males (β = -0.25, p = 0.018) and females (β = -0.26, p ≤ 0.001) were less active at built-up riverfronts than coastal beaches. Females were also less active at inland beaches (β = -0.15, p = 0.013) and watering holes (β = -0.20, p = 0.011) compared with coastal beaches. Children (β = 0.16, p = 0.006) and adolescents, however, were more active at inland beaches (β = 0.32, p ≤ 0.001) than coastal beaches. These results are important to consider when making decisions around access to, and infrastructure within, blue space environments, as different blue space environments influence human behaviour differently for different people., (© The Author(s) 2024. Published by Oxford University Press.)

House flies (Musca domestica L.) (Diptera: Muscidae) are challenging pests to control. Biological control using Carcinops pumilio beetles may help to reduce house fly populations. However, it is unknown if C. pumilio beetles are compatible with Beauveria bassiana, another house fly biological control option. Five strains of commercially available (GHA, HF23, and L90) and newly discovered (NFH10 and PSU1) strains of B. bassiana were used to test the comparative susceptibility of adult house flies and adult C. pumilio using different laboratory exposure methods. Adult house flies were susceptible to B. bassiana in contact filter paper assays (89%-98% mortality) and immersion assays (100% mortality) at the same 108 conidia suspension using 0.1% CapSil as an aqueous surfactant. Carcinops pumilio were less susceptible than flies to B. bassiana infection using the contact and immersion assays at the same 108 conidial concentration, with 4.4%-12.2% and 8.3%-24.6% mortality, respectively. Immersion in an aqueous conidial suspension resulted in higher mortality compared to contact with treated filter papers at the same 108 concentration with house flies and beetles. We conclude that C. pumilio can safely be used as a biological control agent for house flies with B. bassiana in animal production systems., (Published by Oxford University Press on behalf of Entomological Society of America 2024.)

High-dose (HD) IL-2 was the first immuno-oncology agent approved for treating advanced renal cell carcinoma and metastatic melanoma, but its use was limited because of substantial toxicities. Multiple next-generation IL-2 agents are being developed to improve tolerability. However, a knowledge gap still exists for the genomic markers that define the target pharmacology for HD IL-2 itself. In this retrospective observational study, we collected PBMC samples from 23 patients with metastatic renal cell carcinoma who were treated with HD IL-2 between 2009 and 2015. We previously reported the results of flow cytometry analyses. In this study, we report the results of our RNA-sequencing immunogenomic survey, which was performed on bulk PBMC samples from immediately before (day 1), during (day 3), and after treatment (day 5) in cycle 1 and/or cycle 2 of the first course of HD IL-2. As part of a detailed analysis of immunogenomic response to HD IL-2 treatment, we analyzed the changes in individual genes and immune gene signatures. By day 3, most lymphoid cell types had transiently decreased, whereas myeloid transcripts increased. Although most genes and/or signatures generally returned to pretreatment expression levels by day 5, certain ones representative of B cell, NK cell, and T cell proliferation and effector functions continued to increase, along with B cell (but not T cell) oligoclonal expansion. Regulatory T cells progressively expanded during and after treatment. They showed strong negative correlation with myeloid effector cells. This detailed RNA-sequencing immunogenomic survey of IL-2 pharmacology complements results of prior flow cytometry analyses. These data provide valuable pharmacological context for assessing PBMC gene expression data from patients dosed with IL-2-related compounds that are currently in development., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Purpose: Postmastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and improves overall survival (OS) in patients with breast cancer. Young age has been recognized as a risk factor for LRR. The primary objective of this study was to determine if recommendations for PMRT differed among patients younger than 50 years as compared to women aged 50 years or older., Methods: We reviewed medical records of patients with breast cancer who underwent mastectomy with or without PMRT from 2010 through 2018. Univariable and multivariable models were used to estimate the association of age with PMRT., Results: Of 2471 patients, 839 (34%) were <50 years; 1632 (66%) were ≥50 years. Patients <50 years had a higher percentage of grade 3 tumors, hormone receptor (HR) negative and/or Her-2/neu positive tumors, clinical stage T2/T3 tumors, and nodal involvement. Compared with patients ≥50 years, patients <50 years were more likely to undergo PMRT (OR 1.57; P = .001) and regional node irradiation (RNI) to the internal mammary nodes. Advanced clinical and pathologic stage, invasive tumor histology, the presence of lymphovascular invasion, and treatment with systemic chemotherapy were predictors of PMRT receipt for patients <50 years (P < .05). PMRT was associated with improved OS and recurrence free survival (RFS) among all patients (P < .01)., Conclusion: Patients <50 years were more likely to undergo PMRT and to receive RNI to the internal mammary nodes but were also more likely to have other risk factors for recurrence that would warrant a PMRT recommendation. PMRT improved OS and RFS for all patients., Competing Interests: Disclosure The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The assignment of structure by tandem mass spectrometry (MS/MS) relies on the interpretation of the fragmentation behavior of gas-phase ions. Mass spectra were acquired for a series of heterocyclic mimetics of acidic amino acids and a related series of nitrile amino acids. All amino acids were readily protonated or deprotonated by electrospray ionization (ESI), and distinctive fragmentation processes were observed when the ions were subjected to collision-induced dissociation (CID). The deprotonated heterocycles showed bond cleavages of the 3-hydroxyfurazan ring with formation of oxoisocyanate and the complementary deprotonated nitrile amino acid. Further fragmentation of the deprotonated nitrile amino acids was greatly dependent on the length of the alkyl nitrile side chain. Competing losses of CO 2 versus HCN occurred from α-cyanoglycinate (shortest chain), whereas water was lost from 2-amino-5-cyanopentanoate (longest chain). Interestingly, loss of acrylonitrile by a McLafferty-type fragmentation process was detected for 2-amino-4-cyanobutanoate, and several competing processes were observed for β-cyanoalanate. In one process, cyanide ion was formed either by consecutive losses of ammonia, carbon dioxide, and acetylene or by a one-step decarboxylative elimination. In another, complementary ions were obtained from β-cyanoalanate by loss of acetonitrile or HN=CHCO 2 H. Fragmentation of the protonated 3-hydroxyfurazan and nitrile amino acids resulted in the cumulative loss (H 2 O + CO), a loss that is commonly observed for protonated aliphatic α-amino acids. Overall, the distinct fragmentation behavior of the multifunctional 3-hydroxyfurazan amino acids correlated with the charged site, whereas fragmentations of the deprotonated nitrile amino acids showed cooperative interactions between the nitrile and the carboxylate groups., (© 2024 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons Ltd.)

Introduction: Breast cancer, although the second most common malignancy in women in the United States, is rare in patients under the age of 40 y. However, this young patient population has high recurrence and mortality rates, with chemotherapy frequently used as adjuvant treatment. We aimed to determine whether age is an independent predictor of chemotherapy recommendation and subsequent treatment and the relationship to Oncotype Dx (ODX) recurrence score (RS)., Methods: The National Cancer Database was retrospectively reviewed from 2010-2016 to identify women with early-stage (pT1-pT3, pN0-pN1mic, M0), hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer who underwent ODX RS testing., Results: Of 95,382 patients who met the inclusion criteria, risk groups using the traditional ODX RS cutoffs were 59% low, 33% intermediate, and 8% high. Using Trial Assigning Individualized Options for Treatment RS cutoffs, risk groups were 23% low, 62% intermediate, and 15% high. Chemotherapy recommendation decreased as age at diagnosis increased (P < 0.001). Increasing age was associated with decreased odds of chemotherapy recommendation in univariate models both continuously (odds ratio: 0.98, 95% confidence interval 0.97-0.98; P < 0.001) and categorically by decade (P < 0.001). Age by decade remained an independent prognosticator of chemotherapy recommendation (P < 0.001), adjusted for risk groups., Conclusions: Chemotherapy recommendation and treatment differs by age among patients with early-stage hormone receptor positive breast cancer who undergo ODX testing. While molecular profiling has been shown to accurately predict the benefit of chemotherapy, younger age at diagnosis is a risk factor for discordant use of ODX RS for treatment strategies in breast cancer; with patients aged 18-39 disproportionately affected., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gas phase fragmentation reactions of monoprotonated 4-(3-aminopropyl)- and 4-(4-aminobutyl)-3-hydroxyfurazan were investigated to examine potential interactions between functional groups. The two heterocyclic alkyl amines were ionized by electrospray ionization (ESI, positive mode) and fragmented using tandem mass spectrometry (MS/MS). The fragmentation pathways were characterized using pseudo MS 3 experiments, precursor-ion scans, and density functional computations. For both heterocyclic ions, loss of ammonia was the only fragmentation process observed at low collision energies. Computational analysis indicated that the most feasible mechanism was intramolecular nucleophilic displacement of ammonia from the protonated ω-aminoalkyl side chain by N5 of the furazan ring. The alkylated nitrogen in the resulting bicyclic product ion facilitated N-O bond cleavage; subsequent neutral losses of nitric oxide (NO) and carbon monoxide (CO) occurred by homolytic bond cleavages. Next in the multistep sequence, neutral loss of ethylene from a radical cation was observed. A less favorable, competing fragmentation pathway of protonated 4-(3-aminopropyl)-3-hydroxyfurazan was consistent with cleavage of the 3-hydroxyfurazan ring and losses of NO and CO. Overall, the similar fragmentation behavior found for protonated 4-(3-aminopropyl)- and 4-(4-aminobutyl)-3-hydroxyfurazan differed from that previously characterized for furazan analogs with shorter alkyl chains. These observations demonstrate that a small change in the structure of multifunctional, heterocyclic alkyl amines may significantly influence interactions between distinct functional groups and the nature of the fragmentation process., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: This study sought to identify β-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRβ), affect these targets to alter natural history or treatment response in patients., Experimental Design: In vitro experiments utilized primary desmoid cell lines to examine regulation of β-catenin targets. Relevance of results was assessed in vivo using Alliance trial A091105 correlative biopsies., Results: CTNNB1 knockdown inhibited hypoxia-regulated gene expression in vitro and reduced levels of HIF1α protein. ChIP-seq identified ABL1 as a β-catenin transcriptional target that modulated HIF1α and desmoid cell proliferation. Abrogation of either CTNNB1 or HIF1A inhibited desmoid cell-induced VEGFR2 phosphorylation and tube formation in endothelial cell co-cultures. Sorafenib inhibited this activity directly but also reduced HIF1α protein expression and c-Abl activity while inhibiting PDGFRβ signaling in desmoid cells. Conversely, c-Abl activity and desmoid cell proliferation were positively regulated by PDGF-BB. Reduction in PDGFRβ and c-Abl phosphorylation was commonly observed in biopsy samples from patients after treatment with sorafenib; markers of PDGFRβ/c-Abl pathway activation in baseline samples were associated with tumor progression in patients on the placebo arm and response to sorafenib in patients receiving treatment., Conclusions: The β-catenin transcriptional target ABL1 is necessary for proliferation and maintenance of HIF1α in desmoid cells. Regulation of c-Abl activity by PDGF signaling and targeted therapies modulates desmoid cell proliferation, thereby suggesting a reason for variable biologic behavior between tumors, a mechanism for sorafenib activity in desmoids, and markers predictive of outcome in patients., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Postnatal depression (PND) is a leading cause of illness and death among women following childbirth. Physical inactivity, sedentary behaviour, poor sleep, and sub-optimal diet quality are behavioural risk factors for PND. A feasible, sustainable, and scalable intervention to improve healthy behaviours and reduce PND symptoms among women at postpartum is needed. This study aims to examine the effectiveness of a multi-behavioural home-based program Food, Move, Sleep (FOMOS) for Postnatal Mental Health designed to improve PND symptoms in women at postpartum., Methods: This randomised clinical trial will recruit 220 Australian women (2-12 months postpartum) experiencing heightened PND symptoms (Edinburgh Postnatal Depression Scale score ≥ 10). Participants will be randomised to FOMOS or wait-list control receiving standard clinical care. FOMOS is a 6-month mobile health (mHealth) intervention targeting diet quality, physical activity, sedentary behaviour, sleep, and mental health. The intervention, informed by the Social Cognitive Theory and incorporating behaviour change techniques defined in the CALO-RE taxonomy and Cognitive Behavioural Treatment of Insomnia, provides exercise equipment, and educational/motivational material and social support via mHealth and social media. Data collection pre-intervention and at 3, 6 and 12 months will assess the primary outcome of PND symptoms and secondary outcomes (diet quality, physical activity, sitting time, sleep quality) using self-report and device measures. Process evaluation will explore acceptability, appropriateness, cost-effectiveness, feasibility, and sustainability via analytic tools, record keeping, interviews, and surveys., Discussion: If effective, FOMOS could be a feasible and potentially scalable management strategy to support improvement of health behaviours and mental health for women with PND symptoms., Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12622001079730p., 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. Published by Elsevier Inc.)

There is increasing evidence that the left lateral frontal cortex is hierarchically organized such that higher-order regions have an asymmetric top-down influence over lower order regions. However, questions remain about the underlying neuroarchitecture of this hierarchical control organization. Within the frontal cortex, dopamine plays an important role in cognitive control functions, and we hypothesized that dopamine may preferentially influence top-down connections within the lateral frontal hierarchy. Using a randomized, double-blind, within-subject design, we analyzed resting-state fMRI data of 66 healthy young participants who were scanned once each after administration of bromocriptine (a dopamine agonist with preferential affinity for D2 receptor), tolcapone (an inhibitor of catechol-O-methyltransferase), and placebo, to determine whether dopaminergic stimulation modulated effective functional connectivity between hierarchically organized frontal regions in the left hemisphere. We found that dopaminergic drugs modulated connections from the caudal middle frontal gyrus and the inferior frontal sulcus to both rostral and caudal frontal areas. In dorsal frontal regions, effectivity connectivity strength was increased, whereas in ventral frontal regions, effective connectivity strength was decreased. These findings suggest that connections within frontal cortex are differentially modulated by dopamine, which may bias the influence that frontal regions exert over each other., (© 2023 Massachusetts Institute of Technology.)

The design and performance of an apparatus for heating and cooling samples during variable temperature infrared spectroscopy studies are described. The apparatus incorporates two thermoelectric device modules in a stacked configuration. The cascaded devices are powered in parallel and contained within a metal enclosure that maintains their alignment and applies clamping pressure between them to maximize thermal conductivity. By using this apparatus, sample temperatures can be increased or decreased at 2 °C s -1 rates and isothermal temperatures can be maintained precisely (±0.1 °C). The rapid heating and cooling capabilities of the apparatus facilitate programmed temperature step heating/cooling profiles with isothermal infrared spectrum measurements at pre-selected temperatures. Using linear heating and cooling temperature ramps, subtle temperature-dependent poly(styrene) infrared spectrum changes are elucidated and correlated with sample temperature. Results obtained by using a temperature step sample heating profile are compared with those obtained by using linear temperature ramp heating and cooling to characterize silica gel dehydration and re-hydration processes. By comparing infrared spectra acquired at different temperatures while heating and cooling the sample, silica gel spectrum changes associated with water desorption/adsorption and the thermal expansion/contraction of the Si-O-Si network are differentiated.

Background: The purpose of this study was to evaluate the delay in initiating adjuvant radiation therapy (RT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer who underwent oncoplastic reduction mammoplasty (ORM) following BCS compared with a matched cohort of patients who did not undergo ORM between BCS and RT., Methods: Medical records of 112 women (56 ORMs and 56 matched non-ORMs) with carcinoma in situ or early-stage breast cancer treated with BCS were reviewed. ORM was performed in a delayed manner following BCS, allowing confirmation of negative surgical margins. Time to RT was defined as time from last oncologic surgery to start of RT., Results: The median follow-up time was 6.8 years for the ORM cohort and 6.7 years for the control non-ORM cohort. Patients who underwent ORM following BCS experienced a significant delay in initiating RT (>8 weeks) than matched patients not undergoing ORM (66% vs. 34%; p < 0.001). Wound complications occurred in 44.6% (n = 25) of patients in the ORM cohort, which were mostly minor, including delayed wound healing and/or infection (39%). There was no significant difference in local recurrence between patients in the non-ORM and ORM cohorts (p = 0.32)., Conclusions: This study demonstrates that ORM following BCS has the potential to delay RT >8 weeks, largely as a result of increased risk of wound complications; however, this delay did not impact local control. ORM can be safely considered for appropriately selected patients with breast cancer., (© 2023. Society of Surgical Oncology.)

Background: Tissue expanders in breast reconstruction are traditionally placed retropectoral. Increasingly, patients are undergoing prepectoral placement. The impact of this placement on the initiation of adjuvant treatment is unknown., Methods: A retrospective review was conducted to identify women diagnosed with breast cancer who underwent mastectomy followed by radiation and/or chemotherapy. Women were divided into 3 groups: prepectoral tissue expander placement, retropectoral tissue expander placement, and no immediate reconstruction. A treatment delay was defined as greater than 8 weeks between tissue expander placement and adjuvant therapy., Results: Of 634 women, 205 (32%) underwent tissue expander placement, and 429 (68%) did not have immediate reconstruction. Of those with tissue expanders placed, 84 (41%) had prepectoral placement, and 121 (59%) had retropectoral placement. The median time to adjuvant therapy was 49 days for the entire cohort: no reconstruction, 47 days; prepectoral, 57 days; and retropectoral, 55 days. Treatment delays were observed in 34% of women: no reconstruction, 28%; prepectoral, 51%; and retropectoral, 46% ( P < 0.001). Tissue expander placement was associated with a delay to adjuvant therapy when compared with no reconstruction ( P < 0.001). The location of the tissue expander did not impact the odds of having a delay. On multivariable analysis, having reconstruction, having postoperative infection, not undergoing chemotherapy treatment, and being a current smoker were associated with a delay to adjuvant therapy. A delay to treatment was not associated with worse survival., Conclusions: Placement of a tissue expander delayed adjuvant therapy. The location of tissue expander placement, retropectoral versus prepectoral, did not impact the time to adjuvant treatment., Competing Interests: Conflicts of interest and sources of funding: None declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There are few quality metrics and benchmarks specific to surgical oncology. Development of a surgeon-level performance metrics system based on peer comparisons is hypothesized to positively influence surgical decision-making. This study established a tracking and reporting system comprised of evidence and consensus-based metrics to assess breast care delivered by individual surgeons., Methods: Surgeons' performance is assessed by a surveillance tracking system of metrics pertaining to referrals and surgical elements. This retrospective analysis of prospectively collected breast care data reports on recurring 6-month and cumulative data from nine care locations from 2015 to 2021., Results: Breast care was provided to 6659 patients by 41 surgeons. A total of 27 breast care metrics were evaluated over 7 years. Metrics with consistent, proficient results were retired after 18 months, including the rate of core biopsy, specimen orientation, and referrals to medical oncology, genetics, and fertility, among others. In clinically node-negative, hormone receptor-positive patients 70 years of age or older, the cumulative rate of sentinel lymph node (SLN) biopsy significantly decreased by 40% over 5.5 years (p < .001). The overall breast conservation rate for T0-T2 cancer increased 10% over 7 years. At the surgeon level, improvements were made in the median number of SLNs removed and in operative note documentation., Conclusions: Implementation of a surgeon-specific, peer comparison-based metric and tracking system has yielded substantive changes in breast care management. This process and governance structure can serve as a model for quantification of breast care at other institutions and for other disease sites., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Importance: Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials., Objective: To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST)., Design, Setting, and Participants: Prospective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)-positive breast cancer with no pathologic evidence of residual disease following standard NST enrolled from March 6, 2017, to November 9, 2021. Validated PRO measures were administered at baseline and 6, 12, and 36 months post-radiotherapy. Data were analyzed from January to February 2023., Interventions: PRO measures included the Decision Regret Scale (DRS), Functional Assessment of Cancer Therapy-Lymphedema (FACT-B+4), and Breast Cancer Treatment Outcomes Scale (BCTOS)., Main Outcomes and Measures: Changes in PRO measure scores and subscores over time., Results: Among 31 patients, the median (IQR) age was 61 (56-66) years, 26 (84%) were White, and 26 (84%) were non-Hispanic. A total of 15 (48%) had triple-negative disease and 16 (52%) had ERBB2-positive disease. Decisional comfort was high at baseline (median [IQR] DRS score 10 [0-25] on a 0-100 scale, with higher scores indicating higher decisional regret) and significantly increased over time (median [IQR] DRS score at 36 months, 0 [0-20]; P < .001). HRQOL was relatively high at baseline (median [IQR] FACT-B composite score 121 [111-134] on a 0-148 scale, with higher scores indicating higher HRQOL) and significantly increased over time (median [IQR] FACT-B score at 36 months, 128 [116-137]; P = .04). Perceived differences between the affected breast and contralateral breast were minimal at baseline (median [IQR] BCTOS score 1.05 [1.00-1.23] on a 1-4 scale, with higher scores indicating greater differences) and increased significantly over time (median [IQR] BCTOS score at 36 months, 1.36 [1.18-1.64]; P < .001). At 36 months postradiotherapy, the cosmetic subscore was 0.45 points higher than baseline (95% CI, 0.16-0.74; P = .001), whereas function, pain, and edema subscores were not significantly different than baseline., Conclusions and Relevance: In this nonrandomized phase 2 clinical trial, analysis of PROs demonstrated an overall positive experience for trial participants, with longitudinal improvements in decisional comfort and overall HRQOL over time and minimal lasting adverse effects of therapy., Trial Registration: ClinicalTrials.gov Identifier: NCT02945579.

The use of English as the common language of science represents a major impediment to maximising the contribution of non-native English speakers to science. Yet few studies have quantified the consequences of language barriers on the career development of researchers who are non-native English speakers. By surveying 908 researchers in environmental sciences, this study estimates and compares the amount of effort required to conduct scientific activities in English between researchers from different countries and, thus, different linguistic and economic backgrounds. Our survey demonstrates that non-native English speakers, especially early in their careers, spend more effort than native English speakers in conducting scientific activities, from reading and writing papers and preparing presentations in English, to disseminating research in multiple languages. Language barriers can also cause them not to attend, or give oral presentations at, international conferences conducted in English. We urge scientific communities to recognise and tackle these disadvantages to release the untapped potential of non-native English speakers in science. This study also proposes potential solutions that can be implemented today by individuals, institutions, journals, funders, and conferences. Please see the Supporting information files (S2-S6 Text) for Alternative Language Abstracts and Figs 5 and 6., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Amano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)