Search

Introduction: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown. Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry). Results: We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis. Median overall survival from metastatic diagnosis was 7.3 (95% confidence interval [CI]: 4.6–12.8) months. Of patients with metastatic disease, 58 (78%) received first-line systemic treatment. Most often, patients received chemo and immunotherapy combination (41%), chemotherapy alone (33%), or immunotherapy alone (16%). Median progression-free survival from start of systemic therapy was 1.9 (95% CI: 1.4–14.5) months for chemo and immunotherapy, 1.6 (95% CI: 1.1–5.8) months for chemotherapy, and 3.3 (95% CI: 1.2–undefined) months for immunotherapy alone. Five patients had durable responses (≥2 y); all received immunotherapy as part of first-line regimens. Nine (16%) of 55 tumor samples tested had programmed death-ligand 1 expression more than or equal to 50%, with 24 (44%) negative samples. Tumor mutational burden was available in 48 cases (52%), and median was 10.5 (range: 2–48) mutations per megabase. Conclusions: This multi-institution retrospective cohort analysis revealed a population of patients with short progression-free survival to standard therapies and poor overall survival. A few patients had remarkable response to regimens including immunotherapy. Prospective clinical studies are urgently needed to identify better therapeutic approaches to treat this aggressive malignancy, and this analysis may serve as a benchmark for future clinical trial design.

Purpose: Determine if there is a difference in adverse events (AE) between right or left hepatic percutaneous biliary drain placement (PTBD) in patients with biliary strictures. Materials & methods: This retrospective study included patients with benign or malignant biliary stricture treated with PTBD at a single institution from 7/28/2004–3/30/2021. 357 patients met inclusion criteria, 77 (21.6 %) had PTBD on the left and 280 (78.4 %) on the right. AEs associated with the initial drain placement or during subsequent intervention were collected and categorized. AEs that were grouped as periprocedural included: surgery, infection, hemorrhage, and drain failure. AEs in the postprocedural group included: chills, catheter displacement, cholangitis, biliary stones, drain malfunction, fever resolving without treatment, and pericatheter leakage. Surgery was considered a major AE and the remaining AEs were categorized as minor. Statistical analyses were performed using Logistic Regression Analysis and p-values less than 0.05 were considered statistically significant. Results: Overall, there was no statistically significant difference in AEs between right and left drains in the periprocedural and postprocedural period (p = 0.832, OR = 0.95 and p = 0.808, OR = 0.93 respectively). When analyzing minor AEs individually, only cholangitis occurred at a higher rate on the right side (p = 0.033, OR = 0.43). There was no statistical difference in the rate of major AEs in the periprocedural period between left and right drains (p = 0.311, OR = 1.37). Conclusion: Current literature is equivocal when comparing right versus left percutaneous biliary drains. This analysis describes no statistically significant difference in AEs between right and left hepatobiliary drains aside from slightly higher incidence of cholangitis for right sided drains.

Purpose: A scoring mechanism called the scorecard that objectively quantifies the dosimetric plan quality of pancreas stereotactic body radiation therapy treatment plans is introduced. Methods and Materials: A retrospective analysis of patients with pancreatic ductal adenocarcinoma receiving stereotactic body radiation therapy at our institution between November 2019 and November 2020 was performed. Ten patients were identified. All patients were treated to 36 Gy in 5 fractions, and organs at risk (OARs) were constrained based on Alliance A021501. The scorecard awarded points for OAR doses lower than those cited in Alliance A021501. A team of 3 treatment planners and 2 radiation oncologists, including a physician resident without plan optimization experience, discussed the relative importance of the goals of the treatment plan and added additional metrics for OARs and plan quality indexes to create a more rigorous scoring mechanism. The scorecard for this study consisted of 42 metrics, each with a unique piecewise linear scoring function which is summed to calculate the total score (maximum possible score of 365). The scorecard-guided plan, the planning and optimization for which were done exclusively by the physician resident with no prior plan optimization experience, was compared with the clinical plan, the planning and optimization for which were done by expert dosimetrists, using the Sign test. Results: Scorecard-guided plans had, on average, higher total scores than those clinically delivered for each patient, averaging 280.1 for plans clinically delivered and 311.7 for plans made using the scorecard (P = .003). Additionally, for most metrics, the average score of each metric across all 10 patients was higher for scorecard-guided plans than for clinically delivered plans. The scorecard guided the planner toward higher coverage, conformality, and OAR sparing. Conclusions: A scorecard tool can help clarify the goals of a treatment plan and provide an objective method for comparing the results of different plans. Our study suggests that a completely novice treatment planner can use a scorecard to create treatment plans with enhanced coverage, conformality, and improved OAR sparing, which may have significant effects on both tumor control and toxicity. These tools, including the scorecard used in this study, have been made freely available.

This case presents a family with multiple individuals diagnosed with congenital heart disease (CHD) secondary to a novel TAK1-binding protein 2 pathogenic variant. This case advocates the use of cardiovascular genetic testing in individuals with CHD as part of a comprehensive approach to managing infants with CHD. (Level of Difficulty: Advanced.)

Major depressive disorder in children and adolescents is a common condition that affects physical, emotional, and social development. Risk factors include a family history of depression, parental conflict, poor peer relationships, deficits in coping skills, and negative thinking. Diagnostic criteria are the same for children and adults, with the exception that children and adolescents may express irritability rather than sad or depressed mood, and weight loss may be viewed in terms of failure to reach appropriate weight milestones. Treatment must take into account the severity of depression, suicidality, developmental stage, and environmental and social factors. Cognitive behavior therapy and interpersonal therapy are recommended for patients with mild depression and are appropriate adjuvant treatments to medication in those with moderate to severe depression. Pharmacotherapy is recommended for patients with moderate or severe depression. Tricyclic antidepressants are not effective in children and adolescents. Antidepressants have a boxed warning for the increased risk of suicide; therefore, careful assessment, follow-up, safety planning, and patient and family education should be included when treatment is initiated. [ABSTRACT FROM AUTHOR]

To establish normative data for tests of verbal and non-verbal memory for midlife Australian-born women, and in so doing investigate factors which contribute to variation in test performance. Two hundred and fifty-seven healthy women aged 56-67 years (mean age 60), who are participating in the Melbourne Women's Midlife Longitudinal Health Project, were administered two word list learning tasks, a story recall task (the East Boston Memory Test) and the Faces subtest from the Wechsler Memory Scale III as part of a larger neuropsychological battery. Word list learning tasks consisted of either 16 semantically related words, derived from the California Verbal Learning Test II, or a list of 10 unrelated words. Mood was assessed by the Center for Epidemiological Studies Depression questionnaire. Education was significantly related to memory performance and there was a non-significant trend for test scores to decline with age. Mood was unrelated to test performance. A confirmatory factor analysis indicated a clear distinction between verbal and non-verbal memory performances. Mean scores were stratified by education (less than 12 years vs. 12 or more years) and age (56-59 vs. 60-67 years), and scaled normative data were constructed for all the tests. This study provides education-based normative data for tests of verbal and non-verbal memory for midlife Australian women. The establishment of population-based normative data will facilitate future investigations of ageing and dementia in Australian women. [ABSTRACT FROM AUTHOR]

PURPOSE: To provide evidence for the utility of a single item measure designed to quantify disability in the past 30 days. METHOD: Australian data from studies comprising a community-dwelling elderly sample (N = 328) and a sample of chronic osteoarthritis (OA) patients (N = 119) are reported. Degree of disability was classified as 0-30 days, 0 vs. 1 or more days, and 0-9 vs. 10 or more days. Associations between disability and a range of demographic, health-related, and psychological variables were assessed. RESULTS: Participants with OA reported a significantly higher level of disability than participants from the community sample regardless of how disability was classified. Modest levels of association were noted between the number of disability days (0-30) and both health and psychological indices in both samples. The three alternative classifications of disability made little difference to the significance of associations. On balance, the comparison of 0-9 vs. 10 or more days appeared the more predictive classification of disability. CONCLUSIONS: The performance of the single item measure of disability was generally very satisfactory. Future investigations into the clinical application of the item across a range of patient groups are encouraged. [ABSTRACT FROM AUTHOR]

The focus of the study was the effect on spouse dementia caregivers of relinquishing care. The study used a longitudinal design, in which a group of 150 dementia caregivers were interviewed 2 years apart (designated Time 1 and Time 2), with data collected from both continuing caregivers and those who had relinquished care. The aims were to determine the extent to which changes over time in quality of life differed between continuing caregivers, those who had yielded to formal care, and those who had been widowed; and to examine whether change in quality of life variables was associated with time since yielding to formal care and time since death of the spouse. Quality of life was defined in terms of health status, psychological well-being, and activity participation. All participants were interviewed in their own homes. Three groups of participants were identified at Time 2: those who continued to provide care for their spouses (n=60); those who had yielded their caregiver role by admitting their spouses to permanent residential care (n=53); and those who had admitted their spouses to permanent institutional care, but whose spouse had then died (n=37). Different patterns of quality of life changes were observed between the three groups, with both positives and negatives associated with disengagement from the caregiving role. Positive changes were particularly evident in psychological well-being and activity participation. These findings were discussed in terms of their relevance for a life transitions approach to the relinquishment of caregiving. [ABSTRACT FROM AUTHOR]

Background: Remediation and early intervention for family medicine residents who experience performance problems represent a challenge for programs, faculty, and residents. Some evidence suggests that identifying those at risk for performance problems and providing support early may prevent more serious issues later in residency., Objectives: We wanted to explore the perspectives of content experts to identify best practices for early intervention and remediation to address common challenges and create a framework for more effective and inclusive early intervention and remediation., Methods: We used a Delphi approach to identify themes and best practices for early intervention and remediation, including qualitative interviews, identification of themes, clarification of essential practices, and confirmation of agreement with core medical faculty., Results: Our qualitative interviews and Delphi methodology identified best practices in five main categories: (a) early assessment and identification, (b) feedback, (c) resident engagement, (d) intervention strategies and resources, and (e) documentation. From an initial pool of 38 recommendations, we identified a final group of 11 practices that generated broad agreement among behavioral science faculty and core medical faculty., Conclusions: Key principles for early intervention and remediation include early skill assessment, data-driven feedback, collaborative processes, diverse resources, clear documentation, and faculty training for providing actionable feedback. While our Delphi study provided in-depth insights into various programs' practices, it may not capture unique practices across all programs. Future research on early intervention and remediation should explore current practices, aiming for specific, collaborative, and transparent processes, with insights from experienced faculty, to enhance equity and effectiveness.

Background: Despite being recognised as a global problem, our understanding of human-mediated antimicrobial resistance (AMR) spread to remote regions of the world is limited. Antarctica, often referred to as "the last great wilderness", is experiencing increasing levels of human visitation through tourism and expansion of national scientific operations. Therefore, it is critical to assess the impact that these itinerant visitors have on the natural environment. This includes monitoring human-mediated AMR, particularly around population concentrations such as visitor sites and Antarctic research stations. This study takes a sequencing discovery-led approach to investigate levels and extent of AMR around the Rothera Research Station (operated by the UK) on the Antarctic Peninsula., Results: Amplicon sequencing of biofilms and sediments from the vicinity of Rothera Research Station revealed highly variable and diverse microbial communities. Analysis of AMR genes generated from long-reads Nanopore MinION sequencing showed similar site variability in both drug class and resistance mechanism. Thus, no site sampled was more or less diverse than the other, either in the biofilm or sediment samples. Levels of enteric bacteria in biofilm and sediment samples were low at all sites, even in biofilm samples taken from the station sewage treatment plant (STP). It would appear that incorporation of released enteric bacteria in wastewater into more established biofilms or associations with sediment was poor. This was likely due to the inactivation and vulnerability of these bacteria to the extreme environmental conditions in Antarctica., Conclusions: Our results suggest minimal effect of a strong feeder source (i.e. sewage effluent) on biofilm and sediment microbial community composition, with each site developing its unique niche community. The factors producing these niche communities need elucidation, alongside studies evaluating Antarctic microbial physiologies. Our data from cultivated bacteria show that they are highly resilient to different environmental conditions and are likely to thrive in a warmer world. Our data show that AMR in the Antarctic marine environment is far more complex than previously thought. Thus, more work is required to understand the true extent of the Antarctic microbiota biodiversity, their associated resistomes and the impact that human activities have on the Antarctic environment., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Higher prevalence of multiple sclerosis at higher latitudes is associated with reduced sunlight during childhood. Alterations in inflammatory Th17 and regulatory T cells (Treg) are associated with autoimmunity. In Hobart, Australia (latitude 42.8° south), thirteen girls (aged 12-13) and sixteen women had blood collected in the evening in daylight in February/March, (post 15 h daylight) and at the same time in the dark in August/September (post 9 h daylight). Height and weight were measured. Participants completed online surveys prior around menstruation, sleep, exercise and time outside. Proportions of Th17 (CD4 + , CXCR3-, CCR4 + , CCR6 + , CD161 +), total Treg (CD4 + , CD25 + , CD127low), naïve Treg (CD45RA + , CD4 + , CD25 + , CD127low) and memory Treg (CD45RA low, CD4 + , CD25 + , CD127low) were enumerated by flow cytometry (Cytek Aurora). Hours spent outside was greater in summer than winter (12.5 v 10.5, p = 0.0003). The %Treg/CD4 + was higher in summer than winter (7.3% vs 7%, p = 0.004) including memory Treg (3.1% vs 2.9%, p = 0.02) for all females (n = 29), and naïve Treg were 13% higher in summer in women (3.2% vs 2.8%, p = 0.0009), whereas %Th17 remained unchanged. In women, a negative correlation between the number of hours spent outside in summer and %Th17 was observed (r = - 0.53, p = 0.035). The %Th17 cells were higher in women than girls (4.9% vs 3.1%, p = 0.001), whereas girls had a higher total %Treg (7.6% vs 6.7%, p = 0.005), consisting of a higher naïve Treg (5.5% vs 3.7%, p = 0.0001) while the women had a higher %memory Treg (3.4% vs 2.6%, p = 0.0001). These light-dependent seasonal differences may influence immune development in adolescents., Competing Interests: Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. The Author(s).)

The Antarctic seabed harbors significant biodiversity, and almost 90% of oceanic environments are permanently below 5 °C (i.e., deep sea and polar regions). However, organisms whose entire lifecycle occurs around 0 °C are understudied, leaving this large and diverse proportion of the global biome poorly understood. To address this question at the cellular level, tools are required for high-resolution imaging of biological systems under physiological conditions. This poses severe technical challenges. High-resolution imaging objectives require short working distances and immersion media, causing rapid heat transfer from the microscope to the sample. This affects the viability of live specimens and the interpretability of results. Here, we present a method for high-fidelity imaging of live biological samples at temperatures of around, or below, 0 °C. It relies on hardware additions to traditional microscopy, namely as a cooling collar, 10% ethanol as an immersion medium, and nitrogen flow to reduce condensation It can be straightforwardly implemented on different microscopy modalities, including super-resolution imaging. The method is demonstrated in live cell cultures derived from Antarctic fish and highlights the need to maintain physiological conditions for these fragile samples. Future applications include evolutionary biology, biophysics and biotechnology., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

Laypeople believe that sharing their emotional experiences with others will improve their understanding of those experiences, but no clear empirical evidence supports this belief. To address this gap, we used data from four daily life studies ( N = 659; student and community samples) to explore the association between social sharing and subsequent emotion differentiation, which involves labeling emotions with a high degree of complexity. Contrary to our expectations, we found that social sharing of emotional experiences was linked to greater subsequent emotion differentiation on occasions when people ruminated less than usual about these experiences. In contrast, on occasions when people ruminated more than usual about their experiences, social sharing of these experiences was linked to lower emotion differentiation. These effects held when we controlled for levels of negative emotion. Our findings suggest that putting feelings into words through sharing may only enable emotional precision when that sharing occurs without dwelling or perseverating.

Existing emotion regulation research focuses on how individuals use different strategies to manage their own emotions-also called intra-personal emotion regulation. However, people often leverage connections with others to regulate their own emotions-interpersonal emotion regulation. The goal of the present studies was to develop a comprehensive and efficient scale-the Emotion Regulation Strategies Scale (ERSS)-to assess nine specific emotion regulation strategies that individuals use both intra-personally and interpersonally. These emotion regulation strategies were cognitive reappraisal, distraction, situation selection, problem solving, acceptance, calming, savoring, rumination, and expressive suppression. Data were collected between 2020 and 2022. Study 1 adopted a qualitative approach to establish original scale items. Results of the confirmatory factor analysis in Study 2 confirmed a nine-factor solution for both the intra- and the interpersonal scales and finalized scale items. A second confirmatory factor analysis in Study 3 found the ERSS for both the intra-personal and interpersonal scale models to possess good model fit. Correlations from Study 3 showed the ERSS subscales to be related in expected ways to existing emotion regulation scales, yet not redundant with these scales. The degree to which individuals used the range of intra- and interpersonal emotion regulation strategies assessed on the ERSS also related to the levels of clinical symptoms. The ERSS represents a comprehensive novel scale that can flexibly assess a range of specific emotion regulation strategies used both intra- and interpersonally. Future work should be conducted using the ERSS cross culturally and in clinical samples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The affect of temperature on tissue protein synthesis rates has been reported in temperate and tropical, but not Antarctic fishes. Previous studies have generally demonstrated low growth rates in Antarctic fish species in comparison to temperate relatives and elevated levels of protein turnover. This study investigates how low temperatures effect tissue protein synthesis and hence tissue growth in a polar fish species. Groups of Antarctic, Harpagifer antarcticus and temperate, Lipophrys pholis, were acclimated to a range of overlapping water temperatures and protein synthesis was measure in white muscle (WM), liver and gastrointestinal tract (GIT). WM protein synthesis rates increased linearly with temperature in both species (H. antarcticus 0.16-0.23%.d -1 , L. pholis, 0.31-0.76%.d -1 ), while liver (H. antarcticus 0.24-0.27%.d -1 , L. pholis, 0.44-1.03%.d -1 ) and GIT were unaffected by temperature in H. antarcticus but increased non-linearly in L.pholis (H. antarcticus 0.22-0.26%.d -1 , L. pholis, 0.40-0.86%.d -1 ). RNA to protein ratios were unaffected by temperature in H. antarcticus but increased weakly, in L.pholis WM and liver. In L.pholis, RNA translational efficiency increased significantly with temperature in all tissues, but only in liver in H. antarcticus. At the overlapping temperature of 3 °C, protein synthesis (WM 26%, Liver, 39%, GIT, 35%) and RNA translational efficiency (WM 273%, Liver, 271%, GIT, 300%) were significantly lower in H. antarcticus than L.pholis, while RNA to protein ratios were significantly higher (WM 270%, Liver 170%, GIT 186%). Tissue specific effects of temperature are detectable in both species. This study provides the first evidence, that tissue protein synthesis rates are constrained in Antarctic fishes., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin releasing factor (CRF) has been previously documented. Here we provide a comprehensive analysis of their identity and functional role in shaping reward learning., Methods: To do this, we took a multidisciplinary approach that included florescent in situ hybridization (N mice ≥ 3), tract tracing (N mice = 5), ex vivo electrophysiology (N cells ≥ 30), in vivo calcium imaging with fiber photometry (N mice ≥ 4) and use of viral strategies in transgenic lines to selectively delete CRF peptide from NAc neurons (N mice ≥ 4). Behaviors used were instrumental learning, sucrose preference and spontaneous exploration in an open field., Results: Here we show that the vast majority of NAc CRF-containing (NAc CRF ) neurons are spiny projection neurons (SPNs) comprised of dopamine D1-, D2- or D1/D2-containing SPNs that primarily project and connect to the ventral pallidum and to a lesser extent the ventral midbrain. As a population, they display mature and immature SPN firing properties. We demonstrate that NAc CRF neurons track reward outcomes during operant reward learning and that CRF release from these neurons acts to constrain initial acquisition of action-outcome learning, and at the same time facilitates flexibility in the face of changing contingencies., Conclusion: We conclude that CRF release from this sparse population of SPNs is critical for reward learning under normal conditions.

Antarctic marine ectotherms live in the constant cold and are characterised by limited resilience to elevated temperature. Here we tested three of the central paradigms underlying this resilience. Firstly, we assessed the ability of eight species, from seven classes representing a range of functional groups, to survive, for 100 to 303 days, at temperatures 0 to 4 °C above previously calculated long-term temperature limits. Survivors were then tested for acclimation responses to acute warming and acclimatisation, in the field, was tested in the seastar Odontaster validus collected in different years, seasons and locations within Antarctica. Finally, we tested the importance of oxygen limitation in controlling upper thermal limits. We found that four of 11 species studied were able to survive for more than 245 days (245-303 days) at higher than previously recorded temperatures, between 6 and 10 °C. Only survivors of the anemone Urticinopsis antarctica did not acclimate CT max and there was no evidence of acclimatisation in O. validus . We found species-specific effects of mild hyperoxia (30% oxygen) on survival duration, which was extended (two species), not changed (four species) or reduced (one species), re-enforcing that oxygen limitation is not universal in dictating thermal survival thresholds. Thermal sensitivity is clearly the product of multiple ecological and physiological capacities, and this diversity of response needs further investigation and interpretation to improve our ability to predict future patterns of biodiversity.

We theorize that expressing emotion often will enhance listening and responsiveness in communal relationships because the nature of cooperation called for in communal relationships often matches five functions that expressing emotion can serve. The same is less frequently true for other types of relationships., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss 'omics' approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain., (© 2023. The Author(s).)