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Indigenous LGBTIQSB+ individuals occupy a unique intersection of identities that inform their lived experiences and the ways in which they navigate colonial settler educational institutions. Despite a considerable body of evidence demonstrating the importance of inclusion, educational policies in Australia remain outdated. These policies are frequently informed by a deficit approach that justifies the absence of Indigenous and gender/sexuality diverse content within school curricula. This further acts to shore up discriminatory practices and policies. Using interviews and workshops held with young Indigenous LGTBIQSB+ people, this article reports on the ways participants experienced educational institutional settings. First, participants reported on the kinds of policies and curriculum content that discriminated against and marginalised them, as well as highlighting some positive aspects of school and university. Participants also revealed the potentialities for Indigenous and LGBTIQSB+ inclusivity that could be facilitated within educational spaces. The article demonstrates the need for safer and more inclusive educational environments, which could be achieved through the decentring of settler knowledges and heteronormativity, transforming educational spaces at an institutional level to facilitate safety at interpersonal and collective levels.

Introduction A feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is no consensus on the dosages and current recommendations are based on a low evidence level. The objective is to compare the effect of a single versus multiple doses of prophylactic antibiotics administered within 24 hours on PJI.Methods and analysis The study is designed as a cross-over, cluster randomised, non-inferiority trial. All clinical centres use both antibiotic practices (1 year of each intervention). All Danish orthopaedic surgery departments will be involved: Based on quality databases, 2-year cohorts of approximately 20 000 primary THAs conducted at 39 public and private hospitals, will be included. Inclusion criteria: age ≥18 years, all indications for THA except patients operated due to acute or sequelae from proximal femoral or pelvic fractures or bone tumour or metastasis. The primary outcome is PJI within 90 days after primary THA. Secondary outcomes include (1) serious adverse events, (2) potential PJI, (3) length of hospitalisation stay, (4) cardiovascular events, (5) hospital-treated infections, (6) community-based antibiotic use, (7) opioid use and (8) use of acetaminophen and non-steroidal anti-inflammatory drugs. All outcome measures will be extracted from national databases. Analyses will be based on the intention-to-treat population. Non-inferiority will be shown if the upper limit of the two-sided 95% CI for the OR is less than 1.32 for the single dose as compared with multiple doses. The results will establish best practice on antibiotic prophylaxis dosages in the future.Ethics and dissemination This study has been approved by Committees on Health Research Ethics for The Capital Region of Denmark (21069108) and The Danish Medicines Agency (2021091723). All results will be presented in peer-reviewed medical journals and international conferences.Trial registration number NCT05530551.

The human rights of both LGBTIQ+ and Indigenous peoples are far from realized. When conjoined, intersecting identities reveal how racism and queer phobia affect well-being, negating the right to health and resulting in devastating impacts on people’s social, cultural, and emotional well-being. This paper documents the lived experiences of a sample of young gender- and sexuality-diverse Aboriginal and Torres Strait Islander peoples from a research project conducted in New South Wales, Australia. Their perspectives reveal how, for this cohort, discrimination and privation is manifest at the family, community, and institutional levels. This paper informs an understanding of human rights as experienced by Aboriginal and Torres Strait Islander LGBTIQ+-identified peoples, where racism and queer phobia are evident in the spheres of education, employment, and service provision. Adopting a critical human rights stance, our analysis illustrates how settler colonialism manifests through the processes and outcomes of settler colonial institutions and structures.

Access to adequate and appropriate service provision has a direct positive impact on health and wellbeing. Experiences of inaccessible, discriminatory, and culturally unsafe services and/or service providers are considered a root cause for the health inequalities that exist among Indigenous queer youth. Experiences of discrimination and cultural inappropriateness are commonplace, with Indigenous queer youth noting issues related to access to services and treatment, stereotyping, and a lack of quality in the care provided, which discourage Indigenous people from accessing care. This paper examines the perspectives of Indigenous LGBTIQ+ youth and health service providers to identify what challenges, obstacles and opportunities are currently being faced and what could be implemented to improve the health and wellbeing outcomes for Indigenous LGBTIQ+ youth in the future.

Background and purpose: Limited data exists on the implementation process and safety of discharge on the day of surgery after primary hip and knee arthroplasty in a multicenter setting. We report our study protocol on the investigation of the feasibility, safety, and socioeconomic aspects following discharge on day of surgery after hip and knee arthroplasty across 8 fast-track centers. Patients and methods: This is a study protocol for a prospective cohort study on discharge on day of surgery from the Center for Fast-track Hip and Knee Replacement. The collaboration includes 8 centers covering 40% of the primary hip and knee arthroplasty procedures undertaken in Denmark. All patients scheduled for surgery are screened for eligibility using well-defined inclusion and exclusion criteria. Eligible patients fulfilling discharge criteria will be discharged on day of surgery. We expect to screen 9,000 patients annually. Duration and outcome: Patients will be enrolled over a 3-year period from September 2022 and reporting of results will run continuously until December 2025. We shall report the proportion of eligible patients and patients discharged on day of surgery as well as limiting factors. Readmissions and complications within 30 days are recorded with real-time follow-up by research staff. Furthermore, patient-reported information on willingness to repeat discharge on day of surgery, contacts with the healthcare system, complications, and workability is registered 30 days postoperatively. EQ-5D, Oxford Knee Score, and Oxford Hip Score are completed preoperatively and after 3 months and 1 year. Finally, outcome data will be used in the development of a prediction model for successful discharge on the day of surgery.

There is little known about the social, cultural and emotional wellbeing (SCEWB) of Aboriginal and Torres Strait Islander LGBTIQ+ young people in Australia. What research exists does not disaggregate young people’s experiences from those of their adult Aboriginal and Torres Strait Islander LGBTIQ+ peers. The research that forms the basis for this article is one of the first conducted in Australia on this topic. The article uses information from in-depth interviews to inform concepts of social inclusion and exclusion for this population group. The interviews demonstrate the different ways in which social inclusion/exclusion practices, patterns and process within First Nations communities and non-Indigenous LGBTIQ+ communities impact on the SCEWB of these young people. The research demonstrates the importance of acceptance and support from families in particular the centrality of mothers to young people feeling accepted, safe and able to successfully overcome challenges to SCEWB. Non-Indigenous urban LGBTIQ+ communities are at times seen as a “second family” for young people, however, structural racism within these communities is also seen as a problem for young people’s inclusion. This article contributes significant new evidence on the impact of inclusion/exclusion on the SCEWB of Australian First Nations LGBTIQ+ youth.

This thematic issue of Social Inclusion highlights the connections between First Nations LGBTIQ+ people’s intersecting identities and inclusionary and exclusionary process in settler-colonial Australia. In this editorial, we briefly introduce key concepts and summarise the different contributions in the issue, providing some general conclusions and guidance on a possible future research agenda.

Abstract Background Young women with breast cancer tend to report lower quality of life and higher levels of stress than older women with breast cancer, and this may have implications for other psychosocial factors including finances. We sought to determine if stress, anxiety, and depression at diagnosis were associated with changes in household income over 12-months in young women with breast cancer in the United States. Methods This study was a prospective, longitudinal cohort study comprised of women enrolled in the Young and Strong trial. Of the 467 women aged 18–45 newly diagnosed with early-stage breast cancer enrolled in the Young and Strong trial from 2012 to 2013, 356 (76%) answered income questions. Change in household income from baseline to 12 months was assessed and women were categorized as having lost, gained, maintained the same household income

ABSTRACT Although public health recommendations encourage educators to include nutrition into the school day to prevent obesity, teachers cite lack of time as a common barrier. Thus, they are often told to integrate nutrition across the curriculum. The purpose of this project was to create an educational program integrating easy-to-demonstrate experiments with lessons illustrating key concepts in microbiology, nutrition, and food history for elementary school groups visiting a museum. Programs were created by researching and developing short lessons with visual aids, hands-on science experiments, handouts, and teacher’s guides that could be used by museum staff. These lessons were aligned with New Jersey elementary school curricula and learning standards. This project illustrated a creative approach to integrating microbiology, nutrition, and history content into the curriculum so that teachers could more easily fit nutrition into the school day.

Background: Interferon-γ release assays (IGRAs) have been incorporated into several national guidelines for latent TB infection (LTBI) diagnosis. However, their optimal application is still controversial and evolving. The aim of this study is to evaluate the performance of confirmatory IGRAs in addition to tuberculin skin tests (TSTs) in high school students with TST-positive (TST+) results who have had contact with another student who had TB (referred to in this article as "contacts") in TB outbreaks in a high BCG-vaccinated population.Methods: We conducted a retrospective observational study of contacts in five school TB outbreaks in South Korea. The progression rates of TB within 2 years were compared among the groups based on the results of TSTs and QuantiFERON-TB gold assays (QFT-Gs).Results: Among 1,826 contacts, 21 (1.2%) developed active TB. Of the untreated groups, the rate of progression to TB was higher in the group with TST-positive (TST+) results (6.1%, six of 99) than in that with TST-negative (TST-) results (0.6%, 10 of 1,556; P < .001). Among TST+ contacts, the rate of progression to TB was higher in the group with QFT-G-positive (QFT-G+) results (18.75%, six of 32) than that with QFT-G-negative (QFT-G(-)) results (0%, 0 of 67; P = .001). None of the 67 contacts with TST+/QFT-G(-) results progressed to active TB.Conclusions: The addition of a confirmatory IGRA for TST+ contacts could effectively focus the targeting of LTBI treatment to fewer contacts in an intermediate-incidence setting in a high BCG-vaccinated population. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose Effective mentorship is critical to the success of early stage investigators, and has been linked to enhanced mentee productivity, self-efficacy, and career satisfaction. The mission of the National Research Mentoring Network (NRMN) is to provide all trainees across the biomedical, behavioral, clinical, and social sciences with evidence-based mentorship and professional development programming that emphasizes the benefits and challenges of diversity, inclusivity, and culture within mentoring relationships, and more broadly the research workforce. The purpose of this paper is to describe the structure and activities of NRMN. Key highlights NRMN serves as a national training hub for mentors and mentees striving to improve their relationships by better aligning expectations, promoting professional development, maintaining effective communication, addressing equity and inclusion, assessing understanding, fostering independence, and cultivating ethical behavior. Training is offered in-person at institutions, regional training, or national meetings, as well as via synchronous and asynchronous platforms; the growing training demand is being met by a cadre of NRMN Master Facilitators. NRMN offers career stage-focused coaching models for grant writing, and other professional development programs. NRMN partners with diverse stakeholders from the NIH-sponsored Diversity Program Consortium (DPC), as well as organizations outside the DPC to work synergistically towards common diversity goals. NRMN offers a virtual portal to the Network and all NRMN program offerings for mentees and mentors across career development stages. NRMNet provides access to a wide array of mentoring experiences and resources including MyNRMN, Guided Virtual Mentorship Program, news, training calendar, videos, and workshops. National scale and sustainability are being addressed by NRMN “Coaches-in-Training” offerings for more senior researchers to implement coaching models across the nation. “Shark Tanks” provide intensive review and coaching for early career health disparities investigators, focusing on grant writing for graduate students, postdoctoral trainees, and junior faculty. Implications Partners from diverse perspectives are building the national capacity and sparking the institutional changes necessary to truly diversify and transform the biomedical research workforce. NRMN works to leverage resources towards the goals of sustainability, scalability, and expanded reach.

Abstract Background Well-designed research trials are critical for determining the efficacy and effectiveness of nutrition education interventions. To determine whether behavioral and/or cognition changes can be attributed to an intervention, the experimental design must include a control or comparison condition against which outcomes from the experimental group can be compared. Despite the impact different types of control groups can have on study outcomes, the treatment provided to participants in the control condition has received limited attention in the literature. Methods A systematic review of control groups in nutrition education interventions was conducted to better understand how control conditions are described in peer-reviewed journal articles compared with experimental conditions. To be included in the systematic review, articles had to be indexed in CINAHL, PubMed, PsycINFO, WoS, and/or ERIC and report primary research findings of controlled nutrition education intervention trials conducted in the United States with free-living consumer populations and published in English between January 2005 and December 2015. Key elements extracted during data collection included treatment provided to the experimental and control groups (e.g., overall intervention content, tailoring methods, delivery mode, format, duration, setting, and session descriptions, and procedures for standardizing, fidelity of implementation, and blinding); rationale for control group type selected; sample size and attrition; and theoretical foundation. Results The search yielded 43 publications; about one-third of these had an inactive control condition, which is considered a weak study design. Nearly two-thirds of reviewed studies had an active control condition considered a stronger research design; however, many failed to report one or more key elements of the intervention, especially for the control condition. None of the experimental and control group treatments were sufficiently detailed to permit replication of the nutrition education interventions studied. Conclusions Findings advocate for improved intervention study design and more complete reporting of nutrition education interventions.

Background. Parent-reported measurement of child height is common in public health research but may be inaccurate, especially for preschoolers. A standardized protocol and tools to improve measurement accuracy are needed. The purpose of this study was to develop and test materials to improve parents’ accuracy when measuring their preschooler’s height. Methods. In Phase A, 24 parents were observed measuring child height using written instructions and an easy-to-read tape measure; after each of 3 testing rounds, instructions were refined based on observed errors and parent versus researcher measurements. In Phase B, a video replaced written instructions and was refined over 4 rounds with 37 parents. Results. The height kit with written instructions, tape measure, plumb line, and explanatory video helped parents accurately measure child height. Compared to written instructions alone, parents rated the video as having significantly greater clarity and likelihood of improving measurements. Although no significant differences in accuracy were found between paper and video instructions, observations indicated written instructions were more difficult for parents with less education to use with fidelity. Conclusions. The kit may improve parent measurement of preschooler height, thereby improving accuracy of body mass index calculations, tracking of obesity prevalence, and obesity prevention and treatment.

Background: Telemedicine has emerged as an efficient means of distributing professional medical expertise over a broad geographic area with few limitations to the various services that can be provided around the globe. Telepathology is particularly well suited to distributing subspecialty expertise in certain environments in an economical fashion, while preserving centers of excellence. Materials and Methods: After a decade of intrainstitutional teleneuropathology for intraoperative consultation, we expanded our practice to cross state lines and communicate between geographically and financially separate medical centers. Results: The result was an effective means of distributing neuropathological expertise while at the same time preserving a professional center of excellence. While technical and legal (i.e., physician licensing) barriers were surmounted, expected and unexpected issues related to communication required commitment on the part of multiple individuals with diverse expertise and responsibilities. Conclusion: Lessons learned from this successful venture can be used to facilitate future efforts in this ever-growing practical vehicle for distributing pathology subspecialty expertise.

The temporal order of propagation in the blood-oxygen-level-dependent (BOLD) infra-slow activity (ISA, 0.01-0.1 Hz) of functional magnetic resonance imaging (fMRI) can indicate the functional organization of the brain. While prior studies have revealed the temporal order of propagation of BOLD ISA during rest, how it emerges during cognitive tasks remains unclear. Furthermore, its differences between the gray and white matters at the whole-brain scale are unexplored. In this study, we probed the propagation of BOLD ISA using a publicly available fMRI dataset from participants performing visual detection and discrimination tasks (N = 46, 29 females). We examined the temporal order of propagation based on ISA oscillatory phase differences among brain parcels. During visual task performance, ISA in both the gray and white matters propagated in a direction from the visual cortex to the association cortex, including the default mode network (DMN). This result differs from the previously reported propagation direction during rest that traveled from the visual and somatosensory cortices to the DMN, suggesting that the functional organization may change when performing cognitive tasks. In addition, the propagation in the white matter represented more complex patterns than that in the gray matter, exhibiting that the cingulum preceded DMN. Our results may help the understanding of how task performance alters the sensory-DMN propagation according of ISA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Background: Although clinical trials should be accessible to all patients, persistent racial and ethnic disparities in clinical trial enrollment exist. Herein, we examine racial disparities in clinical trial enrollment among prostate cancer patients from a large population-based cohort of oncology practices in the United States. Methods: Using CancerLinQ Discovery, we identified men with regional (N1+) and/or metastatic (M1) prostate cancer diagnosed from 2011 to 2023. Enrollment into a clinical trial for prostate cancer was the primary outcome. Multivariable logistic regression and Cox proportional hazard regression were used for analysis. Results: Within our dataset, we identified 17,028 patients with advanced prostate cancer, of which only 2.6% of patients were enrolled in a clinical trial ( n  = 450). There was variance in the proportion of patients accrued over time with a low of 0.30% in 2011 to a high of 3.94% in 2018 and decreasing to 2.37% in 2023. On multivariable analysis, older age was associated with lower odds of clinical trial enrollment ( p < 0.001). Compared to White patients, Hispanics/Latino (OR: 0.35; CI: 0.161-0.744, p =0.04) and patients with self-identified other race or ethnicity (OR: 0.23; CI: 0.295-0.931, p < 0.01) had lower odds of clinical trial enrollment on multivariable analysis. Black men with prostate cancer did not have a statistically significant difference compared to White men for clinical trial enrollment. (OR: 1.033; CI: 0.771-1.384, p =0.828). Conclusion: While clinical trial enrollment remains low for men with advanced prostate cancer in this contemporary population-based cohort, rates of participation for Hispanic/Latino men, but not Black men, are significantly lower. Increased attention is needed to better understand the reasons behind these racial disparities and to develop effective interventions to promote access., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Brett M. Wiesen et al.)

Objective: In the pursuit of refining P300-based brain-computer interfaces (BCIs), our research aims to propose a novel stimulus design focused on selective attention and task relevance to address the challenges of P300-based BCIs, including the necessity of repetitive stimulus presentations, accuracy improvement, user variability, and calibration demands., Approach: In the oddball task for P300-based BCIs, we develop a stimulus design involving task-relevant dynamic stimuli implemented as finger-tapping to enhance the elicitation and consistency of event-related potentials (ERPs). We further improve the performance of P300-based BCIs by optimizing ERP feature extraction and classification in offline analyses., Main Results: With the proposed stimulus design, online P300-based BCIs in 37 healthy participants achieve an accuracy of 91.2% and an information transfer rate (ITR) of 28.37 bits/min with two stimulus repetitions. With optimized computational modeling in BCIs, our offline analyses reveal the possibility of single-trial execution, showcasing an accuracy of 91.7% and an ITR of 59.92 bits/min. Furthermore, our exploration into the feasibility of across-subject zero-calibration BCIs through offline analyses, where a BCI built on a dataset of 36 participants is directly applied to a left-out participant with no calibration, yields an accuracy of 94.23% and the ITR of 31.56 bits/min with two stimulus repetitions and the accuracy of 87.75% and the ITR of 52.61 bits/min with single-trial execution. When using the finger-tapping stimulus, the variability in performance among participants is the lowest, and a greater increase in performance is observed especially for those showing lower performance using the conventional color-changing stimulus. Signficance. Using a novel task-relevant dynamic stimulus design, this study achieves one of the highest levels of P300-based BCI performance to date. This underscores the importance of coupling stimulus paradigms with computational methods for improving P300-based BCIs., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Black rice bran, a waste product from the commercial milling of black rice that removes the bran and germ leaving the starchy endosperm, contains bioactive anthocyanin, phenolic, and phytosteroid compounds that may have health benefits. This study determined the effect of a polysaccharide-rich bioprocessed (fermented) black rice bran and a green tea extract individually and in combination on weight loss in orally fed mice on a high-fat diet and on concurrent changes in blood glucose and insulin as well as in cholesterol, triglyceride, and high-density and low-density lipoproteins (HDL and LDL). At the end of the eight-week feeding study, the combination diet resulted in a 67% lower weight gain than mice on a high-fat diet alone, a greater effect than that of bioprocessed black rice bran or green tea extract individually. The weight loss caused by the combination diet seems to be the result of decreased dietary efficiency. The observed trends in the glucose and insulin data suggest that the combined diet also has anti-diabetic properties, and the corresponding trends in the levels of the serum lipoproteins suggest that the combined diet might also protect against heart disease. Effects on the content, structure, and function of white adipose and liver tissues and on obesity-related biomarkers support the trends in the weight loss data. Based on the observed beneficial effects in 3T3-L1 pre-adipocyte cells and mice, we suggest the need to investigate if the new multifunctional combination food product can also protect against obesity and chronic diseases in humans. Mechanistic aspects that govern the anti-obesity effects and suggestions for future research are discussed.

Objective: Drug-induced parkinsonism (DIP) ranks second to Parkinson's disease (PD) in causing parkinsonism. Despite sharing similar symptoms, DIP results from exposure to specific medications or substances, underscoring the need for accurate diagnosis. Here, we used resting-state electroencephalography (rsEEG) to investigate neural markers characterizing DIP and PD., Methods: We conducted a retrospective analysis of rsEEG recordings from 18 DIP patients, 43 de novo PD patients, and 12 healthy controls (HC). After exclusions, data from 15 DIP, 41 PD, and 12 HC participants were analyzed. EEG spectral power and inter-channel coherence were compared across the groups., Results: Our results demonstrated significant differences in rsEEG patterns among DIP, PD, and HC groups. DIP patients exhibited increased theta band power compared with PD patients and HC. Moreover, DIP patients showed higher delta band coherence compared with PD patients., Conclusion: The current study highlights the differences in EEG spectral power and inter-channel coherence between DIP and PD patients., Significance: Our results suggest that rsEEG holds promise as a valuable tool for capturing differential characteristics between DIP and PD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: In metastatic hormone-sensitive prostate cancer (mHSPC), androgen deprivation therapy and standard of care treatment intensification with docetaxel and/or an androgen receptor signaling inhibitor (ARSI) are associated with improved survival outcomes for appropriate patients., Methods: This retrospective study selected patients with de novo mHSPC diagnosed between 2014 and 2023 from CancerLinQ Discovery®, a United States (US)-based, de-identified clinical database. Patient-level data, including clinical characteristics, treatments, and demographics, were collected from CancerLinQ. Treatment intensification was defined as the use of docetaxel, abiraterone, apalutamide, enzalutamide, or docetaxel plus abiraterone or darolutamide. Patient characteristics and treatment intensification data were analyzed descriptively and using multivariable logistic regression., Results: Of the 3,684 patients with mHSPC, the overall rate of treatment intensification was 58.4% but increased from 32.5% in 2014 to 67.5% in 2023. A relative decline in docetaxel use was accompanied by an increase in ARSI use. Black patients with mHSPC were less likely to receive treatment identification (OR 0.78, 95% CI 0.64-0.95, P = 0.013). Treatment intensification was also less likely for patients of older age and increased ECOG performance status. Despite increasing treatment intensification for Black patients with mHSPC over time, rates of docetaxel use are disproportionately declining relative to White patients., Conclusions: Treatment intensification rates are increasing to include the majority of patients with mHSPC. However, treatment disparities exist for Black patients, who are less likely to receive intensification. These findings illustrate the importance of promoting treatment intensification in appropriate patients and addressing racial treatment disparities., Competing Interests: Declaration of competing interest CJE, EMK, TPR, and SPK have no relevant conflicts of interest to disclose. TWF reports leadership, stock, and other ownership interests in Aurora Oncology; consulting for Seagen and Janssen Oncology; research funding from Novartis, Bavarian Nordic, Dendreon, GTx Janssen Oncology, Medication, Sanofi, Pfizer, Bristol-Myers Squibb, Roche/Genentech, Exelixis, Aragon Pharmaceuticals, Sotio, Tokai Pharmaceuticals, Atrazeneca/MedImmune, Lilly, Astellas Pharma, Agensys, Seagen, La Rocher-Posay, Merck, Seagen, Myovant Sciences, and Criterium; and patents, royalties, and other intellectual property related to 2 patents filed by the University of Colorado related to early-stage bladder cancer treatment and detection (not currently commercialized or in active clinical development)., (Copyright © 2024. Published by Elsevier Inc.)

Sorting spikes from extracellular recordings, obtained by sensing neuronal activity around an electrode tip, is essential for unravelling the complexities of neural coding and its implications across diverse neuroscientific disciplines. However, the presence of overlapping spikes, originating from neurons firing simultaneously or within a short delay, has been overlooked because of the difficulty in identifying individual neurons due to the lack of ground truth. In this study, we propose a method to identify overlapping spikes in extracellular recordings and to recover hidden spikes by decomposing them. We initially estimate spike waveform templates through a series of steps, including discriminative subspace learning and the isolation forest algorithm. By leveraging these estimated templates, we generate synthetic spikes and train a classifier using their feature components to identify overlapping spikes from observed spike data. The identified overlapping spikes are then decomposed into individual hidden spikes using a particle swarm optimization. Results from the testing of the proposed approach, using the simulation dataset we generated, demonstrated that employing synthetic spikes in the overlapping spike classifier accurately identifies overlapping spikes among the detected ones (the maximum F1 score of 0.88). Additionally, the approach can infer the synchronization between hidden spikes by decomposing the overlapped spikes and reallocating them into distinct clusters. This study advances spike sorting by accurately identifying overlapping spikes, providing a more precise tool for neural activity analysis., Competing Interests: Declarations. Ethics approval and consent to participate: The animal experimentation was conducted at Center for Neuroscience Imaging Research within the Institute for Basic Science (IBS), Sungkyunkwan University and approved by its Institutional Animal Care and Use Committee (SKKUIACUC2023-10-21-1), as part of a collaboration with Catholic Kwandong University. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Small cell prostate cancer (SCPC) is a rare, aggressive disease with limited clinical data to guide treatment. In this retrospective study, we evaluated clinical, treatment, and outcomes data for patients with SCPC., Methods: Patients with SCPC were selected from CancerLinQ Discovery ® , a United States-based de-identified clinical database derived from the electronic health records of over 60 medical oncology organizations. A diagnosis of SCPC was made based on a tumor histology code of small cell carcinoma. The primary outcome of this study was assessing first-line systemic therapy within 1 year of diagnosis of SCPC., Results: 74 patients with SCPC who received systemic therapy between 2010-2023 were identified. The majority had documented metastatic disease (45 patients, 60.8%) and a low PSA (median 2.8 ng/dL) at SCPC diagnosis. Platinum chemotherapy plus etoposide was the most common systemic treatment (62, 83.8%) and carboplatin plus etoposide was the most common regimen (42, 56.8%) used in the first line. Median overall survival (OS) was 8.3 months for patients with metastatic SCPC. Patients treated with cisplatin plus etoposide had improved survival versus those receiving carboplatin plus etoposide (odds ratio 3.15, 95% CI 1.57-6.30; p = 0.001). 45.9% of patients with SCPC received second-line systemic therapies, which were highly varied., Conclusions: This contemporary real-world data represent one of the largest descriptions of the treatment of SCPC. Clear consensus on the optimal systemic therapy for SCPC is lacking. While additional research is needed, real-world practice patterns can serve as a resource when considering a treatment approach for this rare disease., Competing Interests: Competing interests: CJE, EMK, TPR, and SPK have no relevant conflicts of interest to disclose. TWF reports leadership, stock, and other ownership interests in Aurora Oncology; consulting for Seagen and Janssen Oncology; research funding from Novartis, Bavarian Nordic, Dendreon, GTx Janssen Oncology, Medication, Sanofi, Pfizer, Bristol-Myers Squibb, Roche/Genentech, Exelixis, Aragon Pharmaceuticals, Sotio, Tokai Pharmaceuticals, Atrazeneca/MedImmune, Lilly, Astellas Pharma, Agensys, Seagen, La Rocher-Posay, Merck, Seagen, Myovant Sciences, and Criterium; and patents, royalties, and other intellectual property related to 2 patents filed by the University of Colorado related to early-stage bladder cancer treatment and detection (not currently commercialized or in active clinical development). Ethics approval and consent to participate: This study used a large, deidentified dataset and was determined to be exempt from review by the Colorado Multiple Institutional Review Board, reference 21–3083. Due to the deidentified and retrospective nature of the secondary-use health data, informed consent could not feasibly be obtained., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Mitochondrial dysfunction induced by mitochondrial DNA (mtDNA) mutations has been implicated in various human diseases. A comprehensive analysis of mitochondrial genetic disorders requires suitable animal models for human disease studies. While gene knockout via premature stop codons is a powerful method for investigating the unique functions of target genes, achieving knockout of mtDNA has been rare. Here, we report the genotypes and phenotypes of heteroplasmic MT-ND5 gene-knockout mice. These mutant mice presented damaged mitochondrial cristae in the cerebral cortex, hippocampal atrophy, and asymmetry, leading to learning and memory abnormalities. Moreover, mutant mice are susceptible to obesity and thermogenetic disorders. We propose that these mtDNA gene-knockdown mice could serve as valuable animal models for studying the MT-ND5 gene and developing therapies for human mitochondrial disorders in the future., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Meaningful variation in internal states that impacts cognition and behavior remains challenging to discover and characterize. Here we leveraged trial-to-trial fluctuations in the brain-wide signal recorded using functional MRI to test if distinct sets of brain regions are activated on different trials when accomplishing the same task. Across three different perceptual decision-making experiments, we estimated the brain activations for each trial. We then clustered the trials based on their similarity using modularity-maximization, a data-driven classification method. In each experiment, we found multiple distinct but stable subtypes of trials, suggesting that the same task can be accomplished in the presence of widely varying brain activation patterns. Surprisingly, in all experiments, one of the subtypes exhibited strong activation in the default mode network, which is typically thought to decrease in activity during tasks that require externally focused attention. The remaining subtypes were characterized by activations in different task-positive areas. The default mode network subtype was characterized by behavioral signatures that were similar to the other subtypes exhibiting activation with task-positive regions. These findings demonstrate that the same perceptual decision-making task is accomplished through multiple brain activation patterns., Competing Interests: Competing interests: Authors declare that they have no competing interests.

Patients suffering from various neurological disorders, including major depressive disorder (MDD), often exhibit abnormal brain connectivity. In particular, patients with MDD show atypical brain oscillations propagation. This study aims to investigate an association between abnormal brain connectivity and atypical oscillatory propagation of electroencephalogram (EEG) signals in patients with a history of MDD. Previous findings of functional hyperconnectivity in beta oscillations (15-25 Hz) lead us to hypothesize that patients would experience abnormal beta oscillation propagation. Using the local phase gradient (LPG) method, we analyze a publicly available EEG dataset recorded during a probabilistic learning task. Our findings indicate that, upon receiving positive feedback during the learning task, patients with a history of MDD show more pronounced propagation directions of beta oscillations observed in the right frontal region compared to healthy controls. This directional pattern may help differentiate patients with a history of MDD from healthy controls. The observed abnormalities in brain oscillation propagation suggest that cognitive deficits in patients with a history of MDD might stem from excessive and negatively biased information transmission between brain regions., Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00433-9., Competing Interests: Competing interestsThe authors have no relevant financial or non-financial interests to disclose., (© Korean Society of Medical and Biological Engineering 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This study investigated the antiobesity effects of black ginger extract (BGE) in high-fat diet (HFD)-induced obese mice. Mice were divided into six groups: normal diet control (NC, AIN-93G normal diet), 60% HFD control (HFD), HFD containing metformin at 250 mg/kg b.w. (Met, positive control), and HFD containing BGE at 5, 10, or 20 mg/kg b.w. for 15 weeks. BGE administration significantly prevented HFD-induced increases in weight gain, organ weight, and adipose tissue mass. Furthermore, it resulted in decreased adipogenesis and lipogenesis-related factors, including phosphorylated mitogen-activated protein kinase, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins, sterol regulatory element-binding protein 1, phosphorylated cAMP response element-binding protein, glucose-6-phosphate dehydrogenase, fatty acid synthase, dephosphorylated ATP-citrate lyase, dephosphorylated acetyl-CoA carboxylase, and lipoprotein lipase, in white adipose tissues. Moreover, BGE administration enhanced lipolysis in white adipose tissue, as evidenced by elevated levels of adipose triglyceride lipase, phosphorylated hormone-sensitive lipase, and protein kinase A, along with reduced levels of perilipin and phosphodiesterase 3B. BGE induced thermogenesis in brown adipose tissues, as reflected by the increased expression of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1 and decreased levels of fatty acid-binding protein 4. In conclusion, this study provides comprehensive evidence supporting the antiobesity effects of BGE, elucidating the underlying molecular mechanisms involved in preventing weight gain, suppressing adipogenesis, promoting lipolysis, and stimulating thermogenesis. These findings suggest the potential therapeutic utility of BGE in combating obesity and associated metabolic disorders (KHGASP-2023-034).

Background/objectives: Meditation induces changes in the nervous system, which presumably underpin positive psychological and physiological effects. Such neural changes include alterations in the arousal fluctuation, as well as in infraslow brain activity (ISA, <0.1 Hz). Furthermore, it is known that fluctuations of arousal over time correlate with the oscillatory phase of ISA. However, whether this arousal-ISA correlation changes after meditation practices remains unanswered.; Methods: The present study aims to address this question by analyzing a publicly available electroencephalogram (EEG) dataset recorded during meditation sessions in the groups of experienced meditators and novices. The arousal fluctuation is measured by galvanic skin responses (GSR), and arousal-ISA correlations are measured by phase synchronization between GSR and EEG ISAs.; Results: While both groups exhibit arousal-ISA correlations, experienced meditators display higher correlations than novices. These increased arousal-ISA correlations in experienced meditators manifest more clearly when oscillatory phase differences between GSR and EEG ISAs are either 0 or π radians. As such, we further investigate the characteristics of these phase differences with respect to spatial distribution over the brain. We found that brain regions with the phase difference of either 0 or π radians form distinct spatial clusters, and that these clusters are spatially correlated with functional organization estimated by the principal gradient, based on functional connectivity.; Conclusions: Since increased arousal-ISA correlations reflect enhanced global organization of the central and autonomic nervous systems, our findings imply that the positive effects of meditation might be mediated by enhanced global organization of the nervous system.

Objective. This study investigates the impact of conversation on the performance of visual event-related potential (ERP)-based brain-computer interfaces (BCIs), considering distractions in real life environment. The research aims to understand how cognitive distractions from speaking and listening activities affect ERP-BCI performance. Approach. The experiment employs a dual-task paradigm where participants control a smart light using visual ERP-BCIs while simultaneously conducting speaking or listening tasks. Main results. The findings reveal that speaking notably degrades BCI accuracy and the amplitude of ERP components, while increases the latency variability of ERP components and occipital alpha power. In contrast, listening and simple syllable repetition tasks have a lesser impact on these variables. The results suggest that speaking activity significantly distracts visual attentional processes critical for BCI operation Significance . This study highlights the need to take distractions by daily conversation into account of the design and implementation of ERP-BCIs., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Adoptive cell transfer (ACT) with neoantigen-reactive T lymphocytes can mediate cancer regression. Here we isolated unique, personalized, neoantigen-reactive T cell receptors (TCRs) from tumor-infiltrating lymphocytes of patients with metastatic gastrointestinal cancers and incorporated the TCR α and β chains into gamma retroviral vectors. We transduced autologous peripheral blood lymphocytes and adoptively transferred these cells into patients after lymphodepleting chemotherapy. In a phase 2 single-arm study, we treated seven patients with metastatic, mismatch repair-proficient colorectal cancers who had progressive disease following multiple previous therapies. The primary end point of the study was the objective response rate as measured using RECIST 1.1, and the secondary end points were safety and tolerability. There was no prespecified interim analysis defined in this study. Three patients had objective clinical responses by RECIST criteria including regressions of metastases to the liver, lungs and lymph nodes lasting 4 to 7 months. All patients received T cell populations containing ≥50% TCR-transduced cells, and all T cell populations were polyfunctional in that they secreted IFNγ, GM-CSF, IL-2 and granzyme B specifically in response to mutant peptides compared with wild-type counterparts. TCR-transduced cells were detected in the peripheral blood of five patients, including the three responders, at levels ≥10% of CD3 + cells 1 month post-ACT. In one patient who responded to therapy, ~20% of CD3 + peripheral blood lymphocytes expressed transduced TCRs more than 2 years after treatment. This study provides early results suggesting that ACT with T cells genetically modified to express personalized neoantigen-reactive TCRs can be tolerated and can mediate tumor regression in patients with metastatic colorectal cancers. ClinicalTrials.gov registration: NCT03412877 ., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Behaviors often involve a sequence of events, and learning and reproducing it is essential for sequential memory. Brain loop structures refer to loop-shaped inter-regional connection structures in the brain such as cortico-basal ganglia-thalamic and cortico-cerebellar loops. They are thought to play a crucial role in supporting sequential memory, but it is unclear what properties of the loop structure are important and why., Methods: In this study, we investigated conditions necessary for the learning of sequential memory in brain loop structures via computational modeling. We assumed that sequential memory emerges due to delayed information transmission in loop structures and presented a basic neural activity model and validated our theoretical considerations with spiking neural network simulations., Results: Based on this model, we described the factors for the learning of sequential memory: first, the information transmission delay should decrease as the size of the loop structure increases; and second, the likelihood of the learning of sequential memory increases as the size of the loop structure increases and soon saturates. Combining these factors, we showed that moderate-sized brain loop structures are advantageous for the learning of sequential memory due to the physiological restrictions of information transmission delay., Discussion: Our results will help us better understand the relationship between sequential memory and brain loop structures., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sihn and Kim.)

Background: The across-trial correlation of neurons' coactivity patterns emerges to be important for information coding, but methods for finding their temporal structures remain largely unexplored., New Method: In the present study, we propose a method to find time clusters in which coactivity patterns of neurons are correlated across trials. We transform the multidimensional neural activity at each timing into a coactivity pattern of binary states, and predict the coactivity patterns at different timings. We devise a method suitable for these coactivity pattern predictions, call general event prediction. Cross-temporal prediction accuracy is then used to estimate across-trial correlations between coactivity patterns at two timings. We extract time clusters from the cross-temporal prediction accuracy by a modified k-means algorithm., Results: The feasibility of the proposed method is verified through simulations based on ground truth. We apply the proposed method to a calcium imaging dataset recorded from the motor cortex of mice, and demonstrate time clusters of motor cortical coactivity patterns during a motor task., Comparison With Existing Methods: While the existing cosine similarity method, which does not account for across-trial correlation, shows temporal structures only for contralateral neural responses, the proposed method reveals those for both contralateral and ipsilateral neural responses, demonstrating the effect of across-trial correlations., Conclusions: This study introduces a novel method for measuring the temporal structure of neuronal ensemble activity., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: To investigate the actual cost of hematuria evaluation using nationally representative claims data, given that the workup for hematuria burdens the healthcare system with significant associated costs. We hypothesized that evaluation with contrast-enhanced computed tomography (CT) confers more cost to hematuria evaluation than renal ultrasound (US)., Methods: Using a national, privately insured database (MarketScan), we identified all individuals with an incident diagnosis of hematuria. We included patients who underwent cystoscopy and upper tract imaging within 3 months of diagnosis. We tabulated the costs of the imaging study as well as the total healthcare cost per patient. A multivariable model was developed to evaluate patient factors associated with total healthcare costs., Results: We identified 318,680 patients with hematuria who underwent evaluation. Median costs associated with upper tract imaging were $362 overall, $504 for CT with contrast, $163 for US, $680 for magnetic resonance imaging (MRI), $283 for CT without contrast, and $294 for retrograde pyelogram. Median cystoscopy cost was $283. Total healthcare costs per patient were highest when utilizing MRI and CT imaging. When adjusted for comorbidities, the use of any imaging other than ultrasound was associated with higher costs., Conclusions: In this nationally representative analysis, hematuria evaluation confers a significant cost burden, while the primary factor associated with higher costs of screening was imaging type. Based upon reduced cost of US-based strategies, further investigation should delineate its cost-effectiveness in the diagnosis of urological disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis., Methods: We identified 136 patients aged 2-17 years with newly diagnosed IBD (94 Crohn's disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes., Results: Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively., Conclusion: This study is the first in Korea to estimate the prevalence of pediatric IBDU. This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Objective: To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy improves overall survival (OS), progression-free survival (PFS), and pathologic complete response (pCR) for patients with muscle-invasive bladder cancer with secondary analyses of pathological downstaging and toxicity., Materials and Methods: This systematic review and meta-analysis identified studies of patients with muscle-invasive bladder cancer treated with neoadjuvant GC compared to ddMVAC from PubMed, Web of Science, and EMBASE. Random-effect models for pooled log-transformed hazard ratios (HR) for OS and PFS and pooled odds ratios for pCR and downstaging were developed using the generic inverse variance method and Mantel-Haenszel method, respectively., Results: Ten studies were identified (4 OS, 2 PFS, and 6 pCR clinical endpoints). Neoadjuvant ddMVAC improved OS (HR 0.71 [95% confidence intervals 0.56; 0.90]), PFS (HR 0.76 [95% confidence intervals 0.60; 0.97]), and pathological downstaging (odds ratio 1.34 [95% confidence interval 1.01; 1.78]) as compared to GC. There was no significant difference between regimens for pCR rates (odds ratio 1.38 [95% confidence interval 0.90; 2.12]). Treatment toxicity was greater with ddMVAC. Limitations result from differences in number of ddMVAC cycles and patient selection between studies., Conclusion: Neoadjuvant ddMVAC is associated with improved OS and PFS vs gemcitabine/cisplatin for patients with muscle-invasive bladder cancer before radical cystectomy. Although rates of pathological complete response were not significantly different, pathological downstaging correlated with OS. ddMVAC should be preferred over gemcitabine/cisplatin for patients with muscle-invasive bladder cancer who can tolerate its greater toxicity., Competing Interests: Declaration of Competing Interest Adam Warren is supported by the Cancer Center Support Grant (P30CA046934). Elizabeth Molina Kuna is supported by the Cancer Center Support Grant (P30CA046934). Simon P. Kim is supported by the Schramm Foundation. Thomas W. Flaig reports leadership, stock, and other ownership interests in Aurora Oncology; consulting for Seagen and Janssen Oncology; research funding from Novartis, Bavarian Nordic, Dendreon, GTx Janssen Oncology, Medication, Sanofi, Pfizer, Bristol-Myers Squibb, Roche/Genentech, Exelixis, Aragon Pharmaceuticals, Sotio, Tokai Pharmaceuticals, Atrazeneca/MedImmune, Lilly, Astellas Pharma, Agensys, Seagen, La Rocher-Posay, Merck, Seagen, Myovant Sciences, and Criterium; and patents, royalties, and other intellectual property related to 2 patents filed by the University of Colorado related to early-stage bladder cancer treatment and detection (not currently commercialized or in active clinical development)., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Propagation of electroencephalogram (EEG) oscillations, often referred to as traveling waves, reflects the role of brain oscillations in neural information transmission. This propagation can be distorted by brain disorders such as schizophrenia that features disconnection of neural information transmission (i.e., disconnection syndrome). However, this possibility of the disruption of EEG oscillation propagation in patients with schizophrenia remains largely unexplored., Methods: Using a publicly shared dataset (N = 19 and 24; patients with schizophrenia and healthy controls, respectively), we investigated EEG oscillation propagation by analyzing the local phase gradients (LPG) of alpha (8-12 Hz) oscillations in both healthy participants and patients with schizophrenia., Results: Our results showed significant directionality in the propagation of alpha oscillations in healthy participants. Specifically, alpha oscillations propagated in an anterior-to-posterior direction along mid-line and a posterior-to-anterior direction laterally. In patients with schizophrenia, some of alpha oscillation propagation were notably disrupted, particularly in the central midline area where alpha oscillations propagated from anterior to posterior areas., Conclusion: Our finding lends support to the hypothesis of a disconnection syndrome in schizophrenia, underscoring a disruption in the anterior-to-posterior propagation of alpha oscillations., Significance: This study identified disruption of alpha oscillation propagation observed in scalp EEG as a biomarker for schizophrenia., Competing Interests: Conflict of Interest Statement None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, and ex vivo expansion can further reduce their frequencies. This complicates the identification of neoantigen-reactive T-cell receptors (TCRs) and the development of TIL products with high reactivity for patient treatment., Methods: We tested whether TILs could be in vitro stimulated against neoantigens to achieve selective expansion of neoantigen-reactive TILs. Given their prevalence, mutant p53 or RAS were studied as models of human neoantigens. An in vitro stimulation method, termed "NeoExpand", was developed to provide neoantigen-specific stimulation to TILs. 25 consecutive patient TILs from tumors harboring p53 or RAS mutations were subjected to NeoExpand., Results: We show that neoantigenic stimulation achieved selective expansion of neoantigen-reactive TILs and broadened the neoantigen-reactive CD4 + and CD8 + TIL clonal repertoire. This allowed the effective isolation of novel neoantigen-reactive TCRs. Out of the 25 consecutive TIL samples, neoantigenic stimulation enabled the identification of 16 unique reactivities and 42 TCRs, while conventional TIL expansion identified 9 reactivities and 14 TCRs. Single-cell transcriptome analysis revealed that neoantigenic stimulation increased neoantigen-reactive TILs with stem-like memory phenotypes expressing IL-7R, CD62L, and KLF2. Furthermore, neoantigenic stimulation improved the in vivo antitumor efficacy of TILs relative to the conventional OKT3-induced rapid TIL expansion in p53-mutated or KRAS-mutated xenograft mouse models., Conclusions: Taken together, neoantigenic stimulation of TILs selectively expands neoantigen-reactive TILs by frequencies and by their clonal repertoire. NeoExpand led to improved phenotypes and functions of neoantigen-reactive TILs. Our data warrant its clinical evaluation., Trial Registration Number: NCT00068003, NCT01174121, and NCT03412877., Competing Interests: Competing interests: NL, SPK and SAR have a pending patent application. The rest of the authors report no competing interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To date, no intervention has definitively improved outcomes for families of critical illness survivors. An integrated perspective on caregivers' needs after critical illness could help identify high-priority intervention targets and improve outcomes., Objectives: To obtain diverse perspectives on the needs, barriers and facilitators, and social determinants of health associated with family caregiving across the critical illness continuum and assess the extent to which successful caregiving interventions in other populations may be adapted to the critical illness context., Methods: This qualitative content analysis of 31 semistructured interviews and 10 focus groups with family caregivers, health care providers, and health care administrators explored family caregivers' needs during post- intensive care unit (ICU) transitions and the barriers and facilitators associated with addressing them. Trained coders analyzed transcripts, identified patterns and categories among the codes, and generated themes., Results: Caregivers have 3 instrumental needs: formal and informal support, involvement in care planning, and education and training. Only caregivers described their self-care and mental health needs. Social determinants of health are the key barriers and facilitators shaping the caregivers' journey, and caregiving as a social determinant of health was a prominent theme., Conclusions: Caregivers have instrumental, self-care, and mental health needs after critical illness. Adapting hands-on and skills training interventions to the post-ICU setting, while tailoring interventions to caregivers' health-related social context, may improve caregiver outcomes., (©2024 American Association of Critical-Care Nurses.)