tbuckley/cabot-search huggingface dataset:
The effect of informal caring on mental health among adolescents and young adults in Australia: a population-based longitudinal study
Authors: Ludmila Fleitas Alfonzo, George Disney, Ankur Singh, Koen Simons, Tania King
Journal: The Lancet Public Health (2024)

BackgroundYoung carers are people aged up to 25 years who provide unpaid care to a relative or a friend living with a long-term condition or a disability. Providing informal care is associated with poor mental health. Longitudinal evidence on this relationship among young people is scarce. To address this gap, we assessed the mental health of people aged 15–25 years when providing informal care compared with when not providing informal care.MethodsWe conducted a population-based longitudinal study using 20 years of data between 2001 and 2020 from the Household Income and Labour Dynamics in Australia (HILDA) survey. We included observations of participants aged 15–25 years with at least two observations across 20 waves of HILDA. Informal care was categorised as 0 h per week, 1–19 h per week, and 20 or more h per week. Mental health was measured using the Mental Health Inventory (MHI-5) from the 36-Item Short Form Survey (SF-36). Multivariate linear fixed-effects regression models were fitted to assess within-person changes in mental health when providing different levels of informal care.FindingsOf 44 663 people with 410 658 observations who participated in HILDA waves 1 to 20, 32 726 were excluded with 351 445 observations. 11 937 young people (with 59 213 observations) were deemed eligible for this study and, of these, 8996 participants with 43 231 observations were included in the complete case analytical sample. When caring for 1–19 h per week, young carers had an MHI-5 score of –1·98 points (95% CI –3·06 to –0·89) compared with when caring for 0 h per week. Mental health was worse when caring for 20 or more h per week, with participants displaying an MHI-5 score of –3·47 points (95% CI –6·02 to –0·92) compared with when caring for 0 h per week. Our findings were consistent across sensitivity tests.InterpretationOur findings suggest potential mental health effects of informal care in young people, particularly when providing an intense amount of caregiving. Reducing young caring loads could be a possible avenue for intervention.FundingMelbourne Disability Institute Scholarship, University of Melbourne Research Training Program Scholarship, Australian Research Council Discovery Early Career Researcher Award, National Health and Medical Research Council of Australia funded Centre of Research Excellence in Disability and Health.
Minimally invasive thoracic surgery in Sierra Leone and Liberia
Authors: Tom M Gresnigt, Mustapha Kabba, Souheil Boubia, Rehginah Davies, Marta Lado, Mark I Kapuwa, Peter S Coleman, Trésor Mabanza, Kebede Gofer, Diego Gonzalez-Rivas
Journal: The Lancet Respiratory Medicine (2024)
Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS)
Authors: Shankar Siva, Alexander V Louie, Rupesh Kotecha, Melissa N Barber, Muhammad Ali, Zhenwei Zhang, Matthias Guckenberger, Mi-Sook Kim, Marta Scorsetti, Alison C Tree, Ben J Slotman, Arjun Sahgal, Simon S Lo
Journal: The Lancet Oncology (2024)
PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0): a report of the RANO group
Authors: Nathalie L Albert, Norbert Galldiks, Benjamin M Ellingson, Martin J van den Bent, Susan M Chang, Francesco Cicone, John de Groot, Eng-Siew Koh, Ian Law, Emilie Le Rhun, Maximilian J Mair, Giuseppe Minniti, Roberta Rudà, Andrew M Scott, Susan C Short, Marion Smits, Bogdana Suchorska, Nelleke Tolboom, Tatjana Traub-Weidinger, Joerg-Christian Tonn, Antoine Verger, Michael Weller, Patrick Y Wen, Matthias Preusser
Journal: The Lancet Oncology (2024)
Effectiveness of two systems-level interventions to address perinatal depression in obstetric settings (PRISM): an active-controlled cluster-randomised trial
Authors: Nancy Byatt, Linda Brenckle, Padma Sankaran, Julie Flahive, Jean Y Ko, Cheryl L Robbins, Martha Zimmermann, Jeroan Allison, Sharina Person, Tiffany A Moore Simas
Journal: The Lancet Public Health (2024)

BackgroundPerinatal depression is a common and undertreated condition, with potential deleterious effects on maternal, obstetric, infant, and child outcomes. We aimed to compare the effectiveness of two systems-level interventions in the obstetric setting—the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms and the PRogram In Support of Moms (PRISM)—in improving depression symptoms and participation in mental health treatment among women with perinatal depression.MethodsIn this cluster-randomised, active-controlled trial, obstetric practices across Massachusetts (USA) were allocated (1:1) via covariate adaptive randomisation to either continue participating in the MCPAP for Moms intervention, a state-wide, population-based programme, or to participate in the PRISM intervention, which involved MCPAP for Moms plus a proactive, multifaceted, obstetric practice-level intervention with intensive implementation support. English-speaking women (aged ≥18 years) who screened positive for depression (Edinburgh Postnatal Depression Scale [EPDS] score ≥10) were recruited from the practices. Patients were followed up at 4–25 weeks of gestation, 32–40 weeks of gestation, 0–3 months postpartum, 5–7 months postpartum, and 11–13 months postpartum via telephone interview. Participants were masked to the intervention; investigators were not masked. The primary outcome was change in depression symptoms (EPDS score) between baseline assessment and 11–13 months postpartum. Analysis was done by intention to treat, fitting generalised linear mixed models adjusting for age, insurance status, education, and race, and accounting for clustering of patients within practices. This trial is registered with ClinicalTrials.gov, NCT02760004.FindingsBetween July 29, 2015, and Sept 20, 2021, ten obstetric practices were recruited and retained; five (50%) practices were randomly allocated to MCPAP for Moms and five (50%) to PRISM. 1265 participants were assessed for eligibility and 312 (24·7%) were recruited, of whom 162 (51·9%) were enrolled in MCPAP for Moms practices and 150 (48·1%) in PRISM practices. Comparing baseline to 11–13 months postpartum, EPDS scores decreased by 4·2 (SD 5·2; p<0·0001) among participants in MCPAP for Moms practices and by 4·3 (SD 4.5; p<0·0001) among those in PRISM practices (estimated difference between groups 0·1 [95% CI –1·2 to 1·4]; p=0·87).InterpretationBoth the MCPAP for Moms and PRISM interventions were equally effective in improving depression symptoms. This finding is important because the 4-point decrease in EPDS score is clinically significant, and MCPAP for Moms has a lower intensity and greater population-based reach than does PRISM.FundingUS Centers for Disease Control and Prevention.
Racial and ethnic disparities in diagnosis and treatment outcomes among US-born people diagnosed with tuberculosis, 2003–19: an analysis of national surveillance data
Authors: Mathilda Regan, Yunfei Li, Nicole A Swartwood, Terrika Barham, Garrett R Beeler Asay, Ted Cohen, Andrew N Hill, C Robert Horsburgh, Awal Khan, Suzanne M Marks, Ranell L Myles, Joshua A Salomon, Julie L Self, Nicolas A Menzies
Journal: The Lancet Public Health (2024)

BackgroundPersistent racial and ethnic disparities in tuberculosis incidence exist in the USA, however, less is known about disparities along the tuberculosis continuum of care. This study aimed to describe how race and ethnicity are associated with tuberculosis diagnosis and treatment outcomes.MethodsIn this analysis of national surveillance data, we extracted data from the US National Tuberculosis Surveillance System on US-born patients with tuberculosis during 2003–19. To estimate the association between race and ethnicity and tuberculosis diagnosis (diagnosis after death, cavitation, and sputum smear positivity) and treatment outcomes (treatment for more than 12 months, treatment discontinuation, and death during treatment), we fitted log-binomial regression models adjusting for calendar year, sex, age category, and regional division. Race and ethnicity were defined based on US Census Bureau classification as White, Black, Hispanic, Asian, American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and people of other ethnicities. We quantified racial and ethnic disparities as adjusted relative risks (aRRs) using non-Hispanic White people as the reference group. We also calculated the Index of Disparity as a summary measure that quantifies the dispersion in a given outcome across all racial and ethnic groups, relative to the population mean. We estimated time trends in each outcome to evaluate whether disparities were closing or widening.FindingsFrom 2003 to 2019, there were 72 809 US-born individuals diagnosed with tuberculosis disease of whom 72 369 (35·7% women and 64·3% men) could be included in analyses. We observed an overall higher risk of any adverse outcome (defined as diagnosis after death, treatment discontinuation, or death during treatment) for non-Hispanic Black people (aRR 1·27, 95% CI 1·22–1·32), Hispanic people (1·20, 1·14–1·27), and American Indian or Alaska Native people (1·24, 1·12–1·37), relative to non-Hispanic White people. The Index of Disparity for this summary outcome remained unchanged over the study period.InterpretationThis study, based on national surveillance data, indicates racial and ethnic disparaties among US-born tuberculosis patients along the tuberculosis continuum of care. Initiatives are needed to reduce diagnostic delays and improve treatment outcomes for US-born racially marginalised people in the USA.FundingUS Centers for Disease Control and Prevention.
Mitochondrial isocitrate dehydrogenase impedes CAR T cell function by restraining antioxidant metabolism and histone acetylation
Authors: Xiaohui Si, Mi Shao, Xinyi Teng, Yue Huang, Ye Meng, Longyuan Wu, Jieping Wei, Lianxuan Liu, Tianning Gu, Junzhe Song, Ruirui Jing, Xingyuan Zhai, Xin Guo, Delin Kong, Xiujian Wang, Bohan Cai, Ying Shen, Zhaoru Zhang, Dongrui Wang, Yongxian Hu, Pengxu Qian, Gang Xiao, He Huang
Journal: Cell Metabolism (2024)
Mitochondrial-derived vesicles in metabolism, disease, and aging
Authors: Tim König, Heidi M. McBride
Journal: Cell Metabolism (2024)

Mitochondria are central hubs of cellular metabolism and are tightly connected to signaling pathways. The dynamic plasticity of mitochondria to fuse, divide, and contact other organelles to flux metabolites is central to their function. To ensure bona fide functionality and signaling interconnectivity, diverse molecular mechanisms evolved. An ancient and long-overlooked mechanism is the generation of mitochondrial-derived vesicles (MDVs) that shuttle selected mitochondrial cargoes to target organelles. Just recently, we gained significant insight into the mechanisms and functions of MDV transport, ranging from their role in mitochondrial quality control to immune signaling, thus demonstrating unexpected and diverse physiological aspects of MDV transport. This review highlights the origin of MDVs, their biogenesis, and their cargo selection, with a specific focus on the contribution of MDV transport to signaling across cell and organ barriers. Additionally, the implications of MDVs in peroxisome biogenesis, neurodegeneration, metabolism, aging, and cancer are discussed.
Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD
Authors: Alia Ghrayeb, Alexandra C. Finney, Bella Agranovich, Daniel Peled, Sumit Kumar Anand, M. Peyton McKinney, Mahasen Sarji, Dongshan Yang, Natan Weissman, Shani Drucker, Sara Isabel Fernandes, Jonatan Fernández-García, Kyle Mahan, Zaid Abassi, Lin Tan, Philip L. Lorenzi, James Traylor, Jifeng Zhang, Ifat Abramovich, Y. Eugene Chen, Oren Rom, Inbal Mor, Eyal Gottlieb
Journal: Cell Metabolism (2024)
Repression of latent NF-κB enhancers by PDX1 regulates β cell functional heterogeneity
Authors: Benjamin J. Weidemann, Biliana Marcheva, Mikoto Kobayashi, Chiaki Omura, Marsha V. Newman, Yumiko Kobayashi, Nathan J. Waldeck, Mark Perelis, Louise Lantier, Owen P. McGuinness, Kathryn Moynihan Ramsey, Roland W. Stein, Joseph Bass
Journal: Cell Metabolism (2024)

Interactions between lineage-determining and activity-dependent transcription factors determine single-cell identity and function within multicellular tissues through incompletely known mechanisms. By assembling a single-cell atlas of chromatin state within human islets, we identified β cell subtypes governed by either high or low activity of the lineage-determining factor pancreatic duodenal homeobox-1 (PDX1). β cells with reduced PDX1 activity displayed increased chromatin accessibility at latent nuclear factor κB (NF-κB) enhancers. Pdx1 hypomorphic mice exhibited de-repression of NF-κB and impaired glucose tolerance at night. Three-dimensional analyses in tandem with chromatin immunoprecipitation (ChIP) sequencing revealed that PDX1 silences NF-κB at circadian and inflammatory enhancers through long-range chromatin contacts involving SIN3A. Conversely, Bmal1 ablation in β cells disrupted genome-wide PDX1 and NF-κB DNA binding. Finally, antagonizing the interleukin (IL)-1β receptor, an NF-κB target, improved insulin secretion in Pdx1 hypomorphic islets. Our studies reveal functional subtypes of single β cells defined by a gradient in PDX1 activity and identify NF-κB as a target for insulinotropic therapy.
A framework for the clinical implementation of optical genome mapping in hematologic malignancies
Authors: Brynn Levy, Rashmi Kanagal‐Shamanna, Nikhil S. Sahajpal, Kornelia Neveling, Katrina Rack, Barbara Dewaele, Daniel Olde Weghuis, Marian Stevens‐Kroef, Anna Puiggros, Mar Mallo, Benjamin Clifford, Tuomo Mantere, Alexander Hoischen, Blanca Espinet, Ravindra Kolhe, Francesc Solé, Gordana Raca, Adam C. Smith
Journal: American Journal of Hematology (2024)

Optical Genome Mapping (OGM) is rapidly emerging as an exciting cytogenomic technology both for research and clinical purposes. In the last 2 years alone, multiple studies have demonstrated that OGM not only matches the diagnostic scope of conventional standard of care cytogenomic clinical testing but it also adds significant new information in certain cases. Since OGM consolidates the diagnostic benefits of multiple costly and laborious tests (e.g., karyotyping, fluorescence in situ hybridization, and chromosomal microarrays) in a single cost-effective assay, many clinical laboratories have started to consider utilizing OGM. In 2021, an international working group of early adopters of OGM who are experienced with routine clinical cytogenomic testing in patients with hematological neoplasms formed a consortium (International Consortium for OGM in Hematologic Malignancies, henceforth "the Consortium") to create a consensus framework for implementation of OGM in a clinical setting. The focus of the Consortium is to provide guidance for laboratories implementing OGM in three specific areas: validation, quality control and analysis and interpretation of variants. Since OGM is a complex technology with many variables, we felt that by consolidating our collective experience, we could provide a practical and useful tool for uniform implementation of OGM in hematologic malignancies with the ultimate goal of achieving globally accepted standards.
Risk Assessment for Gastrointestinal Diseases via Clinical Dimension and Genome-Wide Polygenic Risk Scores of Type 2 Diabetes: A Population-Based Cohort Study
Authors: Tian Fu, Yuhao Sun, Shiyuan Lu, Jianhui Zhao, Lintao Dan, Wenming Shi, Jie Chen, Yan Chen, Xue Li
Journal: Diabetes Care (2024)

OBJECTIVE We aimed to evaluate whether individuals with type 2 diabetes (T2D) were at higher risk of developing a wide range of gastrointestinal diseases based on a population-based cohort study. RESEARCH DESIGN AND METHODS This study included 374,125 participants free of gastrointestinal disorders at baseline; of them, 19,719 (5.27%) with T2D were followed-up by linking to multiple medical records to record gastrointestinal disease diagnoses. Multivariable Cox models were used to estimate the hazard ratios (HRs) and CIs. Logistic models were used to examine the associations between polygenic risk scores (PRS) and clinical gastrointestinal phenotypes. RESULTS During a median follow-up of 12.0 years, we observed the new onset of 15 gastrointestinal diseases. Compared with nondiabetes, participants with T2D had an increased risk of gastritis and duodenitis (HR 1.58, 95% CI 1.51–1.65), peptic ulcer (HR 1.56, 95% CI 1.43–1.71), diverticular disease (HR 1.19, 95% CI 1.14–1.24), pancreatitis (HR 1.45, 95% CI 1.24–1.71), nonalcoholic fatty liver disease (HR 2.46, 95% CI 2.25–2.69), liver cirrhosis (HR 2.92, 95% CI 2.58–3.30), biliary disease (HR 1.18, 95% CI 1.10–1.26), gastrointestinal tract cancers (HR 1.28, 95% CI 1.17–1.40), and hepatobiliary and pancreatic cancer (HR 2.32, 95% CI 2.01–2.67). Positive associations of PRS of T2D with gastritis, duodenitis, and nonalcoholic fatty liver disease were also observed. CONCLUSIONS In this large cohort study, we found that T2D was associated with increased risks of a wide range of gastrointestinal outcomes. We suggest the importance of early detection and prevention of gastrointestinal disorders among patients with T2D.
Genetic effects of sequence-conserved enhancer-like elements on human complex traits
Authors: Xiang Zhu, Shining Ma, Wing Hung Wong
Journal: Genome biology (2024)

Abstract Background The vast majority of findings from human genome-wide association studies (GWAS) map to non-coding sequences, complicating their mechanistic interpretations and clinical translations. Non-coding sequences that are evolutionarily conserved and biochemically active could offer clues to the mechanisms underpinning GWAS discoveries. However, genetic effects of such sequences have not been systematically examined across a wide range of human tissues and traits, hampering progress to fully understand regulatory causes of human complex traits. Results Here we develop a simple yet effective strategy to identify functional elements exhibiting high levels of human-mouse sequence conservation and enhancer-like biochemical activity, which scales well to 313 epigenomic datasets across 106 human tissues and cell types. Combined with 468 GWAS of European (EUR) and East Asian (EAS) ancestries, these elements show tissue-specific enrichments of heritability and causal variants for many traits, which are significantly stronger than enrichments based on enhancers without sequence conservation. These elements also help prioritize candidate genes that are functionally relevant to body mass index (BMI) and schizophrenia but were not reported in previous GWAS with large sample sizes. Conclusions Our findings provide a comprehensive assessment of how sequence-conserved enhancer-like elements affect complex traits in diverse tissues and demonstrate a generalizable strategy of integrating evolutionary and biochemical data to elucidate human disease genetics.
T Cell Exhaustion
Authors: Andrew Baessler, Dario A.A. Vignali
Journal: Annual Review of Immunology (2024)

T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage to healthy cells and preventing autoimmunity. T cell exhaustion serves as a regulatory mechanism to limit the activity and effector function of T cells undergoing chronic antigen stimulation. Exhausted T cells exhibit poor proliferative potential; high inhibitory receptor expression; altered transcriptome, epigenome, and metabolism; and, most importantly, reduced effector function. While exhaustion helps to restrain damage caused by aberrant T cells in settings of autoimmune disease, it also limits the ability of cells to respond against persistent infection and cancer, leading to disease progression. Here we review the process of T cell exhaustion, detailing the key characteristics and drivers as well as highlighting our current understanding of the underlying transcriptional and epigenetic programming. We also discuss how exhaustion can be targeted to enhance T cell functionality in cancer.
Price negotiation and pricing of anticancer drugs in China: An observational study
Authors: Jing Zhou, Tianjiao Lan, Hao Lu, Jay Pan
Journal: PLoS Medicine (2024)

While China has implemented reimbursement-linked drug price negotiation annually since 2017, emphasizing value-based pricing to achieve a value-based strategic purchase of medical insurance, whether drug prices became better aligned with clinical value after price negotiation has not been sufficiently established. This study aimed to assess the changes in prices and their relationship with the clinical value of anticancer drugs after the implementation of price negotiations in China.
Critical Advances for Democratizing Ultrasound Diagnostics in Human and Veterinary Medicine
Authors: Ahmed El Kaffas, Jenny M. Vo-Phamhi, John F. Griffin, Kenneth Hoyt
Journal: Annual Review of Biomedical Engineering (2024)

The democratization of ultrasound imaging refers to the process of making ultrasound technology more accessible. Traditionally, ultrasound imaging has been predominately used in specialized medical facilities by trained professionals. Advancements in technology and changes in the health-care landscape have inspired efforts to broaden the availability of ultrasound imaging to various settings such as remote and resource-limited areas. In this review, we highlight several key factors that have contributed to the ongoing democratization of ultrasound imaging, including portable and handheld devices, recent advancements in technology, and training and education. Examples of diagnostic point-of-care ultrasound (POCUS) imaging used in emergency and critical care, gastroenterology, musculoskeletal applications, and other practices are provided for both human and veterinary medicine. Open challenges and the future of POCUS imaging are presented, including the emerging role of artificial intelligence in technology development.
Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues
Authors: Deva D. Chan, Farshid Guilak, Robert L. Sah, Sarah Calve
Journal: Annual Review of Biomedical Engineering (2024)

Hyaluronan (HA) plays well-recognized mechanical and biological roles in articular cartilage and synovial fluid, where it contributes to tissue structure and lubrication. An understanding of how HA contributes to the structure of other musculoskeletal tissues, including muscle, bone, tendon, and intervertebral discs, is growing. In addition, the use of HA-based therapies to restore damaged tissue is becoming more prevalent. Nevertheless, the relationship between biomechanical stimuli and HA synthesis, degradation, and signaling in musculoskeletal tissues remains understudied, limiting the utility of HA in regenerative medicine. In this review, we discuss the various roles and significance of endogenous HA in musculoskeletal tissues. We use what is known and unknown to motivate new lines of inquiry into HA biology within musculoskeletal tissues and in the mechanobiology governing HA metabolism by suggesting questions that remain regarding the relationship and interaction between biological and mechanical roles of HA in musculoskeletal health and disease.