tbuckley/cabot-search huggingface dataset:
Rare and severe adverse events in children with inflammatory bowel disease: analysis of data from the PIBD-SETQuality Safety Registry
Authors: Renz C W Klomberg, Astrid E Hellendoorn, Polychronis Kemos, Dimitris Rizopoulos, Frank M Ruemmele, Nicholas M Croft, Lissy de Ridder
Journal: The Lancet Child & Adolescent Health (2024)
Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial
Authors: Christian L Roth, Cecilia Scimia, Ashley H Shoemaker, Michael Gottschalk, Jennifer Miller, Guojun Yuan, Sonali Malhotra, M Jennifer Abuzzahab
Journal: The Lancet Diabetes & Endocrinology (2024)
Eye Care in Federally Qualified Health Centers
Authors: Maria A. Woodward, Patrice M. Hicks, Kristen Harris-Nwanyanwu, Bobeck Modjtahedi, R.V. Paul Chan, Emily L. Vogt, Ming-Chen Lu, Paula Anne Newman-Casey, R.V. Paul Chan, Aiyin Chen, Jeffery Henderer, Bobeck Modjtahedi, Kelly Muir, Paula Anne Newman-Casey, Diane Russo, Angelica C. Scanzera, Lindsay Rhodes, Maria A. Woodward
Journal: Ophthalmology (2024)
Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors
Authors: Aman Chauhan, Kelley Chan, Thorvardur R. Halfdanarson, Andrew M. Bellizzi, Guido Rindi, Dermot O’Toole, Phillip S. Ge, Dhanpat Jain, Arvind Dasari, Daniel A. Anaya, Emily Bergsland, Erik Mittra, Alice C. Wei, Thomas A. Hope, Ayse T. Kendi, Samantha M. Thomas, Sherlonda Flem, James Brierley, Elliot A. Asare, Kay Washington, Chanjuan Shi
Journal: CA A Cancer Journal for Clinicians (2024)

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.
Structural and Cognitive Mechanisms of Group Cohesion in Primates
Authors: R I M Dunbar
Journal: Behavioral and Brain Sciences (2024)

Abstract Group-living creates stresses that, all else equal, naturally lead to group fragmentation, and hence loss of the benefits that group-living provides. How species that live in large stable groups counteract these forces is not well understood. I use comparative data on grooming networks and cognitive abilities in primates to show that living in large, stable groups has involved a series of structural solutions designed to create chains of ‘friendship’ (friends-of-friends effects), increased investment in bonding behaviours (made possible by dietary adjustments) to ensure that coalitions work effectively, and neuronally expensive cognitive skills of the kind known to underpin social relationships in humans. The first ensures that individuals synchronise their activity cycles; the second allows the stresses created by group-living to be defused; and the third allows a large number of weak ties to be managed. Between them, these create a form of multilevel sociality based on strong versus weak ties similar to that found in human social networks. In primates, these strategies appear successively at quite specific group sizes, suggesting that they are solutions to ‘glass ceilings’ that would otherwise limit the range of group sizes that animals can live in (and hence the habitats they can occupy). This sequence maps closely onto the grades now known to underpin the Social Brain Hypothesis and the fractal pattern that is known to optimise information flow round networks.
Kinase-inactivated CDK6 preserves the long-term functionality of adult hematopoietic stem cells
Authors: Isabella Maria Mayer, Eszter Doma, Thorsten Klampfl, Michaela Prchal-Murphy, Sebastian Kollmann, Alessia Schirripa, Lisa Scheiblecker, Markus Zojer, Natalia Kunowska, Lea Gebrail, Lisa E Shaw, Ulrike Mann, Alex Farr, Reinhard Grausenburger, Gerwin Heller, Eva Zebedin-Brandl, Matthias Farlik, Marcos Malumbres, Veronika Sexl, Karoline Kollmann
Journal: Blood (2024)

Abstract Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and to replenish the hematopoietic system. The cell-cycle kinase cyclin-dependent kinase 6 (CDK6) regulates transcription, whereby it has both kinase-dependent and kinase-independent functions. Herein, we describe the complex role of CDK6, balancing quiescence, proliferation, self-renewal, and differentiation in activated HSCs. Mouse HSCs expressing kinase-inactivated CDK6 show enhanced long-term repopulation and homing, whereas HSCs lacking CDK6 have impaired functionality. The transcriptomes of basal and serially transplanted HSCs expressing kinase-inactivated CDK6 exhibit an expression pattern dominated by HSC quiescence and self-renewal, supporting a concept, in which myc-associated zinc finger protein (MAZ) and nuclear transcription factor Y subunit alpha (NFY-A) are critical CDK6 interactors. Pharmacologic kinase inhibition with a clinically used CDK4/6 inhibitor in murine and human HSCs validated our findings and resulted in increased repopulation capability and enhanced stemness. Our findings highlight a kinase-independent role of CDK6 in long-term HSC functionality. CDK6 kinase inhibition represents a possible strategy to improve HSC fitness.
HA-1–targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation
Authors: Elizabeth F. Krakow, Michelle Brault, Corinne Summers, Tanya M. Cunningham, Melinda A. Biernacki, R. Graeme Black, Kyle B. Woodward, Nicole Vartanian, Sami B. Kanaan, Albert C. Yeh, Robson G. Dossa, Merav Bar, Ryan D. Cassaday, Ann Dahlberg, Brian G. Till, Andrew E. Denker, Cecilia C. S. Yeung, Ted A. Gooley, David G. Maloney, Stanley R. Riddell, Philip D. Greenberg, Aude G. Chapuis, Evan W. Newell, Scott N. Furlan, Marie Bleakley
Journal: Blood (2024)
Sex and ethnic disparities in hepatitis B evaluation and treatment across the world
Authors: Sahith Kudaravalli, Daniel Q Huang, Ming-Lun Yeh, Lindsey Trinh, P C Tsai, Yao-Chun Hsu, Leslie Y Kam, Vy H Nguyen, Eiichi Ogawa, Dong Hyun Lee, Takanori Ito, Tsunamasa Watanabe, Masaru Enomoto, Carmen Monica Preda, Michael K L Ko, Rex Wan-Hin Hui, Masanori Atsukawa, Takanori Suzuki, Sebastian Marciano, Ana Barreira, Son Do, Haruki Uojima, Hirokazu Takahashi, Sabrina X Z Quek, Htet Htet Toe Wai Khine, Masatoshi Ishigami, Norio Itokawa, Min Seok Go, Ritsuzo Kozuka, Raluca Ioana Marin, Irina Sandra, Jiayi Li, Jian Q Zhang, Christopher Wong, Yoko Yoshimaru, Dang K H Vo, Cheng-Hao Tseng, Chul-Jin Lee, Kaori Inoue, Mayumi Maeda, Joseph K Hoang, Angela Chau, Wan-Long Chuang, Chia-Yen Dai, Jee-Fu Huang, Chung-Feng Huang, Maria Buti, Yasuhito Tanaka, Adrian Carlos Gadano, Man-Fung Yuen, Ramsey Cheung, Seng Gee Lim, Huy N Trinh, Hidenori Toyoda, Ming-Lung Yu, Mindie H Nguyen
Journal: Journal of Hepatology (2024)
Differences across the lifespan between females and males in the top 20 causes of disease burden globally: a systematic analysis of the Global Burden of Disease Study 2021
Authors: Vedavati Patwardhan, Gabriela F Gil, Alejandra Arrieta, Jack Cagney, Erin DeGraw, Molly E Herbert, Mariam Khalil, Erin C Mullany, Erin M O’Connell, Cory N Spencer, Caroline Stein, Aiganym Valikhanova, Emmanuela Gakidou, Luisa S Flor
Journal: The Lancet Public Health (2024)

BackgroundSex and gender shape health. There is a growing body of evidence focused on comprehensively and systematically examining the magnitude, persistence, and nature of differences in health between females and males. Here, we aimed to quantify differences in the leading causes of disease burden between females and males across ages and geographies.MethodsWe used the Global Burden of Disease Study 2021 to compare disability-adjusted life-year (DALY) rates for females and males for the 20 leading causes of disease burden for individuals older than 10 years at the global level and across seven world regions, between 1990 and 2021. We present absolute and relative differences in the cause-specific DALY rates between females and males.FindingsGlobally, females had a higher burden of morbidity-driven conditions with the largest differences in DALYs for low back pain (with 478·5 [95% uncertainty interval 346·3–632·8] more DALYs per 100 000 individuals among females than males), depressive disorders (348·3 [241·3–471·0]), and headache disorders (332·9 [48·3–731·9]), whereas males had higher DALY rates for mortality-driven conditions with the largest differences in DALYs for COVID-19 (with 1767·8 [1581·1–1943·5] more DALYs per 100 000 among males than females), road injuries (1012·2 [934·1–1092·9]), and ischaemic heart disease (1611·8 [1405·0–1856·3]). The differences between sexes became larger over age and remained consistent over time for all conditions except HIV/AIDS. The largest difference in HIV/AIDS was observed among those aged 25–49 years in sub-Saharan Africa with 1724·8 (918·8–2613·7) more DALYs per 100 000 among females than males.InterpretationThe notable health differences between females and males point to an urgent need for policies to be based on sex-specific and age-specific data. It is also important to continue promoting gender-sensitive research, and ultimately, implement interventions that not only reduce the burden of disease but also achieve greater health equity.FundingBill & Melinda Gates Foundation.
Age-specific and cause-specific mortality contributions to the socioeconomic gap in life expectancy in Germany, 2003–21: an ecological study
Authors: Fabian Tetzlaff, Markus Sauerberg, Pavel Grigoriev, Juliane Tetzlaff, Michael Mühlichen, Jens Baumert, Niels Michalski, Annelene Wengler, Enno Nowossadeck, Jens Hoebel
Journal: The Lancet Public Health (2024)

Earlier death among people in socioeconomically deprived circumstances has been found internationally and for various causes of death, resulting in a considerable life-expectancy gap between socioeconomic groups. We examined how age-specific and cause-specific mortality contributions to the socioeconomic gap in life expectancy have changed at the area level in Germany over time.
Interventions that prevent or respond to intimate partner violence against women and violence against children: a systematic review
Authors: Loraine J Bacchus, Manuela Colombini, Isabelle Pearson, Anik Gevers, Heidi Stöckl, Alessandra C Guedes
Journal: The Lancet Public Health (2024)

Efforts to prevent or respond to intimate partner violence (IPV) and violence against children (VAC) are still disparate worldwide, despite increasing evidence of intersections across these forms of violence. We conducted a systematic review to explore interventions that prevent or respond to IPV and VAC by parents or caregivers, aiming to identify common intervention components and mechanisms that lead to a reduction in IPV and VAC. 30 unique interventions from 16 countries were identified, with 20 targeting both IPV and VAC. Key mechanisms for reducing IPV and VAC in primary prevention interventions included improved communication, conflict resolution, reflection on harmful gender norms, and awareness of the adverse consequences of IPV and VAC on children. Therapeutic programmes for women and children who were exposed to IPV facilitated engagement with IPV-related trauma, increased awareness of the effects of IPV, and promoted avoidance of unhealthy relationships. Evidence gaps in low-income and middle-income countries involved adolescent interventions, post-abuse interventions for women and children, and interventions addressing both prevention and response to IPV and VAC. Our findings strengthen evidence in support of efforts to address IPV and VAC through coordinated prevention and response programmes. However, response interventions for both IPV and VAC are rare and predominantly implemented in high-income countries. Although therapeutic programmes for parents, caregivers, and children in high-income countries are promising, their feasibility in low-income and middle-income countries remains uncertain. Despite this uncertainty, there is potential to improve the use of health services to address IPV and VAC together.
Building disability-inclusive health systems
Authors: Hannah Kuper, Luthfi Azizatunnisa’, Danae Rodríguez Gatta, Sara Rotenberg, Lena Morgon Banks, Tracey Smythe, Phyllis Heydt
Journal: The Lancet Public Health (2024)

Health systems often fail people with disabilities, which might contribute to their shorter life expectancy and poorer health outcomes than people without disabilities. This Review provides an overview of the existing evidence on health inequities faced by people with disabilities and describes existing approaches to making health systems disability inclusive. Our Review documents a broad range of health-care inequities for people with disabilities (eg, lower levels of cancer screening), which probably contribute towards health differentials. We identified 90 good practice examples that illustrate current strategies to reduce inequalities. Implementing such strategies could help to ensure that health systems can expect, accept, and connect people with disabilities worldwide, deliver on their right to health, and achieve health for all.
The association between disability and mortality: a mixed-methods study
Authors: Hannah Kuper, Sara Rotenberg, Luthfi Azizatunnisa’, Lena Morgon Banks, Tracey Smythe
Journal: The Lancet Public Health (2024)

BackgroundGlobally, 1·3 billion people have a disability and are more likely to experience poor health than the general population. However, little is known about the mortality or life expectancy gaps experienced by people with disabilities. We aimed to undertake a systematic review and meta-analysis of the association between disability and mortality, compare these findings to the evidence on the association of impairment types and mortality, and model the estimated life expectancy gap experienced by people with disabilities.MethodsWe did a mixed-methods study, which included a systematic review and meta-analysis, umbrella review, and life expectancy modelling. For the systematic review and meta-analysis, we searched MEDLINE, Global Health, PsycINFO, and Embase for studies published in English between Jan 1, 2007, and June 7, 2023, investigating the association of mortality and disability. We included prospective and retrospective cohort studies and randomised controlled trials with a baseline assessment of disability and a longitudinal assessment of all-cause mortality or cause-specific mortality. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. We did a random-effects meta-analysis to calculate a pooled estimate of the mortality rate ratio for people with disabilities compared with those without disabilities. We did an umbrella review of meta-analyses examining the association between different impairment types and mortality. We used life table modelling to translate the mortality rate ratio into an estimate of the life expectancy gap between people with disabilities and the general population. The systematic review and meta-analysis is registered with PROSPERO, CRD42023433374.FindingsOur search identified 3731 articles, of which 42 studies were included in the systematic review. The meta-analysis included 31 studies. Pooled estimates showed that all-cause mortality was 2·24 times (95% CI 1·84–2·72) higher in people with disabilities than among people without disabilities, although heterogeneity between the studies was high (τ2=0·28, I2=100%). Modelling indicated a median gap in life expectancy of 13·8 years (95% CI 13·1–14·5) by disability status. Cause-specific mortality was also higher for people with disabilities, including for cancer, COVID-19, cardiovascular disease, and suicide. The umbrella review identified nine meta-analyses, which showed consistently elevated mortality rates among people with different impairment types.InterpretationMortality inequities experienced by people with disabilities necessitate health system changes and efforts to address inclusion and the social determinants of health.FundingNational Institute for Health and Care Research, Rhodes Scholarship, Indonesia Endowment Funds for Education, Foreign, Commonwealth and Development Office (Programme for Evidence to Inform Disability Action), and the Arts and Humanities Research Council.
Disability inclusivity: time to step up
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2024)

Worldwide, an estimated 1·3 billion people live with a disability—"long-term physical, mental, intellectual or sensory impairments which in interaction with various barriers may hinder their full and effective participation in society on an equal basis with others" according to the 2006 UN Convention on the Rights of Persons with Disabilities. People with disabilities too often die earlier and have poorer health than those without disabilities. With the ageing of the population their number grows annually, yet progress in tackling inequity and improving inclusivity has been disappointingly limited.
A Biomimetic Leaflet Scaffold for Aortic Valve Remodeling
Authors: Kenneth J. De Jesus Morales, Utari Santosa, Olga Brazhkina, Pranshu Rajurkar, Hanjoong Jo, Michael E. Davis
Journal: Advanced Healthcare Materials (2024)

Heart valve disease poses a significant clinical challenge, especially in pediatric populations, due to the inability of existing valve replacements to grow or respond biologically to their microenvironment. Tissue-engineered heart valves (TEHVs) provide a solution by facilitating patient-specific models for self-repair and remodeling. In this study, a 3D-bioprinted TEHV is designed to emulate the trilayer leaflet structure of an aortic valve. A cell-laden hydrogel scaffold made from gelatin methacrylate and polyethylene glycol diacrylate (GelMA/PEGDA) incorporates valvular interstitial-like (VIC-like) cells, being reinforced with a layer of polycaprolactone (PCL). The composition of the hydrogel scaffold remains stable over 7 days, having increased mechanical strength compared to pure GelMA. The scaffold maintains VIC-like cell function and promotes extracellular matrix (ECM) protein expression up to 14 days under two dynamic culture conditions: shear stress and stretching; replicating heart valve behavior within a more physiological-like setting and suggesting remodeling potential via ECM synthesis. This TEHV offers a promising avenue for valve replacements, closely replicating the structural and functional attributes of a native aortic valve, leading to mechanical and biological integration through biomaterial-cellular interactions.
ROS‐Responsive Injectable Hydrogel Loaded with SLC7A11‐modRNA Inhibits Ferroptosis and Mitigates Intervertebral Disc Degeneration in Rats
Authors: Tian Gao, Guangyu Xu, Tiancong Ma, Xiao Lu, Kaiwen Chen, Huanhuan Luo, Gang Chen, Jian Song, Xiaosheng Ma, Wei Fu, Chaojun Zheng, Xinlei Xia, Jianyuan Jiang
Journal: Advanced Healthcare Materials (2024)

Abstract Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, low back pain imposes a significant global economic burden. However, the effectiveness of treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective IVDD treatments by focusing on oxidative stress as a starting point. In this study, an injectable reactive oxygen species‐responsive hydrogel (PVA‐tsPBA@SLC7A11 modRNA) is developed, designed to achieve rapid loading and selective release of chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA is specifically used to upregulate the expression of the ferroptosis marker SLC7A11. The local injection of PVA‐tsPBA@SLC7A11 modRNA into the degenerated intervertebral disc (IVD) results in the cleavage of PVA‐tsPBA, leading to the release of enclosed SLC7A11 modRNA. The extent of SLC7A11 modRNA release is directly proportional to the severity of IVDD, ultimately ameliorating IVDD by inhibiting ferroptosis in nucleus pulposus cells (NPCs). This study proposes an innovative system of PVA‐tsPBA hydrogel‐encapsulated modRNA, representing a potential novel treatment strategy for patients with early‐stage IVDD.
RAS G12C Inhibitors: Three Birds with One Stone
Authors: Tessa Seale, Sandra Misale
Journal: Cancer Discovery (2024)

Summary: In this issue, Rubinson, Tanaka, and colleagues demonstrate that differences among G12C inhibitors rely on their ability to covalently bind not only G12C mutant KRAS but also NRAS and HRAS, proposing sotorasib as a potent NRAS G12C inhibitor. See related article by Rubinson et al., p. 727 (6).
Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura
Authors: Marie Scully, Ana Antun, Spero R. Cataland, Paul Coppo, Claire Dossier, Nathalie Biebuyck, Wolf-Achim Hassenpflug, Karim Kentouche, Paul Knöbl, Johanna A. Kremer Hovinga, M. Fernanda López-Fernández, Masanori Matsumoto, Thomas L. Ortel, Jerzy Windyga, Indranil Bhattacharya, Michael Cronin, Hong Li, Björn Mellgård, Munjal Patel, Parth Patwari, Shan Xiao, Pinghai Zhang, Linda T. Wang
Journal: New England Journal of Medicine (2024)

Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known.
Trial Update of Pitavastatin to Prevent Cardiovascular Events in HIV Infection
Authors: Steven K Grinspoon, Heather J Ribaudo, Pamela S Douglas
Journal: New England Journal of Medicine (2024)

In the final results of a randomized trial involving patients with HIV infection, pitavastatin reduced the incidence of adverse cardiovascular events at 5.6 years of follow-up as compared with placebo.
Neurometabolic Features of Takotsubo Syndrome
Authors: Francesco Santoro, Pierluigi Selvaggi, Rosaria D’apollo, Tommaso Martino, Mattia Veronese, Elena Carapelle, Ilaria Ragnatela, Damiano D’Alessandro, Enrica Vitale, Adriana Mallardi, Alessandra Leopizzi, Rosa Cetera, Matteo Di Biase, Sergio Modoni, Natale Daniele Brunetti
Journal: JACC. Cardiovascular imaging (2024)