tbuckley/cabot-search huggingface dataset:
Table of contents
Authors: Emily Baumrin, Alison Loren, Sandy Falk, Jacqueline Mays, Edward Cowen, Dirk Elston, Brett Sloan, Jonathan Kantor, A Clinician', Shima Ahmady, Patty Nelemans, Nicole Kelleners-Smeets, Aimee Arits, Michette De Rooij, Janneke Kessels, Brigitte Essers, Klara Mosterd, Helena Escola, Beatriz Llombart, Alba Escola `-Rodrı ´guez, Lucı ´a Barchino-Ortiz, Joaquim Marcoval, Inmaculada Alcaraz, So Nia Bea `-Arde ´bol, Agustı ´toll, Roma ´n Miñano-Medrano, Pedro Rodrı ´guez-Jime ´nez, Marı ´a Lo ´pez-Nuñez, Carla Ferra ´ndiz-Pulido, Ane Jaka, Emili Masferrer, Rafael Aguayo-Ortiz, Mireia Ye ´benes, Jorge Arandes-Marcocci, Vero ´nica Ruiz-Salas, ´a Turrio ´n-Merino, Miquel Just, Ju ´lia Sa ´nchez-Schmidt, Lorena Leal, Fa ´tima Mayo-Martı ´nez, Lara Haya-Martı ´nez, Alejandra Sandoval-Clavijo, Greta Dradi, Yolanda Delgado, Ju ´lia Verdaguer-Faja, Daniel Lo ´pez-Castillo, Ramon Pujol, Gustavo Deza, Michael Kwa, Alexandra Guttentag, Lauren Chase, Jeroen Van Meijgaard, Henry Lim, Bruce Strober, Laura Ferris, Kristina Duffin, Jud Janak, Adam Sima, Thomas Eckmann, Manish Patel, Huzefa Photowala, Vishvas Garg, April Armstrong, Eduardo Corona-Rodarte, Luis Cano-Aguilar, Luisa Fernanda Baldassarri-Ortego, Antonella Tosti, Daniel Asz-Sigall, Ogechi Ezemma, Shivali Devjani, Balaji Jothishankar, Kristen Kelley, Maryanne Senna, Maria Schneeweiss, Richard Wyss, Sebastian Schneeweiss, Priyanka Anand, Yinzhu Jin, Elyse Dicesare, Robert Glynn, Joseph Merola
Journal: Journal of the American Academy of Dermatology (2023)
Dysregulated iron homeostasis in dystrophin-deficient cardiomyocytes: correction by gene editing and pharmacological treatment
Authors: Kalina Andrysiak, Gabriela Machaj, Dominik Priesmann, Olga Woźnicka, Alicja Martyniak, Guillem Ylla, Marcus Krüger, Elżbieta Pyza, Anna Potulska-Chromik, Anna Kostera-Pruszczyk, Agnieszka Łoboda, Jacek Stępniewski, Józef Dulak
Journal: Cardiovascular Research (2023)

Abstract Aims Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a serious life-threatening complication, the mechanisms of which have not been fully established, and therefore no effective treatment is currently available. The purpose of the study was to identify new molecular signatures of the cardiomyopathy development in DMD. Methods and results For modelling of DMD-associated cardiomyopathy, we prepared three pairs of isogenic control and dystrophin-deficient human induced pluripotent stem cell (hiPSC) lines. Two isogenic hiPSC lines were obtained by CRISPR/Cas9-mediated deletion of DMD exon 50 in unaffected cells generated from healthy donor and then differentiated into cardiomyocytes (hiPSC-CM). The latter were subjected to global transcriptomic and proteomic analyses followed by more in-depth investigation of selected pathway and pharmacological modulation of observed defects. Proteomic analysis indicated a decrease in the level of mitoNEET protein in dystrophin-deficient hiPSC-CM, suggesting alteration in iron metabolism. Further experiments demonstrated increased labile iron pool both in the cytoplasm and mitochondria, a decrease in ferroportin level and an increase in both ferritin and transferrin receptor in DMD hiPSC-CM. Importantly, CRISPR/Cas9-mediated correction of the mutation in the patient-derived hiPSC reversed the observed changes in iron metabolism and restored normal iron levels in cardiomyocytes. Moreover, treatment of DMD hiPSC-CM with deferoxamine (DFO, iron chelator) or pioglitazone (mitoNEET stabilizing compound) decreased the level of reactive oxygen species in DMD hiPSC-CM. Conclusion To our knowledge, this study demonstrated for the first time impaired iron metabolism in human DMD cardiomyocytes, and potential reversal of this effect by correction of DMD mutation or pharmacological treatment. This implies that iron overload-regulating compounds may serve as novel therapeutic agents in DMD-associated cardiomyopathy.
Highlights of FDA Oncology Approvals in 2023: Bispecific T-cell Engagers, Pediatric Indications, and Inclusive Drug Development
Authors: Joshua M. Donaldson, Marjilla Seddiq, Michael J. Fusco, Shyamli Singla, Gulsum E. Pamuk, Rosa J. Lee-Alonzo, Bronwyn D. Mixter, Kirsten B. Goldberg, Laleh Amiri-Kordestani, R. Angelo de Claro, Nicole Drezner, Nicole J. Gormley, Bindu Kanapuru, Steven J. Lemery, Lola A. Fashoyin-Aje, Nicholas C. Richardson, Harpreet Singh, Daniel L. Suzman, Marc R. Theoret, Paul G. Kluetz, Richard Pazdur
Journal: Cancer Discovery (2023)

Summary: Cancer drug development remained robust in 2023. Highlights of U.S. drug approvals this year include new immunotherapies and targeted drug development in adult and pediatric patients as well as patients with rare diseases.
Endotrophin, a Key Marker and Driver for Fibroinflammatory Disease
Authors: Kim Henriksen, Federica Genovese, Alexander Reese-Petersen, Laurent P Audoly, Kai Sun, Morten A Karsdal, Philipp E Scherer
Journal: Endocrine Reviews (2023)

Our overview covers several key areas related to recent results obtained for collagen type VI and endotrophin (ETP). (1) An introduction to the history of ETP, including how it was identified, how it is released, and its function and potential receptors. (2) An introduction to the collagen family, with a focus on what differentiates collagen type VI from an evolutionary standpoint. (3) An overview of collagen type VI, the 6 individual chains (COL6A1, A2, A3, A4, A5, and A6), their differences and similarities, as well as their expression profiles and function. (4) A detailed analysis of COL6A3, including the cleaved product endotrophin, and what separates it from the other 5 collagen 6 molecules, including its suggested function based on insights gained from knockout and gain of function mouse models. (5) The pathology of ETP. What leads to its presence and release and what are the consequences thereof? (6) Functional implications of circulating ETP. Here we review the data with the functional roles of ETP in mind. (7) We propose that ETP is a mediator for fibrotic (or fibroinflammatory) disorders. Based on what we know about ETP, we have to consider it as a target for the treatment of fibrotic (or fibroinflammatory) disorders. What segment(s) of the patient population would most dramatically respond to an ETP-targeted intervention? How can we find the population that would profit most from an intervention? We aim to present a broad overview over the ETP field at large, providing an assessment of where the future research efforts need to be placed to tap into the vast potential of ETP, both as a marker and as a target in different diseases.
Climate change perception and its association with cancer screening intent
Authors: Zhiyu Qian, Edoardo Beatrici, Quoc-Dien Trinh, Adam S Kibel, Stacy Loeb, Hari S Iyer, Alexander P Cole
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract As the climate crisis deepens, its adverse effects on human health are becoming evident, including impacts on cancer pathogenesis and treatment. This study explored the link between individuals’ awareness of the health impacts of climate change and interest in cancer screening. Using the 2021 Health Information National Trends Survey, our study demonstrated a statistically significant association between recognition of climate change as a personal health threat and interest in cancer screening. Although the study’s retrospective nature and self-reported data pose some limitations, these findings signal a promising avenue for future research on the intersection of climate and cancer risk. This research supports the development of public health interventions that incorporate components of environmental health literacy alongside cancer screening efforts.
Beyond antiviral: Interferon induced by bacteria maintains tolerance in the gut
Authors: Yi Yang, Ken Cadwell
Journal: The Journal of Experimental Medicine (2023)

Type I interferons are best known for their antiviral role. Here, Ayala et al. (https://doi.org/10.1084/jem.20230063) reveal that commensal bacteria elicit tonic type I interferons to prime dendritic cells and induce regulatory T cells that maintain a tolerogenic intestinal milieu.
Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial
Authors: Andrew McGarry, Shane Rosanbalm, Mika Leinonen, C Warren Olanow, Dennis To, Adam Bell, Daniel Lee, Jamie Chang, Jordan Dubow, Rohit Dhall, Daniel Burdick, Sotirios Parashos, Jeanne Feuerstein, Joseph Quinn, Rajesh Pahwa, Mitra Afshari, Aldolfo Ramirez-Zamora, Kelvin Chou, Arjun Tarakad, Corneliu Luca, Kevin Klos, Yvette Bordelon, Marie-Helene St Hiliare, David Shprecher, Seulki Lee, Ted M Dawson, Viktor Roschke, Karl Kieburtz
Journal: The Lancet Neurology (2023)
Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study
Authors: Angela Schulz, Nicola Specchio, Emily de los Reyes, Paul Gissen, Miriam Nickel, Marina Trivisano, Shawn C Aylward, Anupam Chakrapani, Christoph Schwering, Eva Wibbeler, Lena Marie Westermann, Douglas J Ballon, Jonathan P Dyke, Anu Cherukuri, Shailesh Bondade, Peter Slasor, Jessica Cohen Pfeffer
Journal: The Lancet Neurology (2023)
Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis
Authors: Christos Thomadakis, Ilias Gountas, Erika Duffell, Konstantinos Gountas, Benjamin Bluemel, Thomas Seyler, Filippo Maria Pericoli, Irene Kászoni-Rückerl, Ziad El-Khatib, Martin Busch, Irene Schmutterer, Thomas Vanwolleghem, Sofieke Klamer, Els Plettinckx, Laure Mortgat, Dominique Van Beckhoven, Tonka Varleva, Mirjana Lana Kosanovic Licina, Tatjana Nemeth Blazic, Diana Nonković, Fanitsa Theophanous, Vratislav Nemecek, Marek Maly, Peer Brehm Christensen, Susan Cowan, Kristi Rüütel, Henrikki Brummer-Korvenkontio, Cécile Brouard, Gyde Steffen, Amrei Krings, Sandra Dudareva, Ruth Zimmermann, Georgia Nikolopoulou, Zsuzsanna Molnár, Emese Kozma, Magnús Gottfredsson, Niamh Murphy, Loreta A. Kondili, Maria Elena Tosti, Anna Rita Ciccaglione, Barbara Suligoi, Raina Nikiforova, Renate Putnina, Ligita Jancoriene, Carole Seguin-Devaux, Tanya Melillo, Anders Boyd, Marc van der Valk, Eline Op de Coul, Robert Whittaker, Hilde Kløvstad, Małgorzata Stępień, Magdalena Rosińska, Cristina Valente, Rui Tato Marinho, Odette Popovici, Mária Avdičová, Jana Kerlik, Irena Klavs, Mojca Maticic, Asuncion Diaz, Julia del Amo, Josefine Lundberg Ederth, Maria Axelsson, Georgios Nikolopoulos
Journal: The Lancet Regional Health - Europe (2023)

Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. ECDC.
Invasive group A streptococcal infections in children and adolescents in Denmark during 2022–23 compared with 2016–17 to 2021–22: a nationwide, multicentre, population-based cohort study
Authors: Ulrikka Nygaard, Ulla Birgitte Hartling, Charlotte Munkstrup, Allan Bybeck Nielsen, Kia Hee Schultz Dungu, Lisbeth Samsø Schmidt, Jonathan Glenthøj, Astrid Thaarup Matthesen, Maren Johanne Heilskov Rytter, Mette Holm
Journal: The Lancet Child & Adolescent Health (2023)
Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial
Authors: Mukul Sharma, Carlos A Molina, Kazunori Toyoda, Daniel Bereczki, Shrikant I Bangdiwala, Scott E Kasner, Helmi L Lutsep, Georgios Tsivgoulis, George Ntaios, Anna Czlonkowska, Ashfaq Shuaib, Pierre Amarenco, Matthias Endres, Byung-Woo Yoon, David Tanne, Danilo Toni, Laetitia Yperzeele, Paul von Weitzel-Mudersbach, Gisele Sampaio Silva, Alvaro Avezum, Jesse Dawson, Daniel Strbian, Turgut Tatlisumak, Jens Eckstein, Sebastián F Ameriso, Joerg R Weber, Else Charlotte Sandset, Nana Goar Pogosova, Pablo M Lavados, Antonio Arauz, David Gailani, Hans-Christoph Diener, Richard A Bernstein, Charlotte Cordonnier, Anja Kahl, Grigor Abelian, Mark Donovan, Chahin Pachai, Danshi Li, Graeme J Hankey
Journal: The Lancet Neurology (2023)
Neurological adverse events of immune checkpoint inhibitors and the development of paraneoplastic neurological syndromes
Authors: Antonio Farina, Macarena Villagrán-García, Alberto Vogrig, Anastasia Zekeridou, Sergio Muñiz-Castrillo, Roser Velasco, Amanda C Guidon, Bastien Joubert, Jérôme Honnorat
Journal: The Lancet Neurology (2023)
Early growth, stress, and socioeconomic factors as predictors of the rate of multimorbidity accumulation across the life course: a longitudinal birth cohort study
Authors: Markus J Haapanen, Davide L Vetrano, Tuija M Mikkola, Amaia Calderón-Larrañaga, Serhiy Dekhtyar, Eero Kajantie, Johan G Eriksson, Mikaela B von Bonsdorff
Journal: The Lancet Healthy Longevity (2023)

BackgroundEarly growth, stress, and socioeconomic factors are associated with future risk of individual chronic diseases. It is uncertain whether they also affect the rate of multimorbidity accumulation later in life. This study aimed to explore whether early life factors are associated with the rate at which chronic diseases are accumulated across older age.MethodsIn this national birth cohort study, we studied people born at Helsinki University Central Hospital, Helsinki, Finland between Jan 1, 1934, and Dec 31, 1944, who attended child welfare clinics in the city, and were living in Finland in 1971. Individuals who had died or emigrated from Finland before 1987 were excluded, alongside participants without any registry data and who died before the end of the registry follow-up on Dec 31, 2017. Early anthropometry, growth, wartime parental separation, and socioeconomic factors were recorded from birth, child welfare clinic, or school health-care records, and Finnish National Archives. International Classification of Diseases codes of diagnoses for chronic diseases were obtained from the Care Register for Health Care starting from 1987 (when participants were aged 42–53 years) until 2017. Linear mixed models were used to study the association between early-life factors and the rate of change in the number of chronic diseases over 10-year periods.FindingsFrom Jan 1, 1934, to Dec 31, 2017, 11 689 people (6064 [51·9%] men and 5625 [48·1%] women) were included in the study. Individuals born to mothers younger than 25 years (β 0·09; 95% CI 0·06–0·12), mothers with a BMI of 25–30 kg/m2 (0·08; 0·05–0·10), and mothers with a BMI more than 30 kg/m2 (0·26; 0·21–0·31) in late pregnancy accumulated chronic diseases faster than those born to older mothers (25–30 years) and those with a BMI of less than 25 kg/m2. Individuals with a birthweight less than 2·5 kg (0·17; 0·10–0·25) and those with a rapid growth in height and weight from birth until age 11 years accumulated chronic diseases faster during their life course. Additionally, paternal occupational class (manual workers vs upper-middle class 0·27; 0·23–0·30) and wartime parental separation (0·24; 0·19–0·29 for boys; 0·31; 0·25–0·36 for girls) were associated with a faster rate of chronic disease accumulation.InterpretationOur findings suggest that the foundation for accumulating chronic diseases is established early in life. Early interventions might be needed for vulnerable populations, including war evacuee children and children with lower socioeconomic status.FundingFinska Läkaresällskapet, Liv och Hälsa rf, the Finnish Pediatric Research Foundation, and Folkhälsan Research Center.TranslationsFor the Finnish and Swedish translations of the abstract see Supplementary Materials section.
Longitudinal pathways between childhood BMI, body dissatisfaction, and adolescent depression: an observational study using the UK Millennium Cohort Study
Authors: Emma Blundell, Bianca L De Stavola, Madelaine Davies Kellock, Yvonne Kelly, Gemma Lewis, Anne McMunn, Dasha Nicholls, Praveetha Patalay, Francesca Solmi
Journal: The Lancet Psychiatry (2023)

BackgroundGlobally, more adolescents are having depressive symptoms than in the past. High BMI is a risk factor for depressive symptoms, potentially acting via increased body dissatisfaction. Robust longitudinal evidence of these associations could help to inform preventive interventions, but such evidence remains scarce. We investigated the longitudinal associations between BMI at age 7 years and depressive symptoms at age 14 years (objective 1), BMI at age 7 years and body dissatisfaction at age 11 years (objective 2), and body dissatisfaction at age 11 years and depression at age 14 years (objective 3). We also investigated the extent to which body dissatisfaction mediated the association between BMI and depressive symptoms (objective 4).MethodsThis study used data from the Millennium Cohort Study, a representative longitudinal general population cohort of UK children born between Sept 1, 2000, and Jan 11, 2002. We used univariable and multivariable linear regression models to investigate the associations in objectives 1–3 adjusting for a range of child-level and family-level confounders. For mediation analyses we used non-parametric g-formula (objective 4). We reported stratified results in presence of sex differences. All analyses were based on participants with complete BMI data and imputed confounders and outcomes.FindingsOur sample included 13 135 participants. Of these, 6624 (50·4%) were male participants and 6511 (49·6%) were female participants; 11 096 (84·4%) were of White ethnicity and 2039 (15·6%) were from a minority ethnic background. At baseline, mean age was 7·2 years (SD 0·25, range 6·3–8·3). In multivariable models, an SD increase in BMI at age 7 years was associated with greater depressive symptoms at age 14 years (estimated regression coefficient [coeff]: 0·30, 95% CI 0·17–0·43) and greater body dissatisfaction at age 11 years (coeff 0·15, 0·12–0·18). Greater body dissatisfaction at age 11 years was associated with higher depressive symptoms at age 14 years (coeff 0·60, 0·52–0·68). All these associations were twice as large in girls as in boys. Body dissatisfaction explained 43% of the association between BMI and depression in girls.InterpretationOur findings bear relevance for interventions aimed at reducing weight in childhood and reducing body dissatisfaction. Implementation of evidence-based body image interventions and identification of drivers of weight stigma should be key public health priorities. Interventions aiming to reduce weight in childhood need to avoid increasing body dissatisfaction and should target environmental drivers of weight rather than individuals.FundingWellcome Trust; The Royal Society; Economic and Social Research Council; and the National Institute for Health and Care Research.
Leveraging Lymphatic System Targeting in Systemic Lupus Erythematosus for Improved Clinical Outcomes
Authors: K.T. Babalola, M. Arora, R. Ganugula, S.K. Agarwal, C. Mohan, M.N.V. Ravi Kumar
Journal: Pharmacological Reviews (2023)

<h3>Abstract</h3> The involvement of the prostaglandin E2 (PGE2) system in cancer progression has long been recognized. PGE2 functions as an autocrine and paracrine signaling molecule with pleiotropic effects in the human body. High levels of intratumoral PGE2 and overexpression of the key metabolic enzymes of PGE2 have been observed and suggested to contribute to tumor progression. This has been claimed for different types of solid tumors, including, but not limited to, lung, breast, and colon cancer. PGE2 has direct effects on tumor cells and angiogenesis that are known to promote tumor development. However, one of the main mechanisms behind PGE2 driving cancerogenesis is currently thought to be anchored in suppressed antitumor immunity, thus providing possible therapeutic targets to be used in cancer immunotherapies. EP2 and EP4, two receptors for PGE2, are emerging as being the most relevant for this purpose. This review aims to summarize the known roles of PGE2 in the immune system and its functions within the tumor microenvironment. <h3>Significance Statement</h3> Prostaglandin E2 (PGE2) has long been known to be a signaling molecule in cancer. Its presence in tumors has been repeatedly associated with disease progression. Elucidation of its effects on immunological components of the tumor microenvironment has highlighted the potential of PGE2 receptor antagonists in cancer treatment, particularly in combination with immune checkpoint inhibitor therapeutics. Adjuvant treatment could increase the response rates and the efficacy of immune-based therapies.