tbuckley/cabot-search huggingface dataset:
Targeting Interferon Signalling in Systemic Lupus Erythematosus: Lessons Learned
Authors: Sarah A. Jones, Eric F. Morand
Journal: Drugs (2024)

The development of new medicines for systemic lupus erythematosus (SLE) has not addressed unmet clinical need, with only three drugs receiving regulatory approval for SLE in the last 60 years, one of which was specifically licensed for lupus nephritis. In the last 20 years it has become clear that activation of type 1 interferons (IFN) is reproducibly detected in the majority of SLE patients, and the actions of IFN in the immune system and on target tissues is consistent with a pathogenic role in SLE. These findings led to considerable drug discovery activity, first with agents directly targeting IFN family cytokines, with results that were encouraging but underwhelming. In contrast, targeting the type I IFN receptor with the monoclonal antibody anifrolumab, thereby blocking all IFN family members, was effective in a phase II clinical trial. This led to a pair of phase III trials, one of which was negative and the other positive, reflecting the difficulty of obtaining outcomes from trials in this complex disease. Nonetheless, the balance of evidence resulted in approval of anifrolumab in multiple jurisdictions from 2021 onwards. Multiple approaches to targeting the type 1 IFN pathway have subsequently had positive phase II clinical trials, including antibodies targeting cells that produce IFN, and small molecules targeting the receptor kinase TYK2, required for IFN signalling. Despite multiple hurdles, it is clear that IFN targeting in SLE is here to stay. The story of IFN-targeting therapy in SLE has lessons for drug development overall in this disease.
Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production
Authors: Xiaoying Sun, Liu Liu, Jiao Wang, Xiaorong Luo, Meng Wang, Chunxiao Wang, Jiale Chen, Yaqiong Zhou, Hang Yin, Yuanbin Song, Yuanyan Xiong, Hongjin Li, Meiling Zhang, Bo Zhu, Xin Li
Journal: Cellular and Molecular Immunology (2024)
Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma
Authors: Bruno Sangro, Peter R. Galle, Robin Kate Kelley, Chaiyut Charoentum, Enrico N. De Toni, Yurii Ostapenko, Jeong Heo, Ann-Lii Cheng, Andrea Wilson Woods, Charu Gupta, Jayne Abraham, Carrie L. McCoy, Nikunj Patel, Alejandra Negro, Arndt Vogel, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2024)

In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here.
CRISPR-Cas13b-mediated suppression of HBV replication and protein expression
Authors: Laura C. McCoullough, Mohamed Fareh, Wenxin Hu, Vitina Sozzi, Christina Makhlouf, Yianni Droungas, Chee Leng Lee, Mina Takawy, Stewart A. Fabb, Thomas J. Payne, Colin W. Pouton, Hans J. Netter, Sharon R. Lewin, Damian FJ. Purcell, Jacinta A. Holmes, Joseph A. Trapani, Margaret Littlejohn, Peter A. Revill
Journal: Journal of Hepatology (2024)

New antiviral approaches that target multiple aspects of the HBV replication cycle to improve rates of functional cure are urgently required. HBV RNA represents a novel therapeutic target. Here, we programmed CRISPR-Cas13b endonuclease to specifically target the HBV pregenomic RNA and viral mRNAs in a novel approach to reduce HBV replication and protein expression.
Engineering a Hydrazone and Triazole Crosslinked Hydrogel for Extrusion‐Based Printing and Cell Delivery
Authors: Matthew W. Jaeschke, Alexandra N. Borelli, Nathaniel P. Skillin, Timothy J. White, Kristi S. Anseth
Journal: Advanced Healthcare Materials (2024)

Abstract Covalent adaptable crosslinks, such as the alkyl‐hydrazone, endow hydrogels with unique viscoelastic properties applicable to cell delivery and bioink systems. However, the alkyl‐hydrazone crosslink lacks stability in biologically relevant environments. Furthermore, when formed with biopolymers such as hyaluronic acid (HA), low molecular weight polymers (&lt;60 kDa), or low polymer content (&lt;2 wt%) hydrogels are typically employed as entanglements reduce injectability. Here, a high molecular weight (&gt;60 kDa) HA alkyl‐hydrazone crosslinked hydrogel is modified with benzaldehyde‐poly(ethylene glycol) 3 ‐azide to incorporate azide functional groups. By reacting azide‐modified HA with a multi‐arm poly(ethylene glycol) (PEG) functionalized with bicyclononyne, stabilizing triazole bonds are formed through strain‐promoted azide‐alkyne cycloaddition (SPAAC). Increasing the fraction of triazole bonds within the hydrogel network from 0% to 12% SPAAC substantially increases stability. The slow gelation kinetics of the SPAAC reaction in the 12% SPAAC hydrogel enables transient self‐healing properties and a similar extrusion force as the 0% SPAAC hydrogel. Methyl‐PEG 4 ‐hydrazide is then introduced to further slowdown network evolution, which temporarily lowers the extrusion force, improves printability, and increases post‐extrusion mesenchymal stem cell viability and function in the 12% SPAAC hydrogel. This work demonstrates improved stability and temporal injectability of high molecular weight HA‐PEG hydrogels for extrusion‐based printing and cell delivery.
Backtracking NOM1::ETV6 fusion to neonatal pathogenesis of t(7;12) (q36;p13) infant AML
Authors: Pablo Bousquets-Muñoz, Oscar Molina, Ignacio Varela, Ángel Álvarez-Eguiluz, Javier Fernández-Mateos, Ana Gómez, Elena G. Sánchez, Milagros Balbín, David Ruano, Manuel Ramírez-Orellana, Xose S. Puente, Pablo Menéndez, Talia Velasco-Hernandez
Journal: Leukemia (2024)
ePRINT: exonuclease assisted mapping of protein-RNA interactions
Authors: Sophie Hawkins, Alexandre Mondaini, Seema C Namboori, Grady G Nguyen, Gene W Yeo, Asif Javed, Akshay Bhinge
Journal: Genome biology (2024)

Abstract RNA-binding proteins (RBPs) regulate key aspects of RNA processing including alternative splicing, mRNA degradation and localization by physically binding RNA molecules. Current methods to map these interactions, such as CLIP, rely on purifying single proteins at a time. Our new method, ePRINT, maps RBP-RNA interaction networks on a global scale without purifying individual RBPs. ePRINT uses exoribonuclease XRN1 to precisely map the 5′ end of the RBP binding site and uncovers direct and indirect targets of an RBP of interest. Importantly, ePRINT can also uncover RBPs that are differentially activated between cell fate transitions, including neural progenitor differentiation into neurons.
Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of the cell cycle
Authors: Carys S. Johnson, Matthew Williams, Kendig Sham, Serena Belluschi, Wenjuan Ma, Xiaonan Wang, Winnie W. Y. Lau, Kerstin B. Kaufmann, Gabriela Krivdova, Emily F. Calderbank, Nicole Mende, Jessica McLeod, Giovanna Mantica, Juan Li, Charlotte Grey-Wilson, Michael Drakopoulos, Shaaezmeen Basheer, Shubhankar Sinha, Evangelia Diamanti, Christina Basford, Nicola K. Wilson, Steven J. Howe, John E. Dick, Berthold Göttgens, Anthony R. Green, Natalie Francis, Elisa Laurenti
Journal: Blood (2024)

Loss of long-term hematopoietic stem cell (LT-HSC) function ex vivo hampers the success of clinical protocols that rely on culture. However, the kinetics and mechanisms through which this occurs remain incompletely characterized. In this study, through time-resolved single-cell RNA sequencing, matched in vivo functional analysis, and the use of a reversible in vitro system of early G1 arrest, we defined the sequence of transcriptional and functional events that occur during the first ex vivo division of human LT-HSCs. We demonstrated that the sharpest loss in LT-HSC repopulation capacity happens early on, between 6 and 24 hours of culture, before LT-HSCs commit to cell cycle progression. During this time window, LT-HSCs adapt to the culture environment, limit the global variability in gene expression, and transiently upregulate gene networks involved in signaling and stress responses. From 24 hours, LT-HSC progression past early G1 contributes to the establishment of differentiation programs in culture. However, contrary to the current assumptions, we demonstrated that the loss of HSC function ex vivo is independent of cell cycle progression. Finally, we showed that targeting LT-HSC adaptation to culture by inhibiting the early activation of JAK/STAT signaling improves HSC long-term repopulating function ex vivo. Collectively, our study demonstrated that controlling early LT-HSC adaptation to ex vivo culture, for example, via JAK inhibition, is critically important to improve HSC gene therapy and expansion protocols.
Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia.
Authors: Luisa Corrêa de Araujo Koury, Haesook T Kim, Maria Soledad Undurraga, Juan Ramon Navarro-Cabrera, Victor Salinas, Pablo Muxi, Raul A. M. Melo, Ana Beatriz F Gloria, Katia B.B. Pagnano, Elenaide C. Nunes, Rosane Isabel Bittencourt, Ninoska Rojas, Shirley Milenca Quintana Truyenque, Ana Ilda Ayala-Lugo, Ana Carolina Oliver, Lorena Lobo de Figueiredo-Pontes, Fabiola Traina, Frederico Moreira, Evandro M. Fagundes, Bruno Kosa L Duarte, Analí Pamela Mora-Alferez, Percy Ortiz, Jose Luis Untama, Martin S. Tallman, Raul C. Ribeiro, Arnold Ganser, Richard James Dillon, Peter J.M. Valk, Miguel A. Sanz, Bob Löwenberg, Nancy Berliner, Eduardo M. Rego
Journal: Blood (2024)
CD20-bispecific antibodies improve response to CD19-CAR T-cells in lymphoma in-vitro and CLL in-vivo models
Authors: Berit J. Brinkmann, Alessia Floerchinger, Christina Schniederjohann, Tobias Roider, Mariana Coelho, Norman Mack, Peter-Martin Bruch, Nora Liebers, Sarah Dötsch, Dirk H. Busch, Michael Schmitt, Frank Neumann, Philipp M. Roessner, Martina Seiffert, Sascha Dietrich
Journal: Blood (2024)
Barriers to engagement in the care cascade for tuberculosis disease in India: A systematic review of quantitative studies
Authors: Tulip A Jhaveri, Disha Jhaveri, Amith Galivanche, Maya Lubeck-Schricker, Dominic Voehler, Mei Chung, Pruthu Thekkur, Vineet Chadha, Ruvandhi Nathavitharana, Ajay M V Kumar, Hemant Deepak Shewade, Katherine Powers, Kenneth H Mayer, Jessica E Haberer, Paul Bain, Madhukar Pai, Srinath Satyanarayana, Ramnath Subbaraman
Journal: PLoS Medicine (2024)

India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India.
Response by Henriksen et al Regarding Article, “Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I–Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial”
Authors: Peter A. Henriksen, Peter Hall, Ninian N. Lang
Journal: Circulation (2024)
MicroRNA-122–Mediated Liver Detargeting Enhances the Tissue Specificity of Cardiac Genome Editing
Authors: Luzi Yang, Zhanzhao Liu, Gonglie Chen, Zhan Chen, Congting Guo, Xiangwen Ji, Qinghua Cui, Yueshen Sun, Xiaomin Hu, Yanjiang Zheng, Yifei Li, Fei Gao, Liang Chen, Pingzhu Zhou, William T. Pu, Yuxuan Guo
Journal: Circulation (2024)
Prenatal Magnesium Sulfate and Functional Connectivity in Offspring at Term-Equivalent Age
Authors: Steven Ufkes, Eleanor Kennedy, Tanya Poppe, Steven P. Miller, Benjamin Thompson, Jessie Guo, Jane E. Harding, Caroline A. Crowther
Journal: JAMA Network Open (2024)

Importance Understanding the effect of antenatal magnesium sulfate (MgSO 4 ) treatment on functional connectivity will help elucidate the mechanism by which it reduces the risk of cerebral palsy and death. Objective To determine whether MgSO 4 administered to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks is associated with increased functional connectivity and measures of functional segregation and integration in infants at term-equivalent age, possibly reflecting a protective mechanism of MgSO 4 . Design, Setting, and Participants This cohort study was nested within a randomized placebo-controlled trial performed across 24 tertiary maternity hospitals. Participants included infants born to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks who participated in the MAGENTA (Magnesium Sulphate at 30 to 34 Weeks’ Gestational Age) trial and underwent magnetic resonance imaging (MRI) at term-equivalent age. Ineligibility criteria included illness precluding MRI, congenital or genetic disorders likely to affect brain structure, and living more than 1 hour from the MRI center. One hundred and fourteen of 159 eligible infants were excluded due to incomplete or motion-corrupted MRI. Recruitment occurred between October 22, 2014, and October 25, 2017. Participants were followed up to 2 years of age. Analysis was performed from February 1, 2021, to February 27, 2024. Observers were blind to patient groupings during data collection and processing. Exposures Women received 4 g of MgSO 4 or isotonic sodium chloride solution given intravenously over 30 minutes. Main Outcomes and Measures Prior to data collection, it was hypothesized that infants who were exposed to MgSO 4 would show enhanced functional connectivity compared with infants who were not exposed. Results A total of 45 infants were included in the analysis: 24 receiving MgSO 4 treatment and 21 receiving placebo; 23 (51.1%) were female and 22 (48.9%) were male; and the median gestational age at scan was 40.0 (IQR, 39.1-41.1) weeks. Treatment with MgSO 4 was associated with greater voxelwise functional connectivity in the temporal and occipital lobes and deep gray matter structures and with significantly greater clustering coefficients (Hedge g , 0.47 [95% CI, −0.13 to 1.07]), transitivity (Hedge g , 0.51 [95% CI, −0.10 to 1.11]), local efficiency (Hedge g , 0.40 [95% CI, −0.20 to 0.99]), and global efficiency (Hedge g , 0.31 [95% CI, −0.29 to 0.90]), representing enhanced functional segregation and integration. Conclusions and Relevance In this cohort study, infants exposed to MgSO 4 had greater voxelwise functional connectivity and functional segregation, consistent with increased brain maturation. Enhanced functional connectivity is a possible mechanism by which MgSO 4 protects against cerebral palsy and death.
Mobile Mindfulness Intervention for Psychological Distress Among Intensive Care Unit Survivors
Authors: Christopher E. Cox, John A. Gallis, Maren K. Olsen, Laura S. Porter, Tina Gremore, Jeffrey M. Greeson, Cynthia Morris, Marc Moss, Catherine L. Hough
Journal: JAMA Internal Medicine (2024)

Although psychological distress is common among survivors of critical illness, there are few tailored therapies.
Mortality Risk Among Women With Premenstrual Disorders in Sweden
Authors: Marion Opatowski, Unnur Anna Valdimarsdóttir, Anna Sara Oberg, Elizabeth R. Bertone-Johnson, Donghao Lu
Journal: JAMA Network Open (2024)

Premenstrual disorders (PMDs) adversely affect the quality of life of millions of women worldwide, yet research on the long-term consequences of PMDs is limited, and the risk of mortality has not been explored.
Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Nephrolithiasis in Clinical Practice
Authors: Po-Ren Hsiao, James Cheng-Chung Wei
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Drinking Water of Patients With Chronic Kidney Disease—Get the Lead Out
Authors: Alexandra L. Polasko, Chi-yuan Hsu, May Chien
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Value in Optimizing the Components of App Interventions Before Final Testing
Authors: Heather Gwynn Allore, Mitchell H. Katz
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Financial Burden of Health Care in the Privately Insured US Population
Authors: Sukruth A. Shashikumar, ZhaoNian Zheng, Karen E. Joynt Maddox, Rishi K. Wadhera
Journal: JAMA Internal Medicine (2024)

This cross-sectional study examines how changes in privately insured families’ contributions to insurance premiums and out-of-pocket spending have affected the financial burden of health care in recent decades.
Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit
Authors: Mariana Parenti, Rebecca J. Schmidt, Daniel J. Tancredi, Irva Hertz-Picciotto, Cheryl K. Walker, Carolyn M. Slupsky
Journal: JAMA Network Open (2024)

Importance Disturbances in maternal, placental, and fetal metabolism are associated with developmental outcomes. Associations of maternal, placental, and fetal metabolism with subsequent neurodevelopmental outcomes in the child are understudied. Objective To investigate the metabolic associations within the maternal-placental-fetal unit and subsequent neurodevelopmental outcomes in younger siblings of children with autism spectrum disorder (ASD). Design, Setting, and Participants This cohort study was conducted within a subset of the Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) cohort. MARBLES is a prospective birth cohort of younger siblings of children with ASD assessed for neurodevelopmental outcomes at approximately age 36 months. Participants in MARBLES were recruited through the UC Davis MIND Institute. This subset of the MARBLES cohort included younger siblings born between 2009 and 2015. Maternal third trimester serum, placental tissue, and umbilical cord serum samples were collected from participants. Only pregnancies with at least 2 of these sample types were included in this analysis. Data analysis was conducted from March 1, 2023, to March 15, 2024. Exposures Quantitative metabolomics analysis was conducted on maternal third trimester serum, as well as placental tissue and umbilical cord serum collected at delivery. Main Outcomes and Measures Using the Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning, outcomes were classified as ASD, other nontypical development (non-TD), and typical development (TD). Results This analysis included 100 maternal serum samples, 141 placental samples, and 124 umbilical cord serum samples from 152 pregnancies (median [IQR] maternal age, 34.6 [30.8-38.3] years; median [IQR] gestational age, 39.0 [38.6-39.7] weeks; 87 [57.2%] male infants). There was no evidence that the maternal third trimester serum metabolome was significantly associated with the other metabolomes. The placental and cord serum metabolomes were highly correlated (first latent variate pair: R 2 = 0.75; P &amp;amp;lt; .001) and the variate scores for each tissue were significantly associated with reduced risk of non-TD (placenta: relative risk [RR], 0.13; 95% CI, 0.02-0.71; cord: RR, 0.13; 95% CI, 0.03-0.70) but not ASD (placenta: RR, 1.09; 95% CI, 0.42-2.81; cord: RR, 0.63; 95% CI, 0.23-1.73) compared with the TD reference group. Conclusions and Relevance In this cohort study of children with high familial risk of ASD, placental and cord serum metabolism at delivery were highly correlated. Furthermore, placental and cord serum metabolic profiles were associated with risk of non-TD.