tbuckley/cabot-search huggingface dataset:
Clinically meaningful improvements in patient‐reported outcomes in mitapivat‐treated patients with pyruvate kinase deficiency
Authors: Kevin H. M. Kuo, Rachael F. Grace, Eduard J. van Beers, Wilma Barcellini, Andreas Glenthøj, Susanne Holzhauer, Vanessa Beynon, Susan Morris, Junlong Li, Erin Zagadailov, Parija Patel, Hanny Al‐Samkari
Journal: American Journal of Hematology (2024)

Clinically meaningful benefits in the signs, symptoms, and impacts of #PKDeficiency as assessed by disease-specific patient-reported outcome measures were observed in mitapivat-treated adult patients in two phase 3 clinical trials.
Poly (Betulinic Acid) Nanoparticles Loaded with bFGF Improve Functional Recovery After Spinal Cord Injury (Adv. Healthcare Mater. 12/2024)
Authors: Xianghang Chen, Beini Wang, Yongxiu Zhou, Xuejuan Wu, Anyu Du, Abdullah Al Mamun, Yitie Xu, Shuangshuang Wang, Chang Jiang, Ling Xie, Kailiang Zhou, Siwang Hu, Jian Xiao
Journal: Advanced Healthcare Materials (2024)
Adeno‐Associated Virus‐Encapsulated Alginate Microspheres Loaded in Collagen Gel Carriers for Localized Gene Transfer (Adv. Healthcare Mater. 12/2024)
Authors: Yuta Kurashina, Sho Kurihara, Takeshi Kubota, Shuhei Takatsuka, Motoki Hirabayashi, Hajime Shimmura, Hideo Miyahara, Aiki Hioki, Yutaka Matsushita, Jumpei Muramatsu, Yuki Ogawa, Masato Fujioka, Hirotaka J. Okano, Hiroaki Onoe
Journal: Advanced Healthcare Materials (2024)
Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension
Authors: Stefanos Zafeiropoulos, Umair Ahmed, Alexandra Bekiaridou, Naveen Jayaprakash, Ibrahim T. Mughrabi, Nafiseh Saleknezhad, Chrystal Chadwick, Anna Daytz, Izumi Kurata-Sato, Yemil Atish-Fregoso, Kaitlin Carroll, Yousef Al-Abed, Marat Fudim, Christopher Puleo, George Giannakoulas, Mark R. Nicolls, Betty Diamond, Stavros Zanos
Journal: Circulation Research (2024)

Inflammation is pathogenically implicated in pulmonary arterial hypertension; however, it has not been adequately targeted therapeutically. We investigated whether neuromodulation of an anti-inflammatory neuroimmune pathway involving the splenic nerve using noninvasive, focused ultrasound stimulation of the spleen (sFUS) can improve experimental pulmonary hypertension.
Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia
Authors: Xiaoli Gong, Wei He, Wan Jin, Hongwei Ma, Gang Wang, Jiaxin Li, Yu Xiao, Yangyu Zhao, Qiong Chen, Huanhuan Guo, Jiexia Yang, Yiming Qi, Wei Dong, Meng Fu, Xiaojuan Li, Jiusi Liu, Xinghui Liu, Aihua Yin, Yi Zhang, Yuan Wei
Journal: Genome biology (2024)

Abstract Background Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. Results By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. Conclusions Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal–fetal interface formation.
How to hit the allergy target: A critical appraisal of intralymphatic immunotherapy with practical recommendations on ultrasound‐guided injections
Authors: Stephan Flory, Bjarke Hviid‐Vyff, Lara Šošić, Johannes M. Schmid, Lars Ahlbeck, Emma C. J. Widmer, Claudia C. V. Lang, Kristian Ikenberg, Thomas M. Kündig, Hans Jürgen Hoffmann, Pål Johansen
Journal: Allergy (2024)

Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported, despite the recognized fact that treatment efficacy relies on the ability to inject the allergen intranodally.
Multimodal data fusion using sparse canonical correlation analysis and cooperative learning: a COVID-19 cohort study
Authors: Ahmet Gorkem Er, Daisy Yi Ding, Berrin Er, Mertcan Uzun, Mehmet Cakmak, Christoph Sadee, Gamze Durhan, Mustafa Nasuh Ozmen, Mine Durusu Tanriover, Arzu Topeli, Yesim Aydin Son, Robert Tibshirani, Serhat Unal, Olivier Gevaert
Journal: npj Digital Medicine (2024)

Through technological innovations, patient cohorts can be examined from multiple views with high-dimensional, multiscale biomedical data to classify clinical phenotypes and predict outcomes. Here, we aim to present our approach for analyzing multimodal data using unsupervised and supervised sparse linear methods in a COVID-19 patient cohort. This prospective cohort study of 149 adult patients was conducted in a tertiary care academic center. First, we used sparse canonical correlation analysis (CCA) to identify and quantify relationships across different data modalities, including viral genome sequencing, imaging, clinical data, and laboratory results. Then, we used cooperative learning to predict the clinical outcome of COVID-19 patients: Intensive care unit admission. We show that serum biomarkers representing severe disease and acute phase response correlate with original and wavelet radiomics features in the LLL frequency channel (cor(Xu
Plasma Metabolic Profiles-Based Prediction of Induction Chemotherapy Efficacy in Nasopharyngeal Carcinoma: Results of a Bidirectional Clinical Trial
Authors: Tingxi Tang, Zhenhua Zhou, Min Chen, Nan Li, Jianda Sun, Zekai Chen, Ting Xiao, Xiaoqing Wang, Longshan Zhang, Yingqiao Wang, Hanbin Zhang, Xiuting Zheng, Bei Chen, Feng Ye, Jian Guan
Journal: Clinical Cancer Research (2024)

The efficacy of induction chemotherapy (IC) as a primary treatment for advanced nasopharyngeal carcinoma (NPC) remains a topic of debate, with a lack of dependable biomarkers for predicting its efficacy. This study seeks to establish a predictive classifier using plasma metabolomics profiles.
Spondylothoracic Dysostosis: Crab-like Rib Cage Configuration in a Jarcho-Levin Syndrome Neonate
Authors: Kimberly D. García-Irizarry, Joseph J. Perez-Ortiz, Jesús M. Meléndez-Montañez, Wilfredo De Jesús-Rojas
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Spondylothoracic Dysostosis: Crab-like Rib Cage Configuration in a Jarcho-Levin Syndrome Neonate." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Risk of Adverse Neonatal Outcomes After Combined Prenatal Cannabis and Nicotine Exposure
Authors: B. Adam Crosland, Bharti Garg, Gretchen E. Bandoli, Ava D. Mandelbaum, Sarena Hayer, Kimberly S. Ryan, Lyndsey E. Shorey-Kendrick, Cindy T. McEvoy, Eliot R. Spindel, Aaron B. Caughey, Jamie O. Lo
Journal: JAMA Network Open (2024)

Importance The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone. Objective To assess the perinatal outcomes associated with combined cannabis and nicotine exposure compared with each substance alone during pregnancy. Design, Setting, and Participants This retrospective population-based cohort study included linked hospital discharge data (obtained from the California Department of Health Care Access and Information) and vital statistics (obtained from the California Department of Public Health) from January 1, 2012, through December 31, 2019. Pregnant individuals with singleton gestations and gestational ages of 23 to 42 weeks were included. Data were analyzed from October 14, 2023, to March 4, 2024. Exposures Cannabis-related diagnosis and prenatal nicotine product use were captured using codes from International Classification of Diseases, Ninth Revision, Clinical Modification , and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification . Main Outcome and Measures The main outcomes were infant and neonatal death, infants small for gestational age, and preterm delivery. Results were analyzed by multivariable Poisson regression models. Results A total of 3 129 259 pregnant individuals were included (mean [SD] maternal age 29.3 [6.0] years), of whom 23 007 (0.7%) had a cannabis-related diagnosis, 56 811 (1.8%) had a nicotine-use diagnosis, and 10 312 (0.3%) had both in pregnancy. Compared with nonusers, those with cannabis or nicotine use diagnoses alone had increased rates of infant (0.7% for both) and neonatal (0.3% for both) death, small for gestational age (14.3% and 13.7%, respectively), and preterm delivery (&amp;amp;lt;37 weeks) (12.2% and 12.0%, respectively). Moreover, risks in those with both cannabis and nicotine use were higher for infant death (1.2%; adjusted risk ratio [ARR], 2.18 [95% CI, 1.82-2.62]), neonatal death (0.6%; ARR, 1.76 [95% CI, 1.36-2.28]), small for gestational age (18.0%; ARR, 1.94 [95% CI, 1.86-2.02]), and preterm delivery (17.5%; ARR, 1.83 [95% CI, 1.75-1.91]). Conclusions and Relevance These findings suggest that co-occurring maternal use of cannabis and nicotine products in pregnancy is associated with an increased risk of infant and neonatal death and maternal and neonatal morbidity compared with use of either substance alone. Given the increasing prevalence of combined cannabis and nicotine use in pregnancy, these findings can help guide health care practitioners with preconception and prenatal counseling, especially regarding the benefits of cessation.
Phosphorylation-Dependent Regulation of Guanylyl Cyclase (GC)-A and Other Membrane GC Receptors
Authors: Lincoln R Potter
Journal: Endocrine Reviews (2024)

Receptor guanylyl cyclases (GCs) are single membrane spanning, multidomain enzymes, that synthesize cGMP in response to natriuretic peptides or other ligands. They are evolutionarily conserved from sea urchins to humans and regulate diverse physiologies. Most family members are phosphorylated on 4 to 7 conserved serines or threonines at the beginning of their kinase homology domains. This review describes studies that demonstrate that phosphorylation and dephosphorylation are required for activation and inactivation of these enzymes, respectively. Phosphorylation sites in GC-A, GC-B, GC-E, and sea urchin receptors are discussed, as are mutant receptors that mimic the dephosphorylated inactive or phosphorylated active forms of GC-A and GC-B, respectively. A salt bridge model is described that explains why phosphorylation is required for enzyme activation. Potential kinases, phosphatases, and ATP regulation of GC receptors are also discussed. Critically, knock-in mice with glutamate substitutions for receptor phosphorylation sites are described. The inability of opposing signaling pathways to inhibit cGMP synthesis in mice where GC-A or GC-B cannot be dephosphorylated demonstrates the necessity of receptor dephosphorylation in vivo. Cardiac hypertrophy, oocyte meiosis, long-bone growth/achondroplasia, and bone density are regulated by GC phosphorylation, but additional processes are likely to be identified in the future.
<i>Curcuma Longa</i>: Nutraceutical Use and Association With Nanotechnology
Authors: Gabriela Corrêa Carvalho, Gabriel Davi Marena, Micaela Gaspar Gonçalves Fernandes, Gabriela Ricci Leonardi, Hélder A. Santos, Marlus Chorilli
Journal: Advanced Healthcare Materials (2024)

Curcumin is a natural product found in the rhizome of Curcuma longa (L.) and other Curcuma spp. As a lipophilic molecule, it has greater affinity for polar, non-polar, alkaline, or extremely acidic organic solvents. Several studies indicate that curcumin has several benefits for human health, for example, against degenerative diseases, cancer, and infectious diseases. To obtain a quality product with nutraceutical properties, it is necessary to know its physicochemical characteristics and preserve it from cultivation until ingestion by the human. However, its low solubility leads to low absorption; in this context, nanotechnological systems can contribute to increase curcumin bioavailability. This review aims to highlight important issues in all stages that curcumin goes through: from aspects related to its extraction to its association with nanotechnology. Although curcumin extraction process is already well established, it is possible to observe more and more research focused on increasing yield and being more environmentally friendly. Further, curcumin's low absorption is notable due to its physicochemical characteristics, mainly due to its low aqueous solubility. However, its association with nanotechnology shows to be promising and an increasingly growing trend because the use of this "Indian solid gold" is the hope of many patients.
Neurological or Psychiatric Disorders After Dengue Fever
Authors: Hong-Ci Lin, Hsueh-Pu Chou, Yung-Chih Chiang, Renin Chang, Yao-Shen Chen, Yu-Chung Juan
Journal: JAMA Network Open (2024)

This cohort study investigates the association between dengue fever and risk of neurological and psychiatric disorders among adults in Taiwan.
Improved CAR-T cell activity associated with increased mitochondrial function primed by galactose
Authors: Golda Gross, Suha Alkadieri, Amilia Meir, Orit Itzhaki, Yarden Aharoni-Tevet, Shahar Ben Yosef, Angi Zenab, Liat Shbiro, Amos Toren, Tal Yardeni, Elad Jacoby
Journal: Leukemia (2024)
Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression
Authors: Qingwen Qian, Mark Li, Zeyuan Zhang, Shannon W. Davis, Kamal Rahmouni, Andrew W. Norris, Huojun Cao, Wen-Xing Ding, Gökhan S. Hotamisligil, Ling Yang
Journal: Cell Metabolism (2024)
Engaging Patients in Decision Making about Treatment of Kidney Failure
Authors: Jennifer deGraauw, Susan P.Y. Wong
Journal: Journal of the American Society of Nephrology (2024)

1New Mexico VA Health Care System, University of New Mexico, Albuquerque, New Mexico 2Renal Dialysis Unit, VA Puget Sound Health Care System, University of Washington, Seattle, Washington Correspondence: Dr. Susan P.Y. Wong, email: [email protected] See related article, "Decision-Making Engagement Preferences among Older Adults with CKD," on pages 772–781.
Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury
Authors: Yuan Gui, Haiyan Fu, Zachary Palanza, Jianling Tao, Yi-Han Lin, Wenjian Min, Yi Qiao, Christopher Bonin, Geneva Hargis, Yuanyuan Wang, Peng Yang, Donald L. Kreutzer, Yanlin Wang, Yansheng Liu, Yanbao Yu, Youhua Liu, Dong Zhou
Journal: Journal of Clinical Investigation (2024)

The smoothened (Smo) receptor facilitates hedgehog signaling between kidney fibroblasts and tubules during acute kidney injury (AKI). Tubule-derived hedgehog is protective in AKI, but the role of fibroblast-selective Smo is unclear. Here, we report that Smo-specific ablation in fibroblasts reduced tubular cell apoptosis and inflammation, enhanced perivascular mesenchymal cells activities, and preserved kidney function after AKI. Global proteomics of these kidneys identified extracellular matrix proteins, and nidogen-1 glycoprotein in particular, as key response markers to AKI. Intriguingly, Smo was bound to nidogen-1 in cells, suggesting that loss of Smo could impact nidogen-1 accessibility. Phosphoproteomics revealed that the 'AKI protector' Wnt signaling pathway was activated in these kidneys. Mechanistically, nidogen-1 interacted with integrin β1 to induce Wnts in tubules to mitigate AKI. Altogether, our results support that fibroblast-selective Smo dictates AKI fate through cell-matrix interactions, including nidogen-1, and offers a robust resource and path to further dissect AKI pathogenesis.
Combined low dose dobutamine and exercise stress echocardiography: a new hybrid protocol to detect inducible ischaemia
Authors: Konstantinos Vakalis, Max Berrill, Majimen Jimeno, Ruth Chester, Shelley Rahman-Haley, Anthony Barron, Aigul Baltabaeva
Journal:  (2024)

Abstract Aims Myocardial response to stress echocardiography may be elicited physiologically, through exercise, or pharmacologically, often with dobutamine. Both have advantages but also limitations due to reduced exercise capacity or side-effects to stressor agent/lack of closeness to true pathophysiology of ischaemic cascade. We have combined low-dose dobutamine and exercise, creating a ‘hybrid’ protocol to utilize the advantages of both techniques and limit the drawbacks. The aim of the study was to evaluate its safety and feasibility. Methods and results In the hybrid protocol, low-dose dobutamine infusion (up to 10 µg/kg/min) is enhanced by supine bicycle exercise at 3-min increments of workload of 25 W to achieve target heart rate (THR). We analysed safety and outcome data for all the patients who underwent this protocol from 2017 to 2022. Out of 835, 727 (87.1%) patients referred for evaluation of ischaemia underwent the hybrid protocol. The median age was 61 years old and 61% (442/727) were men. The median exercise time was 11 (9–13.5) min with a median maximum workload of 100 W (75–125). Out of 727, 670 (92.2%) achieved THR. Atropine was not used. Out of 727, 192 (26.4%) of studies were positive for ischaemia. Out of 122, 102 (83.6%) with positive stress who underwent invasive angiography had significant coronary disease. The incidence of complications was low: 1/727—severe arrhythmia, 5/727 (0.7%) developed a vasovagal episode, and 14/727 (1.9%) had a hypertensive response to exercise. Conclusion Our findings suggest that this protocol is safe, feasible, and has a high success rate in achieving THR.
Evaluation of the Hemocompatibility of the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices
Authors: Palak Shah, Mary Looby, Matthew Dimond, Pramita Bagchi, Bhruga Shah, Iyad Isseh, Allman T. Rollins, Ahmad A. Abdul-Aziz, Jamie Kennedy, Daniel G. Tang, Katherine M. Klein, Samantha Casselman, Christen Vermeulen, Wendy Sheaffer, Meredith Snipes, Shashank S. Sinha, Christopher M. O’Connor
Journal: JACC Heart Failure (2024)

Patients on left ventricular assist device (LVAD) support require chronic anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant which has become first-line therapy; however, its safety in LVAD patients has not been well-described. In patients with a fully magnetically levitated LVAD, treatment with apixaban will be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAE: stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non-CNS thromboembolism) as compared to treatment with warfarin. The evaluation of the hemocompatibility of the Direct Oral Anti-Coagulant apixaban in Left Ventricular Assist Devices (DOAC LVAD) trial is a Phase 2, open-label trial of LVAD patients randomized 1:1 to either apixaban twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed for 24 weeks to evaluate the primary composite outcome. 30 patients were randomized: 14 to warfarin and 16 to apixaban. Median patient age 60 years (IQR:52,71) and 47% were Black patients. The median time from LVAD implant to randomization was 115 days (IQR:56,859). At 24-weeks, the primary composite outcome occurred in no patients receiving apixaban and 2 patients (14%) receiving warfarin (p=0.12); these 2 patients experienced major bleeding from gastrointestinal sources. Anticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAE or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD patients.
Social Determinants of Health in Cardio-Oncology
Authors: Foster Osei Baah, Sonal Sharda, Kimberly Davidow, Sadhana Jackson, Daphney Kernizan, Joshua A. Jacobs, Yvonne Baumer, Corinna L. Schultz, Carissa M. Baker-Smith, Tiffany M. Powell-Wiley
Journal: JACC CardioOncology (2024)

Addressing the need for more equitable cardio-oncology care requires attention to existing disparities in cardio-oncologic disease prevention and outcomes. This is particularly important among those affected by adverse social determinants of health (SDOH). The intricate relationship of SDOH, cancer diagnosis, and outcomes from cardiotoxicities associated with oncologic therapies is influenced by sociopolitical, economic, and cultural factors. Furthermore, mechanisms in cell signaling and epigenetic effects on gene expression link adverse SDOH to cancer and the CVD-related complications of oncologic therapies. To mitigate these disparities, a multifaceted strategy is needed that includes attention to health care access, policy, and community engagement for improved disease screening and management. Interdisciplinary teams must also promote cultural humility and competency and leverage new health technology to foster collaboration in addressing the impact of adverse SDOH in cardio-oncologic outcomes.
Health Literacy, Individual and Community Engagement, and Cardiovascular Risks and Disparities
Authors: Lauren L. Taylor, Arthur S. Hong, Kristine Hahm, Dohyeong Kim, Carolyn Smith-Morris, Vlad G. Zaha
Journal: JACC CardioOncology (2024)

Cardiovascular and cancer outcomes intersect within the realm of cardio-oncology survivorship care, marked by disparities across ethnic, racial, social, and geographical landscapes. Although the clinical community is increasingly aware of this complex issue, effective solutions are trailing. To attain substantial public health impact, examinations of cancer types and cardiovascular risk mitigation require complementary approaches that elicit the patient's perspective, scale it to a population level, and focus on actionable population health interventions. Adopting such a multidisciplinary approach will deepen our understanding of patient awareness, motivation, health literacy, and community resources for addressing the unique challenges of cardio-oncology. Geospatial analysis aids in identifying key communities in need within both granular and broader contexts. In this review, we delineate a pathway that navigates barriers from individual to community levels. Data gleaned from these perspectives are critical in informing interventions that empower individuals within diverse communities and improve cardio-oncology survivorship.