tbuckley/cabot-search huggingface dataset:
Shared Decision-Making in Cardiovascular Risk Factor Management
Authors: Sabrina Elias, Yuling Chen, Xiaoyue Liu, Sarah Slone, Ruth-Alma Turkson-Ocran, Bunmi Ogungbe, Sabena Thomas, Samuel Byiringiro, Binu Koirala, Reiko Asano, Diana-Lyn Baptiste, Nicole L. Mollenkopf, Nwakaego Nmezi, Yvonne Commodore-Mensah, Cheryl R. Dennison Himmelfarb
Journal: JAMA Network Open (2024)

Importance The effect of shared decision-making (SDM) and the extent of its use in interventions to improve cardiovascular risk remain unclear. Objective To assess the extent to which SDM is used in interventions aimed to enhance the management of cardiovascular risk factors and to explore the association of SDM with decisional outcomes, cardiovascular risk factors, and health behaviors. Data Sources For this systematic review and meta-analysis, a literature search was conducted in the Medline, CINAHL, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov databases for articles published from inception to June 24, 2022, without language restrictions. Study Selection Randomized clinical trials (RCTs) comparing SDM-based interventions with standard of care for cardiovascular risk factor management were included. Data Extraction and Synthesis The systematic search resulted in 9365 references. Duplicates were removed, and 2 independent reviewers screened the trials (title, abstract, and full text) and extracted data. Data were pooled using a random-effects model. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Main Outcomes and Measures Decisional outcomes, cardiovascular risk factor outcomes, and health behavioral outcomes. Results This review included 57 RCTs with 88 578 patients and 1341 clinicians. A total of 59 articles were included, as 2 RCTs were reported twice. Nearly half of the studies (29 [49.2%]) tested interventions that targeted both patients and clinicians, and an equal number (29 [49.2%]) exclusively focused on patients. More than half (32 [54.2%]) focused on diabetes management, and one-quarter focused on multiple cardiovascular risk factors (14 [23.7%]). Most studies (35 [59.3%]) assessed cardiovascular risk factors and health behaviors as well as decisional outcomes. The quality of studies reviewed was low to fair. The SDM intervention was associated with a decrease of 4.21 points (95% CI, −8.21 to −0.21) in Decisional Conflict Scale scores (9 trials; I 2 = 85.6%) and a decrease of 0.20% (95% CI, −0.39% to −0.01%) in hemoglobin A 1c (HbA 1c ) levels (18 trials; I 2 = 84.2%). Conclusions and Relevance In this systematic review and meta-analysis of the current state of research on SDM interventions for cardiovascular risk management, there was a slight reduction in decisional conflict and an improvement in HbA 1c levels with substantial heterogeneity. High-quality studies are needed to inform the use of SDM to improve cardiovascular risk management.
Exploring Exclusive Breastfeeding and Childhood Cancer Using Linked Data
Authors: Helen D. Bailey
Journal: JAMA Network Open (2024)

Signe Holst Søegaard, PhD; Mie Mølgaard Andersen, BSc; Klaus Rostgaard, MSc; Olafur Birgir Davidsson, MSc; Sjurdur Frodi Olsen, DMSc; Kjeld Schmiegelow, DMSc; Henrik Hjalgrim, DMSc
A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children
Authors: Adam J. de Smith, Lara Wahlster, Soyoung Jeon, Linda Kachuri, Susan Black, Jalen Langie, Liam D. Cato, Nathan Nakatsuka, Tsz-Fung Chan, Guangze Xia, Soumyaa Mazumder, Wenjian Yang, Steven Gazal, Celeste Eng, Donglei Hu, Esteban González Burchard, Elad Ziv, Catherine Metayer, Nicholas Mancuso, Jun J. Yang, Xiaomei Ma, Joseph L. Wiemels, Fulong Yu, Charleston W.K. Chiang, Vijay G. Sankaran
Journal: Cell Genomics (2024)

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.
A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats
Authors: Tristan V. de Jong, Yanchao Pan, Pasi Rastas, Daniel Munro, Monika Tutaj, Huda Akil, Chris Benner, Denghui Chen, Apurva S. Chitre, William Chow, Vincenza Colonna, Clifton L. Dalgard, Wendy M. Demos, Peter A. Doris, Erik Garrison, Aron M. Geurts, Hakan M. Gunturkun, Victor Guryev, Thibaut Hourlier, Kerstin Howe, Jun Huang, Ted Kalbfleisch, Panjun Kim, Ling Li, Spencer Mahaffey, Fergal J. Martin, Pejman Mohammadi, Ayse Bilge Ozel, Oksana Polesskaya, Michal Pravenec, Pjotr Prins, Jonathan Sebat, Jennifer R. Smith, Leah C. Solberg Woods, Boris Tabakoff, Alan Tracey, Marcela Uliano-Silva, Flavia Villani, Hongyang Wang, Burt M. Sharp, Francesca Telese, Zhihua Jiang, Laura Saba, Xusheng Wang, Terence D. Murphy, Abraham A. Palmer, Anne E. Kwitek, Melinda R. Dwinell, Robert W. Williams, Jun Z. Li, Hao Chen
Journal: Cell Genomics (2024)

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.
An implantable device for wireless monitoring of diverse physio-behavioral characteristics in freely behaving small animals and interacting groups
Authors: Wei Ouyang, Keith J. Kilner, Rachael M.P. Xavier, Yiming Liu, Yinsheng Lu, Sophia M. Feller, Kayla M. Pitts, Mingzheng Wu, Jokubas Ausra, Ian Jones, Yunyun Wu, Haiwen Luan, Jacob Trueb, Elizabeth M. Higbee-Dempsey, Iwona Stepien, Nayereh Ghoreishi-Haack, Chad R. Haney, Hao Li, Yevgenia Kozorovitskiy, Mitra Heshmati, Anthony R. Banks, Sam A. Golden, Cameron H. Good, John A. Rogers
Journal: Neuron (2024)
The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis
Authors: Arumugam Balasubramanian, Alan Y. Hsu, Laxman Ghimire, Muhammad Tahir, Pascal Devant, Pietro Fontana, Gang Du, Xing Liu, Dang Fabin, Hiroto Kambara, Xuemei Xie, Fei Liu, Tomoya Hasegawa, Rong Xu, Hongbo Yu, Mei Chen, Steven Kolakowski, Sunia Trauger, Martin Røssel Larsen, Wenyi Wei, Hao Wu, Jonathan C. Kagan, Judy Lieberman, Hongbo R. Luo
Journal: Science Immunology (2024)

Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a proteomic approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner. S-palmitoylation of GSDMD at Cys
Primary Care Physicians’ Satisfaction With Interoperable Health Information Technology
Authors: Jordan Everson, Nathaniel Hendrix, Robert L. Phillips, Julia Adler-Milstein, Andrew Bazemore, Vaishali Patel
Journal: JAMA Network Open (2024)

Importance Enabling widespread interoperability—the ability of health information technology systems to exchange information and to use that information without special effort—is a primary focus of public policy on health information technology. More information on clinicians’ experience using that technology can serve as one measure of the impact of that policy. Objective To assess primary care physician perspectives on the state of interoperability. Design, Setting, and Participants A cross-sectional survey of family medicine physicians in the US was conducted from December 12, 2021, to October 12, 2022. A sample of family medicine physicians who completed the Continuous Certification Questionnaire (CCQ), a required part of the American Board of Family Medicine certification process, which has a 100% response rate, were invited to participate. Main Outcomes and Measures Eighteen items on the CCQ assessed experience accessing and using various information from outside organizations, including medications, immunizations, and allergies. Results A total of 2088 physicians (1053 women [50%]; age reported categorically as either ≥50 years or &amp;amp;lt;50 years) completed the CCQ interoperability questions in 2022. Of these respondents, 35% practiced in hospital or health system–owned practices, while 27% practiced in independently owned practices. Eleven percent were very satisfied with their ability to electronically access all 10 types of information from outside organizations included on the questionnaire, and a mean of 70% were at least somewhat satisfied. A total of 23% of family medicine physicians reported information from outside organizations was very easy to use, and an additional 65% reported that information was somewhat easy to use. Only 8% reported that information from different electronic health record (EHR) developers’ products was very easy to use compared with 38% who reported information from the same EHR developer’s product was very easy to use. Conclusions and Relevance This survey study of family medicine physicians found modest and uneven improvement in physicians’ experience with interoperability. These findings suggest that substantial heterogeneity in satisfaction by information type, source of information, EHR, practice type, ownership, and patient population necessitates diverse policy and strategies to improve interoperability.
Of Mucus and Microbes: The Sticky Issue of Mucin-Microbiome Interactions in COPD
Authors: Yvonne J Huang
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Of Mucus and Microbes: The Sticky Issue of Mucin-Microbiome Interactions in COPD ." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Induction of immortal-like and functional CAR T cells by defined factors
Authors: Lixia Wang, Gang Jin, Qiuping Zhou, Yanyan Liu, Xiaocui Zhao, Zhuoyang Li, Na Yin, Min Peng
Journal: The Journal of Experimental Medicine (2024)

Long-term antitumor efficacy of chimeric antigen receptor (CAR) T cells depends on their functional persistence in vivo. T cells with stem-like properties show better persistence, but factors conferring bona fide stemness to T cells remain to be determined. Here, we demonstrate the induction of CAR T cells into an immortal-like and functional state, termed TIF. The induction of CARTIF cells depends on the repression of two factors, BCOR and ZC3H12A, and requires antigen or CAR tonic signaling. Reprogrammed CARTIF cells possess almost infinite stemness, similar to induced pluripotent stem cells while retaining the functionality of mature T cells, resulting in superior antitumor effects. Following the elimination of target cells, CARTIF cells enter a metabolically dormant state, persisting in vivo with a saturable niche and providing memory protection. TIF represents a novel state of T cells with unprecedented stemness, which confers long-term functional persistence of CAR T cells in vivo and holds broad potential in T cell therapies.
Recombinant snake antivenoms get closer to the clinic
Authors: Andreas H. Laustsen
Journal: Trends in Immunology (2024)

Snakebite envenomings kill ~100 000 victims each year and leave many more with permanent sequelae. Antivenoms have been available for more than 125 years but are in need of innovation. A new study by Khalek et al. highlights broadly neutralizing human monoclonal antibodies (mAbs) that might be used to develop recombinant antivenoms with superior therapeutic benefits.
Erratum: “Climate Change, Summer Temperature, and Heat-Related Mortality in Finland: Multicohort Study with Projections for a Sustainable vs. Fossil-Fueled Future to 2050”
Authors: Mika Kivimäki, G. David Batty, Jaana Pentti, Juuso Suomi, Solja T. Nyberg, Joonas Merikanto, Kalle Nordling, Jenni Ervasti, Sakari B. Suominen, Antti-Ilari Partanen, Sari Stenholm, Jukka Käyhkö, Jussi Vahtera
Journal: Environmental Health Perspectives (2024)
Bioethics’ Duty to Conference in Qatar: Reply to Magnus
Authors: Nancy S. Jecker, Julian Savulescu, Arthur Caplan, Alexander Capron, John McMillan, Mohammed Ghaly, Gustavo Ortiz Millán, Caesar Atuire, Jeff McMahan, Voo Teck Chuan, Jean-Christophe Bélisle-Pipon, Vina Viswani, Vardit Ravitsky
Journal: The American Journal of Bioethics (2024)
Outcomes of patients with multiple myeloma refractory to standard dose vs low dose lenalidomide
Authors: Utkarsh Goel, Charalampos Charalampous, Prashant Kapoor, Moritz Binder, Francis K. Buadi, David Dingli, Angela Dispenzieri, Amie Fonder, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Miriam A. Hobbs, Yi L. Hwa, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Rahma M. Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Journal: Blood Cancer Journal (2024)

Abstract Refractoriness to lenalidomide is an important factor determining the choice of therapy at first relapse in multiple myeloma (MM). It remains debatable if resistance to lenalidomide varies among MM refractory to standard doses vs low dose maintenance doses. In this study, we assessed the outcomes with subsequent therapies in patients with MM refractory to standard dose vs low dose lenalidomide. We retrospectively reviewed all patients with MM at our institution who received first line therapy with lenalidomide containing regimens, and assessed progression free survival (PFS) and overall survival for these patients for second line therapy, and with lenalidomide retreatment. For second line therapy, we found no difference in the PFS between standard dose refractory and low dose refractory groups (median PFS 14 months vs 14 months, p = 0.95), while the PFS for both these groups was inferior to the not refractory group (median PFS 30 months, p &lt; 0.001 for both pairs). Similar trends were seen among these groups on lenalidomide retreatment, and on multivariable analysis. These data suggest that refractoriness to lenalidomide is not dose dependent, and definition of lenalidomide refractoriness should not depend on the dose of lenalidomide to which the disease was considered refractory.
How comparable are patient outcomes in the “real-world” with populations studied in pivotal AML trials?
Authors: Ing Soo Tiong, Meaghan Wall, Ashish Bajel, Akash Kalro, Shaun Fleming, Andrew W. Roberts, Nisha Thiagarajah, Chong Chyn Chua, Maya Latimer, David Yeung, Paula Marlton, Amanda Johnston, Anoop Enjeti, Chun Yew Fong, Gavin Cull, Stephen Larsen, Glen Kennedy, Anthony Schwarer, David Kipp, Sundra Ramanathan, Emma Verner, Campbell Tiley, Edward Morris, Uwe Hahn, John Moore, John Taper, Duncan Purtill, Pauline Warburton, William Stevenson, Nicholas Murphy, Peter Tan, Ashanka Beligaswatte, Howard Mutsando, Mark Hertzberg, Jake Shortt, Ferenc Szabo, Karin Dunne, Andrew H. Wei
Journal: Blood Cancer Journal (2024)

Abstract Despite an increasing desire to use historical cohorts as “synthetic” controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012–2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.
Potential digenic inheritance of <i>SERPINB7</i> and <i>SERPINA12</i> variants in Chinese patients with Nagashima-type palmoplantar keratosis
Authors: Yihe Liu, Juan Liu, Yuqi Chen, Ran Mo, Ruiyu Xiang, Zhongya Song, Yong Yang, Zhiming Chen
Journal: British Journal of Dermatology (2024)

Nagashima-type palmoplantar keratosis, caused by biallelic loss-of-function variants in SERPINB7, is the most prevalent palmoplantar keratoderma in East Asia and manifests as diffuse palmoplantar erythema and hyperkeratosis. We report four different variants of SERPINA12 in six Chinese individuals and identified the recurrent variant c.970_971del as a founder variant among East Asians.
Psychometric evaluation of the multidimensional Uraemic Pruritus in Dialysis patients (UP-Dial) scale: comparison of haemodialysis and peritoneal dialysis patients with chronic pruritus
Authors: Surapon Nochaiwong, Chidchanok Ruengorn, Kednapa Thavorn, Kajohnsak Noppakun, Manish M Sood, Greg A Knoll, Jonathan A Bernstein, Jacek C Szepietowski, Mati Chuamanochan
Journal: British Journal of Dermatology (2024)

Abstract Background High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. Objectives To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uraemic Pruritus in Dialysis patients (UP-Dial) 14-item scale, by comparing haemodialysis and peritoneal dialysis modality. Methods This validation study used data from the Thai Renal Outcomes Research-Uraemic Pruritus, a prospective, multicentre, longitudinal study. Data for this study were collected from 1 February 2019 to 31 May 2022. The adult sample of 226 haemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across haemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8) and Patient Health Questionnaire-9 (PHQ-9). Results From the patient’s perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73–0.74) with global itching, a positively moderate correlation (0.33–0.58) with DLQI, PSQI, global fatigue, SSS-8 and PHQ-9, and a negatively moderate correlation (–0.39 to –0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach’s α = 0.89 and McDonald’s ω = 0.90) and reproducibility (intraclass correlation 0.84–0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P &amp;gt; 0.05). Conclusions The findings reaffirm good measurement properties of the UP-Dial 14-item scale in haemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.
Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease
Authors: Anubha Agarwal, Priya M. Mehta, Tyler Jacobson, Nilay S. Shah, Jiancheng Ye, JingJing Zhu, Q. Eileen Wafford, Ehete Bahiru, Angharad N. de Cates, Shah Ebrahim, Dorairaj Prabhakaran, Anthony Rodgers, Mark D. Huffman
Journal: Nature Medicine (2024)
RAF inhibitor re-challenge therapy in BRAF-aberrant pan-cancers: the RE-RAFFLE study
Authors: Blessie Elizabeth Nelson, Jason Roszik, Jibran Ahmed, Carmelia Maria Noia Barretto, Mirella Nardo, Erick Campbell, Amber M Johnson, Sarina A. Piha-Paul, Isabella C. Glitza Oliva, Shiao-Pei Weathers, Maria Cabanillas, Milind Javle, Funda Meric-Bernstam, Vivek Subbiah
Journal: Molecular Cancer (2024)

Abstract Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable responses with PR and SD lasting &gt; 6 months. The median progression-free survival on therapy with second RAF inhibitor in the rechallenge setting either as monotherapy or combination was shorter at 2.7 months (0.9-30.1 m) compared to 8.6 months (6.5-11.5 m) with RAF-1i. However, the median PFS with RAF-2i responders (PFS-2) improved at 12.8 months compared to 11.4 months with RAF-1i responders. The median OS from retreatment with RAF-2i was 15.5 months (11.1-30.8 m). Further prospective studies are needed to validate these results and expand targeted therapy options for RAF -aberrant cancers.