tbuckley/cabot-search huggingface dataset:
Monitoring of Leukemia Clones in B-cell Acute Lymphoblastic Leukemia at Diagnosis and During Treatment by Single-cell DNA Amplicon Sequencing
Authors: Sarah Meyers, Llucia Alberti-Servera, Olga Gielen, Margot Erard, Toon Swings, Jolien De Bie, Lucienne Michaux, Barbara Dewaele, Nancy Boeckx, Anne Uyttebroeck, Kim De Keersmaecker, Johan Maertens, Heidi Segers, Jan Cools, Sofie Demeyer
Journal: HemaSphere (2022)

Acute lymphoblastic leukemia (ALL) is characterized by the presence of chromosomal changes, including numerical changes, translocations, and deletions, which are often associated with additional single-nucleotide mutations. In this study, we used single cell-targeted DNA sequencing to evaluate the clonal heterogeneity of B-ALL at diagnosis and during chemotherapy treatment. We designed a custom DNA amplicon library targeting mutational hotspot regions (in 110 genes) present in ALL, and we measured the presence of mutations and small insertions/deletions (indels) in bone marrow or blood samples from 12 B-ALL patients, with a median of 7973 cells per sample. Nine of the 12 cases showed at least 1 subclonal mutation, of which cases with PAX5 alterations or high hyperdiploidy (with intermediate to good prognosis) showed a high number of subclones (1 to 7) at diagnosis, defined by a variety of mutations in the JAK/STAT, RAS, or FLT3 signaling pathways. Cases with RAS pathway mutations had multiple mutations in FLT3, NRAS, KRAS, or BRAF in various clones. For those cases where we detected multiple mutational clones at diagnosis, we also studied blood samples during the first weeks of chemotherapy treatment. The leukemia clones disappeared during treatment with various kinetics, and few cells with mutations were easily detectable, even at low frequency (<0.1%). Our data illustrate that about half of the B-ALL cases show >2 subclones at diagnosis and that even very rare mutant cells can be detected at diagnosis or during treatment by single cell-targeted DNA sequencing.
Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment
Authors: Paula Byrne, Maryanne Demasi, Mark Jones, Susan M. Smith, Kirsty K. O’Brien, Robert DuBroff
Journal: JAMA Internal Medicine (2022)

The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear.To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy.PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021.Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years.Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken.Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke.Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive.The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.
OCCURRENCE OF STEMI AMONG WOMEN IN INTERNATIONAL HOSPITALS: A REPORT FROM THE AMERICAN COLLEGE OF CARDIOLOGY-GLOBAL HEART ATTACK TREATMENT INITIATIVE
Authors: Cesar J. Herrera, Benny J. Levenson, Angela Natcheva, Ana Corina Lucca, Kyoko Miki, Alyssa McCormick, B. Hadley Wilson
Journal: Journal of the American College of Cardiology (2022)
THE ASSOCIATION OF SEX-SPECIFIC HORMONES WITH HIGH-RISK CORONARY ARTERY PLAQUE IN WOMEN FROM MIAMI HEART (MIHEART) STUDY
Authors: Garima Sharma, Yaa Kwapong, Javier Valero Elizondo, Miguel Cainzos Achirica, Shozab Siddiq Ali, Michael Blaha, Ron Blankstein, Michael D. Shapiro, Lara Arias, Matthew J. Budoff, Theodore Feldman, Jack A. Ziffer, Ricardo C. Cury, Laxmi S. Mehta, Jonathan A. Fialkow, Khurram Nasir
Journal: Journal of the American College of Cardiology (2022)
YIA22-003: Quantifying Minimal Residual Disease in Patients With Small Cell Lung Cancer
Authors: Wade Iams, Prasad Kopparapu, Yingjun Yan, Selina Wong, Thereasa Rich, Mai Dao, Natalie Busby, Donavan Cheng, Elena Zotenko, Princy Parsana, Jin Hyun Ju, Christine Lovly
Journal: Journal of the National Comprehensive Cancer Network (2022)
Missed Signs of Acute Pulmonary Embolism in Electrocardiogram Findings
Authors: Yun-Tao Zhao, Lei Wang
Journal: JAMA Internal Medicine (2022)

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 Publications 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 2023 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
Finding flow: exploring the potential for sustainable fulfilment
Authors: Amy Isham, Tim Jackson
Journal: The Lancet Planetary Health (2022)

Materialistic values and lifestyles have been associated with detrimental effects on both personal and planetary health. Therefore, there is a pressing need to identify activities and lifestyles that both promote human wellbeing and protect ecological wellbeing. In this Personal View, we explore the dynamics of a psychological state known as flow, in which people are shown to experience high levels of wellbeing through involvement in challenging activities that require some level of skill, and can often involve less materially intensive activities. By synthesising the results of a series of experience sampling, survey, and experimental studies, we identify optimal activities that are shown to have low environmental costs and high levels of human wellbeing. We also confirm that materialistic values tend to undermine people's ability to experience a flow state. In seeking to understand the reasons for this negative association between materialism and flow experiences, we are drawn towards a key role for what psychologists call self-regulation. We show, in particular, that the tendency to experience a flow state can be limited when self-regulatory strength is low and when people evade rather than confront negative or undesirable thoughts and situations. We reflect on the implications of these findings for the prospect of sustainable and fulfilling lifestyles.
First‐ versus second‐generation Bruton tyrosine kinase inhibitors in Waldenström's Macroglobulinemia: A systematic review and meta‐analysis
Authors: Hassan Abushukair, Sebawe Syaj, Obada Ababneh, Aref Qarqash, Carolina Schinke, Sharmilan Thanendrarajan, Maurizio Zangari, Frits van Rhee, Samer Al Hadidi
Journal: American Journal of Hematology (2022)

Abstract Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second‐generation BTKi are associated with improved outcomes and/or better safety profile remains unclear. We did a systematic review and meta‐analysis of clinical trials that reported data on the outcomes of patients with WM who received either first‐ or second‐generation BTKi in the period between January 2010 and August 2021. Studies with twenty or fewer patients were excluded. The primary outcomes were efficacy measured by response and survival data. Eleven studies met the eligibility criteria and were included in the final analysis ( n = 730 patients). A total of 298 patients received 1st‐generation BTKi and 432 received a 2nd‐generation BTKi. Pooled overall response rate (ORR) and major response rate (MRR) for both generations were similar (94.2% and 78.5% in 1st vs. 88.9% and 75.1% in 2nd, respectively). MRR for both generations was higher in MYD88 Mut/CXCR4 WT patients compared to MYD88 Mut/CXCR4 Mut patients (odds ratio [OR]: 3.9, 95% CI: 2.2 to 5.5). Pooled 18‐mo progression‐free survival (PFS) was similar for both generations (88.5% vs. 87.3%). Grade 3/4 atrial fibrillation was higher in 1st‐generation BTKi (3.1% vs. 0.4%); however, grade‐3/‐4 infections and neutropenia were more frequent in 2nd‐generarion BTKi (20.9% vs. 13.2%, 17.7% vs. 12%, respectively). The efficacy of 1st‐ and 2nd‐generation BTKis is comparable. The 1st‐generation BTKi were associated with a higher risk of atrial fibrillation, whereas infections and neutropenia occurred more frequently in 2nd‐generation BTKi.
IS TAVR AN ALTERNATIVE TO HIGH-RISK SURGERY IN A PATIENT WITH TREATED BUT COMPLICATED AORTIC VALVE INFECTIVE ENDOCARDITIS?
Authors: Madhura Myla, Kathleen M. Allen, Gerald A. Charlton, Michelle Ratliff, Subhash Banerjee, Amer Alaiti, Jerrold M. Grodin, Carlos Adalberto Roldan
Journal: Journal of the American College of Cardiology (2022)
Spectrum of Nonkeratinocyte Skin Cancer Risk Among Solid Organ Transplant Recipients in the US
Authors: Michael R. Sargen, Elizabeth K. Cahoon, Kelly J. Yu, Margaret M. Madeleine, Yun Zeng, Judy R. Rees, Charles F. Lynch, Eric A. Engels
Journal: JAMA Dermatology (2022)

<h3>Importance</h3> Nonkeratinocyte skin cancers are an important cause of morbidity and mortality for immunosuppressed solid organ transplant recipients (SOTRs), but the spectrum of disease and risk factor characteristics are unknown. <h3>Objective</h3> To characterize the spectrum of disease and risk factors for common and rare nonkeratinocyte skin cancers in SOTRs. <h3>Design, Setting, and Participants</h3> This population-based cohort study included 444 497 SOTRs who underwent a transplant in the US between January 1, 1987, and December 31, 2017, using linked data from the national transplant registry and 32 cancer registries. Data analysis was conducted from April 1, 2021, to September 30, 2021. <h3>Main Outcomes and Measures</h3> Standardized incidence ratios (SIRs) were used to assess risk relative to the general population, and Poisson regression was used to evaluate risk factors. <h3>Results</h3> A total of 2380 nonkeratinocyte skin cancers were identified among 444 497 SOTRs (median age at transplant, 50 years; range, 0-96 years; 274 276 [61.7%] male; 272 241 [61.2%] non-Hispanic White). Melanoma was the most common cancer (1471 [61.8%]), followed by Merkel cell carcinoma (334 [14.0%]), Kaposi sarcoma (186 [7.8%]), sebaceous carcinoma (170 [7.1%]), and cutaneous lymphomas (108 [4.5%]). Risks were most strongly elevated for cancers associated with viruses, including Kaposi sarcoma (SIR, 20.5; 95% CI, 17.7-23.7), Merkel cell carcinoma (SIR, 16.2; 95% CI, 14.5-18.1), and extranodal natural killer/T-cell lymphoma (SIR, 44.3; 95% CI, 5.37-160). Risks were also significantly elevated for sebaceous carcinoma (SIR, 15.2; 95% CI, 13.0-17.7), anaplastic large cell lymphoma (SIR, 6.82; 95% CI, 4.53-9.85), and diffuse large B-cell lymphoma (SIR, 5.17; 95% CI, 3.28-7.76). Several characteristics were independently associated with greater risk for multiple skin cancer types, including male sex, older age at transplant, factors associated with UV radiation exposure (non-Hispanic White race and ethnicity, living in an area with higher UV radiation exposure, and posttransplant diagnosis of keratinocyte carcinoma), and increasing time since transplantation. Treatment with mammalian target of rapamycin inhibitors was associated with reduced melanoma incidence (incidence rate ratio, 0.75; 95% CI, 0.57-0.98). A total of 847 skin cancers (39.4%) occurred on the head and neck. <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that viruses, UV radiation exposure, and immunosuppression are associated with the development of skin cancer in SOTRs. Certain high-risk subgroups may benefit from increased skin surveillance, and treatment with mammalian target of rapamycin inhibitors could be effective for melanoma chemoprevention in the transplant population.
Do basophil activation tests help elucidate allergic reactions to the ingredients in COVID‐19 vaccines?
Authors: Bernadette Eberlein, Sonja Mathes, Jörg Fischer, Ulf Darsow, Tilo Biedermann, Knut Brockow
Journal: Allergy (2022)

The worldwide use of COVID-19 vaccines has shown that immediate allergic reactions to the ingredients are rare but should be clarified by means of an allergological work-up. This review aims to highlight the current state of knowledge and possible pathogenesis based on the literature published to date. In addition to recording a detailed history and performing skin tests, cellular tests (basophil activation or basophil histamine release test) by using the vaccines or modified compounds containing polyethylene glycol (PEG), rather than unmodified PEGs, have proven to be particularly helpful. Negative results with vaccines seem to indicate tolerance. Details of the performance of these cellular tests with different vaccines, PEGs of different molecular weights, other ingredients of the vaccines, as well as other PEGylated drugs, and the results in the context of COVID-19 vaccination of various working groups worldwide are summarized.
A Vegfc-Emilin2a-Cxcl8a Signaling Axis Required for Zebrafish Cardiac Regeneration
Authors: Hadil El-Sammak, Bingyuan Yang, Stefan Guenther, Wenbiao Chen, Rubén Marín-Juez, Didier Y.R. Stainier
Journal: Circulation Research (2022)

Background: Ischemic heart disease following the obstruction of coronary vessels leads to the death of cardiac tissue and the formation of a fibrotic scar. In contrast to adult mammals, zebrafish can regenerate their heart after injury, enabling the study of the underlying mechanisms. One of the earliest responses following cardiac injury in adult zebrafish is coronary revascularization. Defects in this process lead to impaired cardiomyocyte repopulation and scarring. Hence, identifying and investigating factors that promote coronary revascularization holds great therapeutic potential. Methods: We used wholemount imaging, immunohistochemistry and histology to assess various aspects of zebrafish cardiac regeneration. Deep transcriptomic analysis allowed us to identify targets and potential effectors of Vegfc (vascular endothelial growth factor C) signaling. We used newly generated loss- and gain-of-function genetic tools to investigate the role of Emilin2a (elastin microfibril interfacer 2a) and Cxcl8a (chemokine (C-X-C) motif ligand 8a)-Cxcr1 (chemokine (C-X-C) motif receptor 1) signaling in cardiac regeneration. Results: We first show that regenerating coronary endothelial cells upregulate vegfc upon cardiac injury in adult zebrafish and that Vegfc signaling is required for their proliferation during regeneration. Notably, blocking Vegfc signaling also significantly reduces cardiomyocyte dedifferentiation and proliferation. Using transcriptomic analyses, we identified emilin2a as a target of Vegfc signaling and found that manipulation of emilin2a expression can modulate coronary revascularization as well as cardiomyocyte proliferation. Mechanistically, Emilin2a induces the expression of the chemokine gene cxcl8a in epicardium-derived cells, while cxcr1 , the Cxcl8a receptor gene, is expressed in coronary endothelial cells. We further show that Cxcl8a-Cxcr1 signaling is also required for coronary endothelial cell proliferation during cardiac regeneration. Conclusions: These data show that after cardiac injury, coronary endothelial cells upregulate vegfc to promote coronary network reestablishment and cardiac regeneration. Mechanistically, Vegfc signaling upregulates epicardial emilin2a and cxcl8a expression to promote cardiac regeneration. These studies aid in understanding the mechanisms underlying coronary revascularization in zebrafish, with potential therapeutic implications to enhance revascularization and regeneration in injured human hearts.
Secondary Osteoporosis
Authors: Peter R Ebeling, Hanh H Nguyen, Jasna Aleksova, Amanda J Vincent, Phillip Wong, Frances Milat
Journal: Endocrine Reviews (2021)

Abstract Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although postmenopausal osteoporosis is most common, up to 30% of postmenopausal women, &amp;gt; 50% of premenopausal women, and between 50% and 80% of men have secondary osteoporosis. Exclusion of secondary causes is important, as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis, with advanced investigations reserved for premenopausal women and men aged &amp;lt; 50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤ −2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual-energy x-ray absorptiometry, may underestimate fracture risk in some chronic diseases, including glucocorticoid-induced osteoporosis, type 2 diabetes, and obesity, and may overestimate fracture risk in others (eg, Turner syndrome). FRAX and trabecular bone score may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥ 40 years and ≥ 50 years, respectively. In addition, FRAX requires adjustment in some chronic conditions, such as glucocorticoid use, type 2 diabetes, and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed.
TARGETED PROTEOMICS IMPROVES CARDIOVASCULAR RISK PREDICTION IN SECONDARY PREVENTION PATIENTS
Authors: Nick S. Nurmohamed, Joao P. Belo Pereira, Renate M. Hoogeveen, Jeffrey Kroon, Jordan M. Kraaijenhof, Farahnaz Waissi, Nathalie Timmerman, Michiel Bom, Imo Hoefer, Paul Knaapen, Alberico L. Catapano, Wolfgang Koenig, Dominique de Kleijn, Frank Visseren, Evgeni Levin, Erik S.G. Stroes
Journal: Journal of the American College of Cardiology (2022)
CLO22-086: A Phase 2, Multi-Arm Study of Anti-CD47 Antibody Magrolimab in Combination With Docetaxel in Patients With Locally Advanced or Metastatic Solid Tumors
Authors: Vivek Subbiah, Ulka Vaishampayan, Sonam Puri, Lanjia Lin, Mark Chao, Giri Ramsingh, Shivaani Kummar, James F Strauss, Sandip P Patel
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-086: A Phase 2, Multi-Arm Study of Anti-CD47 Antibody Magrolimab in Combination With Docetaxel in Patients With Locally Advanced or Metastatic Solid Tumors" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Surgeon Use of Shared Decision-making for Older Adults Considering Major Surgery
Authors: Nathan D. Baggett, Kathryn Schulz, Anne Buffington, Nicholas Marka, Bret M. Hanlon, Christopher Zimmermann, Jennifer Tucholka, Dan Fox, Justin T. Clapp, Robert M. Arnold, Margaret L. Schwarze
Journal: JAMA Surgery (2022)

Because major surgery carries significant risks for older adults with comorbid conditions, shared decision-making is recommended to ensure patients receive care consistent with their goals. However, it is unknown how often shared decision-making is used for these patients.To describe the use of shared decision-making during discussions about major surgery with older adults.This study is a secondary analysis of conversations audio recorded during a randomized clinical trial of a question prompt list. Data were collected from June 1, 2016, to November 31, 2018, from 43 surgeons and 446 patients 60 years or older with at least 1 comorbidity at outpatient surgical clinics at 5 academic centers.Patients received a question prompt list brochure that contained questions they could ask a surgeon.The 5-domain Observing Patient Involvement in Decision-making (OPTION5) score (range, 0-100, with higher scores indicating greater shared decision-making) was used to measure shared decision-making.A total of 378 surgical consultations were analyzed (mean [SD] patient age, 71.9 [7.2] years; 206 [55%] male; 312 [83%] White). The mean (SD) OPTION5 score was 34.7 (20.6) and was not affected by the intervention. The mean (SD) score in the group receiving the question prompt list was 36.7 (21.2); in the control group, the mean (SD) score was 32.9 (19.9) (effect estimate, 3.80; 95% CI, -0.30 to 8.00; P = .07). Individual surgeon use of shared decision-making varied greatly, with a lowest median score of 10 (IQR, 10-20) to a high of 65 (IQR, 55-80). Lower-performing surgeons had little variation in OPTION5 scores, whereas high-performing surgeons had wide variation. Use of shared decision-making increased when surgeons appeared reluctant to operate (effect estimate, 7.40; 95% CI, 2.60-12.20; P = .003). Although longer conversations were associated with slightly higher OPTION5 scores (effect estimate, 0.69; 95% CI, 0.52-0.88; P < .001), 57% of high-scoring transcripts were 26 minutes long or less. On multivariable analysis, patient age and gender, patient education, surgeon age, and surgeon gender were not significantly associated with OPTION5 scores.These findings suggest that although shared decision-making is important to support the preferences of older adults considering major surgery, surgeon use of shared decision-making is highly variable. Skillful shared decision-making can be done in less than 30 minutes; however, surgeons who engage in high-scoring shared decision-making are more likely to do so when surgical intervention is less obviously beneficial for the patient.ClinicalTrials.gov Identifier: NCT02623335.