tbuckley/cabot-search huggingface dataset:
Association of Residual Cancer Burden After Neoadjuvant Therapy and Event-Free Survival in Breast Cancer—Reply
Authors: Rita Mukhtar, W. Fraser Symmans, Laura J. Esserman
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
<i>In vitro</i> assessment of triple combination therapy for the most common disease-associated mutation in cystic fibrosis
Authors: Han-I Yeh, Tzyh-Chang Hwang
Journal: European Respiratory Journal (2022)

<b>F508del-CFTR, the most common disease-associated mutation in cystic fibrosis, may lose its responsiveness to the CFTR potentiator ivacaftor upon prolonged exposure to the newly developed CF drug Trikafta</b>https://bit.ly/3A22MKQ
Trends in Disenrollment and Reenrollment Within US Commercial Health Insurance Plans, 2006-2018
Authors: Hanming Fang, Molly Frean, Gosia Sylwestrzak, Benjamin Ukert
Journal: JAMA Network Open (2022)

The commercial health insurance market is characterized by consistently high enrollee turnover. Turnover can disrupt care continuity for patients and create challenges for insurers in managing the health of their enrollee populations. Yet the extent to which enrollees reenroll is not widely known.To characterize rates of disenrollment (hereafter, external turnover) and reenrollment in commercial health plans.In this retrospective longitudinal cohort study, trends in turnover and reenrollment in commercial health plans between January 1, 2006, and August 31, 2018, were analyzed. Data analysis was conducted from January 21, 2020, through December 23, 2021. Participants included 3 018 633 primary members and their dependents with employer-sponsored coverage.Primary outcomes included external turnover from commercial coverage and subsequent reenrollment into any line of business with the insurer (commercial, Medicaid Managed Care, and Medicare Advantage). Within commercial coverage, external turnover was analyzed separately for group (ie, employer-sponsored) and individual markets.In the sample of 3 018 633 members, 50.2% were men; mean (SD) age, including dependents, was 30.68 (19.05) years. A total of 2.2% of members experienced external turnover each month and 21.5% experienced external turnover each year. The individual market had the highest average monthly turnover rate of 3.4% compared with 2.1% in the group market. December had the highest rate of external turnover, with 13.8% experiencing external turnover in the individual market and 6.9% of members experiencing external turnover in the group market. Fourteen percent of the members who left the insurer from an individual plan reenrolled with the insurer after 1 year, and 34% had reenrolled after 5 years. Among members who left the insurer from a group plan, 12% reenrolled after 1 year and 32% reenrolled after 5 years. After 10 years, reenrollment reached 47% in the 2 markets. More than 80% of enrollees returned to the same line of business and within the same state, suggesting findings may generalize to smaller insurers.The findings of this cohort study suggest that insurers may benefit from investing in members' long-term health outcomes despite substantial short-term turnover rates.
The Weight of Place: Built Environment Correlates of Obesity and Diabetes
Authors: Nicholas A Howell, Gillian L Booth
Journal: Endocrine Reviews (2022)

In recent decades, the prevalence of obesity and diabetes has risen substantially in North America and worldwide. To address these dual epidemics, researchers and policymakers alike have been searching for effective means to promote healthy lifestyles at a population level. As a consequence, there has been a proliferation of research examining how the "built" environment in which we live influences physical activity levels, by promoting active forms of transportation, such as walking and cycling, over passive ones, such as car use. Shifting the transportation choices of local residents may mean that more members of the population can participate in physical activity during their daily routine without structured exercise programs. Increasingly, this line of research has considered the downstream metabolic consequences of the environment in which we live, raising the possibility that "healthier" community designs could help mitigate the rise in obesity and diabetes prevalence. This review discusses the evidence examining the relationship between the built environment, physical activity, and obesity-related diseases. We also consider how other environmental factors may interact with the built environment to influence metabolic health, highlighting challenges in understanding causal relationships in this area of research.
Evolution of therapy for limited stage diffuse large B-cell lymphoma
Authors: Alexandra E. Rojek, Sonali M. Smith
Journal: Blood Cancer Journal (2022)

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), with limited-stage DLBCL defined as stage I or II disease. Risk stratification, initial treatment options, and relapse patterns are distinct from advanced-stage DLBCL, but there is limited data on the impact of biologic features on outcome. Patients have excellent outcomes, with ~90% survival at 2 years. Over the past several years, sequential prospective trials and large registry studies have evaluated the optimal number of chemotherapy cycles and implemented PET-adapted approaches to reduce the need for radiotherapy. Special consideration must still be given to cases of bulky disease, extranodal disease, fully resected scenarios, and adverse biologic features such as high-grade B-cell lymphoma with double/triple hit rearrangements. This review presents the evolution of a modern management approach, with a discussion of recent treatment-defining studies.
Targeting Apoptosis Pathways With BCL2 and MDM2 Inhibitors in Adult B-cell Acute Lymphoblastic Leukemia
Authors: Helena Hohtari, Matti Kankainen, Shady Adnan-Awad, Bhagwan Yadav, Swapnil Potdar, Aleksandr Ianevski, Olli Dufva, Caroline Heckman, Veronika Sexl, Soili Kytölä, Satu Mustjoki, Kimmo Porkka
Journal: HemaSphere (2022)

In adult patients, the treatment outcome of acute lymphoblastic leukemia (ALL) remains suboptimal. Here, we used an ex vivo drug testing platform and comprehensive molecular profiling to discover new drug candidates for B-ALL. We analyzed sensitivity of 18 primary B-ALL adult patient samples to 64 drugs in a physiological concentration range. Whole-transcriptome sequencing and publicly available expression data were used to examine gene expression biomarkers for observed drug responses. Apoptotic modulators targeting BCL2 and MDM2 were highly effective. Philadelphia chromosome-negative (Ph-) samples were sensitive to both BCL2/BCL-W/BCL-XL-targeting agent navitoclax and BCL2-selective venetoclax, whereas Ph-positive (Ph+) samples were more sensitive to navitoclax. Expression of BCL2 was downregulated and BCL-W and BCL-XL upregulated in Ph+ ALL compared with Ph- samples, providing elucidation for the observed difference in drug responses. A majority of the samples were sensitive to MDM2 inhibitor idasanutlin. The regulatory protein MDM2 suppresses the function of tumor suppressor p53, leading to impaired apoptosis. In B-ALL, the expression of MDM2 was increased compared with other hematological malignancies. In B-ALL cell lines, a combination of BCL2 and MDM2 inhibitor was synergistic. In summary, antiapoptotic proteins including BCL2 and MDM2 comprise promising targets for future drug studies in B-ALL.
Calcium in Electromechanical Dissociation
Authors: Edwin Bollerup
Journal: JAMA (1988)

<h3>To the Editor.</h3> —We noted that in the latest standards for emergency cardiac care published in<i>JAMA</i>,<sup>1</sup>calcium was no longer recommended as a drug to be given for electromechanical dissociation. Furthermore, the guidelines for neonatal advanced life support state that "there is no current evidence that two previously recommended drugs, atropine and calcium, are useful in the acute phase of neonatal resuscitation."<sup>1</sup>Overall, this recommendation seems reasonable, since calcium may have a detrimental role in cardiac disease<sup>2,3</sup>and has not been shown to be of benefit in prehospital cardiac arrest<sup>4</sup>or in the treatment of electromechanical dissociation.<sup>5,6</sup>However, in a certain subset of patients it may deserve another look. We report two cases in which a 10% infusion of gluconate calcium (0.5 mL/kg) immediately corrected hyperkalemia-associated electromechanical dissociation. <h3>Report of Cases.</h3><h3>Case 1.</h3> —Triplet "C" was a girl born at 28 weeks of gestation
Changes in Suicide Rates — United States, 2019 and 2020
Authors: Daniel C. Ehlman, Ellen Yard, Deborah M. Stone, Christopher M. Jones, Karin A. Mack
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Suicide was among the 10 leading causes of death in the United States in 2020 among persons aged 10-64 years, and the second leading cause of death among children and adolescents aged 10-14 and adults aged 25-34 years (1). During 1999-2020, nearly 840,000 lives were lost to suicide in the United States. During that period, the overall suicide rate peaked in 2018 and declined in 2019 and 2020 (1). Despite the recent decline in the suicide rate, factors such as social isolation, economic decline, family stressors, new or worsening mental health symptoms, and disruptions to work and school associated with the COVID-19 pandemic have raised concerns about suicide risk in the United States. During 2020, a total of 12.2 million U.S. adults reported serious thoughts of suicide and 1.2 million attempted suicide (2). To understand how changes in suicide death rates might have varied among subpopulations, CDC analyzed counts and age-adjusted suicide rates during 2019 and 2020 by demographic characteristics, mechanism of injury, county urbanization level, and state. From 2019 to 2020, the suicide rate declined by 3% overall, including 8% among females and 2% among males. Significant declines occurred in seven states but remained stable in the other states and the District of Columbia. Despite two consecutive years of declines, the overall suicide rate remains 30% higher compared with that in 2000 (1). A comprehensive approach to suicide prevention that uses data driven decision-making and implements prevention strategies with the best available evidence, especially among disproportionately affected populations (3), is critical to realizing further declines in suicide and reaching the national goal of reducing the suicide rate by 20% by 2025 (4).
Efficacy of CDK9 inhibition in therapy of post-myeloproliferative neoplasm (MPN) secondary (s) AML cells
Authors: Warren Fiskus, Taghi Manshouri, Christine Birdwell, Christopher P. Mill, Lucia Masarova, Prithviraj Bose, Tapan M. Kadia, Naval Daver, Courtney D. DiNardo, Gautam Borthakur, Joseph D. Khoury, Srdan Verstovsek, Kapil N. Bhalla
Journal: Blood Cancer Journal (2022)
Pattern of treatment failures in patients with central nervous system non-germinomatous germ cell tumors (CNS-NGGCT): A pooled analysis of clinical trials
Authors: Adriana Fonseca, Cecile Faure-Conter, Matthew J Murray, Jason Fangusaro, Shivani Bailey, Stewart Goldman, Soumen Khatua, Didier Frappaz, Gabriele Calaminus, Girish Dhall, James C Nicholson, Eric Bouffet, Ute Bartels
Journal: Neuro-Oncology (2022)

Central Nervous System Non-Germinomatous Germ Cell Tumors (CNS-NGGCT) are rare but curable tumors. Due to their rarity, patients with treatment failures remain a poorly characterized group with unfavorable outcomes. In this study, we sought to characterize patients with treatment failures in a large, prospectively treated cohort.European and North American clinical trials for patients with CNS-NGGCT (SIOP-GCT-96, SFOP-TGM-TC 90/92, COG-ACNS0122, and COG-ACNS1123) were pooled for analysis. Additionally, patients included and treated in the UK and France national registries under strict protocol guidelines were included as an independent, non-overlapping cohort.A total of 118 patients experienced a treatment failure. Twenty-four patients had progressive disease during therapy, and additional 11 patients were diagnosed with growing teratoma syndrome (GTS). Patients with GTS are significantly younger and present with local failures and negative tumor markers. Eighty-three individuals experienced disease relapses after treatment ended. Patients' metastatic relapses presented significantly earlier than local relapses and were associated with tumor marker elevation (OR: 4.39; P = .026). In our analysis, focal or whole-ventricular radiation therapy was not associated with an increased risk of metastatic relapses.Herein, we present the largest pooled dataset of prospectively treated patients with relapsed CNS-NGGCT. Our study identified younger age and negative tumor markers to be characteristic of GTS. Additionally, we elucidated that metastatic relapses occur earlier than local relapses are associated with elevated tumor markers and are not associated with the field of radiation therapy. These findings are of utmost importance for the planning of future clinical trials and the implementation of surveillance strategies in these patients.
Antigen Test Positivity After COVID-19 Isolation — Yukon-Kuskokwim Delta Region, Alaska, January–February 2022
Authors: Brian Lefferts, Ian Blake, Dana Bruden, Melissa B. Hagen, Ellen Hodges, Hannah L. Kirking, Elizabeth Bates, Amanda Hoeldt, Brenda Lamont, Sharon Saydah, Adam MacNeil, Michael G. Bruce, Ian D. Plumb
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Isolation is recommended during acute infection with SARS-CoV-2, the virus that causes COVID-19, but the duration of infectiousness varies among individual persons. Rapid antigen test results have been correlated with detection of viable virus (1-3) and might inform isolation guidance, but data are limited for the recently emerged SARS-CoV-2 B.1.1.529 (Omicron) variant. On January 5, 2022, the Yukon-Kuskokwim Health Corporation (YKHC) recommended that persons with SARS-CoV-2 infection isolate for 10 days after symptom onset (or, for asymptomatic persons, 10 days after a positive nucleic acid amplification or antigen test result). However, isolation could end after 5-9 days if symptoms were resolving or absent, fever was absent for ≥24 hours without fever-reducing medications, and an Abbott BinaxNOW COVID-19 Ag (BinaxNOW) rapid antigen test result was negative. Antigen test results and associated individual characteristics were analyzed among 3,502 infections reported to YKHC during January 1-February 9, 2022. After 5-9 days, 396 of 729 persons evaluated (54.3%) had a positive antigen test result, with a declining percentage positive over time. In a multivariable model, a positive antigen test result was more likely after 5 days compared with 9 days (adjusted odds ratio [aOR] = 6.39) or after symptomatic infection (aOR = 9.63), and less likely after previous infection (aOR = 0.30), receipt of a primary COVID-19 vaccination series (aOR = 0.60), or after both previous infection and receipt of a primary COVID-19 vaccination series (aOR = 0.17). Antigen tests might be a useful tool to guide recommendations for isolation after SARS-CoV-2 infection. During the 10 days after infection, persons might be infectious to others and are recommended to wear a well-fitting mask when around others, even if ending isolation after 5 days.
Mapping the developing human cardiac endothelium at single-cell resolution identifies MECOM as a regulator of arteriovenous gene expression
Authors: Ian R McCracken, Ross Dobie, Matthew Bennett, Rainha Passi, Abdelaziz Beqqali, Neil C Henderson, Joanne C Mountford, Paul R Riley, Chris P Ponting, Nicola Smart, Mairi Brittan, Andrew H Baker
Journal: Cardiovascular Research (2022)

Abstract Aims Coronary vasculature formation is a critical event during cardiac development, essential for heart function throughout perinatal and adult life. However, current understanding of coronary vascular development has largely been derived from transgenic mouse models. The aim of this study was to characterize the transcriptome of the human foetal cardiac endothelium using single-cell RNA sequencing (scRNA-seq) to provide critical new insights into the cellular heterogeneity and transcriptional dynamics that underpin endothelial specification within the vasculature of the developing heart. Methods and results We acquired scRNA-seq data of over 10 000 foetal cardiac endothelial cells (ECs), revealing divergent EC subtypes including endocardial, capillary, venous, arterial, and lymphatic populations. Gene regulatory network analyses predicted roles for SMAD1 and MECOM in determining the identity of capillary and arterial populations, respectively. Trajectory inference analysis suggested an endocardial contribution to the coronary vasculature and subsequent arterialization of capillary endothelium accompanied by increasing MECOM expression. Comparative analysis of equivalent data from murine cardiac development demonstrated that transcriptional signatures defining endothelial subpopulations are largely conserved between human and mouse. Comprehensive characterization of the transcriptional response to MECOM knockdown in human embryonic stem cell-derived EC (hESC-EC) demonstrated an increase in the expression of non-arterial markers, including those enriched in venous EC. Conclusions scRNA-seq of the human foetal cardiac endothelium identified distinct EC populations. A predicted endocardial contribution to the developing coronary vasculature was identified, as well as subsequent arterial specification of capillary EC. Loss of MECOM in hESC-EC increased expression of non-arterial markers, suggesting a role in maintaining arterial EC identity.
Immunogenic hydrogel toolkit disturbing residual tumor “seeds” and pre-metastatic “soil” for inhibition of postoperative tumor recurrence and metastasis
Authors: Minglu Zhou, Qingting Zuo, Yuan Huang, Lian Li
Journal: Acta Pharmaceutica Sinica B (2022)

Tumor recurrence and metastasis is the leading cause of mortality for postoperative breast cancer patients. However, chemotherapy intervention after surgery is often unsatisfactory, because residual microtumors are difficult to target and require frequent administration. Here, an all-in-one and once-for-all drug depot based on in situ-formed hydrogel was applied to fit the irregular surgical trauma, and enable direct contact with residual tumors and sustained drug release. Our immunological analysis after resection of orthotopic breast tumor revealed that postsurgical activation of CXCR4-CXCL12 signal exacerbated the immunosuppression and correlated with adaptive upregulation of PD-L1 in recurrent tumors. Thus, a multifunctional hydrogel toolkit was developed integrating strategies of CXCR4 inhibition, immunogenicity activation and PD-L1 blockade. Our results showed that the hydrogel toolkit not only exerted local effect on inhibiting residual tumor cell "seeds" but also resulted in abscopal effect on disturbing pre-metastatic "soil". Furthermore, vaccine-like effect and durable antitumor memory were generated, which resisted a secondary tumor rechallenge in 100% cured mice. Strikingly, one single dose of such modality was able to eradicate recurrent tumors, completely prevent pulmonary metastasis and minimize off-target toxicity, thus providing an effective option for postoperative intervention.
Interim Guidance: 4-Month Rifapentine-Moxifloxacin Regimen for the Treatment of Drug-Susceptible Pulmonary Tuberculosis — United States, 2022
Authors: Wendy Carr, Ekaterina Kurbatova, Angela Starks, Neela Goswami, Leeanna Allen, Carla Winston
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

On May 5, 2021, CDC's Tuberculosis Trials Consortium and the National Institutes of Health (NIH)-sponsored AIDS Clinical Trials Group (ACTG) published results from a randomized controlled trial indicating that a 4-month regimen containing rifapentine (RPT), moxifloxacin (MOX), isoniazid (INH), and pyrazinamide (PZA) was as effective as the standard 6-month regimen for tuberculosis (TB) treatment (1).On the basis of these findings, CDC recommends the 4-month regimen as a treatment option for U.S. patients aged ≥12 years with drug-susceptible pulmonary TB and provides implementation considerations for this treatment regimen.
Neutralizing Antibody LY-CoV555 for Outpatient Covid-19
Authors: Arturo Casadevall, Michael J Joyner, Liise-Anne Pirofski
Journal: New England Journal of Medicine (2020)

Neutralizing Antibody LY-CoV555 for Outpatient Covid-19To the Editor: IgG monoclonal antibodies such as LY-CoV555 are divalent molecules that mediate their effects by means of viral neutralization, antibody-dependent cellular cytotoxicity, complement activation, and Fc-receptor engagement. 1 Consequently, determination of the dose is not straightforward.Chen et al. (published online on Oct. 28) 2 tested various doses of the monoclonal antibody LY-CoV555 -700 mg, 2800 mg, and 7000 mg -in patients with coronavirus disease 2019 (Covid-19) and found that antiviral activity was highest with the middle dose.This type of dose-response relationship raises the possibility of a prozone-like effect in which the efficacy of the monoclonal antibody decreases at higher doses.Prozone-like effects remain poorly understood, but several mechanisms by which antibody efficacy can decrease at higher concentrations have been described. 3,4Prozone-like effects are known to occur in vitro in diagnostic assays and were known in the days of serum therapy. 5However, such effects were never convincingly documented with polyclonal antibody products in clinical practice, possibly because immune serum specimens contain antibodies to multiple microbial determinants, rather than to just one.Given the dose-response findings with LY-CoV555, careful studies of the dose-response relationships of this and other monoclonal antibodies for the treatment of Covid-19 are called for, since it is possible that the maximal activity with such therapy may be at a dose different from one in the range tested.
Futility of Suppressing Seizurelike Activity in Postresuscitation Coma
Authors: Eelco F.M. Wijdicks
Journal: New England Journal of Medicine (2022)

The introduction of electroencephalography (EEG) into hospital practice generated interest in monitoring patients with severe brain injury after cardiac arrest. As early as 1964, a study involving 50 comatose patients who had been resuscitated after cardiac arrest showed "bursts of very large amplitude spikes, sharp waves, or complex wave forms over an entirely flat background," which purportedly predicted a poor outcome.1 Subsequent studies confirmed that low-voltage alpha waves that were detected beyond their typical location in the parietal and occipital lobes, and absent reactivity of the EEG background to physical stimuli, portended a poor outcome. Synchronous spike-wave discharges, burst suppression, . . .