tbuckley/cabot-search huggingface dataset:
Reason for Late-Stage Breast Cancer: Absence of Screening or Detection, or Breakdown in Follow-up?
Authors: S. H. Taplin, L. Ichikawa, M. U. Yood, M. M. Manos, A. M. Geiger, S. Weinmann, J. Gilbert, J. Mouchawar, W. A. Leyden, R. Altaras, R. K. Beverly, D. Casso, E. O. Westbrook, K. Bischoff, J. G. Zapka, W. E. Barlow
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Mammography screening increases the detection of early-stage breast cancers. Therefore, implementing screening should reduce the percentage of women who are diagnosed with late-stage disease. However, despite high national mammography screening rates, late-stage breast cancers still occur, possibly because of failures in screening implementation. Methods: Using data from seven health care plans that included 1.5 million women aged 50 years or older, we conducted retrospective reviews of chart and automated data for 3 years before 1995–1999 diagnoses of late-stage (metastatic and/or tumor size ≥3 cm; case subjects, n = 1347) and early-stage breast cancers (control subjects, n = 1347). We categorized the earliest screening mammogram during the period 13–36 months before diagnosis as none (absence of screening), negative (absence of detection), or positive (potential breakdown in follow-up). We compared the proportion of case and control subjects in each category of screening implementation and estimated the likelihood (odds ratio [OR] with 95% confidence intervals [CIs]) of late-stage breast cancer. We also evaluated demographic characteristics associated with absence of screening in women with late-stage disease. All statistical tests were two-sided. Results: Absence of screening, absence of detection, and potential breakdown in follow-up were distributed differently among case (52.1%, 39.5%, and 8.4%, respectively) and control subjects (34.4%, 56.9%, and 8.8%, respectively) ( P = .03). Among all women, the odds of having late-stage cancer were higher among women with an absence of screening (OR = 2.17, 95% CI = 1.84 to 2.56; P <.001). Among case patients, women were more likely to be in the absence-of-screening group if they were aged 75 years or older (OR = 2.77, 95% CI = 2.10 to 3.65), unmarried (OR = 1.78, 95% CI = 1.41 to 2.24), or without a family history of breast cancer (OR = 1.84, 95% CI = 1.45 to 2.34). A higher proportion of women from census blocks with less education (58.5% versus 49.4%; P = .003) or lower median annual income (54.4% versus 42.9%; P = .004) were in the absence-of-screening category compared with the proportion for the other two categories combined. Conclusions: To reduce late-stage breast cancer occurrence, reaching unscreened women, including elderly, unmarried, low-income, and less educated women, should be made a top priority for screening implementation.
The Cancer Consultation
Authors: Barry R. Meisenberg
Journal: JAMA Oncology (2021)

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
Invasive Fungal Infection in COVID-19–Recovered Patient Detected on 18F-FDG–Labeled Leukocytes PET/CT Scan
Authors: Divya Manda, Ishita Sen, Parul Thakral, Subha Shankar Das, Virupakshappa CB, Dharmender Malik
Journal: Clinical Nuclear Medicine (2021)

Occurrence of invasive fungal infections has gained significant attention during recent times in patients with COVID-19. Patients with severe form of COVID-19, such as those treated in the intensive care unit with prolonged steroid use, are particularly vulnerable to secondary bacterial and fungal infections. Disseminated systemic mycosis is a life-threatening condition, especially in immunocompromised patients. Here, we report a case of a recovered severe COVID-19 patient, who presented with persistent fever. 18F-FDG-labeled leukocyte scan revealed focal accumulation of radiotracer in the small intestine and right lung lower lobe. Subsequently, performed biopsy revealed mucormycosis.
Discovery of novel 4-phenylquinazoline-based BRD4 inhibitors for cardiac fibrosis
Authors: Zhangxu He, Haomiao Jiao, Qi An, Xin Zhang, Dan Zengyangzong, Jiale Xu, Hongmin Liu, Liying Ma, Wen Zhao
Journal: Acta Pharmaceutica Sinica B (2021)

Bromodomain containing protein 4 (BRD4), as an epigenetic reader, can specifically bind to the acetyl lysine residues of histones and has emerged as an attractive therapeutic target for various diseases, including cancer, cardiac remodeling and heart failure. Herein, we described the discovery of hit 5 bearing 4-phenylquinazoline skeleton through a high-throughput virtual screen using 2,003,400 compound library (enamine). Then, structure-activity relationship (SAR) study was performed and 47 new 4-phenylquinazoline derivatives toward BRD4 were further designed, synthesized and evaluated, using HTRF assay set up in our lab. Eventually, we identified compound C-34, which possessed better pharmacokinetic and physicochemical properties as well as lower cytotoxicity against NRCF and NRCM cells, compared to the positive control JQ1. Using computer-based molecular docking and cellular thermal shift assay, we further verified that C-34 could target BRD4 at molecular and cellular levels. Furthermore, treatment with C-34 effectively alleviated fibroblast activation
Medical Debt in the US, 2009-2020
Authors: Raymond Kluender, Neale Mahoney, Francis Wong, Wesley Yin
Journal: JAMA (2021)

<h3>Importance</h3> Medical debt is an increasing concern in the US, yet there is limited understanding of the amount and distribution of medical debt, and its association with health care policies. <h3>Objective</h3> To measure the amount of medical debt nationally and by geographic region and income group and its association with Medicaid expansion under the Affordable Care Act. <h3>Design, Setting, and Participants</h3> Data on medical debt in collections were obtained from a nationally representative 10% panel of consumer credit reports between January 2009 and June 2020 (reflecting care provided prior to the COVID-19 pandemic). Income data were obtained from the 2014-2018 American Community Survey. The sample consisted of 4.1 billion person-month observations (nearly 40 million unique individuals). These data were used to estimate the amount of medical debt (nationally and by geographic region and zip code income decile) and to examine the association between Medicaid expansion and medical debt (overall and by income group). <h3>Exposures</h3> Geographic region (US Census region), income group (zip code income decile), and state Medicaid expansion status. <h3>Main Outcomes and Measures</h3> The stock (all unpaid debt listed on credit reports) and flow (new debt listed on credit reports during the preceding 12 months) of medical debt in collections that can be collected on by debt collectors. <h3>Results</h3> In June 2020, an estimated 17.8% of individuals had medical debt (13.0% accrued debt during the prior year), and the mean amount was $429 ($311 accrued during the prior year). The mean stock of medical debt was highest in the South and lowest in the Northeast ($616 vs $167; difference, $448 [95% CI, $435-$462]) and higher in poor than in rich zip code income deciles ($677 vs $126; difference, $551 [95% CI, $520-$581]). Between 2013 and 2020, the states that expanded Medicaid in 2014 experienced a decline in the mean flow of medical debt that was 34.0 percentage points (95% CI, 18.5-49.4 percentage points) greater (from $330 to $175) than the states that did not expand Medicaid (from $613 to $550). In the expansion states, the gap in the mean flow of medical debt between the lowest and highest zip code income deciles decreased by $145 (95% CI, $95-$194) while the gap increased by $218 (95% CI, $163-$273) in the nonexpansion states. <h3>Conclusions and Relevance</h3> This study provides an estimate of the amount of medical debt in collections in the US based on consumer credit reports from January 2009 to June 2020, reflecting care delivered prior to the COVID-19 pandemic, and suggests that the amount of medical debt was highest among individuals living in the South and in lower-income communities. However, further study is needed regarding debt related to COVID-19.
Abstract 8322: Obesity-Related Alteration of Arterial Compliance Associated with Concentric Left Ventricular Hypertrophy Begins to Appear in Childhood
Authors: Kenji Harada, Yukiko Harada, Manatomo Toyono
Journal: Circulation (2011)

Background: Obesity is associated with worsening arterial compliance, but there is little information when arterial functional change begins to appear. The ratio of pulse pressure/stroke volume is a novel index for arterial compliance. The purpose of this study is to assess the relationship between body mass index (BMI) and this index and to investigate their relations to left ventricular (LV) geometry and function from childhood to adolescence. Methods: Echocardiography with tissue Doppler imaging was performed in 389 healthy subjects. Subjects were divided into 3 age groups: pre-school children group, 4 to 6 years (5±1 years, n = 125); school children group, 7 to 12 years (9±3 years, n = 176); and adolescents group, 13 to 20 years (15± 3 years, n = 88). Left ventricular (LV) end-diastolic volume and LV mass were measured and LV mass-to-volume ratio was calculated. Stroke volume (SV) was calculated using aortic diameter and pulsed Doppler velocity profile. SV was indexed for body surface area (SVI). Total arterial compliance (Ca) was estimated by the ratio of pulse pressure/SVI. Tissue Doppler-derived myocardial performance index (MPI) was calculated. Quantitative B-mode ultrasound scans were used to measure intima-media thickness (IMT) of the common carotid artery. Results: There was no significant relationship between BMI and Ca in the pre-school children group. However, in the school children and adolescents groups, weak but significant correlations between Ca and BMI were found (r = 0.29 and o.25, respectively, p &lt; 0.01). Within each group, LV mass-to-volume ratio increased significantly with BMI. Ca did not correlate with LV mass-to-volume ratio in the pre-school children group, however, increased Ca correlated significantly with increased LV mass-to-volume ratio in the school and adolescents groups (r = 0.17 and 0.23, respectively, p &lt; 0.01). There were weak but significant relationships between Ca and MPI and carotid IMT (r = 0.25 and 0.24, respectively, p &lt; 0.01) in the adolescents group. Conclusions: Obesity-related changes in arterial compliance and LV geometry and function begin to appear in younger school children. Our findings suggest that primary prevention programs should be initiated in early childhood.
Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Timothy A. Yap, Matthew G. Krebs, Sophie Postel-Vinay, Anthony El-Khouiery, Jean-Charles Soria, Juanita Lopez, Alienor Berges, S.Y. Amy Cheung, Itziar Irurzun-Arana, Andrew Goldwin, Brunella Felicetti, Gemma N. Jones, Alan Lau, Paul Frewer, Andrew J. Pierce, Glen Clack, Christine Stephens, Simon A. Smith, Emma Dean, Simon J. Hollingsworth
Journal: Clinical Cancer Research (2021)

This study reports the safety, tolerability, MTD, recommended phase II dose (RP2D), pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of ceralasertib combined with carboplatin in patients with advanced solid tumors. It also examined exploratory predictive and pharmacodynamic biomarkers.Eligible patients (n = 36) received a fixed dose of carboplatin (AUC5) with escalating doses of ceralasertib (20 mg twice daily to 60 mg once daily) in 21-day cycles. Sequential and concurrent combination dosing schedules were assessed.Two ceralasertib MTD dose schedules, 20 mg twice daily on days 4-13 and 40 mg once daily on days 1-2, were tolerated with carboplatin AUC5; the latter was declared the RP2D. The most common treatment-emergent adverse events (Common Terminology Criteria for Adverse Events grade ≥3) were anemia (39%), thrombocytopenia (36%), and neutropenia (25%). Dose-limiting toxicities of grade 4 thrombocytopenia (n = 2; including one grade 4 platelet count decreased) and a combination of grade 4 thrombocytopenia and grade 3 neutropenia occurred in 3 patients. Ceralasertib was quickly absorbed (tmax ∼1 hour), with a terminal plasma half-life of 8-11 hours. Upregulation of pRAD50, indicative of ataxia telangiectasia mutated (ATM) activation, was observed in tumor biopsies during ceralasertib treatment. Two patients with absent or low ATM or SLFN11 protein expression achieved confirmed RECIST v1.1 partial responses. Eighteen of 34 (53%) response-evaluable patients had RECIST v1.1 stable disease.The RP2D for ceralasertib plus carboplatin was established as ceralasertib 40 mg once daily on days 1-2 administered with carboplatin AUC5 every 3 weeks, with pharmacokinetic and pharmacodynamic studies confirming pharmacodynamic modulation and preliminary evidence of antitumor activity observed.
Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study
Authors: Elisabeth R. Mathiesen, Norsiah Ali, Amra C. Alibegovic, Eleni Anastasiou, Katarzyna Cypryk, Harold de Valk, Jorge Dores, Fidelma Dunne, Mari-Anne Gall, Santiago Duran Garcia, Hélène P. Hanaire, Lise Lotte N. Husemoen, Marina Ivanišević, Hans-Peter Kempe, David R. McCance, Peter Damm
Journal: Diabetes Care (2021)

OBJECTIVE To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes. RESEARCH DESIGN AND METHODS Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins. RESULTS Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI −0.01, 0.04]; adjusted risk difference −0.003 [95% CI −0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (−0.032 [95% CI −0.064, 0.000]) and after (−0.036 [95% CI –0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference −0.181 [95% CI −0.300, −0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; −0.139 [95% CI −0.232, −0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference −0.030 [95% CI −0.058, −0.002]), preeclampsia (6.4% vs. 10.0%; −0.036 [95% CI −0.064, −0.007]), and stillbirth (0.4% vs. 1.8%; −0.013 [95% CI −0.024, −0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment. CONCLUSIONS Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.
FDG PET/CT in Sacroiliac IgG4 Disease
Authors: Sherif Elsobky, Vruti Dattani, Thomas Wagner, Sri Mandumula, Aniket Tavare
Journal: Clinical Nuclear Medicine (2021)

Abstract A 68-year-old woman with abdominal pain and a raised C-reactive protein was investigated with a CT of the abdomen. CT showed an irregular soft tissue mass anterior to the aorta, which was thought to be neoplastic. The patient underwent 18 F-FDG PET/CT, which demonstrated hypermetabolic activity in this mass, as well as further foci of hypermetabolic activity in head and neck, sacroiliac joints, and pelvic floor muscles. A CT-guided biopsy of the sacroiliac joint was performed and revealed IgG4-related disease.
Self-assembly of differentiated progenitor cells facilitates spheroid human skin organoid formation and planar skin regeneration
Authors: Patricia Ebner-Peking, Linda Krisch, Martin Wolf, Sarah Hochmann, Anna Hoog, Balázs Vári, Katharina Muigg, Rodolphe Poupardin, Cornelia Scharler, Sabine Schmidhuber, Elisabeth Russe, Harald Stachelscheid, Achim Schneeberger, Katharina Schallmoser, Dirk Strunk
Journal: Theranostics (2021)

Self-assembly of solid organs from single cells would greatly expand applicability of regenerative medicine.Stem/progenitor cells can self-organize into micro-sized organ units, termed organoids, partially modelling tissue function and regeneration.Here we demonstrated 3D self-assembly of adult and induced pluripotent stem cell (iPSC)-derived fibroblasts, keratinocytes and endothelial progenitors into both, planar human skin in vivo and a novel type of spheroid-shaped skin organoids in vitro, under the aegis of human platelet lysate.Methods: Primary endothelial colony forming cells (ECFCs), skin fibroblasts (FBs) and keratinocytes (KCs) were isolated from human tissues and polyclonally propagated under 2D xeno-free conditions.Human tissue-derived iPSCs were differentiated into endothelial cells (hiPSC-ECs), fibroblasts (hiPSC-FBs) and keratinocytes (hiPSC-KCs) according to efficiency-optimized protocols.Cell identity and purity were confirmed by flow cytometry and clonogenicity indicated their stem/progenitor potential.Triple cell type floating spheroids formation was promoted by human platelet-derived growth factors containing culture conditions, using nanoparticle cell labelling for monitoring the organization process.Planar human skin regeneration was assessed in full-thickness wounds of immune-deficient mice upon transplantation of hiPSC-derived single cell suspensions.Results: Organoids displayed a distinct architecture with surface-anchored keratinocytes surrounding a stromal core, and specific signaling patterns in response to inflammatory stimuli.FGF-7 mRNA transfection was required to accelerate keratinocyte long-term fitness.Stratified human skin also self-assembled within two weeks after either adult-or iPSC-derived skin cell-suspension liquid-transplantation, healing deep wounds of mice.Transplant vascularization significantly accelerated in the presence of co-transplanted endothelial progenitors.Mechanistically, extracellular vesicles mediated the multifactorial platelet-derived trophic effects.No tumorigenesis occurred upon xenografting.Conclusion: This illustrates the superordinate progenitor self-organization principle and permits novel rapid 3D skin-related pharmaceutical high-content testing opportunities with floating spheroid skin organoids.Multi-cell transplant self-organization facilitates development of iPSC-based organ regeneration strategies using cell suspension transplantation supported by human platelet factors.
Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement From the American Heart Association
Authors: Michael H. Criqui, Kunihiro Matsushita, Victor Aboyans, Connie N. Hess, Caitlin W. Hicks, Tak W. Kwan, Mary M. McDermott, Sanjay Misra, Francisco Ujueta
Journal: Circulation (2021)

Lower extremity peripheral artery disease (PAD) affects >230 million adults worldwide and is associated with increased risk of various adverse clinical outcomes (other cardiovascular diseases such as coronary heart disease and stroke and leg outcomes such as amputation). Despite its prevalence and clinical importance, PAD has been historically underappreciated by health care professionals and patients. This underappreciation seems multifactorial (eg, limited availability of the first-line diagnostic test, the ankle-brachial index, in clinics; incorrect perceptions that a leg vascular disease is not fatal and that the diagnosis of PAD would not necessarily change clinical practice). In the past several years, a body of evidence has indicated that these perceptions are incorrect. Several studies have consistently demonstrated that many patients with PAD are not receiving evidence-based therapies. Thus, this scientific statement provides an update for health care professionals regarding contemporary epidemiology (eg, prevalence, temporal trends, risk factors, and complications) of PAD, the present status of diagnosis (physiological tests and imaging modalities), and the major gaps in the management of PAD (eg, medications, exercise therapy, and revascularization). The statement also lists key gaps in research, clinical practice, and implementation related to PAD. Orchestrated efforts among different parties (eg, health care providers, researchers, expert organizations, and health care organizations) will be needed to increase the awareness and understanding of PAD and improve the diagnostic approaches, management, and prognosis of PAD.
High-affinity T-cell receptor specific for MyD88 L265P mutation for adoptive T-cell therapy of B-cell malignancies
Authors: Özcan Çınar, Bernadette Brzezicha, Corinna Grunert, Peter Michael Kloetzel, Christin Beier, Caroline Anna Peuker, Ulrich Keller, Antonio Pezzutto, Antonia Busse
Journal: Journal for ImmunoTherapy of Cancer (2021)

Adoptive transfer of engineered T cells has shown remarkable success in B-cell malignancies. However, the most common strategy of targeting lineage-specific antigens can lead to undesirable side effects. Also, a substantial fraction of patients have refractory disease. Novel treatment approaches with more precise targeting may be an appealing alternative. Oncogenic somatic mutations represent ideal targets because of tumor specificity. Mutation-derived neoantigens can be recognized by T-cell receptors (TCRs) in the context of MHC-peptide presentation.Here we have generated T-cell lines from healthy donors by autologous in vitro priming, targeting a missense mutation on the adaptor protein MyD88, changing leucine at position 265 to proline (MyD88 L265P), which is one of the most common driver mutations found in B-cell lymphomas.Generated T-cell lines were selectively reactive against the mutant HLA-B*07:02-restricted epitope but not against the corresponding wild-type peptide. Cloned TCRs from these cell lines led to mutation-specific and HLA-restricted reactivity with varying functional avidity. T cells engineered with a mutation-specific TCR (TCR-T cells) recognized and killed B-cell lymphoma cell lines characterized by intrinsic MyD88 L265P mutation. Furthermore, TCR-T cells showed promising therapeutic efficacy in xenograft mouse models. In addition, initial safety screening did not indicate any sign of off-target reactivity.Taken together, our data suggest that mutation-specific TCRs can be used to target the MyD88 L265P mutation, and hold promise for precision therapy in a significant subgroup of B-cell malignancies, possibly achieving the goal of absolute tumor specificity, a long sought-after dream of immunotherapy.