tbuckley/cabot-search huggingface dataset:
Select Antitumor Cytotoxic CD8+ T Clonotypes Expand in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib
Authors: Maria Joao Baptista, Sivasubramanian Baskar, Erika M. Gaglione, Keyvan Keyvanfar, Inhye E. Ahn, Adrian Wiestner, Clare Sun
Journal: Clinical Cancer Research (2021)

Abstract Purpose: In chronic lymphocytic leukemia (CLL), the T-cell receptor (TCR) repertoire is skewed and tumor-derived antigens are hypothesized as drivers of oligoclonal expansion. Ibrutinib, a standard treatment for CLL, inhibits not only Bruton tyrosine kinase of the B-cell receptor signaling pathway, but also IL2-inducible kinase of the TCR signaling pathway. T-cell polarization and activation are affected by ibrutinib, but it is unknown whether T cells contribute to clinical response. Experimental Design: High-throughput TCRβ sequencing was performed in 77 longitudinal samples from 26 patients with CLL treated with ibrutinib. TCRβ usage in CD4+ and CD8+ T cells and granzyme B expression were assessed by flow cytometric analysis. Antitumor cytotoxicity of T cells expanded with autologous CLL cells or with antigen-independent anti-CD3/CD28/CD137 beads was tested. Results: The clonality of the TCR repertoire increased at the time of response. With extended treatment, TCR clonality remained stable in patients with sustained remission and decreased in patients with disease progression. Expanded clonotypes were rarely shared between patients, indicating specificity for private antigens. Flow cytometry demonstrated a predominance of CD8+ cells among expanded clonotypes. Importantly, bulk T cells from responding patients were cytotoxic against autologous CLL cells in vitro and selective depletion of major expanded clonotypes reduced CLL cell killing. Conclusions: In patients with CLL, established T-cell responses directed against tumor are suppressed by disease and reactivated by ibrutinib. See related commentary by Zent, p. 4465
Infant Mortality Associated With Prenatal Opioid Exposure
Authors: JoAnna K. Leyenaar, Andrew P. Schaefer, Jared R. Wasserman, Erika L. Moen, A. James O’Malley, David C. Goodman
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> Knowledge of health outcomes among opioid-exposed infants is limited, particularly for those not diagnosed with neonatal opioid withdrawal syndrome (NOWS). <h3>Objectives</h3> To describe infant mortality among opioid-exposed infants and identify how mortality risk differs in opioid-exposed infants with and without a diagnosis of NOWS compared with infants without opioid exposure. <h3>Design, Setting, and Participants</h3> A retrospective cohort study of maternal-infant dyads was conducted, linking health care claims with vital records for births from January 1, 2010, to December 31, 2014, with follow-up of infants until age 1 year (through 2015). Maternal-infant dyads were included if the infant was born in Texas at 22 to 43 weeks’ gestational age to a woman aged 15 to 44 years insured by Texas Medicaid. Data analysis was performed from May 2019 to October 2020. <h3>Exposure</h3> The primary exposure was prenatal opioid exposure, with infants stratified by the presence or absence of a diagnosis of NOWS during the birth hospitalization. <h3>Main Outcomes and Measures</h3> Risk of infant mortality (death at age &lt;365 days) was examined using Kaplan-Meier and log-rank tests. A series of logistic regression models was estimated to determine associations between prenatal opioid exposure and mortality, adjusting for maternal and neonatal characteristics and clustering infants at the maternal level to account for statistical dependence owing to multiple births during the study period. <h3>Results</h3> Among 1 129 032 maternal-infant dyads, 7207 had prenatal opioid exposure, including 4238 diagnosed with NOWS (mean [SD] birth weight, 2851 [624] g) and 2969 not diagnosed with NOWS (mean [SD] birth weight, 2971 [639] g). Infant mortality was 20 per 1000 live births for opioid-exposed infants not diagnosed with NOWS, 11 per 1000 live births for infants with NOWS, and 6 per 1000 live births in the reference group (<i>P</i> &lt; .001). After adjusting for maternal and neonatal characteristics, mortality in infants with a NOWS diagnosis was not significantly different from the reference population (odds ratio, 0.82; 95% CI, 0.58-1.14). In contrast, the odds of mortality in opioid-exposed infants not diagnosed with NOWS was 72% greater than the reference population (odds ratio, 1.72; 95% CI, 1.25-2.37). <h3>Conclusions and Relevance</h3> In this study, opioid-exposed infants appeared to be at increased risk of mortality, and the treatments and supports provided to those diagnosed with NOWS may be protective. Interventions to support opioid-exposed maternal-infant dyads are warranted, regardless of the perceived severity of neonatal opioid withdrawal.
Studies in the Home Treatment of Streptococcal Disease
Authors: Daniel N. Mohler, David G. Wallin, Edward G. Dreyfus
Journal: New England Journal of Medicine (1955)

ORAL administration of penicillin has been shown by many investigators to be an effective form of treatment of appropriate bacterial infections.1 2 3 4 5 However, it has been remarked that one of the disadvantages of the oral route is that a large share of the responsibility for carrying out the prescribed therapy rests with the patient.6 7 8 This may lead to a failure to complete the full course of treatment and may thereby significantly influence effective control and prevention of disease. It appears from the studies done by the Streptococcal Disease Laboratory in Cheyenne, Wyoming, and from other investigations that rheumatic fever can be . . .
The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude
Authors: Zhong-Yin Li, Rosemary E. Morman, Emma Hegermiller, Mengxi Sun, Elizabeth T. Bartom, Mark Maienschein-Cline, Mikael Sigvardsson, Barbara L. Kee
Journal: The Journal of Experimental Medicine (2021)

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and temporal dynamics of the transcription factor TCF1. TCF1 promotes immature NK cell expansion and restrains differentiation. The increased TCF1 expression in ID2-deficient NK cells arrests their maturation and alters cell surface receptor expression. Moreover, TCF1 limits NK cell functions, such as cytokine-induced IFN-γ production and the ability to clear metastatic melanoma in ID2-deficient NK cells. Our data demonstrate that ID2 sets a threshold for TCF1 during NK cell development, thus controlling the balance of immature and terminally differentiated cells that support future NK cell responses.
Deep learning reconstruction of digital breast tomosynthesis images for accurate breast density and patient-specific radiation dose estimation
Authors: Jonas Teuwen, Nikita Moriakov, Christian Fedon, Marco Caballo, Ingrid Reiser, Pedrag Bakic, Eloy García, Oliver Diaz, Koen Michielsen, Ioannis Sechopoulos
Journal: Medical Image Analysis (2021)

The two-dimensional nature of mammography makes estimation of the overall breast density challenging, and estimation of the true patient-specific radiation dose impossible. Digital breast tomosynthesis (DBT), a pseudo-3D technique, is now commonly used in breast cancer screening and diagnostics. Still, the severely limited 3rd dimension information in DBT has not been used, until now, to estimate the true breast density or the patient-specific dose. This study proposes a reconstruction algorithm for DBT based on deep learning specifically optimized for these tasks. The algorithm, which we name DBToR, is based on unrolling a proximal-dual optimization method. The proximal operators are replaced with convolutional neural networks and prior knowledge is included in the model. This extends previous work on a deep learning-based reconstruction model by providing both the primal and the dual blocks with breast thickness information, which is available in DBT. Training and testing of the model were performed using virtual patient phantoms from two different sources. Reconstruction performance, and accuracy in estimation of breast density and radiation dose, were estimated, showing high accuracy (density <±3%; dose <±20%) without bias, significantly improving on the current state-of-the-art. This work also lays the groundwork for developing a deep learning-based reconstruction algorithm for the task of image interpretation by radiologists.
Laboratory Modeling of SARS-CoV-2 Exposure Reduction Through Physically Distanced Seating in Aircraft Cabins Using Bacteriophage Aerosol — November 2020
Authors: Watts L. Dietrich, James S. Bennett, Byron W. Jones, Mohammad H. Hosni
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Aircraft can hold large numbers of persons in close proximity for long periods, which can increase the risk for transmission of infectious disease.*Current CDC guidelines recommend against travel for persons who have not been vaccinated against COVID-19, and a January 2021 CDC order requires masking for all persons while on airplanes.†, § Research suggests that seating proximity on aircraft is associated with increased risk for infection with SARS-CoV-2, the virus that causes COVID-19 (1,2).However, studies quantifying the benefit of specific distancing strategies to prevent transmission, such as keeping aircraft cabin middle seats vacant, are limited.Using bacteriophage MS2 virus as a surrogate for airborne SARS-CoV-2, CDC and Kansas State University (KSU) modeled the relationship between SARS-CoV-2 exposure and aircraft seating proximity, including full occupancy and vacant middle seat occupancy scenarios.Compared with exposures in full occupancy scenarios, relative exposure in vacant middle seat scenarios was reduced by 23% to 57% depending upon the modeling approach.A 23% exposure reduction was observed for a single passenger who was in the same row and two seats away from the SARS-COV-2 source, rather than in an adjacent middle seat.When quantifying exposure reduction to a full 120-passenger cabin rather than to a single person, exposure reductions ranging from 35.0% to 39.4% were predicted.A 57% exposure reduction was observed under the vacant middle seat condition in a scenario involving a three-row section that contained a mix of SARS-CoV-2 sources and other passengers.Based on this laboratory model, a vacant middle seat reduces risk for exposure to SARS-CoV-2 from nearby passengers.These data suggest that increasing physical distance between passengers and lowering passenger density could help reduce potential COVID-19 exposures during air travel.Physical distancing of airplane passengers, including through policies such as middle seat vacancy, could provide additional reductions in SARS-CoV-2 exposure risk.The study consisted of three components.The first involved analysis of data on virus aerosol dispersion in aircraft cabin mock-ups from a previous study conducted at KSU during
Non-Alcoholic Fatty Liver Disease Progression to Non-Alcoholic Steatohepatitis-Related Primary Liver Cancer
Authors: Utibe-Abasi Udoh, Juan D Sanabria, Pradeep K Rajan, Moumita Banerjee, Mathew Schade, Jacqueline A Sanabria, Gary Smith, Gideon Udoh, Komal Sodhi, Sandrine Pierre, Joseph I Shapiro, Juan R Sanabria
Journal: Liver Cancer (2021)

Hepatocellular carcinoma is the most common type of primary liver cancer and constitutes about 90-95% of all hepatic malignancies. It is the second and fastest-growing cause of cancer-related mortality worldwide. Although there is multiplicity in the etiology of hepatocellular carcinoma, accumulating evidence shows that non-alcoholic fatty liver disease has risen to become the top etiological factor for hepatocellular carcinoma in the United States and other developed nations, mainly because of the metabolic disturbances from obesity, a western epidemic. Non-alcoholic fatty liver disease comprises a spectrum of hepatic pathologies, ranging from simple steatosis to its inflammatory form, non-alcoholic steatohepatitis. With its concomitant increasing liver collagen deposition, non-alcoholic steatohepatitis paves the pathway for hepatocellular carcinoma development, which may occur with or without established cirrhosis. This chapter focuses on the current knowledge related to the epidemiology and cellular mechanisms that underpin the progression of non-alcoholic fatty liver disease to malignancy. Furthermore, it gives insight into the diagnosis, treatment options, and future directions for non-alcoholic steatohepatitis-related tumorigenesis.
Reporting of Study Participant Demographic Characteristics and Demographic Representation in Premarketing and Postmarketing Studies of Novel Cancer Therapeutics
Authors: Tanvee Varma, Joshua D. Wallach, Jennifer E. Miller, Dominic Schnabel, Joshua J. Skydel, Audrey D. Zhang, Michaela A. Dinan, Joseph S. Ross, Cary P. Gross
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Adequate representation of demographic subgroups in premarketing and postmarketing clinical studies is necessary for understanding the safety and efficacy associated with novel cancer therapeutics. <h3>Objective</h3> To characterize and compare the reporting of demographic data and the representation of individuals by sex, age, and race in premarketing and postmarketing studies used by the Food and Drug Administration (FDA) to evaluate novel cancer therapeutics. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, premarketing and postmarketing studies for novel cancer therapeutics approved by the FDA from 2012 through 2016 were identified. Study demographic information was abstracted from publicly available sources, and US cancer population demographic data was abstracted from US Cancer Statistics. Analyses were conducted from February 25 through September 21, 2020. <h3>Main Outcomes and Measures</h3> The percentages of trials reporting sex, age, and race/ethnicity were calculated, and participation to prevalence ratios (PPRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the US cancer population in each group. PPRs were constructed for premarketing and postmarketing studies and by cancer type. Underrepresentation was defined as PPR less than 0.8. <h3>Results</h3> From 2012 through 2016, the FDA approved 45 cancer therapeutics. The study sample included 77 premarketing studies and 56 postmarketing studies. Postmarketing studies, compared with premarketing studies, were less likely to report patient sex (42 studies reporting [75.0%] vs 77 studies reporting [100%];<i>P</i> &lt; .001) and race (27 studies reporting [48.2%] vs 62 studies reporting [80.5%];<i>P</i> &lt; .001). Women were adequately represented in premarketing studies (mean [SD] PPR, 0.91; 95% CI, 0.90-0.91) and postmarketing studies (mean PPR, 1.00; 95% CI, 1.00-1.01). Although older adults and Black patients were underrepresented in premarketing studies (older adults: mean PPR, 0.73; 95% CI, 0.72-0.74; Black patients: mean PPR, 0.32; 95% CI, 0.31-0.32), these groups continued to be underrepresented in postmarketing studies (older adults: mean PPR, 0.75; 95% CI, 0.75-0.76; Black patients: mean PPR, 0.21; 95% CI, 0.21-0.21). <h3>Conclusions and Relevance</h3> This study found that older adults and Black patients were underrepresented in postmarketing studies of novel cancer therapeutics to a similar degree that they were underrepresented in premarketing studies. These findings suggest that postmarketing studies are not associated with improvements to gaps in demographic representation present at the time of FDA approval.
Complete response in a patient with advanced melanoma following anti‐PD‐1 therapy is associated with a high frequency of melanoma‐infiltrating CXCR3 <sup>+</sup> resident memory CD8 <sup>+</sup> T cells and multiple chemokine pathways
Authors: L. Dousset, C. Martins, C. Jacquemin, S. Amico, T. Schatton, K. Boniface, J. Seneschal
Journal: British Journal of Dermatology (2021)
The impact of corona virus disease- 2019 on breast services at university hospitals of North Midlands, United Kingdom
Authors: M. S. Gowda, K. Kabeer, F. Mansour, A. Hasan, E. Nael, V. Gopalan, D. Gahir, A. Jegannathen, S. Marla, S. Soumian, S. Narayanan, S. J. Bhoy
Journal: Cancer Research (2021)

Introduction: The COVID-19 pandemic has disrupted routine cancer care and training globally  Breast units adopted modified national guidelines in the UK, and significant changes were implemented to ensure the safety of patients and staff  The national breast screening services were temporarily suspended from March 2020  Patients underwent surgery in COVID-19 free zones  Complex oncoplastic procedures and immediate reconstructions were not offered  Adjuvant treatments were modified to reduce the risk of complications and hospital readmission  The objective of our study is to assess the impact of COVID-19 on breast cancer management and surgical training  Methods: The resource reallocation was implemented for 100 days, commencing from the 16th of March,2020  Patients diagnosed with breast cancer during this period were identified from the cancer database, and a comparison was made with patients diagnosed last year within the same time frame  We assessed the time taken from the decision to treatment and modifications made to cancer management due to the pandemic  The impact on resident training was evaluated by comparing the number of cases performed or assisted during this period  Results: During the pandemic period, out of 1064 patients seen in the Breast one-stop clinic, 64 patients (6 0%) were diagnosed with breast cancer  During the same time frame in 2019, out of 1881 new symptomatic patients, 90 (4 8%) were diagnosed with cancer  In 2019, sixty-three patients were treated for screen-detected cancer, whereas only 23 patients entered the screening pathway before the services were suspended  Majority of patients underwent surgery in 2019 as compared to 2020 (80% versus 36%)  Fifty-six percent of patients received endocrine treatmentas primary or bridging therapy;whereas, in 2019, only 12% received primary endocrine therapy  In 2020, time fromdecision to surgical treatment has decreased by half as compared to 2019 (8 6 versus 19 1 days)  One patient whounderwent surgery developed COVID-19 infection after two weeks, and no postoperative mortality was reported  Onaverage, each trainee was involved in 35 procedures during 2020;whereas in 2019, 54 procedures were assisted orperformed by a trainee  Conclusion: Our study shows that COVID-19 has made a significant impact on patients'management and surgical training  Majority of the patients were commenced on neoadjuvant endocrine therapyinstead of surgery  The conversion rate to cancers in one-stop clinic improved possibly due to a smaller number of benign referrals during the pandemic  The impact on surgical training is due to the reduction in the number of patients operated during this period, and constraints of performing complex oncoplastic procedures and breastreconstruction
Thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, sulfonylureas, and hepatocellular carcinoma risk: A meta-analysis
Authors: Ashwini Arvind, Zoe N. Memel, Lisa L. Philpotts, Hui Zheng, Kathleen E. Corey, Tracey G. Simon
Journal: Metabolism (2021)
Genomic Basis of Striking Fin Shapes and Colors in the Fighting Fish
Authors: Le Wang, Fei Sun, Zi Yi Wan, Baoqing Ye, Yanfei Wen, Huiming Liu, Zituo Yang, Hongyan Pang, Zining Meng, Bin Fan, Yuzer Alfiko, Yubang Shen, Bin Bai, May Shu Qing Lee, Francesc Piferrer, Manfred Schartl, Axel Meyer, Gen Hua Yue
Journal: Molecular Biology and Evolution (2021)

Resolving the genomic basis underlying phenotypic variations is a question of great importance in evolutionary biology. However, understanding how genotypes determine the phenotypes is still challenging. Centuries of artificial selective breeding for beauty and aggression resulted in a plethora of colors, long-fin varieties, and hyper-aggressive behavior in the air-breathing Siamese fighting fish (Betta splendens), supplying an excellent system for studying the genomic basis of phenotypic variations. Combining whole-genome sequencing, quantitative trait loci mapping, genome-wide association studies, and genome editing, we investigated the genomic basis of huge morphological variation in fins and striking differences in coloration in the fighting fish. Results revealed that the double tail, elephant ear, albino, and fin spot mutants each were determined by single major-effect loci. The elephant ear phenotype was likely related to differential expression of a potassium ion channel gene, kcnh8. The albinotic phenotype was likely linked to a cis-regulatory element acting on the mitfa gene and the double-tail mutant was suggested to be caused by a deletion in a zic1/zic4 coenhancer. Our data highlight that major loci and cis-regulatory elements play important roles in bringing about phenotypic innovations and establish Bettas as new powerful model to study the genomic basis of evolved changes.
Comprehensive large-scale nucleic acid–testing strategies support China’s sustained containment of COVID-19
Authors: Zhongjie Li, Fengfeng Liu, Jinzhao Cui, Zhibin Peng, Zhaorui Chang, Shengjie Lai, Qiulan Chen, Liping Wang, George F. Gao, Zijian Feng
Journal: Nature Medicine (2021)
Effect of an electronic nicotine delivery system with 0, 8, or 36 mg/mL liquid nicotine versus a cigarette substitute on tobacco-related toxicant exposure: a four-arm, parallel-group, randomised, controlled trial
Authors: Caroline O Cobb, Jonathan Foulds, Miao-Shan Yen, Susan Veldheer, Alexa A Lopez, Jessica M Yingst, Christopher Bullen, Le Kang, Thomas Eissenberg, Sophia I. Allen, Phoebe Brosnan, Christopher Bullen, Nadia Chowdhury, Caroline O. Cobb, Thomas Eissenberg, Jonathan Foulds, Jacob T. Graham, Erin Hammett, Sharilee Hrabovsky, Breianna L. Hummer, Le Kang, Courtney Lester, Alexa A. Lopez, John P. Richie, Christopher Sciamanna, Shumei Sun, Thokozeni Lipato, Susan Veldheer, Miao-Shan Yen, Jessica M. Yingst
Journal: The Lancet Respiratory Medicine (2021)