tbuckley/cabot-search huggingface dataset:
<i>In Vivo</i> Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification
Authors: Jinghang Xie, Meghan A. Rice, Zixin Chen, Yunfeng Cheng, En-Chi Hsu, Min Chen, Guosheng Song, Liyang Cui, Kaixiang Zhou, Jessa B. Castillo, Chiyuan A. Zhang, Bin Shen, Frederick T. Chin, Christian A. Kunder, James D. Brooks, Tanya Stoyanova, Jianghong Rao
Journal: Cancer Research (2021)

Prostate cancer is one of the most common malignancies worldwide, yet limited tools exist for prognostic risk stratification of the disease. Identification of new biomarkers representing intrinsic features of malignant transformation and development of prognostic imaging technologies are critical for improving treatment decisions and patient survival. In this study, we analyzed radical prostatectomy specimens from 422 patients with localized disease to define the expression pattern of methionine aminopeptidase II (MetAP2), a cytosolic metalloprotease that has been identified as a druggable target in cancer. MetAP2 was highly expressed in 54% of low-grade and 59% of high-grade cancers. Elevated levels of MetAP2 at diagnosis were associated with shorter time to recurrence. Controlled self-assembly of a synthetic small molecule enabled design of the first MetAP2-activated PET imaging tracer for monitoring MetAP2 activity in vivo. The nanoparticles assembled upon MetAP2 activation were imaged in single prostate cancer cells with post-click fluorescence labeling. The fluorine-18-labeled tracers successfully differentiated MetAP2 activity in both MetAP2-knockdown and inhibitor-treated human prostate cancer xenografts by micro-PET/CT scanning. This highly sensitive imaging technology may provide a new tool for noninvasive early-risk stratification of prostate cancer and monitoring the therapeutic effect of MetAP2 inhibitors as anticancer drugs. SIGNIFICANCE: This study defines MetAP2 as an early-risk stratifier for molecular imaging of aggressive prostate cancer and describes a MetAP2-activated self-assembly small-molecule PET tracer for imaging MetAP2 activity in vivo.
Nightmare Case of Complex Neonatal Truncus Arteriosus
Authors: Nabil Tahhan, Taleb Jammal
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Neonatal management of severe quadricuspid truncal valve insufficiency is very challenging with high risk of postoperative mortality. Aortic valve reconstruction is the unique rescue and should be consider and previously planned in case of truncal valvuloplasty failure. Many extracardiac malformations can be associated to truncus arteriosus, therefore a cardiac and chest computed tomography scan must be performed before the elective surgical repair.
Abstract PS1-66: Current practice in implant-based breast reconstruction: A french long-term follow-up study
Authors: Lea Pauly, Benoit Couturaud, Fabien Reyal
Journal: Cancer Research (2021)

Abstract Background: There is a lack of data on the use of breast implants and the path of patients reconstructed after breast cancer in France. This study aims to identify the paths of patients reconstructed by breast implant in France and assess their impact on survival, but also estimate the quality of the reconstruction, determined by early removal or replacement of implants.Methods : We performed a multicentric retrospective cohort study on women who underwent immediate or delayed implant-based reconstruction after curative or prophylactic mastectomy between 2002 and 2010 in three French private health institutions of public interest.Results : We identified 9 care pathways according to the type of disease, the type of surgery, the addition or not of adjuvant radiotherapy, and the timing of reconstruction. Theses courses concern 2,499 patients, and 3,191 breasts on which at least one implant has been placed. Five implant brands were mainly used during this period: PIP, Mentor, Allergan, Sebbin, and Perthese - with a total of 4,106 implants. The median of follow-up is 6 years [0 ;12 ;1]. The number of implants per breast is significantly different according to the reconstruction pathways (p&amp;lt;0.001). The overall survival and removal incidence of implants are significantly different according to the differents profiles of reconstruction (Log-Rank test: p &amp;lt;0.001).Conclusion : The profiles of patients reconstructed by implants are very heterogeneous, according to their disease, their surgery, the adjunction of adjuvant radiotherapy, and the reconstruction time. This leads to very differents overall survival and breast implants removal rates. By identifying specific pathways despite the heterogeneity of the population, this study makes it possible to identify patients at risk more precisely and to have a more global vision on implant reconstruction in France in the 2000s, over a decade of PIP breast implant use. Citation Format: Lea Pauly, Benoit Couturaud, Fabien Reyal. Current practice in implant-based breast reconstruction: A french long-term follow-up study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-66.
Abstract PS1-20: Pathologic lymph lode status of patients with T1 HER2-positive breast cancer who did not receive neoadjuvant chemotherapy using the national cancer database
Authors: Laura DeCesare, Claudia Perez, Neha Nimmagadda, Yanyu Zhang, Samantha Terranella, Nicholas Skertich, Aaron Wiegmann, Andrea Madrigrano, Rosalinda Alvarado, Cristina O'Donoghue
Journal: Cancer Research (2021)

Abstract Purpose: HER2 directed neoadjuvant therapies for locally advanced HER2-positive breast cancer have improved complete pathologic response and event-free survival. For T1 breast cancer, lymph node status often determines whether neoadjuvant treatment is indicated. The aim of this study was to identify patient and tumor characteristics using the National Cancer Database.Methods: A retrospective review of patents diagnosed with T1 clinically node negative (cT1N0) HER2-positive breast cancers was performed using the American College of Surgeons National Cancer Database (ACS NCDB) from 2004-2016. Exclusion criteria included age &amp;lt;18 years and neoadjuvant treatment. Primary outcome was lymph node status. Additional variables included: age, tumor size, tumor location, histology, grade, lymphovascular invasion (LVI), grade, and estrogen receptor (ER) and progesterone receptor (PR) status. Chi-Square tests were performed to evaluate the relationship between these variables and lymph node positive disease. Results: A total of 57,366 T1 HER2-positive patients were identified with 8,994 patients (15.68%) having positive lymph nodes. Characteristics associated with lymph node involvement included age (p&amp;lt;0.001), tumor location (p&amp;lt;0.001), lymphovascular involvement (p&amp;lt;0.001), ER positivity (p=0.021), and PR positivity (p&amp;lt;0.001). There was a significant difference in tumor size when comparing lymph node positive and negative disease (19.06 mm vs. 13.11 mm, p&amp;lt;0.001). Conclusion: Age, tumor location, LVI, ER positivity, PR positivity, and larger tumor size are associated with lymph node involvement in cT1N0 HER2-positive breast cancers. Future research includes determining best practices to identify which patients in this population would benefit from neoadjuvant chemotherapy. Citation Format: Laura DeCesare, Claudia Perez, Neha Nimmagadda, Yanyu Zhang, Samantha Terranella, Nicholas Skertich, Aaron Wiegmann, Andrea Madrigrano, Rosalinda Alvarado, Cristina O'Donoghue. Pathologic lymph lode status of patients with T1 HER2-positive breast cancer who did not receive neoadjuvant chemotherapy using the national cancer database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-20.
Adaptive Admixture of HLA Class I Allotypes Enhanced Genetically Determined Strength of Natural Killer Cells in East Asians
Authors: Zhihui Deng, Jianxin Zhen, Genelle F Harrison, Guobin Zhang, Rui Chen, Ge Sun, Qiong Yu, Neda Nemat-Gorgani, Lisbeth A Guethlein, Liumei He, Mingzhong Tang, Xiaojiang Gao, Siqi Cai, William H Palmer, Jonathan A Shortt, Christopher R Gignoux, Mary Carrington, Hongyan Zou, Peter Parham, Wenxu Hong, Paul J Norman
Journal: Molecular Biology and Evolution (2021)

Abstract Human natural killer (NK) cells are essential for controlling infection, cancer, and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B, and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B, and -C genes, we show that the Chinese Southern Han (CHS) are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the CHS KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C-specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B-specific receptors. In all these characteristics, the CHS represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity, and effector strength, likely augmenting resistance to endemic viral infections.
The Invisibility of Asian Americans in COVID-19 Data, Reporting, and Relief
Authors: Jennifer L. Young, Mildred K. Cho
Journal: The American Journal of Bioethics (2021)

Click to increase image sizeClick to decrease image sizeThis article refers to:Structural Racism in the COVID-19 Pandemic: Moving ForwardThis article is referred to by:An Open Dialogue on Health Disparities and Structural Racism: Response to Open Peer Commentaries
Extreme endoscopy: direct jejunostomy, re-anastomosis of bowel, percutaneous assisted transprosthetic endoscopic drainage in Roux-en-Y gastric bypass
Authors: Álvaro Martínez-Alcalá  García, Ivan Jovanovic, Ali M. Ahmed, Marco D’Assuncao, Thomas Kröner, Klaus Mönkemüller
Journal: Endoscopy (2021)

A 52-year-old female with history of Roux-en-Y gastric bypass underwent resection of a huge cystic tumor of the pancreas. Postoperatively an amylase-rich retroperitoneal fluid collection was noted. The patient was referred for double-balloon endoscopic retrograde cholangiopancreatography (ERCP) for a suspected pancreatic duct leak. The patient had anemia, anasarca, and severe malnutrition (albumin level of 1.8 g/dl – normal range 3.5 to 4.6 g/dl; hemoglobin 9 g/dl – normal range 11.5 to 14.5). During endoscopy performed under general anesthesia, it became evident that the jejunal esophageal anastomosis was disrupted, communicating with a large pleuroperitoneal abscess. At this time a change in plans became mandatory.
The pathophysiological role of novel pulmonary arterial hypertension gene<i>SOX17</i>
Authors: Yukyee Wu, John Wharton, Rachel Walters, Eleni Vasilaki, Jurjan Aman, Lan Zhao, Martin R. Wilkins, Christopher J. Rhodes
Journal: European Respiratory Journal (2021)

Pulmonary arterial hypertension (PAH) is a progressive disease predominantly targeting pre-capillary blood vessels. Adverse structural remodelling and increased pulmonary vascular resistance result in cardiac hypertrophy and ultimately failure of the right ventricle. Recent whole-genome and whole-exome sequencing studies have identified SOX17 as a novel risk gene in PAH, with a dominant mode of inheritance and incomplete penetrance. Rare deleterious variants in the gene and more common variants in upstream enhancer sites have both been associated with the disease, and a deficiency of SOX17 expression may predispose to PAH. This review aims to consolidate the evidence linking genetic variants in SOX17 to PAH, and explores the numerous targets and effects of the transcription factor, focusing on the pulmonary vasculature and the pathobiology of PAH.
Factor XII plays a pathogenic role in organ failure and death in baboons challenged with <i>Staphylococcus aureus</i>
Authors: Robert Silasi, Ravi S. Keshari, Girija Regmi, Cristina Lupu, Constantin Georgescu, Joe H. Simmons, Michael Wallisch, Tia C. L. Kohs, Joseph J. Shatzel, Sven R. Olson, Christina U. Lorentz, Cristina Puy, Erik I. Tucker, David Gailani, Sidney Strickland, András Gruber, Owen J. T. McCarty, Florea Lupu
Journal: Blood (2021)
Development and validation of a reinforcement learning algorithm to dynamically optimize mechanical ventilation in critical care
Authors: Arne Peine, Ahmed Hallawa, Johannes Bickenbach, Guido Dartmann, Lejla Begic Fazlic, Anke Schmeink, Gerd Ascheid, Christoph Thiemermann, Andreas Schuppert, Ryan Kindle, Leo Celi, Gernot Marx, Lukas Martin
Journal: npj Digital Medicine (2021)

Abstract The aim of this work was to develop and evaluate the reinforcement learning algorithm VentAI, which is able to suggest a dynamically optimized mechanical ventilation regime for critically-ill patients. We built, validated and tested its performance on 11,943 events of volume-controlled mechanical ventilation derived from 61,532 distinct ICU admissions and tested it on an independent, secondary dataset (200,859 ICU stays; 25,086 mechanical ventilation events). A patient “data fingerprint” of 44 features was extracted as multidimensional time series in 4-hour time steps. We used a Markov decision process, including a reward system and a Q-learning approach, to find the optimized settings for positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO 2 ) and ideal body weight-adjusted tidal volume (Vt). The observed outcome was in-hospital or 90-day mortality. VentAI reached a significantly increased estimated performance return of 83.3 (primary dataset) and 84.1 (secondary dataset) compared to physicians’ standard clinical care (51.1). The number of recommended action changes per mechanically ventilated patient constantly exceeded those of the clinicians. VentAI chose 202.9% more frequently ventilation regimes with lower Vt (5–7.5 mL/kg), but 50.8% less for regimes with higher Vt (7.5–10 mL/kg). VentAI recommended 29.3% more frequently PEEP levels of 5–7 cm H 2 O and 53.6% more frequently PEEP levels of 7–9 cmH 2 O. VentAI avoided high (&gt;55%) FiO 2 values (59.8% decrease), while preferring the range of 50–55% (140.3% increase). In conclusion, VentAI provides reproducible high performance by dynamically choosing an optimized, individualized ventilation strategy and thus might be of benefit for critically ill patients.
Abstract PS4-39: Efficacy of combined CDK4/6 inhibitor and PARP inhibitor in the treatment of BRCA1 mutant triple negative breast cancer
Authors: Xiuzhi Zhu, Li Chen, Zhonghua Wang
Journal: Cancer Research (2021)

Abstract Background: PARP inhibitors (PARPi) benefit only a fraction of breast cancer with BRCA mutation, and are even more limited in triple negative breast cancer (TNBC), due to clinical primary and acquired resistance. Here we found that the efficacy of PARPi in TNBC can be expanded with CDK4/6 inhibitors (CDK4/6i). Methods: We screened sensitive and resistant PARPi cell lines from existing TNBC cell lines and cultured PARPi-resistant strains by gradient concentration increase method. The effects of PARP inhibitor Olaparib and CDK4/6 inhibitor Palbociclib on TNBC cells lines were examined in vitro and in vivo. Combination index (CI) was used to evaluate the synergistic effects of drug combination. Results: We screened out the cell line MDA-MB-436, which was the most sensitive to PARPi, and the cell lines HCC1937 and SUM149, which were relatively resistant to PARPi, all of which were BRCA1 mutants. We demonstrated for the first time that the combination of PARPi and CDK4/6i has synergistic effects against some TNBCs both in vitro and in vivo, and was verified by CI&amp;lt;0.9. Further experiments confirmed that PARPi combined with CDK4/6i inhibited cell proliferation and migration, and increased apoptosis and DNA damage. In the PARPi sensitive BRCA-/TNBC cell (MDA-MB-436), the inhibitory effect of monotherapy PARPi was obvious; In the PARPi resistant BRCA-/TNBC cells (HCC1937 and SUM149), CDK4/6i was added to achieve significant growth inhibition. In the timing of medication, PARPi followed by CDK4/6i had better inhibitory effect.Conclusions: In some BRCA-/ TNBCs, PARPi combined with CDK4/6i had a synergistic effect. Even in PARPi-resistant cells, combined treatment could enhance the efficacy and might reverse the drug resistance to some extent. The combination index index of HCC1937 at different drug concentrations (uM)The combination index index of HCC1937 at different drug concentrations (uM)OlaparibPalbociclib25.0016.6711.117.414.943.292.191.460.980.65P-25.000.459110.668320.866540.869640.993450.989890.97841.003221.073741.00809P-20.000.537090.851131.022651.149561.231561.270271.189071.145021.14811.25795P-15.000.594121.018141.134481.056960.928140.955670.889760.842040.81060.81348P-10.000.475540.860580.77190.717480.62330.615880.561390.52960.510250.49752P-5.000.509450.762230.746560.683340.56030.499410.467390.41490.390670.37502P-2.500.573130.706410.714750.661230.519270.455960.350980.29340.319310.2756 Citation Format: Xiuzhi Zhu, Li Chen, Zhonghua Wang. Efficacy of combined CDK4/6 inhibitor and PARP inhibitor in the treatment of BRCA1 mutant triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-39.
Abstract SP020: Beyond Hormones: Newer Pharmacologic Approaches
Authors: P Brown
Journal: Cancer Research (2021)

Abstract It is now possible to prevent many breast cancers inhigh-risk women using anti-estrogen hormonal drugs. Several Phase III breast cancer preventiontrials demonstrated that hormonal drugs such as the “selective estrogenreceptor modulators” tamoxifen and raloxifene, and aromatase inhibitors preventthe development of 50% of ER-positive breast cancers in women. However, mostwomen at high risk of breast cancer do not use these cancer preventive drugsdue to concerns about their side effects. To overcome this problem, recent studies havefocused on testing novel approaches for the prevention of breast cancer. Results of preclinical and clinical studiestesting targeted drugs and vaccines for breast cancer prevention show that itis possible to prevent breast cancer with reduced toxicity. Studies seeking to prevent all forms ofbreast cancer, including ER-positive, HER2-positive, and “triple-negative”breast cancer, will be presented and discussed. Novel approaches testing targeted therapies including signalinginhibitors, combinations of preventive agents, and vaccines, will be presented. Many of these interventions prevent breastcancer in animal models, and are now being tested in human clinicaltrials. Results from studies testing novel drugdelivery approaches will also be discussed. Topical gels containing anti-estrogen drugs are being used to reducebreast cell growth and mammographic density in Phase II clinical trials. This topical approach has the potential toprevent ER-positive breast cancers without the toxicity of oral hormonaldrugs. All of these novel preventive measuresoffer great promise to effectively prevent all forms of breast cancer withminimal toxicity. Citation Format: P Brown. Beyond Hormones: Newer Pharmacologic Approaches [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP020.
Food anaphylaxis in the United Kingdom: analysis of national data, 1998-2018
Authors: Alessia Baseggio Conrado, Despo Ierodiakonou, M Hazel Gowland, Robert J Boyle, Paul J Turner
Journal: BMJ (2021)

Abstract Objective To describe time trends for hospital admissions due to food anaphylaxis in the United Kingdom over the past 20 years. Design Analysis of national data, 1998-2018. Setting Data relating to hospital admissions for anaphylaxis and deaths, and prescription data for adrenaline autoinjector devices. Participants UK population as a whole and devolved nations (England, Scotland, Wales, and Northern Ireland). Main outcome measures Time trends, age, and sex distributions for hospital admissions for anaphylaxis due to food and non-food triggers, and how these admission rates compare with the case fatality rate (number of fatalities as a proportion of hospital admissions). Results Between 1998 and 2018, 101 891 people were admitted to hospital for anaphylaxis. Of these admissions, 30 700 (30.1%) were coded as due to a food trigger. Food anaphylaxis admissions increased from 1.23 to 4.04 per 100 000 population per year (from 1998 to 2018), an annual increase of 5.7% (95% confidence interval 5.5% to 5.9%, P&lt;0.001). The largest increase in hospital admissions was observed in children younger than 15 years, with an increase from 2.1 to 9.2 admissions per 100 000 population per year (an annual increase of 6.6%, 95% confidence interval 6.3% to 7.0%). For comparison, the annual increase was 5.9% (5.6% to 6.2%) in people aged 15-59 years and 2.1% (1.8% to 3.1%) in those aged 60 years and older. 152 deaths were identified where the fatal event was probably caused by food induced anaphylaxis. The case fatality rate decreased from 0.7% to 0.19% for confirmed fatal food anaphylaxis (rate ratio 0.931, 95% confidence interval 0.904 to 0.959, P&lt;0.001) and to 0.30% for suspected fatal food anaphylaxis (0.970, 0.945 to 0.996, P=0.024). At least 46% (86 of 187, which also includes 35 deaths in 1992-98) of deaths were triggered by peanut or tree nut. Cow’s milk was responsible for 17 of 66 (26%) deaths in school aged children. Over the same time period, prescriptions for adrenaline autoinjectors increased by 336% (estimated rate ratio 1.113, 95% confidence interval 1.112 to 1.113; an increase of 11% per year). Conclusions Hospital admissions for food induced anaphylaxis have increased from 1998 to 2018, however the case fatality rate has decreased. In school aged children, cow’s milk is now the most common single cause of fatal anaphylaxis.
Caution Against Overinterpreting Time-Restricted Eating Results
Authors: Grant M. Tinsley, Courtney M. Peterson, Benjamin D. Horne
Journal: JAMA Internal Medicine (2021)

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