tbuckley/cabot-search huggingface dataset:
Abstract PO-010: Feature pyramid network for revealing tumour infiltrating lymphocyte presence and distribution in a whole slide image
Authors: Jonathan Mazurski, Sharon Nofech-Mozes, Dina Bassiouny, Anne L. Martel
Journal: Clinical Cancer Research (2021)

Abstract Ductal Carcinoma in Situ (DCIS) is a subtype of non-invasive breast cancer contained in the ducts of the breast. DCIS is not a life-threatening condition however a small number of cases will progress to or reoccur as invasive breast cancer. Clinical workflows lack a robust biomarker to determine which patients will reoccur. Recently pathologists have turned towards investigating the tumour microenvironment to predict cancer recurrence. Machine learning models present an opportunity to analyze these features on large amounts of data with minimal requirement of pathologist time. One feature of recent interest are Tumour infiltrating lymphocytes or TILs, lymphocytes within a small region around a cancerous duct. Through a method of bootstrapping a U-Net on top of a fully convolutional network we have designed a network that is able to segment lymphocyte and malignant cells in H&amp;E Images of Ductal Carcinoma In Situ. The original network was trained on a private set of cellularity data in breast cancer, manually annotated by pathologists to mark the centre and type of each cell in a patch. Probabilistic output from this model was used to generate segmentation maps on a much larger dataset of DCIS images from the Ontario DCIS Cohort. These segmentation maps were used as training data for a feature pyramid network. The results of this bootstrapping method was a significant increase to speed of the model in addition to much larger flexibility in the input size and shape for the model, which came at a small cost to overall model accuracy. In addition to the original segmentation target, the use of this model to generate lower resolution WSI heat-maps has been investigated for this work. This model can generate low resolution heat-maps for a 20X magnification whole slide image showing the presence of malignant cells in addition to the location and distribution of TILs around ducts. This can provide a visual overview of differences between slides and we will be examining the potential for this output to serve as information for analytical methods to process to predict recurrence free survival. Citation Format: Jonathan Mazurski, Sharon Nofech-Mozes, Dina Bassiouny, Anne L. Martel. Feature pyramid network for revealing tumour infiltrating lymphocyte presence and distribution in a whole slide image [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-010.
ST Segment Elevation in a Patient With Myocardial Metastases
Authors: Jonathan R. Salik, Erika J. Parisi, Rahul Sakhuja
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Alcohol Withdrawal Rates in Hospitalized Patients During the COVID-19 Pandemic
Authors: Ram A. Sharma, Keshab Subedi, Bayo M. Gbadebo, Beverly Wilson, Claudine Jurkovitz, Terry Horton
Journal: JAMA Network Open (2021)

order (Figure).The largest IRR in 2020 vs 2019 (IRR, 1.84; 95% CI, 1.30-2.60)occurred in the last 2 weeks of the stay-at-home order (Table ).AW rates in hospitalized patients increased by 34% in 2020 during the pandemic (March 25 to September 22) compared with the same period in 2019 (IRR, 1.34; 95% CI, 1.22-1.48).
Epigenetic silencing of miR-144/451a cluster contributes to HCC progression via paracrine HGF/MIF-mediated TAM remodeling
Authors: Junlong Zhao, Huichen Li, Shoujie Zhao, Enxin Wang, Jun Zhu, Dayun Feng, Yejing Zhu, Weijia Dou, Qingling Fan, Jie Hu, Lintao Jia, Lei Liu
Journal: Molecular Cancer (2021)

Abstract Background &amp; Aims Hepatocellular carcinoma (HCC) is among the malignancies with the highest mortality. The key regulators and their interactive network in HCC pathogenesis remain unclear. Along with genetic mutations, aberrant epigenetic paradigms, including deregulated microRNAs (miRNAs), exert profound impacts on hepatocyte transformation and tumor microenvironment remodeling; however, the underlying mechanisms are largely uncharacterized. Methods We performed RNA sequencing on HCC specimens and bioinformatic analyses to identify tumor-associated miRNAs. The miRNA functional targets and their effects on tumor-infiltrating immune cells were investigated. The upstream events, particularly the epigenetic mechanisms responsible for miRNA deregulation in HCC, were explored. Results The miR-144/miR-451a cluster was downregulated in HCC and predicted a better HCC patient prognosis. These miRNAs promoted macrophage M1 polarization and antitumor activity by targeting hepatocyte growth factor (HGF) and macrophage migration inhibitory factor (MIF). The miR-144/miR-451a cluster and EZH2, the catalytic subunit of polycomb repressive complex (PRC2), formed a feedback circuit in which miR-144 targeted EZH2 and PRC2 epigenetically repressed the miRNA genes via histone H3K27 methylation of the promoter. The miRNA cluster was coordinately silenced by distal enhancer hypermethylation, disrupting chromatin loop formation and enhancer-promoter interactions. Clinical examinations indicated that methylation of this chromatin region is a potential HCC biomarker. Conclusions Our study revealed novel mechanisms underlying miR-144/miR-451a cluster deregulation and the crosstalk between malignant cells and tumor-associated macrophages (TAMs) in HCC, providing new insights into HCC pathogenesis and diagnostic strategies.
Establishing Equity in Medical Education — Supporting Clinical Trainees with Disabilities
Authors: Suchita Rastogi
Journal: New England Journal of Medicine (2021)

Interview with Dr. Suchita Rastogi on undertaking medical training as a student with a chronic illness. (20:35)Download No road map exists to help medical students with disabilities navigate the wards, and supervisors may challenge students' accommodations or fail to brief their colleagues on students' needs. Systemic change is needed to dismantle these barriers in medical training.
Characteristics of and Mortality Associated With Diabetic Ketoacidosis Among US Patients Hospitalized With or Without COVID-19
Authors: Francisco J. Pasquel, Jordan Messler, Robert Booth, Beata Kubacka, April Mumpower, Guillermo Umpierrez, Joseph Aloi
Journal: JAMA Network Open (2021)

mortality in the COVID-19-positive population is unknown.Contributing factors could include obesity and a more severe stress state (as suggested by higher insulin requirements).These findings are worrisome and warrant further investigation.
Abstract IA-13: Machine learning for improved management of patients with pancreatic cysts
Authors: Rachel Karchin
Journal: Clinical Cancer Research (2021)

Abstract Invasive pancreatic cancer is a deadly disease, with the lowest five year survival rate among all cancers. Cysts in the pancreas are relatively common, but while some have malignant potential, many are entirely benign, while surgical resection of the pancreas has relatively high morbidity and mortality. Clinical management of patients with pancreatic cysts must balance these risks. We developed a supervised machine learning approach to integrate clinical, imaging and molecular data, as part of a large retrospective international study of almost 900 patients with pancreatic cysts. Using the Multivariate Optimization of Combinatorial Alterations (MOCA) algorithm, patients were classified into those who required immediate surgery, those who required routine monitoring, and those who could be discharged without future surveillance, using a stepwise approach. The resulting diagnostic test, called CompCyst, was more accurate than current patient management which relies on imaging and clinical criteria. More than half of the patients sent to surgery were found to have unnecessary resection of their cysts, which could have been avoided by application of the CompCyst test. Our results demonstrate how machine learning and molecular features can be applied to improve pre-surgical diagnostic testing in the clinic. Citation Format: Rachel Karchin. Machine learning for improved management of patients with pancreatic cysts [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-13.
Transitioning from infancy to adulthood: a black box full of opportunities
Authors: Alvar Agusti, Robab Breyer-Kohansal, Rosa Faner
Journal: European Respiratory Journal (2021)

During pregnancy, an obstetrician takes care of both mother's and child's health. After birth, a paediatrician continues to care for the child and, if nothing serious and unexpected happens, most adolescents will be on their own without sanitary control until about their 5th–6th decade of age, where prevalent cardiovascular, respiratory and/or metabolic chronic diseases begin to emerge. This has been described as a "black box" period [1] which, interestingly, may be full of opportunities for prevention, early diagnosis, careful monitoring and, eventually, early intervention. Two recent observations support this possibility. First, between 4 and 12% of young adults (∼25 years of age) in the general population have low lung function and, importantly, they are at a higher risk of respiratory, cardiovascular and metabolic diseases later in life, and die prematurely [2, 3]. A better understanding of the factors that modulate the transition of lung function from infancy to adulthood is key to understanding adult respiratory health <https://bit.ly/3k1mXA0>
Association of Eviction During Pregnancy With Birth Outcomes
Authors: Erika G. Cordova-Ramos, Robert Koenig, Michael Silverstein
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer’s disease: a systematic review and meta-analysis
Authors: Xulong Ding, Shuting Zhang, Lijun Jiang, Lu Wang, Tao Li, Peng Lei
Journal: Translational Neurodegeneration (2021)

Abstract A lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer’s disease (AD). Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral plasma. Here we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181 (ptau181) using four ultrasensitive methods. Meta-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls, and that the plasma tau and ptau181 could predict AD with high-accuracy area under curve of the Receiver Operating Characteristic. Therefore, plasma tau and plasma ptau181 can be considered as biomarkers for AD diagnosis.
Perspectives on palliative oxygen for breathlessness: systematic review and meta-synthesis
Authors: Slavica Kochovska, Diana H. Ferreira, Maja V. Garcia, Jane L. Phillips, David C. Currow
Journal: European Respiratory Journal (2021)

Oxygen therapy is frequently prescribed for the palliation of breathlessness, despite lack of evidence for its effectiveness in people who are not hypoxaemic. This study aimed to compare and contrast patients’, caregivers’ and clinicians’ experiences of palliative oxygen use for the relief of chronic breathlessness in people with advanced life-limiting illnesses, and how this shapes prescribing. A systematic review and meta-synthesis of qualitative data was conducted. MEDLINE, CINAHL and PsycINFO were searched for peer-reviewed studies in English (2000–April 2019) reporting perspectives on palliative oxygen use for reducing breathlessness in people with advanced illnesses in any healthcare setting. After data extraction, thematic synthesis used line-by-line coding of raw data (quotes) to generate descriptive and analytical themes. Of 457 articles identified, 22 met the inclusion criteria by reporting perspectives of patients (n=337), caregivers (n=91) or clinicians (n=616). Themes common to these perspectives were: 1) benefits and burdens of palliative oxygen use, 2) knowledge and perceptions of palliative oxygen use beyond the guidelines, and 3) longitudinal trajectories of palliative oxygen use. There are differing perceptions regarding the benefits and burdens of using palliative oxygen. Clinicians should be aware that oxygen use may generate differing goals of therapy for patients and caregivers. These perceptions should be taken into consideration when prescribing oxygen for the symptomatic relief of chronic breathlessness in patients who do not quality for long-term oxygen therapy.
Heterogeneity in Nectin-4 expression across molecular subtypes of urothelial cancer mediates sensitivity to enfortumab vedotin.
Authors: Carissa Chu, Martin Sjöström, Emily A Egusa, Ewan Gibb, Michelle L Badura, Vadim S Koshkin, Bradley A. Stohr, Maxwell Meng, Raj Pruthi, Terence W. Friedlander, Yair Lotan, Peter C. Black, Sima P. Porten, Felix Y Feng, Jonathan Chou
Journal: Journal of Clinical Oncology (2021)

463 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) targeting Nectin-4 (encoded by the PVRL4/NECTIN4 gene ) approved for treatment-refractory metastatic urothelial cancer. Factors that mediate sensitivity or resistance to EV are unknown. In the present study, we sought to 1) examine heterogeneity of NECTIN4 gene expression across molecular subtypes of bladder cancer and 2) determine if Nectin-4 expression mediates EV sensitivity or resistance. Methods: NECTIN4 expression data from seven muscle-invasive bladder cancer clinical cohorts (n = 1912 total patients) were used to compare relative NECTIN4 expression across molecular subtypes. The outcome of the gene expression analysis was relative NECTIN4 expression in the consensus molecular subtypes of bladder cancer. Expression of NECTIN4 was validated in multiple bladder cancer cell lines. NECTIN4 was stably over-expressed or knocked down in basal (TCCSUP and UMUC-3) and luminal (HT-1376, HT-1197 and UMUC-9) bladder cancer cell lines, respectively, and EV dose-response assays were performed, as measured by cell proliferation and clonogenic assays. Results: NECTIN4 expression is heterogenous across molecular subtypes of bladder cancer and significantly enriched in luminal subtypes (p &lt; 0.001). NECTIN4 expression is positively correlated with the luminal markers GATA3, FOXA1, and PPARG across cohorts (Spearman’s rank correlation r = 0.57, p &lt; 0.0001 for GATA3, r = 0.37, p &lt; 0.0001 for FOXA1, and r = 0.56, p &lt; 0.0001 for PPARG). NECTIN4 expression is both necessary and sufficient for EV sensitivity in luminal and basal subtypes of urothelial bladder cancer cells. Downregulation of NECTIN4 led to EV resistance, and EV-resistant cell lines expressed decreased levels of Nectin-4. Conclusions: Results of this pre-clinical study suggest that sensitivity to EV is mediated by expression of NECTIN4, which is significantly enriched in luminal subtypes of bladder cancer. Downregulation of NECTIN4 leads to resistance to EV. These findings have implications for biomarker development, patient selection and the inclusion of molecular subtyping in ongoing and future EV clinical trials. Further investigation into Nectin-4 loss as a mechanism of resistance in patients treated on EV is warranted.
Matrix Metalloproteinase‐9‐Responsive Surface Charge‐Reversible Nanocarrier to Enhance Endocytosis as Efficient Targeted Delivery System for Cancer Diagnosis and Therapy
Authors: Qiu‐Ju Han, Xiao‐Tong Lan, Ying Wen, Chuan‐Zeng Zhang, Michael Cleary, Yasra Sayyed, Guangdong Huang, Xiaoling Tuo, Long Yi, Zhen Xi, Lu‐Yuan Li, Qiang‐Zhe Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract Nanoparticles, that can be enriched in the tumor microenvironment and deliver the payloads into cancer cells, are desirable carriers for theranostic agents in cancer diagnosis and treatment. However, efficient targeted delivery and enhanced endocytosis for probes and drugs in theranostics are still major challenges. Here, a nanoparticle, which is capable of charge reversal from negative to positive in response to matrix metalloproteinase 9 (MMP9) in tumor microenvironment is reported. This nanoparticle is based on a novel charge reversible amphiphilic molecule consisting of hydrophobic oleic acid, MMP9‐cleavable peptide, and glutamate‐rich segment (named as OMPE). The OMPE‐modified cationic liposome forms an intelligent anionic nanohybrid (O‐NP) with enhanced endocytosis through surface charge reversal in response to MMP9 in vitro. Successfully, O‐NP nanohybrid performs preferential accumulation and enhances the endocytosis in MMP9‐expressing xenografted tumors in mouse models, which improve the sensitivity of diagnosis agents and the antitumor effects of drugs in vivo by overcoming their low solubility and/or nonspecific enrichment. These results indicate that O‐NP can be a promising delivery platform for cancer diagnosis and therapy.
Decreased monocyte calcium sensing receptor expression in patients with chronic kidney disease is associated with impaired monocyte ability to reduce vascular calcification
Authors: Aurélien Mary, Thibaut Objois, Michel Brazier, Youssef Bennis, Cédric Boudot, Gaëlle Lenglet, Julien Paccou, Jean-Marc Bugnicourt, Gabriel Choukroun, Tilman B. Drueke, Ziad A. Massy, Saïd Kamel, Isabelle Six, Romuald Mentaverri
Journal: Kidney International (2021)

In chronic kidney disease (CKD), calcium-sensing receptor (CaSR) expression and function have been extensively studied in parathyroid tissue and vascular tissues. To examine whether similar changes occurred in other tissues, we measured total and surface CaSR expression in monocytes of patients with various stages of CKD and healthy volunteers respectively in cross-sectional studies. We further explored in vitro the impact of uremic serum on CaSR expression in monocytes (U937 and THP-1 cell lines), and whether human peripheral blood mononuclear cells or U937 and THP-1 monocytes might modify vascular calcium deposition in rat carotid arteries in vitro. CKD was associated with a decrease in peripheral blood mononuclear cell CaSR expression both in total and at the monocyte surface alone (43% and 34%, respectively in CKD stages 4-5). This decrease was associated with a reduction in the ability of monocytes to inhibit vascular calcification in vitro. Pretreatment with the calcimimetic NPSR568 of peripheral blood mononuclear cells isolated from patients with CKD significantly improved monocyte capacity to reduce carotid calcification in vitro. The fewer peripheral blood mononuclear cells expressing cell surface CaSR, the more calcimimetic treatment enhanced the decrease of carotid calcium content. Thus, we demonstrate that monocyte CaSR expression is decreased in patients with CKD and provide in vitro evidence for a potential role of this decrease in the promotion of vascular calcification. Hence, targeting this alteration or following monocyte CaSR expression as an accessible marker might represent a promising therapeutic strategy in CKD-associated arterial calcification.
Impacts of ABO-incompatible platelet transfusions on platelet recovery and outcomes after intracerebral hemorrhage
Authors: Jessica Magid-Bernstein, Charles B. Beaman, Fernanda Carvalho-Poyraz, Amelia Boehme, Eldad A. Hod, Richard O. Francis, Mitchell S. V. Elkind, Sachin Agarwal, Soojin Park, Jan Claassen, E. Sander Connolly, David Roh
Journal: Blood (2021)
Marginally reduced maternal hepatic and splenic ferroportin under severe nutritional iron deficiency in pregnancy maintains systemic iron supply
Authors: Rafał Mazgaj, Paweł Lipiński, Eunice Sindhuvi Edison, Aleksandra Bednarz, Robert Staroń, Olga Haberkiewicz, Małgorzata Lenartowicz, Ewa Smuda, Aneta Jończy, Rafał R. Starzyński
Journal: American Journal of Hematology (2021)

The demand for iron is high in pregnancy to meet the increased requirements for erythropoiesis. Even pregnant females with initially iron-replete stores develop iron-deficiency anemia, due to inadequate iron absorption. In anemic females, the maternal iron supply is dedicated to maintaining iron metabolism in the fetus and placenta. Here, using a mouse model of iron deficiency in pregnancy, we show that iron recycled from senescent erythrocytes becomes a predominant source of this microelement that can be transferred to the placenta in females with depleted iron stores. Ferroportin is a key protein in the molecular machinery of cellular iron egress. We demonstrate that under iron deficiency in pregnancy, levels of ferroportin are greatly reduced in the duodenum, placenta and fetal liver, but not in maternal liver macrophages and in the spleen. Although low expression of both maternal and fetal hepcidin predicted ferroportin up-regulation in examined locations, its final expression level was very likely correlated with tissue iron status. Our results argue that iron released into the circulation of anemic females is taken up by the placenta, as evidenced by high expression of iron importers on syncytiotrophoblasts. Then, a substantial decrease in levels of ferroportin on the basolateral side of syncytiotrophoblasts, may be responsible for the reduced transfer of iron to the fetus. As attested by the lowest decrease in iron content among analyzed tissues, some part is retained in the placenta. These findings confirm the key role played by ferroportin in tuning iron turnover in iron-deficient pregnant mouse females and their fetuses.