tbuckley/cabot-search huggingface dataset:
Abstract PO-018: Computational staining of tumor hypoxia from H&amp;E images using convolutional neural networks
Authors: Mark Zaidi, Haotian Cui, Bo Wang, Trevor D. McKee, Bradly G. Wouters
Journal: Clinical Cancer Research (2021)

Abstract Heterogeneity in the tumor environment can be driven by multiple biochemical processes, such as immune infiltration, cell-to-cell genetic variation, and oxygenation gradients. Low oxygen, termed hypoxia, has been strongly correlated with metastasis, radiation resistance, and poor prognosis. One ongoing challenge is determining the magnitude of how hypoxia influences treatment response relative to other features, such as proliferation and micro vessel density. While it is possible to stain banked tissue for these markers, it is challenging to stain for endogenous markers of hypoxia. Exogenous probes have been developed to overcome this barrier; however, most clinical samples lack such probes. Previously, we have shown that spatial distributions of hypoxia correlate with morphological features of the tumor, such as necrosis and vasculature. Some of these features can be identified in hematoxylin and eosin (H&amp;E)-stained sections, present for nearly all tumor samples. We hypothesize that a trained machine learning algorithm can be used to accurately predict hypoxia distributions given an H&amp;E-stained section. Colorectal, pancreatic, and ovarian cancer cell line xenografts were cut and stained for markers of hypoxia, proliferation, perfusion, vasculature, and H&amp;E. Binary masks of necrosis were generated, and together with the H&amp;E and hypoxia images, were used to train a convolutional neural network. Once the model had been trained, a fairly precise prediction (MSE &amp;lt;0.012) had been obtained relative to the ground-truth hypoxia stained images. We believe a model trained on clinical H&amp;E and hypoxia sections can be used to accurately predict hypoxia distributions from a H&amp;E section. Predicted hypoxia distributions from existing H&amp;E histology can be used to evaluate the influence of hypoxia on treatment outcome, by retroactively comparing a patient’s prognosis with levels of hypoxia. Correlations between hypoxia and prognostic measures such as tumor volume after irradiation, would indicate hypoxia may have modulated the efficacy of the treatment. Thus, computational stain prediction of hypoxia can serve as an invaluable tool in closing the gap between preclinical and clinical implementations of hypoxia-targeted therapies. Citation Format: Mark Zaidi, Haotian Cui, Bo Wang, Trevor D. McKee, Bradly G. Wouters. Computational staining of tumor hypoxia from H&amp;E images using convolutional neural networks [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-018.
Abstract PO-069: A deep learning model assists urine cytology reporting with computational estimates of the nuclear/cytoplasmic ratios of the urothelial cells based on the Paris System
Authors: Wei-Lei Yang, Chi-Bin Li, Yen-Chuan Ou, Yi-Sheng Lin, Tang-Yi Tsao, Ming-Chen Chang, Jen-Fan Hang, Tien-Jen Liu
Journal: Clinical Cancer Research (2021)

Abstract The Paris System (TPS) for Reporting Urinary Cytology is an international system with standardized terminology and cytomorphologic criteria that aims for better risk stratification to identify high-grade urothelial carcinoma in urinary cytology specimens. Based on TPS, the nuclear/cytoplasmic ratio (N/C ratio) of the observed urothelial cells is a crucial criterion and the cutoff values of 0.5 and 0.7 are used for the diagnosis of Atypical Urothelial Cells (AUC) and High-Grade Urothelial Carcinoma (HGUC)/Suspicious for HGUC respectively. Although the N/C ratio is a clear and measurable criterion, there are still challenges for adopting TPS into clinical practice. As urine cytology mainly relies on manual microscopic examination by cytopathologists and cytotechnologists, determining the N/C ratio through the naked eyes results in intra- and inter-observer variations and therefore generates subjective, inconsistent, and unreproducible reports. To overcome the aforementioned issues, the authors developed a deep learning-based image analysis model to assist calculating the N/C ratio and classifying urothelial cells computationally. Deidentified urine cytology slides were digitalized as whole-slide images (WSIs) for analyzing. An “active learning” method was used to improve results over time with only a small amount of upfront training data required. First, a small amount of annotated WSIs were provided to train the initial computational model. Next, the experts reviewed the results predicted by the initial model, and provide feedback for the model to learn and improve. The above steps were repeated by experts reviewing the “improved model” and providing feedbacks, thus improving the initial/intermediate models continuously until a satisfactory result was achieved. Preliminary results showed that our model was able to determine the areas of cytoplasm and nucleus in urothelial cells as well as calculate the N/C ratios using the WSI. Moreover, it enumerates the AUC and HGUC cells on the WSI and provides quantification and distribution information on the whole slide scale. This computational model provides a significant advantage as an objective tool to assist urine cytology analysis of the N/C ratio with greater accuracy and reproducibility. Citation Format: Wei-Lei Yang, Chi-Bin Li, Yen-Chuan Ou, Yi-Sheng Lin, Tang-Yi Tsao, Ming-Chen Chang, Jen-Fan Hang, Tien-Jen Liu. A deep learning model assists urine cytology reporting with computational estimates of the nuclear/cytoplasmic ratios of the urothelial cells based on the Paris System [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-069.
Cellhesion VP enhances the immunomodulating potential of human mesenchymal stem cell-derived extracellular vesicles
Authors: Eun Seo Kim, Katsuhiko Kida, Jongsoo Mok, Yeonwoo Seong, Seo Yeon Jo, Tatsuro Kanaki, Masato Horikawa, Kyung-Hee Kim, Tae Min Kim, Tae Sub Park, Joonghoon Park
Journal: Biomaterials (2021)

Mesenchymal stem cell (MSC) transplantation is a promising therapy for regenerative medicine. However, MSCs grown under two-dimensional (2D) culture conditions differ significantly in cell shape from those in the body, with downregulated stemness genes and secretion of paracrine factors. Here, we evaluated the effect of 3D culture using Cellhesion VP, a water-insoluble material composed of chitin-based polysaccharide fibers, on the characteristics of human Wharton's jelly-derived MSCs (hMSCs). Cellhesion VP significantly increased cell proliferation after retrieval. Transcriptome analyses suggested that genes involved in cell stemness, migration ability, and extracellular vesicle (EV) production were enhanced by 3D culture. Subsequent biochemical analyses showed that the expression levels of stemness genes including OCT4, NANOG, and SSEA4 were upregulated and migration capacity was elevated in 3D-cultured hMSCs. In addition, EV production was significantly elevated in 3D cells, which contained a distinct protein profile from 2D cells. Gene and drug connectivity analyses revealed that the 2D and 3D EVs had similar functions as immunomodulators; however, 3D EVs had completely distinct therapeutic profiles for various infectious and metabolic diseases based on activation of disease-associated signaling pathways. Therefore, EVs from Cellhesion VP-primed hMSCs offer a new treatment for immune and metabolic diseases.
Covid-19: Germany struggles with slow uptake of Oxford AstraZeneca vaccine
Authors: Hristio Boytchev
Journal: BMJ (2021)

Covid-19: Germany struggles with slow uptake of Oxford AstraZeneca vaccine Hristio BoytchevGermany is experiencing a slow uptake of the Oxford AstraZeneca covid-19 vaccine, latest figures show.Data up to 1 March show that of the 1 452 000 doses delivered to the country, a little over a third, (514 426) had been used.
Fetomaternal immune cross talk modifies T-cell priming through sustained changes to DC function
Authors: Matthew Lacorcia, Sonakshi Bhattacharjee, Kristina Laubhahn, Fahd Alhamdan, Marija Ram, Andreas Muschaweckh, Daniel P. Potaczek, Anna Kosinska, Holger Garn, Ulrike Protzer, Harald Renz, Clarissa Prazeres da Costa
Journal: Journal of Allergy and Clinical Immunology (2021)
Gender-affirmation surgery and bariatric surgery in transgender individuals in The Netherlands: Considerations, surgical techniques and outcomes
Authors: Wouter B. van der Sluis, Rick J. M. de Bruin, Thomas D. Steensma, Mark-Bram Bouman
Journal: International Journal of Transgender Health (2021)

The number of transgender individuals seeking medical and surgical care has increased over the last years. Within the transgender population overweight and obesity is more frequently observed when compared to the general population. Little is known on the prevalence of bariatric surgery in the transgender population and the effects on the surgical gender transition path of the individual transgender with overweight or obesity.
Understanding childbirth preferences of women in Benin City, Nigeria: a qualitative study
Authors: Debra Eluobaju, Friday Okonofua, Stevan Weine, Gelila Goba
Journal: The Lancet Global Health (2021)

BackgroundNigeria has the fourth highest maternal mortality rate globally. Use of skilled birth attendants (SBA), doctors, nurses or midwifes at the time of delivery can saves women's lives. In 2018, the World Bank reported only 43% of Nigerian women had an SBA during childbirth despite 64% of women seeing an SBA for prenatal care. The purpose of the study was to gain a holistic understanding of women's preferences surrounding childbirth.MethodsParticipants were recruited from clinics and churches by community health workers via purposive selection. In-depth interviews and focus groups were conducted with women, husbands, traditional birth attendants (TBA), and SBAs. Study participants were asked about their childbirth experiences and socio-cultural factors that influence women's birth preferences. A Grounded Theory approach and Atlas/ti were used to analyse the qualitative data.FindingsBetween July 8, 2019, and Aug 10, 2019, we collected data from 23 interviews and six focus groups. In deciding whether to use an SBA or TBA, women in Nigeria reported considering several factors: having a healthy baby, receiving emotional support, decision making autonomy, clinic costs, the avoidance of medical intervention, modesty and cultural needs such as labour massages and herbal medicines.InterpretationWomen want a birth experience that results in a healthy baby, that is free of verbal and physical abuse, and incorporates cultural practices. Adopting a woman-centred care approach that takes into account women's preferences could allow for a better transition from prenatal care to childbirth with an SBA. At the system level, efforts should be made to investigate how cultural practices and TBAs can be integrated into local health-care systems. Nigeria's move to adopt more Western-based medical practices, may have been at the expense of women's needs in the form of cultural practices. Health-care systems must find a balance between medical innovation and cultural competence. Such a balance would allow women the option to deliver babies safely within a clinic setting while doing so in a manner that is dignified and within their cultural scope.FundingNone.
Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Authors: Al B. Benson, Alan P. Venook, Mahmoud M. Al-Hawary, Mustafa A. Arain, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Linda Farkas, Ignacio Garrido-Laguna, Jean L. Grem, Andrew Gunn, J. Randolph Hecht, Sarah Hoffe, Joleen Hubbard, Steven Hunt, Kimberly L. Johung, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Kristina M. Gregory, Lisa A. Gurski
Journal: Journal of the National Comprehensive Cancer Network (2021)

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation–positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org . Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.
Abstract 12774: Markedly Decreased Myocardial Washout Rate of 123i-BMIPP is a Crucial Index in Diagnosing Triglyceride Deposit Cardiomyovasculopathy
Authors: Masahiro Satoh, Hideyuki Miyauchi, Naoto Mori, Takashi Iimori, Koichi Sawada, Yoichi Kuwabara, Kenichi Hirano, Yoshio Kobayashi
Journal: Circulation (2018)

Introduction: Triglyceride deposit cardiomyovasculopathy (TGCV) is a novel clinical entity that was discovered in Japanese patients waiting for heart transplant. TGCV is characterized by the accumu...
Impact of equal access healthcare on race disparities in bladder cancer.
Authors: Nikhil V. Kotha, Abhishek Kumar, Edmund M. Qiao, Daniel R. Cherry, Vinit Nalawade, A. Karim Kader, Rana R. McKay, Tyler Francis Stewart, Brent S. Rose
Journal: Journal of Clinical Oncology (2021)

399 Background: Outcomes in bladder cancer are disproportionately worse for black patients compared to white patients. We hypothesize these disparities arise in part due to differences in access to healthcare and therefore may be mitigated in an equal access healthcare system, such as the Veterans Affairs’ (VA) system. Here, we examine outcomes by race for patients with bladder cancer within the VA system and then compare these outcomes to those in the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We performed a retrospective cohort study using VA Informatics and Computing Infrastructure (VINCI) and SEER. We included all patients diagnosed with bladder cancer, American Joint Committee on Cancer (AJCC) stage 0-4 diagnosed between 2000 and 2018. Endpoints of overall survival (OS), bladder cancer-specific survival (BCS), and non-bladder cancer-specific survival (NCS) were evaluated in multivariable Cox and Fine-Gray models. Results: Using the VA dataset, we identified 36322 veterans (9.0% black, 91.0% white) with bladder cancer. Black veterans were more likely to have more comorbidities, reside in zip codes with lower median income and education levels, and present with higher stage disease (AJCC stages 2-4) than white veterans (23.3% vs 19%). In multivariable models accounting for disease stage among other covariables, there were no statistically significant differences in any survival endpoint (Table). Using the SEER dataset, we identified 130998 patients (5.9% black, 94.1% white) with bladder cancer. In similar multivariable models, SEER’s black patients had statistically significant inferior outcomes in all survival endpoints compared to SEER’s white patients (Table). Conclusions: While racial disparities for patients with bladder cancer in the SEER database were observed, no differences in survival outcomes between black and white patients were observed in the VA healthcare system. Of note, black veterans presented with more advanced stage, suggesting a delay in diagnosis or a more aggressive cancer phenotype compared to white patients. Our findings underscore the need to bridge healthcare disparities across diverse racial groups. Our study highlights the beneficial impact of an equal access healthcare system in reducing financial and social barriers to healthcare to counteract racial health disparities. Further research is required to delineate these disparities and guide appropriate screening strategies. [Table: see text]
A 5 year old girl with fever and rash
Authors: Sung-Tse Li, Fu-Yuan Huang, Chien-Yu Lin
Journal: BMJ (2021)

A 5 year old girl presented to her doctor in northern Taiwan with pyrexia for five days and a two day history of rash over her face, trunk, and limbs. Twelve days earlier she had returned from Indonesia, where she had spent time with her cousin who had similar symptoms.

Examination showed conjunctivitis, coryza, and widespread erythematous maculopapular exanthema on the face (fig 1), chest, abdomen, and limbs. Lesions resembling salt sprinkles were also present bilaterally on the buccal mucosa.



Fig 1 
Bluish-white lesions on the buccal mucosa (black arrows), and diffuse red maculopapular lesions on the face (arrowheads)



The patient’s vaccinations were up to date according to the vaccination schedule in Taiwan, meaning that she had received one dose of the measles vaccine …
Abstract PO026: Loss of STAT5 in macrophages potentiates tissue remodeling and tumor-promoting phenotype in breast cancer
Authors: Emily A. Jesser, Kathryn L. Schwertfeger
Journal: Cancer Research (2021)

Abstract Despite advances in treating breast cancer, limited targeted therapeutics exist for the triple negative breast cancer (TNBC) subtype, therefore it remains the most fatal relative to other breast cancer subtypes. Since TNBC tumor cells utilize the Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway for growth and proliferation signals, new therapeutics are being developed to target components of this pathway like STAT5. However, this pathway is also important for infiltrating inflammatory cells such as, macrophages, and their function in the tumor microenvironment. My data indicates that STAT5 is critical for tissue remodeling phenotypes and cell survival in macrophages, which can have a significant impact on tumor progression. I have observed increases in macrophage production of extracellular matrix components when STAT5 signaling is impaired, as well as a localization of STAT5-active macrophages at the tumor border suggesting a role in metastatic restraint. I have also shown that loss of STAT5 in tumor-associated macrophages correlates to an increase in tumor metastases in vivo. The goal of my research is to define the specific functional contributions of STAT5 to macrophage polarization and macrophage-mediated resistance of tumors to JAK/STAT inhibition. To address these questions, my research employs the use of mouse mammary tumor models, clinically-relevant JAK/STAT inhibition and conditional knockout strategies to understand how macrophages can shift from tumor-hostile to tumor-friendly, as well as, provide rationale for potential therapeutic interventions to maintain an anti-tumor response against TNBC. Citation Format: Emily A. Jesser, Kathryn L. Schwertfeger. Loss of STAT5 in macrophages potentiates tissue remodeling and tumor-promoting phenotype in breast cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO026.
The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin
Authors: Baode Shen, Chengying Shen, Weifeng Zhu, Hailong Yuan
Journal: Acta Pharmaceutica Sinica B (2021)

In this study, self-discriminating hybrid nanocrystals was utilized to explore the biological fate of quercetin hybrid nanocrystals (QT-HNCs) with diameter around 280 nm (QT-HNCs-280) and 550 nm (QT-HNCs-550) following oral and intravenous administration and the contribution of integral nanocrystals to oral bioavailability enhancement of QT was estimated by comparing the absolute exposure of integral QT-HNCs and total QT in the liver. Results showed that QT-HNCs could reside in vivo as intact nanocrystals for as long as 48 h following oral and intravenous administration. A higher accumulation of integral QT-HNCs in liver and lung was observed for both oral and intravenous administration of QT-HNCs. The particle size affects the absorption and biodistribution of integral QT-HNCs and total QT. As compared to QT-HNCs-550, QT-HNCs-280 with smaller particle size is more easily absorbed, but dissolves faster in vivo, leading to higher distribution of QT (146.90 vs. 117.91 h·μg/mL) but lower accumulation of integral nanocrystals (6.8 2e10 vs. 15.27e10 h·[p/s]/[µW/cm²]) in liver following oral administration. Due to its slower dissolution and enhanced recognition by RES, QT-HNCs-550 with larger diameter shows higher liver distribution for both of QT (1015.80 h·μg/mL) and integral nanocrystals (259.63e10 h·[p/s]/[µW/cm²]) than those of QT-HNCs-280 (673.82 & 77.66e10 h·[p/s]/[µW/cm²]) following intravenous administration. The absolute exposure of integral QT-HNCs in liver following oral administration of QT-HNCs are 8.78% for QT-HNCs-280 and 5.88% for QT-HNCs-550, while the absolute exposure of total QT for QT-HNCs-280 and QT-HNCs-550 are 21.80% and 11.61%, respectively. Owing to imprecise quantification method, a surprisingly high contribution of integral QT-HNCs to oral bioavailability enhancement of QT (40.27% for QT-HNCs-280 and 50.65% for QT-HNCs-550) was obtained. These results revealed significant difference in absorption and biodistrbution between integral nanocrystals and overall drugs following oral and intravenous administration of QT-HNCs, and provided a meaningful reference for the contribution of integral nanocrystals to overall bioavailability enhancement.
Polymicrobial communities in periodontal disease: Their quasi‐organismal nature and dialogue with the host
Authors: George Hajishengallis, Richard J. Lamont
Journal: Periodontology 2000 (2021)

Abstract In health, indigenous polymicrobial communities at mucosal surfaces maintain an ecological balance via both inter‐microbial and host‐microbial interactions that promote their own and the host's fitness, while preventing invasion by exogenous pathogens. However, genetic and acquired destabilizing factors (including immune deficiencies, immunoregulatory defects, smoking, diet, obesity, diabetes and other systemic diseases, and aging) may disrupt this homeostatic balance, leading to selective outgrowth of species with the potential for destructive inflammation. This process, known as dysbiosis, underlies the development of periodontitis in susceptible hosts. The pathogenic process is not linear but involves a positive‐feedback loop between dysbiosis and the host inflammatory response. The dysbiotic community is essentially a quasi‐organismal entity, where constituent organisms communicate via sophisticated physical and chemical signals and display functional specialization (eg, accessory pathogens, keystone pathogens, pathobionts), which enables polymicrobial synergy and dictates the community's pathogenic potential or nososymbiocity. In this review, we discuss early and recent studies in support of the polymicrobial synergy and dysbiosis model of periodontal disease pathogenesis. According to this concept, disease is not caused by individual “causative pathogens” but rather by reciprocally reinforced interactions between physically and metabolically integrated polymicrobial communities and a dysregulated host inflammatory response.