bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactive Classification of Whole-Slide Imaging Data for Cancer Researchers
Authors: Lee Sanghoon , Amgad Mohamed , Mobadersany Pooya , McCormick Matt , Pollack Brian P. , Elfandy Habiba , Hussein Hagar , Gutman David A. , Cooper Lee A.D. 
Published: December 2020

Abstract

Whole-slide histology images contain information that is valuable for clinical and basic science investigations of cancer but extracting quantitative measurements from these images is challenging for researchers who are not image analysis specialists. In this article, we describe HistomicsML2, a software tool for learn-by-example training of machine learning classifiers for histologic patterns in whole-slide images. This tool improves training efficiency and classifier performance by guiding users to the most informative training examples for labeling and can be used to develop classifiers for prospective application or as a rapid annotation tool that is adaptable to different cancer types. HistomicsML2 runs as a containerized server application that provides web-based user interfaces for classifier training, validation, exporting inference results, and collaborative review, and that can be deployed on GPU servers or cloud platforms. We demonstrate the utility of this tool by using it to classify tumor-infiltrating lymphocytes in breast carcinoma and cutaneous melanoma.

Significance:
An interactive machine learning tool for analyzing digital pathology images enables cancer researchers to apply this tool to measure histologic patterns for clinical and basic science studies.
Cancer Cell Fitness Is Dynamic
Authors: Lenz Luana S. , Faccioni Juliano L. , Bracco Paula A. , Santos Jephesson A.F. , Pereira Luiza C. , Buss Julieti H. , Tamborindeguy Mauricio T. , Torgo Daphne , Monteiro Thayana , Mantovani Giovana B. , Santo Carolina N. , Marcolin Julia C. , Dalsin Eloisa , Vigo Alvaro , Callegari-Jacques Sidia M. , Silva Andrew O. , Onzi Giovana R. , Begnini Karine R. , Lenz Guido 
Published: December 2020

Abstract

Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions.

Significance:
Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug.
Current Practices for Screening and Addressing Financial Hardship within the NCI Community Oncology Research Program
Authors: McLouth Laurie E. , Nightingale Chandylen L. , Dressler Emily V. , Snavely Anna C. , Hudson Matthew F. , Unger Joseph M. , Kazak Anne E. , Lee Simon J. Craddock , Edward Jean , Carlos Ruth , Kamen Charles S. , Neuman Heather B. , Weaver Kathryn E. 
Published: December 2020

Abstract

Background:
Cancer-related financial hardship is associated with poor care outcomes and reduced quality of life for patients and families. Scalable intervention development to address financial hardship requires knowledge of current screening practices and services within community cancer care.

Methods:
The NCI Community Oncology Research Program (NCORP) 2017 Landscape Assessment survey assessed financial screening and financial navigation practices within U.S. community oncology practices. Logistic models evaluated associations between financial hardship screening and availability of a cancer-specific financial navigator and practice group characteristics (e.g., safety-net designation, critical access hospital, proportion of racial and ethnic minority patients served).

Results:
Of 221 participating NCORP practice groups, 72% reported a financial screening process and 50% had a cancer-specific financial navigator. Practice groups with more than 10% of new patients with cancer enrolled in Medicaid (adjOR = 2.81, P = 0.02) and with less than 30% racial/ethnic minority cancer patient composition (adjOR = 3.91, P &lt; 0.01) were more likely to screen for financial concerns. Practice groups with less than 30% racial/ethnic minority cancer patient composition (adjOR = 2.37, P &lt; 0.01) were more likely to have a dedicated financial navigator or counselor for patients with cancer.

Conclusions:
Most NCORP practice groups screen for financial concerns and half have a cancer-specific financial navigator. Practices serving more racial or ethnic minority patients are less likely to screen and have a designated financial navigator.

Impact:
The effectiveness of financial screening and navigation for mitigating financial hardship could be tested within NCORP, along with specific interventions to address cancer care inequities.
See related commentary by Yabroff et al., p. 593
Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors
Authors: Papadopoulos Kyriakos P. , Autio Karen , Golan Talia , Dobrenkov Konstantin , Chartash Elliot , Chen Qiusheng , Wnek Richard , Long Georgina V. 
Published: December 2020

Abstract

Purpose:
In this first-in-human phase I study (NCT02132754), we explored MK-4166 [humanized IgG1 agonist mAb targeting glucocorticoid-induced TNF receptor (GITR)] with and without pembrolizumab in advanced solid tumors.

Patients and Methods:
MK-4166 was tested alone (0.0015–900 mg i.v. every 3 weeks for four doses) or with pembrolizumab (200 mg i.v. every 3 weeks for ≤35 doses) in patients with metastatic solid tumors (dose escalation/confirmation) and advanced melanoma (expansion). Primary objectives were to evaluate the safety and tolerability and establish the MTD of MK-4166. Exploratory endpoints were objective response rate (ORR) and T cell–inflamed gene expression profile (GEP) analysis using RNA from baseline tumor samples.

Results:
A total of 113 patients were enrolled [monotherapy, n = 48; combination therapy, n = 65 (20 in the expansion)]. Forty-six patients (40.7%) had grade ≥3 adverse events, 9 (8.0%) of which were treatment related. No treatment-related deaths were observed. One dose-limiting toxicity event with monotherapy (bladder perforation in patient with neobladder) was considered related to study drug. MTD was not reached. MK-4166 pharmacodynamics showed decreased GITR availability on circulating T cells with increasing doses. One objective response (ORR, 2.2%) was achieved with combination therapy in the dose escalation/confirmation (n = 45). In the expansion, 8 of 13 patients with immune checkpoint inhibitor (ICI)-naïve melanoma achieved a response (ORR, 62%; 95% confidence interval, 32–86; 5 complete responses and 3 partial responses). None of the ICI-pretreated patients (n = 7) responded. High response rates were observed in ICI-naïve patients irrespective of GEP status.

Conclusions:
MK-4166 900 mg i.v. every 3 weeks as monotherapy and with pembrolizumab was tolerable. Responses were observed with combination therapy, mostly in patients with ICI-naïve melanoma.
177Lu-DOTA-EB-TATE, a Radiolabeled Analogue of Somatostatin Receptor Type 2, for the Imaging and Treatment of Thyroid Cancer
Authors: Thakur Shilpa , Daley Brianna , Millo Corina , Cochran Craig , Jacobson Orit , Lu Huiyan , Wang Zhantong , Kiesewetter Dale , Chen Xiaoyuan , Vasko Vasyl , Klubo-Gwiezdzinska Joanna 
Published: December 2020

Abstract

Purpose:
The goal of this study was to analyze the role of somatostatin receptor type 2 (SSTR2) as a molecular target for the imaging and treatment of thyroid cancer through analysis of SSTR2 expression and its epigenetic modulation and testing tumor uptake of different radiolabeled SSTR2 analogues.

Experimental Design:
We analyzed SSTR2 expression by immunostaining of 92 thyroid cancer tissue samples and quantified standard uptake values (SUVmax) of SSTR2 analogue, 68Ga-DOTA-TATE, by PET/CT imaging in 25 patients with metastatic thyroid cancer. We utilized human thyroid cancer cell lines characterized by differential SSTR2 expression (TT, BCPAP, and FTC133) and rat pancreatic cell line (AR42J) with intrinsically high SSTR2 expression for functional in vitro studies. SSTR2-high (AR42J) and SSTR2-low (FTC133) xenograft mouse models were used to test the uptake of radiolabeled SSTR2 analogues and their therapeutic efficacy in vivo.

Results:
Thyroid cancer had a higher SSTR2 expression than normal thyroid. Hurthle cell thyroid cancer was characterized by the highest 68Ga-DOTA-TATE uptake [median SUVmax, 16.5 (7.9–29)] than other types of thyroid cancers. In vivo studies demonstrated that radiolabeled DOTA-EB-TATE is characterized by significantly higher tumor uptake than DOTA-TATE (P &lt; 0.001) and DOTA-JR11 (P &lt; 0.001). Treatment with 177Lu-DOTA-EB-TATE extended survival and reduced tumor size in a mouse model characterized by high somatostatin (SST) analogues uptake (SUVmax, 15.16 ± 4.34), but had no effects in a model with low SST analogues uptake (SUVmax, 4.8 ± 0.27).

Conclusions:
A novel SST analogue, 177Lu-DOTA-EB-TATE, has the potential to be translated from bench to bedside for the targeted therapy of patients characterized by high uptake of SST analogues in metastatic lesions.
Postoperative Atrial Fibrillation and Long-Term Risk of Stroke in Patients Undergoing Liver Transplantation
Authors: Koshy Anoop N. , Enyati Anees , Weinberg Laurence , Han Hui-Chen , Horrigan Mark , Gow Paul J. , Ko Jefferson , Thijs Vincent , Testro Adam , Lim Han S. , Farouque Omar , Teh Andrew W. 
Published: December 2020

Background and Purpose:
Postoperative atrial fibrillation (POAF) is the commonest cardiovascular complication following liver transplantation (LT). This study sought to assess a possible association of POAF with subsequent thromboembolic events in patients undergoing LT.

Methods:
A retrospective cohort study of consecutive adults undergoing LT between 2010 and 2018 was undertaken. Patients were classified as POAF if atrial fibrillation (AF) was documented within 30 days of LT without a prior history of AF. Cases of ischemic stroke or systemic embolism were adjudicated by a panel of 2 independent physicians.

Results:

Among the 461 patients included, POAF occurred in 47 (10.2%) a median of 3 days following transplantation. Independent predictors of POAF included advancing age, postoperative sepsis and left atrial enlargement. Over a median follow-up of 4.9 (interquartile range, 2.9–7.2) years, 21 cases of stroke and systemic embolism occurred. Rates of thromboembolic events were significantly higher in patients with POAF (17.0% versus 3.1%;
P
<0.001). After adjustment, POAF remained a strong independent predictor of thromboembolic events (hazard ratio, 8.36 [95% CI, 2.34–29.79]). Increasing CHA
2
DS
2
VASc score was also an independent predictor of thromboembolic events (hazard ratio, 1.58 [95% CI, 1.02–2.46]). A model using POAF and a CHA
2
DS
2
VASc score ≥2 alone yielded a C statistic of 0.77, with appropriate calibration for the prediction of thromboembolic events. However, POAF was not an independent predictor of long-term mortality.

Conclusions:

POAF following LT is associated with an 8-fold increased risk of thromboembolic events and the use of the CHA
2
DS
2
VASc score may facilitate risk stratification of these patients. Prospective studies are warranted to assess whether the use of oral anticoagulants can reduce the risk of thromboembolism following LT.
Multiobjective Evolutionary Algorithms Are Still Good: Maximizing
Monotone Approximately Submodular Minus Modular Functions
Authors: Qian Chao 
Published: December 2020

Abstract
As evolutionary algorithms (EAs) are general-purpose optimization algorithms, recent theoretical studies have tried to analyze their performance for solving general problem classes, with the goal of providing a general theoretical explanation of the behavior of EAs. Particularly, a simple multiobjective EA, that is, GSEMO, has been shown to be able to achieve good polynomial-time approximation guarantees for submodular optimization, where the objective function is only required to satisfy some properties and its explicit formulation is not needed. Submodular optimization has wide applications in diverse areas, and previous studies have considered the cases where the objective functions are monotone submodular, monotone non-submodular, or non-monotone submodular. To complement this line of research, this article studies the problem class of maximizing monotone approximately submodular minus modular functions (i.e., g-c) with a size constraint, where g is a so-called non-negative monotone approximately submodular function and c is a so-called non-negative modular function, resulting in the objective function (g-c) being non-monotone non-submodular in general. Different from previous analyses, we prove that by optimizing the original objective function (g-c) and the size simultaneously, the GSEMO fails to achieve a good polynomial-time approximation guarantee. However, we also prove that by optimizing a distorted objective function and the size simultaneously, the GSEMO can still achieve the best-known polynomial-time approximation guarantee. Empirical studies on the applications of Bayesian experimental design and directed vertex cover show the excellent performance of the GSEMO.
Development and validation of an artificial intelligence system for grading colposcopic impressions and guiding biopsies
Authors: Xue Peng , Tang Chao , Li Qing , Li Yuexiang , Shen Yu , Zhao Yuqian , Chen Jiawei , Wu Jianrong , Li Longyu , Wang Wei , Li Yucong , Cui Xiaoli , Zhang Shaokai , Zhang Wenhua , Zhang Xun , Ma Kai , Zheng Yefeng , Qian Tianyi , Ng Man Tat Alexander , Liu Zhihua , Qiao Youlin , Jiang Yu , Zhao Fanghui 
Published: December 2020

AbstractBackgroundColposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies.MethodsAnonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance.ResultsThe agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516,p < 0.001). For detecting pathological high-grade squamous intraepithelial lesion or worse (HSIL+), CAIADS showed higher sensitivity than the use of colposcopies interpreted by colposcopists at either biopsy threshold (low-grade or worse 90.5%, 95% CI 88.9–91.4% versus 83.5%, 81.5–85.3%; high-grade or worse 71.9%, 69.5–74.2% versus 60.4%, 57.9–62.9%; allp < 0.001), whereas the specificities were similar (low-grade or worse 51.8%, 49.8–53.8% versus 52.0%, 50.0–54.1%; high-grade or worse 93.9%, 92.9–94.9% versus 94.9%, 93.9–95.7%; allp > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758.ConclusionsThe CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.
May the analysis of 1918 influenza pandemic give hints to imagine the possible magnitude of Corona Virus Disease-2019 (COVID-19)?
Authors: Scarpa Raffaele , Caso Francesco , Costa Luisa , Passavanti Saverio , Vitale Maria Grazia , Trojaniello Claudia , Del Puente Antonio , Ascierto Paolo A. 
Published: December 2020

Abstract
Background
In 1918 an unknown infectious agent spread around the world infecting over one-third of the general population and killing almost 50 million people. Many countries were at war, the First World War. Since Spain was a neutral country and Spanish press could report about the infection without censorship, this condition is commonly remembered as “Spanish influenza”. This review examines several aspects during the 1918 influenza pandemic to bring out evidences which might be useful to imagine the possible magnitude of the present coronavirus disease 2019 (COVID-19).

Methods
In the first part of this review we will examine the origin of the SARS-Coronavirus-2 and 1918 Spanish Influenza Virus and the role played by host and environment in its diffusion. We will also include in our analysis an evaluation of different approaches utilized to restrain the spread of pandemic and to treat infected patients. In the second part, we will try to imagine the magnitude of the present COVID-19 pandemic and the possible measures able to restrain in the present environment its spread.

Results
Several factors characterize the outcome in a viral pandemic infection. They include the complete knowledge of the virus, the complete knowledge of the host and of the environment where the host lives and the pandemic develops.

Conclusion
By comparing the situation seen in 1918 with the current one, we are now in a more favourable position. The experience of the past teaches us that their success is linked to a rapid, constant and lasting application. Then, rather than coercion, awareness of the need to observe such prevention measures works better.
SPATIAL AND TEMPORAL VARIATIONS OF K Ca II LINE PROFILE SHAPES IN DIFFERENT STRUCTURES OF THE SOLAR CHROMOSPHERE. II. DETERMINATION TECHNIQUE AND CORRELATION RELATIONSHIPS BETWEEN THE K CA II LINE PARAMETERS FOR K1 AND K2 FEATURES
Authors: Turova Irina , Grigoryeva Sofiya , Ozhogina Olga 
Published: December 2020

We have studied two regions located at the base of a coronal hole. For the K₁ intensity minima and K₂ peaks, which form between the upper photosphere and the lower chromosphere and in the lower chromosphere respectively, a number of Ca II line parameters have been computed. We have improved the determination technique for ∆λᴋ₁ᵥ and ∆λᴋ₁ᵣ, ∆λᴋ₂ᵥ and ∆λᴋ₂ᵣ line profile shifts, including certain cases when their direct determination was complicated. We have determined Iᴋ₁ᵥ, Iᴋ₁ᵣ, Iᴋ₂ᵥ, Iᴋ₂ᵣ intensities, K₁ minima and K₂ peaks separations SEPᴋ₁ = ∆λᴋ₁ᵣ – ∆λᴋ₁ᵥ, SEPᴋ₂ = ∆λᴋ₂ᵣ – ∆λᴋ₂ᵥ, respectively. We have constructed scatter plots and have computed correlation relationships between parameters relating to different levels of atmosphere.
We have obtained the following results.
The intensities observed in the lower and middle chromosphere are connected closer than intensities related to the upper photosphere and middle chromosphere.
The structures with a stronger magnetic field are brighter at the upper photosphere and lower chromosphere levels as compared to the structures with a weaker magnetic field.
K₁ minima separations are of greater value for the structures with a stronger magnetic field relative to the structures with a weaker magnetic field, whereas K₂ peaks separations demonstrate the opposite behavior. They are lower for the structures with a stronger magnetic field. It is true not only for the chosen structures belonging to quiet regions but also for the plage, though we need additional statistics for plages.
The relation between shifts of K₁ minima and K₂ peak intensities for violet and red wings appeared to be weak. This may be due to the considerable contribution of random movements to the velocity field at the upper photosphere and lower chromosphere levels or due to different forming levels for the profile violet and red wings.
Spatial and temporal variations of K CA II line profile shapes in different structures of the solar chromosphere. II. Determination technique and correlation relationships between the K CA II line parameters for K₁ and K₂ features
Authors: Turova Irina , Grigoryeva Sofiya , Ozhogina Olga 
Published: December 2020

We have studied two regions located at the base of a coronal hole. For the K₁ intensity minima and K₂ peaks, which form between the upper photosphere and the lower chromosphere and in the lower chromosphere respectively, a number of Ca II line parameters have been computed. We have improved the determination technique for ∆λᴋ₁ᵥ and ∆λᴋ₁ᵣ, ∆λᴋ₂ᵥ and ∆λᴋ₂ᵣ line profile shifts, including certain cases when their direct determination was complicated. We have determined Iᴋ₁ᵥ, Iᴋ₁ᵣ, Iᴋ₂ᵥ, Iᴋ₂ᵣ intensities, K₁ minima and K₂ peaks separations SEPᴋ₁ = ∆λᴋ₁ᵣ – ∆λᴋ₁ᵥ, SEPᴋ₂ = ∆λᴋ₂ᵣ – ∆λᴋ₂ᵥ, respectively. We have constructed scatter plots and have computed correlation relationships between parameters relating to different levels of atmosphere.
We have obtained the following results.
The intensities observed in the lower and middle chromosphere are connected closer than intensities related to the upper photosphere and middle chromosphere.
The structures with a stronger magnetic field are brighter at the upper photosphere and lower chromosphere levels as compared to the structures with a weaker magnetic field.
K₁ minima separations are of greater value for the structures with a stronger magnetic field relative to the structures with a weaker magnetic field, whereas K₂ peaks separations demonstrate the opposite behavior. They are lower for the structures with a stronger magnetic field. It is true not only for the chosen structures belonging to quiet regions but also for the plage, though we need additional statistics for plages.
The relation between shifts of K₁ minima and K₂ peak intensities for violet and red wings appeared to be weak. This may be due to the considerable contribution of random movements to the velocity field at the upper photosphere and lower chromosphere levels or due to different forming levels for the profile violet and red wings.