tbuckley/cabot-search huggingface dataset:
Segmentation of White Blood Cell, Nucleus and Cytoplasm in Digital Haematology Microscope Images: A Review–Challenges, Current and Future Potential Techniques
Authors: Khamael AL-Dulaimi, Jasmine Banks, Kien Nugyen, Aiman Al-Sabaawi, Inmaculada Tomeo-Reyes, Vinod Chandran
Journal: IEEE Reviews in Biomedical Engineering (2020)

Segmentation of white blood cells in digital haematology microscope images represents one of the major tools in the diagnosis and evaluation of blood disorders. Pathological examinations are being the gold standard in many haematology and histophathology, and also play a key role in the diagnosis of diseases. In clinical diagnosis, white blood cells are analysed by pathologists from peripheral blood smears samples of patients. This analysis is mainly based on morphological features and characteristics of the white blood cells and their nuclei and cytoplasm, including, shapes, sizes, colours, textures, maturity stages and staining processes. Recently, Computer Aided Diagnosis techniques have been rapidly growing in the digital haematology area related to white blood cells, and their nuclei and cytoplasm detection, as well as their segmentation and classification techniques. In digital haematology image analysis, these techniques have played and will continue to play, a vital role for providing traceable clinical information, consolidating pertinent second opinions, and minimizing human intervention. This study outlines, discusses, and introduces the major trends from a particular review of detection and segmentation methods for white blood cells and their nuclei and cytoplasm from digital haematology microscope images. Performance of existing methods have been comprehensively compared, taking into account databases used, number of images and limitations. This study can also help us to identify the challenges that remain, in achieving a robust analysis of white blood cell microscope images, which could support the diagnosis of blood disorders and assist researchers and pathologists in the future. The impact of this work is to enhance the accuracy of pathologists' decisions and their efficiency, and overall benefit the patients for faster and more accurate diagnosis. The significant of the paper on intelligent system is that provides future potential techniques for solving overlapping white blood cell identification and other problems microscopic images. The accurate segmentation and detection of white blood cells can increase the accuracy of cell counting system for diagnosing diseases in the future.
Assessing Solid Organ Donors and Monitoring Transplant Recipients for Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Infection — U.S. Public Health Service Guideline, 2020
Authors: Jefferson M. Jones, Ian Kracalik, Marilyn E. Levi, James S. Bowman, James J. Berger, Danae Bixler, Kate Buchacz, Anne Moorman, John T. Brooks, Sridhar V. Basavaraju
Journal: MMWR Recommendations and Reports (2020)

The recommendations in this report supersede the U.S Public Health Service (PHS) guideline recommendations for reducing transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) through organ transplantation (Seem DL, Lee I, Umscheid CA, Kuehnert MJ. PHS guideline for reducing human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission through organ transplantation. Public Health Rep 2013;128:247-343), hereafter referred to as the 2013 PHS guideline. PHS evaluated and revised the 2013 PHS guideline because of several advances in solid organ transplantation, including universal implementation of nucleic acid testing of solid organ donors for HIV, HBV, and HCV; improved understanding of risk factors for undetected organ donor infection with these viruses; and the availability of highly effective treatments for infection with these viruses. PHS solicited feedback from its relevant agencies, subject-matter experts, additional stakeholders, and the public to develop revised guideline recommendations for identification of risk factors for these infections among solid organ donors, implementation of laboratory screening of solid organ donors, and monitoring of solid organ transplant recipients. Recommendations that have changed since the 2013 PHS guideline include updated criteria for identifying donors at risk for undetected donor HIV, HBV, or HCV infection; the removal of any specific term to characterize donors with HIV, HBV, or HCV infection risk factors; universal organ donor HIV, HBV, and HCV nucleic acid testing; and universal posttransplant monitoring of transplant recipients for HIV, HBV, and HCV infections. The recommendations are to be used by organ procurement organization and transplant programs and are intended to apply only to solid organ donors and recipients and not to donors or recipients of other medical products of human origin (e.g., blood products, tissues, corneas, and breast milk). The recommendations pertain to transplantation of solid organs procured from donors without laboratory evidence of HIV, HBV, or HCV infection. Additional considerations when transplanting solid organs procured from donors with laboratory evidence of HCV infection are included but are not required to be incorporated into Organ Procurement and Transplantation Network policy. Transplant centers that transplant organs from HCV-positive donors should develop protocols for obtaining informed consent, testing and treating recipients for HCV, ensuring reimbursement, and reporting new infections to public health authorities.
Determinants of COVID-19 disease severity in patients with cancer
Authors: Elizabeth V. Robilotti, N. Esther Babady, Peter A. Mead, Thierry Rolling, Rocio Perez-Johnston, Marilia Bernardes, Yael Bogler, Mario Caldararo, Cesar J. Figueroa, Michael S. Glickman, Alexa Joanow, Anna Kaltsas, Yeon Joo Lee, Anabella Lucca, Amanda Mariano, Sejal Morjaria, Tamara Nawar, Genovefa A. Papanicolaou, Jacqueline Predmore, Gil Redelman-Sidi, Elizabeth Schmidt, Susan K. Seo, Kent Sepkowitz, Monika K. Shah, Jedd D. Wolchok, Tobias M. Hohl, Ying Taur, Mini Kamboj
Journal: Nature Medicine (2020)

As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts. Analysis of a large, single-center cohort of patients with cancer who were infected with COVID-19 uncovers factors associated with disease severity and interactions with anti-cancer therapies
Polymeric Nanocarriers with Controlled Chain Flexibility Boost mRNA Delivery In Vivo through Enhanced Structural Fastening
Authors: Takuya Miyazaki, Satoshi Uchida, Satoru Nagatoishi, Kyoko Koji, Taehun Hong, Shigeto Fukushima, Kouhei Tsumoto, Kazuhiko Ishihara, Kazunori Kataoka, Horacio Cabral
Journal: Advanced Healthcare Materials (2020)

Abstract Messenger RNA (mRNA) shows high therapeutic potential, though effective delivery systems are still needed for boosting its application. Nanocarriers loading mRNA via polyion complexation with block catiomers into core‐shell micellar structures are promising systems for enhancing mRNA delivery. Engineering the interaction between mRNA and catiomers through polymer design can promote the development of mRNA‐loaded micelles (mRNA/m) with increased delivery efficiency. Particularly, the polycation chain rigidity may critically affect the mRNA‐catiomer interplay to yield potent nanocarriers, yet its effect remains unknown. Herein, the influence of polycation stiffness on the performance of mRNA/m by developing block complementary catiomers having polycation segments with different flexibility, that is, poly(ethylene glycol)‐poly(glycidylbutylamine) (PEG‐PGBA) and PEG‐poly(L‐lysine) (PEG‐PLL) is studied. PEG‐PGBA allows more than 50‐fold stronger binding to mRNA than the relatively more rigid PEG‐PLL, resulting in mRNA/m with enhanced protection against enzymatic attack and polyanions. mRNA/m from PEG‐PGBA significantly enhances mRNA in vivo bioavailability and increased protein translation, indicating the importance of controlling polycation flexibility for forming stable polyion complexes with mRNA toward improved delivery.
Choosing Anticonvulsant Medications to Manage Status Epilepticus
Authors: Ken Wu, Lawrence J. Hirsch, Franz E. Babl, S. Andrew Josephson
Journal: New England Journal of Medicine (2020)

This interactive feature about a woman with idiopathic generalized epilepsy that has progressed to status epilepticus offers a case vignette accompanied by three essays, each of which recommends treatment with a different non-benzodiazepine medication. Vote and comment at NEJM.org.
Increased risk for severe COVID-19 in patients with inflammatory rheumatic diseases treated with rituximab
Authors: Hendrik Schulze-Koops, Klaus Krueger, Inka Vallbracht, Rebecca Hasseli, Alla Skapenko
Journal: Annals of the Rheumatic Diseases (2020)

It is currently unknown whether immunosuppressive and/or immunomodulating agents such as biological disease-modifying antirheumatic drugs (bDMARDs) affect the rate and the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections of patients with inflammatory rheumatic diseases (IRDs). While several national authorities have defined patients under immunosuppressive therapy as at risk for severe COVID-19,1 accumulating data from individual cases and also from case series, such as a series from Italy published in the Annals of the Rheumatic Diseases by Monti et al 2 and a report about patients with immune-mediated inflammatory diseases from New York,3 suggest that baseline use of bDMARDs is not associated with worse COVID-19 outcome. Although the idea of a potentially protective effect of bDMRADs in COVID-19 is intriguing, we feel that extrapolation of these initial data is dangerous and potentially harmful. In particular, some caution may have to be applied when employing rituximab (RTX), a B-cell depleting bDMARD, in patients with immune-mediated disease. This notion may be illustrated by the following observations:

We recently lost two patients with rheumatoid arthritis (RA) treated with RTX to lethal COVID-19. The first patient, a 71-year-old man with rheumatoid factor positive, …
Recurrent invasive meningococcal infections – quantifying the risk, Germany, 2002 to 2018
Authors: Manuel Krone, Thiên-Trí Lâm, Heike Claus, Ulrich Vogel
Journal: Eurosurveillance (2020)

Introduction Invasive meningococcal disease (IMD) is a rare condition with a high case fatality rate. While most patients suffer from one single episode in life, there is anecdotal evidence for recurrent infection. Aim The German National Reference Laboratory for Meningococci and Haemophilus influenzae (NRZMHi) analysed IMD cases from 2002 to 2018 to retrospectively quantify the risk of recurrent infection. Methods Recurrent IMD was defined as detection of Neisseria meningitidis in a sample of the same patient more than 30 days after the first episode of IMD. Results Among 5,854 patients with a median observation period of 9.4 years, 14 suffered a second IMD episode and one patient a third one. The risk of a recurrent IMD was 29.4 per 100,000 person-years for survivors of the first episode. Rare serogroups (Y, W, E and Z) were more common in patients with recurrent IMD (p &lt; 0.0001). Discussion Patients surviving IMD were at least at a 50-fold risk of another IMD episode compared with the general population. The study most likely underestimated the risk of recurrent infection. Increased risk may be due to undiagnosed complement deficiencies. The high risk of re-infection argues for vaccination of patients who have survived IMD.
Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4+ and PDPN+ CAFs to clinical outcome
Authors: Gil Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, Maya Dadiani, Avi Mayo, Coral Halperin, Meirav Pevsner-Fischer, Hagar Lavon, Shimrit Mayer, Reinat Nevo, Yaniv Stein, Nora Balint-Lahat, Iris Barshack, H. Raza Ali, Carlos Caldas, Einav Nili-Gal-Yam, Uri Alon, Ido Amit, Ruth Scherz-Shouval
Journal: Nature Cancer (2020)
SARS-CoV-2 does not replicate in embryonated hen’s eggs or in MDCK cell lines
Authors: Ian G Barr, Cleve Rynehart, Paul Whitney, Julian Druce
Journal: Eurosurveillance (2020)

The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.
HIV Testing Trends at Visits to Physician Offices, Community Health Centers, and Emergency Departments — United States, 2009–2017
Authors: Karen W. Hoover, Ya-Lin A. Huang, Mary L. Tanner, Weiming Zhu, Naomie W. Gathua, Marc A. Pitasi, Elizabeth A. DiNenno, Suma Nair, Kevin P. Delaney
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In 2019, the U.S. Department of Health and Human Services launched the Ending the HIV Epidemic: A Plan for America (EHE) initiative to end the U.S. human immunodeficiency virus (HIV) epidemic by 2030. A critical component of the EHE initiative involves early diagnosis of HIV infection, along with prevention of new transmissions, treatment of infections, and response to HIV outbreaks (1). HIV testing is the first step in identifying persons with HIV infection who need to be engaged in treatment and care as well as persons with a negative HIV test result and who are at high risk for infection and can benefit from HIV preexposure prophylaxis (PrEP) and other prevention services. These opportunities are often missed for persons receiving clinical services in ambulatory care settings (2). Data from the 2009-2016 National Ambulatory Medical Care Survey (NAMCS) and 2009-2017 National Hospital Ambulatory Medical Care Survey (NHAMCS) were analyzed to estimate trends in HIV testing at visits by males and nonpregnant females to physician offices, community health centers (CHCs), and emergency departments (EDs) in the United States. HIV tests were performed at 0.63% of 516 million visits to physician offices, 2.65% of 37 million visits to CHCs, and 0.55% of 87 million visits to EDs. The percentage of visits with an HIV test did not increase at visits to physician offices during 2009-2016, increased at visits to CHC physicians during 2009-2014, and increased slightly at visits to EDs during 2009-2017. All adolescents and adults should have at least one HIV test in their lifetime (3). Strategies that reduce clinical barriers to HIV testing (e.g., clinical decision supports that use information in electronic health records [EHRs] to order an HIV test for persons who require one or standing orders for routine opt-out testing) are needed to increase HIV testing at ambulatory care visits.
Echocardiographic Characterization of Female Professional Basketball Players in the US
Authors: Sofia Shames, Natalie A. Bello, Allan Schwartz, Shunichi Homma, Nidhi Patel, Juan Garza, Jonathan H. Kim, Marci Goolsby, John P. DiFiori, David J. Engel
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> There is a paucity of data detailing cardiac remodeling in female athletes compared with male athletes. The lack of reference cardiac data for elite female basketball players or female athletes of similar size makes it difficult to differentiate athletic remodeling from potential underlying cardiac disorders in this population of athletes. <h3>Objective</h3> To assess cardiac structure and function in elite female basketball players. <h3>Design, Setting, and Participants</h3> This cross-sectional echocardiographic study included 140 Women's National Basketball Association (WNBA) athletes on active rosters for the 2017 season. The WNBA mandates annual preseason stress echocardiograms for each athlete. The WNBA has partnered with Columbia University to annually perform a review of these studies. Data analysis was performed from June 7, 2017, to October 5, 2017. <h3>Main Outcomes and Measures</h3> Echocardiographic variables included left ventricular (LV) dimensions, wall thickness, mass, prevalence of LV hypertrophy, aortic dimensions, right ventricular (RV) dimension, and right and left atrial size. Linear regression was used to assess the associations between cardiac structure and function with body size quantified as body surface area (BSA) in the primary analysis. <h3>Results</h3> A total of 140 female athletes (mean [SD] age, 26.8 [3.9] years; 105 [75.0%] African American) participated in the study. Mean (SD) athlete height was 183.4 (9.0) cm, and mean (SD) BSA was 2.02 (0.18) m<sup>2</sup>. Compared with guideline-defined normal values, LV enlargement was present in 36 athletes (26.0%) and 57 athletes (42.2%) had RV enlargement. There was a linear correlation between LV and RV cavity sizes and BSA extending to the uppermost biometrics (LV cavity size:<i>r</i>, 0.48; RV cavity size:<i>r</i>, 0.32;<i>P</i> &lt; .001 for both). Maximal left ventricular wall thickness (LVWT) ranged from 0.6 to 1.4 cm, with 78 athletes (55.7%) having LVWT of 1.0 cm or greater and only 1 athlete (0.7%) having LVWT greater than 1.3 cm. Twenty-three athletes (16.4%) met the criteria for left ventricular hypertrophy (LVH) (&gt;95 g/m<sup>2</sup>). Eccentric LVH was present in 16 athletes (69.6%), concentric LVH in 7 athletes (30.4%), and concentric remodeling in 27 athletes (19.3%). Mean aortic root diameter was 3.1 cm (95% CI, 3.0-3.2). Only 2 athletes (1.4%) had guideline-defined aortic enlargement compared with a range of 18% to 42% for left and right ventricular and atrial enlargement. <h3>Conclusions and Relevance</h3> In this study, increased cardiac dimensions were frequently observed in WNBA athletes. Both BSA and physiologic remodeling affected cardiac morphologic findings. This study may provide a framework to define the range of athletic cardiac remodeling exhibited by elite female basketball players.
Retracted: M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring αMβ2 Integrin to Tumor Cells
Authors: Jindao Wu, Wen Gao, Qiyun Tang, Yue Yu, Wei You, Zhengshan Wu, Ye Fan, Long Zhang, Chen Wu, Guoyong Han, Xueliang Zuo, Yao Zhang, Zhiqiang Chen, Wenzhou Ding, Xiangcheng Li, Fengming Lin, Hongbing Shen, Jinhai Tang, Yaqin Zhang, Xuehao Wang
Journal: Hepatology (2020)

Background and Aims The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Tumor‐associated macrophages (TAMs) are deemed a key factor for the tumor microenvironment and attribute to contribute to tumor aggressiveness. However, the detailed mechanism underlying the pro‐metastatic effect of TAMs on HCC remains undefined. Approach and Results The present study proved that TAMs were enriched in HCC. TAMs were characterized by an M2‐polarized phenotype and accelerated the migratory potential of HCC cells in vitro and in vivo . Furthermore, we found that M2‐derived exosomes induced TAM‐mediated pro‐migratory activity. With the use of mass spectrometry, we identified that integrin, α M β 2 (CD11b/CD18), was notably specific and efficient in M2 macrophage–derived exosomes (M2 exos). Blocking either CD11b and/or CD18 elicited a significant decrease in M2 exos–mediated HCC cell metastasis. Mechanistically, M2 exos mediated an intercellular transfer of the CD11b/CD18, activating the matrix metalloproteinase‐9 signaling pathway in recipient HCC cells to support tumor migration. Conclusions Collectively, the exosome‐mediated transfer of functional CD11b/CD18 protein from TAMs to tumor cells may have the potency to boost the migratory potential of HCC cells, thus providing insights into the mechanism of tumor metastasis.
FIP200 Suppresses Immune Checkpoint Therapy Responses in Breast Cancers by Limiting AZI2/TBK1/IRF Signaling Independent of Its Canonical Autophagy Function
Authors: Takako Okamoto, Syn Kok Yeo, Mingang Hao, Mary Rose Copley, Michael A. Haas, Song Chen, Jun-Lin Guan
Journal: Cancer Research (2020)

Abstract Immune checkpoint inhibitors (ICI) have the potential to induce durable therapeutic responses, yet response rates in breast cancer are modest and limited to particular subtypes. To expand the applicability of ICI, we examined the role of an essential autophagy gene, FIP200, which has been shown to be important for tumor progression in mammary tumors. Specific disruption of the autophagy function of FIP200 or complete ablation of FIP200 in genetic mouse models revealed that FIP200 autophagy function was required for progression of PyMT-driven mammary tumors. However, a noncanonical autophagy function of FIP200 was responsible for limiting T-cell recruitment and activation of the TBK1-IFN signaling axis. FIP200 also interacted with the TBK1 adaptor protein, AZI2, which was crucial for activation of TBK1 following FIP200 ablation. Accordingly, disrupting the noncanonical autophagy function of FIP200 in combination with ICI therapy led to superior, durable responses in immune-competent models of breast cancer. Collectively, these insights could guide future development of therapeutic agents against FIP200 for combinatorial ICI therapies in nonresponsive breast cancers. Significance: These findings show that deletion of FIP200 enhances immune checkpoint inhibitor efficacy in nonresponsive breast cancer.
Histone deacetylases as targets for the treatment of neurodegenerative disorders: Challenges and future opportunities
Authors: Daniel A. Rodrigues, Pedro de S. M. Pinheiro, Fernanda S. Sagrillo, Maria L. Bolognesi, Carlos A. M. Fraga
Journal: Medicinal Research Reviews (2020)

Abstract Despite the applicability of histone deacetylase inhibitors (HDACis) for cancer treatment, several works in the literature have shown that these inhibitors can be used in several other diseases, such as neurodegenerative diseases (NDs). This review begins by discussing the signaling pathways of HDACs, focused on the context of NDs, presenting a discussion about the pharmacophoric features of HDACis and crystal structure analysis and discussing interesting case studies from the literature about the development of HDACis. Additionally, a discussion about the consequences of isoform‐selective inhibition vs pan ‐HDACis on neurotoxic effects and clinical trial investigations of HDACis for NDs is also presented. Finally, we describe our perspective related to the future use of these inhibitors in the pharmacotherapy of NDs.