tbuckley/cabot-search huggingface dataset:
An Evaluation of the Performance of Current Morphea Subtype Classifications
Authors: Smriti Prasad, Jane L. Zhu, Kaila Schollaert-Fitch, Kathryn S. Torok, Heidi T. Jacobe
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Numerous classification systems for morphea subtypes exist, but none have been systematically evaluated for their ability to categorize patients with morphea into demographically and clinically coherent groups. Although some subtypes, such as linear morphea, are present across all the classification schemes, others list unique subtypes. This creates confusion among investigators and practitioners and impairs accurate categorization of patients for study and clinical evaluation. <h3>Objective</h3> To evaluate how frequently the commonly used morphea classification systems categorize patients with morphea into clinically relevant subtypes using cross-sectional analysis of 2 large patient cohorts. <h3>Design, Setting, and Participants</h3> This cross-sectional study comprised 944 adults and children from 2 prospective cohorts—the Morphea in Adults and Children at the University of Texas Southwestern Medical Center (Dallas, Texas), which enrolled participants from July 20, 2007, to September 21, 2018, and the National Registry for Childhood-Onset Scleroderma at the University of Pittsburgh (Pittsburgh, Pennsylvania), which enrolled participants from October 23, 2002, to November 13, 2018. <h3>Main Outcomes and Measures</h3> Patient demographic characteristics, morphea subtype, quality-of-life measures, disease activity, and damage as measured by Localized Scleroderma Cutaneous Assessment Tool scores during initial visits. <h3>Results</h3> A total of 944 participants (444 patients with adult-onset morphea and 500 patients with pediatric-onset morphea; 741 female participants [78%]; median age at onset, 16 years [interquartile range, 8-44 years]) were included in this study. Most participants were White (723 [77%]) and had the linear (474 [50%]) or generalized subtype of morphea (244 [26%]). With the use of the previously published Padua criteria, most patients were classified to have linear morphea (474 [50%]), followed by generalized morphea (244 [26%]), plaque morphea (141 [15%]), mixed morphea (38 [4%]), and pansclerotic morphea (3 [0.3%]). Overall, the Padua criteria successfully classified 900 patients (95%) in comparison with the Peterson criteria (533 [56%]) and the European Dermatology Forum classification (487 [52%]). <h3>Conclusions and Relevance</h3> In this cross-sectional study of morphea subtype classification systems, the Padua criteria performed best in classifying patients into subgroups with cohesive demographic and clinical features, supporting its widespread use. However, they have ambiguities that might lead to misclassification, particularly in terms of generalized and pansclerotic morphea and descriptors such as morphea profunda. Consensus-based approaches are needed to address these ambiguities and develop a unified classification scheme.
Sequential Therapy for Hepatocellular Carcinoma after Failure of Atezolizumab plus Bevacizumab Combination Therapy
Authors: Masatoshi Kudo
Journal: Liver Cancer (2021)

Additional Effects of Molecular-Targeted Agents after Immune Checkpoint Inhibitor TherapyAdministration of the anti-PD-1 antibody nivolumab to patients with non-small cell lung cancer results in sustained binding (for about 20 weeks) of nivolumab to PD-1 on lymphocytes [5].Thus, it is also expected that programmed death-ligand 1 (PD-L1) antibody binding to PD-L1 on cancer cells is sustainable.This suggests that administration of a molecular-targeted agent that inhibits vascular endothelial growth factor (VEGF) as a subsequent therapy for patients with progressive disease treat-
Abstract PS18-39: Estrogen receptor beta agonists for triple negative breast cancer
Authors: Jharna Datta, Natalie Willingham, Jasmine Manouchehri, Joel David, Mirisha Sheth, Bhuvaneswari Ramaswamy, Ramesh Ganju, Mathew A Cherian
Journal: Cancer Research (2021)

Abstract Background:Triple negative breast cancer (TNBC) represents about 10-15% of all breast cancers. Given the lack of targeted therapies, chemotherapy and immunotherapy are the only treatment options. The five-year survival rate of TNBC patients is approximately 15% less than other forms of breast cancer. Therefore, there is an urgent need to develop novel effective therapeutics for TNBC.Material and Methods:RNA isolated from human immortalized mammary epithelial MCF10A, and various TNBC cell lines was DNase treated and quantitative RT-PCR (qRT-PCR) performed using gene-specific primers spanning exon-exon junctions that include introns in the corresponding genomic sequence to avoid genomic DNA amplification. Gene expression was calculated by ΔΔCt method using GAPDH as an internal control. Immuno-blot analyses were performed on lysates prepared from cells in log phase of growth. Proteins were detected by Enhanced Chemi-Luminescence (ECL) method. Viability of cells treated with ERβ specific agonists was determined by using CellTiter-Glo® 2.0 assay. MB231 cells were treated with ERβ agonists following transfection with pcDNA3 (vector) or Flag-tagged ESR2 plasmids. Western blot analyses using specific antibodies and qRT-PCR were performed with the protein extracts and RNA isolated from the cells, respectively. Results:Our experiments demonstrate that ESR2 (ERβ) is differentially expressed and its level of expression is about 3 to 22-fold higher in TNBC cell lines tested than MCF10A. We have shown that viability of estrogen receptor (ER) positive breast cancer cell lines can be significantly inhibited by selective activation of ERβ. A highly selective ERβ agonist has been invented in the Drug Development Institute at the Ohio State University. Treatment of TNBC lines with these ERβ agonists exhibited a dramatic reduction of cell viability. While comparable IC50 values were observed with our in house and commercially available compounds, TNBC had 2-3-fold lesser IC50 values than ER-positive cell lines. Increased expression of FOXO3 and c-Myc1 and decreased expression of c-Myc2 isoform was noted in ERβ overexpressing MB231 cells upon treatment with ERβ agonists.Conclusion:Our results demonstrate that treatment with highly selective ERβ agonists could be an effective therapeutic strategy for TNBC patients. To improve and develop novel therapeutics for TNBC understanding the mechanism of action of these compounds will be crucial. Citation Format: Jharna Datta, Natalie Willingham, Jasmine Manouchehri, Joel David, Mirisha Sheth, Bhuvaneswari Ramaswamy, Ramesh Ganju, Mathew A Cherian. Estrogen receptor beta agonists for triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-39.
Proper understanding of grounded procedures of separation needs a dual inheritance approach
Authors: Thomas W. Schubert, David J. Grüning
Journal: Behavioral and Brain Sciences (2021)

Abstract Grounded procedures of separation are conceptualized as a learned concept. The simultaneous cultural universality of the general idea and immense diversity of its implementations might be better understood through the lens of dual inheritance theories. By drawing on examples from developmental psychology and emotion theorizing, we argue that an innate blueprint might underlie learned implementations of cleansing that vary widely.
Abstract PS1-60: Is immediate breast reconstruction safe in post neoadjuvant chemotherapy patients? A single centre audit
Authors: Fatima Mansour, Joseph Meilak, Kirti Kabeer, Manoj Gowda, Sadaf Jafferbhoy, Sekhar Marla, Vallipuram Gopalan, Sankaran Narayanan, Soni Soumian
Journal: Cancer Research (2021)

Abstract Introduction: Neoadjuvant chemotherapy (NACT) is increasingly utilised in the treatment of aggressive breast cancers. There are concerns that this could impact patient recovery following extensive oncoplastic procedures. The literature regarding this is limited and conflicting. We aimed to assess the impact of neoadjuvant chemotherapy on patients undergoing immediate breast reconstructions. Method: A 5-year retrospective single centre audit of prospectively collected data on patients undergoing immediate breast reconstruction following NACT, was completed. The oncoplastic procedures performed included myocutaneous and perforator flaps, therapeutic mammoplasty and implant based reconstruction. Demographic data, length of stay, biochemical measurements, rates of wound infection, haematoma, explantation rates and return to theatre, were collected. For comparison a matched cohort of patients who underwent primary reconstruction without NACT, during the same period, was selected. Results: One hundred and fourteen patients were included in the study (52 post NACT vs 62 controls). There were 52% that underwent implant based reconstruction, 33% flaps and 15% mammoplasties. Overall, the NACT group appeared to have slightly improved outcomes including lower complication rates (19% vs 23%, p= 0.042) and length of stay (1.45 vs 1.59 days, p&amp;gt;0.05). Hypoalbuminemia (25.0%) and low WCC (65.2%) were significantly higher in the NACT group but this was not associated with increased complication rates. Conclusion: Our audit suggests that NACT does not cause a significant increase in post-operative morbidity. Further studies with larger numbers will be required to validate these results. Citation Format: Fatima Mansour, Joseph Meilak, Kirti Kabeer, Manoj Gowda, Sadaf Jafferbhoy, Sekhar Marla, Vallipuram Gopalan, Sankaran Narayanan, Soni Soumian. Is immediate breast reconstruction safe in post neoadjuvant chemotherapy patients? A single centre audit [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-60.
Time to evaluate COVID-19 contact-tracing apps
Authors: Vittoria Colizza, Eva Grill, Rafael Mikolajczyk, Ciro Cattuto, Adam Kucharski, Steven Riley, Michelle Kendall, Katrina Lythgoe, David Bonsall, Chris Wymant, Lucie Abeler-Dörner, Luca Ferretti, Christophe Fraser
Journal: Nature Medicine (2021)
High intensity focused ultrasound: a future alternative to surgery for the treatment of localized pancreatic tumors?
Authors: Martin Fabritius, Thomas Lambin, Elodie Cao, Jade Robert, Laurent Milot, Cyril Lafon, Mathieu Pioche
Journal: Endoscopy (2021)

Corrected by:Correction: High intensity focused ultrasound: a future alternative to surgery for the treatment of localized pancreatic tumors?Endoscopy eFirstDOI: 10.1055/a-1394-0547
Abstract SP133: Oncofertility
Authors: K Ruddy
Journal: Cancer Research (2021)

Abstract Many young women have not completed their desired childbearing when they are diagnosed with breast cancer. This is increasingly true as the average age of first birth rises such that more premenopausal breast cancers are diagnosed in nulliparous women. Even women who already have one or more children at the time of their cancer diagnosis may be hoping to become pregnant again. Because chemotherapy is gonadotoxic and endocrine therapy is contraindicated during pregnancy(allowing natural ovarian aging over the 5-10 years of adjuvant therapy recommended for those with endocrine-sensitive stage 1-3 tumors), breast cancer treatments can impair fertility. Fertility preservation strategies including oocyte cryopreservation and embryo cryopreservation should be considered prior to initiation of systemic therapy for young women with fertility concerns, often using modified ovarian stimulation protocols to minimize delays in cancer treatment. The administration of a gonadotropin-releasing hormone agonist before and during chemotherapy to help maintain ovarian function is more controversial, but can also be considered. It is critical that we offer reproductive counseling and access to fertility preservation techniques at the time of diagnosis, and that we also continue to discuss contraception and fertility planning during and after cancer treatment. Results from the POSITIVE trial, which is assessing pregnancy and cancer outcomes of young women who wished to take a break from adjuvant endocrine therapy to attempt conception, are eagerly awaited to inform these discussions. This talk will address current knowns and unknowns related to the optimal management of reproductive concerns in premenopausal women with breast cancer. Citation Format: K Ruddy. Oncofertility [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP133.
Abstract PS16-11: Potential therapeutic effects of HDACi FK228 on TNBC using various models
Authors: Madlin Alzoubi, Khoa Nguyen, Katherine Hebert, Margarite Matossian, Hope Burks, Bridgette Collins-Burow, Matthew Burow
Journal: Cancer Research (2021)

Abstract Breast cancer is the most prevalent type of cancer among women. Most breast cancers are hormone sensitive, however triple negative breast cancer (TNBC), a more aggressive subtype of breast cancer is characterized by its negative expression of estrogen and progesterone receptors, and lack of Her2/NEU amplification. Because of its receptor status, hormone receptor targeted treatments are ineffective against TNBC making it difficult to treat. FK228, known as Romidepsin, is a histone deacetylase inhibitor (HDACi) that specifically targets the enzymes HDACs 1 and 2, tumor suppressor and other proteins exerting epigenetic changes on tumor cells resulting in anticancer activity. FK228 has not been studied in TNBC, but has been approved by the FDA for the treatment of peripheral T-cell lymphoma (PTCL), where the mechanism of action has demonstrated cell cycle arrest and apoptosis [1,2]. To assess the preliminary role of FK228 in breast cancer, a number of TNBC cell lines were treated with the drug and analyzed for suppression of cell cycle genes. Similar to PTCL, TNBC cell lines showed an increase in cell cycle arrest genes such as p21 and others subsequent to treatment. Moving forward, to recapitulate the tumor microenvironment we have utilized 2D and 3D culture, while PDXs (patient derived xenografts), an excellent translational tool. We first identified changes in morphology and migration in 2k1, MDA-MB 231 and HS-578t cell lines treated with FK228 under in-vitro conditions. Additional molecular studies also show a reversal of the epithelial to mesenchymal transition (EMT) in FK228 treated BC cell lines; specifically in relation to EMT genes CDH1 and ZEB2, both directly connected to HDAC1/2 activity. To further study the effects of FK228, PDXs are implanted into mice to study growth patterns, recurrence, metastatic potential and response to FK228 in different patient tumor models. FK228 showed a drastic suppression in tumorigenesis in model TU-BCX-2O0, prompting the study of several other models in tumorigenesis including TU-BX-4IC, 4M4 and 4QX. Metastasis was also monitored by H&amp;E staining lung and liver tissue for analysis for each model, and using an in vivo model consisting of GFP/luciferase transfected breast cancer cells MDA-MB-231 and SUM-159 to monitor both the proliferation and spread of disease in mice. Ultimately this study aims to characterize the FK228 alteration of pathways involved in tumorigenesis, metastasis and resistance within TNBC. Citation Format: Madlin Alzoubi, Khoa Nguyen, Katherine Hebert, Margarite Matossian, Hope Burks, Bridgette Collins-Burow, Matthew Burow. Potential therapeutic effects of HDACi FK228 on TNBC using various models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-11.
Covid-19: Scotland failed to apply measures identified in pre-pandemic exercises, says report
Authors: Bryan Christie
Journal: BMJ (2021)

The health service in Scotland should have been better prepared to respond to some of the challenges posed by the covid-19 pandemic, the country's auditor general has said.A report on the performance of NHS Scotland in 2020 1 praises the early action taken in the first wave of the pandemic to prevent hospitals from being overwhelmed, but it is critical of the failure to implement measures identified in pre-pandemic planning exercises.Scotland was involved in three pandemic planning exercises in the five years before the covid-19 outbreak.Each highlighted several areas that required improvement, including ensuring the availability and correct use of personal protective equipment and increasing the capacity and capability of social care to cope during a pandemic.Despite these warnings, insufficient action was taken which left patient facing staff unprotected and has resulted in 39% of all covid-19 deaths in Scotland taking place in care homes.
In patients receiving liver transplantation, clinical deterioration necessitating medical emergency team activation is associated with prolonged hospital length of stay and higher morbidity
Authors: Marcus Robertson, Ashley Bloom, William Chung, Ben Johnstone, Elise Cannon, Andrew Huynh, Andrew Tsoi, Tessa O'Halloran, Paul J Gow, Peter W Angus, Daryl Jones
Journal: Hepatology (2020)

Background: Patients undergoing liver transplantation (LT) are at high risk of peri‐operative complications that can lead to rapid clinical deterioration (RCD). The Rapid Response System (RRS) facilitates timely escalation of care for patients identified as high‐risk for RCD, using abnormal observations and vital signs (Table 1) to activate a medical emergency team (MET). The prognostic significance of MET activation is poorly studied in LT patients. We investigated the epidemiology of MET activations in LT patients and the association between MET activation and outcomes. Methods: Patients receiving MET activations pre‐ or post‐LT (in the same admission as LT) were identified from a prospectively collected database of patients undergoing LT at the Victorian Liver Transplant Unit over 84‐months (2011‐2017). Primary outcomes were mortality, length of stay (LOS) and unplanned readmission to ICU Results: 383 patients were included. Median age was 56 years (IQR 48 ‐ 61), 65% were male and median MELD score was 18 (IQR 11 ‐ 26). 131 (34%) patients had ≥1 MET activation, with a total of 266 MET activations recorded (MET event rate 695 per 1000 LT admissions). 106 MET activations occurred in 59 patients pre‐LT (pre‐LT MET) and 160 in 88 patients post‐LT (post‐LT MET). Commonest triggers for MET activation were tachypnoea and hypotension pre‐LT and tachycardia post‐LT. MELD scores were significantly higher in the pre‐LT MET cohort compared to the no‐ and post‐LT MET groups (MELD 27 vs. 16 and 20, p 4 and >12 hours prior to MET activation respectively. MET patients had significantly longer ICU LOS (no‐MET 65 hours vs. post‐LT MET 110 hours (p<0.001) and vs. pre‐LT MET 136 hours (p<0.001)) and hospital LOS (no‐MET 13 days vs. post‐LT MET 23 days (p<0.001) and vs. pre‐LT MET 24 days (p<0.001)). In‐hospital survival was 96% and did not differ between groups. MET patients were significantly more likely to require inpatient rehabilitation (no‐MET 15% vs. post‐LT MET 41% (p<0.001) and vs. pre‐LT MET 56% (p<0.001). Conclusion: LT patients with peri‐operative complications prompting MET activation represent a high‐risk group with increased morbidity, ICU and hospital LOS. Early identification and correction of factors which predispose to MET calls may lead to improved outcomes and a reduction in health‐care costs.
OSI-906, a selective small molecule inhibitor of the IGF-1R kinase, sensitizes tumors to the cytotoxic effects of chemotherapeutic agents by blocking survival pathways
Authors: Alexandra Eyzaguirre, Jonathan Pachter, John Haley, David Epstein, Kenneth Iwata, Mark Miglarese, Elizabeth Buck
Journal: Cancer Research (2008)

4014  Signaling through the receptor for insulin like growth factor (IGF-1R) promotes cell survival in a broad range of tumor types by activating the PI3K-AKT pathway. Tumor cells upregulate IGF-driven AKT activity upon challenge with cytotoxic drugs, providing tumors with a mechanism for adaptive survival in the presence of such agents. OSI-906 is a selective inhibitor of IGF-1R kinase activity that is currently under evaluation in phase 1 clinical trials. In preclinical models, OSI-906 blocks IGF1R-mediated AKT signaling and inhibits the growth of a panel of human tumor cell lines including NSCLC, PaCa, breast, and sarcomas. We assessed whether OSI-906 could augment the activity of cytotoxic chemotherapeutics in vitro. We found that doxorubicin treatment resulted in activation of both the AKT and ERK pathways in selected tumor cell lines including breast carcinomas and sarcomas. Mechanistically, we found that doxorubicin treatment led to upregulation of both IGF-1R and Insulin Receptor activity. The increased AKT and ERK activities evoked by doxorubicin were inhibited by treatment with OSI-906. In selected breast carcinoma cell lines, OSI-906 inhibited doxorubicin-induced AKT activity but did not affect basal AKT activity. Further, the combination of OSI-906 with doxorubicin promoted an increase in overall growth inhibition and evoked a synergistic increase in apoptosis in multiple cell lines. Collectively, these data support a mechanistic foundation for combining OSI-906 with chemotherapeutic agents such as doxorubicin that provoke tumor cells to activate IGF1R/AKT-mediated survival pathways.
Developmental antecedents of cleansing effects: Evidence against domain-generality
Authors: Emily Gerdin, Shruthi Venkatesh, Joshua Rottman, Jasmine M. DeJesus
Journal: Behavioral and Brain Sciences (2021)

Abstract Lee and Schwarz propose grounded procedures of separation as a domain-general mechanism underlying cleansing effects. One strong test of domain generality is to investigate the ontogenetic origins of a process. Here, we argue that the developmental evidence provides weak support for a domain-general grounded procedures account. Instead, it is likely that distinct separation procedures develop uniquely for different content domains.
Antibacterial metals and alloys for potential biomedical implants
Authors: Erlin Zhang, Xiaotong Zhao, Jiali Hu, Ruoxian Wang, Shan Fu, Gaowu Qin
Journal: Bioactive Materials (2021)

Metals and alloys, including stainless steel, titanium and its alloys, cobalt alloys, and other metals and alloys have been widely used clinically as implant materials, but implant-related infection or inflammation is still one of the main causes of implantation failure. The bacterial infection or inflammation that seriously threatens human health has already become a worldwide complaint. Antibacterial metals and alloys recently have attracted wide attention for their long-term stable antibacterial ability, good mechanical properties and good biocompatibility
Red oil staining compared to immunocytochemical staining for milk proteins of alveolar macrophages in chronic respiratory disease of infancy.
Authors: Frans De Baets, Claudia Aarts, Filomeen Haerynck, Van Daele Sabine, Elke De Wachter, Iris De Schutter, Anne Malfroot, Petra Schelstraete
Journal: European Respiratory Journal (2010)