bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO008: Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort
Authors: Kulkarni Madhura , Vaid Pooja M. , Puntambekar Anirudha Puntambekar , Banale Rituja A. , Reddy Ruhi , Unde Rohini , Namewar Namrata , Kelkar Devaki , Shashidhara L.S. , Koppiker C.B. 
Published: March 2021

Abstract
Objectives: Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods: A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results: Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion: Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.
Citation Format: Madhura Kulkarni, Pooja M. Vaid, Anirudha Puntambekar Puntambekar, Rituja A. Banale, Ruhi Reddy, Rohini Unde, Namrata Namewar, Devaki Kelkar, L.S. Shashidhara, C.B. Koppiker. Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort [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 PO008.
Abstract PO017: Role of NF-κB and epiregulin in tumor-associated macrophages promoting therapeutic resistance to JAK inhibition
Authors: Bapat Aditi S. , Jesser Emily , Lassiter Chelsea , Schwertfeger Kaylee 
Published: March 2021

Abstract
Breast cancer is the second leading cause of cancer-related mortalities in women. Triple-negative is the most lethal type of breast cancer with poorest survival rates. Triple-negative breast cancers do not respond to conventional hormone receptor targeted therapies and thus inhibitors for other overactivated signaling pathways are being investigated. The Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) is an oncogenic transcription factor pathway expressed in tumor and stromal cell populations. Inhibitors of this pathway such as ruxolitinib are being studied for treatment of triple-negative breast cancer but their efficacy in patients is limited. A significant barrier to the success of these inhibitors in the clinic is the lack of information about mechanisms of resistance. Tumor-associated macrophages (TAMs) are important components of the immune-suppressive environment within the tumor and are associated with poor outcome. We found that JAK inhibition in TAMs leads to induction of tumor-promoting genes that mediate therapeutic resistance of the tumor to JAK inhibition. A subset of the activated tumor promoting genes are known transcriptional targets of the NF-κB transcription factor pathway. We hypothesize that JAK inhibition activates tumor-promoting pathways in TAMs through activation of the NF-κB pathway and targeting these tumor-promoting pathways in combination with JAK inhibition will be beneficial over single therapy. We aim to elucidate activation of NF-κB in TAMs, to identify the mechanism of the observed pro-tumor response. In addition, we aim to target epiregulin, an EGFR ligand which was observed to be one of the most significantly upregulated genes in TAMs treated with JAK inhibitor. We hypothesize that targeting effects of macrophage-derived epiregulin in combination with JAK inhibition will overcome macrophage-mediated therapeutic resistance. This work will provide useful information about novel pathways that can be targeted to combat the compensatory negative effects of TAMs on tumor-targeted therapies. The results will also pave the way for development of novel inhibitor combinations targeting the tumor microenvironment in addition to targeting the tumor, and ultimately benefit patients who do not respond to single therapies.
Citation Format: Aditi S. Bapat, Emily Jesser, Chelsea Lassiter, Kaylee Schwertfeger. Role of NF-κB and epiregulin in tumor-associated macrophages promoting therapeutic resistance to JAK inhibition [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 PO017.
Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial
Authors: Riely Gregory J. , Neal Joel W. , Camidge D. Ross , Spira Alexander I. , Piotrowska Zofia , Costa Daniel B. , Tsao Anne S. , Patel Jyoti D. , Gadgeel Shirish M. , Bazhenova Lyudmila , Zhu Viola W. , West Howard L. , Mekhail Tarek , Gentzler Ryan D. , Nguyen Danny , Vincent Sylvie , Zhang Steven , Lin Jianchang , Bunn Veronica , Jin Shu , Li Shuanglian , Jänne Pasi A. 
Published: February 2021

Abstract

Mobocertinib, an oral epidermal growth factor receptor (EGFR) inhibitor targeting EGFR gene mutations, including exon 20 insertions (EGFRex20ins), in non–small cell lung cancer, was evaluated in a phase I/II dose-escalation/expansion trial (ClinicalTrials.gov NCT02716116). Dose escalation identified 160 mg/d as the recommended phase 2 dose and maximum tolerated dose. Among 136 patients treated with 160 mg/d, the most common any-grade treatment-related adverse events (TRAE; &gt;25%) were diarrhea (83%), nausea (43%), rash (33%), and vomiting (26%), with diarrhea (21%) the only grade ≥3 TRAE &gt;5%. Among 28 EGFRex20ins patients treated at 160 mg/d, the investigator-assessed confirmed response rate was 43% (12/28; 95% confidence interval, 24%–63%) with median duration of response of 14 months (5.0–not reached) and median progression-free survival of 7.3 months (4.4–15.6). Mobocertinib demonstrated antitumor activity in patients with diverse EGFRex20ins variants with a safety profile consistent with other EGFR inhibitors.

Significance:
No oral EGFR-targeted therapies are currently approved for patients with EGFRex20ins NSCLC. Mobocertinib demonstrated antitumor activity with manageable toxicity in patients with advanced EGFRex20ins NSCLC in this study, supporting additional development of mobocertinib in this patient population.
See related commentary by Pacheco, p. 1617.
This article is highlighted in the In This Issue feature, p. 1601
Mobocertinib (TAK-788): A Targeted Inhibitor ofEGFRExon 20 Insertion Mutants in Non–Small Cell Lung Cancer
Authors: Gonzalvez Francois , Vincent Sylvie , Baker Theresa E. , Gould Alexandra E. , Li Shuai , Wardwell Scott D. , Nadworny Sara , Ning Yaoyu , Zhang Sen , Huang Wei-Sheng , Hu Yongbo , Li Feng , Greenfield Matthew T. , Zech Stephan G. , Das Biplab , Narasimhan Narayana I. , Clackson Tim , Dalgarno David , Shakespeare William C. , Fitzgerald Michael , Chouitar Johara , Griffin Robert J. , Liu Shengwu , Wong Kwok-kin , Zhu Xiaotian , Rivera Victor M. 
Published: February 2021

AbstractMost EGFR exon 20 insertion (EGFRex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting EGFR-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible EGFR TKI, was specifically designed to potently inhibit oncogenic variants containing activating EGFRex20ins mutations with selectivity over wild-type EGFR. The in vitro and in vivo activity of mobocertinib was evaluated in engineered and patient-derived models harboring diverse EGFRex20ins mutations. Mobocertinib inhibited viability of various EGFRex20ins-driven cell lines more potently than approved EGFR TKIs and demonstrated in vivo antitumor efficacy in patient-derived xenografts and murine orthotopic models. These findings support the ongoing clinical development of mobocertinib for the treatment of EGFRex20ins-mutated NSCLC.Significance:No oral EGFR-targeted therapies are approved for EGFR exon 20 insertion (EGFRex20ins) mutation-driven NSCLC. Mobocertinib is a novel small-molecule EGFR inhibitor specifically designed to target EGFRex20ins mutants. Preclinical data reported here support the clinical development of mobocertinib in patients with NSCLC with EGFR exon 20 insertion mutations.See related commentary by Pacheco, p. 1617.This article is highlighted in the In This Issue feature, p. 1601
Circulating Wnt Ligands Activate the Wnt Signaling Pathway in Mature Erythrocytes
Authors: Siman-Tov Ronen , Zelikson Natalie , Caspi Michal , Levi Yakir , Perry Chava , Khair Fayhaa , Stauber Hagit , Sznitman Josué , Rosin-Arbesfeld Rina 
Published: February 2021

Objective:
The deformation ability of erythrocytes is critical for their function and affects their mobility in the circulation. To circulate and travel through narrow vessels, erythrocytes must continuously alter their shape by modifying their cytoskeleton, which controls their elasticity and stability. Erythrocytes lack nuclei and other major organelles, and thus most of the known signaling cascades are thought to be inactive in these cells. As the noncanonical Wnt pathway affects cytoskeleton dynamics by posttranslational modifications, we hypothesized that this signaling pathway may affect erythrocytes.

Approach and Results:
We demonstrate that components of the noncanonical Wnt pathway are expressed in erythrocytes and that incubation of erythrocytes with Wnt ligands prolonged their survival both ex vivo, under storage conditions, and in posttransfusion recipient mice. We show that Wnt ligands modulate the erythrocyte cytoskeleton, enhancing its flexibility and strength. Importantly, we show that the noncanonical Wnt-5A ligand is secreted into the plasma and that monocytes and lymphocytes are a possible source of the Wnt effectors in the blood circulation.

Conclusions:
These findings provide evidence for intracellular signaling activity in enucleated cells and signal transduction in the blood circulation and thus open new and exciting avenues for studying the function of signaling pathways in the bloodstream.
Trading Emerging Technologies: Export Controls Meet Reality
Authors: Jones Scott A. 
Published: February 2021

Abstract
“Emerging technologies” and the growing inventory of their dual-use applications increasingly challenge policymakers with how to balance technological development, economic competitiveness, and national security priorities. While dual-use export control regulators have always struggled with balancing economic and security interests, emerging technologies are challenging controls systems ill-equipped to define or practically control them. As the most advanced case, the US export control effort is an instructive regarding the challenges of deploying conventional controls over defining and controlling rapidly developing technology sets. This article reviews the US case in light of the current challenges posed by emerging and foundational technologies.
Morphological evidence for paraphyly of Holopothrips Hood (Thysanoptera: Phlaeothripidae), a Neotropical genus of gall-inducing thrips
Authors: Lindner Mariana F. , Ferrari Augusto , Cavalleri Adriano 
Published: February 2021

Abstract
Holopothrips is a diverse group of thrips associated to galls in the Neotropics, with a variety of host plants and wide morphological diversity. Relationships to other Neotropical groups have been proposed, but are still untested, and the monophyly of the genus remains doubtful. Here, we perform a phylogenetic analysis of Holopothrips, based on morphological characters. A total of 87 species were included in the matrix and eight analyses were carried out, but all of them failed to recover Holopothrips as a monophyletic grouping. Bremer and Bootstrap support values were low, and the topologies varied among all analyses, with uncertain internal relations for the ingroup. These results indicate that the relationships for Holopothrips species, and the proposed related genera, are more complex than previously reported; and morphological characters may not be enough to recover the evolutionary story within this group. We also discuss the influences of different character coding, continuous characters and weighting schemes in our results.
Time Perspective among Patients Diagnosed with Neurotic and Personality Disorders − an Exploratory, Clinical Study
Authors: Mostowik Joanna , Rutkowski Krzysztof , Ostrowski Tadeusz , Mielimąka Michał 
Published: February 2021

Abstract
(1) An assessment of the structure of time perspective (TP) in a group of patients with neurotic and personality disorders (ICD-10: F4x, F60.x, F61) treated with group psychotherapy. (2) An analysis of the differences between the structure of TP in patients and the general population in order to expand the understanding of the relations between TP and mental health. Data were collected from 49 patients at the University Hospital Day Centre for the Treatment of Neurotic Disorders and Behavioural Syndromes. The measurement of TP was performed with the Zimbardo Time Perspective Inventory. A licensed psychiatrist conducted the diagnosis of neurotic and personality disorders, with additional data obtained from the Symptom Checklist KO ‘O’ and the Neurotic Personality Questionnaire KON-2006. The statistical analysis revealed significant differences in the structure of TP between patients and the general population. Among patients, the intensity of the past experienced negatively was significantly higher, and subsequently, the degree of the past experienced positively was lower. Patients remain in the negative past and concentrate much more on the pain and the worrying memories. They give much less attention to what was and what is valuable and pleasant in their life. Results of this research reveal distinct features of the structure of TP in the studied group. Findings underline the clinical relevance of TP at various stages of therapy. Restoring a balanced time perspective could be regarded as a tenable goal for psychotherapy and perhaps an innovative indicator of the treatment’s effectiveness.
Pilot Study of External Beam Radiotherapy for Recurrent Unremitting Tracheal Stenosis
Authors: Vincent Aurora G. , Barker Jerry L. , Ducic Yadranko 
Published: February 2021

Objective: Tracheal stenosis can have a variety of presentations, severities, causes, and be a difficult condition to treat. Some patients demonstrate recurrent stenosis after multiple endoscopic treatments and are either poor candidates for open procedures or do not desire open surgery. We sought to evaluate low-dose postoperative external beam radiotherapy (EBRT) as a novel therapy for patients with recurrent tracheal stenosis refractory to endoscopic therapies. Method: We performed a retrospective review of patients with recurrent tracheal stenosis who underwent EBRT in addition to endoscopic dilation. We compared the number of endoscopic procedures required in the 6 months before EBRT to the number required in the 6 months after EBRT. Results: Six patients met criteria for inclusion in our study. The cause of stenosis was variable among the study population. In the 6 months leading up to EBRT, patients underwent an average 6.2 endoscopic procedures. This dropped to an average 1.9 procedures in the 6 months following EBRT ( P < .001). Conclusion: Herein, we show that low-dose postoperative external beam radiotherapy (EBRT), a novel therapy for patients with recurrent tracheal stenosis refractory to endoscopic therapies, is effective in decreasing the frequency of endoscopic dilations. Level of Evidence: 4
Opportunity management of the COVID-19 pandemic: testing the crisis from a global perspective
Authors: Kuhlmann Sabine , Bouckaert Geert , Galli Davide , Reiter Renate , Hecke Steven Van 
Published: February 2021

This article provides a conceptual framework for the analysis of COVID-19 crisis governance in the first half of 2020 from a cross-country comparative perspective. It focuses on the issue of opportunity management, that is, how the crisis was used by relevant actors of distinctly different administrative cultures as a window of opportunity. We started from an overall interest in the factors that have influenced the national politics of crisis management to answer the question of whether and how political and administrative actors in various countries have used the crisis as an opportunity to facilitate, accelerate or prevent changes in institutional settings. The objective is to study the institutional settings and governance structures, (alleged) solutions and remedies, and constellations of actors and preferences that have influenced the mode of crisis and opportunity management. Finally, the article summarizes some major comparative findings drawn from the country studies of this Special Issue, focusing on similarities and differences in crisis responses and patterns of opportunity management. Points for practitioners With crises emerging in ever shorter sequences of time, governing turbulence and using crises for strategic institutional decisions has become an increasingly important issue for policymakers. Aiming at effective and proportionate responses, policymakers must take the institutional conditions, administrative traditions and relevant actor constellations of crisis management into account, which are key to learn from other countries’ experiences. Comparing these experiences and analyzing the politics of crisis governance from a cross-country perspective may help policymakers to identify strengths and weaknesses of their own national/regional approaches and to seize crisis-related windows of opportunity for institutional reforms at the national and international levels.
End-of-Life Needs of Dying Patients and Their Families in Mainland China: A Systematic Review
Authors: Cheng Guobin , Chen Chuqian 
Published: February 2021

Objective To map the current research status and understand existing findings regarding end-of-life care needs in Mainland China. Method First-hand, empirical studies on the needs of dying patients and/or their families in Mainland China were searched in Web of Science, Scopus, Proquest, Taylor & Francis Online and CNKI in December 2019. Findings were synthesized. Results A total of 33 (10 qualitative) studies were involved. Chinese dying patients and their families had physical, psychological, social, and spiritual needs and needs for knowledge and information. Prevalent needs of dying patients were mainly symptom control and decent look, being treated kindly by professional caregivers, family accompany, dignity, and comfortable environment. Families mainly need healthcare professionals to take good care of patients and wishes for information, knowledge, and facilities to help themselves become better caregivers. Conclusions Findings lay the foundation for effective and tailored services for Chinese clients and provided insights for future investigations.
Is a fixed low-dose protamine better at reducing postoperative bleeding in off pump coronary artery bypass grafting?
Authors: Murugesh Wali R , Prasad Shetty Shyam , Ramachandrappa Sujay K , Dinesh Kumar Uyyamballi S 
Published: February 2021

Context Protamine is used ubiquitously in all cardiac surgeries for reversal of heparin. Risk of postoperative bleeding is increased with inadequate heparin reversal or due to anticoagulant side effects of protamine; hence, it is important to dose protamine properly. This study compares 80% protamine dose with full dose on postoperative bleeding and transfusion needs in OPCAB. Aims The aim of our study was to find whether lower dose of protamine could reduce postoperative bleeding and need for blood product transfusions in off pump coronary artery bypass grafting as compared to the regular dose of protamine. Settings and design This was a double-blinded randomised controlled trial where patients posted for off pump CABG meeting the inclusion criteria were included in the study. Methods and material Ninety patients were randomised to two groups, group F receiving full dose of protamine of 1 mg per mg heparin used, and group L received 0.8 mg per mg. Postoperative activated clotting time, bleeding at 1 h, 4 h, 24 h and total drainage till drains removal and blood product transfusion requirements were noted. Statistical analysis used: SPSS software. Results Both groups were matched in demographics, preoperative cessation of heparin and aspirin and platelet counts. Both groups received equal heparin dose, activated clotting time before protamine, activated clotting time post protamine in OT and ICU were equal as were the conduits used. There was no significant difference between the groups in post-operative drainage over time or in the need for blood product transfusions. Conclusions Eighty per cent of the dose of protamine can adequately reverse the heparin used during off pump cardiac surgery without any increase in incidence of postoperative bleeding or need for blood product transfusions.