tbuckley/cabot-search huggingface dataset:
Factors Associated With the Professional Success of Female Surgical Department Chairs
Authors: Alexandra B. Columbus, Pamela W. Lu, Susanna S. Hill, Adam C. Fields, Jennifer S. Davids, Nelya Melnitchouk
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Only 7% of US surgical department chairs are occupied by women. While the proportion of women in the surgical workforce continues to increase, women remain significantly underrepresented across leadership roles within surgery. <h3>Objective</h3> To identify commonality among female surgical chairs with attention toward moderators that appear to have contributed to their professional success. <h3>Design, Setting, and Participants</h3> A grounded theory qualitative study was conducted in academic surgical departments within the US. Participants included current and emeritus female chairs of American academic surgical departments. The study was conducted between December 1, 2018, and March 31, 2019. An eligible cohort of 26 women was identified. <h3>Interventions and Exposures</h3> Participants completed semistructured telephone interviews conducted with an interview guide. <h3>Main Outcomes and Measures</h3> Common themes associated with career success. <h3>Results</h3> Of the eligible cohort of 26 women, 20 individuals (77%) participated. Sixteen participants were serving as active department chairs and 4 were former department chairs. Mean (SD) length of time served in the chair position, either active or former, was calculated at 5.6 (2.6) years. Two major themes were identified. First, internal factors emerged prominently. Personality traits, including confidence, resilience, and selflessness, were shared among participants. Adaptability was described as a major facilitator to career success. Second, participants described 2 subtypes of external factors, overt and subtle, each of which included barriers and bolsters to career development. Overt support from mentors of both sexes was described as contributing to success. Subtle factors, such as gender norms, on institutional and cultural levels, affected behavior by creating environments that supported or detracted from career advancement. <h3>Conclusions and Relevance</h3> In this study, participants described both internal and external factors that have been associated with their advancement into leadership roles. Future attention toward encouraging intrinsic strengths, fostering environments that bolster career development, and emphasizing adaptability, along with work-system redesign, may be key components to career success and advancing diversity in surgical leadership roles.
Comparative use of perioperative chemotherapy (CT) in non-small cell lung cancer (NSCLC) between 2004 and 2007
Authors: B. Le Naour, A. Mauguen, D. Fabre, J. Pignon, D. Planchard, J. Soria, P. Dartevelle, B. Besse
Journal: Journal of Clinical Oncology (2009)

7564 Background: Adjuvant (ADJ) platinum-based CT has become a new standard of care for patients (pts) with resected stage II and III NSCLC, and is discussed in selected stage IB pts. Impact of positive randomized trials which showed significant survival improvement (first published in 2004) on the use of ADJ CT has been poorly studied to date. Methods: A retrospective study of consecutive pts with NSCLC who underwent curative surgery during the first half of year 2004 and 2007 in the surgical center Marie Lannelongue (France) was conducted. Logistic regression models were employed to identify cofactors associated with the use of ADJ CT (excluding stage IV). Odds ratio (OR) &gt; 1 corresponds to a more frequent use than in reference group. Results: A total of 240 pts (116 in 2004, 124 in 2007) underwent curative surgery for NSCLC (11% IA; 30% IB; 27% II; 27% III; 5% IV). Among all pts, 12 % received neoADJ CT (less in 2007, 8% vs 16% p=.04), 35% ADJ (4% both). Reasons for not receiving ADJ CT included stage I (34%), death (11%), comorbidities (10%), poor performance status (10%), advanced age (8%), post-operative complications (7%), patient refusal (3%). More ADJ CT was prescribed in 2007 (41% vs 30% in 2004, p=.009). Overall, 45% of pts with stage II-III received ADJ CT in 2004 versus 69% did so in 2007. In multivariate analysis (194 pts), ADJ CT was associated with the year of inclusion (OR=2.67 p=.009), stage (stage II, OR=6.77, stage III, OR=16.85; p&lt;.0001), serious medical history (OR=.41 p=.01) and salvage surgery (OR=.26 p=.03). Cisplatin was the preferred platinum compound in 76% of neoADJ regimens (mostly cisplatin-docetaxel), and 70% of ADJ CT (mostly cisplatin-vinorelbine). Conclusions: The presentation and publication of “positive” ADJ CT trials had significantly increased prescription of ADJ CT in pts with stage II-III NSCLC. Nevertheless 31% of the stage II-III did not received CT mostly because of comorbidities, highlighting the need of a personalized CT. No significant financial relationships to disclose.
Chemosensitivity of newly established human malignant pleural mesothelioma cells: Significant growth inhibition by amrubicin, a novel 9-aminoanthracycline, or cyclooxygenase 2 inhibitor
Authors: T. Hida, S. Ogawa, J. Park, J. Park, J. Shimizu, Y. Horio, K. Yoshida, Y. Sekido
Journal: Journal of Clinical Oncology (2009)

e19060 Background: Malignant pleural mesothelioma is asbestos-related malignancy that is highly resistant to current therapeutic modalities. Survival of patients with malignant mesothelioma is very poor, especially in advanced stage, regardless of a recent advancement of chemotherapeutical modalities of combination with cisplatin and antifolate. Methods: Eleven cell lines derived from malignant mesothelioma were established in our laboratory. Chemosensitivity of these cell lines to nine chemotherapeutic drugs (cisplatin, vinorelbine, irinotecan, gemcitabine, pemetrexed, gefitinib, erlotinib, and amrubicin and its active in vivo substance, amrubicin-13-OH) and four cyclooxygenase 2 inhibitors was tested by MTT assay. Results: Anti-cancer agents, cisplatin, vinorelbine, gemcitabine, gefitinib, or erlotinib, showed little growth inhibition, and pemetrexed and irinotecan showed modest growth inhibition in malignant mesothelioma cells, whereas amrubicin-13-OH showed strong growth inhibition. Cyclooxygenase 2 inhibitors inhibit proliferation of malignant mesothelioma cells in a dose-dependent manner: modest growth inhibition at clinically achievable low concentrations and complete growth inhibition at clinically achievable high concentrations by intrapleural instillation. In addition, enhanced growth suppression was obtained by using amrubicin-13-OH in combination with cyclooxygenase 2 inhibitor. Conclusions: Our study suggests that amrubicin can inhibit proliferation of malignant mesothelioma cells. In addition, the use of a cyclooxygenase 2 inhibitor may be a promising therapeutic approach in the treatment of mesothelioma, because previous studies indicated the presence of increased cyclooxygenase 2 expression in malignant mesothelioma, which is notoriously resistant to chemotherapy. No significant financial relationships to disclose.
Correlates of hospice use in elders with cancer
Authors: C. Owusu, S. Koroukian, E. Madigan
Journal: Journal of Clinical Oncology (2009)

9579 Background: Use of hospice has remained relatively low. We aim to identify correlates of hospice in elders with cancer, hypothesizing that the presence of functional limitations and geriatric syndromes are associated with hospice use, independently of age and comorbidities. Methods: The study population included Ohio residents age 65 years or older, diagnosed with breast (n=774), prostate (n=271), or colorectal cancer (n=1,011) during the period 07/1999–12/2001, receiving care through the Medicare fee-for-service system, and first receiving home health care (HHC) in the 30 days before or after cancer diagnosis. This strategy was aimed at obtaining clinical data at baseline, as documented in the HHC Outcome Assessment Information Set (OASIS). Our data source consisted of records from the Ohio Cancer Incidence Surveillance System (OCISS) linked with Medicare data, and the OASIS. In addition to descriptive analyses, multivariable logistic regression analysis was conducted to evaluate the association between hospice use, comorbidity, functional limitations, and geriatric syndromes, after adjusting for patient and tumor attributes. Results: Respectively across the anatomic cancer sites, hospice was used by 9.8%, 22.5%, and 25.1%, of patients. Hospice use increased significantly with age, and was higher among men than women. No differences in hospice use were observed by race, Medicaid status, or the presence of comorbidities. Conversely, hospice use was significantly higher (p &lt; 0.001) among patients with functional limitations (24.0% vs. 16.5% in all others), and those with geriatric syndromes (23.8% vs. 15.3% in all others). Results from the multivariable logistic regression analysis indicated that comorbidities and functional limitations were not associated with hospice use, whereas patients with geriatric syndromes were 1.5 times as likely as those without geriatric syndromes to use hospice (adjusted odds ratio (AOR): 1.5, 95% confidence interval (1.2–1.9). Conclusions: The findings highlight the importance of clinical data that extend beyond comorbidities, when analyzing hospice use. Given marked differences in the disease trajectory across the anatomical cancer sites, future studies should analyze these associations separately in breast, prostate, and colorectal cancer patients. No significant financial relationships to disclose.
Antigen-specific B cell depletion for precision therapy of mucosal pemphigus vulgaris
Authors: Jinmin Lee, Daniel K. Lundgren, Xuming Mao, Silvio Manfredo-Vieira, Selene Nunez-Cruz, Erik F. Williams, Charles-Antoine Assenmacher, Enrico Radaelli, Sangwook Oh, Baomei Wang, Christoph T. Ellebrecht, Joseph A. Fraietta, Michael C. Milone, Aimee S. Payne
Journal: Journal of Clinical Investigation (2020)

Desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) expressing the pemphigus vulgaris (PV) autoantigen DSG3 fused to CD137-CD3ζ signaling domains, represent a precision cellular immunotherapy approach for antigen-specific B cell depletion. Here, we present definitive preclinical studies enabling a first-in-human trial of DSG3-CAART for mucosal PV. DSG3-CAART specifically lysed human anti-DSG3 B cells from PV patients and demonstrated activity consistent with a threshold dose in vivo, resulting in decreased target cell burden, decreased serum and tissue-bound autoantibodies, and increased DSG3-CAART engraftment. In a PV active immune model with physiologic anti-DSG3 IgG levels, DSG3-CAART inhibited antibody responses against pathogenic DSG3 epitopes and autoantibody binding to epithelial tissues, leading to clinical and histologic resolution of blisters. DSG3 autoantibodies stimulated DSG3-CAART IFN-γ secretion and homotypic clustering, consistent with an activated phenotype. Toxicology screens using primary human cells and high-throughput membrane proteome arrays did not identify off-target cytotoxic interactions. These preclinical data guided the trial design for DSG3-CAART and may help inform CAART preclinical development for other antibody-mediated diseases.
Evidence for action: a One Health learning platform on interventions to tackle antimicrobial resistance
Authors: Didier Wernli, Peter S Jørgensen, E Jane Parmley, Max Troell, Shannon Majowicz, Stephan Harbarth, Anaïs Léger, Irene Lambraki, Tiscar Graells, Patrik J G Henriksson, Carolee Carson, Melanie Cousins, Gunilla Skoog Ståhlgren, Chadag V Mohan, Andrew J H Simpson, Barbara Wieland, Karl Pedersen, Annegret Schneider, Sujith J Chandy, Tikiri Priyantha Wijayathilaka, Jérôme Delamare-Deboutteville, Jordi Vila, Cecilia Stålsby Lundborg, Didier Pittet
Journal: The Lancet Infectious Diseases (2020)
GSK3 inhibitor-loaded osteotropic Pluronic hydrogel effectively mitigates periodontal tissue damage associated with experimental periodontitis
Authors: Yosif Almoshari, Rongguo Ren, Haipeng Zhang, Zhenshan Jia, Xin Wei, Ningrong Chen, Guojuan Li, Sangjin Ryu, Subodh M. Lele, Richard A. Reinhardt, Dong Wang
Journal: Biomaterials (2020)
Continuous sunitinib treatment in patients with unresectable hepatocellular carcinoma (HCC): A multicenter phase II trial (SAKK 77/06 and SASL 23)
Authors: D. Koeberle, M. Montemurro, P. Samaras, P. Majno, M. Simcock, K. Kovacs, R. Inauen, V. Hess, P. Saletti, G. Bodoky
Journal: Journal of Clinical Oncology (2009)

4591 Background: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenetic activity. Evidence for clinical activity in HCC was reported in 2 phase II trials [Zhu et al and Faivre et al, ASCO 2007] using either a 37.5 or a 50 mg daily dose in a 4 weeks on, 2 weeks off regimen. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients (pts) with HCC. Methods: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease and Child-Pugh A or B liver dysfunction. Pts received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression free survival at 12 weeks (PFS12) defined as ‘success’ if the patient was alive and without tumor progression assessed by 12 weeks (± 7 days) after registration. A PFS12 of ≤ 20% was considered uninteresting and promising if ≥ 40%. Using the Simon-two minimax stage design with 90% power and 5% significance the sample size was 45 pts. Secondary endpoints included safety assessments, measurement of serum cobalamin levels and tumor density. Results: From September 2007 to August 2008 45 pts, mostly male (87%), were enrolled in 10 centers. Median age was 63 years, 89% had Child-Pugh A and 47% had distant metastases. Median largest lesion diameter was 84 mm (range: 18 - 280) and 18% had prior TACE. Reasons for stopping therapy were: PD 60%, symptomatic deterioration 16%, toxicity 11%, death 2% (due to tumor), and other reasons 4%; 7% remain on therapy. PFS12 was rated as success in 15 pts (33%) (95% CI: 20%, 49%) and failure in 27 (60%); 3 were not evaluable (due to refusal). Over the whole trial period 1 CR and 40% SD as best response were achieved. Median PFS, duration of disease stabilization, TTP and OS were 2.8, 3.2, 2.8 and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent and all deaths due to the tumor. Conclusions: Continuous SU treatment with 37.5 mg/d daily is feasible and demonstrates moderate activity in pts with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design the therapy is considered promising (&gt; 13 PFS12 successes). No significant financial relationships to disclose.
GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis
Authors: Xichun Xia, Guangchao Cao, Guodong Sun, Leqing Zhu, Yixia Tian, Yueqi Song, Chengbin Guo, Xiao Wang, Jingxiang Zhong, Wei Zhou, Peng Li, Hua Zhang, Jianlei Hao, Zhizhong Li, Liehua Deng, Zhinan Yin, Yunfei Gao
Journal: Journal of Clinical Investigation (2020)

Psoriasis is a severe disease associated with the disturbance of metabolism and inflammation, but the molecular mechanisms underlying these aspects of psoriasis pathology are poorly understood. Here, we report that glutaminase 1-mediated (GLS1-mediated) glutaminolysis was aberrantly activated in patients with psoriasis and in psoriasis-like mouse models, which promoted Th17 and γδ T17 (IL-17A-producing γδ T) cell differentiation through enhancement of histone H3 acetylation of the Il17a promoter, thereby contributing to the immune imbalance and development of psoriasis. We further demonstrate that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) protease was constitutively active in psoriatic CD4+ and γδ T cells, thereby supporting GLS1 expression by stabilizing c-Jun, which directly binds to the GLS1 promoter region. Blocking the activity of either GLS1 or MALT1 protease resolved Th17 and γδ T17 cell differentiation and epidermal hyperplasia in the psoriasis-like mouse models. Finally, IL-17A enhanced GLS1 expression via the MALT1/cJun pathway in keratinocytes, resulting in hyperproliferation of and chemokine production by keratinocytes. Our findings identify the role of the MALT1/cJun/GLS1/glutaminolysis/H3 acetylation/T17 axis in psoriasis pathogenesis and reveal potential therapeutic targets for this disease.
High-flow nasal cannula for COVID-19 patients: risk of bio-aerosol dispersion
Authors: Jie Li, James B. Fink, Stephan Ehrmann
Journal: European Respiratory Journal (2020)

We appreciate the comments of J. Elshof and co-workers on our article "High-flow nasal cannula for COVID-19 patients: low risk of bio-aerosol dispersion" [1] and agree that further research is warranted to reduce the risk of virus transmission from infected patients. The presented in vitro data of J. Elshof and co-workers from a model using light detection of smoke dispersion distance and velocity, suggesting that high-flow nasal cannula (HFNC) generates a larger dispersion distance than non-rebreather masks and Venturi masks, is in contrast to reports from Hui et al. [2] using a similar model. Presumably, because the smoke used by J. Elshof and co-workers was larger (0.3–2.5 µm) than that used by Hui et al. \[2\] (≤1 µm), the larger particles dispersed differently. It should be noted that smoke in both models represents only a small fraction of the range of bio-aerosols generated by patients during breathing, speaking, coughing or sneezing [3]. Using the same size airway model, J. Elshof and co-workers observed that the dispersion distance decreased from 71 cm to 25 cm by changing the nasal cannula size from small to large when HFNC flow was set at 30 L·min−1; however, when HFNC flow was set at 60 L·min−1, the medium-size nasal cannula generated a shorter distance than both small and large nasal cannulas. This raises the role of proper fit of prongs to nares and highlights the limitations of modelling. Regardless of the sizes of nasal cannula, the dispersion distance was farther with 60 L·min−1 than 30 L·min−1, which is in line with the results of Hui et al. [2] and may be expected, as higher velocity of the gas will carry exhaled smoke to a further distance. However, this effect of total flow did not occur when testing the Venturi mask. Surprisingly, the Venturi mask with large open holes and a total gas flow of 40 L·min−1 generated a shorter dispersion distance than normal breathing. These inconsistencies are difficult to interpret without comprehensive peer review of extensive methods and results. Whether smoke imaging models truly reflect the natural features of the transportation and dispersion of bio-aerosols generated by patients has not been established and results from these studies should be interpreted cautiously. High-flow nasal cannula does not generate higher risk of bio-aerosol dispersion than conventional oxygen masks <https://bit.ly/2Yn0RQn>
The DEL-1/β3 integrin axis promotes regulatory T cell responses during inflammation resolution
Authors: Xiaofei Li, Alessandra Colamatteo, Lydia Kalafati, Tetsuhiro Kajikawa, Hui Wang, Jong-Hyung Lim, Khalil Bdeir, Kyoung-Jin Chung, Xiang Yu, Clorinda Fusco, Antonio Porcellini, Salvatore De Simone, Giuseppe Matarese, Triantafyllos Chavakis, Veronica De Rosa, George Hajishengallis
Journal: Journal of Clinical Investigation (2020)

FOXP3+CD4+ regulatory T cells (Tregs) are critical for immune homeostasis and respond to local tissue cues, which control their stability and function. We explored here whether developmental endothelial locus-1 (DEL-1), which, like Tregs, increases during resolution of inflammation, promotes Treg responses. DEL-1 enhanced Treg numbers and function at barrier sites (oral and lung mucosa). The underlying mechanism was dissected using mice lacking DEL-1 or expressing a point mutant thereof, or mice with T cell-specific deletion of the transcription factor RUNX1, identified by RNA sequencing analysis of the DEL-1-induced Treg transcriptome. Specifically, through interaction with αvβ3 integrin, DEL-1 promoted induction of RUNX1-dependent FOXP3 expression and conferred stability of FOXP3 expression upon Treg restimulation in the absence of exogenous TGF-β1. Consistently, DEL-1 enhanced the demethylation of the Treg-specific demethylated region (TSDR) in the mouse Foxp3 gene and the suppressive function of sorted induced Tregs. Similarly, DEL-1 increased RUNX1 and FOXP3 expression in human conventional T cells, promoting their conversion into induced Tregs with increased TSDR demethylation, enhanced stability, and suppressive activity. We thus uncovered a DEL-1/αvβ3/RUNX1 axis that promotes Treg responses at barrier sites and offers therapeutic options for modulating inflammatory/autoimmune disorders.
Augmentation of radiation response with the VEGFR-tyrosine kinase inhibitor ZD6474
Authors: Tien Hoang, Shyh-Min Huang, Eric Armstrong, Paul M. Harari
Journal: Cancer Research (2004)

4138  BACKGROUND. Lung cancer is the leading cause of cancer death in the US. In this study, we perform preclinical studies to investigate a novel molecular approach in treatment of non-small cell lung cancer (NSCLC) by combining radiation with ZD6474, a small molecule vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI). We hypothesize that enhanced tumor control may be achieved by simultaneously targeting tumor (radiation) and tumor vasculature (ZD6474). METHODS. A series of in vitro assays were performed to characterize specific cellular and molecular effects of the investigational approach in NSCLC cell lines (H226 and A549) and endothelial cells (HUVECs). In vivo experiments in athymic mice bearing H226 and A549 xenografts were carried out to evaluate the combined molecular approach of targeting both tumor and vasculature. RESULTS. ZD6474 induced a dose-dependent inhibition of HUVEC growth in culture and inhibited the capillary-like network formation in endothelial cells in vitro angiogenesis assay. ZD6474 also induced a dose-dependent growth inhibition of H226 and A549 cell lines. Flow cytometry analysis using propidium iodide staining demonstrated that ZD6474 induced cell cycle arrest with accumulation of cells in G1 phase and reduction of cells in S phase, while radiation (XRT) arrested cells in G2/M. The combination of ZD6474 and XRT further enhanced G2/M cell cycle arrest and reduced cell population in S phase. In vivo experiments with athymic mice bearing H226 and A549 xenografts (control, ZD6474, XRT and ZD6474/XRT) revealed that the combination of ZD6474 plus XRT resulted in enhanced anti-tumor activity over that achieved with single modality therapy. CONCLUSIONS. Systemic administration of the VEGFR-TKI ZD6474 augments radiation response in NSCLC xenografts. In vitro studies suggest that ZD6474 provides anti-angiogenic and anti-tumor effects. This dual action may reflect the capacity of ZD6474 to influence both VEGFR signaling in endothelial cells and EGFR signaling in tumor cells. Studies which further characterize VEGFR/EGFR mechanisms of action and activity using ZD6474 in combination with radiation will be presented.