tbuckley/cabot-search huggingface dataset:
To Err Is Human, to Apologize Is Hard
Authors: Thalia Margalit Krakower
Journal: JAMA (2021)

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Anti-Immigrant Rhetoric and Policy as Manifestations of Structural Racism—Implications for Advancing Health Equity
Authors: Nadia Islam, Naheed Ahmed
Journal: JAMA Network Open (2021)

Elizabeth A. Samuels, MD, MPH, MHS; Lilla Orr, MA; Elizabeth B. White, BA; Altaf Saadi, MD, MSc; Aasim I. Padela, MD, MSc; Michael Westerhaus, MD, MA; Aarti D. Bhatt, MD; Pooja Agrawal, MD, MPH; Dennis Wang, MD, MPH; Gregg Gonsalves, PhD
The use of online visual analogue scales in idiopathic pulmonary fibrosis
Authors: Catharina C. Moor, Remy L.M. Mostard, Jan C. Grutters, Paul Bresser, Marlies S. Wijsenbeek
Journal: European Respiratory Journal (2021)

Idiopathic pulmonary fibrosis (IPF) is a progressive, deadly disease with a major impact on the lives of patients [1]. Symptom burden and quality of life (QoL) can be assessed with patient-reported outcome measures (PROMs). In the past decade, PROM use was increasingly advocated to capture the impact of treatments and interventions on patients' symptoms and wellbeing [2]. PROMs are often lengthy, on paper, and with difficult scoring systems, hampering direct use in clinical practice [2]. Thus, there is a need for easy-to-use PROMs in IPF and other interstitial lung diseases (ILDs), both for clinical trials and daily practice. The visual analogue scale is a valid and reliable tool to assess symptoms over time in IPF. Because of their simplicity, visual analogue scales have the potential to be used for systematic evaluation of disease course in trials and daily practice. <https://bit.ly/3BuxJsf>
Statin-mediated inhibition of RAS prenylation activates ER stress to enhance the immunogenicity of KRAS mutant cancer
Authors: Gi-Hoon Nam, Minsu Kwon, Hanul Jung, Eunbyeol Ko, Seong A Kim, Yoonjeong Choi, Su Jeong Song, Seohyun Kim, Yeji Lee, Gi Beom Kim, Jihoon Han, Jiwan Woo, Yakdol Cho, Cherlhyun Jeong, Seung-Yoon Park, Thomas M. Roberts, Yong Beom Cho, In-San Kim
Journal: Journal for ImmunoTherapy of Cancer (2021)

Statins preferentially promote tumor-specific apoptosis by depleting isoprenoid such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate. However, statins have not yet been approved for clinical cancer treatment due, in part, to poor understanding of molecular determinants on statin sensitivity. Here, we investigated the potential of statins to elicit enhanced immunogenicity of KRAS-mutant (KRASmut) tumors.The immunogenicity of treated cancer cells was determined by western blot, flow cytometry and confocal microscopy. The immunotherapeutic efficacy of mono or combination therapy using statin was assessed in KRASmut tumor models, including syngeneic colorectal cancer and genetically engineered lung and pancreatic tumors. Using NanoString analysis, we analyzed how statin influenced the gene signatures associated with the antigen presentation of dendritic cells in vivo and evaluated whether statin could induce CD8+ T-cell immunity. Multiplex immunohistochemistry was performed to better understand the complicated tumor-immune microenvironment.Statin-mediated inhibition of KRAS prenylation provoked severe endoplasmic reticulum (ER) stress by attenuating the anti-ER stress effect of KRAS mutation, thereby resulting in the immunogenic cell death (ICD) of KRASmut cancer cells. Moreover, statin-mediated ICD enhanced the cross-priming ability of dendritic cells, thereby provoking CD8+ T-cell immune responses against KRASmut tumors. Combination therapy using statin and oxaliplatin, an ICD inducer, significantly enhanced the immunogenicity of KRASmut tumors and promoted tumor-specific immunity in syngeneic and genetically engineered KRASmut tumor models. Along with immune-checkpoint inhibitors, the abovementioned combination therapy overcame resistance to PD-1 blockade therapies, improving the survival rate of KRASmut tumor models.Our findings suggest that KRAS mutation could be a molecular target for statins to elicit potent tumor-specific immunity.
Bispecific Antibodies with Native Human IgG Structure As Mimetics for FVIII Activity
Authors: Sabine Knappe, Nicolas Fischer, Patrice Robert Douillard, Rudolf Hartmann, Gerald Schrenk, Ulla Ravn, Giovanni Magistrelli, Franck Gueneau, Gerard Didelot, Krzysztof Masternak, Marie Kosco-Vilbois, Friedrich Scheiflinger, Michael Dockal
Journal: Blood (2017)
PREVENTION OF HEMORRHAGIC CYSTITIS AFTER CYCLOPHOSPHAMIDE - RESPONSE
Authors: Lj Loescher, Fl Meyskens
Journal: Annals of Internal Medicine (1990)

increase the risk and severity of their overlapping toxicities, including cystitis. Mary V. Reiling, PharmD St. Jude Children's Research Center Memphis, TN 38101-0318 References l. Loescher W , Welch·MtCattrey DW, Leigh SA, Holfman 8 , Meyskens FL. Surviving adult cancers. Part l : ph ysiologic effects. Ann Intern Correction: Prevention of Hemorrhagic Cystitis after Cyclophosphamide To the Editor: In the urologic effects section (page 418, sec- ond column, first sentence) of the review on surviving adult cancers (I), it is erroneously stated that ifosfamide may pre- vent the occurrence of cystitis after cyclophosphamide admin- istration. l fosfamide is an antineoplastic agent that is a struc- tural isomer of cyclophosphamide. Like cyclophosphamide, it can induce hemorrhagic cystiti~. presumably by the same mechanism (that is, liberation of acrolein in the bladder) (2). Cystitis induced by e ither of these oxazaphosphorines can be prevented l:>y co-administration of mesna (sodium 2-mercapto- ethanesulphonate), a compound that increases free thiol con- centrations in the bladder, which can bind to and detoxify acrolein (3). Mesna is now available commercially in the United States. The authors may have intended to write that mesna can be given with cyclophosphamide to prevent hemorrhagic cystitis. There is no clinical indication for the co-administration of ifosfamide a nd cyclophosphamide, as this would most likely M ed. 1989;111:411 -32. 2. ZaJ,.pskl M, Ba ker LH. Ifosfamide. J Nari Cancer Inst. 1988;80: 3. Shaw I. Mesna and oxauphosphorine cancer chemotherapy. Cancer Trear R eY. 1987;14:359~. Jn response: We agree that giving mesna (not ifosfamide) with cyclophospha.mide can prevent cystitis and that there is no indication for concomitant use of ifosfamide and cyclophos- phamide, which both cause cystitis. There are additional ref- erences related to this issue (I , 2). Lois J. Loescher, MS, RN The University of Arizona College of Medicine Tucson, AZ 85724 Frank L. Meyskens Jr, MD University of California-lrvlne Cancer Center Orange, CA 92668 Rderen I. Schccf W, Kltln HO, Brock N, ti al. Controlled clinical studies with an antidote agains1 the urotoxicity of oxazaphosphorines: preliminary results. Cancer Trent R'P· 1979;63:SOl-5. 2. Shaw IC, Graham Ml. Mcsna-a short review. Cancer Treat Rev. IS April 1990 • A11rtals of Internal Medicine • Volume J 12 • Number 8
IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC
Authors: Mark A. Socinski, Makoto Nishio, Robert M. Jotte, Federico Cappuzzo, Francisco Orlandi, Daniil Stroyakovskiy, Naoyuki Nogami, Delvys Rodríguez-Abreu, Denis Moro-Sibilot, Christian A. Thomas, Fabrice Barlesi, Gene Finley, Shengchun Kong, Anthony Lee, Shelley Coleman, Wei Zou, Mark McCleland, Geetha Shankar, Martin Reck
Journal: Journal of Thoracic Oncology (2021)

IntroductionWe report the final overall survival (OS) analyses of atezolizumab-carboplatin-paclitaxel (ACP [experimental arm]) and OS data with approximately 39.8 months of median follow-up with atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP) versus bevacizumab-carboplatin-paclitaxel (BCP) in chemotherapy-naive patients with metastatic nonsquamous NSCLC in the phase 3 IMpower150 study (NCT02366143).MethodsIn this randomized, open-label study (N = 1202), coprimary end points included investigator-assessed progression-free survival and OS in intention-to-treat (ITT) wild-type (WT; no EGFR or ALK alterations) patients. Secondary and exploratory end points included OS in ITT and programmed death-ligand 1 (PD-L1) subgroups defined by the VENTANA SP142 and SP263 immunohistochemistry assays.ResultsAt the final analysis with ACP versus BCP (data cutoff: September 13, 2019; minimum follow-up: 32.4 mo), ACP had numerical, but not statistically significant, improvements in OS (ITT-WT: median OS = 19.0 versus 14.7 mo; hazard ratio = 0.84; 95% confidence interval: 0.71–1.00). OS benefit was sustained with ABCP versus BCP (ITT-WT: 19.5 versus 14.7 mo; hazard ratio = 0.80; 95% confidence interval: 0.67–0.95). Exploratory analyses in the SP142-defined PD-L1 subgroups revealed longer median OS with ABCP and ACP versus BCP in PD-L1–high and PD-L1–positive subgroups; in the PD-L1–negative subgroups, median OS was similar with ACP and ABCP versus BCP. Safety was consistent with that in earlier analyses (data cutoff: January 22, 2018).ConclusionsAt the final IMpower150 OS analysis, ACP had numerical, but not statistically significant, OS improvement versus BCP. Updated data with an additional 20 months of follow-up revealed continued OS improvement with ABCP versus BCP in all patients.
Translation, cross-cultural adaptation, reliability, and validity of the Turkish version of the Duke Activity Status Index in patients with pulmonary hypertension
Authors: R. Mustafaoglu, R. Demir, G.K. Aslan, U.Y. Sinan, M. Zeren, A. Yildiz, M.S. Kucukoglu
Journal: Pulmonology (2021)

In patients with pulmonary hypertension (PH), shortness of breath, fatigue, chest pain, and syncope limit exercise capacity. Exercise tests are often time-consuming, expensive, and some patients may not be able to perform such procedures and they are also difficult to apply in the studies including large samples. The aim of this study was to translate and culturally adapt the DASI into Turkish and to investigate its reliability and validity in patients with PH. The final Turkish version of the DASI questionnaire was applied to 109 clinically stable patients with a diagnosis of PH. Exercise capacity of the patients was determined by maximal VO 2 achieved in the 6-minute walk test (6MWT) and quality of life by the EmPHasis-10 questionnaire. Cronbach alpha (internal consistency) was used to assess the questionnaire's reliability. The validity assessment was performed by using Spearman correlation. Internal consistency of the DASI was high (Cronbach's alpha = 0.99) and the test-retest reliability was excellent (ICC = 0.98). Validity was supported by significant correlations of DASI-VO 2 scores with estimated VO 2 (6MWT) scores (r = 0.58, p < 0.0001) and EmPHasis-10 (= −0.62, p < 0.0001). No floor or ceiling effect was present for the questionnaire. The Turkish version of the culturally adapted DASI questionnaire was found to be a valid and reliable assessment tool. It is a rapidly administered, simple-toscore questionnaire for assessing the functional ability of individuals with PH. The use of the DASI to assess exercise capacity in patients with PH may assist researchers and clinicians detecting functional impairment in these patients.
A Phase I Study of the Combination of Pexidartinib and Sirolimus to Target Tumor-Associated Macrophages in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors
Authors: Gulam A. Manji, Brian A. Van Tine, Shing M. Lee, Alexander G. Raufi, Ilenia Pellicciotta, Angela C. Hirbe, Jaya Pradhan, Andrew Chen, Raul Rabadan, Gary K. Schwartz
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To evaluate the safety and tolerability in phase I first-in-human combination therapy with pexidartinib, an inhibitor of colony-stimulating factor-1 receptor, and sirolimus, an mTOR inhibitor, to target tumor-associated macrophage (TAM) polarization in soft tissue sarcomas (STS). Patients and Methods: This multicenter phase I study used the time-to-event continual reassessment method (TITE-CRM) to study the combination of sirolimus, doses ranging from 2 to 6 mg, with pexidartinib, doses ranging from 600 to 1,000 mg, both provided continuously on a 28-day cycle, in patients with advanced sarcoma. A total of 24 patients [8 malignant peripheral nerve sheath tumor, 3 tenosynovial giant cell tumor (TGCT), 5 leiomyosarcoma, and 8 with other sarcoma subtypes] were enrolled. The median age was 46 years, 56% were male, and 61% had &amp;gt;2 prior lines of therapy. Results: The recommended phase II dose was 2 mg of sirolimus combined with 1,000 mg of pexidartinib daily. Of the 18 evaluable subjects, 5 experienced dose-limiting toxicities (2 elevated aspartate aminotransferase/alanine aminotransferase, 2 elevated sirolimus trough levels, and 1 grade 5 dehydration). Most common grade 2 or higher treatment-related adverse events included anemia, fatigue, neutropenia, and lymphopenia. Clinical benefit was observed in 12 of 18 (67%) evaluable subjects with 3 partial responses (all in TGCT) and 9 stable disease. Tissue staining indicated a decreased proportion of activated M2 macrophages within tumor samples with treatment. Conclusions: Pexidartinib can be safely administered with sirolimus. These findings support further investigation of this combination to determine clinical efficacy. Clinicaltrials.gov identifier NCT02584647.
Variably methylated retrotransposons are refractory to a range of environmental perturbations
Authors: Tessa M. Bertozzi, Jessica L. Becker, Georgina E. T. Blake, Amita Bansal, Duy K. Nguyen, Denise S. Fernandez-Twinn, Susan E. Ozanne, Marisa S. Bartolomei, Rebecca A. Simmons, Erica D. Watson, Anne C. Ferguson-Smith
Journal: Nature Genetics (2021)
MO3-1 Pneumonitis is common in patients with sequential nivolumab and cetuximab treatment
Authors: Makoto Arai, Meng Meng Fan, Akinobu Tawada, Chiaki Imai, Hiromi Saeki, Keiichi Koshizuka, Syuji Yonekura, Toyoyuki Hanazawa, Yuichi Takiguchi
Journal: Annals of Oncology (2021)
Molecular Pathways Associated with Ibrutinib Resistance in Mantle Cell Lymphoma
Authors: Liang Zhang, Krystle Nomie, Shaojun Zhang, Yang Liu, Hui Guo, Shengjian Huang, Jeffrey Wang, Elyse Lopez, Hui Zhang, Elizabeth A Lorence, Maria Merolle, Swathi Balaji, Makhdum Ahmed, Changying Jiang, Linghua Wang, Michael Wang
Journal: Blood (2017)
The immunodominant antibody response to Zika virus NS1 protein is characterized by cross-reactivity to self
Authors: Cecilia B. Cavazzoni, Vicente B.T. Bozza, Tostes C.V. Lucas, Luciana Conde, Bruno Maia, Luka Mesin, Ariën Schiepers, Jonatan Ersching, Romulo L.S. Neris, Jonas N. Conde, Diego R. Coelho, Tulio M. Lima, Renata G.F. Alvim, Leda R. Castilho, Heitor A. de Paula Neto, Ronaldo Mohana-Borges, Iranaia Assunção-Miranda, Alberto Nobrega, Gabriel D. Victora, Andre M. Vale
Journal: The Journal of Experimental Medicine (2021)

Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue and Zika virus infections have been linked to antibody-mediated autoimmune disorders, including Guillain-Barré syndrome. A unique feature of flaviviruses is the secretion of nonstructural protein 1 (NS1) by infected cells. NS1 is highly immunogenic, and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen associated with the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1. We demonstrate the presence of self-reactive clones in germinal centers after both infection and immunization, some of which present cross-reactivity with NS1. Sequence analysis of anti-NS1 B cell clones showed sequence features associated with pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV-associated autoimmune manifestations.
Letter by Singh et al Regarding Article, “Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF)”
Authors: Jagdeep S. Singh, Allan D. Struthers, Chim C. Lang
Journal: Circulation (2021)
Suicide Attempts of Muslims Compared With Other Religious Groups in the US
Authors: Rania Awaad, Osama El-Gabalawy, Ebony Jackson-Shaheed, Belal Zia, Hooman Keshavarzi, Dalia Mogahed, Hamada Altalib
Journal: JAMA Psychiatry (2021)

Suicide Attempts of Muslims Compared With Other Religious Groups in the USSuicide is one of the leading causes of death and has steadily increased throughout the past 2 decades. 1 Religious affiliation may be associated with a lower risk for both suicide attempt and death through multiple mechanisms, including the promotion of social support, personal empowerment, healthy lifestyle, and commitment to religious life-preserving morals. 2 In the US, Muslim individuals represent a religious minority group who are vulnerable to religious discrimination but may access mental health services more infrequently than other groups.We compare the prevalence of suicide attempts among Muslim adults compared with adults of other faith communities in the US. Methods | Participants completed the 2019 Institute for SocialPolicy and Understanding national community-based survey 3 conducted over landline, cell phone, and online by Social Science Research Solutions during January 2019.Muslim and Jewish participants were oversampled, and other religious groups were weighted to provide nationally representative and projectable estimates of the US adult population 18 years and older.The eMethods in the Supplement include a description of sample design, survey administration, and weighting procedures.The Stanford University institutional review board exempted the study from ethical review because it was an analysis of deidentified poll data.Participant demographics were collected using selfreported items.Participants were asked to self-identify their religion from the following categories: agnostic, atheist, Buddhist, Catholic, Christian, do not know, Hindu, Jewish, Mormon, Muslim, no religion, Orthodox, Protestant, something else, or Unitarian (Universalist).Participants were also asked to self-identify their race and ethnicity using the following categories: African American, Arab, Asian/Chinese/ Japanese/Indian/Pakistani, Native American/American Indian/ Alaska Native, Native Hawaiian/Pacific Islander, mixed, Hispanic, White, or other.Lifetime suicide attempt was assessed with a question adapted from the Columbia-Suicide Severity Rating Scale: "Have you ever tried to do anything to try to kill yourself or make yourself not alive anymore?" 4 Descriptive statistics and cross-tabulations were used to categorize and compare the frequency of the chosen study characteristics of participants.Univariate and multivariate logistic regression analyses were performed using Stata version 15 (StataCorp) to calculate unadjusted and adjusted odds
Deformation analysis of surface and bronchial structures in intraoperative pneumothorax using deformable mesh registration
Authors: Megumi Nakao, Kotaro Kobayashi, Junko Tokuno, Toyofumi Chen-Yoshikawa, Hiroshi Date, Tetsuya Matsuda
Journal: Medical Image Analysis (2021)

The positions of nodules can change because of intraoperative lung deflation, and the modeling of pneumothorax-associated deformation remains a challenging issue for intraoperative tumor localization. In this study, we introduce spatial and geometric analysis methods for inflated/deflated lungs and discuss heterogeneity in pneumothorax-associated lung deformation. Contrast-enhanced CT images simulating intraoperative conditions were acquired from live Beagle dogs. The images contain the overall shape of the lungs, including all lobes and internal bronchial structures, and were analyzed to provide a statistical deformation model that could be used as prior knowledge to predict pneumothorax. To address the difficulties of mapping pneumothorax CT images with topological changes and CT intensity shifts, we designed deformable mesh registration techniques for mixed data structures including the lobe surfaces and the bronchial centerlines. Three global-to-local registration steps were performed under the constraint that the deformation was spatially continuous and smooth, while matching visible bronchial tree structures as much as possible. The developed framework achieved stable registration with a Hausdorff distance of less than 1 mm and a target registration error of less than 5 mm, and visualized deformation fields that demonstrate per-lobe contractions and rotations with high variability between subjects. The deformation analysis results show that the strain of lung parenchyma was 35% higher than that of bronchi, and that deformation in the deflated lung is heterogeneous.
An Ancient Clade of <i>Penelope</i>-Like Retroelements with Permuted Domains Is Present in the Green Lineage and Protists, and Dominates Many Invertebrate Genomes
Authors: Rory J Craig, Irina A Yushenova, Fernando Rodriguez, Irina R Arkhipova
Journal: Molecular Biology and Evolution (2021)

Abstract Penelope-like elements (PLEs) are an enigmatic clade of retrotransposons whose reverse transcriptases (RTs) share a most recent common ancestor with telomerase RTs. The single ORF of canonical endonuclease (EN)+ PLEs encodes RT and a C-terminal GIY–YIG EN that enables intrachromosomal integration, whereas EN− PLEs lack EN and are generally restricted to chromosome termini. EN+ PLEs have only been found in animals, except for one case of horizontal transfer to conifers, whereas EN− PLEs occur in several kingdoms. Here, we report a new, deep-branching PLE clade with a permuted domain order, whereby an N-terminal GIY–YIG EN is linked to a C-terminal RT by a short domain with a characteristic CxC motif. These N-terminal EN+ PLEs share a structural organization, including pseudo-LTRs and complex tandem/inverted insertions, with canonical EN+ PLEs from Penelope/Poseidon, Neptune, and Nematis clades, and show insertion bias for microsatellites, but lack canonical hammerhead ribozyme motifs. However, their phylogenetic distribution is much broader. The Naiads, found in numerous invertebrate phyla, can reach tens of thousands of copies per genome. In spiders and clams, Naiads independently evolved to encode selenoproteins containing multiple selenocysteines. Chlamys, which lack the CCHH motif universal to PLE ENs, occur in green algae, spike mosses (targeting ribosomal DNA), and slime molds. Unlike canonical PLEs, RTs of N-terminal EN+ PLEs contain the insertion-in-fingers domain (IFD), strengthening the link between PLEs and telomerases. Additionally, we describe Hydra, a novel metazoan C-terminal EN+ clade. Overall, we conclude that PLE diversity, taxonomic distribution, and abundance are comparable with non-LTR and LTR-retrotransposons.