tbuckley/cabot-search huggingface dataset:
Response of pleura to surgical trauma in rabbits
Authors: M. L. Dalton
Journal: JAMA (1966)

Knowledge of the morphological response of the pleura to trauma is of interest to the anatomist and the pathologist as well as the thoracic surgeon. Most research efforts have focused upon the alteration of pleural absorptive properties after instillation of various irritants. In 1895, Leathes and Starling<sup>1</sup>reported on the effects of scalding the pleura with hot water or sodium fluoride. Even though the pleura appeared to be opaque, its absorptive power remained unaltered at two hours. Later, Corper<sup>2</sup>reported that absorption of particulate matter by the pleura was delayed by treatment with hydrochloric acid. In 1934, Brock<sup>3</sup>produced pleuritis in rabbits by injecting turpentine and noted that this caused a constant increase in rate of absorption. In one of the few early studies employing histological techniques, Young<sup>4</sup>noted that various electrolyte solutions induced mesothelial hyperplasia and fibroblast proliferation in the submesothelial layer of the pleura.
Intratumoral IL-1R1 expression delineates a distinctive molecular subset with therapeutic resistance in patients with gastric cancer
Authors: Puran Zhang, Yun Gu, Hanji Fang, Yifan Cao, Jieti Wang, Hao Liu, Heng Zhang, He Li, Hongyong He, Ruochen Li, Chao Lin, Jiejie Xu
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background With the essential role of interleukin-1 signaling in cancer-related inflammation, IL-1R1, the main receptor for both IL-1α and IL-1β, demonstrated therapeutic potential in several types of cancer, which has been put into clinical trials. However, the expression profile and critical role of IL-1R1 in gastric cancer (GC) remain obscure. This study aimed to investigate the prognostic significance of IL-1R1 expression and its predictive value for chemotherapy and immunotherapy in GC. Methods The study enrolled three cohorts, consisting of 409 tumor microarray specimens of GC patients from Zhongshan Hospital, 341 transcriptional data from The Cancer Genome Atlas , and 45 transcriptional data from patients treated with pembrolizumab. IL-1R1 mRNA expression was directly acquired from public datasets, and we also detected IL-1R1 protein expression on tumor microarray by immunohistochemistry. Finally, the associations of IL-1R1 expression with clinical outcomes, immune contexture, and genomic features were analyzed. Results High IL-1R1 expression predicted poor prognosis and inferior responsiveness to both 5-fluorouracil-based adjuvant chemotherapy (ACT) and immune checkpoint blockade (ICB). IL-1R1 fostered an immunosuppressive microenvironment characterized by upregulated M2 macrophages and exhausted CD8 + T cells infiltration. Moreover, the expression of IL-1R1 was intrinsically linked to genomic alterations associated with targeted therapies in GC. Conclusions IL-1R1 served as an independent prognosticator and predictive biomarker for ACT and ICB in GC. Furthermore, IL-1R1 antagonists could be a novel agent alone or combined with current therapeutic strategies in GC.
Cell-Free DNA to Detect Heart Allograft Acute Rejection
Authors: Sean Agbor-Enoh, Palak Shah, Ilker Tunc, Steven Hsu, Stuart Russell, Erika Feller, Keyur Shah, Maria E. Rodrigo, Samer S. Najjar, Hyesik Kong, Mehdi Pirooznia, Ulgen Fideli, Alfiya Bikineyeva, Argit Marishta, Kenneth Bhatti, Yanqin Yang, Cedric Mutebi, Kai Yu, Moon Kyoo Jang, Charles Marboe, Gerald J. Berry, Hannah A. Valantine
Journal: Circulation (2021)

Background: After heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker—percent donor-derived cell-free DNA (%ddcfDNA)—for detection of AR in cardiac transplant recipients. Methods: This multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis. Results: The study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1–23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%–0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31–0.83%], versus 0.03% [IQR, 0.01–0.14%]; P &lt;0.001). The rise was detected 0.5 and 3.2 months before histopathologic diagnosis of ACR and AMR. The area under the receiver operator characteristic curve for AR was 0.92. A 0.25%ddcfDNA threshold had a negative predictive value for AR of 99% and would have safely eliminated 81% of EMBx. In addition, %ddcfDNA showed distinctive characteristics comparing AMR with ACR, including 5-fold higher levels (AMR ≥2, 1.68% [IQR, 0.49–2.79%] versus ACR grade ≥2R, 0.34% [IQR, 0.28–0.72%]), higher area under the receiver operator characteristic curve (0.95 versus 0.85), higher guanosine-cytosine content, and higher percentage of short ddcfDNA fragments. Conclusions: We found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02423070.
A simple additive staging system for newly diagnosed multiple myeloma
Authors: Nadine H. Abdallah, Moritz Binder, S. Vincent Rajkumar, Patricia T. Greipp, Prashant Kapoor, Angela Dispenzieri, Morie A. Gertz, Linda B. Baughn, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, David Dingli, Ronald S. Go, Yi L. Hwa, Amie L. Fonder, Miriam A. Hobbs, Yi Lin, Nelson Leung, Taxiarchis Kourelis, Rahma Warsame, Mustaqeem A. Siddiqui, Robert A. Kyle, P. Leif Bergsagel, Rafael Fonseca, Rhett P. Ketterling, Shaji K. Kumar
Journal: Blood Cancer Journal (2022)

Risk stratification in multiple myeloma is important for prognostication, patient selection for clinical trials, and comparison of treatment approaches. We developed and validated a staging system that incorporates additional FISH abnormalities not included in the R-ISS and reflects the additive effects of co-occurring high-risk disease features. We first evaluated the prognostic value of predefined cytogenetic and laboratory abnormalities in 2556 Mayo Clinic patients diagnosed between February 2004 and June 2019. We then used data from 1327 patients to develop a risk stratification model and validated this in 502 patients enrolled in the MMRF CoMMpass study. On multivariate analysis, high-risk IgH translocations [risk ratio (RR): 1.7], 1q gain/amplification (RR: 1.4), chromosome17 abnormalities (RR: 1.6), ISS III (RR: 1.7), and elevated LDH (RR: 1.3) were independently associated with decreased overall survival (OS). Among 1327 evaluable patients, OS was 11.0 (95% CI: 9.2-12.6), 7.0 (95% CI: 6.3-9.2), and 4.5 (95% CI: 3.7-5.2) years in patients with 0 (stage I), 1 (stage II), and ≥2 (stage III) high-risk factors, respectively. In the MMRF cohort, median OS was 7.8 (95% CI: NR-NR), 6.0 (95% CI: 5.7-NR), and 4.3 (95% CI: 2.7-NR) years in the 3 groups, respectively (P < 0.001). This 5-factor, 3-tier system is easy to implement in practice and improves upon the current R-ISS.
Vaccination against COVID-19 Leads to Enhanced Immunity Despite Infection History
Authors: Kelly O'Shea, Charles Schuler, Carmen Gherasim, David Manthei, Jesse Chen, Cristyn Zettel, Jonathan Troost, Andrew Kennedy, Andrew Tai, Donald Giacherio, Riccardo Valdez, James Baldwin, James Baker
Journal: Journal of Allergy and Clinical Immunology (2022)
Article on Microsatellite Instability and Colorectal Cancer Prognosis
Journal: Clinical Cancer Research (2006)

In the article on microsatellite instability and colorectal cancer prognosis in the December 1, 2005 issue of Clinical Cancer Research, [Figs. 3][1] and [4][2] were inaccurate. The correct figures appear here. ![Fig. 3.][3]</img> Fig. 3. Kaplan-Meier curves of 5-year-specific survival of
Letter: Agoraphobia.
Journal: BMJ (1974)

20-month-old baby, who developed a roseolar rash at the same time.Among the types of virus isolated from throat or faecal specimens from my patients at the time of their roseolar reactions were adenovirus 2, 3, and 14, echovirus 9, 11, 27, and 30, Cox- sackie A6 and 9, Coxsackie B2, 4, and 5, and parainfluenza type 1.Most children who received the earlier, less attenuated, measles virus vaccines developed a roseolar reaction as their fever subsided.This rash differed from that of measles in two respects: it began on the trunk instead of the face and it appeared as the tempera- ture dropped and not at the start of the secondary fever.Children who undergo either the fast ("one-spike") or the slow (roseolar) febrile immunizing reaction are as a rule otherwise healthy and free from any localizing signs of infection in the ears, nose, throat, chest, abdomen, or urine.The younger the child, the higher is the temperature likely to be.Presumably the roseolar rash is due to virus particles being neutralized in the skin at the end of a period of viraemia.Perhaps viraemia does not occur in the "one-spike" fever and so no rash appears.Please may sixth disease now disappear from the next edition of textbooks?-Iam, etc., G. I.
Contents
Authors: S Stratton, M Barton, J Petersen, V Ratziu, M Buti, H Janssen, A Brown, P Lampertico, J Schollmeyer, F Zoulim, H Wedemeyer, M Sterneck, T Berg, C Sarrazin, M Lutgehetmann, P Buggisch, T Asselah, S De Muynck, P Broe ¨t, J Masliah-Planchon, M Blanluet, I Bie, ` Che, M Lapalus, M Martinot-Peignoux, O Lada, E Estrabaud, Q Zhang, A Ray, D Vidaud, M.-P Ripault, N Boyer, P Bedossa, D Valla, M Vidaud, P Marcellin, -S Wong, -H Wong, -W Chu, -L Chim, A Ong, -W Yeung, -L Yiu, -T Chu, H.-Y Chan, J Woo, -L Chan, -Y Chan, F Ratziu, V Byrnes, A Miller, D Lowry, E Hill, C Weinstein, D Alsop, R Lenkinski, N Afdhal, C Howell, A Gorden, K Ryan, A Thompson, C Ibrahim, M Fried, J Mchutchison, K Shianna, D Goldstein, A Shuldiner, B Mitchell, R Myers, G Pomier-Layrargues, R Kirsch, A Pollett, M Beaton, M Levstik, A Duarte-Rojo, D Wong, P Crotty, M Elkashab, A Ca ´rdenas, P Gine, P Marotta, F Czerwiec, J Oyuang, M Guevara, E Loggi, L Micco, G Ercolani, A Cucchetti, F Bihl, G Grazi, S Gitto, A Bontadini, M Bernardi, P Grossi, A Nanni Costa, A Pinna, C Brander, P Andreone, K Nakagawa, N Tanaka, M Morita, A Sugioka, S.-I Miyagawa, F Gonzalez, T Aoyama, H Huynh, P Chow, W Tai, S Choo, A Chung, H Ong, K Soo, R Ong, R Linnartz, M Shi, M Kurosaki, N Hiramatsu, M Sakamoto, Y Suzuki, M Iwasaki, A Tamori, K Matsuura, S Kakinuma, F Sugauchi, N Sakamoto, M Nakagawa, N Izumi
Journal: Journal of Hepatology (2012)
Essential diagnostics: mind the gap
Authors: None The Lancet Global Health
Journal: The Lancet Global Health (2021)

This month, WHO released the latest update to its Essential Medicines List. First published in 1977, the list documents all medicines considered essential to address key public health needs globally. It was not until 2018 that WHO published its first Essential Diagnostics List (EDL). Described as the "Cinderella of health systems" in a Comment accompanying The Lancet's 2018 three-part Series on Pathology and Laboratory Medicine (PALM) in low-income and middle-income countries (LMICs), diagnostics are a neglected area of global health.
Surgical therapy of peri‐implantitis
Authors: Frank Schwarz, Søren Jepsen, Karina Obreja, Maria Elisa Galarraga‐Vinueza, Ausra Ramanauskaite
Journal: Periodontology 2000 (2022)

Abstract Peri‐implantitis is caused by a bacterial challenge; therefore, anti‐infective treatment strategies should be employed to manage the disease. As nonsurgical approaches demonstrate limited efficacy in most cases of peri‐implantitis, surgical interventions are often required. Treatment outcomes improve following access flap surgery, with or without adjunctive resective and/or augmentation measures. Whereas nonaugmentative therapies (ie, access flap surgery and resective techniques) primarily aim to resolve inflammation and arrest further disease progression, augmentation approaches also seek to regenerate the bony defect and achieve reosseointegration. Currently, limited evidence supports the superiority of augmentative surgical techniques for peri‐implantitis treatment over nonaugmentation methods, and human histologic evidence for reosseointegration is sparse. For patients involved in regular postoperative maintenance programs, success of peri‐implantitis surgical treatment based on various definitions of success was obtained in over half of the cases after 5‐7 years. Despite surgical treatment, cases of further disease progression that required retreatment or led to implant loss were reported.
Diseases of the Eye.
Journal: JAMA (1898)

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Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue
Authors: Aileen I. Fernandez, Matthew Liu, Andrew Bellizzi, Jane Brock, Oluwole Fadare, Krisztina Hanley, Malini Harigopal, Julie M. Jorns, M. Gabriela Kuba, Amy Ly, Mirna Podoll, Kimmie Rabe, Mary Ann Sanders, Kamaljeet Singh, Olivia L. Snir, T. Rinda Soong, Shi Wei, Hannah Wen, Serena Wong, Esther Yoon, Lajos Pusztai, Emily Reisenbichler, David L. Rimm
Journal: JAMA Oncology (2022)

Trastuzumab deruxtecan (T-DXd) has shown efficacy in patients with breast cancer with ERBB2 immunohistochemistry (IHC) scores of 1+ or 2+ but not 0 as read in central pathology laboratories. The drug is currently being tested in large randomized clinical trials with registration intent for this patient population. To determine the suitability of the current standard ERBB2 IHC assays to select patients with low ERBB2 positivity for treatment with T-DXd. Assessment of data from College of American Pathologists surveys and assessment of analytic data from a Yale University-based study of concordance of 18 pathologists reading 170 breast cancer biopsies. The total survey data set included scores over 2 years from 1391 to 1452 laboratories of 40 ERBB2 cores from each laboratory (20 cores twice a year for a total of 80). College of American Pathologists surveys show that 19% of cases read by the laboratories generate results with less than or equal to 70% concordance for IHC ERBB2 score 0 vs 1+. When 18 pathologists read the scanned slides from a selected set of breast cancer biopsies using a 4-point scale, there was only 26% concordance between 0 and 1+ compared with 58% concordance between 2+ and 3+. In this study using a current standard ERBB2 IHC assay, the scoring accuracy for ERBB2 IHC in the low range (0 and 1+) was poor. This inaccuracy in the real world could lead to misassignment of many patients for treatment with T-DXd.
WNT as a Driver and Dependency in Cancer
Authors: Marie J. Parsons, Tuomas Tammela, Lukas E. Dow
Journal: Cancer Discovery (2021)

Abstract The WNT signaling pathway is a critical regulator of development and adult tissue homeostasis and becomes dysregulated in many cancer types. Although hyperactivation of WNT signaling is common, the type and frequency of genetic WNT pathway alterations can vary dramatically between different cancers, highlighting possible cancer-specific mechanisms for WNT-driven disease. In this review, we discuss how WNT pathway disruption contributes to tumorigenesis in different organs and how WNT affects the tumor cell and immune microenvironment. Finally, we describe recent and ongoing efforts to target oncogenic WNT signaling as a therapeutic strategy. Significance: WNT signaling is a fundamental regulator of tissue homeostasis and oncogenic driver in many cancer types. In this review, we highlight recent advances in our understanding of WNT signaling in cancer, particularly the complexities of WNT activation in distinct cancer types, its role in immune evasion, and the challenge of targeting the WNT pathway as a therapeutic strategy.
LONG-TERM EFFECTIVENESS AND SAFETY OF BENRALIZUMAB FOR UNCONTROLLED EOSINOPHILIC ASTHMA IN REAL-WORD PRACTICE
Authors: Manuel Risco, Jesus Sotomayor, Paloma Alvarez-Sala, Inmaculada Piorno, Rocio Diaz-Campos, Beatriz Moya, Jesus Fernandez Crespo, Consuelo Fernandez, Ismael GarcÃa Moguel
Journal: Journal of Allergy and Clinical Immunology (2022)
Trabectedin for recurrent WHO grade 2 or 3 meningiomas—Paving the road for new opportunities
Authors: Christopher A Alvarez-Breckenridge, Daniel P Cahill, Priscilla K Brastianos
Journal: Neuro-Oncology (2022)

Meningioma is the most common intracranial malignancy, typically presenting as a benign, slow-growing lesion amenable to surgical resection. However, WHO grade 2 and 3 meningiomas can manifest a starkly different clinical picture with parenchymal invasion, increased rate of growth, cellular atypia, and therapeutic resistance. While surgical resection and postoperative radiation remain the standard of care for newly diagnosed and recurrent grade 2/3 meningiomas, patients frequently do not achieve durable disease control—highlighting an unmet clinical need. While a number of systemic therapies have been proposed in exploratory studies, there remains a critical need to rigorously study systemic agents for patients with recurrent grade 2/3 meningiomas. To date, adequately powered, randomized controlled clinical trials exploring systemic therapies for meningioma have been limited. Mazza et al attempted to enroll patients with recurrent WHO grade I-III meningiomas to explore the utility of hydroxyurea alone or in combination with imatinib.1 However, the trial ended prematurely due to limited patient accrual. Using a similar patient population of WHO grade I-III meningiomas, Ji et al examined the role of mifepristone in a multicenter, prospective, randomized, placebo-controlled phase III trial.2 This was the first randomized controlled study in the setting of recurrent meningiomas; however, its broad inclusion criteria, including WHO grade 1 tumors, limited its applicability to patients with more aggressive histological disease. Moreover, despite the encouraging safety profile, there was no observed clinical benefit. These challenges prompted Kaley et al to systematically analyze published trials exploring medical therapy in surgery- and radiation-refractory meningioma.3 This work highlighted the diverse nature of reported study designs; lack of unified criteria for patient inclusion, tumor progression, and treatment response; and need to report pretreatment tumor growth rate. From this work, the only consistently reported outcome for both WHO grade 1 and WHO grade 2 or 3 meningiomas was progression-free survival (PFS)-6-month rate, highlighting the utility of this historical benchmark endpoint in future clinical trials. Collectively, these results highlighted the critical need for appropriately powered, controlled clinical trials with reported PFS-6, particularly among patients with WHO grade 2-3 meningiomas, who have progressed after local therapies.
The <scp>pan‐JAK</scp> inhibitor delgocitinib in a cream formulation demonstrates dose response in chronic hand eczema in a 16‐week randomized phase <scp>IIb</scp> trial*
Authors: Margitta Worm, Jacob P. Thyssen, Sibylle Schliemann, Andrea Bauer, Vivian Y. Shi, Ben Ehst, Sandra Tillmann, Sofie Korn, Katarina Resen, Tove Agner
Journal: British Journal of Dermatology (2022)

Background Chronic hand eczema (CHE) is a burdensome disease, and new well-documented, safe and efficacious treatments are warranted. In a recent CHE phase IIa trial, the pan-Janus kinase (JAK) inhibitor delgocitinib in an ointment formulation was found to be efficacious and well tolerated. Objectives This trial assessed the dose response, efficacy and safety of delgocitinib cream in CHE. Methods In this double-blind, phase IIb dose-ranging trial, adults with CHE and a recent history of inadequate response or contraindication to topical corticosteroids were randomized to delgocitinib cream 1, 3, 8, 20 mg g–1 or vehicle treatment twice daily for 16 weeks. The primary endpoint was the Investigator’s Global Assessment for CHE (IGA-CHE) treatment success [0 (clear) or 1 (almost clear) with a ≥ two-point improvement from baseline to week 16]. Secondary endpoints were the time to IGA-CHE treatment success and changes in Hand Eczema Severity Index (HECSI); other endpoints were itch and pain numerical rating scale (NRS) scores, and Patient’s Global Assessment (PaGA) at week 16. Results Patients (n = 258) were randomized 1 : 1 : 1 : 1 : 1 to delgocitinib cream 1, 3, 8, 20 mg g–1 or vehicle. A significant dose–response relationship was established for IGA-CHE (P < 0.025). IGA-CHE treatment success at week 16 was achieved in 21.2% (1 mg g–1), 7.8% (3 mg g–1), 36.5% (8 mg g–1), 37.7% (20 mg g–1) and 8.0% (vehicle) of patients. Delgocitinib 8 and 20 mg g–1 showed a treatment effect against vehicle (P < 0.001). Similarly, there were improvements in HECSI, itch and pain NRS scores, and PaGA. Delgocitinib cream was well tolerated with the majority of adverse events being mild or moderate and considered unrelated to treatment. The most frequently reported adverse events were nasopharyngitis (17.3–29.4% in delgocitinib groups vs. 40% in vehicle group), eczema (5.8–11.3% in delgocitinib groups vs. 16.0% in vehicle group) and headache (3.8–11.5% in delgocitinib groups vs. 4.0% in vehicle group). Conclusions In this trial, delgocitinib cream showed a dose–response relationship in terms of efficacy and was well tolerated.