tbuckley/cabot-search huggingface dataset:
Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis
Authors: Yasuyuki Mizutani, Hiroki Kobayashi, Tadashi Iida, Naoya Asai, Atsushi Masamune, Akitoshi Hara, Nobutoshi Esaki, Kaori Ushida, Shinji Mii, Yukihiro Shiraki, Kenju Ando, Liang Weng, Seiichiro Ishihara, Suzanne M. Ponik, Matthew W. Conklin, Hisashi Haga, Arata Nagasaka, Takaki Miyata, Makoto Matsuyama, Tomoe Kobayashi, Tsutomu Fujii, Suguru Yamada, Junpei Yamaguchi, Tongtong Wang, Susan L. Woods, Daniel Worthley, Teppei Shimamura, Mitsuhiro Fujishiro, Yoshiki Hirooka, Atsushi Enomoto, Masahide Takahashi
Journal: Cancer Research (2019)

Cancer-associated fibroblasts (CAF) constitute a major component of the tumor microenvironment. Recent observations in genetically engineered mouse models and clinical studies have suggested that there may exist at least two functionally different populations of CAFs, that is, cancer-promoting CAFs (pCAF) and cancer-restraining CAFs (rCAF). Although various pCAF markers have been identified, the identity of rCAFs remains unknown because of the lack of rCAF-specific marker(s). In this study, we found that Meflin, a glycosylphosphatidylinositol-anchored protein that is a marker of mesenchymal stromal/stem cells and maintains their undifferentiated state, is expressed by pancreatic stellate cells that are a source of CAFs in pancreatic ductal adenocarcinoma (PDAC). In situ hybridization analysis of 71 human PDAC tissues revealed that the infiltration of Meflin-positive CAFs correlated with favorable patient outcome. Consistent herewith, Meflin deficiency led to significant tumor progression with poorly differentiated histology in a PDAC mouse model. Similarly, genetic ablation of Meflin-positive CAFs resulted in poor differentiation of tumors in a syngeneic transplantation model. Conversely, delivery of a Meflin-expressing lentivirus into the tumor stroma or overexpression of Meflin in CAFs suppressed the growth of xenograft tumors. Lineage tracing revealed that Meflin-positive cells gave rise to α-smooth muscle actin-positive CAFs that are positive or negative for Meflin, suggesting a mechanism for generating CAF heterogeneity. Meflin deficiency or low expression resulted in straightened stromal collagen fibers, which represent a signature for aggressive tumors, in mouse or human PDAC tissues, respectively. Together, the data suggest that Meflin is a marker of rCAFs that suppress PDAC progression. SIGNIFICANCE: Meflin marks and functionally contributes to a subset of cancer-associated fibroblasts that exert antitumoral effects.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/20/5367/F1.large.jpg.
Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort
Authors: Anthony P. Khawaja, Sharon Chua, Pirro G. Hysi, Stelios Georgoulas, Hannah Currant, Tomas W. Fitzgerald, Ewan Birney, Fang Ko, Qi Yang, Charles Reisman, David F. Garway-Heath, Chris J. Hammond, Peng T. Khaw, Paul J. Foster, Praveen J. Patel, Nicholas Strouthidis, Denize Atan, Tariq Aslam, Sarah A. Barman, Jenny H. Barrett, Paul Bishop, Peter Blows, Catey Bunce, Roxana O. Carare, Usha Chakravarthy, Michelle Chan, Sharon Y.L. Chua, David P. Crabb, Philippa M. Cumberland, Alexander Day, Parul Desai, Bal Dhillon, Andrew D. Dick, Cathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John E.J. Gallacher, David F. Garway-Heath, Jane Gibson, Dan Gore, Jeremy A. Guggenheim, Chris J. Hammond, Alison Hardcastle, Simon P. Harding, Ruth E. Hogg, Pirro Hysi, Pearse A. Keane, Sir Peng T. Khaw, Anthony P. Khawaja, Gerassimos Lascaratos, Andrew J. Lotery, Tom Macgillivray, Sarah Mackie, Keith Martin, Michelle McGaughey, Bernadette McGuinness, Gareth J. McKay, Martin McKibbin, Danny Mitry, Tony Moore, James E. Morgan, Zaynah A. Muthy, Eoin O’Sullivan, Chris G. Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Jugnoo S. Rahi, Alicja R. Rudnikca, Jay Self, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas Strouthidis, Cathie Sudlow, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Veronique Vitart, Stephen A. Vernon, Ananth C. Viswanathan, Cathy Williams, Katie Williams, Jayne V. Woodside, Max M. Yates, Jennifer Yip, Yalin Zheng
Journal: Ophthalmology (2019)
Organ‐on‐a‐Chip: Organ‐on‐a‐Chip for Cancer and Immune Organs Modeling (Adv. Healthcare Mater. 4/2019)
Authors: Wujin Sun, Zhimin Luo, Junmin Lee, Han‐Jun Kim, KangJu Lee, Peyton Tebon, Yudi Feng, Mehmet R. Dokmeci, Shiladitya Sengupta, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2019)

In article number 1801363 Shiladitya Sengupta, Ali Khademhosseini and co-workers show organ-on-a-chip systems can provide high-throughput platforms for drug development, which could potentially bridge the gap between 2D cell culture and animal models. With recent breakthroughs in anticancer immunotherapies, there is an increasing interest in organotypic models for anti-cancer immunotherapy development. This study reviews current progress in cancer-on-a-chip and immune organ-on-a-chip systems with an emphasis on their potential for drug development.
Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus
Authors: Jonathan I. Silverberg, Andreas Pinter, Grazyna Pulka, Yves Poulin, Jean-David Bouaziz, Andreas Wollenberg, Dédée F. Murrell, Andrew Alexis, Lisa Lindsey, Faiz Ahmad, Christophe Piketty, Alan Clucas
Journal: Journal of Allergy and Clinical Immunology (2019)

Nemolizumab targets the IL-31 receptor α subunit involved in atopic dermatitis (AD) pathogenesis.We sought to evaluate a new dosing strategy of nemolizumab in patients with AD.We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n = 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator's Global Assessment (IGA) were assessed. Standard safety assessments were performed.Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (-68.8% vs -52.1%, P = .016); significant differences were observed by week 8 (P ≤ .01). With significant improvement (P = .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P = .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P = .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (-68.6% vs -34.3%, P < .0001) and week 24 (-67.3% vs -35.8%, P < .0001), with a difference by week 1 (P < .001). NRS response rates (≥4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P ≤ .001) and week 24 (P ≤ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection.Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile.
Physical methods of rehabilitation (PMR) in patients with lung cancer.
Authors: Boris Kasparov, Tatiana Semiglazova, Kovlen Denis, Ponomarenko Gennady, Valeriya Kluge, Anton Krutov, Margarita Zernova, Kristina Kondrateva, Khidishyan Karina, Alexey Belyaev, Roman Donskih, Adhamov Bahtyar, Vladislav Semiglazov, Evgeniya Vladimirovna Kharchenko, Nikita Levchenko, Evgeny Levchenko
Journal: Journal of Clinical Oncology (2019)

e23189 Key words: physical therapy, rehabilitation, lung cancer. Background: The strategy of searching evidences for using rehabilitation technologies in patients with lung cancer (LC) is based on scientometric analysis. Methods: Since 1991 to 2018 analysis of 249682 studies was performed. It was completed by using PICO(T) technologies in databases such as PEDro, PubMed, E-library and Cochrane Library. Medical subject headings (lung cancer, rehabilitation, physical therapy, etc) were used to search the information in international databases. The trials were rated by PEDro scale including 10 points of evidence level : randomization, endpoint evaluation, blinding and etc. Results: Almost 55.9% of studies showed the level from 4 to 8 points on the PEDro scale and were verified by distribution profile. One trial had 9 points (0,8 %). Recommended evidence-based use of PRM technology in the rehabilitation of patients with LC (table): Conclusions: This results will form the base of clinical guidelines of new evidence-based Development of Patient Rehabilitation of patients with LC in Russian Federation.[Table: see text]
Patient Perspectives About Decisions to Share Medical Data and Biospecimens for Research
Authors: Jihoon Kim, Hyeoneui Kim, Elizabeth Bell, Tyler Bath, Paulina Paul, Anh Pham, Xiaoqian Jiang, Kai Zheng, Lucila Ohno-Machado
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Patients increasingly demand transparency in and control of how their medical records and biospecimens are shared for research. How much they are willing to share and what factors influence their sharing preferences remain understudied in real settings. <h3>Objectives</h3> To examine whether and how various presentations of consent forms are associated with differences in electronic health record and biospecimen sharing rates and whether these rates vary according to user interface design, data recipients, data and biospecimen items, and patient characteristics. <h3>Design, Setting, and Participants</h3> For this survey study, a data and biospecimen sharing preference survey was conducted at 2 academic hospitals from May 1, 2017, to September 31, 2018, after simple randomization of patients to 1 of 4 options with different layout and formats of indicating sharing preferences: opt-in simple, opt-in detailed, opt-out simple, and opt-out detailed. <h3>Interventions</h3> All participants were presented with a list of data and biospecimen items that could be shared for research within the same health care organization or with other nonprofit or for-profit institutions. Participating patients were randomly asked to select the items that they would share (opt-in) or were asked to select items they would not share (opt-out). Patients in these 2 groups were further randomized to select only among 18 categories vs 59 detailed items (simple vs detailed form layout). <h3>Main Outcomes and Measures</h3> The primary end points were the percentages of patients willing to share data and biospecimen categories or items. <h3>Results</h3> Among 1800 eligible participants, 1246 (69.2%) who completed their data sharing survey were included in the analysis, and 850 of these patients (mean [SD] age, 51.1 [16.7] years; 507 [59.6%] female; 677 [79.6%] white) responded to the satisfaction survey. A total of 46 participants (3.7%) declined sharing with the home institution, 352 (28.3%) with nonprofit institutions, and 590 (47.4%) with for-profit institutions. A total of 836 (67.1%) indicated that they would share all items with researchers from the home institution. When comparing opt-out with opt-in interfaces, all 59 sharing choice variables (100%) were associated with the sharing decision. When comparing simple with detailed forms, only 14 variables (23.7%) were associated with the sharing decision. <h3>Conclusions and Relevance</h3> The findings suggest that most patients are willing to share their data and biospecimens for research. Allowing patients to decide with whom they want to share certain types of data may affect research that involves secondary use of electronic health records and/or biosamples for research.
Dietary flavonoids: Nano delivery and nanoparticles for cancer therapy
Authors: Paola Aiello, Sara Consalvi, Giovanna Poce, Anna Raguzzini, Elisabetta Toti, Maura Palmery, Mariangela Biava, Marco Bernardi, Mohammad A. Kamal, George Perry, Ilaria Peluso
Journal: Seminars in Cancer Biology (2019)
Effect of targeted therapy on renal cell carcinoma with rapid progression.
Authors: Shenhong Wu, Vishal Navnitray Ranpura
Journal: Journal of Clinical Oncology (2013)

e15578 Background: Seven targeted agents so far have been approved for the treatment of advanced renal cell carcinoma (RCC). However, it is not clear whether these agents are effective in patients with rapid progressive disease, which is characterized by progression within three months and associated with poor prognosis. Therefore, we conducted a systematic review and meta-analysis of published randomized controlled clinical trials (RCTs) to assess the effect of targeted therapy on rapid progressive RCC. Methods: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until October, 2012 were searched to identify relevant studies. Rapid progression was defined as progressive disease or death within 3 months after the initiation of clinical trial. Eligible studies included prospective RCTs in which a targeted therapy was compared to a placebo or cytokine control in RCC patients. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated based on the heterogeneity of included studies. Results: A total of 4,628 patients (targeted therapy: 2,461, control: 2,167) with RCC from 10 RCTs were included for analysis. When compared to controls, the targeted therapy significantly reduced the overall risk of rapid progression (23.6%, 95% CI: 19.2-28.6% versus 54.5%, 95% CI: 44.6-64.1%) with an overall RR of 0.46 (95% CI: 0.38-0.54, P&lt;0.001). The effect did not vary significantly with prior therapies (P=0.67), but varied with different prognostic groups (P=0.025). In addition, the effect varied significantly among different agents (p&lt;0.001), with the highest reduction seen in patients treated with pazopanib (RR=0.27; 95% CI: 0.21-0.35). There was no significant difference between mTOR and VEGF inhibitors (P=0.25) in the risk reduction. Furthermore, the targeted therapy significantly reduced the risk of 3-month mortality (RR 0.58, P=0.002) from 10.0% (95% CI: 5.3-18.1%) to 5.5% (95% CI: 3.3-8.9%) in comparison with controls. Conclusions: The targeted therapy may significantly reduce the risk of rapid progression and early death in patients with renal cell carcinoma. Early application of these agents is recommended.
Journals retract 15 Chinese transplantation studies over executed prisoner concerns
Authors: Owen Dyer
Journal: BMJ (2019)

The journals Transplantation 1 and PLOS One 2 have retracted 15 articles reporting studies from China in the past month after the study authors failed to fulfil requests to provide evidence on the source of transplanted kidneys and livers.

Kidney International 3 and the Clinical Journal of the American Society of Nephrology 4 have also both published recent expressions of concern about three kidney transplant studies from China.

In explaining their decisions all four journals referred to an article published in BMJ Open this February, in which a team led by Wendy Rogers of Macquarie University in Sydney, Australia, reviewed 445 transplantation articles from China published from 2000 to 2017.5

They found that 92% of the studies did not report whether organs had …
Using Transitional Changes on High‐Resolution Computed Tomography to Monitor the Impact of Cyclophosphamide or Mycophenolate Mofetil on Systemic Sclerosis–Related Interstitial Lung Disease
Authors: Grace Hyun J. Kim, Donald P. Tashkin, Pechin Lo, Matthew S. Brown, Elizabeth R. Volkmann, David W. Gjertson, Dinesh Khanna, Robert M. Elashoff, Chi‐Hong Tseng, Michael D. Roth, Jonathan G. Goldin
Journal: Arthritis & Rheumatology (2019)

Objective To examine changes in the extent of specific patterns of interstitial lung disease ( ILD ) as they transition from one pattern to another in response to immunosuppressive therapy in systemic sclerosis–related ILD ( SS c‐ ILD ). Methods We evaluated changes in the quantitative extent of specific lung patterns of ILD using volumetric high‐resolution computed tomography ( HRCT ) scans obtained at baseline and after 2 years of therapy in patients treated with either cyclophosphamide ( CYC ) for 1 year or mycophenolate mofetil ( MMF ) for 2 years in Scleroderma Lung Study II . ILD patterns included lung fibrosis, ground glass, honeycombing, and normal lung. Net change was calculated as the difference in the probability of change from one ILD pattern to another. Wilcoxon's signed rank test was used to compare the changes. Results Forty‐seven and 50 patients had baseline and follow‐up scans in the CYC and MMF groups, respectively. Mean net improvements reflecting favorable changes from one ILD pattern to another in the whole lung in the CYC and MMF groups, respectively, were as follows: from lung fibrosis to a normal lung pattern, 21% and 19%; from a ground‐glass pattern to a normal lung pattern, 30% and 28%; and from lung fibrosis to a ground‐glass pattern, 5% and 0.5%. The mean overall improvement in transitioning from a ground‐glass pattern or lung fibrosis to a normal lung pattern was significant for both treatments (all P &lt; 0.001). Conclusion Significantly favorable transitions from both ground‐glass and lung fibrosis ILD patterns to a normal lung pattern were observed in patients undergoing immunosuppressive treatment for SS c‐ ILD , suggesting the usefulness of examining these transitions for insights into the underlying pathobiology of treatment response.
World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management
Authors: William Shomali, Jason Gotlib
Journal: American Journal of Hematology (2019)

The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage.Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 109 /L, and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ-hybridization, flow immunophenotyping, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2", and the MPN subtype, "chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (eg, <1.5 × 109 /L) without symptoms or signs of organ involvement, a watch and wait approach with close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES. Hydroxyurea and interferon-alfa have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. The use of antibodies against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), as well as other targets on eosinophils remains an active area of investigation.
Management of colorectal cancer
Authors: Kilian G M Brown, Michael J Solomon, Kate Mahon, Sarah O’Shannassy
Journal: BMJ (2019)

### What you need to know

Colorectal cancer represents the third most commonly diagnosed cancer and is the fourth most common cause of cancer related mortality globally.1 The highest incidence and mortality rates are seen in high income countries.2

Surgical resection is the mainstay of treatment. Systemic chemotherapy and local pelvic radiotherapy are important adjuvant treatment modalities. The primary care physician plays a critical role in coordinating increasingly complex multi-modal management strategies for patients with colorectal cancer. This article provides an overview of contemporary management of colorectal cancer for general practitioners and other non-specialists.

The presentation and diagnosis of colorectal cancers have been covered recently in another article in The BMJ .3

Endoscopic biopsy followed by histology of the specimen is essential to confirm a new diagnosis of colorectal cancer. Following this, several investigations are necessary for clinical staging. These inform prognosis and guide subsequent management. Some can be arranged by the primary care physician.

### Primary care physicians

UK and Australian guidelines45 advise obtaining a computed tomography (CT) scan of the chest, abdomen, and pelvis to assess the extent of local …
Two Variants of Follicular Lymphoma Grade 3
Authors: Lyubov V. Plastinina, Alla M. Kovrigina, Sergey K. Kravchenko, Tatiana N. Obukhova, Ekaterina S. Nesterova, Aminat U. Magomedova, Yana K. Mangasarova, Anna E. Misyurina, Fatima Babayeva, Sergei M. Kulikov, Valeriy G. Savchenko
Journal: Blood (2017)
A Tale of Two Lungs
Authors: Matthew K. Hensley
Journal: JAMA (2019)

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