tbuckley/cabot-search huggingface dataset:
PTU-003 Real-life prescribing behaviours across european countries: results from an on-line survey
Authors: P Marchi, B Chemittz-Nielsen
Journal: Gut (2017)

Introduction  National and multi-national bodies provide guidance for the treatment of mild-moderate Ulcerative Colitis (UC). How these recommendations are applied in clinical practice is unclear. Very limited data on real-life prescriptions by gastroenterologists are available.  Method  In November 2015, 181 gastroenterologists from 8 EU countries [Czech Republic (CZ): 31 (17%); Denmark (DK): 20 (11%); Finland (FI): 12 (7%); France (FR): 30 (17%); Ireland (IE): 15 (8%); Norway (NO): 11 (6%); Spain (ES): 31 (17%); Sweden (SE): 31 (17%)] were invited to participate in an online survey. The analysis was explorative in nature and descriptive results are presented.  Results  Participating physicians reported seeing and treating on average of 25–71 patients with UC of different severity per month. Of these, 9%–22% were treatment naive, 21%–41% were relapsing, and 43%–64% were in remission. Overall, mesalazine (5-ASA) was the treatment of choice in 72%–97% for patients with mild UC and in 67%–95% with moderate UC, while 6%–44% and 41%–83% of patients with mild and moderate UC were on a combination therapy.  Interestingly, 3%–10% of physicians in ES, IE and DK and 3%–9% of physicians in ES and NO prescribed corticosteroids and/or biologics/biosimilars for newly diagnosed patients with mild disease. The mean mesalazine daily dose for induction/maintenance of remission was of 3.9/2.4g in DK; 3.5/2.1g in SE; 3.5/1.8g in NO; 3.5/1.9g in CZ; 3.4/2.3g in IE; 3.1/2.1g in FI; and 2.4/1.3g in ES.  In case of relapse, 48%–68% of the participating physicians increased the treatment dose, 17%–55% added another therapy while 5%–17% switched to another therapy. In case of add-on therapy, 25%–68% of physicians prescribed corticosteroids, 9%–33% biologics, 3%–20% biosimilars, and 10%–50% azathiopirine. In case of switch to another therapy, 8%–60% of physicians prescribed corticosteroids, 3%–33% biologics, 9%–17% biosimilars, and 5%–58% azathiopirine.  Physicians’ perception of patients’ compliance varied among countries, from a minimum of 40% in CZ to a maximum of 77% in ES.  Conclusion  Several factors, including personalised treatment and the local reimbursement scheme might influence prescription behaviour in different countries. Prescription of corticosteroids and biologics/biosimilars for newly diagnosed patients with mild form of the disease is difficult to explain and might mirror local medical habits or indicate a need for further education.  Disclosure of Interest  P. Marchi Conflict with: Tillotts Pharma AG, B. Chemittz-Nielsen Conflict with: TNF-Sifo Navigare
A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry
Authors: Burcu F. Darst, Peggy Wan, Xin Sheng, Jeannette T. Bensen, Sue A. Ingles, Benjamin A. Rybicki, Barbara Nemesure, Esther M. John, Jay H. Fowke, Victoria L. Stevens, Sonja I. Berndt, Chad D. Huff, Sara S. Strom, Jong Y. Park, Wei Zheng, Elaine A. Ostrander, Patrick C. Walsh, Shiv Srivastava, John Carpten, Thomas A. Sellers, Kosj Yamoah, Adam B. Murphy, Maureen Sanderson, Dana C. Crawford, Susan M. Gapstur, William S. Bush, Melinda C. Aldrich, Olivier Cussenot, Meredith Yeager, Gyorgy Petrovics, Jennifer Cullen, Christine Neslund-Dudas, Rick A. Kittles, Jianfeng Xu, Mariana C. Stern, Zsofia Kote-Jarai, Koveela Govindasami, Anand P. Chokkalingam, Luc Multigner, Marie-Elise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Adam S. Kibel, Eric A. Klein, Phyllis J. Goodman, Bettina F. Drake, Jennifer J. Hu, Peter E. Clark, Pascal Blanchet, Graham Casey, Anselm J.M. Hennis, Alexander Lubwama, Ian M. Thompson, Robin Leach, Susan M. Gundell, Loreall Pooler, Lucy Xia, James L. Mohler, Elizabeth T.H. Fontham, Gary J. Smith, Jack A. Taylor, Rosalind A. Eeles, Laurent Brureau, Stephen J. Chanock, Stephen Watya, Janet L. Stanford, Diptasri Mandal, William B. Isaacs, Kathleen Cooney, William J. Blot, David V. Conti, Christopher A. Haiman
Journal: European Urology (2020)

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry–specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13–7.22) and 33.41 (95% CI = 10.86–102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17–25%) for TA heterozygotes and 38% (95% CI = 13–65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. We found that rs72725854, an African ancestry–specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.
Efficacy of immune checkpoint inhibitors for in-transit melanoma
Authors: Emilia Nan Tie, Julia Lai-Kwon, Michael Alexander Rtshiladze, Lumine Na, James Bozzi, Tavis Read, Victoria Atkinson, George Au-Yeung, Georgina V Long, Grant A McArthur, Shahneen Sandhu, Robyn Saw, Euan Walpole, Alexander Menzies, Mark Smithers, David E Gyorki
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The efficacy of immune checkpoint inhibitors (ICI) in metastatic melanoma is well established. However, there are limited data regarding their efficacy in in-transit melanoma (ITM). This study assessed the efficacy of ICI in patients with ITM. Methods A retrospective review of patients with ITM commenced on an ICI between March 2013 and February 2018 at three tertiary centers in Australia. Patients were excluded if they had previous or synchronous distant metastases. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were based on a composite of radiological and clinical assessments. Results Fifty-four patients were included: 27 (50%) female; median age 75 (range 26–94); 12 (22%) stage IIIB, 40 (74%) stage IIIC and 2 (4%) stage IIID; 10 (19%) BRAF mutant. Forty (74%) received single-agent anti-PD-1 (pembrolizumab or nivolumab), 8 (15%) single agent anti-CTLA-4 (ipilimumab), 5 (9%) combination anti-PD-1/anti-CTLA-4 (ipilimumab and nivolumab or pembrolizumab) and 1 (2%) combination anti-PD-L1 (atezolizumab) and MEK inhibitor (cobimetinib). The median follow-up was 15 months (2–46). ORR to ICI was 54%: 14 (26%) complete responses; 15 (28%) partial responses; 9 (17%) stable disease; 16 (30%) progressive disease. Thirteen (46%) responders had only one ITM lesion. ORR was 58% for single-agent anti-PD-1, 38% for single-agent anti-CTLA4 and 40% for anti-PD-1/anti-CTLA-4. The median PFS was 11.7 months (6.6-not reached). 1-year and 2-year PFS were 48% and 39%, respectively,. Fourteen progressed locoregionally and 11 progressed distantly. The median OS was not reached. 1-year and 2-year OS were 85% and 63%, respectively. No clinicopathological features were associated with ORR. Conclusions and relevance ICI produce objective responses in ITM and should be considered in patients with unresectable ITM or disease recurrence.
SIRT1 Deficiency Compromises Mouse Embryonic Stem Cell Differentiation, and Embryonic and Adult Hematopoiesis In the Mouse.
Authors: Xuan Ou, Hee-Don Chae, Rui-Hong Wang, William C Shelley, Scott Cooper, Tammi Taylor, Young-June Kim, Chu-Xia Deng, Mervin C. Yoder, Hal E. Broxmeyer
Journal: Blood (2010)
Exosome-like vesicles derived from Hertwig's epithelial root sheath cells promote the regeneration of dentin-pulp tissue
Authors: Sicheng Zhang, Yan Yang, Sixun Jia, Hong Chen, Yufeng Duan, Xuebing Li, Shikai Wang, Tao Wang, Yun Lyu, Guoqing Chen, Weidong Tian
Journal: Theranostics (2020)

Background: The formation of dentin-pulp involves complex epithelial-mesenchymal interactions between Hertwig's epithelial root sheath cells (HERS) and dental papilla cells (DPCs). Earlier studies have identified some of the regulatory molecules participating in the crosstalk between HERS and DPCs and the formation of dentin-pulp. In the present study we focused on the role of HERS-secreted exosomes in DPCs and the formation of dentin-pulp. Specifically, we hypothesized that exosome-like vesicles (ELVs) might mediate the function of HERS and trigger lineage-specific differentiation of dental mesenchymal cells. To test our hypothesis, we evaluated the potential of ELVs derived from a HERS cell line (ELVs-H1) in inducing in vitro and in vivo differentiation of DPCs. Methods: ELVs-H1 were characterized using transmission electron microscopy and dynamic light scattering. The proliferation, migration, and odontoblast differentiation of DPCs after treatment with ELVs-H1, was detected by CCK8, transwell, ALP, and mineralization assays, respectively. Real time PCR and western blotting were used to detect gene and protein expression. For in vivo studies, DPC cells were mixed with collagen gel combined with or without ELVs and transplanted into the renal capsule of rats or subcutaneously into nude mice. HE staining and immunostaining were used to verify the regeneration of dentin-pulp and expression of odontoblast differentiation markers. Results: ELVs-H1 promoted the migration and proliferation of DPCs and also induced odontogenic differentiation and activation of Wnt/β-catenin signaling. ELVs-H1 also contributed to tube formation and neural differentiation in vitro. In addition, ELVs-H1 attached to the collagen gel, and were slowly released and endocytosed by DPCs, enhancing cell survival. ELVs-H1 together with DPCs triggered regeneration of dental pulp-dentin like tissue comprised of hard (reparative dentin-like tissue) and soft (blood vessels and neurons) tissue, in an in vivo tooth root slice model. Conclusion: Our data highlighted the potential of ELVs-H1 as biomimetic tools in providing a microenvironment for specific differentiation of dental mesenchymal stem cells. From a developmental perspective, these vesicles might be considered as novel mediators facilitating the epithelial-mesenchymal crosstalk. Their instructive potency might be exploited for the regeneration of dental pulp-dentin tissues.
Reply to: Evaluating two different models of peanut’s origin
Authors: Weijian Zhuang, Xiyin Wang, Andrew H. Paterson, Hua Chen, Meng Yang, Chong Zhang, Pengchuan Sun, Yixiong Zheng, Lihui Wang, Wenping Xie, Wenting Chu, Huiwen Fu, Rajeev K. Varshney
Journal: Nature Genetics (2020)
Efficacy and safety of Qu Xie capsule in metastatic colorectal cancer: A double-blind, randomized, placebo-controlled trial.
Authors: Tong Zhang, Yufei Yang
Journal: Journal of Clinical Oncology (2017)

e15069 Background:Qu Xie capsule was discovered by Li Zhongzi, a traditional Chinese Medicine doctor in the Ming Dynasty. Doctor Yang Yufei improved Qu Xie capsule and used it clinically for more than 10 years. In a previous study, we found that Qu Xie capsule reduces the risk of stage II–III colorectal cancer postoperative recurrence and metastasis and prolongs the survival of patients with metastatic colorectal cancer (mCRC). The present clinical trial was designed to verify the efficacy and safety of Qu Xie capsule in patients with mCRC. Methods: The present study was a randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into two groups at a 1:1 ratio. The treatment group received conventional therapy combined with Qu Xie capsule. The control group was treated with conventional therapy combined with placebo. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Results: A total of 121 patients were enrolled and 60 patients were eligible; 54 patients were analyzed. The median OS was 23 months in the treatment group [95% confidence interval (CI) 15–not calculated] vs. 14 months in the control group (95% CI 11–22) (Kaplan–Meier, Log-rank p = 0.060). The OS of the treatment group tended to be longer than that of the control group, although the difference was not significant. This may have been related to the small sample size. In the subgroups of patients &lt; 65 years old, left-sided colon, and ≥second-line therapy, the treatment group showed a significant survival benefit compared with the control group ( p = 0.006, 0.038, 0.013). There were no significant differences between the two groups in PFS. Safety analysis showed no severe hematological toxicity or liver and renal function injury in the treatment group. In the treatment group, one patient had 'abdominal pain' once, which may have been related to the Qu Xie capsule. No other related adverse events were reported. Conclusions:Qu Xie capsule showed good safety and efficacy, and can prolong the OS of patients with mCRC. Clinical trial information: ChiCTR-IOR-16009733.
An APN-activated NIR photosensitizer for cancer photodynamic therapy and fluorescence imaging
Authors: Xiao Zhou, Haidong Li, Chao Shi, Feng Xu, Zhen Zhang, Qichao Yao, He Ma, Wen Sun, Kun Shao, Jianjun Du, Saran Long, Jiangli Fan, Jingyun Wang, Xiaojun Peng
Journal: Biomaterials (2020)
De-Escalating Breast Cancer Surgery for Low-Risk Ductal Carcinoma in Situ—Reply
Authors: Monica Morrow, Eric Winer
Journal: JAMA Oncology (2020)

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Adult immuno-oncology: using past failures to inform the future
Authors: Maryam Rahman, W Gregory Sawyer, Scott Lindhorst, Loic P Deleyrolle, Jeffrey K Harrison, Aida Karachi, Farhad Dastmalchi, Joseph Flores-Toro, Duane A Mitchell, Michael Lim, Mark R Gilbert, David A Reardon
Journal: Neuro-Oncology (2020)

In oncology, "immunotherapy" is a broad term encompassing multiple means of utilizing the patient's immune system to combat malignancy. Prominent among these are immune checkpoint inhibitors, cellular therapies including chimeric antigen receptor T-cell therapy, vaccines, and oncolytic viruses. Immunotherapy for glioblastoma (GBM) has had mixed results in early trials. In this context, the past, present, and future of immune oncology for the treatment of GBM was discussed by clinical, research, and thought leaders as well as patient advocates at the first annual Remission Summit in 2019. The goal was to use current knowledge (published and unpublished) to identify possible causes of treatment failures and the best strategies to advance immunotherapy as a treatment modality for patients with GBM. The discussion focuses on past failures, current limitations, failure analyses, and proposed best practices moving forward.
Progress Toward Maternal and Neonatal Tetanus Elimination — Worldwide, 2000–2018
Authors: Henry N. Njuguna, Nasir Yusuf, Azhar Abid Raza, Bilal Ahmed, Rania A. Tohme
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Maternal and neonatal tetanus* (MNT) remains a major public health problem, with an 80%-100% case-fatality rate among neonates, especially in areas with poor immunization coverage and limited access to clean deliveries (i.e., delivery in a health facility or assisted by medically trained attendants in sanitary conditions) and umbilical cord care (1). In 1989, the World Health Assembly endorsed the elimination† of neonatal tetanus (NT), and in 1999, the initiative was relaunched and renamed the MNT elimination§ initiative, targeting 59¶ priority countries (1). Elimination strategies include 1) achieving ≥80% coverage with ≥2 doses of tetanus toxoid-containing vaccine (TTCV) among women of reproductive age through routine immunization of pregnant women and supplementary immunization activities (SIAs)** in high-risk areas and districts††; 2) achieving care at ≥70% of deliveries by a skilled birth attendant (SBA)§§; and 3) enhancing surveillance for NT cases (1). This report summarizes progress toward achieving MNT elimination during 2000-2018. Coverage with ≥2 doses of TTCV (2 doses of tetanus toxoid [TT2+] or 2 doses of tetanus-diphtheria toxoid [Td2+]) among women of reproductive age increased by 16%, from 62% in 2000 to 72% in 2018. By December 2018, 52 (88%) of 59 priority countries had conducted TTCV SIAs, vaccinating 154 million (77%) of 201 million targeted women of reproductive age with TT2+/Td2+. Globally, the percentage of deliveries assisted by SBAs increased from 62% during 2000-2005 to 81% during 2013-2018, and estimated neonatal tetanus deaths decreased by 85%, from 170,829 in 2000 to 25,000 in 2018. By December 2018, 45 (76%) of 59 priority countries were validated by WHO as having achieved MNT elimination. To achieve elimination in the remaining 14 countries and sustain elimination in countries that have achieved it, implementation of MNT elimination strategies needs to be maintained and strengthened, and TTCV booster doses need to be included in country immunization schedules as recommended by the World Health Organization (WHO) (2). In addition, integration of maternal, newborn, and child health services with vaccination services is needed, as well as innovative approaches to target hard-to-reach areas for tetanus vaccination and community engagement to strengthen surveillance.
Blockade of Discoidin Domain Receptor 2 as a Strategy for Reducing Inflammation and Joint Destruction in Rheumatoid Arthritis Via Altered Interleukin‐15 and Dkk‐1 Signaling in Fibroblast‐Like Synoviocytes
Authors: Nan Mu, Jin‐Tao Gu, Tong‐Lie Huang, Nan‐Nan Liu, Hui Chen, Xin Bu, Zhao‐Hui Zheng, Bo Jia, Jun Liu, Bao‐Long Wang, Ying‐Mei Wang, Zhen‐Feng Zhu, Yong Zhang, Ying‐Qi Zhang, Xiao‐Chang Xue, Meng Li, Wei Zhang
Journal: Arthritis & Rheumatology (2020)

Objective This study was undertaken to uncover the pathophysiologic role of discoidin domain receptor 2 (DDR‐2), a putative fibrillar collagen receptor, in inflammation promotion and joint destruction in rheumatoid arthritis (RA). Methods In synovial tissue from patients with RA and from mice with collagen antibody–induced arthritis (CAIA) (using Ddr2 −/− and DBA/1 mice), gene and protein expression levels of DDR‐2, interleukin‐15 (IL‐15), and Dkk‐1 were measured by quantitative reverse transcription–polymerase chain reaction, Western blotting, and immunohistochemistry. Gene knockdown of DDR2 in human RA fibroblast‐like synoviocytes (FLS) was conducted via small interfering RNA. Interaction between the long noncoding RNA H19 and microRNA 103a (miR‐103a) was assessed in RA FLS using RNA pulldown assays. Cellular localization of H19 was examined using fluorescence in situ hybridization assays. Chromatin immunoprecipitation and dual luciferase reporter assays were applied to verify H19 transcriptional and posttranscriptional regulation by miR‐103a. Results DDR2 messenger RNA (mRNA) expression was significantly associated with the levels of IL‐15 and Dkk‐1 mRNA in the synovial tissue of RA patients (r 2 = 0.2022–0.3293, all P &lt; 0.05; n = 33) and with the serum levels of IL‐15 and Dkk‐1 in mice with CAIA ( P &lt; 0.05). In human RA FLS, activated DDR‐2 induced the expression of H19 through c‐Myc. Moreover, H19 directly interacted with and promoted the degradation of miR‐103a. Conclusion These results indicate a novel role for activated DDR‐2 in RA FLS, showing that DDR‐2 is responsible for regulating the expression of IL‐15 and Dkk‐1 in RA FLS and is involved in the promotion of inflammation and joint destruction during pathophysiologic development of RA. Moreover, DDR‐2 inhibition, acting through the H19–miR‐103a axis, leads to reductions in the inflammatory reaction and severity of joint destruction in mice with CAIA, suggesting that inhibition of DDR‐2 may be a potential therapeutic strategy for RA.
Diagnostic and therapeutic challenges for patients with ANCA-associated vasculitides at the time of COVID-19. Response to: ‘Rituximab for granulomatosis with polyangiitis in the pandemic of COVID-19: lessons from a case with severe pneumonia’ by Guilpain <i>et al</i>
Authors: Sara Monti, Carlomaurizio Montecucco
Journal: Annals of the Rheumatic Diseases (2020)

We thank Dr Guilpain et al 1 for their comment regarding the case of a patient with granulomatosis with polyangiitis who developed signs of systemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection shortly after having received treatment with rituximab. The comment raises a series of important points of discussion. The differential diagnosis between infectious complications or manifestations of the underlying rheumatological condition has always been a challenge when managing patients with systemic diseases such as antineutrophil cytoplasmic antibody-associated vasculitis (AAV) or connective tissue diseases (CTD). The clinical picture and laboratory and imaging findings in patients with AAV or CTD are often non-specific and need to be differentiated from changes caused by treatment or by infectious complication.2–4 SARS-CoV-2 has been associated with clinical manifestations and complications that can resemble some changes found in AAV or CTD. The cardiovascular risk, including the risk of deep venous thrombosis and pulmonary embolism, is increased also …