tbuckley/cabot-search huggingface dataset:
Abstract 9354: Socioeconomic, Demographic, and Geographic Trends in Mortality from Peripheral Artery Disease in the United States from 2000-2019
Authors: haytham mously, Stephen Kimura, Tarek Hammad, Mehdi H Shishehbor, Jun Li
Journal: Circulation (2021)

Background: Much is known about mortality trends in coronary artery disease (CAD) and cerebrovascular disease (CVD), yet data reporting mortality trends for peripheral artery disease (PAD) are scarce. We sought to explore overall PAD mortality trends in the US. Methods: The Multiple Cause of Death database from the Center for Disease Control was used to identify patients, aged 25 years and older, who died of PAD between years 2000 to 2019. Patients who died from PAD were identified using International Classification of Diseases 10th revision codes. Patient socioeconomic, demographic, and geographic factors were reported and analyzed. Age-adjusted rate were calculated using a standard population and reported in per-million persons (PMP). Finally, PAD mortality trends were compared to CAD and CVD. Results: A total of 854,616 PAD deaths were identified and showed decreasing mortality from 403 to 99 age-adjusted years PMP from 2000-2019. PAD mortality increased with increasing age (crude rate of 1.0 PMP vs 3806 PMP among 25-34 vs &gt;85 year-olds respectively). PAD mortality was also higher among Black individuals from 2000 to 2006, but has equalized to the mortality rate of White individuals. PAD mortality was higher among men compared to women, but the gap has decreased over time. There was significant geographic state-level variation (3 fold) in PAD mortality, with large fringe metros demonstrating the lowest mortality. When compared to CAD and CVD, PAD mortality decreased by 75% from 2000 and 2019, compared with a 61% reduction in CAD mortality and a 46% reduction in CVD mortality (Figure 1). Conclusion: From 2000 to 2019, mortality due to PAD in the US has decreased at a much higher rate compared to CAD and CVD. Despite this trend, PAD remains a major cause of mortality in the US, disproportionately affecting elderly individuals, generally those living in less metropolitan areas, and men of both White and Black ethnicity, although differences in race and gender are diminishing.
In Multiple Myeloma, High-Risk Secondary Genetic Events Observed at Relapse Are Present from the Diagnosis in Tiny Undetectable Subclones
Authors: Herve Avet-Loiseau, Romain Lannes, Aurore Perrot, Céline Mazzotti, Marion Divoux, Titouan Cazaubiel, Xavier Leleu, Anaïs Schavgoulidze, Marie-Lorraine Chretien, Salomon Manier, Didier Adiko, Frédérique Orsini-Piocelle, Francois Lifermann, Sabine Brechignac, Lauris Gastaud, Didier Bouscary, Magaret Macro, Mohamad Mohty, Nikhil C. Munshi, Jill Corre
Journal: Blood (2021)
Bispecific Vγ9Vδ2-T and Type 1 NKT Cell Engager Lava-051 As First-in-Class Clinical Candidate to Target CD1d Expressing CLL, MM and AML
Authors: Roeland Lameris, Jurjen M Ruben, Iris de Weerdt, Rob Roovers, Niels W.C.J. van de Donk, Annemiek Broyl, Arnon P. Kater, Thilo Riedl, Victoria Iglesias, Benjamin Winograd, Anton EP Adang, Tanja D. de Gruijl, Paul W. H. I. Parren, Hans J. van der Vliet
Journal: Blood (2021)
Comprehensive <i>in Vitro</i> Characterization of <i>CXCR4</i>WHIM variants to Decipher Genotype-Phenotype Correlations in WHIM Syndrome
Authors: Katarina Zmajkovicova, Sabine Maier-Munsa, Barbara Maierhofer, Arthur G. Taveras, Adriana Badarau
Journal: Blood (2021)
Event-Free Survival at 24 Months (EFS24) Becomes an Important Clinical Endpoint in Newly Diagnosed Mantle Cell Lymphoma in the New Era
Authors: Yucai Wang, Melissa C. Larson, Alessia Castellino, Matthew J. Maurer, Andrew L. Feldman, Sergei Syrbu, Brian K. Link, Umar Farooq, David J. Inwards, Jonas Paludo, Thomas E. Witzig, Thomas M. Habermann, James R. Cerhan, Grzegorz S. Nowakowski
Journal: Blood (2021)
Rare Case of Dual Right Coronary Artery Intervention Presenting as Acute Coronary Syndrome
Authors: Anish Hirachan
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Dual right coronary artery (RCA) is a very rare coronary anomaly. This anomaly is often undetected and may be totally asymptomatic to presenting as acute coronary syndrome. Here , we present a young diabetic male who presented with acute onset severe chest pain of 30 minutes duration which was managed as acute coronary syndrome ( NSTE-ACS). His urgent coronary angiogram revealed single ostial origin of right coronary artery (RCA) with total occlusion from proximal segment followed by double right coronary arteries with their respective distal branches.
Acute nail changes after manicure with acrylate containing nail polish
Authors: Aaron Secrest, Guilherme Kuceki
Journal: BMJ (2021)

This is contact dermatitis of the periungual and subungual skin of the fingers and thumbs of a woman in her 40s after application of a gel nail polish containing acrylate, dried using ultraviolet light (fig 1).



Fig 1 

One …
Phase II Clinical Trial of Abatacept for Steroid-Refractory Chronic Graft Versus Host Disease
Authors: Anita G. Koshy, Haesook T. Kim, Dina Stroopinsky, Jessica J. Liegel, Jon E. Arnason, Vincent T. Ho, Joseph H. Antin, Robin M. Joyce, Corey Cutler, Mahasweta Gooptu, Sarah Nikiforow, Emma K. Logan, Pavania Elavalakanar, Susan Stephenson, Hassan El Banna, Poorva Bindal, Giulia Cheloni, David Avigan, Robert J. Soiffer, Jacalyn Rosenblatt
Journal: Blood (2021)
Abstract PO-006: CircRTN4 promotes pancreatic cancer progression through a novel circRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein
Authors: Chi Hin Wong, Ut Kei Lou, Frederic Khe-Cheong Fung, Joanna H. M. Tong, Ka-Fai To, Stephen Lam Chan, Yangchao Chen
Journal: Cancer Research (2021)

Abstract Background &amp; Aims: Circular RNAs (circRNAs) play important roles in many biological processes. However, the detailed mechanism underlying the critical roles of circRNAs in cancer remains largely unexplored. We aim to explore the molecular mechanisms of circRTN4 with critical roles in pancreatic ductal adenocarcinoma (PDAC). Methods: CircRTN4 expression level was examined in PDAC primary tumors. The oncogenic roles of circRTN4 in PDAC tumor growth and metastasis were studied in mouse tumor models. Bioinformatics analysis, luciferase assay and miRNA pulldown assay were performed to study the novel circRTN4-miRNA-lncRNA pathway. To identify circRTN4-interacting proteins, we performed circRNA-pulldown and mass spectrometry in PDAC cells. Protein stability assay and 3-Dimensional structure modeling were performed to reveal the role of circRTN4 in stabilizing RAB11FIP1. Results: circRTN4 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that circRTN4 promoted PDAC tumor growth and liver metastasis. Mechanistically, circRTN4 interacted with tumor suppressor miR-497-5p in PDAC cells. CircRTN4 knockdown upregulated miR-497-5p to inhibit the oncogenic lncRNA HOTTIP expression. Furthermore, we identified critical circRTN4-intercting proteins by circRNA-pulldown in PDAC cells. CircRTN4 interacted with important epithelial-mesenchymal transition (EMT)- driver RAB11FIP1 to block its ubiquitination site. We found that circRTN4 knockdown promoted the degradation of RAB11FIP1 by increasing its ubiquitination. Also, circRTN4 knockdown inhibited the expression of RAB11FIP1-regulating EMT-markers Slug, Snai1, Twist, Zeb1 and N-cadherin in PDAC. Conclusion: The upregulated circRTN4 promotes tumor growth and liver metastasis in PDAC through the novel circRTN4-miR-497-5p-HOTTIP pathway. Also, circRTN4 stabilizes RAB11FIP1 to contribute EMT. Citation Format: Chi Hin Wong, Ut Kei Lou, Frederic Khe-Cheong Fung, Joanna H. M. Tong, Ka-Fai To, Stephen Lam Chan, Yangchao Chen. CircRTN4 promotes pancreatic cancer progression through a novel circRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-006.
A Phase 2, Open-Label, Multiarm, Multicenter Study to Evaluate Magrolimab Combined with Antileukemia Therapies for First-Line, Relapsed/Refractory, or Maintenance Treatment of Acute Myeloid Leukemia
Authors: Paresh Vyas, Naval Daver, Mark Chao, Guan Xing, Camille Renard, Giri Ramsingh, Andrew H. Wei, David A. Sallman
Journal: Blood (2021)
From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective
Authors: Xiao-Bing Gao, Tamas L Horvath
Journal: Endocrine Reviews (2021)

Abstract The hypocretin/orexin (Hcrt/Orx) system in the perifornical lateral hypothalamus has been recognized as a critical node in a complex network of neuronal systems controlling both physiology and behavior in vertebrates. Our understanding of the Hcrt/Orx system and its array of functions and actions has grown exponentially in merely 2 decades. This review will examine the latest progress in discerning the roles played by the Hcrt/Orx system in regulating homeostatic functions and in executing instinctive and learned behaviors. Furthermore, the gaps that currently exist in our knowledge of sex-related differences in this field of study are discussed.
Preclinical Development of EDIT301, an Autologous Cell Therapy Comprising AsCas12a-RNP Modified Mobilized Peripheral Blood-CD34 + Cells for the Potential Treatment of Transfusion Dependent Beta Thalassemia
Authors: Patricia Sousa, Tusneem Janoudi, Edouard deDreuzy, Mark S Shearman, Kate Zhang, Kai-Hsin Chang
Journal: Blood (2021)
Allogeneic Stem Cell Transplantation for Patients with Acute Myelogenous Leukemia (AML) in Second Complete Remission (CR2) Transplanted from Unrelated Donors with Post Transplant Cyclophosphamide (PTCy). a Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Authors: Arnon Nagler, Myriam Labopin, Aleksandr D. Kulagin, Hélène Labussière-Wallet, Montserrat Rovira, Didier Blaise, Jan Vydra, Ibrahim Yakoub-Agha, Goda Choi, Yener Koc, Péter Reményi, Fabio Ciceri, Jaime Sanz, Mohamad Mohty
Journal: Blood (2021)
A Clue to Better Select Chronic Lymphocytic Leukemia Patients with Optimal Response to BNT162b2 mRNA COVID-19 Vaccine
Authors: Stefano Molica, Diana Giannarelli, Mirella Lentini, Daniela Zappala, Daniela Loiacono, Valentina Gianfelici, Giuseppina Panduri, Pasquale Minchella, Francesco Talarico, Luciano Levato
Journal: Blood (2021)
Real life triplet FIr/FOx chemotherapy in first line metastatic pancreatic ductal adenocarcinoma: Recommended schedule for expected activity and safety and phase II study
Authors: G. Bruera, S. Massacese, R. Manetta, A. Giordano, S. Carducci, E. Ciacco, E. Ricevuto
Journal: Annals of Oncology (2018)

Introduction: Gemcitabine/nab-paclitaxel and FOLFIRINOX demonstrated significantly increased survival vs gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): objective response rate (ORR) 23 and 31.6%, progression-free survival (PFS) 5.5 and 6.4 months, overall survival (OS) 8.7 and 11.1 months. Phase II study investigated first line triplet FIr/FOx. Methods: Simon two-step design: p0 10%, p1 30%, power 80%, α 5%, β 20%. Projected ORR: I step, 1/10; II 5/29. Schedule: 12h-timed-flat-infusion/5-fluorouracil 750-800-900 mg/m2 d1-2,8-9,15-16,22-23; irinotecan 120-140-160 mg/m2 d1,15; oxaliplatin 70-80 mg/m2 d8,22; every 4 weeks, according to clinical parameters (age, comorbidities, performance status (PS), liver function). Activity, efficacy were evaluated, compared using log-rank; limiting toxicity syndromes (LTS) using chi-square. Results: Twenty-nine consecutive patients ≤65, >65≤75, ≥75 years enrolled, discriminated according to primary/intermediate/secondary Cumulative Illness Rating Scale (CIRS). Median age 62; elderly 13 (44.7%); PS2 3 (10.4%), secondary CIRS 5 (17.2%). Primary endpoint was met: OR 7/13 as-treated (53%), 50% intent-to-treat. Cumulative G3-4 toxicities: diarrhea 17%, asthenia 14%, vomiting 3%, hypertransaminasemy 7%, mucositis 7%, anemia 3%, thrombocytopenia 3%. LTS: 27.5% overall, 38.4% in elderly, multiple vs single site not significantly different. At 3 months follow-up, PFS 4 months, OS 11 months, not significantly different in elderly vs non-elderly. PFS and OS not significantly different according to dosage, tumor location, metastatic sites. PS2 patients showed significantly worse OS (P 0.022). Conclusion: Intensive first-line triplet FIr/FOx is tolerable at adapted doses, confirms high activity/efficacy in metastatic PDAC. Careful selection of patients, PS2 exclusion, to maintain safety profile and efficient dose intensity can increase OS, compared to gemcitabine, in real life.
COVID-19 in Patients with Chronic Myeloid Leukemia: Poor Outcomes for Patients with Comorbidities, Older Age, Advanced Phase Disease, and Those from Low-Income Countries: An Update of the Candid Study
Authors: Katia B Pagnano, Chung Hoow Kok, Michael J. Mauro, Jorge E. Cortes, Nicola Evans, Qian Jiang, Dragana Milojkovic, Beatriz Moiraghi, Franck E. Nicolini, Matilda Ongondi, Daniela Zackova, Delphine Rea, Timothy P. Hughes
Journal: Blood (2021)
Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity
Authors: Jean-Francois Rossi, Hao-Chun Chiang, Zhao-Yang Lu, Kalle Levon, Frits van Rhee, Karan Kanhai, David C Fajgenbaum, Bernard Klein
Journal: Blood (2021)
Training and the future delivery of UK paediatric surgery in the NHS
Authors: Rachel Harwood, Paul D Losty
Journal: BMJ (2021)

Paediatric surgery is a highly specialised surgical field requiring expertise in caring for children with common and rare conditions. The creation of 26 UK paediatric surgery centres has occurred over recent decades, resulting in a geographical disparity, both in location and number of centres.1 Accumulation of experience and advances in medical technologies has resulted in a huge success story for the specialty. Many infants and children, hitherto with severe or potentially fatal conditions, now survive and thrive. General surgeons regularly undertake common paediatric elective and emergency procedures, although nationally there now is a steady drift of these operations being undertaken by specialty paediatric surgeons. Furthermore individual paediatric surgeon specific index case-numbers of some complex rare conditions has led in some instances to the transfer of healthcare to other specialist trusts for multi-disciplinary input and bespoke services.

NHS England and Improvement commissioned a Getting it Right First Time (GIRFT) report into paediatric surgery provision in England in 2018 and its early findings were supported (in principle) by the British Association of Paediatric Surgeons.2 The report describes the crucial need for concentration of sub-specialist surgical services in fewer (nominally 10) institutions in England for the expert care of children with varied index rare conditions. Sub-specialist centres are expected to have a “critical mass” of sub-specialist paediatric upper and lower gastro-intestinal and urology surgeons in addition to specialist paediatric surgeons in other sub-disciplines …
Alan Clark-Jones
Authors: Rosemary Chesson
Journal: BMJ (2021)

Alan Clark-Jones was a much loved GP in Camberwell for 31 years. After semi-retiring in 1990, he spent a further 20 years working as a locum and part time GP in and around south London.

Alan had a great interest in teaching in general practice and attended several courses. He had a succession of no less than 20 GP trainees and numerous medical students from King’s College …
MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength
Authors: Wang Feng, Qian Jin, Yang Ming-yu, He Yang, Tao Xu, Shi You-xing, Bian Xu-ting, Chen Wan, Wang Yun-jiao, Wang Huan, Yang Ai-ning, Li Yan, Tang Hong, Huang Pan, Mu Mi-duo, He Gang, Zhou Mei, Kang Xia, Tang Kang-lai
Journal: Biomaterials (2021)

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSCScx) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924–5p, was highest among miRNAs. miR-6924–5p could directly inhibit osteoclast formation by binding to the 3′-untranslated regions (3′UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924–5p expression reversed the prevention of osteoclastogenic differentiation by BMMSCScx derived exosomes (BMMSCScx-exos). Local injection of BMMSCScx-exos or miR-6924–5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924–5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSCScx-exos or miR-6924–5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.
Maturity State and MCL-1 Dependence Predetermines Response to NOTCH1 Inhibition in T-ALL
Authors: Valeriya Dimitrova, Noori Sotudeh, Anna Montanaro, Huiyoung Yun, Sayalee V. Potdar, Alexandria Van Scoyk, Shruti Bhatt, Praveen Anand, Antonis Kokkalis, Jake A. Kloeber, Julia Frede, Johannes M Waldschmidt, Anthony G. Letai, David M. Weinstock, Jens G. Lohr, Birgit Knoechel
Journal: Blood (2021)
PI3-Kinase Deletion Dysregulates Autophagy in HSCs and Promotes Myelodysplasia
Authors: Kristina Ames, Imit Kaur, Shayda Hemmati, Shira Glushakow-Smith, Lindsay Meg Gurska, Yang Shi, Robert A Dubin, Jidong Shan, Kith Pradhan, Amit Verma, Cristina Montagna, Kira Gritsman
Journal: Blood (2021)
Letter to the editor: prospective, double-blind diagnostic multicentre study of confocal laser endomicroscopy for wheat sensitivity in patients with irritable bowel syndrome
Authors: Lukas Michaja Balsiger, Jan Tack
Journal: Gut (2021)

We read with interest the study of Bojarski et al conducted in non-coeliac disease patients suffering from all subtypes of irritable bowel syndrome (IBS) according to Rome 3 criteria. The investigators showed symptom improvement in 57% of patients with IBS following a gluten-free diet (GFD) over 2 months. Interestingly, improvement of symptoms as well as stool pattern was noted in all IBS subtypes.1 Further, the authors report poor specificity and sensitivity for endoscope-based confocal laser endomicroscopy (eCLE) for detecting wheat sensitivity, defined by the authors as symptomatic improvement on a GFD.1 Based on these observations, the authors advocate an 8-week trial of GFD in patients with IBS, irrespective of …
Randomized Study of Digital Life Coaching during Autologous Stem Cell Transplantation
Authors: Rahul Banerjee, Ann A. Lazar, Chloe Ryan, Jen Knoche, Kelly Jean Brassil, Lindsey Jackson, Dhiren Patel, Mimi Lo, Shagun Arora, Alfred Chung, Sandy W. Wong, Jeffrey L. Wolf, Thomas Martin, Anand Dhruva, Nina Shah
Journal: Blood (2021)
Association of Bariatric Surgery With Cancer Incidence in Patients With Obesity and Diabetes: Long-term Results From the Swedish Obese Subjects Study
Authors: Kajsa Sjöholm, Lena M.S. Carlsson, Per-Arne Svensson, Johanna C. Andersson-Assarsson, Felipe Kristensson, Peter Jacobson, Markku Peltonen, Magdalena Taube
Journal: Diabetes Care (2021)

Obesity and type 2 diabetes are associated with serious adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study.The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of whom underwent bariatric surgery and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years).During follow-up, the incidence rate for first-time cancer was 9.1 per 1,000 person-years (95% CI 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1,000 person-years (95% CI 11.2-17.7) in patients treated with usual obesity care (adjusted hazard ratio 0.63 [95% CI 0.44-0.89], P = 0.008). Moreover, surgery was associated with reduced cancer incidence in women (0.58 [0.38-0.90], P = 0.016), although the sex-treatment interaction was nonsignificant (P = 0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (0.40 [0.22-0.74], P = 0.003).These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes and that durable diabetes remission is associated with reduced cancer risk.
Heparin-Induced Thrombocytopenia Testing: ELISA Based Anti-Platelet Factor 4 Polyspecific and IgG-Specific Antibody Detection Assays Compared to the Unfractionated Heparin Serotonin Release Assay
Authors: Edward C.C. Wong, Laura A. Worfolk, Caixia Bi, Lina J. Noh, Andrew Espinoza, William W. Wu, Mervyn A. Sahud, Frederick K. Racke, Jeffrey S. Dlott
Journal: Blood (2021)
Isatuximab Rescue for Inadequate Response to Lenalidomide and Dexamethasone in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma: Interim Analysis of the Phase II Iril Study of the Australian Myeloma Research Consortium (AMaRC 18-02)
Authors: Slavisa Ninkovic, Nicholas E. Murphy, Hasib Sidiqi, Craig Thomas Wallington-Beddoe, Anish Puliyayil, Costas K. Yannakou, Wojt Janowski, Flora Yuen, Andrew Spencer, Hang Quach
Journal: Blood (2021)
Mature Osteoblasts Are Critical Bone Marrow Niche Cells Regulating Multiple Myeloma Cell Growth, at Least in Part, By Affecting the Local Immune Microenvironment
Authors: Cristina Panaroni, Keertik Fulzele, Rie Nakamoto-Matsubara, Allison Maebius, Chukwuamaka Onyewadume, Tomoaki Mori, Noopur S. Raje
Journal: Blood (2021)