tbuckley/cabot-search huggingface dataset:
Genome-wide spatial expression profiling in formalin-fixed tissues
Authors: Eva Gracia Villacampa, Ludvig Larsson, Reza Mirzazadeh, Linda Kvastad, Alma Andersson, Annelie Mollbrink, Georgia Kokaraki, Vanessa Monteil, Niklas Schultz, Karin Sofia Appelberg, Nuria Montserrat, Haibo Zhang, Josef M. Penninger, Wolfgang Miesbach, Ali Mirazimi, Joseph Carlson, Joakim Lundeberg
Journal: Cell Genomics (2021)

Formalin-fixed paraffin embedding (FFPE) is the most widespread long-term tissue preservation approach. Here, we report a procedure to perform genome-wide spatial analysis of mRNA in FFPE-fixed tissue sections, using well-established, commercially available methods for imaging and spatial barcoding using slides spotted with barcoded oligo(dT) probes to capture the 3′ end of mRNA molecules in tissue sections. We applied this method for expression profiling and cell type mapping in coronal sections from the mouse brain to demonstrate the method's capability to delineate anatomical regions from a molecular perspective. We also profiled the spatial composition of transcriptomic signatures in two ovarian carcinosarcoma samples, exemplifying the method's potential to elucidate molecular mechanisms in heterogeneous clinical samples. Finally, we demonstrate the applicability of the assay to characterize human lung and kidney organoids and a human lung biopsy specimen infected with SARS-CoV-2. We anticipate that genome-wide spatial gene expression profiling in FFPE biospecimens will be used for retrospective analysis of biobank samples, which will facilitate longitudinal studies of biological processes and biomarker discovery.
Copy-Neutral Loss-of-Heterozygosity Adds Diagnostic and Prognostic Information to the Molecular Profiling of Hematological Malignancies
Authors: Wencke Walter, Heiko Müller, Claudia Haferlach, Constance Baer, Stephan Hutter, Niroshan Nadarajah, Wolfgang Kern, Torsten Haferlach, Manja Meggendorfer
Journal: Blood (2021)
Myeloid/Lymphoid Neoplasm with Eosinophilia and a Novel <i> RUFY1-Pdgfrb</i> Rearrangement
Authors: Karly Williams Silva, Carrie L. Cummings, Nahid Rashid, Olga Sala-Torra, Xueyan Chen, Yajuan J. Liu, Vivian G. Oehler
Journal: Blood (2021)
3D Liver Tissue Model with Branched Vascular Networks by Multimaterial Bioprinting (Adv. Healthcare Mater. 23/2021)
Authors: Xin Liu, Xinhuan Wang, Liming Zhang, Lulu Sun, Heran Wang, Hao Zhao, Zhengtao Zhang, Wenli Liu, Yiming Huang, Shen Ji, Jingjinqiu Zhang, Kai Li, Biaobiao Song, Chun Li, Hui Zhang, Song Li, Shu Wang, Xiongfei Zheng, Qi Gu
Journal: Advanced Healthcare Materials (2021)
Effectiveness of an Annular Closure Device to Prevent Recurrent Lumbar Disc Herniation
Authors: Claudius Thomé, Adisa Kuršumović, Peter Douglas Klassen, Gerrit J. Bouma, Richard Bostelmann, Frederic Martens, Martin Barth, Mark Arts, Larry E. Miller, Peter Vajkoczy, Robert Hes, Sandro Eustacchio, Dharmin Nanda, Hans-Peter Köhler, Christopher Brenke, Charlotte Flüh, Erik Van de Kelft, Richard Assaker, Jenny C. Kienzler, Javier Fandino
Journal: JAMA Network Open (2021)

Patients with large annular defects following lumbar microdiscectomy for disc herniation are at increased risk for symptomatic recurrence and reoperation.To determine whether a bone-anchored annular closure device in addition to lumbar microdiscectomy resulted in lower reherniation and reoperation rates vs lumbar microdiscectomy alone.This secondary analysis of a multicenter randomized clinical trial reports 5-year follow-up for enrolled patients between December 2010 and October 2014 at 21 clinical sites. Patients in this study had a large annular defect (6-10 mm width) following lumbar microdiscectomy for treatment of lumbar disc herniation. Statistical analysis was performed from November to December 2020.Lumbar microdiscectomy with additional bone-anchored annular closure device (device group) or lumbar microdiscectomy only (control group).The incidence of symptomatic reherniation, reoperation, and adverse events as well as changes in leg pain, Oswestry Disability Index, and health-related quality of life when comparing the device and control groups over 5 years of follow-up.Among 554 randomized participants (mean [SD] age: 43 [11] years; 327 [59%] were men), 550 were included in the modified intent-to-treat efficacy population (device group: n = 272; 270 [99%] were White); control group: n = 278; 273 [98%] were White) and 550 were included in the as-treated safety population (device group: n = 267; control group: n = 283). The risk of symptomatic reherniation (18.8% [SE, 2.5%] vs 31.6% [SE, 2.9%]; P < .001) and reoperation (16.0% [SE, 2.3%] vs 22.6% [SE, 2.6%]; P = .03) was lower in the device group. There were 53 reoperations in 40 patients in the device group and 82 reoperations in 58 patients in the control group. Scores for leg pain severity, Oswestry Disability Index, and health-related quality of life significantly improved over 5 years of follow-up with no clinically relevant differences between groups. The frequency of serious adverse events was comparable between the treatment groups. Serious adverse events associated with the device or procedure were less frequent in the device group (12.0% vs 20.5%; difference, -8.5%; 95% CI, -14.6% to -2.3%; P = .008).In patients who are at high risk of recurrent herniation following lumbar microdiscectomy owing to a large defect in the annulus fibrosus, this study's findings suggest that annular closure with a bone-anchored implant lowers the risk of symptomatic recurrence and reoperation over 5 years of follow-up.ClinicalTrials.gov Identifier: NCT01283438.
Grit and Burnout in the Physician Workforce—Reply
Authors: D. Brock Hewitt, Yue-Yung Hu, Karl Y. Bilimoria
Journal: JAMA Surgery (2021)

In Reply We thank Stergiopoulos et al and Osinski et al for their interest in our article examining general surgery resident grit and wellness.1 Both groups bring up important points that deserve additional discussion.
Hepatology Highlights
Authors: Iman Waheed Khan, Muhammad Ashar Ali, Daryl T.Y. Lau, Thuy‐Van P. Hang, Preeti A. Reshamwala, Nidhi Jalan‐Sakrikar, Robert E. Schwartz, Shalil Khanal, Enis Kostallari, Anthony J. Choi, Robert S. Brown, Adebowale O. Bamidele, Davide Povero, Wei Zhang, Alyson Kaplan, Jeremy Louissaint, Nabeel Wahid, Jessica L. Maiers
Journal: Hepatology (2021)
Retraction Note: Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma
Authors: Alexandra Garancher, Hiromichi Suzuki, Svasti Haricharan, Lianne Q. Chau, Meher Beigi Masihi, Jessica M. Rusert, Paula S. Norris, Florent Carrette, Megan M. Romero, Sorana A. Morrissy, Patryk Skowron, Florence M. G. Cavalli, Hamza Farooq, Vijay Ramaswamy, Steven J. M. Jones, Richard A. Moore, Andrew J. Mungall, Yussanne Ma, Nina Thiessen, Yisu Li, Alaide Morcavallo, Lin Qi, Mari Kogiso, Yuchen Du, Patricia Baxter, Jacob J. Henderson, John R. Crawford, Michael L. Levy, James M. Olson, Yoon-Jae Cho, Aniruddha J. Deshpande, Xiao-Nan Li, Louis Chesler, Marco A. Marra, Harald Wajant, Oren J. Becher, Linda M. Bradley, Carl F. Ware, Michael D. Taylor, Robert J. Wechsler-Reya
Journal: Nature Neuroscience (2021)
A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
Authors: Yin Peng, Yidan Xu, Xiaojing Zhang, Shiqi Deng, Yuan Yuan, Xiaonuan Luo, Md Tofazzal Hossain, Xiaohui Zhu, Kaining Du, Fan Hu, Yang Chen, Shanshan Chang, Xianling Feng, Xinmin Fan, Hassan Ashktorab, Duane Smoot, Stephen J. Meltzer, Gangqiang Hou, Yanjie Wei, Song Li, Ying Qin, Zhe Jin
Journal: Molecular Cancer (2021)

Circular RNA (circRNA), a subclass of non-coding RNA, plays a critical role in cancer tumorigenesis and metastasis. It has been suggested that circRNA acts as a microRNA sponge or a scaffold to interact with protein complexes; however, its full range of functions remains elusive. Recently, some circRNAs have been found to have coding potential.To investigate the role of circRNAs in gastric cancer (GC), parallel sequencing was performed using five paired GC samples. Differentially expressed circAXIN1 was proposed to encode a novel protein. FLAG-tagged circRNA overexpression plasmid construction, immunoblotting, mass spectrometry, and luciferase reporter analyses were applied to confirm the coding potential of circAXIN1. Gain- and loss-of-function studies were conducted to study the oncogenic role of circAXIN1 and AXIN1-295aa on the proliferation, migration, invasion, and metastasis of GC cells in vitro and in vivo. The competitive interaction between AXIN1-295aa and adenomatous polyposis coli (APC) was investigated by immunoprecipitation analyses. Wnt signaling activity was observed using a Top/Fopflash assay, real-time quantitative RT-PCR, immunoblotting, immunofluorescence staining, and chromatin immunoprecipitation.CircAXIN1 is highly expressed in GC tissues compared with its expression in paired adjacent normal gastric tissues. CircAXIN1 encodes a 295 amino acid (aa) novel protein, which was named AXIN1-295aa. CircAXIN1 overexpression enhances the cell proliferation, migration, and invasion of GC cells, while the knockdown of circAXIN1 inhibits the malignant behaviors of GC cells in vitro and in vivo. Mechanistically, AXIN1-295aa competitively interacts with APC, leading to dysfunction of the "destruction complex" of the Wnt pathway. Released β-catenin translocates to the nucleus and binds to the TCF consensus site on the promoter, inducing downstream gene expression.CircAXIN1 encodes a novel protein, AXIN1-295aa. AXIN1-295aa functions as an oncogenic protein, activating the Wnt signaling pathway to promote GC tumorigenesis and progression, suggesting a potential therapeutic target for GC.
Mass drug administration of ivermectin and dihydroartemisinin–piperaquine against malaria in settings with high coverage of standard control interventions: a cluster-randomised controlled trial in The Gambia
Authors: Edgard D Dabira, Harouna M Soumare, Bakary Conteh, Fatima Ceesay, Mamadou O Ndiath, John Bradley, Nuredin Mohammed, Balla Kandeh, Menno R Smit, Hannah Slater, Koen Peeters Grietens, Henk Broekhuizen, Teun Bousema, Chris Drakeley, Steve W Lindsay, Jane Achan, Umberto D'Alessandro
Journal: The Lancet Infectious Diseases (2021)
Rational Design of Hydrogel Networks with Dynamic Mechanical Properties to Mimic Matrix Remodeling
Authors: Katherine L. Wiley, Bryan P. Sutherland, Babatunde A. Ogunnaike, April M. Kloxin
Journal: Advanced Healthcare Materials (2021)

Engineered hydrogels are increasingly used as extracellular matrix (ECM) surrogates for probing cell function in response to ECM remodeling events related to injury or disease (e.g., degradation followed by deposition/crosslinking). Inspired by these events, this work establishes an approach for pseudo-reversible mechanical property modulation in synthetic hydrogels by integrating orthogonal, enzymatically triggered crosslink degradation, and light-triggered photopolymerization stiffening. Hydrogels are formed by a photo-initiated thiol-ene reaction between multiarm polyethylene glycol and a dually enzymatically degradable peptide linker, which incorporates a thrombin-degradable sequence for triggered softening and a matrix metalloproteinase (MMP)-degradable sequence for cell-driven remodeling. Hydrogels are stiffened by photopolymerization using a flexible, MMP-degradable polymer-peptide conjugate and multiarm macromers, increasing the synthetic matrix crosslink density while retaining degradability. Integration of these tools enables sequential softening and stiffening inspired by matrix remodeling events within loose connective tissues (Young's modulus (E) ≈5 to 1.5 to 6 kPa with >3x ΔE). The cytocompatibility and utility of this approach is examined with breast cancer cells, where cell proliferation shows a dependence on the timing of triggered softening. This work provides innovative tools for 3D dynamic property modulation that are synthetically accessible and cell compatible.
Baseline type 2 biomarker levels and response to tezepelumab in severe asthma
Authors: Jonathan Corren, Tuyet‐Hang Pham, Esther Garcia Gil, Kinga Sałapa, Pin Ren, Jane R. Parnes, Gene Colice, Janet M. Griffiths
Journal: Allergy (2021)

Abstract Background Tezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP). In the phase IIb PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. We evaluated the effects of tezepelumab in reducing type 2 (T2) inflammatory biomarker levels in the PATHWAY population, and the relationship between baseline T2 biomarker levels and AAER. Methods Adults with severe, uncontrolled asthma ( n = 550) were randomized to tezepelumab (70 mg or 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin (Ig)E, interleukin (IL)‐5, IL‐13, periostin, thymus and activation‐regulated chemokine (TARC), and TSLP were measured at baseline and over 52 weeks. AAERs were analyzed by baseline threshold (high/low) biomarker levels. Results Positive correlations were observed between T2 inflammatory biomarkers (blood eosinophil count, FeNO, IL‐5, IL‐13 and periostin) at baseline. At Week 52, treatment with tezepelumab 210 mg reduced all biomarker levels measured from baseline versus placebo. Exacerbations were reduced by 55–83% in the pooled tezepelumab cohort versus placebo, irrespective of baseline blood eosinophil count, FeNO, or serum total IgE, IL‐5, IL‐13, periostin, TARC, or TSLP, when these biomarkers were assessed individually. Conclusion At baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.
Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: a global perspective
Authors: Sarah Halawa, Soni S. Pullamsetti, Charles R. M. Bangham, Kurt R. Stenmark, Peter Dorfmüller, Maria G. Frid, Ghazwan Butrous, Nick W. Morrell, Vinicio A. de Jesus Perez, David I. Stuart, Kevin O’Gallagher, Ajay M. Shah, Yasmine Aguib, Magdi H. Yacoub
Journal: Nature Reviews Cardiology (2021)

The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with severe hypoxia being the cause of death in the most critical cases. Coronavirus disease 2019 (COVID-19) is extremely heterogeneous in terms of severity, clinical phenotype and, importantly, global distribution. Although the majority of affected patients recover from the acute infection, many continue to suffer from late sequelae affecting various organs, including the lungs. The role of the pulmonary vascular system during the acute and chronic stages of COVID-19 has not been adequately studied. A thorough understanding of the origins and dynamic behaviour of the SARS-CoV-2 virus and the potential causes of heterogeneity in COVID-19 is essential for anticipating and treating the disease, in both the acute and the chronic stages, including the development of chronic pulmonary hypertension. Both COVID-19 and chronic pulmonary hypertension have assumed global dimensions, with potential complex interactions. In this Review, we present an update on the origins and behaviour of the SARS-CoV-2 virus and discuss the potential causes of the heterogeneity of COVID-19. In addition, we summarize the pathobiology of COVID-19, with an emphasis on the role of the pulmonary vasculature, both in the acute stage and in terms of the potential for developing chronic pulmonary hypertension. We hope that the information presented in this Review will help in the development of strategies for the prevention and treatment of the continuing COVID-19 pandemic.
Measures of left atrial function predict incident heart failure in a low‐risk general population: <scp>t</scp>he <scp>Copenhagen City Heart Study</scp>
Authors: Ditte Madsen Andersen, Morten Sengeløv, Flemming Javier Olsen, Jacob Louis Marott, Gorm Boje Jensen, Peter Schnohr, Elke Platz, Morten Schou, Rasmus Mogelvang, Tor Biering‐Sørensen
Journal: European Journal of Heart Failure (2021)
Wide Complex Tachycardia and Syncope in the Emergency Department
Authors: Andrés F. Miranda-Arboleda, Shireen Mohammad, Adrian Baranchuk
Journal: Circulation (2021)

A 63-year-old man with a past medical history of type 2 diabetes, persistent atrial fibrillation (AF), and schizophrenia was brought to the emergency room after being found unconscious on the floor, with bladder and bowel incontinence.Physical examination was unremarkable, and the initial laboratory workup was positive for lactic acidosis, elevated creatine kinase, and hypomagnesemia.During cardiac monitoring performed in the emergency room, a wide complex tachycardia (WCT) was observed on telemetry, and a 12-lead ECG was obtained (Figure 1).What is the electrocardiographic diagnosis of this wide complex rhythm?Please turn the page to read the diagnosis.Figure 1.Twelve-lead ECG obtained immediately after syncopal episode.
Characterization of Potent Paracaspase MALT1 Inhibitors for Hematological Malignancies
Authors: Wu Yin, Zhe Nie, Karen Dingley, Michael Trzoss, Goran Krilov, Netonia Marshall, Shulu Feng, Robert Pelletier, Jeff Bell, Paul Devine, Peter Skrdla, Roman Shimanovich, Min Ye, David Calkins, Mary Grimes, Wayne Tang, Andrew Placzek, Morgan Lawrenz, Fiona McRobb, Aleksey Gerasyuto, Victoria Feher, Sayan Mondal, Kristian Jensen, Hamish Wright, Daniel Weiss, Karen Akinsanya
Journal: Blood (2021)
Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up
Authors: P.G. Casali, J.Y. Blay, N. Abecassis, J. Bajpai, S. Bauer, R. Biagini, S. Bielack, S. Bonvalot, I. Boukovinas, J.V.M.G. Bovee, K. Boye, T. Brodowicz, A. Buonadonna, E. De Álava, A.P. Dei Tos, X.G. Del Muro, A. Dufresne, M. Eriksson, A. Fedenko, V. Ferraresi, A. Ferrari, A.M. Frezza, S. Gasperoni, H. Gelderblom, F. Gouin, G. Grignani, R. Haas, A.B. Hassan, N. Hindi, P. Hohenberger, H. Joensuu, R.L. Jones, C. Jungels, P. Jutte, B. Kasper, A. Kawai, K. Kopeckova, D.A. Krákorová, A. Le Cesne, F. Le Grange, E. Legius, A. Leithner, A. Lopez-Pousa, J. Martin-Broto, O. Merimsky, C. Messiou, A.B. Miah, O. Mir, M. Montemurro, C. Morosi, E. Palmerini, M.A. Pantaleo, R. Piana, S. Piperno-Neumann, P. Reichardt, P. Rutkowski, A.A. Safwat, C. Sangalli, M. Sbaraglia, S. Scheipl, P. Schöffski, S. Sleijfer, D. Strauss, S.J. Strauss, K Sundby Hall, A. Trama, M. Unk, M.A.J. van de Sande, W.T.A. van der Graaf, W.J. van Houdt, T. Frebourg, A. Gronchi, S. Stacchiotti
Journal: Annals of Oncology (2021)
Errors in Figures
Journal: JAMA Network Open (2021)

Jung Eun Yoo, MD, PhD; Dong Wook Shin, MD, MBA, DrPH; Kyungdo Han, PhD; Dahye Kim, BS; Su-Min Jeong, MD; Hye Yeon Koo, MD; Su Jong Yu, MD, PhD; Jinsung Park, MD, PhD; Kui Son Choi, PhD
Hydroxyurea Reduces the Transfusion Burden in Children with Sickle Cell Anemia: The Reach Experience
Authors: Alexandra Power-Hays, George A. Tomlinson, Leon Tshilolo, Brigida Santos, Thomas N. Williams, Peter Olupot-Olupot, Patrick T. McGann, Banu Aygun, Adam Lane, Susan E. Stuber, Teresa Latham, Russell E. Ware
Journal: Blood (2021)
Current Issues in the Use of Opioids for the Management of Postoperative Pain
Authors: Pamela E. Macintyre, Jane Quinlan, Nicholas Levy, Dileep N. Lobo
Journal: JAMA Surgery (2021)

Uncontrolled and indiscriminate prescribing of opioids has led to an opioid crisis that started in North America and spread throughout high-income countries. The aim of this narrative review was to explore some of the current issues surrounding the use of opioids in the perioperative period, focusing on drivers that led to escalation of use, patient harms, the move away from using self-reported pain scores alone to assess adequacy of analgesia, concerns about the routine use of controlled-release opioids for the management of acute pain, opioid-free anesthesia and analgesia, and prescription of opioids on discharge from hospital.The origins of the opioid crisis are multifactorial and may include good intentions to keep patients pain free in the postoperative period. Assessment of patient function may be better than unidimensional numerical pain scores to help guide postoperative analgesia. Immediate-release opioids can be titrated more easily to match analgesic requirements. There is currently no good evidence to show that opioid-free anesthesia and analgesia affects opioid prescribing practices or the risk of persistent postoperative opioid use. Attention should be paid to discharge opioid prescribing as repeat and refill prescriptions are risk-factors for persistent postoperative opioid use. Opioid stewardship is paramount, and many governments are passing legislation, while statutory bodies and professional societies are providing advice and guidance to help mitigate the harm caused by opioids.Opioids remain a crucial part of many patients' journey from surgery to full recovery. The last few decades have shown that unfettered opioid use puts patients and societies at risk, so caution is needed to mitigate those dangers. Opioid stewardship provides a multilayered structure to allow continued safe use of opioids as part of broad pain management strategies for those patients who benefit from them most.
Cancer-cell stiffening via cholesterol depletion enhances adoptive T-cell immunotherapy
Authors: Kewen Lei, Armand Kurum, Murat Kaynak, Lucia Bonati, Yulong Han, Veronika Cencen, Min Gao, Yu-Qing Xie, Yugang Guo, Mélanie T. M. Hannebelle, Yangping Wu, Guanyu Zhou, Ming Guo, Georg E. Fantner, Mahmut Selman Sakar, Li Tang
Journal: Nature Biomedical Engineering (2021)
Responsive and self-healing structural color supramolecular hydrogel patch for diabetic wound treatment
Authors: Canwen Chen, Yu Wang, Han Zhang, Hui Zhang, Weiliang Dong, Weijian Sun, Yuanjin Zhao
Journal: Bioactive Materials (2021)

The treatment of diabetic wounds remains a great challenge for medical community. Here, we present a novel structural color supramolecular hydrogel patch for diabetic wound treatment. This hydrogel patch was created by using N-acryloyl glycinamide (NAGA) and 1-vinyl-1,2,4-triazole (VTZ) mixed supramolecular hydrogel as the inverse opal scaffold, and temperature responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel loaded with vascular endothelial cell growth factor (VEGF) as a filler. Supramolecular hydrogel renders hydrogel patch with superior mechanical properties, in which NAGA and VTZ also provide self-healing and antibacterial properties, respectively. Besides, as the existence of PNIPAM, the hydrogel patch was endowed with thermal-responsiveness property, which could release actives in response to temperature stimulus. Given these excellent performances, we have demonstrated that the supramolecular hydrogel patch could significantly enhance the wound healing process in diabetes rats by downregulating the expression of inflammatory factors, promoting collagen deposition and angiogenesis. Attractively, due to responsive optical property of inverse opal scaffold, the hydrogel patch could display color-sensing behavior that was suitable for the wound monitoring and management as well as guidance of clinical treatment. These distinctive features indicate that the presented hydrogel patches have huge potential values in biomedical fields.