tbuckley/cabot-search huggingface dataset:
A rationally designed self-immolative linker enhances the synergism between a polymer-rock inhibitor conjugate and neural progenitor cells in the treatment of spinal cord injury
Authors: E. Giraldo, V.J. Nebot, S. Đorđević, R. Requejo-Aguilar, A. Alastrue-Agudo, O. Zagorodko, A. Armiñan, B. Martinez-Rojas, M.J. Vicent, V. Moreno-Manzano
Journal: Biomaterials (2021)

Rho/ROCK signaling induced after spinal cord injury (SCI) contributes to secondary damage by promoting apoptosis, inflammation, and axon growth inhibition. The specific Rho-kinase inhibitor fasudil can contribute to functional regeneration after SCI, although inherent low stability has hampered its use. To improve the therapeutic potential of fasudil, we now describe a family of rationally-designed bioresponsive polymer-fasudil conjugates based on an understanding of the conditions after SCI, such as low pH, enhanced expression of specific proteases, and a reductive environment. Fasudil conjugated to poly-l-glutamate via a self-immolative redox-sensitive linker (PGA-SS-F) displays optimal release kinetics and, consequently, treatment with PGA-SS-F significantly induces neurite elongation and axon growth in dorsal root ganglia explants, spinal cord organotypic cultures, and neural precursor cells (NPCs). The intrathecal administration of PGA-SS-F after SCI in a rat model prevents early apoptosis and induces the expression of axonal growth- and neuroplasticity-associated markers to a higher extent than the free form of fasudil. Moreover, a combination treatment comprising the acute transplantation of NPCs pre-treated with PGA-SS-F leads to enhanced cell engraftment and reduced cyst formation after SCI. In chronic SCI, combinatory treatment increases the preservation of neuronal fibers. Overall, this synergistic combinatorial strategy may represent a potentially efficient clinical approach to SCI treatment.
A rare complication of endoscopic ligation (“loop-and-let-go”) for management of a giant colonic lipoma
Authors: De-feng Li, Chao Zheng, Su-zhu Zhu, Li-juan Ye, Ben-hua Wu, Jun Yao, Li-sheng Wang
Journal: Endoscopy (2021)

A 65-year-old man presented with a 6-month history of intermittent lower gastrointestinal bleeding and lower abdominal pain. Colonoscopy revealed a soft, yellowish submucosal tumor measuring around 10 cm with a short, wide pedicle in the transverse colon ([Fig. 1 a]). Endoscopic ultrasonography showed a hyperechoic lesion originating from the submucosal layer ([Fig. 1 b]). As the endoscopic signs were compatible with a colonic lipoma, we performed endoscopic ligation (“loop-and-let-go”) to treat the giant lipoma ([Fig. 1 c]). The symptoms of bleeding and abdominal pain were relieved. Unfortunately, on the 15th day after the procedure the patient suffered from severe lower abdominal pain and vomiting. Emergency colonoscopy showed that the shedding tumor was contributing to rectal occlusion ([Fig. 1 d]), and it was removed from the rectum using oval forceps ([Fig. 1 e]; [Video 1]).
MO3-4 Impact of baseline tumor size on overall survival in patients with RR-DTC treated with lenvatinib (SELECT)
Authors: Naomi Kiyota, Makoto Tahara, Bruce Robinson, Martin Schlumberger, Steven Sherman, Sophie Leboulleux, Eun Kyung Lee, Takuya Suzuki, Min Ren, Kazuma Fushimi, Lori Wirth
Journal: Annals of Oncology (2021)
Adverse COVID‐19 outcomes in immune deficiencies: Inequality exists between subclasses
Authors: Elif Karakoc Aydiner, Sevgi Bilgic Eltan, Royale Babayeva, Omer Aydiner, Eda Kepenekli, Burcu Kolukisa, Asena Pinar Sefer, Ezgi Yalcin Gungoren, Esra Karabiber, Esra Ozek Yucel, Oner Ozdemir, Ayca Kiykim, Hasibe Artac, Nalan Yakici, Koray Yalcin, Haluk Cokugras, Tulin Tiraje Celkan, Fazil Orhan, Mehmet Akif Yesilipek, Safa Baris, Ahmet Ozen
Journal: Allergy (2021)

Abstract Background Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes. Methods We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test ( n = 25) and/or a lung tomography scoring (CORADS) ≥4 ( n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p &lt; .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin‐T, ferritin, and total‐lung‐score ( p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG ( p = .012, p = .022, p = .011; respectively). Conclusion Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID‐19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS‐Cov‐2 therapy trials.
Hydrogel Loaded with VEGF/TFEB‐Engineered Extracellular Vesicles for Rescuing Critical Limb Ischemia by a Dual‐Pathway Activation Strategy
Authors: Zheng Xing, Chen Zhao, Siwen Wu, Depeng Yang, Chunchen Zhang, Xinbo Wei, Xinran Wei, Haoran Su, Haifeng Liu, Yubo Fan
Journal: Advanced Healthcare Materials (2021)

Abstract Critical limb ischemia (CLI) is the most severe clinical manifestation of peripheral arterial disease, which causes many amputations and deaths. Conventional treatment strategies for CLI (e.g., stent implantation and vascular surgery) bring surgical risk, which are not suitable for each patient. Extracellular vesicles (EVs) can be a potential solution for CLI. Herein, vascular endothelial growth factor (VEGF; i.e., a crucial molecule related to angiogenesis) and transcription factor EB (TFEB; i.e., a pivotal regulator of autophagy) are chosen as the target gene to improve the bioactivity of EVs derived from endothelial cells. The VEGF/TFEB‐engineered EVs (Engineered‐EVs) are fabricated by genetically engineering the parent cells, and their versatile functions are confirmed using three cell models (human umbilical vein endothelial cells, myoblast, and monocytes). Injectable thermal‐responsive hydrogel are then combined with Engineered‐EVs to combat CLI. These results reveal that the hydrogel can enhance the stability of Engineered‐EVs in vivo and release EVs at different temperatures. Moreover, the results of animal studies indicate that Engineered‐EV/Hydrogel can significantly improve neovascularization, attenuate muscle injury, and recover limb function after CLI. Finally, mechanistic studies shed light on the therapeutic effect of Engineered‐EV/Hydrogel due to the activated VEGF/VEGFR pathway and autophagy‐lysosomal pathway.
Catch me if you can: how AML and its niche escape immunotherapy
Authors: Sarah Tettamanti, Alice Pievani, Andrea Biondi, Gianpietro Dotti, Marta Serafini
Journal: Leukemia (2021)

Abstract In spite of the remarkable progress in basic and preclinical studies of acute myeloid leukemia (AML), the five-year survival rate of AML patients remains poor, highlighting the urgent need for novel and synergistic therapies. Over the past decade, increased attention has been focused on identifying suitable immunotherapeutic strategies for AML, and in particular on targeting leukemic cells and their progenitors. However, recent studies have also underlined the important contribution of the leukemic microenvironment in facilitating tumor escape mechanisms leading to disease recurrence. Here, we describe the immunological features of the AML niche, with particular attention to the crosstalk between the AML blasts and the cellular components of the altered tumor microenvironment (TME) and the mechanisms of immune escape that hamper the therapeutic effects of the most advanced treatments. Considering the AML complexity, immunotherapy approaches may benefit from a rational combination of complementary strategies aimed at preventing escape mechanisms without increasing toxicity.
Black fungus: paranasal mucormycosis
Authors: Gustavo Almeida, Margarida Cardoso, Pedro Escada
Journal: BMJ (2021)

This is invasive rhino-orbito-cerebral mucormycosis on the face of a woman in her 50s (fig 1).



Fig 1 

She presented to her doctor with a history of nasal obstruction and right facial tenderness, with a background of uncontrolled diabetes, and …
MO19-2 INSIGHT2: Tepotinib + osimertinib in pts with EGFR-mutant NSCLC and acquired resistance to 1L osimertinib due to METamp
Authors: Masahiro Morise, Hiroshi Sakai, Terufumi Kato, Takaaki Tokito, Masayuki Takeda, Hiroshi Tanaka, Kenichi Chikamori, Haruko Daga, Takashi Kijima, Kadoaki Ohashi, Niki Karachaliou, Barbara Ellers-Lenz, Yi-Long Wu
Journal: Annals of Oncology (2021)
Burnout is harming GPs’ health and patient care, doctors warn
Authors: Gareth Iacobucci
Journal: BMJ (2021)

High levels of stress are severely harming the health of GPs and their ability to provide care for their patients, doctors have told MPs.

In a parliamentary briefing on 15 July representatives from the Doctors’ Association UK and the campaigning group GP Survival said there was a crisis of “unprecedented scale” in primary care that needed urgent attention.

John Hughes, a retired GP who now chairs GP Survival, said that the pressure on practices had intensified because GP numbers had not increased in line with surging demand, and ministers’ pledges to boost GP numbers had not been delivered. Constrained funding relative to the hospital sector, negative media coverage, and high levels of bureaucracy necessitated by the NHS and regulators had also contributed to GPs feeling burnt out, he added.

“GPs are leaving at a rate of three …
Screening asymptomatic <i>BMPR2</i> mutation carriers: a new frontier for pulmonary hypertension physicians?
Authors: Nicholas W. Morrell
Journal: European Respiratory Journal (2021)

It has been over 20 years since the discovery of heterozygous germline mutations in the gene encoding the bone morphogenetic protein type 2 receptor ( BMPR2 ) in families with pulmonary arterial hypertension (PAH) [1, 2]. Much has been learned since then regarding how mutations in BMPR2 cause PAH, although many questions remain unanswered. Mechanistically, loss of BMPR2 signalling in vascular cells, and particularly endothelial cells, greatly increases the likelihood of initiating the characteristic vascular pathology seen in the lungs of patients with PAH [3]. Although asymptomatic carriers of BMPR2 mutations are at markedly increased risk of developing PAH (at least 10 000-fold greater risk than non-carriers), one of the features of BMPR2 mutations is that they exhibit reduced penetrance [4]. In other words, carriers of BMPR2 mutations do not inevitably develop PAH. This is of great interest scientifically because it implies the need for additional "triggering" factors in the context of BMPR2 mutations that are required in order for disease to develop. The potential triggering factors identified to date come from in vitro studies of patient-derived cells and in genetically modified mice [5, 6]. Inflammation-induced injury seems to stimulate a greater degree of pulmonary vascular remodelling in BMPR2 deficient mice than in wild-type littermates, and BMPR2 deficient mice possess an exaggerated inflammatory response to injury [7]. This amplification of certain inflammatory pathways may initiate and propagate the vascular changes. In addition, the presence of a BMPR2 mutation in pulmonary vascular endothelial cells increases susceptibility to apoptosis and increases vascular permeability in response to injury [8–10]. These extrinsic factors act to further suppress BMPR2 signalling, or exacerbate a dysfunctional endothelium already primed by the presence of mutation. Pulmonary hypertension physicians must embrace this new and exciting aspect of clinical care of PAH patients for the benefit of our present and future patients <https://bit.ly/3pf7GhG>
3D Bioprinted Multicellular Vascular Models
Authors: Karli A. Gold, Biswajit Saha, Navaneeth Krishna Rajeeva Pandian, Brandon K. Walther, Jorge A. Palma, Javier Jo, John P. Cooke, Abhishek Jain, Akhilesh K. Gaharwar
Journal: Advanced Healthcare Materials (2021)

3D bioprinting is an emerging additive manufacturing technique to fabricate constructs for human disease modeling. However, current cell-laden bioinks lack sufficient biocompatibility, printability, and structural stability needed to translate this technology to preclinical and clinical trials. Here, a new class of nanoengineered hydrogel-based cell-laden bioinks is introduced, that can be printed into 3D, anatomically accurate, multicellular blood vessels to recapitulate both the physical and chemical microenvironments of native human vasculature. A remarkably unique characteristic of this bioink is that regardless of cell density, it demonstrates a high printability and ability to protect encapsulated cells against high shear forces in the bioprinting process. 3D bioprinted cells maintain a healthy phenotype and remain viable for nearly one-month post-fabrication. Leveraging these properties, the nanoengineered bioink is printed into 3D cylindrical blood vessels, consisting of living co-culture of endothelial cells and vascular smooth muscle cells, providing the opportunity to model vascular function and pathophysiology. Upon cytokine stimulation and blood perfusion, this 3D bioprinted vessel is able to recapitulate thromboinflammatory responses observed only in advanced in vitro preclinical models or in vivo. Therefore, this 3D bioprinted vessel provides a potential tool to understand vascular disease pathophysiology and assess therapeutics, toxins, or other chemicals.
Automatic skull defect restoration and cranial implant generation for cranioplasty
Authors: Jianning Li, Gord von Campe, Antonio Pepe, Christina Gsaxner, Enpeng Wang, Xiaojun Chen, Ulrike Zefferer, Martin Tödtling, Marcell Krall, Hannes Deutschmann, Ute Schäfer, Dieter Schmalstieg, Jan Egger
Journal: Medical Image Analysis (2021)
Whole Genome Sequencing Reveals the Extent of Structural Variants in Multiple Myeloma and Identifies Recurrent Mutational Hotspots within the Non-Coding Regions
Authors: Cody Cody Ashby, Michael Bauer, Owen W. Stephens, Christopher P. Wardell, Ruslana G. Tytarenko, Aneta Mikulasova, Purvi Patel, Shayu Deshpande, Frits van Rhee, Maurizio Zangari, Sharmilan Thanendrarajan, Carolina D. Schinke, Niels Weinhold, Leo Rasche, Faith E Davies, Gareth J. Morgan, Brian A Walker
Journal: Blood (2017)
Liquid Biopsy Goes Viral: Next-Generation Sequencing to Enhance HPV Detection
Authors: Ariana Rostami, Scott V. Bratman, Kathy Han
Journal: Clinical Cancer Research (2021)

Abstract Liquid biopsy approaches for the detection of viral DNA can provide important information for the diagnosis and identification of virally-associated cancers. Here we discuss the next-generation sequencing-based CaptHPV method for the detection and characterization of plasma human papillomavirus (HPV) DNA in HPV-associated cancers and its potential clinical utility. See related article by Sastre-Garau et al., p. 5307
High-risk Medulloblastoma—Balancing the High Stakes of Molecular Profiling to Enhance Treatment Responsivity
Authors: Allison M. Martin, Sadhana Jackson
Journal: JAMA Oncology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Comments on Computed Tomography for Evaluating Appendicitis
Authors: Diego Schaps, Donald P. Frush, Henry E. Rice
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Fewer Cardiovascular Events With Intensive Blood Pressure Control
Authors: Anita Slomski
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Highly branched poly(β-amino ester)s for gene delivery in hereditary skin diseases
Authors: Ming Zeng, Qian Xu, Dezhong Zhou, Sigen A, Fatma Alshehri, Irene Lara-Sáez, Yue Zheng, Ming Li, Wenxin Wang
Journal: Advanced Drug Delivery Reviews (2021)

Non-viral gene therapy for hereditary skin diseases is an attractive prospect. However, research efforts dedicated to this area are rare. Taking advantage of the branched structural possibilities of polymeric vectors, we have developed a gene delivery platform for the treatment of an incurable monogenic skin disease - recessive dystrophic epidermolysis bullosa (RDEB) - based on highly branched poly(β-amino ester)s (HPAEs). The screening of HPAEs and optimization of therapeutic gene constructs, together with evaluation of the combined system for gene transfection, were comprehensively reviewed. The successful restoration of type VII collagen (C7) expression both in vitro and in vivo highlights HPAEs as a promising generation of polymeric vectors for RDEB gene therapy into the clinic. Considering that the treatment of patients with genetic cutaneous disorders, such as other subtypes of epidermolysis bullosa, pachyonychia congenita, ichthyosis and Netherton syndrome, remains challenging, the success of HPAEs in RDEB treatment indicates that the development of viable polymeric gene delivery vectors could potentially expedite the translation of gene therapy for these diseases from bench to bedside.
Lung Cancer Models Reveal Severe Acute Respiratory Syndrome Coronavirus 2–Induced Epithelial-to-Mesenchymal Transition Contributes to Coronavirus Disease 2019 Pathophysiology
Authors: C. Allison Stewart, Carl M. Gay, Kavya Ramkumar, Kasey R. Cargill, Robert J. Cardnell, Monique B. Nilsson, Simon Heeke, Elizabeth M. Park, Samrat T. Kundu, Lixia Diao, Qi Wang, Li Shen, Yuanxin Xi, Bingnan Zhang, Carminia Maria Della Corte, Youhong Fan, Kiran Kundu, Boning Gao, Kimberley Avila, Curtis R. Pickering, Faye M. Johnson, Jianjun Zhang, Humam Kadara, John D. Minna, Don L. Gibbons, Jing Wang, John V. Heymach, Lauren Averett Byers
Journal: Journal of Thoracic Oncology (2021)

Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which enters host cells through the cell surface proteins ACE2 and TMPRSS2. Using a variety of normal and malignant models and tissues from the aerodigestive and respiratory tracts, we investigated the expression and regulation of ACE2 and TMPRSS2. We find that ACE2 expression is restricted to a select population of epithelial cells. Notably, infection with SARS-CoV-2 in cancer cell lines, bronchial organoids, and patient nasal epithelium induces metabolic and transcriptional changes consistent with epithelial-to-mesenchymal transition (EMT), including up-regulation of ZEB1 and AXL, resulting in an increased EMT score. In addition, a transcriptional loss of genes associated with tight junction function occurs with SARS-CoV-2 infection. The SARS-CoV-2 receptor, ACE2, is repressed by EMT through the transforming growth factor-β, ZEB1 overexpression, and onset of EGFR tyrosine kinase inhibitor resistance. This suggests a novel model of SARS-CoV-2 pathogenesis in which infected cells shift toward an increasingly mesenchymal state, associated with a loss of tight junction components with acute respiratory distress syndrome-protective effects. AXL inhibition and ZEB1 reduction, as with bemcentinib, offer a potential strategy to reverse this effect. These observations highlight the use of aerodigestive and, especially, lung cancer model systems in exploring the pathogenesis of SARS-CoV-2 and other respiratory viruses and offer important insights into the potential mechanisms underlying the morbidity and mortality of coronavirus disease 2019 in healthy patients and patients with cancer alike.