tbuckley/cabot-search huggingface dataset:
FDA Regulation and Approval of Medical Devices: 1976-2020
Authors: Jonathan J. Darrow, Jerry Avorn, Aaron S. Kesselheim
Journal: JAMA (2021)

<h3>Importance</h3> US law generally requires testing of high-risk medical devices prior to approval, as well as premarket evaluation of moderate-risk medical devices, with the goal of ensuring that the benefits of these products exceed their risks. The US Food and Drug Administration (FDA) attempts to balance the need for evidence generation with an approval process that facilitates access and encourages innovation. <h3>Objective</h3> To review the development of laws and standards affecting the evaluation and oversight of medical devices by the US regulatory system and the outcomes of this system from 1976 to 2020. <h3>Evidence Review</h3> Laws enacted by US Congress and regulations promulgated by the FDA through 2020; databases maintained by the FDA of device authorizations from 1976 to 2020; and annual reports of user fees paid to the FDA by industry. <h3>Findings</h3> Since Congress and the FDA initiated premarket review of medical devices in 1976, some fundamental innovations in the device regulation system have included special pathways to accelerate availability of investigational devices, more flexible evidence and review requirements, and increased funding to the FDA through industry-paid user fees. From 1987 to 2020, the annual number of novel devices granted premarket approval (which excludes supplements) ranged from 8 to 56 (median, 32), and the number of clearances for 510(k) devices (those that are "substantially equivalent" to marketed devices) ranged from 2804 to 5762 (median, 3404). User fee funding for devices was established in 2002 and annual fees collected increased from $30 million in 2003 (in 2019 dollars) to more than $208 million in 2019; this represented 43% of FDA funding related to the review of medical devices. Although many new devices have led to considerable patient benefit, such as hypodermic needles and magnetic resonance imaging machines, important adverse events caused by some devices, such as an implanted device for birth control and a surgical mesh implant for pelvic organ prolapse, have led to calls to reexamine the regulatory system for such products. <h3>Conclusions and Relevance</h3> Over the last 45 years, medical device regulation has become more complex, with more regulatory pathways and greater variations in the evidence and controls required for authorization. Increased FDA support from industry and concern about flexible authorization requirements reflect the tension between efficient access and the need for assurances that products will safely benefit patients.
Spinal Cord Neuronal Network Formation in a 3D Printed Reinforced Matrix—A Model System to Study Disease Mechanisms
Authors: Natalie Fischhaber, Jessica Faber, Ezgi Bakirci, Paul D. Dalton, Silvia Budday, Carmen Villmann, Natascha Schaefer
Journal: Advanced Healthcare Materials (2021)

3D cell cultures allow a better mimicry of the biological and mechanical environment of cells in vivo compared to 2D cultures. However, 3D cell cultures have been challenging for ultrasoft tissues such as the brain. The present study uses a microfiber reinforcement approach combining mouse primary spinal cord neurons in Matrigel with melt electrowritten (MEW) frames. Within these 3D constructs, neuronal network development is followed for 21 days in vitro. To evaluate neuronal development in 3D constructs, the maturation of inhibitory glycinergic synapses is analyzed using protein expression, the complex mechanical properties by assessing nonlinearity, conditioning, and stress relaxation, and calcium imaging as readouts. Following adaptation to the 3D matrix-frame, mature inhibitory synapse formation is faster than in 2D demonstrated by a steep increase in glycine receptor expression between days 3 and 10. The 3D expression pattern of marker proteins at the inhibitory synapse and the mechanical properties resemble the situation in native spinal cord tissue. Moreover, 3D spinal cord neuronal networks exhibit intensive neuronal activity after 14 days in culture. The spinal cord cell culture model using ultrasoft matrix reinforced by MEW fibers provides a promising tool to study and understand biomechanical mechanisms in health and disease.
COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020
Journal: Eurosurveillance (2020)

Severe acute respiratory syndrome coronavirus 2 community-wide transmission declined in Spain by early May 2020, being replaced by outbreaks and sporadic cases. From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified nationally, 551 active (&gt;6,200 cases) at the time. More than half of these outbreaks and cases coincided with: (i) social (family/friends’ gatherings or leisure venues) and (ii) occupational (mainly involving workers in vulnerable conditions) settings. Control measures were accordingly applied.
THADA drives Golgi residency and upregulation of PD-L1 in cancer cells and provides promising target for immunotherapy
Authors: Chushu Li, Hao Chi, Shouyan Deng, Ke Xu, Huanbin Wang, Han Yao, Yungang Wang, Dawei Chen, Xun Guo, Jing-Yuan Fang, Fang He, Jie Xu
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The abnormal upregulation of programmed death-ligand 1 (PD-L1) in cancer cells inhibits T cell-mediated cytotoxicity, but the molecular mechanisms that drive and maintain PD-L1 expression are still incompletely understood. Methods Combined analyses of genomes and proteomics were applied to find potential regulators of PD-L1. In vitro experiments were performed to investigate the regulatory mechanism of PD-L1 by thyroid adenoma associated gene (THADA) using human colorectal cancer (CRC) cells. The prevalence of THADA was analyzed using CRC tissue microarrays by immunohistochemistry. T cell killing assay, programmed cell death 1 binding assay and MC38 transplanted tumor models in C57BL/6 mice were developed to investigate the antitumor effect of THADA. Results THADA is critically required for the Golgi residency of PD-L1, and this non-redundant, coat protein complex II (COPII)-associated mechanism maintains PD-L1 expression in tumor cells. THADA mediated the interaction between PD-L1 as a cargo protein with SEC24A, a module on the COPII trafficking vesicle. Silencing THADA caused absence and endoplasmic reticulum (ER) retention of PD-L1 but not major histocompatibility complex-I, inducing PD-L1 clearance through ER-associated degradation. Targeting THADA substantially enhanced T cell-mediated cytotoxicity, and increased CD8+ T cells infiltration in mouse tumor tissues. Analysis on clinical tissue samples supported a potential role of THADA in upregulating PD-L1 expression in cancer. Conclusions Our data reveal a crucial cellular process for PD-L1 maturation and maintenance in tumor cells, and highlight THADA as a promising target for overcoming PD-L1-dependent immune evasion.
24880 A combination of 89% Vichy volcanic mineralizing water and hyaluronic acid after aggressive laser procedure for skin rejuvenating
Authors: Elena Araviiskaia, Martina Kerscher, Julieta Spada, Cecilia Orlandi, Maryna Anifilova, Sonya Abdulla, Catherine Delva, Delphine Kerob, Monika Arenbergerova, Masha Sviatoslav Tuz, Jerry Tan
Journal: Journal of the American Academy of Dermatology (2021)
The SRSF4–GAS5-Glucocorticoid Receptor Axis Regulates Ventricular Hypertrophy
Authors: Javier Larrasa-Alonso, María Villalba-Orero, Carlos Martí-Gómez, Paula Ortiz-Sánchez, Marina M. López-Olañeta, M. Ascensión Rey-Martín, Fátima Sánchez-Cabo, François McNicoll, Michaela Müller-McNicoll, Pablo García-Pavía, Enrique Lara-Pezzi
Journal: Circulation Research (2021)

[Figure: see text].
Cardiac Myoediting Attenuates Cardiac Abnormalities in Human and Mouse Models of Duchenne Muscular Dystrophy
Authors: Ayhan Atmanli, Andreas C. Chai, Miao Cui, Zhaoning Wang, Takahiko Nishiyama, Rhonda Bassel-Duby, Eric N. Olson
Journal: Circulation Research (2021)

[Figure: see text].
Predicted COVID-19 positive cases, hospitalisations, and deaths associated with the Delta variant of concern, June–July, 2021
Authors: Syed Ahmar Shah, Emily Moore, Chris Robertson, Jim McMenamin, Srinivasa Vittal Katikireddi, Colin R Simpson, Ting Shi, Uktarsh Agrawal, Colin McCowan, Sarah Stock, Lewis D Ritchie, Aziz Sheikh
Journal: The Lancet Digital Health (2021)

We previously reported on the speed with which the Delta variant of concern (VOC) took hold in Scotland.1 The Delta VOC has subsequently established itself in many other parts of the world and has emerged as the dominant strain internationally.2 Recent data have shown that the Delta VOC is more transmissible,3 associated with higher rates of hospitalisation than other variants, and that vaccines might be less effective in preventing infection than they are with the Alpha VOC.1,4 Consequently, there are concerns about the extent to which lockdown restrictions can safely be lifted, even in countries with high vaccination coverage.
A look into the future of the COVID-19 pandemic in Europe: an expert consultation
Authors: Emil Nafis Iftekhar, Viola Priesemann, Rudi Balling, Simon Bauer, Philippe Beutels, André Calero Valdez, Sarah Cuschieri, Thomas Czypionka, Uga Dumpis, Enrico Glaab, Eva Grill, Claudia Hanson, Pirta Hotulainen, Peter Klimek, Mirjam Kretzschmar, Tyll Krüger, Jenny Krutzinna, Nicola Low, Helena Machado, Carlos Martins, Martin McKee, Sebastian Bernd Mohr, Armin Nassehi, Matjaž Perc, Elena Petelos, Martyn Pickersgill, Barbara Prainsack, Joacim Rocklöv, Eva Schernhammer, Anthony Staines, Ewa Szczurek, Sotirios Tsiodras, Steven Van Gucht, Peter Willeit
Journal: The Lancet Regional Health - Europe (2021)
Alopecia in a 36-Year-Old Man With HIV Infection
Authors: Maxime J. Billick, Wayne L. Gold
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
Matricellular Protein WISP2 Is an Endogenous Inhibitor of Collagen Linearization and Cancer Metastasis
Authors: Jagadeesh Janjanam, Glendin Pano, Ruishan Wang, Benjamin A. Minden-Birkenmaier, Hannah Breeze-Jones, Eleanor Baker, Cecile Garcin, Georgia Clayton, Abbas Shirinifard, Ana Maria Zaske, David Finkelstein, Myriam Labelle
Journal: Cancer Research (2021)

Abstract Collagen remodeling contributes to many physiologic and pathologic processes. In primary tumors, the linearization of collagen fibers promotes cancer cell invasion and metastasis and is indicative of poor prognosis. However, it remains unknown whether there are endogenous inhibitors of collagen linearization that could be exploited therapeutically. Here, we show that collagen linearization is controlled by two secreted matricellular proteins with antagonistic functions. Specifically, WISP1 was secreted by cancer cells, bound to type I collagen (Col I), and linearized Col I via its cysteine-rich C-terminal (CT) domain. In contrast, WISP2, which lacks a CT domain, inhibited Col I linearization by preventing WISP1-Col I binding. Analysis of patient data revealed that WISP2 expression is lower in most solid tumors, in comparison with normal tissues. Consequently, genetic or pharmacologic restoration of higher WISP2 levels impaired collagen linearization and prevented tumor cell invasion and metastasis in vivo in models of human and murine breast cancer. Thus, this study uncovers WISP2 as the first inhibitor of collagen linearization ever identified and reveals that collagen architecture can be normalized and metastasis inhibited by therapeutically restoring a high WISP2:WISP1 ratio. Significance: Two secreted factors, WISP1 and WISP2, antagonistically regulate collagen linearization, and therapeutically increasing the WISP2:WISP1 ratio in tumors limits collagen linearization and inhibits metastasis. See related commentary by Barcus and Longmore, p. 5611
Patient‐Specific 3D Bioprinted Models of Developing Human Heart (Adv. Healthcare Mater. 15/2021)
Authors: Alexander D. Cetnar, Martin L. Tomov, Liqun Ning, Bowen Jing, Andrea S. Theus, Akaash Kumar, Amanda N. Wijntjes, Sai Raviteja Bhamidipati, Katherine Pham Do, Athanasios Mantalaris, John N. Oshinski, Reza Avazmohammadi, Brooks D. Lindsey, Holly D. Bauser‐Heaton, Vahid Serpooshan
Journal: Advanced Healthcare Materials (2021)

Cardiovascular Modeling In article number 2001169 by Holly D. Bauser-Heaton, Vahid Serpooshan, and co-workers, the integration of 3D bioprinting and perfusion bioreactor technologies is utilized to develop patient-specific 3D models of the developing human heart. This study demonstrates the use of hydrogel-based functional models, as a research enabling platform, to study the cellular function and response to flow during the normal heart development and underlying diseases.
Targeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy
Authors: Yana Pikman, Nicole Ocasio-Martinez, Gabriela Alexe, Boris Dimitrov, Samuel Kitara, Frances F. Diehl, Amanda L. Robichaud, Amy Saur Conway, Linda Ross, Angela Su, Frank Ling, Jun Qi, Giovanni Roti, Caroline A. Lewis, Alexandre Puissant, Matthew G. Vander Heiden, Kimberly Stegmaier
Journal: Leukemia (2021)

Abstract Despite progress in the treatment of acute lymphoblastic leukemia (ALL), T-cell ALL (T-ALL) has limited treatment options, particularly in the setting of relapsed/refractory disease. Using an unbiased genome-scale CRISPR-Cas9 screen we sought to identify pathway dependencies for T-ALL which could be harnessed for therapy development. Disruption of the one-carbon folate, purine and pyrimidine pathways scored as the top metabolic pathways required for T-ALL proliferation. We used a recently developed inhibitor of SHMT1 and SHMT2, RZ-2994, to characterize the effect of inhibiting these enzymes of the one-carbon folate pathway in T-ALL and found that T-ALL cell lines were differentially sensitive to RZ-2994, with the drug inducing a S/G2 cell cycle arrest. The effects of SHMT1/2 inhibition were rescued by formate supplementation. Loss of both SHMT1 and SHMT2 was necessary for impaired growth and cell cycle arrest, with suppression of both SHMT1 and SHMT2 inhibiting leukemia progression in vivo. RZ-2994 also decreased leukemia burden in vivo and remained effective in the setting of methotrexate resistance in vitro. This study highlights the significance of the one-carbon folate pathway in T-ALL and supports further development of SHMT inhibitors for treatment of T-ALL and other cancers.
Cancer as a Global Health Priority
Authors: Satish Gopal, Norman E. Sharpless
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Trends in Breast Cancer Screening in a Safety-Net Hospital During the COVID-19 Pandemic
Authors: Ana I. Velazquez, Jessica H. Hayward, Blake Gregory, Niharika Dixit
Journal: JAMA Network Open (2021)

This cross-sectional study uses electronic health record data to evaluate the association between COVID-19 and breast cancer screening at an urban integrated health system's safety-net hospital between September 2019 and January 2021.
Methyltransferase like 13 mediates the translation of Snail in head and neck squamous cell carcinoma
Authors: Xiaochen Wang, Kang Li, Yuehan Wan, Fangfang Chen, Maosheng Cheng, Gan Xiong, Ganping Wang, Shuang Chen, Zhi Chen, Jianwen Chen, Xiuyun Xu, Cheng Wang, Liang Peng, Demeng Chen
Journal: International Journal of Oral Science (2021)

Abstract Methyltransferase like 13 (METTL13), a kind of methyltransferase, is implicated in protein binding and synthesis. The upregulation of METTL13 has been reported in a variety of tumors. However, little was known about its potential function in head and neck squamous cell carcinoma (HNSCC) so far. In this study, we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level. Increased METTL13 was negatively associated with clinical prognosis. And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro. Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail, the key transcription factor in EMT, hence regulating the progression of EMT. Furthermore, Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes. Altogether, our study had revealed the oncogenic role of METTL13 in HNSCC, and provided a potential therapeutic strategy.
Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic
Authors: Justine Chinn, Shaina Sedighim, Katharine A. Kirby, Samuel Hohmann, Afshan B. Hameed, Jennifer Jolley, Ninh T. Nguyen
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Prior studies on COVID-19 and pregnancy have reported higher rates of cesarean delivery and preterm birth and increased morbidity and mortality. Additional data encompassing a longer time period are needed. <h3>Objective</h3> To examine characteristics and outcomes of a large US cohort of women who underwent childbirth with vs without COVID-19. <h3>Design, Setting, and Participants</h3> This cohort study compared characteristics and outcomes of women (age ≥18 years) who underwent childbirth with vs without COVID-19 between March 1, 2020, and February 28, 2021, at 499 US academic medical centers or community affiliates. Follow-up was limited to in-hospital course and discharge destination. Childbirth was defined by clinical classification software procedural codes of 134-137. A diagnosis of COVID-19 was identified using<i>International Statistical Classification of Diseases and Related Health Problems, Tenth Revision</i>(<i>ICD-10</i>) diagnosis of U07.1. Data were analyzed from April 1 to April 30, 2021. <h3>Exposures</h3> The presence of a COVID-19 diagnosis using<i>ICD-10</i>. <h3>Main Outcomes and Measures</h3> Analyses compared demographic characteristics, gestational age, and comorbidities. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, mechanical ventilation, and discharge status. Continuous variables were analyzed using<i>t</i>test, and categorical variables were analyzed using χ<sup>2</sup>. <h3>Results</h3> Among 869 079 women, 18 715 (2.2%) had COVID-19, and 850 364 (97.8%) did not. Most women were aged 18 to 30 years (11 550 women with COVID-19 [61.7%]; 447 534 women without COVID-19 [52.6%]) and were White (8060 White women [43.1%] in the COVID-19 cohort; 499 501 White women (58.7%) in the non–COVID-19 cohort). There was no significant increase in cesarean delivery among women with COVID-19 (6088 women [32.5%] vs 273 810 women [32.3%];<i>P</i> = .57). Women with COVID-19 were more likely to have preterm birth (3072 women [16.4%] vs 97 967 women [11.5%];<i>P</i> &lt; .001). Women giving birth with COVID-19, compared with women without COVID-19, had significantly higher rates of ICU admission (977 women [5.2%] vs 7943 women [0.9%]; odds ratio [OR], 5.84 [95% CI, 5.46-6.25];<i>P</i> &lt; .001), respiratory intubation and mechanical ventilation (275 women [1.5%] vs 884 women [0.1%]; OR, 14.33 [95% CI, 12.50-16.42];<i>P</i> &lt; .001), and in-hospital mortality (24 women [0.1%] vs 71 [&lt;0.01%]; OR, 15.38 [95% CI, 9.68-24.43];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This retrospective cohort study found that women with COVID-19 giving birth had higher rates of mortality, intubation, ICU admission, and preterm birth than women without COVID-19.
Abstract 11636: Charlson Comorbidity Index Predicts Longer-term Mortality and Re-admission in Isolated CABG
Authors: Garrett N Coyan, Hannah Chin, Ayesha Shah, Yisi Wang, Arman Kilic, Ibrahim Sultan, Christopher M Sciortino, Thomas G Gleason, Danny Chu
Journal: Circulation (2019)

Introduction: The Charlson Comorbidity Index (CCI) is widely utilized for risk stratification by providers, payors, and administrative database researchers for non-cardiac surgical patients. CCI sc...
Gene drives gaining speed
Authors: Ethan Bier
Journal: Nature Reviews Genetics (2021)

Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species. However, concerns have been raised regarding the potential unintended impacts of gene-drive systems. This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas9 and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms. These scientific advances, combined with ethical and social considerations, will facilitate the transparent and responsible advancement of these technologies towards field implementation. In this Review, Ethan Bier discusses how several impactful technical advancements, particularly involving CRISPR-based methods, are providing a diverse toolkit of gene-drive systems for the control of populations such as insect vectors of disease.