Showing papers by "University of Miami published in 2020"
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
TL;DR: The outcomes of a cohort of patients with cancer and COVID-19 are characterised and potential prognostic factors for mortality and severe illness are identified and race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.
1,344 citations
F. Kyle Satterstrom1, F. Kyle Satterstrom2, Jack A. Kosmicki, Jiebiao Wang3 +198 more•Institutions (53)
TL;DR: The largest exome sequencing study of autism spectrum disorder (ASD) to date, using an enhanced analytical framework to integrate de novo and case-control rare variation, identifies 102 risk genes at a false discovery rate of 0.1 or less, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
1,169 citations
TL;DR: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days.
Abstract: Importance Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, −10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49];P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32];P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63];P = .83) (Pfor interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59];P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95];P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18];P Conclusion and Relevance Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration Chinese Clinical Trial Registry:ChiCTR2000029757
1,112 citations
University of Texas MD Anderson Cancer Center1, University of South Florida2, Harvard University3, Cleveland Clinic4, University of California, Los Angeles5, Texas Oncology6, Ohio State University7, Sarah Cannon Research Institute8, Stanford University9, Centre Hospitalier Universitaire de Bordeaux10, Fox Chase Cancer Center11, University of Würzburg12, University of Miami13, University of Rochester14
TL;DR: KTE-X19 induced durable remissions in a majority of patients with relapsed or refractory mantle-cell lymphoma, and led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies.
Abstract: Background Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton’s tyrosine kinase (BTK) inhibitor therapy have a poo...
875 citations
Harvard University1, University of Michigan2, Icahn School of Medicine at Mount Sinai3, Yeshiva University4, Rutgers University5, University of Pennsylvania6, Cornell University7, Rush University Medical Center8, Anschutz Medical Campus9, Northwestern University10, Medical College of Wisconsin11, Rowan University12, Hackensack University Medical Center Mountainside13, Tufts University14, Washington University in St. Louis15, Ochsner Health System16, University of Queensland17, Johns Hopkins University18, Baylor University Medical Center19, Indiana University – Purdue University Indianapolis20, University of Vermont21, Boston University22, University of Miami23, Massachusetts Institute of Technology24, Vanderbilt University25
TL;DR: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.
Abstract: Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.
706 citations
Sadaf G. Sepanlou1, Saeid Safiri2, Catherine Bisignano3, Kevin S Ikuta4 +198 more•Institutions (106)
TL;DR: Mortality, prevalence, and DALY estimates are compared with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries, and a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017.
670 citations
University of Cambridge1, King's College London2, University of Leicester3, Catholic University of the Sacred Heart4, HealthPartners5, Tan Tock Seng Hospital6, Nanyang Technological University7, University of Southampton8, University of Miami9, University of Amsterdam10, Centre national de la recherche scientifique11, Anschutz Medical Campus12, Monash University13, Imperial College London14, State University of Campinas15, The Chinese University of Hong Kong16, Peking University17
TL;DR: An international panel of experts in the field of diabetes and endocrinology is formed to provide some guidance and practical recommendations for the management of diabetes during the COVID-19 pandemic.
659 citations
TL;DR: How the immune system regulates mood and the potential causes of the dysregulated inflammatory responses in depressed patients are described, and inflammation is likely a critical disease modifier, promoting susceptibility to depression.
604 citations
TL;DR: A map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users is provided, which reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages.
Abstract: Distrust in scientific expertise1–14 is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks2–4, as happened for measles in 20195,6. Homemade remedies7,8 and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice9–11. There is a lack of understanding about how this distrust evolves at the system level13,14. Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change11, and highlight the key role of network cluster dynamics in multi-species ecologies15. Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.
417 citations
Centers for Disease Control and Prevention1, University of Miami2, New York City Department of Health and Mental Hygiene3, Broad Institute4, Harvard University5, United States Department of Health and Human Services6, University of Southern Maine7, Maine Medical Center8, Louisiana State University9, Veterans Health Administration10, Emory University11, United States Department of Energy12
TL;DR: Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms, and interventions that prevent COVID-19 might prevent MIS-B, as well as the role for antibody testing in identifying similar cases among adults.
Abstract: During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition.
Stony Brook University1, University of Minnesota2, University Health Network3, University of Strasbourg4, Duke University5, University of Kansas6, Scott & White Hospital7, Brigham and Women's Hospital8, University of California, San Francisco9, Case Western Reserve University10, University of Miami11, University of Virginia Health System12, University of Colorado Hospital13, University of Texas MD Anderson Cancer Center14, Yale University15, Harvard University16
TL;DR: This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations based on a comprehensive search and review of literature up to September 2019.
Abstract: This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages.The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.
University of Texas MD Anderson Cancer Center1, University of South Florida2, Stanford University3, Washington University in St. Louis4, Mayo Clinic5, University of Maryland, Baltimore6, University of Nebraska Medical Center7, University of Miami8, University of Rochester9, Vanderbilt University10, University of Kansas11, Wayne State University12, University of Pittsburgh13, Cleveland Clinic14, University of California, San Francisco15
TL;DR: The safety and efficacy of axi-cel in the standard-of-care (SOC) setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.
Abstract: PURPOSEAxicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of ...
TL;DR: Animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects and treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.
Abstract: During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with renin-angiotensin system blockers. Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. The present article discusses this concept. ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.
TL;DR: In a multicenter, prospective clinical trial, it is demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%).
Abstract: Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery1. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive2,3. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce4. In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH)5-7, a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20-30 min)2. In a multicenter, prospective clinical trial (n = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory.
Baylor College of Medicine1, Oakland University2, Scripps Health3, Beth Israel Deaconess Medical Center4, Emory University5, Ochsner Medical Center6, Cedars-Sinai Medical Center7, University of Texas Health Science Center at San Antonio8, University of Alabama at Birmingham9, University of Washington10, University of Miami11, Washington University in St. Louis12, Icahn School of Medicine at Mount Sinai13, University of Colorado Denver14, University of California, Irvine15, Grady Memorial Hospital16
TL;DR: The objective of this study was to establish a baseline for the development of a strategy to manage the inflammatory bowel disease-related complications of type 2 diabetes using a proprotein convertase-like mechanism.
Duke University1, University of California, Los Angeles2, Tufts University3, Queen's University Belfast4, University of Miami5, University of Bonn6, University of Paris7, Vita-Salute San Raffaele University8, Tokyo Medical and Dental University9, University of Wisconsin-Madison10, Peking University11, University of Pennsylvania12, Case Western Reserve University13, University College London14, Emory University15, Oregon Health & Science University16, University of Melbourne17, National Institutes of Health18, Massachusetts Institute of Technology19
TL;DR: The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.
University Hospital Bonn1, University of Miami2, All India Institute of Medical Sciences3, University of the Witwatersrand4, University of Texas MD Anderson Cancer Center5, University of Panama6, Kenyatta National Hospital7, University of Navarra8, Indiana University9, Mongolian National University10, King's College London11, University of Lausanne12, Makerere University13, American University of Beirut14, George Washington University15, University of Oxford16, Catholic University of Korea17
TL;DR: The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span.
TL;DR: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon.
Abstract: Background Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration–approved medical therapy is available...
Newcastle University1, Mayo Clinic2, University of Strasbourg3, Nagoya University4, University of Cambridge5, McGill University6, King's College London7, University of Exeter8, University of Chieti-Pescara9, University of Miami10, University of California, San Diego11, Northwestern University12, Harvard University13, Columbia University14, Osaka University15, Cleveland Clinic16, University of Sydney17, Sunnybrook Health Sciences Centre18, University of Washington19, University College London20, University of Toronto21
TL;DR: This work proposes operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for Use in clinical practice and are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease.
Abstract: The prodromal phase of dementia with Lewy bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.
TL;DR: This work summarizes the recent advances in PPIs modulators, including small molecules, peptides, and antibodies, hoping to provide some guidance to the design of novel drugs targeting PPIs in the future.
Abstract: Protein–protein interactions (PPIs) have pivotal roles in life processes. The studies showed that aberrant PPIs are associated with various diseases, including cancer, infectious diseases, and neurodegenerative diseases. Therefore, targeting PPIs is a direction in treating diseases and an essential strategy for the development of new drugs. In the past few decades, the modulation of PPIs has been recognized as one of the most challenging drug discovery tasks. In recent years, some PPIs modulators have entered clinical studies, some of which been approved for marketing, indicating that the modulators targeting PPIs have broad prospects. Here, we summarize the recent advances in PPIs modulators, including small molecules, peptides, and antibodies, hoping to provide some guidance to the design of novel drugs targeting PPIs in the future.
Michael A. Gillette1, Michael A. Gillette2, Shankha Satpathy2, Song Cao3 +186 more•Institutions (16)
TL;DR: Comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK.
Harvard University1, University of Pennsylvania2, University of Texas Southwestern Medical Center3, Cornell University4, University of Miami5, Ludwig Maximilian University of Munich6, Henry Ford Health System7, Medical University of South Carolina8, Saint Louis University9, University of California, San Francisco10
TL;DR: This study highlights the array of cutaneous manifestations associated with COVID-19, finding that many morphologies were non-specific, while others may provide insight into potential immune or inflammatory pathways in CO VID-19 pathophysiology.
Abstract: Background Coronavirus disease 2019 (COVID-19) has associated cutaneous manifestations. Objective To characterize the diversity of cutaneous manifestations of COVID-19 and facilitate understanding of the underlying pathophysiology. Methods Case series from an international registry from the American Academy of Dermatology and International League of Dermatological Societies. Results The registry collected 716 cases of new-onset dermatologic symptoms in patients with confirmed/suspected COVID-19. Of the 171 patients in the registry with laboratory-confirmed COVID-19, the most common morphologies were morbilliform (22%), pernio-like (18%), urticarial (16%), macular erythema (13%), vesicular (11%), papulosquamous (9.9%), and retiform purpura (6.4%). Pernio-like lesions were common in patients with mild disease, whereas retiform purpura presented exclusively in ill, hospitalized patients. Limitations We cannot estimate incidence or prevalence. Confirmation bias is possible. Conclusions This study highlights the array of cutaneous manifestations associated with COVID-19. Many morphologies were nonspecific, whereas others may provide insight into potential immune or inflammatory pathways in COVID-19 pathophysiology.
TL;DR: This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record.
TL;DR: COVID-19 diagnoses were associated with counties with greater monolingual Spanish speakers, employment rates, heart disease deaths, less social distancing, and days since the first reported case, and age (fewer <35yo).
NewYork–Presbyterian Hospital1, University of Texas MD Anderson Cancer Center2, Memorial Sloan Kettering Cancer Center3, Institut Gustave Roussy4, Ohio State University5, Johns Hopkins University6, Northwestern University7, Emory University8, Sarah Cannon Research Institute9, University of Alabama at Birmingham10, University of California, San Francisco11, University of Colorado Denver12, City of Hope National Medical Center13, Washington University in St. Louis14, University of Miami15, Harvard University16, Agios Pharmaceuticals17
TL;DR: Ivosidenib monotherapy was well tolerated and induced durable remissions and transfusion independence in patients with newly diagnosed acute myeloid leukemia (AML).
TL;DR: A comprehensive proteogenomic characterization of endometrial carcinomas revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways.
TL;DR: In this paper, the authors evaluated the safety and efficacy of pegcetacoplan (APL-2), a complement C3 inhibitor, for the treatment of Geographic Atrophy (GA), a major cause of irreversible blindness.
University of Cambridge1, National Institutes of Health2, Brigham and Women's Hospital3, Netherlands Cancer Institute4, Chapel Allerton Hospital5, University of Helsinki6, Lunenfeld-Tanenbaum Research Institute7, University Hospitals of Leicester NHS Trust8, Memorial Sloan Kettering Cancer Center9, City of Hope National Medical Center10, Lund University11, Ghent University12, University of Florida13, McGill University Health Centre14, McGill University15, University of Southern California16, Curie Institute17, University of Pennsylvania18, Leipzig University19, Manchester Academic Health Science Centre20, Harvard University21, Mayo Clinic22, University of Cologne23, University of Miami24, Vilnius University25, First Faculty of Medicine, Charles University in Prague26, National University of Singapore27, Mines ParisTech28, University of Eastern Finland29, University of California, Irvine30, University of Vermont31, Ludwig Maximilian University of Munich32, University of Toronto33, University of Malaya34, Oulu University Hospital35, University of Melbourne36, Monash University, Clayton campus37, University of Chicago38, Sapienza University of Rome39, Hannover Medical School40, University of Oulu41, University of New South Wales42, Garvan Institute of Medical Research43, Princess Anne Hospital44, Aarhus University Hospital45, Peter MacCallum Cancer Centre46, Copenhagen University Hospital47, Huntsman Cancer Institute48, QIMR Berghofer Medical Research Institute49, French Institute of Health and Medical Research50, Université de Montréal51, Vanderbilt University Medical Center52
TL;DR: PALB2 is confirmed as a major breast cancer susceptibility gene and substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers are established.
Abstract: PURPOSETo estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germl...