Showing papers by "Wayne State University published in 2020"
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
Christopher J L Murray1, Christopher J L Murray2, Christopher J L Murray3, Aleksandr Y. Aravkin3 +2269 more•Institutions (286)
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.
3,059 citations
TL;DR: The unfolded protein response comprises a network of signalling pathways that reprogramme transcription, translation and protein modifications to relieve the load of unfolded or misfolded proteins in the endoplasmic reticulum lumen and restore proteostasis.
Abstract: Cellular stress induced by the abnormal accumulation of unfolded or misfolded proteins at the endoplasmic reticulum (ER) is emerging as a possible driver of human diseases, including cancer, diabetes, obesity and neurodegeneration. ER proteostasis surveillance is mediated by the unfolded protein response (UPR), a signal transduction pathway that senses the fidelity of protein folding in the ER lumen. The UPR transmits information about protein folding status to the nucleus and cytosol to adjust the protein folding capacity of the cell or, in the event of chronic damage, induce apoptotic cell death. Recent advances in the understanding of the regulation of UPR signalling and its implications in the pathophysiology of disease might open new therapeutic avenues.
835 citations
Baylor College of Medicine1, Northwestern University2, Johns Hopkins University3, Harvard University4, Baystate Medical Center5, Wayne State University6, Rutgers University7, Columbia University8, Ohio State University9, University of Pennsylvania10, University of Washington11, University of Texas Health Science Center at Houston12, Children's National Medical Center13
TL;DR: The burden of COVID-19 infection in North American PICUs is described and confirmed that severe illness in children is significant but far less frequent than in adults and prehospital comorbidities appear to be an important factor in children.
Abstract: Importance The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). Objective To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. Design, Setting, and Participants This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. Main Outcomes and Measures Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. Results Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. Conclusions and Relevance This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.
758 citations
University of Jena1, University of Bologna2, Cornell University3, Wayne State University4, Imperial College London5, University of Liverpool6, Georgia Regents University7, Huntsman Cancer Institute8, Norwegian University of Science and Technology9, University of South Australia10, University of Amsterdam11, University of Texas MD Anderson Cancer Center12, Catholic University of Korea13, University of Chicago14, University of Toronto15, University of Bordeaux16, Masaryk University17, Leipzig University18, University of Naples Federico II19, Fred Hutchinson Cancer Research Center20, Lund University21, University of Turin22, Heidelberg University23, Russian Academy24
TL;DR: An expert panel to critically evaluate and update the evidence to achieve goals to achieve a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR) in chronic myeloid leukemia.
Abstract: The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
683 citations
TL;DR: The FLUXNET2015 dataset provides ecosystem-scale data on CO 2 , water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe, and is detailed in this paper.
Abstract: The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.
681 citations
TL;DR: This review systematically analyzes the available human studies to identify harmful stressors, vulnerable periods during pregnancy, specificities in the outcome and biological correlates of the relation between maternal stress and offspring outcome.
653 citations
Eugene Applebaum College of Pharmacy and Health Sciences1, University of Montana2, Albany College of Pharmacy and Health Sciences3, Wayne State University4, University of California, San Diego5, Fred Hutchinson Cancer Research Center6, University of Michigan7, University of Southern California8, University of Minnesota9, University of Illinois at Urbana–Champaign10, Arkansas Children's Hospital11, Albany Medical College12
TL;DR: The primary recommendations consisted of eliminating routine monitoring of serum peak concentrations, emphasizing a ratio of area under the curve over 24 hours to minimum inhibitory concentration (AUC/ MIC) of ≥400 as the primary PK/ PD predictor of vancomycin activity, and promoting serum trough concentrations of 15 to 20 mg/L as a surrogate marker for the optimal vancomYcin AUC/MIC if the MIC was ≤1mg/L in patients with normal renal function.
Abstract: Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400-600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.
622 citations
01 Jun 2020
TL;DR: In this case series involving 463 consecutive patients with confirmed coronavirus disease 2019 evaluated at a 5-hospital system serving metropolitan Detroit, a high proportion were admitted and required intensive care unit admission and invasive mechanical ventilation with a mortality rate of 40.4% among patients in theintensive care unit.
Abstract: Importance In late December 2019, an outbreak caused by a novel severe acute respiratory syndrome coronavirus 2 emerged in Wuhan, China. Data on the clinical characteristics and outcomes of infected patients in urban communities in the US are limited. Objectives To describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and to perform a comparative analysis of hospitalized and ambulatory patient populations. Design, Setting, and Participants This study is a case series of 463 consecutive patients with COVID-19 evaluated at Henry Ford Health System in metropolitan Detroit, Michigan, from March 9 to March 27, 2020. Data analysis was performed from March to April 2020. Exposure Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures Demographic data, underlying comorbidities, clinical presentation, complications, treatment, and outcomes were collected. Results Of 463 patients with COVID-19 (mean [SD] age, 57.5 [16.8] years), 259 (55.9%) were female, and 334 (72.1%) were African American. Most patients (435 [94.0%]) had at least 1 comorbidity, including hypertension (295 patients [63.7%]), chronic kidney disease (182 patients [39.3%]), and diabetes (178 patients [38.4%]). Common symptoms at presentation were cough (347 patients [74.9%]), fever (315 patients [68.0%]), and dyspnea (282 patients [60.9%]). Three hundred fifty-five patients (76.7%) were hospitalized; 141 (39.7%) required intensive care unit management and 114 (80.8%) of those patients required invasive mechanical ventilation. Male sex (odds ratio [OR], 2.0; 95% CI, 1.3-3.2;P = .001), severe obesity (OR, 2.0; 95% CI, 1.4-3.6;P = .02), and chronic kidney disease (OR, 2.0; 95% CI, 1.3-3.3;P = .006) were independently associated with intensive care unit admission. Patients admitted to the intensive care unit had longer length of stay and higher incidence of respiratory failure and acute respiratory distress syndrome requiring invasive mechanical ventilation, acute kidney injury requiring dialysis, shock, and mortality (57 patients [40.4%] vs 15 patients [7.0%]) compared with patients in the general practice unit. Twenty-nine (11.2%) of those discharged from the hospital were readmitted and, overall, 20.0% died within 30 days. Male sex (OR, 1.8; 95% CI, 1.1-3.1;P = .03) and age older than 60 years (OR, 5.3; 95% CI, 2.9-9.7;P Conclusions and Relevance In this review of urban metropolitan patients with COVID-19, most were African American with a high prevalence of comorbid conditions and high rates of hospitalization, intensive care unit admission, complications, and mortality due to COVID-19.
478 citations
TL;DR: The role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19 was evaluated, and the primary outcome was in-hospital mortality.
447 citations
Mayo Clinic1, Yeshiva University2, University of Texas MD Anderson Cancer Center3, National Institutes of Health4, Medical College of Wisconsin5, Washington University in St. Louis6, Emory University7, Université de Montréal8, Wayne State University9, University of Rochester10, University of Wisconsin-Madison11, University of Arizona12, Northwestern University13, University of Chicago14, Thomas Jefferson University15, Vanderbilt University16
TL;DR: HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.
Abstract: PURPOSERadiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy dur...
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 ...
Johns Hopkins University1, Royal Brisbane and Women's Hospital2, University of Queensland3, University Hospitals of Cleveland4, Wayne State University5, Sheba Medical Center6, Başkent University7, Erasmus University Rotterdam8, Karolinska Institutet9, University of St. Gallen10, Kitasato University11, Samsung Medical Center12, Columbia University Medical Center13, Merck & Co.14, Institute of Cancer Research15
TL;DR: Pembrolizumab monotherapy shows antitumor activity with an acceptable safety profile in a subset of patients with RECIST-measurable and bone-predominant mCRPC previously treated with docetaxel and targeted endocrine therapy.
Abstract: PURPOSEPembrolizumab has previously shown antitumor activity against programmed death ligand 1 (PD-L1)–positive metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed the antitu...
TL;DR: In-depth analysis of TEGs is presented, starting by an extensive description of their working principle, types, used materials, figure of merit, improvement techniques including different thermoelectric materials arrangement (conventional, segmented and cascaded), and used technologies and substrates types (silicon, ceramics and polymers).
TL;DR: The reason why pregnant women are more susceptible to COVID-19 and the potential maternal and fetal complications from an immunological viewpoint is focused on.
TL;DR: To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—the authors estimated additional population equivalents with UHC effective coverage from 2018 to 2023, and quantified frontiers of U HC effective coverage performance on the basis of pooled health spending per capita.
Abstract: There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like XYZ states at BESIII and B factories, and the observation of an intriguing proton-antiproton threshold enhancement and the possibly related X(1835) meson state at BESIII, as well as the threshold measurements of charm mesons and charm baryons. We present a detailed survey of the important topics in tau-charm physics and hadron physics that can be further explored at BESIII during the remaining operation period of BEPCII. This survey will help in the optimization of the data-taking plan over the coming years, and provides physics motivation for the possible upgrade of BEPCII to higher luminosity.
TL;DR: For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.
Abstract: New sets of CMS underlying-event parameters (“tunes”) are presented for the pythia8 event generator. These tunes use the NNPDF3.1 parton distribution functions (PDFs) at leading (LO), next-to-leading (NLO), or next-to-next-to-leading (NNLO) orders in perturbative quantum chromodynamics, and the strong coupling evolution at LO or NLO. Measurements of charged-particle multiplicity and transverse momentum densities at various hadron collision energies are fit simultaneously to determine the parameters of the tunes. Comparisons of the predictions of the new tunes are provided for observables sensitive to the event shapes at LEP, global underlying event, soft multiparton interactions, and double-parton scattering contributions. In addition, comparisons are made for observables measured in various specific processes, such as multijet, Drell–Yan, and top quark-antiquark pair production including jet substructure observables. The simulation of the underlying event provided by the new tunes is interfaced to a higher-order matrix-element calculation. For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.
Harvard University1, University of Washington2, Humboldt University of Berlin3, Imperial College London4, University of Belgrade5, Istituto Nazionale di Fisica Nucleare6, Technical University of Berlin7, University of Bordeaux8, University of Oxford9, University of Valencia10, Rutherford Appleton Laboratory11, University of Strathclyde12, King's College London13, Foundation for Research & Technology – Hellas14, University of Birmingham15, University College London16, University of Liverpool17, National Physical Laboratory18, University of Nottingham19, University of Sussex20, Fermilab21, Northern Illinois University22, Peking University23, University of Pisa24, University of California, Riverside25, University of Nevada, Reno26, CERN27, University of Niš28, National Institute of Chemical Physics and Biophysics29, British University in Egypt30, Beni-Suef University31, Leibniz University of Hanover32, Paul Sabatier University33, University of Paris34, University of Cambridge35, Wayne State University36, Stanford University37, University of Bergen38, University of Amsterdam39, Northwestern University40, University of Bristol41, University of Warsaw42, University of Illinois at Urbana–Champaign43, Fayoum University44, University of Crete45, Queen's University Belfast46, Brandeis University47, University of Bologna48, Cochin University of Science and Technology49, German Aerospace Center50, University of Manchester51, University of Copenhagen52, University of Düsseldorf53, University of Vienna54, Florida State University55, University of Florence56, University of Illinois at Chicago57, University of Bremen58, University of Mainz59, Chinese Academy of Sciences60, University of Cincinnati61
TL;DR: The Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE) as mentioned in this paper is a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments.
Abstract: We propose in this White Paper a concept for a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments. This interdisciplinary experiment, called Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE), will also complement other planned searches for dark matter, and exploit synergies with other gravitational wave detectors. We give examples of the extended range of sensitivity to ultra-light dark matter offered by AEDGE, and how its gravitational-wave measurements could explore the assembly of super-massive black holes, first-order phase transitions in the early universe and cosmic strings. AEDGE will be based upon technologies now being developed for terrestrial experiments using cold atoms, and will benefit from the space experience obtained with, e.g., LISA and cold atom experiments in microgravity.
TL;DR: The potential of exploiting the modulation of ACE2/ MAS pathway as a natural protection of lung injury by modulation ofACE2/MAS axis or by developing targeted drugs to inhibit proteases required for viral entry is speculated.
Abstract: The rapidly evolving pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection worldwide cost many lives. The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. As such, it is now receiving renewed attention as a potential target for anti-viral therapeutics. We review the physiological functions of ACE2 in the cardiovascular system and the lungs, and how the activation of ACE2/MAS/G protein coupled receptor contributes in reducing acute injury and inhibiting fibrogenesis of the lungs and protecting the cardiovascular system. In this perspective, we predominantly focus on the impact of SARS-CoV-2 infection on ACE2 and dysregulation of the protective effect of ACE2/MAS/G protein pathway vs. the deleterious effect of Renin/Angiotensin/Aldosterone. We discuss the potential effect of invasion of SARS-CoV-2 on the function of ACE2 and the loss of the protective effect of the ACE2/MAS pathway in alveolar epithelial cells and how this may amplify systemic deleterious effect of renin-angiotensin aldosterone system (RAS) in the host. Furthermore, we speculate the potential of exploiting the modulation of ACE2/MAS pathway as a natural protection of lung injury by modulation of ACE2/MAS axis or by developing targeted drugs to inhibit proteases required for viral entry.
TL;DR: This work constitutes the most precise measurements of R(D) and R (D^{*}) performed to date as well as the first result for R( D) based on a semileptonic tagging method.
Abstract: The experimental results on the ratios of branching fractions $\mathcal{R}(D) = {\cal B}(\bar{B} \to D \tau^- \bar{
u}_{\tau})/{\cal B}(\bar{B} \to D \ell^- \bar{
u}_{\ell})$ and $\mathcal{R}(D^*) = {\cal B}(\bar{B} \to D^* \tau^- \bar{
u}_{\tau})/{\cal B}(\bar{B} \to D^* \ell^- \bar{
u}_{\ell})$, where $\ell$ denotes an electron or a muon, show a long-standing discrepancy with the Standard Model predictions, and might hint to a violation of lepton flavor universality. We report a new simultaneous measurement of $\mathcal{R}(D)$ and $\mathcal{R}(D^*)$, based on a data sample containing $772 \times 10^6$ $B\bar{B}$ events recorded at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB $e^+ e^-$ collider. In this analysis the tag-side $B$ meson is reconstructed in a semileptonic decay mode and the signal-side $\tau$ is reconstructed in a purely leptonic decay. The measured values are $\mathcal{R}(D)= 0.307 \pm 0.037 \pm 0.016$ and $\mathcal{R}(D^*) = 0.283 \pm 0.018 \pm 0.014$, where the first uncertainties are statistical and the second are systematic. These results are in agreement with the Standard Model predictions within $0.2$, $1.1$ and $0.8$ standard deviations for $\mathcal{R}(D)$, $\mathcal{R}(D^*)$ and their combination, respectively. This work constitutes the most precise measurements of $\mathcal{R}(D)$ and $\mathcal{R}(D^*)$ performed to date as well as the first result for $\mathcal{R}(D)$ based on a semileptonic tagging method.
Memorial Sloan Kettering Cancer Center1, Columbia University Medical Center2, NewYork–Presbyterian Hospital3, Hackensack University Medical Center4, Karolinska Institutet5, Northwestern University6, University of Colorado Boulder7, Yale University8, Harvard University9, University of Belgrade10, National Institutes of Health11, Syracuse University12, University of Rochester13, Fred Hutchinson Cancer Research Center14, University of São Paulo15, University of Pennsylvania16, Duke University17, Roswell Park Cancer Institute18, Rush University Medical Center19, Wayne State University20, Nottingham University Hospitals NHS Trust21, St James's University Hospital22, Royal Bournemouth Hospital23, Western General Hospital24, Leicester Royal Infirmary25, The Royal Marsden NHS Foundation Trust26, University of Birmingham27, Beatson West of Scotland Cancer Centre28, King's College London29, University of Oslo30, University of Oxford31
TL;DR: The data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death.
TL;DR: The molecular profile of gastric tumors, the success, and challenges with available therapeutic targets along with newer biomarkers and emerging targets are discussed.
Abstract: Gastric cancer remains a major unmet clinical problem with over 1 million new cases worldwide. It is the fourth most commonly occurring cancer in men and the seventh most commonly occurring cancer in women. A major fraction of gastric cancer has been linked to variety of pathogenic infections including but not limited to Helicobacter pylori (H. pylori) or Epstein Barr virus (EBV). Strategies are being pursued to prevent gastric cancer development such as H. pylori eradication, which has helped to prevent significant proportion of gastric cancer. Today, treatments have helped to manage this disease and the 5-year survival for stage IA and IB tumors treated with surgery are between 60 and 80%. However, patients with stage III tumors undergoing surgery have a dismal 5-year survival rate between 18 and 50% depending on the dataset. These figures indicate the need for more effective molecularly driven treatment strategies. This review discusses the molecular profile of gastric tumors, the success, and challenges with available therapeutic targets along with newer biomarkers and emerging targets.
TL;DR: It is reported that co-transcription of ACE2 and TMPRSS2 is negligible in the placenta, thus not a likely path of vertical transmission for SARS-CoV-2.
Abstract: The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 10 million people, including pregnant women. To date, no consistent evidence for the vertical transmission of SARS-CoV-2 exists. The novel coronavirus canonically utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and the serine protease TMPRSS2 for cell entry. Herein, building upon our previous single-cell study (Pique-Regi et al., 2019), another study, and new single-cell/nuclei RNA-sequencing data, we investigated the expression of ACE2 and TMPRSS2 throughout pregnancy in the placenta as well as in third-trimester chorioamniotic membranes. We report that co-transcription of ACE2 and TMPRSS2 is negligible in the placenta, thus not a likely path of vertical transmission for SARS-CoV-2. By contrast, receptors for Zika virus and cytomegalovirus, which cause congenital infections, are highly expressed by placental cell types. These data show that the placenta minimally expresses the canonical cell-entry mediators for SARS-CoV-2.
TL;DR: In this paper, a practical guide to conducting latent profile analysis (LPA) in the Mplus software system is presented, which is intended for researchers familiar with some latent variable modes.
Abstract: The present guide provides a practical guide to conducting latent profile analysis (LPA) in the Mplus software system. This guide is intended for researchers familiar with some latent variable mode...
TL;DR: Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared.
Abstract: Objective To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese. Design Systematic review and network meta-analysis of randomised trials. Data sources Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews. Study selection Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet. Outcomes and measures Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up. Review methods Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets. Results 121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 v 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty v 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 v 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty v 7.08 mg/dL, moderate certainty v 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (−1.88 mg/dL, moderate certainty) and moderate macronutrient (−0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared. Conclusions Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear. Systematic review registration PROSPERO CRD42015027929.
UCLA Medical Center1, Fred Hutchinson Cancer Research Center2, Brigham and Women's Hospital3, Stanford University4, University of Washington5, University of Pittsburgh6, Wayne State University7, Stony Brook University8, University of Tennessee Health Science Center9, Albert Einstein College of Medicine10, Ohio State University11, University of Florida Health12
TL;DR: This long-term follow-up study of 2 placebo-controlled randomized clinical trials found prior randomized use of CEE alone, compared with placebo, among women who had a previous hysterectomy was significantly associated withLower breast cancer incidence and lower breast cancer mortality, whereas prior randomizedUse of Cee plus MPA, comparedWithplace, amongWomen who had an intact uterus, was significant associated with a higher breast cancers incidence but no significant difference in breast cancer deaths.
Abstract: Importance The influence of menopausal hormone therapy on breast cancer remains unsettled with discordant findings from observational studies and randomized clinical trials. Objective To assess the association of prior randomized use of estrogen plus progestin or prior randomized use of estrogen alone with breast cancer incidence and mortality in the Women’s Health Initiative clinical trials. Design, Setting, and Participants Long-term follow-up of 2 placebo-controlled randomized clinical trials that involved 27 347 postmenopausal women aged 50 through 79 years with no prior breast cancer and negative baseline screening mammogram. Women were enrolled at 40 US centers from 1993 to 1998 with follow-up through December 31, 2017. Interventions In the trial involving 16 608 women with a uterus, 8506 were randomized to receive 0.625 mg/d of conjugated equine estrogen (CEE) plus 2.5 mg/d of medroxyprogesterone acetate (MPA) and 8102, placebo. In the trial involving 10 739 women with prior hysterectomy, 5310 were randomized to receive 0.625 mg/d of CEE alone and 5429, placebo. The CEE-plus-MPA trial was stopped in 2002 after 5.6 years’ median intervention duration, and the CEE-only trial was stopped in 2004 after 7.2 years’ median intervention duration. Main Outcomes and Measures The primary outcome was breast cancer incidence (protocol prespecified primary monitoring outcome for harm) and secondary outcomes were deaths from breast cancer and deaths after breast cancer. Results Among 27 347 postmenopausal women who were randomized in both trials (baseline mean [SD] age, 63.4 years [7.2 years]), after more than 20 years of median cumulative follow-up, mortality information was available for more than 98%. CEE alone compared with placebo among 10 739 women with a prior hysterectomy was associated with statistically significantly lower breast cancer incidence with 238 cases (annualized rate, 0.30%) vs 296 cases (annualized rate, 0.37%; hazard ratio [HR], 0.78; 95% CI, 0.65-0.93;P = .005) and was associated with statistically significantly lower breast cancer mortality with 30 deaths (annualized mortality rate, 0.031%) vs 46 deaths (annualized mortality rate, 0.046%; HR, 0.60; 95% CI, 0.37-0.97;P = .04). In contrast, CEE plus MPA compared with placebo among 16 608 women with a uterus was associated with statistically significantly higher breast cancer incidence with 584 cases (annualized rate, 0.45%) vs 447 cases (annualized rate, 0.36%; HR, 1.28; 95% CI, 1.13-1.45;P Conclusions and Relevance In this long-term follow-up study of 2 randomized trials, prior randomized use of CEE alone, compared with placebo, among women who had a previous hysterectomy, was significantly associated with lower breast cancer incidence and lower breast cancer mortality, whereas prior randomized use of CEE plus MPA, compared with placebo, among women who had an intact uterus, was significantly associated with a higher breast cancer incidence but no significant difference in breast cancer mortality.
University of California, San Francisco1, Yale University2, Harvard University3, Roswell Park Cancer Institute4, University of Queensland5, Memorial Sloan Kettering Cancer Center6, Cleveland Clinic7, Stanford University8, Wayne State University9, Medical College of Wisconsin10, Monash University11, University of Pittsburgh12, University of Arizona13, University of Chicago14, Icahn School of Medicine at Mount Sinai15, University of Washington16, Rush University Medical Center17, Ronald Reagan UCLA Medical Center18, University of Nebraska Medical Center19, Ottawa Hospital20
TL;DR: A phase 1 clinical trial with a small molecule A2AR antagonist is found that this molecule can safely block adenosine signaling in vivo and represents a targetable immune checkpoint distinct from PD-(L)1 that restricts anti-tumor immunity.
Abstract: Adenosine mediates immunosuppression within the tumor microenvironment through triggering adenosine 2A receptors (A2AR) on immune cells. To determine whether this pathway could be targeted as an immunotherapy, we performed a phase I clinical trial with a small-molecule A2AR antagonist. We find that this molecule can safely block adenosine signaling in vivo. In a cohort of 68 patients with renal cell cancer (RCC), we also observe clinical responses alone and in combination with an anti-PD-L1 antibody, including subjects who had progressed on PD-1/PD-L1 inhibitors. Durable clinical benefit is associated with increased recruitment of CD8+ T cells into the tumor. Treatment can also broaden the circulating T-cell repertoire. Clinical responses are associated with an adenosine-regulated gene-expression signature in pretreatment tumor biopsies. A2AR signaling, therefore, represents a targetable immune checkpoint distinct from PD-1/PD-L1 that restricts antitumor immunity. SIGNIFICANCE: This first-in-human study of an A2AR antagonist for cancer treatment establishes the safety and feasibility of targeting this pathway by demonstrating antitumor activity with single-agent and anti-PD-L1 combination therapy in patients with refractory RCC. Responding patients possess an adenosine-regulated gene-expression signature in pretreatment tumor biopsies.See related commentary by Sitkovsky, p. 16.This article is highlighted in the In This Issue feature, p. 1.
TL;DR: The results suggest that performing even light physical activity during the COVID-19 pandemic may help alleviate some of the negative mental health impacts that older adults may be experiencing while isolated and adhering to SDG during theCOVD-19Pandemic.
Abstract: Objective To determine the relationship between the amount and intensity of physical activity performed by older adults in North America (United States and Canada) and their depression and anxiety symptoms while currently under social distancing guidelines (SDG) for the COVID-19 pandemic. Design Descriptive cross-sectional study. Setting Online survey conducted between April 9 and April 30, 2020, during the COVD-19 pandemic. Participants About 1,046 older adults over the age of 50 who live in North America. Measurements Participants were asked about their basic demographic information, current health status, and the impact of the current SDG on their subjective state of mental health. Participants completed the Physical Activity Scale for the Elderly, to determine the amount and intensity of physical activity performed, as well as both the Geriatric Depression Scale and Geriatric Anxiety Scale, to ascertain the extent of their depression and anxiety-like symptoms. Results Ninety-seven percent of participants indicated that they adhered to current SDG “Most of the time” or “Strictly.” Participants who performed greater levels of physical activity experienced lower levels of depression-like symptoms when age, sex, and education were accounted for; however, no relationship between physical activity and anxiety-like symptoms was found. A hierarchical regression analysis that incorporated the intensity of physical activity performed (light, moderate, and vigorous) in the model indicated that greater light and strenuous activity, but not moderate, predicted lower depression-like symptoms. Conclusions These results suggest that performing even light physical activity during the COVID-19 pandemic may help alleviate some of the negative mental health impacts that older adults may be experiencing while isolated and adhering to SDG during the COVID-19 pandemic.
TL;DR: This comprehensive review discusses the current published literature surrounding the SARS-CoV-2 virus and identifies and provides insight into controversies and research gaps for the current pandemic to assist with future research ideas.
Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that is responsible for the 2019-2020 pandemic. In this comprehensive review, we discuss the current published literature surrounding the SARS-CoV-2 virus. We examine the fundamental concepts including the origin, virology, pathogenesis, clinical manifestations, diagnosis, laboratory, radiology, and histopathologic findings, complications, and treatment. Given that much of the information has been extrapolated from what we know about other coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), we identify and provide insight into controversies and research gaps for the current pandemic to assist with future research ideas. Finally, we discuss the global response to the coronavirus disease-2019 (COVID-19) pandemic and provide thoughts regarding lessons for future pandemics.