Showing papers by "Istanbul University published in 2021"
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
Hacettepe University1, Turkish Ministry of Health2, Yıldırım Beyazıt University3, Ankara University4, Kocaeli University5, İzmir University6, Uludağ University7, Istanbul University8, Ege University9, Akdeniz University10, Acıbadem University11, Çukurova University12, Marmara University13, Karadeniz Technical University14, Dicle University15, İnönü University16, University of Gaziantep17
TL;DR: CoronaVac as discussed by the authors has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2.
616 citations
Başkent University1, Hacettepe University2, Istanbul Medeniyet University3, Dniepropetrovsk State Medical Academy4, Istanbul University5, Bezmialem Foundation University6, Trakya University7, Illawarra Health & Medical Research Institute8, Chulalongkorn University9, Columbia University Medical Center10, Regeneron11, Çukurova University12
TL;DR: In this paper, the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50% was examined in a multicentre, open-label, global, phase 3 study.
342 citations
University of Manchester1, Kansai Medical University2, Institut Gustave Roussy3, Complutense University of Madrid4, Katholieke Universiteit Leuven5, Sarah Cannon Research Institute6, VU University Amsterdam7, Johns Hopkins University8, Memorial Sloan Kettering Cancer Center9, Peking Union Medical College10, Istanbul University11, Chungbuk National University12, Yonsei University13, AstraZeneca14
TL;DR: These updated, exploratory analyses demonstrate durable PFS and sustained OS benefit with durvalumab following CRT, and are consistent with the primary analyses.
299 citations
TL;DR: In this paper, the authors investigated the prevalence of delirium and coma, and risk factors for delirius in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirious and associated sequelae.
296 citations
Abstract: Summary Background First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum–etoposide) showed a significant improvement in overall survival versus platinum–etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide alone. Methods CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum–etoposide, durvalumab plus platinum–etoposide, or platinum–etoposide alone. In all groups, patients received etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL/min or cisplatin 75–80 mg/m2 on day 1 of each cycle. Patients in the platinum–etoposide group received up to six cycles of platinum–etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum–etoposide versus platinum–etoposide and for durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 patients in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation First-line durvalumab plus platinum–etoposide showed sustained overall survival improvement versus platinum–etoposide but the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide. These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding AstraZeneca.
274 citations
TL;DR: In this paper, the authors assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma.
Abstract: Summary Background PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. Methods KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov , number NCT02853305 . Findings Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7–36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5–8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4–7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65–0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5–19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3–16·7) in the chemotherapy group (0·86, 0·72–1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1–17·9] with pembrolizumab vs 14·3 months [12·3–16·7] with chemotherapy; HR 0·92, 95% CI 0·77–1·11) and the population with CPS of at least 10 (16·1 months [13·6–19·9] with pembrolizumab vs 15·2 months [11·6–23·3] with chemotherapy; 1·01, 0·77–1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. Interpretation The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. Funding Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.
262 citations
Vita-Salute San Raffaele University1, University of Foggia2, University of Milan3, University of Florence4, Aberdeen Royal Infirmary5, Selçuk University6, Istanbul University7, Universidad Francisco de Vitoria8, Katholieke Universiteit Leuven9, Manchester Royal Infirmary10, University of Catania11, Imperial College London12, University of Salerno13, Charing Cross Hospital14
TL;DR: The European Association of Urology (EAU) guidelines on male sexual health were updated in March 2019, with a last comprehensive update in January 2019 as mentioned in this paper, with a systematic review of the evidence or a consensus opinion from the expert panel.
231 citations
French Institute of Health and Medical Research1, Claude Bernard University Lyon 12, UCL Institute of Neurology3, Autonomous University of Barcelona4, University Hospital of Basel5, University of Düsseldorf6, National and Kapodistrian University of Athens7, University of Florence8, University of Southern Denmark9, University of Pennsylvania10, Children's Hospital of Philadelphia11, Anschutz Medical Campus12, Children's Hospital at Westmead13, Harvard University14, University of Paris-Sud15, University of Strasbourg16, Fukushima Medical University17, Cleveland Clinic18, Walton Centre19, Ruhr University Bochum20, Medical University of Vienna21, John Radcliffe Hospital22, University of Glasgow23, Ludwig Maximilian University of Munich24, Humboldt University of Berlin25, University College London26, Moorfields Eye Hospital27, National Institute for Health Research28, Mayo Clinic29, Innsbruck Medical University30, Pontifícia Universidade Católica do Rio Grande do Sul31, University of Warmia and Mazury in Olsztyn32, Istanbul University33, University of Paris34, University of British Columbia35, University of California, San Francisco36, Technische Universität München37
TL;DR: In this paper, the authors identify myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) as a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination.
Abstract: Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD.
225 citations
Free University of Berlin1, Hospital Kuala Lumpur2, Cleveland Clinic3, Mater Dei Hospital4, Kantonsspital St. Gallen5, University of Zurich6, Medical University of Vienna7, Montreal Children's Hospital8, University of Cincinnati9, University of Southern Denmark10, Technische Universität München11, Opole University12, Federal University of Paraná13, University of Southampton14, Federal University of São Paulo15, New York University16, University of Debrecen17, Istanbul University18, Pompeu Fabra University19, University of Coimbra20, Vrije Universiteit Brussel21, Bethel University22, Laval University23, Hiroshima University24, Medical University of South Carolina25, Hannover Medical School26, Rappaport Faculty of Medicine27, Koç University28, Mahidol University29, University of Helsinki30, Royal Free Hospital31, Fraunhofer Society32, National and Kapodistrian University of Athens33, University of Groningen34, Nippon Medical School35, University of Milan36, Universidad Nacional de Asunción37, Johns Hopkins University38, Hacettepe University39, University of Paris40, University of Mainz41, University of Perugia42, University of Toronto43, University of Copenhagen44, Aarhus University Hospital45, Peking University46
TL;DR: This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) on 3 December 2020 as mentioned in this paper, with the participation of 64 delegates of 50 national and international societies and from 31 countries.
Abstract: This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
223 citations
Ohio State University1, St James's University Hospital2, Vita-Salute San Raffaele University3, University of Amsterdam4, Mayo Clinic5, NewYork–Presbyterian Hospital6, University of California, Irvine7, Istanbul University8, University of Debrecen9, University of Pennsylvania10, Peter MacCallum Cancer Centre11, University of Ulm12, Medical University of Łódź13, AstraZeneca14
TL;DR: Among Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutanib, which is hypothesized to improve continuous therapy tolerability as mentioned in this paper.
Abstract: PURPOSEAmong Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutinib, which we hypothesized would improve continuous therapy tolerability. We conducted an open-lab...
TL;DR: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free... as discussed by the authors.
Abstract: PURPOSEThe first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free...
TL;DR: The nurses caring for patients diagnosed with COVID-19 in Turkey were adversely affected, both psychologically and socially, by the pandemic; they used short-term coping strategies, and they needed psychosocial support and resource management.
Abstract: Background:Nurses, who are playing an important role during the coronavirus disease 2019 (COVID-19) outbreak, are exposed to a range of psychosocial stressors due to unforeseen risks.Objectives:The...
Charing Cross Hospital1, University of Foggia2, University of Milan3, University of Florence4, University of Aberdeen5, Aberdeen Royal Infirmary6, Selçuk University7, Istanbul University8, Katholieke Universiteit Leuven9, Manchester Royal Infirmary10, University of Catania11, University of Salerno12, Vita-Salute San Raffaele University13
TL;DR: The European Association of Urology (EAU) has updated its guidelines on sexual and reproductive health for 2021 as mentioned in this paper, including advances and areas of controversy in male infertility, and a strength rating for each recommendation was included that was based either on a systematic review of the literature or consensus opinion from the expert panel, where applicable.
TL;DR: The findings of this study showed that in order to raise psychological resilience of healthcare professionals working during the COVID-19 pandemic their quality of sleep, positive emotions and life satisfaction need to be enhanced.
Abstract: The COVID-19 pandemic as a public health issue has spread to the rest of the world. Although the wellbeing and emotional resilience of healthcare professionals are key components of continuing healthcare services during the COVID-19 pandemic, healthcare professionals have been observed in this period to experience serious psychological problems and to be at risk in terms of mental health. Therefore, this study aims to probe psychological resilience of healthcare workers. The findings of this study showed that in order to raise psychological resilience of healthcare professionals working during the COVID-19 pandemic their quality of sleep, positive emotions and life satisfaction need to be enhanced. Psychological resilience levels of healthcare workers in their later years were found to be higher. Doctors constitute the group with the lowest levels of psychological resilience among healthcare workers. The current study is considered to have contributed to the literature in this regard. Primary needs such as sleep which are determinants of quality of life, life satisfaction and psychological resilience should be met.
TL;DR: The current study provides valuable information for policymakers and mental health professionals worldwide regarding associations between the mental health of individuals and the ongoing outbreak, COVİD-19.
Abstract: Aim:The aim of this study was to investigate the association between the COVID-19 pandemic and psychological fatigue as a mental health issue among the population of Istanbul, Turkey.Participants a...
TL;DR: In this article, the ATLAS particle-flow reconstruction method is used to reconstruct the topo-clusters of the proton-proton collision data with a center-of-mass energy of 13$ TeV collected by the LHC.
Abstract: Jet energy scale and resolution measurements with their associated uncertainties are reported for jets using 36-81 fb$^{-1}$ of proton-proton collision data with a centre-of-mass energy of $\sqrt{s}=13$ TeV collected by the ATLAS detector at the LHC. Jets are reconstructed using two different input types: topo-clusters formed from energy deposits in calorimeter cells, as well as an algorithmic combination of charged-particle tracks with those topo-clusters, referred to as the ATLAS particle-flow reconstruction method. The anti-$k_t$ jet algorithm with radius parameter $R=0.4$ is the primary jet definition used for both jet types. Jets are initially calibrated using a sequence of simulation-based corrections. Next, several $\textit{in situ}$ techniques are employed to correct for differences between data and simulation and to measure the resolution of jets. The systematic uncertainties in the jet energy scale for central jets ($|\eta| 2.5$ TeV). The relative jet energy resolution is measured and ranges from ($24 \pm 1.5$)% at 20 GeV to ($6 \pm 0.5$)% at 300 GeV.
City of Hope National Medical Center1, Yale Cancer Center2, University of Vic3, Katholieke Universiteit Leuven4, New Generation University College5, National Cheng Kung University6, The Royal Marsden NHS Foundation Trust7, Samsung Medical Center8, Istanbul University9, University of Chicago10, Mayo Clinic11, Merck & Co.12, University of California, Los Angeles13
TL;DR: In this paper, the authors evaluated the antitumor activity of pembrolizumab therapy vs chemotherapy among patients with gastric or gastroesophageal junction (G/GEJ) cancer regardless of the line of therapy in which it was received.
Abstract: Importance Immunotherapy has been associated with improved outcomes among patients who have received previous treatment for microsatellite instability-high (MSI-H) tumors Objective To evaluate the antitumor activity of pembrolizumab therapy vs chemotherapy among patients with MSI-H advanced gastric or gastroesophageal junction (G/GEJ) cancer regardless of the line of therapy in which it was received Design, setting, and participants This post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial and the phase 3 KEYNOTE-061 (second-line treatment) and KEYNOTE-062 (first-line treatment) randomized trials included patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062 Patients were enrolled from March 2, 2015, to March 26, 2016, in KEYNOTE-059; from June 4, 2015, to July 26, 2016, in KEYNOTE-061; and from September 18, 2015, to May 26, 2017, in KEYNOTE-062, with data cutoff dates of August 8, 2018; October 26, 2017; and March 26, 2019; respectively Interventions Pembrolizumab monotherapy in KEYNOTE-059, pembrolizumab monotherapy or chemotherapy (paclitaxel) in KEYNOTE-061, and pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin and 5-fluorouracil or capecitabine), or chemotherapy alone in KEYNOTE-062 Main outcomes and measures Response was assessed centrally using Response Evaluation Criteria in Solid Tumours (RECIST), version 11; MSI-H status was determined centrally by polymerase chain reaction testing Results At data cutoff, 7 of 174 patients (40%) in KEYNOTE-059, 27 of 514 patients (53%) in KEYNOTE-061, and 50 of 682 patients (73%) in KEYNOTE-062 had MSI-H tumors Among those with MSI-H tumors, the median overall survival was not reached (NR) for pembrolizumab in KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 or for pembrolizumab plus chemotherapy in KEYNOTE-062 The median progression-free survival (PFS) for pembrolizumab was NR (95% CI, 11 months to NR) in KEYNOTE-059 and 178 months (95% CI, 27 months to NR) in KEYNOTE-061 (vs 35 months [95% CI, 20-98 months] for chemotherapy) In KEYNOTE-062, the median PFS was 112 months (95% CI, 15 months to NR) for pembrolizumab, NR (95% CI, 36 months to NR) for pembrolizumab plus chemotherapy, and 66 months (95% CI, 44-83 months) for chemotherapy The objective response rate (ORR) for pembrolizumab was 571% in KEYNOTE-059 and 467% (vs 167% for chemotherapy) in KEYNOTE-061 In KEYNOTE-062, the ORR was 571% for pembrolizumab , 647% for pembrolizumab plus chemotherapy, and 368% for chemotherapy Conclusions and relevance Findings from this study indicate that MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced G/GEJ cancer regardless of the line of therapy in which it was received Trial registration ClinicalTrialsgov Identifiers: NCT02335411, NCT02370498, and NCT02494583
Daphne Donis1, Evanthia Mantzouki1, Daniel Frank Mcginnis1, Dominic Vachon2 +199 more•Institutions (65)
TL;DR: In this article, Verspagen, van Herk and van Wijk present a collection of essays with the same authors, including a discussion of the role of gender in the relationship between women and women's empowerment.
Abstract: Output Status: Forthcoming/Available Online Additional co-authors: Jolanda Verspagen, Maria van Herk, Maria G. Antoniou, Nikoletta Tsiarta, Valerie McCarthy, Victor C. Perello, Danielle Machado-Vieira, Alinne Gurjao de Oliveira, Dubravka Spoljaric Maronic, Filip Stevic, Tanja Žuna Pfeiffer, Itana Bokan Vucelic, Petar Žutinic, Marija Gligora Udovic, Anđelka Plenkovic-Moraj, Ludek Blaha, Rodan Geris, Marketa Frankova, Kirsten Seestern Christoffersen, Trine Perlt Warming, Tonu Feldmann, Alo Laas, Kristel Panksep, Lea Tuvikene, Kersti Kangro, Judita Koreiviene, Jurate Karosiene, Jurate Kasperoviciene, Ksenija Savadova-Ratkus, Irma Vitonyte, Kerstin Haggqvist, Pauliina Salmi, Lauri Arvola, Karl Rothhaupt, Christos Avagianos, Triantafyllos Kaloudis, Spyros Gkelis, Manthos Panou, Theodoros Triantis, Sevasti-Kiriaki Zervou, Anastasia Hiskia, Ulrike Obertegger, Adriano Boscaini, Giovanna Flaim, Nico Salmaso, Leonardo Cerasino, Sigrid Haande, Birger Skjelbred, Magdalena Grabowska, Maciej Karpowicz, Damian Chmura, Lidia Nawrocka, Justyna Kobos, Hanna Mazur-Marzec, Pablo Alcaraz-Parraga, Elzbieta Wilk-Wozniak, Wojciech Krzton, Edward Walusiak, Ilona Gagala-Borowska, Joana Mankiewicz-Boczek, Magdalena Toporowska, Barbara Pawlik-Skowronska, Michal Niedzwiecki, Wojciech Peczula, Agnieszka Napiorkowska-Krzebietke, Julita Dunalska, Justyna Sienska, Daniel Szymanski, Marek Kruk, Agnieszka Budzynska, Ryszard Goldyn, Anna Kozak, Joanna Rosinska, Elzbieta Szeląg-Wasielewska, Piotr Domek, Natalia Jakubowska-Krepska, Kinga Kwasizur, Beata Messyasz, Aleksandra Pelechata, Mariusz Pelechaty, Mikolaj Kokocinski, Beata Madrecka-Witkowska, Iwona Kostrzewska-Szlakowska, Magdalena Frąk, Agnieszka Bankowska-Sobczak, Michal Wasilewicz, Agnieszka Ochocka, Agnieszka Pasztaleniec, Iwona Jasser, Ana M. Antao-Geraldes, Manel Leira, Vitor Vasconcelos, Joao Morais, Micaela Vale, Pedro M. Raposeiro, Vitor Goncalves, Boris Aleksovski, Svetislav Krstic, Hana Nemova, Iveta Drastichova, Lucia Chomova, Spela Remec-Rekar, Tina Elersek, Lars-Anders Hansson, Pablo Urrutia-Cordero, Andrea G. Bravo, Moritz Buck, William Colom-Montero, Kristiina Mustonen, Don Pierson, Yang Yang, Christine Edwards, Hannah Cromie, Jordi Delgado-Martin, David Garcia, Jose Luis Cereijo, Joan Goma, Mari Carmen Trapote, Teresa Vegas-Vilarrubia, Biel Obrador, Ana Garcia-Murcia, Monserrat Real, Elvira Romans, Jordi Noguero-Ribes, David Parreno Duque, Elisabeth Fernandez-Moran, Barbara Ubeda, Jose Angel Galvez, Nuria Catalan, Carmen Perez-Martinez, Eloisa Ramos-Rodriguez, Carmen Cillero-Castro, Enrique Moreno-Ostos, Jose Maria Blanco, Valeriano Rodriguez, Jorge Juan Montes-Perez, Roberto L. Palomino, Estela Rodriguez-Perez, Armand Hernandez, Rafael Carballeira, Antonio Camacho, Antonio Picazo, Carlos Rochera, Anna C. Santamans, Carmen Ferriol, Susana Romo, Juan Miguel Soria, Arda Ozen, Tunay Karan, Nilsun Demir, Meryem Beklioglu, Nur Filiz, Eti Levi, Ugur Iskin, Gizem Bezirci, Ulku Nihan Tavsanoglu, Kemal Celik, Koray Ozhan, Nusret Karakaya, Mehmet Ali Turan Kocer, Mete Yilmaz, Faruk Maras¸lioglu, Ozden Fakioglu, Elif Neyran Soylu, Meral Apaydin Yagci, Sakir Cinar, Kadir Capkin, Abdulkadir Yagci, Mehmet Cesur, Fuat Bilgin, Cafer Bulut, Rahmi Uysal, Koker Latife, Reyhan Akcaalan, Meric Albay, Mehmet Tahir Alp, Korhan Ozkan, Tugba Ongun Sevindik, Hatice Tunca, Burcin Onem, Hans Paerl, Cayelan C. Carey, Bastiaan W. Ibelings
TL;DR: In this paper, the performance of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC is presented, based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb$^{-1}$.
Abstract: The performance is presented of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC. The reported results are based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb$^{-1}$. Results obtained from lead-lead collision data collected at $\sqrt{s_\mathrm{NN}}=$ 5.02 TeV are also presented. Innovative techniques are used to reconstruct the electron and photon signals in the detector and to optimize the energy resolution. Events with electrons and photons in the final state are used to measure the energy resolution and energy scale uncertainty in the recorded events. The measured energy resolution for electrons produced in Z boson decays in proton-proton collision data ranges from 2 to 5%, depending on electron pseudorapidity and energy loss through bremsstrahlung in the detector material. The energy scale in the same range of energies is measured with an uncertainty smaller than 0.1 (0.3)% in the barrel (endcap) region in proton-proton collisions and better than 1 (3)% in the barrel (endcap) region in heavy ion collisions. The timing resolution for electrons from Z boson decays with the full 2016-2018 proton-proton collision data set is measured to be 200 ps.
TL;DR: In order to prevent transmission of SARS-CoV-2, hygienic rules should be pursued in the community, social distancing should be observed, and the family members and contacts of patients who have been diagnosed should be screened and isolated.
Abstract: SARS-CoV-2, a RNA virus that emerged in December 2019 in the city of Wuhan in China and took hold of the whole world, affects children as well as all age groups. In our country, we started to observe the first cases by March 2020. SARS-CoV-2, which is transmitted by droplets and by way of contact with surfaces contaminated by these droplets, is generally transmitted to children from adults through close contact. There is no proven information about other transmission routes such as fecal-oral transmission. Similar to adults, the primary symptoms at presentation include fever, cough, sore throat, malaise, nasal discharge, and rarely, vomiting and diarrhea in children. Although the majority of pediatric patients are asymptomatic or have a mild clinical course, severe cases have been reported in children with underlying chronic diseases. There is currently no specific antiviral treatment against the SARS-CoV-2 virus. Supportive treatment is recommended in children with a mild course, and some treatments are recommended in children with comorbidities or in children who are observed to have a more severe course. Asymptomatic pediatric patients or pediatric patients who have a mild course constitute an important group in terms of transmission of the infection to the advanced age group who carry high risk. Prevention of infection is very important in terms of reducing new cases and alleviating the load on the healthcare system. In order to prevent transmission of SARS-CoV-2, hygienic rules should be pursued in the community, social distancing should be observed, and the family members and contacts of patients who have been diagnosed should be screened and isolated.
TL;DR: In this article, steel slag usage in the cement and concrete industry and its environmental effects were examined, and the benefits of both economic and ecological balance were examined. And opinions and recommendations were presented.
TL;DR: It is suggested that COVID-19 patients are prone to substantial psychological distress in the first few months after the infection, and these were closely related to the posttraumatic symptoms.
Abstract: We investigated the psychiatric symptomatology and the protracted symptoms in patients who had recovered from the acute COVID-19 infection. Two hundred and eighty-four patients completed a web-based or a paper survey on socio-demographic and clinical data. The psychiatric status was assessed using Impact of Events Scale-Revised (IES-R), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), and MINI suicidality scale. Patients completed a checklist for the protracted symptoms that were experienced after the acute infection. After a mean of almost 50 days following the diagnosis, 98 patients (34.5%) reported clinically significant PTSD, anxiety, and/or depression, with PTSD being the most common condition reported (25.4%). One hundred and eighteen patients (44.3%) reported one or more protracted symptom(s). Predictors of PTSD symptom severity were the female gender, past traumatic events, protracted symptoms, stigmatization, and a negative view on the COVID-19 pandemic. PTSD symptom severity was the sole independent predictor of the protracted symptoms. Our results suggest that COVID-19 patients are prone to substantial psychological distress in the first few months after the infection. The protracted symptoms were frequent in this period, and these were closely related to the posttraumatic symptoms.
TL;DR: Wang et al. as discussed by the authors presented a living review aiming to critically appraise available data about secondary attack rates from people with asymptomatic, pre-symptomatic and symptomatic SARS-CoV-2 infection.
TL;DR: In this paper, the authors describe the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139.5 million collision data collected between 2015 and 2018 during Run 2 of the LHC, and show that the improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution.
Abstract: This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 $$\hbox {fb}^{-1}$$
fb
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1
of pp collision data at $$\sqrt{s}=13$$
s
=
13
TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of $$Z\rightarrow \mu \mu $$
Z
→
μ
μ
and $$J/\psi \rightarrow \mu \mu $$
J
/
ψ
→
μ
μ
decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of $$|\eta |<2.7$$
|
η
|
<
2.7
.
TL;DR: This study aimed to determine how the optimum investment decisions could be taken at the renewable energy sector in Turkey by using the Fuzzy Analytical Hierarchy Process and the Evaluation Based on Distance from Average Solution methods.
University of Bologna1, Medical University of Warsaw2, Institut Gustave Roussy3, Memorial Sloan Kettering Cancer Center4, Hebron University5, Erasmus University Rotterdam6, University of Lausanne7, Vita-Salute San Raffaele University8, University Hospital of Basel9, University of Melbourne10, Istanbul University11, National and Kapodistrian University of Athens12, King's College London13, Mario Negri Institute for Pharmacological Research14, Humanitas University15, Trinity College, Dublin16, University of Erlangen-Nuremberg17, University of Paris18, University of Verona19, Uppsala University20, Aix-Marseille University21, Innsbruck Medical University22, University of Duisburg-Essen23, University of Texas MD Anderson Cancer Center24
TL;DR: The European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs).
Albert M. Sirunyan1, Robin Erbacher2, C. A. Carrillo Montoya, Wagner Carvalho3 +2448 more•Institutions (210)
TL;DR: In this paper, evidence for Higgs boson decay to a pair of muons was presented, which was performed using proton-proton collision data at 13 TeV, corresponding to an integrated luminosity of 137 fb$−1}, recorded by the CMS experiment at the CERN LHC.
Abstract: Evidence for Higgs boson decay to a pair of muons is presented. This result combines searches in four exclusive categories targeting the production of the Higgs boson via gluon fusion, via vector boson fusion, in association with a vector boson, and in association with a top quark-antiquark pair. The analysis is performed using proton-proton collision data at $ \sqrt{s} $ = 13 TeV, corresponding to an integrated luminosity of 137 fb$^{−1}$, recorded by the CMS experiment at the CERN LHC. An excess of events over the back- ground expectation is observed in data with a significance of 3.0 standard deviations, where the expectation for the standard model (SM) Higgs boson with mass of 125.38 GeV is 2.5. The combination of this result with that from data recorded at $ \sqrt{s} $ = 7 and 8 TeV, corresponding to integrated luminosities of 5.1 and 19.7 fb$^{−1}$, respectively, increases both the expected and observed significances by 1%. The measured signal strength, relative to the SM prediction, is $ {1.19}_{-0.39}^{+0.40}{\left(\mathrm{stat}\right)}_{-0.14}^{+0.15}\left(\mathrm{syst}\right) $. This result constitutes the first evidence for the decay of the Higgs boson to second generation fermions and is the most precise measurement of the Higgs boson coupling to muons reported to date.[graphic not available: see fulltext]
Maria Lc Iurilli1, Bin Zhou1, James E. Bennett1, Rodrigo M. Carrillo-Larco1 +1399 more•Institutions (374)
TL;DR: In this article, the authors investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants.
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
TL;DR: LV-GLS and RV-LS are independent predictors of in-hospital mortality in patients with COVID-19, and the presence of cardiac injury, D-dimer, arterial oxygen saturation (SaO2), LV-G LS and LV-LS were identified as independent predictor of mortality via multivariate analysis.
Abstract: A new infectious outbreak sustained by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now spreading all around the world. The aim of this study was to evaluate the prognostic value of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) in patients with coronavirus disease 2019 (COVID-19). In this prospective, single-center study, data were gathered from patients treated for COVID-19 between April 15 and April 30, 2020. Two-dimensional echocardiography (2-DE) and speckle tracking echocardiography (STE) images were obtained for all patients. Patients were divided into three groups: those with severe COVID-19 infection, those with non-severe COVID-19 infection, and those without COVID-19 infection (the control group). Data regarding clinical characteristics and laboratory findings were obtained from electronic medical records. The primary endpoint was in-hospital mortality. A total of 100 patients hospitalized for COVID-19 were included in this study. The mean age of the severe group (n = 44) was 59.1 ± 12.9, 40% of whom were male. The mean age of the non-severe group (n = 56) was 53.7 ± 15.1, 58% of whom were male. Of these patients, 22 died in the hospital. In patients in the severe group, LV-GLS and RV-LS were decreased compared to patients in the non-severe and control groups (LV-GLS: − 14.5 ± 1.8 vs. − 16.7 ± 1.3 vs. − 19.4 ± 1.6, respectively [p < 0.001]; RV-LS: − 17.2 ± 2.3 vs. − 20.5 ± 3.2 vs. − 27.3 ± 3.1, respectively [p < 0.001]). The presence of cardiac injury, D-dimer, arterial oxygen saturation (SaO2), LV-GLS (OR 1.63, 95% confidence interval [CI] 1.08–2.47; p = 0.010) and RV-LS (OR 1.55, 95% CI 1.07–2.25; p = 0.019) were identified as independent predictors of mortality via multivariate analysis. LV-GLS and RV-LS are independent predictors of in-hospital mortality in patients with COVID-19.