Practice patterns and clinical outcomes in acute appendicitis differ in the elderly patient

Background: Appendicitis is the most frequent global abdominal surgical emergency. An ageing population, who often exhibit atypical symptoms and delayed presentations, challenge conventional diagnostic and treatment paradigms. Objectives: This study aims to delineate disparities in presentation, management, and outcomes between elderly patients and younger adults suffering from acute appendicitis. Methods: This subgroup analysis forms part of ESTES SnapAppy, a time-bound multi-center prospective, observational cohort study. It includes patients aged 15 years and above who underwent laparoscopic appendectomy during a defined 90-day observational period across multiple centers. Statistical comparisons were performed using appropriate tests with significance set at p < 0.05. Results: The study cohort comprised 521 elderly patients (≥65 years) and 4,092 younger adults (18–64 years). Elderly patients presented later (mean duration of symptoms: 7.88 vs. 3.56 days; p < 0.001) and frequently required computed tomography (CT) scans for diagnosis (86.1% vs. 54.0%; p < 0.001). The incidence of complicated appendicitis was higher in the elderly (46.7% vs. 20.7%; p < 0.001). Delays in surgical intervention were notable in the elderly (85.0% operated within 24 h vs. 88.7%; p = 0.018), with longer operative times (71.1 vs. 60.3 min; p < 0.001). Postoperative complications were significantly higher in the elderly (27.9% vs. 12.9%; p < 0.001), including severe complications (6.9% vs. 2.4%; p < 0.001) and prolonged hospital stays (7.9 vs. 3.6 days; p < 0.001). Conclusions: Our findings highlight significant differences in the clinical course and outcomes of acute appendicitis in the elderly compared to younger patients, suggesting a need for age-adapted diagnostic pathways and treatment strategies to improve outcomes in this vulnerable population

Machine learning in Alzheimer’s disease genetics

: Traditional statistical approaches have advanced our understanding of the genetics of complex diseases, yet are limited to linear additive models. Here we applied machine learning (ML) to genome-wide data from 41,686 individuals in the largest European consortium on Alzheimer's disease (AD) to investigate the effectiveness of various ML algorithms in replicating known findings, discovering novel loci, and predicting individuals at risk. We utilised Gradient Boosting Machines (GBMs), biological pathway-informed Neural Networks (NNs), and Model-based Multifactor Dimensionality Reduction (MB-MDR) models. ML approaches successfully captured all genome-wide significant genetic variants identified in the training set and 22% of associations from larger meta-analyses. They highlight 6 novel loci which replicate in an external dataset, including variants which map to ARHGAP25, LY6H, COG7, SOD1 and ZNF597. They further identify novel association in AP4E1, refining the genetic landscape of the known SPPL2A locus. Our results demonstrate that machine learning methods can achieve predictive performance comparable to classical approaches in genetic epidemiology and have the potential to uncover novel loci that remain undetected by traditional GWAS. These insights provide a complementary avenue for advancing the understanding of AD genetics

International Impact of COVID-19 on the Diagnosis of Heart Disease

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified.OBJECTIVES The study sought to assess COVID-19`s impact on global cardiovascular diagnostic procedural volumes and safety practices.METHODS The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained.RESULTS Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoradc echocardiography decreased by 59%, transesophageat echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p &lt; 0.001 for each procedure). hi multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and teteheatth.CONCLUSIONS COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

An embedding technique to determine ττ backgrounds in proton-proton collision data

The Secretaría de Estado de Investigación, Desarrollo e Innovación, Programa ConsoliderIngenio 2010, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, Plan de Ciencia, Tecnología e Innovación 2013–2017 del Principado de Asturias, and Fondo Europeo de Desarrollo Regional, Spain. Individuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract No. 675440 (European Union); the Programa de Excelencia María de Maeztu, and the Programa Severo Ochoa del Principado de Asturias (...)Sirunyan, A.M., Tumasyan, A., Adam, W., Ambrogi, F., Asilar, E., Bergauer, T., Brandstetter, J., Dragicevic, M., Erö, J., Escalante Del Valle, A., Flechl, M., Frühwirth, R., Ghete, V.M., Hrubec, J., Jeitler, M., Krammer, N., Krätschmer, I., Liko, D., Madlener, T., Mikulec, I., Rad, N., Rohringer, H., Schieck, J., Schöfbeck, R., Spanring, M., Spitzbart, D., Waltenberger, W., Wittmann, J., Wulz, C.-E., Zarucki, M., Chekhovsky, V., Mossolov, V., Suarez Gonzalez, J., De Wolf, E.A., Di Croce, D., Janssen, X., Lauwers, J., Lelek, A., Pieters, M., Van Haevermaet, H., Van Mechelen, P., Van Remortel, N., Blekman, F., D'Hondt, J., De Clercq, J., Deroover, K., Flouris, G., Lontkovskyi, D., Lowette, S., Marchesini, I., Moortgat, S., Moreels, L., Python, Q., Skovpen, K., Tavernier, S., Van Doninck, W., Van Mulders, P., Van Parijs, I., Beghin, D., Bilin, B., Brun, H., Clerbaux, B., De Lentdecker, G., Delannoy, H., Dorney, B., Fasanella, G., Favart, L., Grebenyuk, A., Kalsi, A.K., Luetic, J., Popov, A., Postiau, N., Starling, E., Thomas, L., Vander Velde, C., Vanlaer, P., Vannerom, D., Wang, Q., Cornelis, T., Dobur, D., Fagot, A., Gul, M., Khvastunov, I., Roskas, C., Trocino, D., Tytgat, M., Verbeke, W., Vermassen, B., Vit, M., Zaganidis, N., Bakhshiansohi, H., Bondu, O., Bruno, G., Caputo, C., David, P., Delaere, C., Delcourt, M., Giammanco, A., Krintiras, G., Lemaitre, V., Magitteri, A., Piotrzkowski, K., Saggio, A., Vidal Marono, M., Vischia, P., Zobec, J., Alves, F.L., Alves, G.A., Correia Silva, G., Hensel, C., Moraes, A., Pol, M.E., Rebello Teles, P., Belchior Batista Das Chagas, E., Carvalho, W., Chinellato, J., Coelho, E., Da Costa, E.M., Da Silveira, G.G., De Jesus Damiao, D., De Oliveira Martins, C., Fonseca De Souza, S., Huertas Guativa, L.M., Malbouisson, H., Matos Figueiredo, D., Melo De Almeida, M., Mora Herrera, C., Mundim, L., Nogima, H., Prado Da Silva, W.L., Sanchez Rosas, L.J., Santoro, A., Sznajder, A., Thiel, M., Tonelli Manganote, E.J., Torres Da Silva De Araujo, F., Vilela Pereira, A., Ahuja, S., Bernardes, C.A., Calligaris, L., Fernandez Perez Tomei, T.R., Gregores, E.M., Mercadante, P.G., Novaes, S.F., Padula, S.S., Aleksandrov, A., Hadjiiska, R., Iaydjiev, P., Marinov, A., Misheva, M., Rodozov, M., Shopova, M., Sultanov, G., Dimitrov, A., Litov, L., Pavlov, B., Petkov, P., Fang, W., Gao, X., Yuan, L., Ahmad, M., Bian, J.G., Chen, G.M., Chen, H.S., Chen, M., Chen, Y., Jiang, C.H., Leggat, D., Liao, H., Liu, Z., Shaheen, S.M., Spiezia, A., Tao, J., Yazgan, E., Zhang, H., Zhang, S., Zhao, J., Ban, Y., Chen, G., Levin, A., Li, J., Li, L., Li, Q., Mao, Y., Qian, S.J., Wang, D., Wang, Y., Avila, C., Cabrera, A., Carrillo Montoya, C.A., Chaparro Sierra, L.F., Florez, C., González Hernández, C.F., Segura Delgado, M.A., Godinovic, N., Lelas, D., Puljak, I., Sculac, T., Antunovic, Z., Kovac, M., Brigljevic, V., Ferencek, D., Kadija, K., Mesic, B., Roguljic, M., Starodumov, A., Susa, T., Ather, M.W., Attikis, A., Kolosova, M., Mavromanolakis, G., Mousa, J., Nicolaou, C., Ptochos, F., Razis, P.A., Rykaczewski, H., Finger, M., Finger, M., Jr., Ayala, E., Carrera Jarrin, E., Ellithi Kamel, A., Mahmoud, M.A., Salama, E., Bhowmik, S., Carvalho Antunes Deoliveira, A., Dewanjee, R.K., Ehataht, K., Kadastik, M., Raidal, M., Veelken, C., Eerola, P., Kirschenmann, H., Pekkanen, J., Voutilainen, M., Havukainen, J., Heikkilä, J.K., Järvinen, T., Karimäki, V., Kinnunen, R., Lampén, T., Lassila-Perini, K., Laurila, S., Lehti, S., Lindén, T., Luukka, P., Mäenpää, T., Siikonen, H., Tuominen, E., Tuominiemi, J., Tuuva, T., Besancon, M., Couderc, F., Dejardin, M., Denegri, D., Faure, J.L., Ferri, F., Ganjour, S., Givernaud, A., Gras, P., Hamel De Monchenault, G., Jarry, P., Leloup, C., Locci, E., Malcles, J., Negro, G., Rander, J., Rosowsky, A., Sahin, M.Ö., Titov, M., Abdulsalam, A., Amendola, C., Antropov, I., Beaudette, F., Busson, P., Charlot, C., Diab, B., Granier De Cassagnac, R., Kucher, I., Lobanov, A., Martin Blanco, J., Martin Perez, C., Nguyen, M., Ochando, C., Ortona, G., Paganini, P., Rembser, J., Salerno, R., Sauvan, J.B., Sirois, Y., Stahl Leiton, A.G., Zabi, A., Zghiche, A., Agram, J.-L., Andrea, J., Bloch, D., Bourgatte, G., Brom, J.-M., Chabert, E.C., Cherepanov, V., Collard, C., Conte, E., Fontaine, J.-C., Gelé, D., Goerlach, U., Jansová, M., Le Bihan, A.-C., Tonon, N., Van Hove, P., Gadrat, S., Beauceron, S., Bernet, C., Boudoul, G., Chanon, N., Chierici, R., Contardo, D., Depasse, P., El Mamouni, H., Fay, J., Gascon, S., Gouzevitch, M., Grenier, G., Ille, B., Lagarde, F., Laktineh, I.B., Lattaud, H., Lethuillier, M., Mirabito, L., Perries, S., Sordini, V., Touquet, G., Vander Donckt, M., Viret, S., Khvedelidze, A., Tsamalaidze, Z., Autermann, C., Feld, L., Kiesel, M.K., Klein, K., Lipinski, M., Preuten, M., Rauch, M.P., Schomakers, C., Schulz, J., Teroerde, M., Wittmer, B., Albert, A., Erdmann, M., Erdweg, S., Esch, T., Fischer, R., Ghosh, S., Hebbeker, T., Heidemann, C., Hoepfner, K., Keller, H., Mastrolorenzo, L., Merschmeyer, M., Meyer, A., Millet, P., Mukherjee, S., Novak, A., Pook, T., Pozdnyakov, A., Radziej, M., Reithler, H., Rieger, M., Schmidt, A., Teyssier, D., Thüer, S., Flügge, G., Hlushchenko, O., Kress, T., Müller, T., Nehrkorn, A., Nowack, A., Pistone, C., Pooth, O., Roy, D., Sert, H., Stahl, A., Aldaya Martin, M., Arndt, T., Asawatangtrakuldee, C., Babounikau, I., Beernaert, K., Behnke, O., Behrens, U., Bermúdez Martínez, A., Bertsche, D., Bin Anuar, A.A., Borras, K., Botta, V., Campbell, A., Connor, P., Contreras-Campana, C., Danilov, V., De Wit, A., Defranchis, M.M., Diez Pardos, C., Domínguez Damiani, D., Eckerlin, G., Eichhorn, T., Elwood, A., Eren, E., Gallo, E., Geiser, A., Grados Luyando, J.M., Grohsjean, A., Guthoff, M., Haranko, M., Harb, A., Jung, H., Kasemann, M., Keaveney, J., Kleinwort, C., Knolle, J., Krücker, D., Lange, W., Lenz, T., Leonard, J., Lipka, K., Lohmann, W., Mankel, R., Melzer-Pellmann, I.-A., Meyer, A.B., Meyer, M., Missiroli, M., Mittag, G., Mnich, J., Myronenko, V., Pflitsch, S.K., Pitzl, D., Raspereza, A., Saibel, A., Savitskyi, M., Saxena, P., Schütze, P., Schwanenberger, C., Shevchenko, R., Singh, A., Tholen, H., Turkot, O., Vagnerini, A., Van De Klundert, M., Van Onsem, G.P., Walsh, R., Wen, Y., Wichmann, K., Wissing, C., Zenaiev, O., Aggleton, R., Bein, S., Benato, L., Benecke, A., Blobel, V., Dreyer, T., Ebrahimi, A., Garutti, E., Gonzalez, D., Gunnellini, P., Haller, J., Hinzmann, A., Karavdina, A., Kasieczka, G., Klanner, R., Kogler, R., Kovalchuk, N., Kurz, S., Kutzner, V., Lange, J., Marconi, D., Multhaup, J., Niedziela, M., Niemeyer, C.E.N., Nowatschin, D., Perieanu, A., Reimers, A., Rieger, O., Scharf, C., Schleper, P., Schumann, S., Schwandt, J., Sonneveld, J., Stadie, H., Steinbrück, G., Stober, F.M., Stöver, M., Vormwald, B., Zoi, I., Akbiyik, M., Barth, C., Baselga, M., Baur, S., Bechtel, J., Brommer, S., Butz, E., Caspart, R., Chwalek, T., Colombo, F., De Boer, W., Dierlamm, A., El Morabit, K., Faltermann, N., Freund, B., Giffels, M., Gottmann, A., Harrendorf, M.A., Hartmann, F., Heindl, S.M., Husemann, U., Katkov, I., Kudella, S., Mitra, S., Mozer, M.U., Müller, Th., Musich, M., Plagge, M., Quast, G., Rabbertz, K., Schröder, M., Shvetsov, I., Simonis, H.J., Ulrich, R., Wayand, S., Weber, M., Weiler, T., Wöhrmann, C., Wolf, R., Anagnostou, G., Daskalakis, G., Geralis, T., Kyriakis, A., Loukas, D., Paspalaki, G., Agapitos, A., Karathanasis, G., Kontaxakis, P., Panagiotou, A., Papavergou, I., Saoulidou, N., Vellidis, K., Bakas, G., Kousouris, K., Papakrivopoulos, I., Tsipolitis, G., Evangelou, I., Foudas, C., Gianneios, P., Katsoulis, P., Kokkas, P., Mallios, S., Manitara, K., Manthos, N., Papadopoulos, I., Paradas, E., Strologas, J., Triantis, F.A., Tsitsonis, D., Bartók, M., Csanad, M., Filipovic, N., Major, P., Mandal, K., Mehta, A., Nagy, M.I., Pasztor, G., Surányi, O., Veres, G.I., Bencze, G., Hajdu, C., Horvath, D., Hunyadi, Á., Sikler, F., Vámi, T.Á., Veszpremi, V., Vesztergombi, G., Beni, N., Czellar, S., Karancsi, J., Makovec, A., Molnar, J., Szillasi, Z., Raics, P., Trocsanyi, Z.L., Ujvari, B., Choudhury, S., Komaragiri, J.R., Tiwari, P.C., Bahinipati, S., Kar, C., Mal, P., Nayak, A., Roy Chowdhury, S., Sahoo, D.K., Swain, S.K., Bansal, S., Beri, S.B., Bhatnagar, V., Chauhan, S., Chawla, R., Dhingra, N., Gupta, R., Kaur, A., Kaur, M., Kaur, S., Kumari, P., Lohan, M., Meena, M., Sandeep, K., Sharma, S., Singh, J.B., Virdi, A.K., Walia, G., Bhardwaj, A., Choudhary, B.C., Garg, R.B., Gola, M., Keshri, S., Kumar, A., Malhotra, S., Naimuddin, M., Priyanka, P., Ranjan, K., Shah, A., Sharma, R., Bhardwaj, R., Bharti, M., Bhattacharya, R., Bhattacharya, S., Bhawandeep, U., Bhowmik, D., Dey, S., Dutt, S., Dutta, S., Ghosh, S., Maity, M., Mondal, K., Nandan, S., Purohit, A., Rout, P.K., Roy, A., Saha, G., Sarkar, S., Sarkar, T., Sharan, M., Singh, B., Thakur, S., Behera, P.K., Muhammad, A., Chudasama, R., Dutta, D., Jha, V., Kumar, V., Mishra, D.K., Netrakanti, P.K., Pant, L.M., Shukla, P., Suggisetti, P., Aziz, T., Bhat, M.A., Dugad, S., Mohanty, G.B., Sur, N., Verma, R., Banerjee, S., Bhattacharya, S., Chatterjee, S., Das, P., Guchait, M., Jain, S.A., Karmakar, S., Kumar, S., Majumder, G., Mazumdar, K., Sahoo, N., Chauhan, S., Dube, S., Hegde, V., Kapoor, A., Kothekar, K., Pandey, S., Rane, A., Rastogi, A., Sharma, S., Chenarani, S., Eskandari Tadavani, E., Etesami, S.M., Khakzad, M., Mohammadi Najafabadi, M., Naseri, M., Rezaei Hosseinabadi, F., Safarzadeh, B., Zeinali, M., Felcini, M., Grunewald, M., Abbrescia, M., Calabria, C., Colaleo, A., Creanza, D., Cristella, L., De Filippis, N., De Palma, M., Di Florio, A., Errico, F., Fiore, L., Gelmi, A., Iaselli, G., Ince, M., Lezki, S., Maggi, G., Maggi, M., Miniello, G., My, S., Nuzzo, S., Pompili, A., Pugliese, G., Radogna, R., Ranieri, A., Selvaggi, G., Sharma, A., Silvestris, L., Venditti, R., Verwilligen, P., Abbiendi, G., Battilana, C., Bonacorsi, D., Borgonovi, L., Braibant-Giacomelli, S., Campanini, R., Capiluppi, P., Castro, A., Cavallo, F.R., Chhibra, S.S., Codispoti, G., Cuffiani, M., Dallavalle, G.M., Fabbri, F., Fanfani, A., Fontanesi, E., Giacomelli, P., Grandi, C., Guiducci, L., Iemmi, F., Lo Meo, S., Marcellini, S., Masetti, G., Montanari, A., Navarria, F.L., Perrotta, A., Primavera, F., Rossi, A.M., Rovelli, T., Siroli, G.P., Tosi, N., Albergo, S., Di Mattia, A., Potenza, R., Tricomi, A., Tuve, C., Barbagli, G., Chatterjee, K., Ciulli, V., Civinini, C., D'Alessandro, R., Focardi, E., Latino, G., Lenzi, P., Meschini, M., Paoletti, S., Russo, L., Sguazzoni, G., Strom, D., Viliani, L., Benussi, L., Bianco, S., Fabbri, F., Piccolo, D., Ferro, F., Mulargia, R., Robutti, E., Tosi, S., Benaglia, A., Beschi, A., Brivio, F., Ciriolo, V., Di Guida, S., Dinardo, M.E., Fiorendi, S., Gennai, S., Ghezzi, A., Govoni, P., Malberti, M., Malvezzi, S., Menasce, D., Monti, F., Moroni, L., Paganoni, M., Pedrini, D., Ragazzi, S., Tabarelli De Fatis, T., Zuolo, D., Buontempo, S., Cavallo, N., De Iorio, A., Di Crescenzo, A., Fabozzi, F., Fienga, F., Galati, G., Iorio, A.O.M., Lista, L., Meola, S., Paolucci, P., Sciacca, C., Voevodina, E., Azzi, P., Bacchetta, N., Bisello, D., Boletti, A., Bragagnolo, A., Carlin, R., Checchia, P., Dall'Osso, M., De Castro Manzano, P., Dorigo, T., Dosselli, U., Gasparini, F., Gasparini, U., Gozzelino, A., Hoh, S.Y., Lacaprara, S., Lujan, P., Margoni, M., Meneguzzo, A.T., Pazzini, J., Presilla, M., Ronchese, P., Rossin, R., Simonetto, F., Tiko, A., Torassa, E., Tosi, M., Zanetti, M., Zotto, P., Zumerle, G., Braghieri, A., Magnani, A., Montagna, P., Ratti, S.P., Re, V., Ressegotti, M., Riccardi, C., Salvini, P., Vai, I., Vitulo, P., Biasini, M., Bilei, 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W.A.T., Yusli, M.N., Zolkapli, Z., Benitez, J.F., Castaneda Hernandez, A., Murillo Quijada, J.A., Castilla-Valdez, H., De La Cruz-Burelo, E., Duran-Osuna, M.C., Heredia-De La Cruz, I., Lopez-Fernandez, R., Mejia Guisao, J., Rabadan-Trejo, R.I., Ramirez-Sanchez, G., Reyes-Almanza, R., Sanchez-Hernandez, A., Carrillo Moreno, S., Oropeza Barrera, C., Ramirez-Garcia, M., Vazquez Valencia, F., Eysermans, J., Pedraza, I., Salazar Ibarguen, H.A., Uribe Estrada, C., Morelos Pineda, A., Krofcheck, D., Bheesette, S., Butler, P.H., Ahmad, A., Ahmad, M., Asghar, M.I., Hassan, Q., Hoorani, H.R., Khan, W.A., Shah, M.A., Shoaib, M., Waqas, M., Bialkowska, H., Bluj, M., Boimska, B., Frueboes, T., Górski, M., Kazana, M., Szleper, M., Traczyk, P., Zalewski, P., Bunkowski, K., Byszuk, A., Doroba, K., Kalinowski, A., Konecki, M., Krolikowski, J., Misiura, M., Olszewski, M., Pyskir, A., Walczak, M., Araujo, M., Bargassa, P., Beirão Da Cruz E Silva, C., Di Francesco, A., Faccioli, P., Galinhas, B., 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Hormonemate Derivatives from <i>Dothiora</i> sp., an Endophytic Fungus

A search for cytotoxic agents from cultures of the endophytic fungus Dothiora sp., isolated from the endemic plant Launaea arborescens, led to the isolation of six new compounds structurally related to hormonemate, with moderate cytotoxic activity against different cancer cell lines. By using a bioassay-guided fractionation approach, hormonemates A–D (1–4), hormonemate (5), and hormonemates E (6) and F (7) were obtained from the acetone extract of this fungus. Their structures were determined using a combination of HRMS, ESI-qTOF-MS/MS, 1D and 2D NMR experiments, and chemical degradation. The cytotoxic activities of these compounds were evaluated by microdilution colorimetric assays against human breast adenocarcinoma (MCF-7), human liver cancer cells (HepG2), and pancreatic cancer cells (MiaPaca_2). Most of the compounds displayed cytotoxic activity against this panel

Searches for pair production of charginos and top squarks in final states with two oppositely charged leptons in proton-proton collisions at vs=13 TeV

SEIDI, CPAN, PCTI and FEDER (Spain); Individuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract No. 675440 (European Union); the Programa Severo Ochoa del Principado de AsturiasSirunyan, A.M., Tumasyan, A., Adam, W., Ambrogi, F., Asilar, E., Bergauer, T., Brandstetter, J., Dragicevic, M., Erö, J., Escalante Del Valle, A., Flechl, M., Frühwirth, R., Ghete, V.M., Hrubec, J., Jeitler, M., Krammer, N., Krätschmer, I., Liko, D., Madlener, T., Mikulec, I., Rad, N., Rohringer, H., Schieck, J., Schöfbeck, R., Spanring, M., Spitzbart, D., Taurok, A., Waltenberger, W., Wittmann, J., Wulz, C.-E., Zarucki, M., Chekhovsky, V., Mossolov, V., Suarez Gonzalez, J., De Wolf, E.A., Di Croce, D., Janssen, X., Lauwers, J., Pieters, M., Van De Klundert, M., Van Haevermaet, H., Van Mechelen, P., Van Remortel, N., Abu Zeid, S., Blekman, F., D’Hondt, J., De Bruyn, I., De Clercq, J., Deroover, K., Flouris, G., Lontkovskyi, D., Lowette, S., Marchesini, I., Moortgat, S., Moreels, L., Python, Q., Skovpen, K., Tavernier, S., Van Doninck, W., Van Mulders, P., Van Parijs, I., Beghin, D., Bilin, B., Brun, H., Clerbaux, B., De Lentdecker, G., Delannoy, H., Dorney, B., Fasanella, G., Favart, L., Goldouzian, R., Grebenyuk, A., Kalsi, A.K., Lenzi, T., Luetic, J., Postiau, N., Starling, E., Thomas, L., Vander Velde, C., Vanlaer, P., Vannerom, D., Wang, Q., Cornelis, T., Dobur, D., Fagot, A., Gul, M., Khvastunov, I., Poyraz, D., Roskas, C., Trocino, D., Tytgat, M., Verbeke, W., Vermassen, B., Vit, M., Zaganidis, N., Bakhshiansohi, H., Bondu, O., Brochet, S., Bruno, G., Caputo, C., David, P., Delaere, C., Delcourt, M., Francois, B., Giammanco, A., Krintiras, G., Lemaitre, V., Magitteri, A., Mertens, A., Musich, M., Piotrzkowski, K., Saggio, A., Vidal Marono, M., Wertz, S., Zobec, J., Alves, F.L., Alves, G.A., Brito, L., Correa Martins Junior, M., Correia Silva, G., Hensel, C., Moraes, A., Pol, M.E., Rebello Teles, P., Belchior Batista Das Chagas, E., Carvalho, W., Chinellato, J., Coelho, E., Da Costa, E.M., Da Silveira, G.G., De Jesus Damiao, D., De Oliveira Martins, C., Fonseca De Souza, S., Malbouisson, H., Matos Figueiredo, D., Melo De Almeida, M., Mora Herrera, C., Mundim, L., Nogima, H., Prado Da Silva, W.L., Sanchez Rosas, L.J., Santoro, A., Sznajder, A., Thiel, M., Tonelli Manganote, E.J., Torres Da Silva De Araujo, F., Vilela Pereira, A., Ahuja, S., Bernardes, C.A., Calligaris, L., Fernandez Perez Tomei, T.R., Gregores, E.M., Mercadante, P.G., Novaes, S.F., Padula, S.S., Romero Abad, D., Aleksandrov, A., Hadjiiska, R., Iaydjiev, P., Marinov, A., Misheva, M., Rodozov, M., Shopova, M., Sultanov, G., Dimitrov, A., Litov, L., Pavlov, B., Petkov, P., Fang, W., Gao, X., Yuan, L., Ahmad, M., Bian, J.G., Chen, G.M., Chen, H.S., Chen, M., Chen, Y., Jiang, C.H., Leggat, D., Liao, H., Liu, Z., Romeo, F., Shaheen, S.M., Spiezia, A., Tao, J., Wang, C., Wang, Z., Yazgan, E., Zhang, H., Zhao, J., Ban, Y., Chen, G., Levin, 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C., Colaleo, A., Creanza, D., Cristella, L., De Filippis, N., De Palma, M., Di Florio, A., Errico, F., Fiore, L., Gelmi, A., Iaselli, G., Ince, M., Lezki, S., Maggi, G., Maggi, M., Miniello, G., My, S., Nuzzo, S., Pompili, A., Pugliese, G., Radogna, R., Ranieri, A., Selvaggi, G., Sharma, A., Silvestris, L., Venditti, R., Verwilligen, P., Zito, G., Abbiendi, G., Battilana, C., Bonacorsi, D., Borgonovi, L., Braibant-Giacomelli, S., Campanini, R., Capiluppi, P., Castro, A., Cavallo, F.R., Chhibra, S.S., Ciocca, C., Codispoti, G., Cuffiani, M., Dallavalle, G.M., Fabbri, F., Fanfani, A., Giacomelli, P., Grandi, C., Guiducci, L., Iemmi, F., Marcellini, S., Masetti, G., Montanari, A., Navarria, F.L., Perrotta, A., Primavera, F., Rossi, A.M., Rovelli, T., Siroli, G.P., Tosi, N., Albergo, S., Di Mattia, A., Potenza, R., Tricomi, A., Tuve, C., Barbagli, G., Chatterjee, K., Ciulli, V., Civinini, C., D’Alessandro, R., Focardi, E., Latino, G., Lenzi, P., Meschini, M., Paoletti, S., Russo, L., 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Ibrahim, Z.A., Md Ali, M.A.B., Mohamad Idris, F., Wan Abdullah, W.A.T., Yusli, M.N., Zolkapli, Z., Castaneda Hernandez, A., Murillo Quijada, J.A., Castilla-Valdez, H., De La Cruz-Burelo, E., Duran-Osuna, M.C., Heredia-De La Cruz, I., Lopez-Fernandez, R., Mejia Guisao, J., Rabadan-Trejo, R.I., Ramirez-Garcia, M., Ramirez-Sanchez, G., Reyes-Almanza, R., Sanchez-Hernandez, A., Carrillo Moreno, S., Oropeza Barrera, C., Vazquez Valencia, F., Eysermans, J., Pedraza, I., Salazar Ibarguen, H.A., Uribe Estrada, C., Morelos Pineda, A., Krofcheck, D., Bheesette, S., Butler, P.H., Ahmad, A., Ahmad, M., Asghar, M.I., Hassan, Q., Hoorani, H.R., Saddique, A., Shah, M.A., Shoaib, M., Waqas, M., Bialkowska, H., Bluj, M., Boimska, B., Frueboes, T., Górski, M., Kazana, M., Nawrocki, K., Szleper, M., Traczyk, P., Zalewski, P., Bunkowski, K., Byszuk, A., Doroba, K., Kalinowski, A., Konecki, M., Krolikowski, J., Misiura, M., Olszewski, M., Pyskir, A., Walczak, M., Bargassa, P., Beirão Da Cruz E Silva, C., Di Francesco, A., Faccioli, P., Galinhas, B., Gallinaro, M., Hollar, J., Leonardo, N., Lloret Iglesias, L., Nemallapudi, M.V., Seixas, J., Strong, G., Toldaiev, O., Vadruccio, D., Varela, J., Afanasiev, S., Alexakhin, V., Bunin, P., Gavrilenko, M., Golunov, A., Golutvin, I., Gorbounov, N., Karjavin, V., Lanev, A., Malakhov, A., Matveev, V., Moisenz, P., Palichik, V., Perelygin, V., Savina, M., Shmatov, S., Smirnov, V., Voytishin, N., Zarubin, A., Golovtsov, V., Ivanov, Y., Kim, V., Kuznetsova, E., Levchenko, P., Murzin, V., Oreshkin, V., Smirnov, I., Sosnov, D., Sulimov, V., Uvarov, L., Vavilov, S., Vorobyev, A., Andreev, Y., Dermenev, A., Gninenko, S., Golubev, N., Karneyeu, A., Kirsanov, M., Krasnikov, N., Pashenkov, A., Tlisov, D., Toropin, A., Epshteyn, V., Gavrilov, V., Lychkovskaya, N., Popov, V., Pozdnyakov, I., Safronov, G., Spiridonov, A., Stepennov, A., Stolin, V., Toms, M., Vlasov, E., Zhokin, A., Aushev, T., Chadeeva, M., Parygin, P., Philippov, D., Polikarpov, S., Popova, E., Rusinov, V., Andreev, V., Azarkin, M., Dremin, I., Kirakosyan, M., Rusakov, S.V., Terkulov, A., Baskakov, A., Belyaev, A., Boos, E., Dubinin, M., Dudko, L., Ershov, A., Gribushin, A., Klyukhin, V., Kodolova, O., Lokhtin, I., Miagkov, I., Obraztsov, S., Petrushanko, S., Savrin, V., Snigirev, A., Blinov, V., Dimova, T., Kardapoltsev, L., Shtol, D., Skovpen, Y., Azhgirey, I., Bayshev, I., Bitioukov, S., Elumakhov, D., Godizov, A., Kachanov, V., Kalinin, A., Konstantinov, D., Mandrik, P., Petrov, V., Ryutin, R., Slabospitskii, S., Sobol, A., Troshin, S., Tyurin, N., Uzunian, A., Volkov, A., Babaev, A., Baidali, S., Okhotnikov, V., Adzic, P., Cirkovic, P., Devetak, D., Dordevic, M., Milosevic, J., Alcaraz Maestre, J., Álvarez Fernández, A., Bachiller, I., Barrio Luna, M., Brochero Cifuentes, J.A., Cerrada, M., Colino, N., De La Cruz, B., Delgado Peris, A., Fernandez Bedoya, C., Fernández Ramos, J.P., Flix, J., Fouz, M.C., Gonzalez Lopez, O., Goy Lopez, S., Hernandez, J.M., Josa, M.I., 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Impact of COVID-19 on Cardiovascular Testing in the United States Versus the Rest of the World

OBJECTIVES This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.BACKGROUND The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.METHODS Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.RESULTS Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p 1/4 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p &lt; 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.CONCLUSIONS We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Whole-genome sequencing reveals host factors underlying critical COVID-19

: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease