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20,085 results on '"Elias, A."'

6. Imaging Prognostic Biomarkers in Hepatocellular Carcinoma: A Comprehensive Review.

Author

Elias-Neto, Abrahão, Gonzaga, Ana Paula F.C., Braga, Fernanda A., Gomes, Natália B.N., Torres, Ulysses S., and D'Ippolito, Giuseppe

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide with its incidence on the rise globally. This paper provides a comprehensive review of prognostic imaging markers in HCC, emphasizing their role in risk stratification and clinical decision-making. We explore quantitative and qualitative criteria derived from imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI), which can offer valuable insights into the biological behavior of the tumor. While many of these markers are not yet widely integrated into current clinical guidelines, they represent a promising future direction for approaching this highly heterogeneous cancer. However, standardization and validation of these markers remain important challenges. We conclude by emphasizing the importance of ongoing research to enhance clinical practices and improve outcomes for patients with HCC. [ABSTRACT FROM AUTHOR]

Published
2024
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7. The role of connective interventions in the collective management of public-bad problems: Evidence from a socio-ecological system perspective.

Author

Galarza-Villamar, Julissa A., McCampbell, Mariette, Agyekumhene, Christopher, Asingizwe, Domina, Attoh, Emmanuel M. N. A. N., Damtew, Elias, Chepkwony, Richard, Cieslik, Katarzyna, Munthali, Nyamwaya, Murindahabi, Marilyn M., Mutavi, Faith, Nyamekye, Andy B, Tafesse, Shiferaw, Struik, Paul C., and Leeuwis, Cees

Abstract

Managing public-bad problems is difficult and arriving at an effective collective response can be an even bigger challenge. Using a socio-ecological systems framework, we explore the role of communication-focused interventions in the management of public bads in six African case-studies. We analyse case-specific livelihood units, public-bad risk conditions, and threats, and the strategies to prevent and control a public bad. We assess the impact of connective interventions on existing risk governance systems and problem management. Our findings show that connective interventions enable people to define risk boundaries, learn about the costs and benefits of public-bad management, and develop capacity for collective decision-making and problem monitoring. However, connective interventions cannot work in isolation and require complementary strategies, and trust in broader governance and institutional arrangements. Our research demonstrates the value of the social ecological systems framework in synthesizing lessons and insights from diverse interdisciplinary studies. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Strong convergence of a nonparametric relative error regression estimator under missing data with functional predictors.

Author

Boucetta, Adel, Guessoum, Zohra, and Ould-Said, Elias

Abstract

In this paper, we develop a nonparametric estimator of the regression function for a functional explanatory variable and a scalar response variable that is subject to left truncation and right censoring. The estimator is constructed by minimizing the mean squared relative error, which is a robust criterion that reduces the impact of outliers relatively to the Nadaraya Watson estimator. We prove the pointwise and uniform convergence of the estimator under some regular conditions and assess its performance by a numerical study. We also investigate the robustness of the estimator using the influence function as a measure of sensitivity to outliers and apply the estimator to a real dataset. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Evaluation of acute and midterm outcomes after complex combined antegrade/retrograde recanalization for occlusions of the femoropopliteal and infrapopliteal arteries.

Author

Noory, Elias, Böhme, Tanja, Staus, Paulina Ines, Eltity-Uhl, Dinah, Horakh, Andrea, Bollenbacher, Roaa, Westermann, Dirk, and Zeller, Thomas

Abstract

When antegrade recanalization of femoropopliteal and/or infrapopliteal occlusions fails, retrograde access has become an established option. To evaluate the results of combined antegrade and retrograde recanalization of femoropopliteal and infrapopliteal occlusions, patients undergoing secondary retrograde recanalization attempts were analyzed retrospectively. The primary end point was the success of the procedure (successful occlusion crossing using the antegrade/retrograde technique). Secondary end points include complication rate, primary patency and target lesion revascularization (TLR) rate, amputation rate, changes in ankle-brachial index, and Rutherford-Becker class. Predictors for procedure failure and TLR were analyzed. We included 888 patients: 362 with femoropopliteal (group 1), 353 with infrapopliteal (group 2), and 173 with multilevel (group 3) recanalization. Critical limb-threatening ischemia was present in group 1, 2, and 3 in 36%, 62%, and 76% of patients, respectively. The intervention was successful in 92.5%, 93.8%, and 90.8% of the respective cases (P =.455). The overall peri-interventional complication rate was 7.2%. At 6, 12, and 24 months, primary patency was highest in group 1 (63.9%, 45.8%, and 33.3%), followed by group 3 (59.8%, 46.1%, and 33.3%), and group 2 (58.5%, 43.1%, and 30.4%; P =.537). The risk of undergoing repeated TLR within 24 months was 31.4% for group 1, 39.1% for group 2, and 45.7% for group 3. At 24 months, the survival rates in groups 1, 2, and 3 were 93.8%, 79.4%, and 87.5%, respectively. Over 24 months, 75 patients (8.4%) had to undergo amputation. Significant improvements in both ankle-brachial index and Rutherford-Becker class were present at discharge as well as at 6, 12, and 24 months (P <.001). Dialysis dependency was a predictor of unsuccessful antegrade/retrograde recanalization (P =.048). Lesion length (P =.0043), dialysis (P =.033), and recanalization level (P =.013) increase the risk of TLR. Using a combined antegrade/retrograde access, recanalization of occluded femoropopliteal and/or infrapopliteal arteries can be achieved in a large number of cases. Owing to the high rate of repeated TLR across all lesion localizations, the indication for antegrade and retrograde recanalization may be limited to patients with critical limb-threatening ischemia. [ABSTRACT FROM AUTHOR]

Published
2024
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10. High delta angle after reverse total shoulder arthroplasty increases stresses of the acromion: biomechanical study of different implant positions.

Author

Schenk, Pascal, Sutter, Nikita, Molina, Erasmo, Wieser, Karl, Gerber, Christian, and Bachmann, Elias

Abstract

Acromial fractures after reverse total shoulder arthroplasty (RTSA) are a common complication. Nevertheless, only a few studies have identified risk factors for acromial fractures after RTSA. High delta angle (combination of inferiorization and medialization of the center of rotation [COR]) after RTSA was identified as a risk factor in recent studies. The aim of this study was the biomechanical exploration of different delta angles and implant configurations with regard to the acromial stress. In a rigid body model of the upper extremity muscle, forces of the deltoid muscle were calculated before and after implanting RTSA in different arm and implant positions. The deltoid muscle was divided into an anterior, middle, and posterior part. Implant positions of the glenoid components were changed in the medialization, lateralization, and inferiorization of the COR as well as lateralization of the humeral component. Further, in a finite element model of the upper extremity, the stresses of the acromion in the same implant design configurations were measured. Differences in acromial stress between different delta angle model configurations were observed. Lateralization (5 and 10 mm) of the glenosphere reduced the maximal acromial stress by 21% (1.5 MPa) and 31% (1.3 MPa), respectively. Inferiorization (5 and 10 mm) of the glenosphere increased the maximal acromial stress by 5% (2.0 MPa) and 15% (2.2 MPa), respectively. Changes in positioning the humeral component was found to have the highest impact in this model configuration. A 10-mm-lateralized humeral component reduced acromial stress by 37% (1.2 MPa), whereas in the 6-mm-medialized configuration, an increase in acromial stress by 83% (3.48 MPa) was observed. There was a high correlation between the delta angle and acromial stress (R 2 = 0.967). Implant design configuration has an impact on the acromial stress. High delta angles correlate with an increase in acromial stress. Both lateralization of the COR and the humerus decreased the acromial stress in our study. The lateralization of the humerus has the highest impact in influencing acromial stress. Because of contrary results in the current literature, further studies with focus on the acromial stress influenced by different anatomic variants of the shoulder and the acromion are needed before a clinical recommendation can be made. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Control of SAG-GaN at the Nanoscale.

Author

Semlali, Elias, Gil, Evelyne, Avit, Geoffrey, André, Yamina, Sauvagnat, Arthur, Jridi, Jihen, Moskalenko, Andriy V., Shields, Philip A., Rochat, Névine, Grenier, Adeline, and Trassoudaine, Agnès

Published
2024
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18. An in vitro study of fluoride-preloaded halloysite nanotubes to enhance the fluoride release in conventional and resin-modified glass ionomer cements.

Author

García-Moreno, Martha Esperanza, Salmerón-Valdés, Elias Nahum, Morales-Valenzuela, Adriana Alejandra, Velázquez-Enríquez, Ulises, Toral-Rizo, Víctor Hugo, and Lara-Carrillo, Edith

Abstract

The purpose of the study was to compare the fluoride release in two conventional glass ionomer cements (Ionobond, Ketac Molar) and two resin-modified glass ionomer cements (Vitrebond, Fuji II LC) adapted with halloysite nanotubes preloaded with sodium fluoride at different concentrations. In total, 96 samples were prepared and distributed into four control groups and eight experimental groups (5 % and 10 %). Totals of 10 % and 5 % of the total weight of ionomer powder needed to prepare the samples were replaced with nanotubes, preloaded at 2,000 parts per million, respectively. The experimental groups were followed for 120 days at seven time intervals. All the samples were stored at 37 °C. All the experimental groups showed significant differences compared with the control groups; likewise, differences were observed between the concentrations of 5% and 10%. The experimental groups (conventional and resin-modified glass ionomer cements adapted with preloaded nanotubes) released a higher and more constant amount of fluoride compared to the control groups. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Saving lives and restoring hope: Enhancing outcomes through comprehensive understanding of maxillofacial surgery in disaster medicine.

Author

Grillo, Ricardo, Samieirad, Sahand, Balel, Yunus, Borba, Alexandre Meireles, Machado dos Reis, Philippi, and Melhem-Elias, Fernando

Subjects
DISASTER medicine, RESCUE work, EMERGENCY management, ORAL surgeons, LITERATURE reviews
Abstract

This article delves into the profound impact of various types of disasters, examining some specific contexts. It provides insights into the unique challenges posed by different disasters, ultimately highlighting the invaluable role of maxillofacial surgery in addressing the critical healthcare needs of affected populations. A comprehensive review of the literature was conducted to analyze the role of maxillofacial surgery in disaster management. Relevant studies were examined to gather evidence supporting the criticality of maxillofacial surgeons in disaster response. Continuous training, coordination, and international collaboration among maxillofacial surgeons were reported as key factors in enhancing preparedness and improving post-disaster recovery. Sharing experiences, implementing best practices, and staying updated with advancements in the field seemed crucial for maximizing the impact of maxillofacial surgery in disaster medicine. By prioritizing the inclusion of maxillofacial surgeons in disaster response teams, lives can be saved, functional outcomes can be improved, and hope can be restored in affected communities. Understanding the intricacies and patterns associated with various types of disasters can be crucial details for successful rescue operations. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Tranq Dope: Characterization of an ED cohort treated with a novel opioid withdrawal protocol in the era of fentanyl/xylazine.

Author

London, Kory, Li, Yutong, Kahoud, Jennifer L., Cho, Davis, Mulholland, Jamus, Roque, Sebastian, Stugart, Logan, Gillingham, Jeffrey, Borne, Elias, and Slovis, Benjamin

Abstract

Treating opioid use disorder has reached a new level of challenge. Synthetic opioids and xylazine have joined the non-medical opioid supply, multiplying the complexities of caring for individuals in emergency departments (ED). This combination, known as 'tranq dope,' is poorly described in literature. Inadequate withdrawal treatment results in a disproportionately high rate of patient-directed discharges (also known as against medical advice dispositions, or AMA). This study aimed to describe a cohort of individuals who received a novel order set for suspected fentanyl and xylazine withdrawal in the ED. This is a descriptive study evaluating a cohort of ED patients who received withdrawal medications from a novel protocol and electronic health record order set. Individuals being assessed in the ED while suffering from withdrawal were eligible. Individuals under age 18, on stable outpatient MOUD or who were pregnant were excluded. Treatment strategies included micro-induction buprenorphine, short acting opioids, non-opioid analgesics, and other adjunctive medications. Data collected included: demographics including zip code, urine toxicology screening, order set utilization and disposition data. Clinical Opiate Withdrawal Scale (COWS) scores were recorded, where available, before and following exposure to the medications. There were 270 patient encounters that occurred between September 14, 2022, and March 9, 2023 included in the total study cohort. Of those, 66 % were male, mean age 37 with 71 % residing within Philadelphia zip codes. 100 % of urine toxicology screenings were positive for fentanyl. Of the 177 patients with both pre- and post-exposure COWS scores documented, constituting the final cohort, patients receiving medications had their COWS score decrease from a median of 12 to a median of 4 (p < 0.001). The AMA rate for this cohort was 3.9 %, whereas the baseline for the population with OUD was 10.7 %. Recorded adverse effects were few and resolved without complication. Fentanyl and xylazine withdrawal are challenging for patients and providers. A novel tranq dope withdrawal order set may reduce both COWS scores and rate of patient-directed discharge in this cohort of patients, though further investigation is needed to confirm findings. • Fentanyl and Xylazine are contaminating an ever-growing portion of non-medical opioid supply in the United States • The withdrawal syndromes faced by those using fentanyl and xylazine are unprecedented in their severity and complexity • Use of a multi-modal strategy to address pain, sympathetic activation and other features of the withdrawal may be important. • Potential options include micro-induction dosed buprenorphine, short acting conventional opioids and adjunctive medications. • Use of treatments may reduce withdrawal severity and risk of patient-directed discharge (against medical advice disposition). [ABSTRACT FROM AUTHOR]

Published
2024
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27. Fragments from Ottoman Zagori: continuity and change in a montane landscape through a local perspective.

Author

Moudopoulos-Athanasiou, Faidon and Kolovos, Elias

Subjects
ELITE (Social sciences), LAND settlement patterns, FOURTEENTH century, NINETEENTH century, SIXTEENTH century, CULTURAL landscapes, LANDSCAPE archaeology
Abstract

This article discusses elite continuity and settlement pattern change in Zagori (NW Greece) from the late fourteenth to the nineteenth century. The peaceful assimilation of the regional and local elites into the Ottoman Empire (1430) led to adaptations in the montane landscape. Imperial and local archival research, ethnography, and landscape archaeology reveal that the Ottoman administration divided large decentralized settlements into smaller villages to accommodate local elites and new timariots. This topography of division (fifteenth to sixteenth centuries) gave way to a topography of adaptation (seventeenth to nineteenth centuries) when local elites influenced settlement patterns in forming the administrative unit the Zagorisian League. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Gender-focused Training for Non-university Teachers in Spain, through Social Media.

Author

Said-Hung, Elias, Martín-Gutiérrez, Angela, and Conde-Jiménez, Jesús

Subjects
TEACHER development, TEACHER role, SCIENTIFIC knowledge, TEACHER training, WOMEN teachers
Abstract

The growth of social media has been suggested as a potential tool for teacher training and development. This study aims to identify patterns of SM use in the ongoing education of non-university teachers in Spain from a gender perspective. The research was based on a survey conducted between November 2021 and January 2022 involving 462 male and female non-university teachers. The data presented in this work reveals differences between teachers based on gender and associated patterns. It also highlights variables contributing to a better understanding of SM use and responsible use among female and male teachers. This study emphasizes teachers' role in implementing strategies to increase SM use among the studied population in Spain. This role requires promoting the dissemination and access to scientific knowledge from educational centres, training institutions, and university academic institutions. Actions should focus on providing relevant scientific content in appropriate and attractive formats to increase the use of SM as a continuous training resource. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Nonlinear Data-Driven Control Part II: qLPV Predictive Control with Parameter Extrapolation.

Author

Morato, Marcelo Menezes, Normey-Rico, Julio Elias, and Sename, Olivier

Abstract

We present a novel data-driven Model Predictive Control (MPC) algorithm for nonlinear systems. The method is based on recent extensions of behavioural theory and Willem's Fundamental Lemma for nonlinear systems by the means of adequate Input–Output (IO) quasi-Linear Parameter-Varying (qLPV) embeddings. Thus, the MPC is formulated to ensure regulation and IO constraints satisfaction, based only on measured datasets of sufficient length (and under persistent excitation). The main innovation is to consider the knowledge of the function that maps the qLPV realisation, and apply an extrapolation procedure in order to generate the corresponding future scheduling trajectories, at each sample. Accordingly, we briefly discuss the issues of closed-loop IO stability and recursive feasibility certificates of the method. The algorithm is tested and discussed with the aid of a numerical application. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Nonlinear Data-Driven Control Part I: An Overview of Trajectory Representations.

Author

Morato, Marcelo Menezes, Normey-Rico, Julio Elias, and Sename, Olivier

Abstract

In the literature, a recent debate has been brought up regarding how linear time-invariant systems can be represented by trajectories features. That is, how a single input–output (IO) data dictionary can be exploited to span all possible system trajectories, as long as the input is persistently exciting. Indeed, the so-called behavioural framework is a promising alternative for controller synthesis without the necessity of system identification procedures. In this paper, we provide an overview of the available results. In particular, we focus on how quasi-Linear Parameter Varying (qLPV) embeddings, in the data-driven context, can be used to represent nonlinear dynamical systems along suitable IO coordinates. We debate the topics of nonlinear data-driven simulation and predictions, as proposed in recent works. The effectiveness of the surveyed tools is tested in practice and shown to provide accurate descriptions of the nonlinear dynamics by the means of a linear representation structure. For such, we consider a high-fidelity nonlinear simulator of a rotational pendulum benchmark simulator and an electro-mechanical positioning experimental validation test-bench. We also debate that, even if the qLPV scheduling function is erroneously selected, the framework is still able to offer a reasonably trustworthy representation of the system. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Author

Naghavi, Mohsen, Vollset, Stein Emil, Ikuta, Kevin S, Swetschinski, Lucien R, Gray, Authia P, Wool, Eve E, Robles Aguilar, Gisela, Mestrovic, Tomislav, Smith, Georgia, Han, Chieh, Hsu, Rebecca L, Chalek, Julian, Araki, Daniel T, Chung, Erin, Raggi, Catalina, Gershberg Hayoon, Anna, Davis Weaver, Nicole, Lindstedt, Paulina A, Smith, Amanda E, Altay, Umut, Bhattacharjee, Natalia V, Giannakis, Konstantinos, Fell, Frederick, McManigal, Barney, Ekapirat, Nattwut, Mendes, Jessica Andretta, Runghien, Tilleye, Srimokla, Oraya, Abdelkader, Atef, Abd-Elsalam, Sherief, Aboagye, Richard Gyan, Abolhassani, Hassan, Abualruz, Hasan, Abubakar, Usman, Abukhadijah, Hana J, Aburuz, Salahdein, Abu-Zaid, Ahmed, Achalapong, Sureerak, Addo, Isaac Yeboah, Adekanmbi, Victor, Adeyeoluwa, Temitayo Esther, Adnani, Qorinah Estiningtyas Sakilah, Adzigbli, Leticia Akua, Afzal, Muhammad Sohail, Afzal, Saira, Agodi, Antonella, Ahlstrom, Austin J, Ahmad, Aqeel, Ahmad, Sajjad, Ahmad, Tauseef, Ahmadi, Ali, Ahmed, Ayman, Ahmed, Haroon, Ahmed, Ibrar, Ahmed, Mohammed, Ahmed, Saeed, Ahmed, Syed Anees, Akkaif, Mohammed Ahmed, Al Awaidy, Salah, Al Thaher, Yazan, Alalalmeh, Samer O, AlBataineh, Mohammad T, Aldhaleei, Wafa A, Al-Gheethi, Adel Ali Saeed, Alhaji, Nma Bida, Ali, Abid, Ali, Liaqat, Ali, Syed Shujait, Ali, Waad, Allel, Kasim, Al-Marwani, Sabah, Alrawashdeh, Ahmad, Altaf, Awais, Al-Tammemi, Alaa B., Al-Tawfiq, Jaffar A, Alzoubi, Karem H, Al-Zyoud, Walid Adnan, Amos, Ben, Amuasi, John H, Ancuceanu, Robert, Andrews, Jason R, Anil, Abhishek, Anuoluwa, Iyadunni Adesola, Anvari, Saeid, Anyasodor, Anayochukwu Edward, Apostol, Geminn Louis Carace, Arabloo, Jalal, Arafat, Mosab, Aravkin, Aleksandr Y, Areda, Demelash, Aremu, Abdulfatai, Artamonov, Anton A, Ashley, Elizabeth A, Asika, Marvellous O, Athari, Seyyed Shamsadin, Atout, Maha Moh'd Wahbi, Awoke, Tewachew, Azadnajafabad, Sina, Azam, James Mba, Aziz, Shahkaar, Azzam, Ahmed Y., Babaei, Mahsa, Babin, Francois-Xavier, Badar, Muhammad, Baig, Atif Amin, Bajcetic, Milica, Baker, Stephen, Bardhan, Mainak, Barqawi, Hiba Jawdat, Basharat, Zarrin, Basiru, Afisu, Bastard, Mathieu, Basu, Saurav, Bayleyegn, Nebiyou Simegnew, Belete, Melaku Ashagrie, Bello, Olorunjuwon Omolaja, Beloukas, Apostolos, Berkley, James A, Bhagavathula, Akshaya Srikanth, Bhaskar, Sonu, Bhuyan, Soumitra S, Bielicki, Julia A, Briko, Nikolay Ivanovich, Brown, Colin Stewart, Browne, Annie J, Buonsenso, Danilo, Bustanji, Yasser, Carvalheiro, Cristina G, Castañeda-Orjuela, Carlos A, Cenderadewi, Muthia, Chadwick, Joshua, Chakraborty, Sandip, Chandika, Rama Mohan, Chandy, Sara, Chansamouth, Vilada, Chattu, Vijay Kumar, Chaudhary, Anis Ahmad, Ching, Patrick R, Chopra, Hitesh, Chowdhury, Fazle Rabbi, Chu, Dinh-Toi, Chutiyami, Muhammad, Cruz-Martins, Natalia, da Silva, Alanna Gomes, Dadras, Omid, Dai, Xiaochen, Darcho, Samuel D, Das, Saswati, De la Hoz, Fernando Pio, Dekker, Denise Myriam, Dhama, Kuldeep, Diaz, Daniel, Dickson, Benjamin Felix Rothschild, Djorie, Serge Ghislain, Dodangeh, Milad, Dohare, Sushil, Dokova, Klara Georgieva, Doshi, Ojas Prakashbhai, Dowou, Robert Kokou, Dsouza, Haneil Larson, Dunachie, Susanna J, Dziedzic, Arkadiusz Marian, Eckmanns, Tim, Ed-Dra, Abdelaziz, Eftekharimehrabad, Aziz, Ekundayo, Temitope Cyrus, El Sayed, Iman, Elhadi, Muhammed, El-Huneidi, Waseem, Elias, Christelle, Ellis, Sally J, Elsheikh, Randa, Elsohaby, Ibrahim, Eltaha, Chadi, Eshrati, Babak, Eslami, Majid, Eyre, David William, Fadaka, Adewale Oluwaseun, Fagbamigbe, Adeniyi Francis, Fahim, Ayesha, Fakhri-Demeshghieh, Aliasghar, Fasina, Folorunso Oludayo, Fasina, Modupe Margaret, Fatehizadeh, Ali, Feasey, Nicholas A, Feizkhah, Alireza, Fekadu, Ginenus, Fischer, Florian, Fitriana, Ida, Forrest, Karen M, Fortuna Rodrigues, Celia, Fuller, John E, Gadanya, Muktar A, Gajdács, Márió, Gandhi, Aravind P, Garcia-Gallo, Esteban E, Garrett, Denise O, Gautam, Rupesh K, Gebregergis, Miglas Welay, Gebrehiwot, Mesfin, Gebremeskel, Teferi Gebru, Geffers, Christine, Georgalis, Leonidas, Ghazy, Ramy Mohamed, Golechha, Mahaveer, Golinelli, Davide, Gordon, Melita, Gulati, Snigdha, Gupta, Rajat Das, Gupta, Sapna, Gupta, Vijai Kumar, Habteyohannes, Awoke Derbie, Haller, Sebastian, Harapan, Harapan, Harrison, Michelle L, Hasaballah, Ahmed I, Hasan, Ikramul, Hasan, Rumina Syeda, Hasani, Hamidreza, Haselbeck, Andrea Haekyung, Hasnain, Md Saquib, Hassan, Ikrama Ibrahim, Hassan, Shoaib, Hassan Zadeh Tabatabaei, Mahgol Sadat, Hayat, Khezar, He, Jiawei, Hegazi, Omar E, Heidari, Mohammad, Hezam, Kamal, Holla, Ramesh, Holm, Marianne, Hopkins, Heidi, Hossain, Md Mahbub, Hosseinzadeh, Mehdi, Hostiuc, Sorin, Hussein, Nawfal R, Huy, Le Duc, Ibáñez-Prada, Elsa D, Ikiroma, Adalia, Ilic, Irena M, Islam, Sheikh Mohammed Shariful, Ismail, Faisal, Ismail, Nahlah Elkudssiah, Iwu, Chidozie Declan, Iwu-Jaja, Chinwe Juliana, Jafarzadeh, Abdollah, Jaiteh, Fatoumatta, Jalilzadeh Yengejeh, Reza, Jamora, Roland Dominic G, Javidnia, Javad, Jawaid, Talha, Jenney, Adam W J, Jeon, Hyon Jin, Jokar, Mohammad, Jomehzadeh, Nabi, Joo, Tamas, Joseph, Nitin, Kamal, Zul, Kanmodi, Kehinde Kazeem, Kantar, Rami S, Kapisi, James Apollo, Karaye, Ibraheem M, Khader, Yousef Saleh, Khajuria, Himanshu, Khalid, Nauman, Khamesipour, Faham, Khan, Ajmal, Khan, Mohammad Jobair, Khan, Muhammad Tariq, Khanal, Vishnu, Khidri, Feriha Fatima, Khubchandani, Jagdish, Khusuwan, Suwimon, Kim, Min Seo, Kisa, Adnan, Korshunov, Vladimir Andreevich, Krapp, Fiorella, Krumkamp, Ralf, Kuddus, Mohammed, Kulimbet, Mukhtar, Kumar, Dewesh, Kumaran, Emmanuelle A P, Kuttikkattu, Ambily, Kyu, Hmwe Hmwe, Landires, Iván, Lawal, Basira Kankia, Le, Thao Thi Thu, Lederer, Ingeborg Maria, Lee, Munjae, Lee, Seung Won, Lepape, Alain, Lerango, Temesgen Leka, Ligade, Virendra S, Lim, Cherry, Lim, Stephen S, Limenh, Liknaw Workie, Liu, Chaojie, Liu, Xiaofeng, Liu, Xuefeng, Loftus, Michael J, M Amin, Hawraz Ibrahim, Maass, Kelsey Lynn, Maharaj, Sandeep B, Mahmoud, Mansour Adam, Maikanti-Charalampous, Panagiota, Makram, Omar M, Malhotra, Kashish, Malik, Ahmad Azam, Mandilara, Georgia D, Marks, Florian, Martinez-Guerra, Bernardo Alfonso, Martorell, Miquel, Masoumi-Asl, Hossein, Mathioudakis, Alexander G, May, Juergen, McHugh, Theresa A, Meiring, James, Meles, Hadush Negash, Melese, Addisu, Melese, Endalkachew Belayneh, Minervini, Giuseppe, Mohamed, Nouh Saad, Mohammed, Shafiu, Mohan, Syam, Mokdad, Ali H, Monasta, Lorenzo, Moodi Ghalibaf, AmirAli, Moore, Catrin E, Moradi, Yousef, Mossialos, Elias, Mougin, Vincent, Mukoro, George Duke, Mulita, Francesk, Muller-Pebody, Berit, Murillo-Zamora, Efren, Musa, Sani, Musicha, Patrick, Musila, Lillian A, Muthupandian, Saravanan, Nagarajan, Ahamarshan Jayaraman, Naghavi, Pirouz, Nainu, Firzan, Nair, Tapas Sadasivan, Najmuldeen, Hastyar Hama Rashid, Natto, Zuhair S, Nauman, Javaid, Nayak, Biswa Prakash, Nchanji, G Takop, Ndishimye, Pacifique, Negoi, Ionut, Negoi, Ruxandra Irina, Nejadghaderi, Seyed Aria, Nguyen, QuynhAnh P, Noman, Efaq Ali, Nwakanma, Davis 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Usha, Rashidi, Mohammad-Mahdi, Rathish, Devarajan, Rattanavong, Sayaphet, Rawaf, Salman, Redwan, Elrashdy Moustafa Mohamed, Reyes, Luis Felipe, Roberts, Tamalee, Robotham, Julie V, Rosenthal, Victor Daniel, Ross, Allen Guy, Roy, Nitai, Rudd, Kristina E, Sabet, Cameron John, Saddik, Basema Ahmad, Saeb, Mohammad Reza, Saeed, Umar, Saeedi Moghaddam, Sahar, Saengchan, Weeravoot, Safaei, Mohsen, Saghazadeh, Amene, Saheb Sharif-Askari, Narjes, Sahebkar, Amirhossein, Sahoo, Soumya Swaroop, Sahu, Maitreyi, Saki, Morteza, Salam, Nasir, Saleem, Zikria, Saleh, Mohamed A, Samodra, Yoseph Leonardo, Samy, Abdallah M, Saravanan, Aswini, Satpathy, Maheswar, Schumacher, Austin E, Sedighi, Mansour, Seekaew, Samroeng, Shafie, Mahan, Shah, Pritik A, Shahid, Samiah, Shahwan, Moyad Jamal, Shakoor, Sadia, Shalev, Noga, Shamim, Muhammad Aaqib, Shamshirgaran, Mohammad Ali, Shamsi, Anas, Sharifan, Amin, Shastry, Rajesh P, Shetty, Mahabalesh, Shittu, Aminu, Shrestha, Sunil, Siddig, Emmanuel Edwar, Sideroglou, Theologia, Sifuentes-Osornio, Jose, Silva, Luís Manuel Lopes Rodrigues, Simões, Eric A F, Simpson, Andrew J H, Singh, Amit, Singh, Surjit, Sinto, Robert, Soliman, Sameh S M, Soraneh, Soroush, Stoesser, Nicole, Stoeva, Temenuga Zhekova, Swain, Chandan Kumar, Szarpak, Lukasz, T Y, Sree Sudha, Tabatabai, Shima, Tabche, Celine, Taha, Zanan Mohammed-Ameen, Tan, Ker-Kan, Tasak, Nidanuch, Tat, Nathan Y, Thaiprakong, Areerat, Thangaraju, Pugazhenthan, Tigoi, Caroline Chepngeno, Tiwari, Krishna, Tovani-Palone, Marcos Roberto, Tran, Thang Huu, Tumurkhuu, Munkhtuya, Turner, Paul, Udoakang, Aniefiok John, Udoh, Arit, Ullah, Noor, Ullah, Saeed, Vaithinathan, Asokan Govindaraj, Valenti, Mario, Vos, Theo, Vu, Huong T L, Waheed, Yasir, Walker, Ann Sarah, Walson, Judd L, Wangrangsimakul, Tri, Weerakoon, Kosala Gayan, Wertheim, Heiman F L, Williams, Phoebe C M, Wolde, Asrat Arja, Wozniak, Teresa M, Wu, Felicia, Wu, Zenghong, Yadav, Mukesh Kumar Kumar, Yaghoubi, Sajad, Yahaya, Zwanden Sule, Yarahmadi, Amir, Yezli, Saber, Yismaw, Yazachew Engida, Yon, Dong Keon, Yuan, Chun-Wei, Yusuf, Hadiza, Zakham, Fathiah, Zamagni, Giulia, Zhang, Haijun, Zhang, Zhi-Jiang, Zielińska, Magdalena, Zumla, Alimuddin, Zyoud, Sa'ed H. H, Zyoud, Samer H, Hay, Simon I, Stergachis, Andy, Sartorius, Benn, Cooper, Ben S, Dolecek, Christiane, and Murray, Christopher J L

Abstract

Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts.

Published
2024
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33. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Author

Deanfield, John, Verma, Subodh, Scirica, Benjamin M, Kahn, Steven E, Emerson, Scott S, Ryan, Donna, Lingvay, Ildiko, Colhoun, Helen M, Plutzky, Jorge, Kosiborod, Mikhail N, Hovingh, G Kees, Hardt-Lindberg, Søren, Frenkel, Ofir, Weeke, Peter E, Rasmussen, Søren, Goudev, Assen, Lang, Chim C, Urina-Triana, Miguel, Pietilä, Mikko, Lincoff, A Michael, Abe, Mitsunori, Abhaichand, Rajpal K, Abhayaratna, Walter P, Abhyankar, Atul, Abidin, Imran B Zainal, Abou Assi, Hiba, Accini Mendoza, Jose L, Adas, Mine, Agaiby, John M, Agarwal, Devendra K, Agha, Maher, Ahmed, Azazuddin, Ahtiainen, Petteri, Aigner, Elmar, Ajay, Naik, Ali, Norsiah, Al-Karadsheh, Amer, Allison, Roy, Allison, Dale C, Alpenidze, Diana, Altuntas, Yuksel, Al-Zoebi, Ayham, Ambuj, Roy, Amerena, John, Anderson, Robert J, Ando, Toshiaki, Andrews, Robert, Antonova, Elizaveta, Appel, Karl-Friedrich, Arantes, Flávia B, Araz, Mustafa, Arbel, Yaron, Arenas León, José L, Argyrakopoulou, Georgia, Ariani, Mehrdad, Arias Mendoza, Maria A, Arif, Ahmed A, Arneja, Jaspal, Aroda, Vanita R, Aronne, Louis J, Arstall, Margaret, Asamoah, Njaimeh, Asanin, Milika, Audish, Hanid, Avram, Rodica, Badat, Aysha, Badiu, Corin V, Bakdash, Wa'el, Bakiner, Okan S, Bandezi, Vuyokazi N, Bang, Liew H, Bansal, Sandeep, Baranyai, Marietta, Barbarash, Olga, Barber, Mark, Barnum, Otis, Barone Rochette, Gilles, Bashkin, Amir, Baum, Seth, Bays, Harold E, Bazzoni Ruiz, Alberto E, Beckowski, Maciej, Beerachee, Yaswin, Bellary, Srikanth, Belousova, Lidia, Berk, Martin, Bernstein, Marc, Berra, Cesare, Beshay, Isaac, Bhagwat, Ajit, Bhan, Arti, Biggs, William C, Billings, Liana, Bitar, Fahed, Block, Bradley, Bo, Simona, Bogdanski, Pawel, Bolshakova, Olga O, Boshchenko, Alla A, Bosworth, Hayden, Botero Lopez, Rodrigo, Bôttcher, Morten, Bourgeois, Ronald, Brautigam, Donald, Breton, Cristian F, Broadley, Andrew, Brockmyre, Andrew P, Brodie, Steven K, Bucci, Marco, Budincevic, Hrvoje, Budoff, Matthew J, Buffman, Barry, Buljubasic, Nediljka, Buranapin, Supawan, Burgess, Lesley, Burguera, Bartolomé, Buriakovska, Olena, Buscemi, Silvio, Busch, Robert, Buse, John B, Buynak, Robert, Byrne, Maria, Caceaune, Elena, Cadena Bonfanti, Alberto J, Calinescu, Cornell V, Call, Robert S, Canecki Varzic, Silvija, Cannon, Kevin, Capehorn, Matt, Cariou, Bertrand, Carr, Jeffrey, Carrillo-Jimenez, Rodolfo, Casas, Marcelo, Castro, Almudena, Celik, Ahmet, Cercato, Cintia, Cermak, Ondrej, Cha, James Y, Chacon, Carolina, Chaicha-Brom, Tira, Chandra, Sandeep, Chettibi, Mohamed, Chevts, Julia, Christopher, Johann, Chrustowski, Witold, Cif, Adriana, Clark, Rebecca, Clark, Wayne, Clifford, Piers, Coetzee, Kathleen, Cogni, Giulia, Colao, Anna Maria, Colquhoun, David M, Concha, Mauricio, Condit, Jonathan, Constance, Christian, Constantin, Ciprian, Constantinescu, Silviana, Corbett, Clive, Cornett, George M, Correia, Marcelo, Cortinovis, Fiorenzo, Cosma, Dana, Creely, Steven, Cross, David, Curtis, Brian, Czochra, Wojciech, Daboul, Nizar Y, Dagdelen, Selcuk, 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Frittitta, Lucia, Froer, Michael, Fuckar, Krunoslav, Fujii, Kenshi, Fujita, Ryoko, Fukushima, Yasushi, Fulat, Mohamed, Fulwani, Mahesh, Gajos, Grzegorz, Galyavich, Albert, Gambill, Michael L, Gandotra, Dheeraj, Winston, Gandy, Garcia Hernandez, Pedro A, García Reza, Raymundo, Garg, Naveen, Garg, Sandeep, Garvey, William T, Garza, Juan C, Gatta-Cherifi, Blandine, Gelev, Valeri, Geller, Steven A, Geohas, Jeffrey G, Georgiev, Borislav, Ghazi, Adline, Gilbert, Matthew P, Gilinskaya, Olga, Gislason, Gunnar, Gogas Yavuz, Dilek, González Albarrán, Olga, Gordeev, Ivan G, Gorton, Sidney C, Goudev, Assen, Gretland Valderhaug, Tone, Groenemeijer, Bjorn, Gul, Ibrahim, Gullestad, Lars, Gurieva, Irina, Guseva, Galina N, Hagenow, Andreas, Haluzik, Martin, Halvorsen, Sigrun, Hammoudi, Naima, Hanaoka, Keiichi, Hancu, Nicolae, Hanusch, Ursula, Harris, Kathleen, Harris, Barry, Hartleib, Michael, Hartman, Aaron N, Hata, Yoshiki, Heimer, Brian, Herman, Lee, Herzog, William, Hewitt, Eric, Heymer, Peter, Hiremath, Shirish, Hjelmesaeth, Joeran, Høgalmen, Rasmus Geir, Høivik, Hans Olav, Holmer, Helene, Horoshko, Olha, Houser, Patricia M, Hove, Jens D, Hsieh, I-Chang, Hulot, Jean-Sébastien, Hussein, Zanariah, Ilashchuk, Tetiana, Ilveskoski, Erkki, Ipatko, Irina, Iranmanesh, Ali, Isawa, Tsuyoshi, Issa, Moises, Iteld, Bruce, Iwasawa, Takamasa, Jabbar, Danish, Jackson, Richard A, Jackson-Voyzey, Ewart, Jacob, Stephan, Jaffrani, Naseem A, Jardula, Michael F, Jastreboff, Ania, Jensen, Svend E, Jerkins, Terri, Jimenez-Ramos, Silvia A, Jitendra Pal Singh, Sawhney, Johnson, Wallace, Joyce, John M, Jozefowska, Malgorzata, Jugnundan, Prakash, Jungmair, Wolfgang, Jurowiecki, Jaroslaw, Kadokami, Toshiaki, Kahali, Dhiman, Kahrmann, Gerd, Kaiser, Sergio E, Kalmucki, Piotr, Kanadasi, Mehmet, Kandath, David, Kania, Grzegorz, Kannan, J, Kapp, Cornelia, Karczmarczyk, Agnieszka, Kartalis, Athanasios, Kaser, Susanne, Kasim, Sazzli Shahlan, Kastelic, Richard, Kato, Toshiaki, Katova, Tzvetana, Kaul, Upendra, Kautzky-Willer, Alexandra, Kawanishi, Masahiro, Kayikcioglu, Meral, Kazakova, Elena E, Keeling, Philip, Kempe, Hans-Peter, Kereiakes, Dean J, Kerneis, Mathieu, Keski-Opas, Tiina, Khadra, Suhail, Khaisheva, Larisa, Kharakhulakh, Marina, Khlevchuk, Tatiana, Khoo, Jeffrey, Kiatchoosakun, Songsak, Kinoshita, Noriyuki, Kinoshita, Masaharu, Kitamura, Ryoji, Kiyosue, Arihiro, Klavina, Irina, Klein, Eric J, Klimsa, Zdenek, Klonoff, David, Klug, Eric, Kobalava, Zhanna, Kodera, Satoshi, Koga, Tokushi, Kokkinos, Alexander, Koleckar, Pavel, Könyves, László, Koren, Michael J, Kormann, Adrian P, Kostner, Karam, Kreutzmann, Kristin, Krishinan, Saravanan, Krishnasamy, Sathya S, Krivosheeva, Inga, Kruljac, Ivan, Kubicki, Ted, Kuchar, Ladislav, Kujawiak, Monika, Kunishige, Hideyuki, Kurtinecz, Melinda, Kurtz Lisboa, Hugo R, Kushnir, Mykola, Kyyak, Yulian, Lace, Arija, Lakka, Timo, Lalic, Nebojsa, Lalic, Katarina, Lambadiari, Vaia, Lanaras, Leonidas, Lang, Chim, Langlois, Marie-France, Lash, Joseph, Latkovskis, Gustavs, Lau, David, Lazcano Soto, José Roberto, Le Roux, Carel, Ledesma, Gilbert N, Lee, Li Yuan, Lee, Thung-Lip, Lee, Kelvin, Lehrke, Michael, Leite, Silmara O, Leksycka, Agata, Lenzmeier, Thomas, Leonetti, Frida, Leonidova, Viktoriia, Lepor, Norman, Leung, Melissa, Levchenko, Olena, Levins, Peter, Levy, Louis J, Lewis, Matthew, Liberopoulos, Evangelos, Liberty, Idit, Lindholm, Carl-Johan, Lingvay, Ildiko, Linhart, Ales, Liu, Ming-En, Liu, Jenny, Lofton, Holly, Logemann, Timothy, Lombaard, Johannes J, Lombard, Landman, Lorraine, Richard, Lovell, Charles F, Ludvik, Bernhard, Lukaszewicz, Monika, Lupkovics, Géza, Lupovitch, Steven, Lupu, Sirona, Lynch, Mary, Lysak, Zoreslava, Lysenko, Tatyana A, Maeda, Hajime, Maeda, Itaru, Mæng, Michael, Mahajan, Ajay U, Maher, Vincent, Maia, Lilia N, Makotoko, Ellen M, Malavazos, Alexis, Malecha, Jan, Malicherova, Emilia, Manita, Mamoru, Mannucci, Edoardo, Mareev, Viacheslav, Marin, Liliana, Markova, Tatiana, Marso, Steven P, Martens, F.M.A.C., Martinez, Cuper, Martinez Cano, Carlos A, Martins, Cristina, Masmiquel Comas, Luis, Matsumoto, Takashi, Mcdonald, Kenneth, Mcgowan, Barbara, Mcgrew, Frank, Mclean, Barry K, Mcpherson, David D, Merino Torres, Juan Francisco, Meyers, Peter, Meyhöfer, Sebastian, Mezquita Raya, Pedro, Milanova, Maria, Milicic, Davor, Miller, Gary, Mills, Richard E, Mîndrescu, Nicoleta M, Mingrone, Geltrude, Minkova, Dotska A, Mirani, Marco, Miras, Alexander, Mistodie, Cristina V, Mitomo, Satoru, Mittal, Sanjay, Miyake, Taiji, Miyamoto, Naomasa, Molony, David, Monteiro, Pedro, Mooe, Thomas, Moosa, Naeem, Morales Portillo, Cristobal, Morales Villegas, Enrique C, Morawski, Emily J, Morbey, Claire, Morin, Robert P, Morisaki, Kuniaki, Morosanu, Magdalena, Mosenzon, Ofri, Mostovoy, Yuriy, Munir, Iqbal, Muratori, Fabrizio, Murray, Ryan, Murthy, Avinash, Myint, Min, Myshanych, Galyna, Nafornita, Valerica, Nagano, Takuya, Nair, Sunil, Nakhle, Samer N, Natsuaki, Masahiro, Nayak, Bindu M, Nibouche, Djamel Eddine, Nicholls, Stephen, Nicolau, José C, Nicolescu, Georgiana, Nierop, Peter, Niskanen, Leo, Ntaios, George, Nygård, Ottar Kjell, Oaks, Joshua B, Obrezan, Andrey, O'donnell, Philip, Oguri, Mitsutoshi, Oguzhan, Abdurrahman, Oh, Fumiki, Ohsugi, Mitsuru, Okada, Yoshio, Okayama, Hideki, Onaca, Adriana, Onaka, Haruhiko, Oneil, Patrick, Ong, Tiong Kiam, Ong, Stephen, Ono, Yasuhiro, Opsahl, Paul J, Ostrowska, Lucyna, Oviedo, Alejandra, Ozdogan, Oner, Ozpelit, Ebru, Pagkalos, Emmanouil, Pagotto, Uberto, Páll, Dénes, Pandey, Amritanshu- Shekhar, Parkhomenko, Oleksandr, Parvathareddy, Krishna Malakondareddy, Patel, Minesh B, Patsilinakos, Sotirios, Paul, Neil, Pedersen, Sue, Pereira, Isabel, Pereira, Edward Scott, Perez Terns, Paula, Perez-Vargas, Elba A, Pergaeva, Yulia, Perkelvald, Alexander, Peskov, Andrey B, Peter, Jonathan, Peters, Karina, Petit, Catherine, Petrov, Ivo, Philis-Tsimikas, Athena, Pietilä, Mikko, Pinto, Fausto, Piros, Annamária, Piyayotai, Dilok, Platonov, Dmitriy, Poirier, Paul, Pop, Lavinia, Popa, Bogdan, Pop-Busui, Rodica, Poremba, John, Porto, Alejandro, Postadzhiyan, Arman, Pothineni, Ramesh B, Potu, Ranganatha P, Powell, Talessa, Prafulla, Kerkar G, Prager, Rudolf, Prakova-Teneva, Zhulieta R, Pratley, Richard E, Price, Hermione, Pulka, Grazyna, Pullman, John, Punt, Zelda E, Purighalla, Raman S, Purnell, Peter, Qureshi, Mansoor, Rabasa-Lhoret, Remi, Raikhel, Marina A, Rancane, Gita, Randeva, Harpal, Rasouli, Neda, Reurean Pintilei, Delia V, Reyes, Ciro R, Rezgale, Inga, Rice, Eva, Riley, Thaddeus H, Risser, Joseph A, Ristic, Arsen, Rivas Fernández, Margarita, Robbins, David, Robitaille, Yves, Rodbard, Helena W, Rodriguez Plazas, Jaime A, Römer, T.J., Rosen, Glenn, Rosman, Dr Azhari, Rossi, Paulo, Rudenko, Leonid, Ruffin, Omari, Ruhani, Anwar Irawan, Runev, Nikolay, Ruyatkin, Dmitriy, Ruzic, Alen, Ryabov, Vyacheslav V, Rydén, Lars, Saggar, Suraj, Sakamoto, Tomohiro, Salter, Tim, Samal, Aditya K, Samoilova, Yulia, Sanabria, Hugo D, Sancak, Seda, 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Selcukbiricik, Ozlem, Spaic, Tamara, Spriggs, Douglas, Sreenan, Seamus, Stahl, Hans-Detlev, Stamatelopoulos, Kimon, Stanislavchuk, Mykola, Stankovic, Goran, Stasek, Josef, Steg, Gabriel, Steindorf, Joerg, Stephan, Dominique, Stewart, John, Still, Christopher, St-Maurice, Francois, Stogowska-Nikiciuk, Barbara, Stoker, Jeff, Stokic, Edita, Strzelecka, Anna, Sturm, Kerstin, Sueyoshi, Atsushi, Sugiura, Toshiyuki, Sultan, Senan, Suplotova, Lyudmila A, Suwanagool, Arisara, Suwanwalaikorn, Sompongse, Sveklina, Tatiana, Swanson, Neil, Swart, Henk, Swenson, Bradley P, Szyprowska, Ewa, Tait, Graeme, Takács, Róbert, Takeuchi, Yuzo, Tamirisa, Aparna, Tanaka, Hideki, Tatovic, Danijela, Tellier, Guy, Teragawa, Hiroki, Teterovska, Dace, Thomas, Nihal, Thuan, Jean-Francois, Tinahones, Francisco, Tisheva-Gospodinova, Snezhanka, Toarba, Cristina, Todoriuk, Liudmyla, Tokmakova, Mariya, Tonstad, Serena, Toplak, Hermann, Tran, Henry, Tripathy, Devjit, Trusau, Aliaksandr, Tsabedze, Nqoba, Tsougos, Elias, 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Wallace, James, Wan Mohamed, Wan Mohd Izani, Wander, Gurpreet S, Ward, Kathleen, Warren, Mark L, Watanabe, Atsuyuki, Weber, Bruce, Weintraub, Howard, Weisnagel, John, Welker, James, Wendisch, Ulrich, Wenocur, Howard S, Wierum, Craig, Wilding, John, William, Maged, Wilson, Pete, Wilson, Jonathan P, Wong, Yuk-Ki, Wongcharoen, Wanwarang, Wozniak, Iwona, Wu, Chau-Chung, Wyatt, Nell, Wynne, Alan, Yamaguchi, Hiroshi, Yamasaki, Masahiro, Yazici, Dilek, Yeh, Hung-I, Yotov, Yoto, Yuan, Qingyang, Zacher, Jeffrey, Zagrebelnaya, Olga, Zaidman, Cesar J, Zalevskaya, Alsu, Zarich, Stuart, Zatelli, Maria Chiara, Zeller, Helga, Zhdanova, Elena A, Zornitzki, Taiba, Zrazhevskiy, Konstantin, Zykov, Mikhail, Lincoff, A Michael, Ryan, Donna H, Colhoun, Helen M, Deanfield, John E, Emerson, Scott S, Kahn, Steven E, Kushner, Robert F, Plutzky, Jorge, Brown-Frandsen, Kirstine, Hovingh, G Kees, Hardt-Lindberg, Soren, and Tornøe, Christoffer W

Abstract

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure.

Published
2024
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34. Mechanical and optical properties of multilayer yttria-stabilized zirconia for dental prostheses

Author

de Lima Gomes, Patrick, dos Santos, Claudinei, Fernandes, Ana Melissa, Vasconcelos Amarante, José Eduardo, dos Santos, Heraldo Elias Salomão, and Elias, Carlos Nelson

Abstract

Dental multilayer zirconia ceramics are attractive materials for restorative dentistry because they offer significant esthetic advantages over monolithic, white, or monocolored zirconia. They enable anatomical adjustments in dental prostheses, making them more similar to natural teeth. New categories of dental ceramics have been developed using varying translucency and color within the same piece to meet esthetic requirements. This technique employs zirconia with different yttria (Y2O3) contents to achieve varying levels of translucency. This study investigated two types of dental ceramics based on multilayer zirconia, correlating their mechanical properties, translucency, and color variations concerning their application in dental prostheses. Two types of multilayer zirconia pre-sintered blocks with different Y2O3content were examined: 1) blocks with a Y2O3gradient chemical composition between 3 mol.% and 4 mol.%, named M3-4YSZ; 2) blocks with a Y2O3gradient chemical composition between 4 mol.% and 5 mol.%, named as M4-5YSZ. Samples were cut in cross-section to separate the layers based on Y2O3content and color and were then sintered at 1530 °C for 2 h. The sintered samples were characterized by relative density, crystalline phases, microstructure, Vickers hardness, fracture toughness (KIC), and optical properties (color and contrast ratio). Fully dense ceramics were obtained after sintering. Layers containing a greater amount of Y2O3in the zirconia matrix have a higher content of the ZrO2cubic phase, while layers with a lower content of Y2O3in the matrix are predominantly tetragonal ZrO2. No statistical variation in hardness was observed depending on the layers of the material. However, fracture toughness values showed significant statistical variations, with an increase in the tetragonal phase content responsible for the increase in fracture toughness. KICin M3-4YSZ samples varied between 3.63 and 7.73 MPa.m1/2, while M4-5YSZ samples ranged from 2.70 to 5.65 MPa.m1/2. The smooth and gradual variations in color and translucency observed between the layers of the two groups of dental ceramics studied indicate stability and homogeneity between the layers, contributing significantly to esthetic effects in dental applications.

Published
2024
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35. Comparative analysis of production performance, carcase traits, and meat quality in yearling beef of Limousine, Sardo-Bruna, and their crosses

Author

Lunesu, Mondina Francesca, Mellino, Maria Rita, Carta, Silvia, Battacone, Gianni, Zgheib, Elias, Pulina, Giuseppe, and Nudda, Anna

Abstract

AbstractThe aim of this study was to compare animal performance and meat quality of a local cattle breed of Sardinia Island with specialised meat purebred or obtained by crossbreeding. For this purpose, 10 Sardo-Bruna (SB; 5 males, 5 females), 10 Limousine (L; 5 males, 5 females) and 10 Limousine × Sardo-Bruna crossbreed (L × SB; 5 males, 5 females) were compared simultaneously from 12 to 20 ± 1 (mean ± SEM) months old. During the trial, body weight (BW) was recorded once a month for estimating the average daily gain (ADG). At slaughter, carcase measurements, pH and colour traits were recorded from the left side of the carcase. Proximate composition, fatty acid (FA) profile, cooking and drip losses were evaluated using the Longissimus thoracis et lumborummuscle. The SB group showed a lower cold carcase yield compared to L and L × SB genetic types. Males had a higher ADG, slaughter weight, hot and cold carcase weights, hot and cold carcase yields, and cooking losses than females. Females group showed a higher intramuscular fat content and rib fat thickness compared to males. No relevant differences among genetic types and between sexes were observed for meat and fat colours and pH. Concerning the FA profile, SB genetic type evidenced a higher oleic acid content and a better nutritional index than other genetic types while males had a higher PUFA content than females. In conclusion, the results of this study showed that the Limousine breed can be effectively used to enhance carcase yield of local breed without effects on meat quality.

Published
2024
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36. Asymmetric Migratory Tsuji–Wacker Oxidation Enables the Enantioselective Synthesis of Hetero- and Isosteric Diarylmethanes

Author

Frank, Eduard, Park, Sooyoung, Harrer, Elias, Flügel, Jana L., Fischer, Marcel, Nuernberger, Patrick, Rehbein, Julia, and Breder, Alexander

Abstract

Diarylmethanes play, in part, a pivotal role in the design of highly potent, chiral, nonracemic drugs whose bioactivity is typically affected by the substitution pattern of their arene units. In this context, certain arenes such as para-substituted benzenes or unsubstituted heteroarenes cause particular synthetic challenges, since such isosteric residues at the central methane carbon atom are typically indistinguishable for a chiral catalyst. Hence, the stereoselective incorporation of isosteric (hetero)arenes into chiral methane scaffolds requires the use of stoichiometrically differentiated building blocks, which is typically realized through preceding redox-modifying operations such as metalation or halogenation and thus associated with disadvantageous step- and redox-economic traits. As a counter-design, we report herein a generalized enantioselective synthesis of chiral diarylmethanes by means of an asymmetric migratory Tsuji–Wacker oxidation of simple stilbenes. The title protocol relies on the well-adjusted interplay of aerobic photoredox and selenium-π-acid catalysis to allow for the installation of a broad variety of arenes, including isosteric ones, into the methane core. Facial differentiation and regioselectivity are solely controlled by the selenium catalyst, which (a) renders the E/Z-configuration of the stilbene substrates inconsequential and (b) permits the stereodivergent synthesis of both product enantiomers from a single catalyst enantiomer, simply by employing constitutionally isomeric starting materials. Altogether, this multicatalytic platform offers the target structures with high levels of enantioselectivity in up to 97% ee, which has also been successfully exploited in expedited syntheses of antihistaminic (R)- and (S)-neobenodine.

Published
2024
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37. Considerations for prioritising clinical research using bacteriophage

Author

Edwards, Sarah J.L., Tao, Yiran, Elias, Rodas, and Schooley, Robert

Abstract

Antimicrobial resistance (AMR) poses a significant global health threat, as it contributes to prolonged illness, higher mortality rates and increased healthcare costs. As traditional antibiotics become less effective, treatments such as bacteriophage therapy offer potential solutions. The question remains, however, on how to set research priorities in the face of a growing number of antibiotic-resistant pathogens, some common and/or dangerous. One standard way of making decisions about which research to prioritise is by using the disability-adjusted life year metric to estimate the current global impact of a disease or condition, combined with considerations of social justice although decisions made at a national level by governments, especially in low income countries with forecasting potential over future needs may look very different. Another approach is based on the needs of researchers and regulators given what we know about the technology itself. The biological characteristics of bacteriophage therapies set challenges to a universal and standardised prioritisation method. A proof of principle is still arguably needed. With a preliminary discussion of the scope and complexity of AMR and AMR therapeutics, we propose some implications of regulatory frameworks aiming to integrate bacteriophage therapy into mainstream medical practice while gathering scientific data on safety and efficacy, enhancing the collective action needed to combat AMR.

Published
2024
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38. Oxygen Adsorption at the Electrochemical Metal/Water Interface: Au(111) vs Pt(111)

Author

Dudzinski, Alexandra M., Diesen, Elias, Reuter, Karsten, and Bukas, Vanessa J.

Abstract

Reaction mechanisms in heterogeneous electrocatalysis have been known to change through the local field that arises at the electrified metal/liquid interface. First-principles simulations specifically predict that such a field can significantly modify the surface binding of dipolar or polarizable intermediates along a catalytic reaction path. This dependence can then lead to a corresponding dependence upon applied potential even for so-called “chemical” reaction steps that do not involve an explicit proton-coupled electron transfer such as, e.g., O2adsorption during the oxygen reduction reaction (ORR). And yet, such effects are only now starting to be systematically explored at the atomic level. In this study, we directly compare the potential dependence of O2adsorption as the first ORR step on Au(111) vs Pt(111). Using ab initio molecular dynamics and free energy sampling, we find that the strong dependence previously predicted at Au(111) is specifically lost at Pt(111). By decoupling the O2potential response into contributions of different physical origin, we explain this contrast through the inherently different reactivity of the two metals. We finally discuss an indirect effect of potential through the surface coverage that can promote a dissociative-type mechanism at Pt(111) by breaking the O–O bond already during the first step of the ORR mechanism. Our results thus overall suggest a more complex mechanistic picture than hitherto anticipated; one where the local field may manifest in different, yet potentially equally important, ways over different systems.

Published
2024
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39. Gliocidin is a nicotinamide-mimetic prodrug that targets glioblastoma

Author

Chen, Yu-Jung, Iyer, Swathi V., Hsieh, David Chun-Cheng, Li, Buren, Elias, Harold K., Wang, Tao, Li, Jing, Ganbold, Mungunsarnai, Lien, Michelle C., Peng, Yu-Chun, Xie, Xuanhua P., Jayewickreme, Chenura D., van den Brink, Marcel R. M., Brady, Sean F., Lim, S. Kyun, and Parada, Luis F.

Abstract

Glioblastoma is incurable and in urgent need of improved therapeutics1. Here we identify a small compound, gliocidin, that kills glioblastoma cells while sparing non-tumour replicative cells. Gliocidin activity targets a de novo purine synthesis vulnerability in glioblastoma through indirect inhibition of inosine monophosphate dehydrogenase 2 (IMPDH2). IMPDH2 blockade reduces intracellular guanine nucleotide levels, causing nucleotide imbalance, replication stress and tumour cell death2. Gliocidin is a prodrug that is anabolized into its tumoricidal metabolite, gliocidin–adenine dinucleotide (GAD), by the enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) of the NAD+salvage pathway. The cryo-electron microscopy structure of GAD together with IMPDH2 demonstrates its entry, deformation and blockade of the NAD+pocket3. In vivo, gliocidin penetrates the blood–brain barrier and extends the survival of mice with orthotopic glioblastoma. The DNA alkylating agent temozolomide induces Nmnat1expression, causing synergistic tumour cell killing and additional survival benefit in orthotopic patient-derived xenograft models. This study brings gliocidin to light as a prodrug with the potential to improve the survival of patients with glioblastoma.

Published
2024
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41. Outcomes of Patients With Newly Diagnosed AML and Hyperleukocytosis

Author

Haddad, Fadi G., Sasaki, Koji, Senapati, Jayastu, Xiao, Lianchun, Park, Grace, Abuasab, Tareq, Venugopal, Sangeetha, Rivera, Daniel, Bazinet, Alexandre, Babakhanlou, Rodrick, Kim, Kunhwa, Ong, Faustine, Desikan, Sai, Pemmaraju, Naveen, Loghavi, Sanam, Borthakur, Gautam, DiNardo, Courtney, Abbas, Hussein A., Short, Nicholas J., Daver, Naval, Jabbour, Elias, Garcia-Manero, Guillermo, Ravandi, Farhad, Kantarjian, Hagop, and Kadia, Tapan

Published
2024
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42. PhenoBench: A Large Dataset and Benchmarks for Semantic Image Interpretation in the Agricultural Domain

Author

Weyler, Jan, Magistri, Federico, Marks, Elias, Chong, Yue Linn, Sodano, Matteo, Roggiolani, Gianmarco, Chebrolu, Nived, Stachniss, Cyrill, and Behley, Jens

Abstract

The production of food, feed, fiber, and fuel is a key task of agriculture, which has to cope with many challenges in the upcoming decades, e.g., a higher demand, climate change, lack of workers, and the availability of arable land. Vision systems can support making better and more sustainable field management decisions, but also support the breeding of new crop varieties by allowing temporally dense and reproducible measurements. Recently, agricultural robotics got an increasing interest in the vision and robotics communities since it is a promising avenue for coping with the aforementioned lack of workers and enabling more sustainable production. While large datasets and benchmarks in other domains are readily available and enable significant progress, agricultural datasets and benchmarks are comparably rare. We present an annotated dataset and benchmarks for the semantic interpretation of real agricultural fields. Our dataset recorded with a UAV provides high-quality, pixel-wise annotations of crops and weeds, but also crop leaf instances at the same time. Furthermore, we provide benchmarks for various tasks on a hidden test set comprised of different fields: known fields covered by the training data and a completely unseen field.

Published
2024
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43. Datopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial

Author

Khoury, Katia, Meisel, Jane L., Yau, Christina, Rugo, Hope S., Nanda, Rita, Davidian, Marie, Tsiatis, Butch, Chien, A. Jo, Wallace, Anne M., Arora, Mili, Rozenblit, Mariya, Hershman, Dawn L., Zimmer, Alexandra, Clark, Amy S., Beckwith, Heather, Elias, Anthony D., Stringer-Reasor, Erica, Boughey, Judy C., Nangia, Chaitali, Vaklavas, Christos, Omene, Coral, Albain, Kathy S., Kalinsky, Kevin M., Isaacs, Claudine, Tseng, Jennifer, Roussos Torres, Evanthia T., Thomas, Brittani, Thomas, Alexandra, Sanford, Amy, Balassanian, Ronald, Ewing, Cheryl, Yeung, Kay, Sauder, Candice, Sanft, Tara, Pusztai, Lajos, Trivedi, Meghna S., Outhaythip, Ashton, Li, Wen, Onishi, Natsuko, Asare, Adam L., Beineke, Philip, Norwood, Peter, Brown-Swigart, Lamorna, Hirst, Gillian L., Matthews, Jeffrey B., Moore, Brian, Fraser Symmans, W., Price, Elissa, Beedle, Carolyn, Perlmutter, Jane, Pohlmann, Paula, Shatsky, Rebecca A., DeMichele, Angela, Yee, Douglas, van ‘t Veer, Laura J., Hylton, Nola M., and Esserman, Laura J.

Abstract

Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab–deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin–cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2−Immune−DNA repair deficiency−subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2−Immune−DNA repair deficiency−signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379.

Published
2024
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44. Datopotamab–deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial

Author

Shatsky, Rebecca A., Trivedi, Meghna S., Yau, Christina, Nanda, Rita, Rugo, Hope S., Davidian, Marie, Tsiatis, Butch, Wallace, Anne M., Chien, A. Jo, Stringer-Reasor, Erica, Boughey, Judy C., Omene, Coral, Rozenblit, Mariya, Kalinsky, Kevin, Elias, Anthony D., Vaklavas, Christos, Beckwith, Heather, Williams, Nicole, Arora, Mili, Nangia, Chaitali, Roussos Torres, Evanthia T., Thomas, Brittani, Albain, Kathy S., Clark, Amy S., Falkson, Carla, Hershman, Dawn L., Isaacs, Claudine, Thomas, Alexandra, Tseng, Jennifer, Sanford, Amy, Yeung, Kay, Boles, Sarah, Chen, Yunni Yi, Huppert, Laura, Jahan, Nusrat, Parker, Catherine, Giridhar, Karthik, Howard, Frederick M., Blackwood, M. Michele, Sanft, Tara, Li, Wen, Onishi, Natsuko, Asare, Adam L., Beineke, Philip, Norwood, Peter, Brown-Swigart, Lamorna, Hirst, Gillian L., Matthews, Jeffrey B., Moore, Brian, Symmans, W. Fraser, Price, Elissa, Heditsian, Diane, LeStage, Barbara, Perlmutter, Jane, Pohlmann, Paula, DeMichele, Angela, Yee, Douglas, van ’t Veer, Laura J., Hylton, Nola M., and Esserman, Laura J.

Abstract

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody–drug conjugate, datopotamab–deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin–cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin–cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.

Published
2024
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45. Community members as design partners: Codesign workshops of the families tackling tough times together program

Author

Rosenberger, Claire A., Elias, Cezanne, Ruiz, Yumary, Toombs, Austin, Lee, Sohee, Marceau, Kristine, MacDermid Wadsworth, Shelley, Kimiecik, Carly, Millspaugh, Lillian, Cloutier, Chloe, Rutherford, Lauren, Che, Liying, and McCormick, Carolyn E.B.

Abstract

This community‐engaged codesign project identified the changes needed to tailor a family resilience‐building program, the Families Tackling Tough Times Together (FT), into a community setting. There is a need for low‐burden resources to help families mitigate stressful times and build resilience. Guided by Walsh's family resilience framework, FT aims to improve families' ability to cope, recover, and build resilience. Due to the success of FT during the COVID‐19 pandemic, the program is now being modified to help families in the state of Indiana. Three codesign workshops were held with community service providers (CSP) and families. Participants engaged with the FT materials and discussions related to program usability and feasibility. Data were analyzed using a rapid analysis approach. CSPs stated that FT program materials fit with their goals and workload. Families felt the FT program aligned with their personal needs and day‐to‐day lives. Challenges and concerns with the FT materials included activities that required additional resources or that may be intimidating for families to complete. Both CSPs and families provided helpful suggestions on how to modify the materials. The FT program was well received by participants and was viewed as a valuable addition to the services CSPs offer. Modifications will be made to the FT materials based on knowledge gained from the workshops. This work highlights the collaborative nature of the codesign process as well as the insights gained from participants regarding the use of the FT materials by CSPs as part of their routine service delivery with families in the community.

Published
2024
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46. In VitroAssessment of Metarhizium AnisopliaePathogenicity Against Aedes AegyptiLife Stages

Author

Ribeiro, Matheus Lopes, Bitencourt, Ricardo de Oliveira Barbosa, Moreira, Haika Victória Sales, Golo, Patrícia Silva, Bittencourt, Vânia Rita Elias Pinheiro, and Angelo, Isabele da Costa

Abstract

Aedes aegyptitransmits the arboviruses that cause dengue, zika, and chikungunya. Entomopathogenic fungi are beneficial microorganisms that can be incorporated into current strategies against mosquitoes of public health concern. This study molecularly identified the Metarhizium anisopliaeCG 153 isolate and evaluated its virulence against larvae, pupae, and adults (both males and females) of Ae. aegypti. Different concentrations of conidia were used (1 × 104–8conidia mL−1). Larval and pupal survival was monitored daily for seven and three days, respectively, while adults were monitored for 15 days. The efficacy of M. anisopliaesensu stricto was concentration-dependent, with higher concentrations achieving better results, demonstrating greater virulence against larval and adult stages of Ae. aegypti. The fungus reduced the larval survival by 95,5% (1 × 108con.mL−1), 94,4% (1 × 107con.mL−1), 78,9% (1 × 106con.mL−1), 62,2% (1 × 105con.mL−1), and 41,1% (1 × 104con.mL−1) after seven days. Adults also showed susceptibility to the fungus, with no observed difference in susceptibility between males and females. Over 15 days of monitoring, adult survival rates ranged from approximately 6.7% to 72%. Pupae exhibited lower susceptibility to the fungus across different concentrations, with survival rates ranging from approximately 87.8% to 100%. This study highlights the high effectiveness of M. anisopliaeCG 153 against both Ae. aegyptilarvae and adults (male and female) under controlled conditions, suggesting its promising potential for further evaluation and application in field conditions.

Published
2024
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47. Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells

Author

Lanz, Michael C., Zhang, Shuyuan, Swaffer, Matthew P., Ziv, Inbal, Götz, Luisa Hernández, Kim, Jacob, McCarthy, Frank, Jarosz, Daniel F., Elias, Joshua E., and Skotheim, Jan M.

Abstract

Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how cell size influences physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be compositionally different. In the present study, we utilize the natural heterogeneity of hepatocyte ploidy and yeast genetics to establish that the ploidy-to-cell size ratio is a highly conserved determinant of proteome composition. In both mammalian and yeast cells, genome dilution by cell growth elicits a starvation-like phenotype, suggesting that growth in large cells is restricted by genome concentration in a manner that mimics a limiting nutrient. Moreover, genome dilution explains some proteomic changes ascribed to yeast aging. Overall, our data indicate that genome concentration drives changes in cell composition independently of external environmental cues.

Published
2024
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48. Surgical Management of Gestational Trophoblastic Neoplasia

Author

Elias, Kevin M., Berkowitz, Ross S., and Horowitz, Neil S.

Abstract

Gestational trophoblastic neoplasia (GTN) is primarily treated with chemotherapy, but surgery plays a key role at different steps in disease management, including initial diagnosis, primary therapy, and salvage options. Initial diagnosis is usually made by electric or manual vacuum aspiration for molar pregancy or uterine curettage for other forms of GTN. Excisional procedures of localized disease, whether second curettage or hysterectomy, can obviate chemotherapy, but patients still require monitoring for relapse. Resection remains a useful adjunct for either the management of isolated foci of chemoresistant disease or the management of bleeding complications.

Published
2024
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49. Ultra High-risk Gestational Trophoblastic Neoplasia

Author

Elias, Kevin M., Berkowitz, Ross S., and Horowitz, Neil S.

Abstract

Ultra high-risk gestational trophoblastic neoplasia (GTN) refers to patients with World Health Organization prognostic risk scores of at least 13. The mortality risk for these patients averages 30%. Ultra high-risk GTN more frequently presents with higher tumor volume, liver and/or brain metastases, and very high human chorionic gonadotropin levels. The diagnostic evaluation must include a thorough evaluation for central nervous system disease. Prompt initiation of cisplatin – etoposide induction chemotherapy reduces the risks of early death. Collaborative services such as neurosurgery, radiation oncology, and interventional radiology may be required to manage hemorrhagic lesions.

Published
2024
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50. Live Biotherapeutic Products for the Prevention of Recurrent Clostridioides difficileInfection

Author

Pettit, Natasha N., Shaeer, Kristy M., and Chahine, Elias B.

Abstract

Objective: To review the efficacy, safety, and role of live biotherapeutic products (LBPs) in the prevention of recurrent Clostridioides difficileinfection (rCDI).Data Sources: A literature search was performed using PubMed and Google Scholar (through February 2024) with search terms RBX2660, SER-109, and fecal microbiota. Other resources included abstracts presented at recent conferences, national clinical practice guidelines, and manufacturers’ websites.Study Selection and Data Extraction: All relevant studies, trial updates, conference abstracts, and guidelines in the English language were included.Data Synthesis: Two LBPs were recently approved by the Food and Drug Administration for the prevention of recurrence in adults following antibiotic treatment for rCDI. Fecal microbiota, live-jslm is administered rectally as a retention enema, whereas fecal microbiota spores, live-brpk is given orally after bowel preparation. Several phase 2 and phase 3 clinical trials have established the safety and efficacy of these LBPs in reducing rates of rCDI compared with placebo. Patients with severe immunosuppression and those with inflammatory bowel disease were largely excluded from these trials.Relevance to Patient Care and Clinical Practice in Comparison with Existing Drugs: Live biotherapeutic products offer a similar mechanism to conventional fecal microbiota transplant (FMT) in preventing rCDI through microbiota restoration. The primary advantages of LBPs over FMT are their standardized composition and donor stool screening processes for transmissible pathogens. Bezlotoxumab is also available for the prevention of Clostridioides difficileinfection; however, there are no clinical data available to compare the efficacy of LBPs with bezlotoxumab, and the benefit of simultaneous use of these preventative therapies is unclear.Conclusions: Live biotherapeutic products provide a safe and effective option for the prevention of rCDI and represent an improvement over conventional FMT. Additional studies are needed to further determine their place in therapy relative to bezlotoxumab and in the setting of immunosuppression and inflammatory bowel disease.

Published
2024
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