Article
Medicine, Research & Experimental
Edward O'Neill, Michael Mosley, Bart Cornelissen
Summary: An effective absorbed dose response relationship has not yet been established for Lutetium-177 based radionuclide therapies. The inherent biological heterogeneity of neuroendocrine and prostate cancers may make it difficult to establish cohort-based dose-response relationships. Instead, an individual-based approach that monitors the dose-response within each tumor could provide a valuable metric for monitoring treatment efficacy.
Article
Geriatrics & Gerontology
Chiara Grasselli, Silvia Bombelli, Stefano Eriani, Giulia Domenici, Riccardo Galluccio, Chiara Tropeano, Sofia De Marco, Maddalena M. Bolognesi, Barbara Torsello, Cristina Bianchi, Laura Antolini, Fabio Rossi, Paolo Mazzola, Valerio Leoni, Giuseppe Bellelli, Roberto A. Perego
Summary: Frailty is an age-related syndrome that increases vulnerability and often leads to negative outcomes, including mortality. The mechanisms behind frailty are still unclear, but oxidative stress and DNA damage are believed to play a significant role. Early diagnosis and targeted treatments could potentially slow down the progression of frailty.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jelena Nesovic Ostojic, Maja Zivotic, Sanjin Kovacevic, Milan Ivanov, Predrag Brkic, Nevena Mihailovic-Stanojevic, Danijela Karanovic, Una Jovana Vajic, Zoran Miloradovic, Djurdjica Jovovic, Sanja Radojevic Skodric
Summary: The study evaluated the immunohistochemical pattern of histone H2A variants' expression in an experimental model of ischemia-reperfusion-induced acute kidney injury. The results showed an inverse ratio between two histone H2AX variants, with increasing extent of H2AXY142ph and decreasing expression of ?H2AX. Different structures dominated in the expression of these variants. Moderate sporadic nuclear H2AZ expression was observed in distal tubules and collecting ducts, surrounded by dilated tubules with positive casts. These findings have potential clinical and prognostic implications regarding postischemic AKI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Laura Gennaccaro, Claudia Fuchs, Manuela Loi, Riccardo Pizzo, Sara Alvente, Chiara Berteotti, Leonardo Lupori, Giulia Sagona, Giuseppe Galvani, Antonia Gurgone, Alessandra Raspanti, Giorgio Medici, Marianna Tassinari, Stefania Trazzi, Elisa Ren, Roberto Rimondini, Tommaso Pizzorusso, Giovanna Zoccoli, Maurizio Giustetto, Elisabetta Ciani
Summary: CDD is a severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene, characterized by early-onset epilepsy, intellectual disability, motor impairment, and autistic-like features. The decline in behaviors in older Cdk15 KO mice was associated with decreased neuronal survival, but not worsened neuroanatomical alterations. Evidence was found that CDKL5 may play a fundamental role in neuronal survival during brain aging, suggesting a possible worsening with age of the clinical picture in CDD patients.
Review
Biochemistry & Molecular Biology
Magdalena Adamczyk, Ewa Wender-Ozegowska, Malgorzata Kedzia
Summary: This paper summarizes the knowledge on epigenetic mechanisms in eutopic endometrium in patients with both endometriosis and infertility. The study found impaired DNA methylation patterns and significant differences in histone acetylation and methylation in the endometrium of women with endometriosis. Aberrant expression of candidate genes may lead to immunological dysfunction, inflammatory reaction, and apoptotic response in the endometrium. The role of TET proteins in endometrial pathology is not fully understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jiangbin Wei, Qiwu Shi, Lidan Xiong, Guang Xin, Tao Yi, Yunqing Xiao, Wanxia Huang
Summary: The study investigated the biological effects of radiation from the SG-III prototype laser facility on HaCat cells and PC12 cells, finding that the damage to cells was dose-dependent and induced DNA damage and apoptotic necrosis. Transcriptome and protein analysis revealed pathways involving proliferation, transformation, necrosis, inflammation response, apoptosis, and DNA damage repair were activated, suggesting potential harm to biological safety.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Ezekiel Mecha, Roselydiah Makunja, Jane B. Maoga, Agnes N. Mwaura, Muhammad A. Riaz, Charles O. A. Omwandho, Ivo Meinhold-Heerlein, Lutz Konrad
Summary: Thoracic endometriosis (TE) is a rare form of endometriosis where endometrial tissue is found in or around the lungs, often presenting as catamenial pneumothorax (CP). Immunohistochemical evaluation is considered crucial for diagnosing and classifying the disease effectively.
Article
Oncology
Cholpon S. Djuzenova, Thomas Fischer, Astrid Katzer, Dmitri Sisario, Tessa Korsa, Gudrun Steussloff, Vladimir L. Sukhorukov, Michael Flentje
Summary: In this study, the triple-target inhibitor PI-103 sensitized MO59K cells to radiation, but unexpectedly caused radioresistance in the MO59J line. The difference is likely due to low expression of the DNA-PK substrate p53 in MO59J cells, which was further reduced by PI-103. This led to decreased apoptosis in comparison to drug-free MO59J cells and enhanced survival through partially abolished cell-cycle arrest. The findings suggest that the lack of DNA-PK-dependent NHEJ in MO59J line might be compensated by DNA-PK independent DSB repair via an unknown mechanism.
Article
Multidisciplinary Sciences
Zheng-Mei Xiong, Xiaojing Mao, Mason Trappio, Chanda Arya, Jasmin El Kordi, Kan Cao
Summary: Methylene blue, as a premier antioxidant, has shown potential as a sunscreen active ingredient for UV radiation protection. In comparison to oxybenzone, it exhibits better UVB absorption efficiency, prevents UVB-induced DNA damage, and does not harm coral reefs, suggesting its promise as a coral reef-friendly sunscreen active ingredient.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Xinyu Wang, Liwen Fan, Xuanzhong Wang, Tianfei Luo, Linlin Liu
Summary: This study reveals for the first time that shikonin induces glioma cell death through the activation of CypA and the subsequent nuclear translocation of AIF and formation of gamma-H2AX. CypA targeted mitochondria and triggered mitochondrial superoxide overproduction, promoting AIF translocation and intensifying gamma-H2AX formation. The CypA in the nucleus formed DNA degradation complexes with AIF and gamma-H2AX, promoting chromatinolysis.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Judith Reindl, P. Kundrat, S. Girst, M. Sammer, B. Schwarz, G. Dollinger
Summary: The human body is exposed to ionizing radiation of different qualities, and the exposure to high-LET particles increases due to new tumor therapy methods. The current method for measuring this exposure has limitations, and this study developed a new method to count DSB that are separated by a distance of 140 nm, allowing for proper dosimetry of high-LET or mixed particle radiation exposure.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Cell Biology
Jake Atkinson, Eva Bezak, Ivan Kempson
Summary: DNA double-strand breaks play a fundamental role in cell biology, but there is a lack of a reliable assay for quantitatively visualizing DSBs. Relying on proxy detection methods can lead to misinterpretation of conventional assays, highlighting the need for the development of more accurate DSB detection methods.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Article
Obstetrics & Gynecology
Kashmira Bane, Junita Desouza, Diksha Shetty, Prakash Choudhary, Shalaka Kadam, R. R. Katkam, Gwendolyn Fernandes, Raj Sawant, Uddhavraj Dudhedia, Neeta Warty, Anahita Chauhan, Uddhav Chaudhari, Rahul Gajbhiye, Geetanjali Sachdeva
Summary: The study indicates that the DNA damage response is dysregulated in the eutopic endometrium of women with endometriosis, with higher expression of DDR genes compared to those without the disease. Additionally, DNA repair genes are also up-regulated in the eutopic endometrium of women with endometriosis.
HUMAN REPRODUCTION
(2021)
Article
Medicine, General & Internal
Anna C. Loeffelmann, Alena Hoerscher, Muhammad A. Riaz, Felix Zeppernick, Ivo Meinhold-Heerlein, Lutz Konrad
Summary: In endometriosis, the localization of claudin-10 is impaired, but the epithelial phenotype remains preserved. Claudin-10 is highly expressed in endometriosis and adenomyosis, but there are differences in its localization between the two conditions.
Article
Biochemistry & Molecular Biology
Masae Ikura, Kanji Furuya, Tomonari Matsuda, Tsuyoshi Ikura
Summary: This study reveals the importance of de novo NAD(+) production in the cell nucleus for protection against cellular senescence and tumorigenesis. It also demonstrates that the enzymatic activity of NAD syn1 is crucial for the ADP ribosylation activity of PARP-1 and the dynamics of H2AX at DNA damage sites.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Review
Pediatrics
Rian Hayes, Jack Hartnett, Gergana Semova, Cian Murray, Katherine Murphy, Leah Carroll, Helena Plapp, Louise Hession, Jonathan O'Toole, Danielle McCollum, Edna Roche, Elinor Jenkins, David Mockler, Tim Hurley, Matthew McGovern, John Allen, Judith Meehan, Frans B. Plotz, Tobias Strunk, Willem P. de Boode, Richard Polin, James L. Wynn, Marina Degtyareva, Helmut Kuester, Jan Janota, Eric Giannoni, Luregn J. Schlapbach, Fleur M. Keij, Irwin K. M. Reiss, Joseph Bliss, Joyce M. Koenig, Mark A. Turner, Christopher Gale, Eleanor J. Molloy
Summary: Neonatal sepsis, a leading cause of infant mortality, has diverse definitions based on microbiological culture, laboratory tests, and clinical signs. An international consensus-based definition could improve research comparability and clinical outcomes.
PEDIATRIC RESEARCH
(2023)
Review
Pediatrics
Cian J. Henry, Gergana Semova, Ellen Barnes, Isabel Cotter, Tara Devers, Aisyah Rafaee, Andreea Slavescu, Niamh O. Cathain, Danielle McCollum, Edna Roche, David Mockler, John Allen, Judith Meehan, Claus Klingenberg, Jos M. Latour, Agnes van den Hoogen, Tobias Strunk, Eric Giannoni, Luregn J. Schlapbach, Marina Degtyareva, Frans B. Plotz, Willem P. de Boode, Lars Naver, James L. Wynn, Helmut Kuster, Jan Janota, Fleur M. Keij, Irwin K. M. Reiss, Joseph M. Bliss, Richard Polin, Joyce M. Koenig, Mark A. Turner, Christopher Gale, Eleanor J. Molloy
Summary: This article reports a wide variation in outcome reporting among RCTs on the management of neonatal sepsis. The lack of standardized outcome reporting hinders comparison and synthesis of data, making it unlikely for future meta-analyses to provide conclusive recommendations on the management of neonatal sepsis.
PEDIATRIC RESEARCH
(2022)
Review
Medical Informatics
J. Preston, B. Nafria, A. Ohmer, S. Gaillard, P. Dicks, L. West, M. A. Turner
Summary: This paper emphasizes the importance of involving children and families in the design and implementation of pediatric clinical research to improve pediatric healthcare, medicine development, and technological advances. It introduces the International Children's Advisory Network (iCAN) and European Young Person's Advisory Group Network (eYPAGnet) as examples of how children and families have been engaged in pediatric clinical research, providing practical solutions and lessons learned.
THERAPEUTIC INNOVATION & REGULATORY SCIENCE
(2022)
Article
Pediatrics
Louise F. Hill, Michelle N. Clements, Mark A. Turner, Daniele Dona, Irja Lutsar, Evelyne Jacqz-Aigrain, Paul T. Heath, Emmanuel Roilides, Louise Rawcliffe, Clara Alonso-Diaz, Eugenio Baraldi, Andrea Dotta, Mari-Liis Ilmoja, Ajit Mahaveer, Tuuli Metsvaht, George Mitsiakos, Vassiliki Papaevangelou, Kosmas Sarafidis, A. Sarah Walker, Michael Sharland
Summary: The study compared the efficacy of an optimized vancomycin regimen with a standard regimen in infants with late onset Gram-positive sepsis. The results showed that the optimized regimen did not demonstrate non-inferiority in terms of efficacy and a potential hearing safety signal was identified. Therefore, this study highlights the importance of robust clinical safety assessments of antibiotic dosing regimens in infants.
LANCET CHILD & ADOLESCENT HEALTH
(2022)
Letter
Obstetrics & Gynecology
Charlotte Leeson, Joshua Odendaal, Siobhan Quenby
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2023)
Review
Pharmacology & Pharmacy
Catherine Litalien, Sophie Berube, Catherine Tuleu, Andrea Gilpin, Emilie Kate Landry, Marie Valentin, Robert Strickley, Mark A. Turner
Summary: Developing suitable paediatric formulations and ensuring access to them are crucial for optimal pharmacotherapy for children. While progress has been made in the acceptability of solid oral dosage forms in children, further research is needed. Additionally, access to paediatric formulations is fragmented and unequal, requiring a more globalized registration approach.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Medical Informatics
Morenike Oluwatoyin Folayan, Magda Conway, Carolyn Russo, Nilza Diniz, Lungile P. Jafta, Nadia A. Sam-Agudu, Sarah Bernays, Victor M. Santana, Carla Epps, Mark A. Turner
Summary: The concept of health equity requires equitable access to healthcare, including pediatric drug development. However, many communities are under-represented in pediatric drug development programs. Community engagement and collaboration are recognized as crucial for building a more equitable healthcare system.
THERAPEUTIC INNOVATION & REGULATORY SCIENCE
(2022)
Article
Obstetrics & Gynecology
Ian Henderson, Lauren Lacey, Muhammad Ahsan Akhtar, Siobhan Quenby
Summary: This study aimed to understand the risk differences of different assisted reproductive technology (ART) failure types by ethnic group and explore the role of maternal age and suspected etiology as mediators. The study conducted an observational analysis of 48,750 women who underwent ART treatment in the United Kingdom. The results showed that black women had the highest risk of all failure types, while Asian women had an intermediate risk compared to white women. Some of the risks among black women may be mediated by maternal age.
FERTILITY AND STERILITY
(2023)
Article
Pediatrics
Karel Allegaert, Heidrun Hildebrand, Kanwaljit Singh, Mark A. A. Turner
Summary: The International Neonatal Consortium aims to define reference ranges for commonly used laboratory values in neonates, but there is a lack of standardized and complete published information on these values. This hinders treatment comparison, safety monitoring, and clinical management.
PEDIATRIC RESEARCH
(2023)
Article
Obstetrics & Gynecology
R. K. Dhillon-Smith, P. Melo, A. J. Devall, P. P. Smith, M. Al-Memar, K. Barnhart, G. Condous, O. B. Christiansen, M. Goddijn, D. Jurkovic, D. Lissauer, A. Maheshwari, O. T. Oladapo, J. Preisler, L. Regan, R. Small, M. Stephenson, C. Wijeyaratne, S. Quenby, T. Bourne, A. Coomarasamy
Summary: The objective of this study was to develop core outcome sets (COS) for miscarriage management and prevention. Through a modified Delphi survey and consensus development meeting, stakeholders from 15 countries were included. The final COS for miscarriage management and prevention were established, providing important guidance for future randomized trials and systematic reviews.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2023)
Article
Medicine, General & Internal
Peter W. Horby, Jonathan R. Emberson, Buddha Basnyat, Mark Campbell, Leon Peto, Guilherme Pessoa-Amorim, Natalie Staplin, Raph L. Hamers, John Amuasi, Jeremy Nel, Evelyne Kestelyn, Manisha Rawal, Roshan Kumar Jha, Nguyen Thanh Phong, Uun Sumardi, Damodar Paudel, Pham Ngoc Thach, Nasronudin Nasronudin, Emma Stratton, Louise Mew, Rahuldeb Sarkar, J. Kenneth Baillie, Maya H. Buch, Jeremy Day, Saul N. Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Marian Knight, Wei Shen Lim, Marion Mafham, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Richard Haynes, Martin J. Landray
Summary: This study evaluated the use of high-dose corticosteroids in COVID-19 patients. The results showed that in hospitalized patients with COVID-19, high-dose corticosteroids increased the risk of death compared to low-dose corticosteroids.
Article
Medicine, General & Internal
Siobhan Quenby, Katie Booth, Louise Hiller, Arri Coomarasamy, Paulien G. de Jong, Eva N. Hamulyak, Luuk J. Scheres, Thijs F. van Haaps, Lauren Ewington, Mariette Gojjin, Shreeya Tewary, Saskia Middeldorp
Summary: The use of low-molecular-weight heparin (LMWH) did not increase livebirth rates in women with recurrent pregnancy loss and inherited thrombophilia. Therefore, the use of LMWH is not recommended in these women.
Article
Physiology
Ronan Muir, Raheela Khan, Anatoly Shmygol, Siobhan Quenby, Matthew Elmes
Summary: Maternal obesity is associated with prolonged and dysfunctional labor and emergency caesarean section. A translational rat model has been established to investigate the mechanisms behind uterine dystocia associated with maternal obesity.
PHYSIOLOGICAL REPORTS
(2023)
Review
Obstetrics & Gynecology
Rhiannon White, Anna Wilson, Natasha Bechman, Stephen D. Keay, Lucy McAvan, Siobhan Quenby, Joshua Odendaal
Summary: This systematic review aimed to investigate the effectiveness and safety of fertility preservation strategies in pre-menopausal women with breast cancer. The results showed that fertility preservation interventions were associated with higher fertility outcomes and a reduced rate of disease recurrence. This suggests that fertility preservation is effective in preserving reproductive function and safe with regard to disease recurrence, disease free survival, and overall survival in premenopausal women with breast cancer.
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
(2023)
Article
Medicine, General & Internal
Peter W. Horby, Jonathan R. Emberson, Marion Mafham, Mark Campbell, Leon Peto, Guilhenne Pessoa-Amorim, Enti Spata, Natalie Staplin, Catherine Lowe, David R. Chadwick, Christopher Brightling, Richard Stewart, Paul Collini, Abdul Ashish, Christopher A. Green, Ben Prudon, Timothy Felton, Anthony Kerry, J. Kenneth Baillie, Maya H. Such, Jeremy Day, Saul N. Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Marian Knight, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Richard Haynes, Martin J. Landray
Summary: This study evaluated the use of baricitinib in the treatment of patients hospitalized with COVID-19. The results showed that baricitinib significantly reduced the risk of death, although the effect size was slightly smaller than previous trials. Overall evidence suggests that JAK inhibitors can reduce mortality in hospitalized COVID-19 patients by about 20%.