Article
Biochemistry & Molecular Biology
Emmi Rotgers, Barbara Nicol, Karina Rodriguez, Saniya Rattan, Jodi A. Flaws, Humphrey Hung-Chang Yao
Summary: The study found that overexpression of NR5A1 in female mice leads to reproductive dysfunction and metabolic imbalance, resulting in premature infertility. These results provide a new model for studying not only the molecular actions of NR5A1, but also the crosstalk between endocrine, reproductive, and metabolic systems.
Article
Multidisciplinary Sciences
Camilla H. K. Hughes, Olivia E. Smith, Marie-Charlotte Meinsohn, Mylene Brunelle, Nicolas Gevry, Bruce D. Murphy
Summary: This study identifies SF-1 as a key regulator of the formation of the ovarian reserve, with its depletion leading to smaller ovaries and reduced primordial follicles. The study also identifies the dysregulated pathways and genes involved in follicle formation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Yayoi Ikeda, Ayako Tagami, Mamiko Maekawa, Akiko Nagai
Summary: The study demonstrates the essential role of NR5A1 in gonadal development, as loss of NR5A1 affects steroidogenic and germ cell differentiation, potentially leading to gonadal sex reversal.
SCIENTIFIC REPORTS
(2021)
Article
Dermatology
Isabelle Sahut-Barnola, Anne-Marie Lefrancois-Martinez, Damien Dufour, Jean-Marie Botto, Crystal Kamilaris, Fabio R. Faucz, Constantine A. Stratakis, Pierre Val, Antoine Martinez
Summary: Carney complex is a rare familial multineoplastic syndrome characterized by skin lesions. This study demonstrates that inactivation of the Prkar1a gene leads to familial skin pigmentation alterations, revealing the pathogenesis of cutaneous manifestations in Carney complex.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Arnaud Zuber, Adriana Peric, Nicola Pluchino, David Baud, Milos Stojanov
Summary: The human body is colonised by microorganisms, including the genital tract which has been linked to male infertility and pathological conditions like prostate cancer. However, research on the microbiota of the male genital tract remains lacking due to difficulties in sampling and low abundance of microbiota. This narrative review aims to present the results of studies using next-generation sequencing to examine bacterial colonisation patterns in different anatomical compartments of the male genital tract and highlight their findings and limitations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Obstetrics & Gynecology
Nicole Banks, Fangbai Sun, Stephen A. Krawetz, R. Matthew Coward, Puneet Masson, James F. Smith, J. C. Trussell, Nanette Santoro, Heping Zhang, Anne Z. Steiner
Summary: This study found no significant association between vitamin D levels in the male partner and treatment outcomes, but a lower 25(OH)D level (<20 ng/mL) was associated with a higher rate of pregnancy loss. Further research is needed to better understand the impact of male vitamin D deficiency on miscarriage rates in couples.
FERTILITY AND STERILITY
(2021)
Review
Immunology
Jin Chen, Jinyu Chen, Yiwei Fang, Qiuzi Shen, Kai Zhao, Chunyan Liu, Huiping Zhang
Summary: Up to 50% of male infertility is caused by various factors such as varicocele, orchitis, prostatitis, oligospermia, asthenospermia, and azoospermia. Recent studies have highlighted the increasing role of microorganisms in the development of these diseases. This review discusses the microbiological changes associated with male infertility in terms of etiology and explores how microorganisms affect the normal function of the male reproductive system through immune mechanisms. Linking male infertility with the microbiome and immunomics can provide insights into the immune response in different disease states, leading to targeted immune therapies for these conditions and even the possibility of combined immunotherapy and microbial therapy for male infertility.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Obstetrics & Gynecology
Kim Joana Westerich, Solveig Reinecke, Jana Emich, Margot Julia Wyrwoll, Birgit Stallmeyer, Matthias Meyer, Manon S. Oud, Daniela Fietz, Adrian Pilatz, Sabine Kliesch, Michal Reichman-Fried, Katsiaryna Tarbashevich, Tamara Limon, Martin Stehling, Corinna Friedrich, Frank Tuettelmann, Erez Raz
Summary: Combining patient genetic data with functional in vivo assays in zebrafish reveals a possible role for DND1 in human male fertility.
HUMAN REPRODUCTION
(2023)
Article
Andrology
Jaafar Haris Bello, Muhammad Jadoon Khan, Saira Amir, Hoor Gulalai Kakakhel, Faheem Tahir, Sikandar Sultan, Syed Qasim Raza, Charalampos Mamoulakis, Athanasios Zachariou, Aristidis Tsatsakis, Nikolaos Sofikitis, Syed Tahir Abbas Shah
Summary: The study found that mitochondrial sirtuin genes were significantly down-regulated in the semen of infertile men compared to fertile men. The expression levels of mitochondrial sirtuin genes were correlated with mitochondrial HSP90 expression, which may be associated with human male infertility and compromised functional and structural integrity of sperm.
Article
Endocrinology & Metabolism
Olivia E. Smith, Vickie Roussel, Fanny Morin, Luisina Ongaro, Xiang Zhou, Micka C. Bertucci, Daniel J. Bernard, Bruce D. Murphy
Summary: This study demonstrates the essential role of SF-1 in female reproductive function. Depletion of SF-1 leads to infertility in female mice due to the absence of ovulation. Abnormal signaling and lipid accumulation may contribute to these outcomes.
Article
Reproductive Biology
Laura Danti, Karolina Lundin, Kirsi Sepponen, Dawit A. Yohannes, Juha Kere, Timo Tuuri, Juha S. Tapanainen
Summary: By combining the processes of gonadal differentiation and conditional gene activation, this study showed that NR5A1 induction predominantly upregulates female gonadal markers and steroidogenic markers. Differentially expressed genes were highly associated with adrenal and ovarian steroidogenesis pathways. The study provides insights into the role of NR5A1 in gonadal differentiation of a female stem cell line.
JOURNAL OF OVARIAN RESEARCH
(2023)
Article
Multidisciplinary Sciences
Idoia Martinez de Lapiscina, Chrysanthi Kouri, Josu Aurrekoetxea, Mirian Sanchez, Rawda Naamneh Elzenaty, Kay-Sara Sauter, Nuria Camats, Gema Grau, Itxaso Rica, Amaia Rodriguez, Amaia Vela, Alicia Cortazar, Maria Concepcion Alonso-Cerezo, Pilar Bahillo, Laura Bertholt, Isabel Esteva, Luis Castano, Christa E. Flueck
Summary: NR5A1/SF-1 variants can lead to differences in sex development and may be present in both affected individuals and healthy carriers. The common p.Gly146Ala variant of NR5A1/SF-1 has been suggested to be a susceptibility factor for adrenal disease or cryptorchidism, but its disease-causing effect has been questioned due to its high frequency in the general population and inconclusive functional testing results.
Article
Biochemistry & Molecular Biology
Alenka Hodzic, Ales Maver, Branko Zorn, Daniel Petrovic, Tanja Kunej, Borut Peterlin
Summary: This study aimed to identify genes involved in the pathogenesis of idiopathic male infertility based on transcriptomic and genomic data. By analyzing gene expression in testis biopsy samples and conducting a systematic review, four genes were found to be associated with male infertility, while three other genes were identified as promising candidates.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Aristeidis Giannakopoulos, Amalia Sertedaki, Dionisios Chrysis
Summary: This study examines the phenotype of a female patient and analyzes the genetic interaction between genes involved in pituitary and ovarian development, which may result in similar disease phenotypes.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Review
Cell Biology
Yong Xu, Qianqian Pang
Summary: The male-specific Y chromosome plays a significant role in testis development and function. It has unique characteristics such as diverse repetitive sequences and palindrome structure. Deletions of certain sequences can lead to spermatogenesis disorders and male infertility, as well as increase the susceptibility to reproductive system cancers. Additionally, the Y chromosome has special value in forensic medicine for personal identification and parentage testing. However, the analysis of Y chromosome sequences and the study of Y-gene function still face unresolved problems due to the high complexity and limitations of sequencing technology.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Sinead M. McGlacken-Byrne, Polona Le Quesne Stabej, Ignacio Del Valle, Louise Ocaka, Andrey Gagunashvili, Berta Crespo, Nadjeda Moreno, Chela James, Chiara Bacchelli, Mehul T. Dattani, Hywel J. Williams, Dan Kelberman, John C. Achermann, Gerard S. Conway
Summary: In this study, a genetic mechanism underlying early-onset POI in two sisters was identified. The disruption of the ZSWIM7 gene was found to be associated with POI in humans and may play an important role in human homologous recombination. This study expands the range of genes associated with POI in women.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Pediatrics
Sheena Visram, Deirdre Leyden, Oceiah Annesley, Dauda Bappa, Neil J. Sebire
Summary: This article investigates the attitudes of children and young people towards the application of Artificial Intelligence (AI) in medicine and healthcare. It found that they were more open to certain applications of AI than others, with a focus on human-centeredness, governance, and trust. The article suggests that educational workshops and practical examples can help address concerns and build trust in AI.
PEDIATRIC RESEARCH
(2023)
Review
Medicine, General & Internal
Ben Gordon, Clara Fennessy, Susheel Varma, Jake Barrett, Enez McCondochie, Trevor Heritage, Oenone Duroe, Richard Jeffery, Vishnu Rajamani, Kieran Earlam, Victor Banda, Neil Sebire
Summary: This study objectively evaluated freely available data profiling software tools for their applicability in healthcare data. Several tools showed high potential and functionality for use with healthcare datasets. In a synthetic dataset of 1000 patients, two tools consistently performed well across multiple tasks including completeness, consistency, uniqueness, validity, accuracy, and distribution metrics.
Review
Radiology, Nuclear Medicine & Medical Imaging
Susan C. Shelmerdine, Richard D. White, Hantao Liu, Owen J. Arthurs, Neil J. Sebire
Summary: Most research and commercial efforts have focused on using artificial intelligence (AI) for fracture detection in adults, but the long-term clinical and medicolegal implications of missed fractures in children are more significant. This study assessed the available literature on the diagnostic performance of AI tools for pediatric fracture assessment on imaging, and compared this with the performance of human readers. The literature exhibits wide heterogeneity and limited information on algorithm performance on external datasets, making it difficult to understand how these tools may generalize to a wider pediatric population.
INSIGHTS INTO IMAGING
(2022)
Review
Respiratory System
Nicole Filipow, Eleanor Main, Neil J. Sebire, John Booth, Andrew M. Taylor, Gwyneth Davies, Sanja Stanojevic
Summary: This paper discusses the application of machine learning in predicting clinical outcomes of chronic respiratory diseases in children. It identifies limitations in model development and highlights the importance of clinician involvement and consideration of diversity, equity, and inclusion.
BMJ OPEN RESPIRATORY RESEARCH
(2022)
Article
Oncology
Laura Privitera, Layla Musleh, Irene Paraboschi, Olumide Ogunlade, Olumide Ogunbiyi, J. Ciaran Hutchinson, Neil Sebire, Paul Beard, Stefano Giuliani
Summary: Neuroblastoma (NB), the most common extracranial tumor in children, can be better treated with the help of imaging techniques such as photoacoustic imaging (PAI) to distinguish viable malignant tissue from necrotic and surrounding healthy tissue. The study found that post-chemotherapy, viable areas of differentiating NBs and ganglioneuroblastomas have higher vascular density, while early necrotic regions have higher vascular density than late necrotic and viable regions. Calcified areas have significantly lower vascular density. The results suggest that PAI can potentially guide surgical resection by identifying different vasculature signatures.
Article
Multidisciplinary Sciences
Bojidar Rangelov, Alexandra Young, Watjana Lilaonitkul, Shahab Aslani, Paul Taylor, Eyjolfur Guomundsson, Qianye Yang, Yipeng Hu, John R. Hurst, David J. Hawkes, Joseph Jacob
Summary: The COVID-19 pandemic has presented a significant challenge to healthcare systems worldwide. This study developed an unsupervised data-driven model called SuStaIn, which can be used to predict short-term infectious diseases like COVID-19 based on commonly recorded clinical measures. The model identified three COVID-19 subtypes and introduced disease severity stages, both of which were predictive of in-hospital mortality or escalation of treatment. This model can be adapted for future outbreaks of COVID-19 or other infectious diseases.
SCIENTIFIC REPORTS
(2023)
Article
Developmental Biology
Nada Mufti, Joanna Chappell, Patrick O'Brien, George Attilakos, Hassna Irzan, Magda Sokolska, Priya Narayanan, Trevor Gaunt, Paul D. Humphries, Premal Patel, Elspeth Whitby, Eric Jauniaux, J. Ciaran Hutchinson, Neil J. Sebire, David Atkinson, Giles Kendall, Sebastien Ourselin, Tom Vercauteren, Anna L. David, Andrew Melbourne
Summary: The study investigates the use of super-resolution reconstruction (SRR) MRI to improve placental assessment and predict adverse maternal outcomes. The results show that SRR imaging and paired imaging can enhance the detection of pathological MRI markers, aiding in surgical planning.
Article
Multidisciplinary Sciences
Taryn D. Treger, John E. G. Lawrence, Nathaniel D. Anderson, Tim H. H. Coorens, Aleksandra Letunovska, Emilie Abby, Henry Lee-Six, Thomas R. W. Oliver, Reem Al-Saadi, Kjell Tullus, Guillaume Morcrette, J. Ciaran Hutchinson, Dyanne Rampling, Neil Sebire, Kathy Pritchard-Jones, Matthew D. Young, Thomas J. Mitchell, Philip H. Jones, Maxine Tran, Sam Behjati, Tanzina Chowdhury
Summary: In this study, we examined somatic changes in reninoma and discovered structural variants involving NOTCH1 and NRARP, resulting in excessive renin and NOTCH1 signaling but normal expression of NRARP. Additionally, our findings were supported by previous studies that also found dysregulated Notch pathway signaling in reninoma.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Jenifer P. Suntharalingham, Miho Ishida, Antoinette Cameron-Pimblett, Sinead M. McGlacken-Byrne, Federica Buonocore, Ignacio del Valle, Gaganjit Kaur Madhan, Tony Brooks, Gerard S. Conway, John C. Achermann
Summary: This study aimed to investigate the global genetic variability in women with Turner syndrome (TS), whether common variants in X genes are associated with phenotype, and the replication of the association between autosomal TIMP3 variants and congenital cardiovascular anomalies (CCA). The results showed that there was no excess of genetic variability in women with TS, no obvious X-chromosome variants driving phenotype were found, but several possible genes/variants of interest emerged. Additionally, the association between autosomal TIMP3 variants and CCA was replicated.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Rebecca Spencer, Kasia Maksym, Kurt Hecher, Karel Marsal, Francesc Figueras, Gareth Ambler, Harry Whitwell, Nuno Rocha Nene, Neil J. Sebire, Stefan R. Hansson, Anke Diemert, Jana Brodszki, Eduard Gratacos, Yuval Ginsberg, Tal Weissbach, Donald M. Peebles, Ian Zachary, Neil Marlow, Angela Huertas-Ceballos, Anna L. David
Summary: This study investigates the use of maternal serum protein and ultrasound measurements to predict outcomes in pregnancies affected by severe, early-onset fetal growth restriction (FGR). The results demonstrate that ultrasound measurements and maternal serum PlGF concentration can predict important pregnancy outcomes for patients and clinicians.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Sinead M. McGlacken-Byrne, John C. Achermann, Gerard S. Conway
Summary: A girl presenting with delayed puberty and elevated gonadotropins may have a range of conditions requiring a specialized and multidisciplinary approach to investigation and management. Next-generation sequencing has identified genetic causes for some of these conditions, potentially enabling personalized care in the future. The psychological challenges posed by these conditions should also be addressed. Shared decision-making and support groups can empower young people and their families to manage these conditions.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)
Correction
Multidisciplinary Sciences
Gerda Kildisiute, Waleed M. Kholosy, Matthew D. Young, Kenny Roberts, Rasa Elmentaite, Sander R. van Hooff, Clarissa N. Pacyna, Eleonora Khabirova, Alice Piapi, Christine Thevanesan, Eva Bugallo-Blanco, Christina Burke, Lira Mamanova, Lira Mamanova, Kaylee M. Keller, Karin P. S. Langenberg-Ververgaert, Philip Lijnzaad, Thanasis Margaritis, Frank C. P. Holstege, Michelle L. Tas, Marc H. W. A. Wijnen, Max M. van Noesel, Ignacio Del Valle, Giuseppe Barone, Reinier van der Linden, Catriona Duncan, John Anderson, John C. Achermann, Muzlifah Haniffa, Sarah A. Teichmann, Dyanne Rampling, Neil J. Sebire, Xiaoling He, Ronald R. de Krijger, Roger A. Barker, Kerstin B. Meyer, Omer Bayraktar, Karin Straathof, Jan J. Molenaar, Sam Behjati
Article
Endocrinology & Metabolism
Avinaash Maharaj, Tulay Guran, Federica Buonocore, John C. Achermann, Louise Metherell, Rathi Prasad, Semra Cetinkaya
Summary: Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is a multisystemic disorder characterized by steroid-resistant nephrotic syndrome and primary adrenal insufficiency. This case report presents a young girl with a novel homozygous variant in SGPL1, p.D350G, who developed primary adrenal insufficiency and later primary hypothyroidism during follow-up.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)
Correction
Multidisciplinary Sciences
Tim H. H. Coorens, Thomas R. W. Oliver, Rashesh Sanghvi, Ulla Sovio, Emma Cook, Roser Vento-Tormo, Muzlifah Haniffa, Matthew D. Young, Raheleh Rahbari, Neil Sebire, Peter J. Campbell, D. Stephen Charnock-Jones, Gordon C. S. Smith, Sam Behjati