tbuckley/cabot-search huggingface dataset:
Survivorship after adolescent and young adult cancer: models of care, disparities, and opportunities
Authors: Amy M Berkman, Andrea C Betts, Melissa Beauchemin, Susan K Parsons, David R Freyer, Michael E Roth
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Survivors of adolescent and young adult (AYA; age 15-39 years at diagnosis) cancer are a growing population with the potential to live for many decades after treatment completion. Survivors of AYA cancer are at risk for adverse long-term outcomes including chronic conditions, secondary cancers, impaired fertility, poor psychosocial health and health behaviors, and financial toxicity. Furthermore, survivors of AYA cancer from racially minoritized and low socioeconomic status populations experience disparities in these outcomes, including lower long-term survival. Despite these known risks, most survivors of AYA cancer do not receive routine survivorship follow-up care, and research on delivering high-quality, evidence-based survivorship care to these patients is lacking. The need for survivorship care was initially advanced in 2006 by the Institute of Medicine. In 2019, the Quality of Cancer Survivorship Care Framework (QCSCF) was developed to provide an evidence-based framework to define key components of optimal survivorship care. In this commentary focused on survivors of AYA cancer, we apply the QCSCF framework to describe models of care that can be adapted for their unique needs, multilevel factors limiting equitable access to care, and opportunities to address these factors to improve short- and long-term outcomes in this vulnerable population.
Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa—Results of the HIT 2000 trial
Authors: Martin Mynarek, Anne Rossius, Anika Guiard, Holger Ottensmeier, Katja von Hoff, Denise Obrecht-Sturm, Lisa Bußenius, Carsten Friedrich, Andre O von Bueren, Nicolas U Gerber, Thomas Traunwieser, Rolf-Dieter Kortmann, Monika Warmuth-Metz, Brigitte Bison, Ulrich-W Thomale, Juergen Krauss, Torsten Pietsch, Steven C Clifford, Stefan M Pfister, Dominik Sturm, Felix Sahm, Tanja Tischler, Stefan Rutkowski
Journal: Neuro-Oncology (2024)

Abstract Background Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization, and biology in pediatric survivors of a posterior fossa tumor. Methods Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic tool based on Cattell–Horn–Carroll’s model for intelligence were analyzed. Results Cognitive performance 5.14 years (mean; range = 1.52–13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had a strong impact on most subtests. pCMS was associated with psychomotor abilities (β = –0.25 to –0.16) and processing speed (β = –0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β = –0.20) and short-term memory (β = –0.15), age with crystallized intelligence (β = 0.15) and psychomotor abilities (β = –0.16 and β = –0.17). Scores for fluid intelligence (β = –0.23), short-term memory (β = –0.17) and visual processing (β = –0.25) declined, and scores for selective attention improved (β = 0.29) with time after diagnosis. Conclusions The dose of CSI was strongly associated with neurocognitive outcomes. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI dose and toxicity caused by other treatment modalities.
Integrating multi‐omics approaches in deciphering atopic dermatitis pathogenesis and future therapeutic directions
Authors: Saeko Nakajima, Satoshi Nakamizo, Takashi Nomura, Yoshihiro Ishida, Yu Sawada, Kenji Kabashima
Journal: Allergy (2024)

Atopic dermatitis (AD), a complex and heterogeneous chronic inflammatory skin disorder, manifests in a spectrum of clinical subtypes. The application of genomics has elucidated the role of genetic variations in predisposing individuals to AD. Transcriptomics, analyzing gene expression alterations, sheds light on the molecular underpinnings of AD. Proteomics explores the involvement of proteins in AD pathophysiology, while epigenomics examines the impact of environmental factors on gene expression. Lipidomics, which investigates lipid profiles, enhances our understanding of skin barrier functionalities and their perturbations in AD. This review synthesizes insights from these omics approaches, highlighting their collective importance in unraveling the intricate pathogenesis of AD. The review culminates by projecting future trajectories in AD research, particularly the promise of multi-omics in forging personalized medicine and novel therapeutic interventions. Such an integrated multi-omics strategy is poised to transform AD comprehension and management, steering towards more precise and efficacious treatment modalities.
A novel Mediterranean diet-inspired supplement ameliorates cognitive, microbial, and metabolic deficits in a mouse model of low-grade inflammation
Authors: Matthew G. Pontifex, Emily Connell, Gwenaelle Le Gall, Leonie Lang, Line Pourtau, David Gaudout, Cristina Angeloni, Lorenzo Zallocco, Maurizio Ronci, Laura Giusti, Michael Müller, David Vauzour
Journal: Gut Microbes (2024)

The Mediterranean diet (MD) and its bioactive constituents have been advocated for their neuroprotective properties along with their capacity to affect gut microbiota speciation and metabolism. Mediated through the gut brain axis, this modulation of the microbiota may partly contribute to the neuroprotective properties of the MD. To explore this potential interaction, we evaluated the neuroprotective properties of a novel bioactive blend (Neurosyn240) resembling the Mediterranean diet in a rodent model of chronic low-grade inflammation. Behavioral tests of cognition, brain proteomic analysis, 16S rRNA sequencing, and 1H NMR metabolomic analyses were employed to develop an understanding of the gut-brain axis interactions involved. Recognition memory, as assessed by the novel object recognition task (NOR), decreased in response to LPS insult and was restored with Neurosyn240 supplementation. Although the open field task performance did not reach significance, it correlated with NOR performance indicating an element of anxiety related to this cognitive change. Behavioral changes associated with Neurosyn240 were accompanied by a shift in the microbiota composition which included the restoration of the Firmicutes: Bacteroidota ratio and an increase in Muribaculum, Rikenellaceae Alloprevotella, and most notably Akkermansia which significantly correlated with NOR performance. Akkermansia also correlated with the metabolites 5-aminovalerate, threonine, valine, uridine monophosphate, and adenosine monophosphate, which in turn significantly correlated with NOR performance. The proteomic profile within the brain was dramatically influenced by both interventions, with KEGG analysis highlighting oxidative phosphorylation and neurodegenerative disease-related pathways to be modulated. Intriguingly, a subset of these proteomic changes simultaneously correlated with Akkermansia abundance and predominantly related to oxidative phosphorylation, perhaps alluding to a protective gut-brain axis interaction. Collectively, our results suggest that the bioactive blend Neurosyn240 conferred cognitive and microbiota resilience in response to the deleterious effects of low-grade inflammation.
Colorectal cancer microbiome programs DNA methylation of host cells by affecting methyl donor metabolism
Authors: Zhi Liu, Qingqing Zhang, Hong Zhang, Zhongyuan Yi, Huihui Ma, Xiaoyi Wang, Jingjing Wang, Yang Liu, Yi Zheng, Weijia Fang, Ping Huang, Xingyin Liu
Journal: Genome Medicine (2024)

Colorectal cancer (CRC) arises from complex interactions between host and environment, which include the gut and tissue microbiome. It is hypothesized that epigenetic regulation by gut microbiota is a fundamental interface by which commensal microbes dynamically influence intestinal biology. The aim of this study is to explore the interplay between gut and tissue microbiota and host DNA methylation in CRC.
Mechanisms of myocardial reverse remodelling and its clinical significance: A scientific statement of the ESC Working Group on Myocardial Function
Authors: Inês Falcão‐Pires, Ana Filipa Ferreira, Fábio Trindade, Luc Bertrand, Michele Ciccarelli, Valeria Visco, Dana Dawson, Nazha Hamdani, Linda W. Van Laake, Frank Lezoualc'h, Wolfgang A. Linke, Ida G Lunde, Peter P. Rainer, Mahmoud Abdellatif, Jolanda Van der Velden, Nicola Cosentino, Alessia Paldino, Giulio Pompilio, Serena Zacchigna, Stephane Heymans, Thomas Thum, Carlo Gabriele Tocchetti
Journal: European Journal of Heart Failure (2024)

Cardiovascular disease (CVD) is the leading cause of morbimortality in Europe and worldwide. CVD imposes a heterogeneous spectrum of cardiac remodelling, depending on the insult nature, that is, pressure or volume overload, ischaemia, arrhythmias, infection, pathogenic gene variant, or cardiotoxicity. Moreover, the progression of CVD-induced remodelling is influenced by sex, age, genetic background and comorbidities, impacting patients' outcomes and prognosis. Cardiac reverse remodelling (RR) is defined as any normative improvement in cardiac geometry and function, driven by therapeutic interventions and rarely occurring spontaneously. While RR is the outcome desired for most CVD treatments, they often only slow/halt its progression or modify risk factors, calling for novel and more timely RR approaches. Interventions triggering RR depend on the myocardial insult and include drugs (renin-angiotensin-aldosterone system inhibitors, beta-blockers, diuretics and sodium-glucose cotransporter 2 inhibitors), devices (cardiac resynchronization therapy, ventricular assist devices), surgeries (valve replacement, coronary artery bypass graft), or physiological responses (deconditioning, postpartum). Subsequently, cardiac RR is inferred from the degree of normalization of left ventricular mass, ejection fraction and end-diastolic/end-systolic volumes, whose extent often correlates with patients' prognosis. However, strategies aimed at achieving sustained cardiac improvement, predictive models assessing the extent of RR, or even clinical endpoints that allow for distinguishing complete from incomplete RR or adverse remodelling objectively, remain limited and controversial. This scientific statement aims to define RR, clarify its underlying (patho)physiologic mechanisms and address (non)pharmacological options and promising strategies to promote RR, focusing on the left heart. We highlight the predictors of the extent of RR and review the prognostic significance/impact of incomplete RR/adverse remodelling. Lastly, we present an overview of RR animal models and potential future strategies under pre-clinical evaluation.
TL1A and IL-18 synergy promotes GM-CSF-dependent thymic granulopoiesis in mice
Authors: Mario Ruiz Pérez, Christian Maueröder, Wolf Steels, Bruno Verstraeten, Sahine Lameire, Wei Xie, Laura Wyckaert, Jelle Huysentruyt, Tatyana Divert, Ria Roelandt, Amanda Gonçalves, Riet De Rycke, Kodi Ravichandran, Bart N. Lambrecht, Tom Taghon, Georges Leclercq, Peter Vandenabeele, Peter Tougaard
Journal: Cellular and Molecular Immunology (2024)

Abstract Acute systemic inflammation critically alters the function of the immune system, often promoting myelopoiesis at the expense of lymphopoiesis. In the thymus, systemic inflammation results in acute thymic atrophy and, consequently, impaired T-lymphopoiesis. The mechanism by which systemic inflammation impacts the thymus beyond suppressing T-cell development is still unclear. Here, we describe how the synergism between TL1A and IL-18 suppresses T-lymphopoiesis to promote thymic myelopoiesis. The protein levels of these two cytokines were elevated in the thymus during viral-induced thymus atrophy infection with murine cytomegalovirus (MCMV) or pneumonia virus of mice (PVM). In vivo administration of TL1A and IL-18 induced acute thymic atrophy, while thymic neutrophils expanded. Fate mapping with Ms4a3 -Cre mice demonstrated that thymic neutrophils emerge from thymic granulocyte-monocyte progenitors (GMPs), while Rag1 -Cre fate mapping revealed a common developmental path with lymphocytes. These effects could be modeled ex vivo using neonatal thymic organ cultures (NTOCs), where TL1A and IL-18 synergistically enhanced neutrophil production and egress. NOTCH blockade by the LY411575 inhibitor increased the number of neutrophils in the culture, indicating that NOTCH restricted steady-state thymic granulopoiesis. To promote myelopoiesis, TL1A, and IL-18 synergistically increased GM-CSF levels in the NTOC, which was mainly produced by thymic ILC1s. In support, TL1A- and IL-18-induced granulopoiesis was completely prevented in NTOCs derived from Csf2rb -/- mice and by GM-CSFR antibody blockade, revealing that GM-CSF is the essential factor driving thymic granulopoiesis. Taken together, our findings reveal that TL1A and IL-18 synergism induce acute thymus atrophy while promoting extramedullary thymic granulopoiesis in a NOTCH and GM-CSF-controlled manner.
The risk of subsequent skin cancer in patients with atypical fibroxanthoma or pleomorphic dermal sarcoma compared to the general population
Authors: José van der Waa, Dominique van Midden, Jan Willem Albert Mellink, Uta Flucke, Johannes Jozef Bonenkamp, Pètra Manou Braam, Meggie Margaretha Catharina Maria Drissen, Marieke Louwman, Avital Leonie Amir, Satish Frank Kishore Lubeek
Journal: Journal of the American Academy of Dermatology (2024)
Landscape of fungal detection in the lungs of patients with severe pneumonia in the ICU, a multicenter study based on clinical metagenomics
Authors: Xin Wei, Xiaohan Huang, Silan Gu, Hongliu Cai, Mingqiang Wang, Hongyu Wang, Shengfeng Wang, Chao Jiang, Lingtong Huang
Journal: Journal of Infection (2024)
HIF-1α and MIF enhance neutrophil-driven type 3 immunity and chondrogenesis in a murine spondyloarthritis model
Authors: Akihiro Nakamura, Sungsin Jo, Sayaka Nakamura, Mansi K. Aparnathi, Shaghayegh Foroozan Boroojeni, Mariia Korshko, Ye-Soo Park, Himanshi Gupta, Sandra Vijayan, Jason S. Rockel, Mohit Kapoor, Igor Jurisica, Tae-Hwan Kim, Nigil Haroon
Journal: Cellular and Molecular Immunology (2024)
Early versus delayed weight-bearing following operatively treated ankle fracture (WAX): a non-inferiority, multicentre, randomised controlled trial
Authors: Christopher Patrick Bretherton, Juul Achten, Vidoushee Jogarah, Stavros Petrou, Nicholas Peckham, Felix Achana, Duncan Appelbe, Rebecca Kearney, Harry Claireux, Philip Bell, Xavier L Griffin, Andrew McAndrew, Neal Jacobs, Justin Forder, Thomas Hester, Charlotte Cross, Tony Bateman, Will Kieffer, Tristan Barton, Richard Walter, Nick Savva, Daniel Marsland, Barry Rose, Zine Beech, Togay Koc, Bethany Armstead, Ben Ollivere, Owen Diamond, Kar Teoh, Paul Magill, Jitendra Mangwani, Paul Hodgson, Robbie Ray, Baljinder Dhinsa, Haroon Majeed, John Wong-Chung, Jonathan Young, Agnes Lagare, Akash Soogumbur, Albina Morozova, Alexander Hunt, Amanda Adamson, Angie Dempster, Ann McCormack, Azra Arif, Bethany Armstead, Charlotte Vye, Chetan Dojode, Chloe Brown, Christina Haines, Christopher To, Ciaran Brennan, Dan Winson, Elizabeth McGough, Ellen Jessup-Dunton, Fiona Bintcliffe, Fiona Thompson, Gabriel Omogra, Georgia Scott, Helen Samuel, Hossam Fraig, Ina Burokiene, Isabel Odysseos-Beaumont, James Rand, Janet Edkins, Joe Barrett-Lee, John McFall, Karim Wahed, Kate Herbert, Kelly Death, Laura Beddard, Leanne Dupley, Leeann Bryce, Lianne Wright, Lucy Bailey, Lucy Maling, Marjan Raad, Matt Morris, Matthew Williams, May Labidi, Natalie Holmes, Nikki Staines, Paul A Matthews, Philip McCormac, Rashmi Easow, Scott Matthews, Smriti Kapoor, Sophie Harris, Susan Wagland, Timothy Cobb, Tracey White
Journal: The Lancet (2024)

After surgery for a broken ankle, patients are usually instructed to avoid walking for 6 weeks (delayed weight-bearing). Walking 2 weeks after surgery (early weight-bearing) might be a safe and preferable rehabilitation strategy. This study aimed to determine the clinical and cost effectiveness of an early weight-bearing strategy compared with a delayed weight-bearing strategy.
IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts
Authors: Chao Li, Shiqian Li, Guangyu Zhang, Qinfeng Li, Weidan Song, Xiaoding Wang, Jane A. Cook, Miesje van der Stoel, Bradley W. Wright, Francisco Altamirano, Erica L. Niewold, Jungsoo Han, Garrett Kimble, Pengfei Zhang, Xiang Luo, Hery Urra, Herman I. May, Anwarul Ferdous, Xue-Nan Sun, Yingfeng Deng, Elina Ikonen, Claudio Hetz, Randal J. Kaufman, Kezhong Zhang, Thomas G. Gillette, Philipp E. Scherer, Joseph A. Hill, Jin Chen, Zhao V. Wang
Journal: Circulation (2024)

Cardiomyocyte growth is coupled with active protein synthesis, which is one of the basic biological processes in living cells. However, it is unclear whether the unfolded protein response transducers and effectors directly take part in the control of protein synthesis. The connection between critical functions of the unfolded protein response in cellular physiology and requirements of multiple processes for cell growth prompted us to investigate the role of the unfolded protein response in cell growth and underlying molecular mechanisms.
Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction
Authors: Barbara Schormair, Chen Zhao, Steven Bell, Maria Didriksen, Muhammad S. Nawaz, Nathalie Schandra, Ambra Stefani, Birgit Högl, Yves Dauvilliers, Cornelius G. Bachmann, David Kemlink, Karel Sonka, Walter Paulus, Claudia Trenkwalder, Wolfgang H. Oertel, Magdolna Hornyak, Maris Teder-Laving, Andres Metspalu, Georgios M. Hadjigeorgiou, Olli Polo, Ingo Fietze, Owen A. Ross, Zbigniew K. Wszolek, Abubaker Ibrahim, Melanie Bergmann, Volker Kittke, Philip Harrer, Joseph Dowsett, Sofiene Chenini, Sisse Rye Ostrowski, Erik Sørensen, Christian Erikstrup, Ole B. Pedersen, Mie Topholm Bruun, Kaspar R. Nielsen, Adam S. Butterworth, Nicole Soranzo, Willem H. Ouwehand, David J. Roberts, John Danesh, Brendan Burchell, Nicholas A. Furlotte, Priyanka Nandakumar, Amélie Bonnefond, Louis Potier, Christopher J. Earley, William G. Ondo, Lan Xiong, Alex Desautels, Markus Perola, Pavel Vodicka, Christian Dina, Monika Stoll, Andre Franke, Wolfgang Lieb, Alexandre F. R. Stewart, Svati H. Shah, Christian Gieger, Annette Peters, David B. Rye, Guy A. Rouleau, Klaus Berger, Hreinn Stefansson, Henrik Ullum, Kari Stefansson, David A. Hinds, Emanuele Di Angelantonio, Konrad Oexle, Juliane Winkelmann
Journal: Nature Genetics (2024)

Abstract Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes ( r g = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82–0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.
Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results
Authors: Hui Wang, Yuxin Chen, Jun Lv, Xiaoting Cheng, Qi Cao, Daqi Wang, Longlong Zhang, Biyun Zhu, Min Shen, Chunxin Xu, Mengzhao Xun, Zijing Wang, Honghai Tang, Shaowei Hu, Chong Cui, Luoying Jiang, Yanbo Yin, Luo Guo, Yi Zhou, Lei Han, Ziwen Gao, Jiajia Zhang, Sha Yu, Kaiyu Gao, Jinghan Wang, Bing Chen, Wuqing Wang, Zheng-Yi Chen, Huawei Li, Yilai Shu
Journal: Nature Medicine (2024)

Abstract Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was &gt;95 dB (&gt;95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .