Featured
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Article
| Open AccessInhibition mechanism of the fungal β−1,3-glucan synthases by triterpenoid antifungal drugs
Here, the authors present structural and mechanistic insights into the inhibition of fungal β-1,3-glucan synthase, a key enzyme in fungal cell wall synthesis, by triterpenoid drugs.
- Zi-Long You
- , Lei Sun
- & Lin Bai
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Review Article
| Open AccessIntegrated action for skin NTDs: Deconstructing transmission, addressing knowledge gaps, and championing one health strategies
This review calls for integrated Skin NTD action, using One Health to analyze complex human, animal, and environmental transmission. It highlights knowledge gaps and urges expanded, standardized diagnostics and systematic data collection on social/financial barriers for patient-centered control.
- Lydia Mosi
- , Bishwanath Acharya
- & Heather Jordan
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Article
| Open AccessIntradermal delivery of lipophilic siRNAs enables prolonged skin retention and sustained gene silencing in a porcine model
Skin-targeted siRNA therapies require optimized delivery to achieve therapeutic efficacy. Here, authors show that increasing conjugate hydrophobicity enhances siRNA skin retention and gene silencing in porcine and human models while limiting systemic tissue exposure.
- Hassan H. Fakih
- , Mohammad Zain UI Abideen
- & Julia F. Alterman
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Article
| Open AccessEngineered bacterial therapy suppresses Enterohemorrhagic Escherichia coli through metabolic competition and virulence silencing
Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen where therapeutic antibiotic treatment can release toxins and disrupt gut microbiota. Here the authors demonstrate a therapeutic strategy where an engineered Escherichia coli Nissle 1917 limits the glucuronic acid utilization by EHEC.
- Guozhen Ma
- , Ruiying Liu
- & Yutao Liu
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Article
| Open AccessNeurocognitive characterization of behaviour and mental illness through time-varying brain network analysis
Here, the authors find that time-varying brain network analysis better captures cognitive processing than static methods and reveals network measurement linked to task performance and psychopathology that offer precise neural markers for mental health risks.
- Xiao Chang
- , Tianye Jia
- & Gunter Schumann
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Article
| Open AccessGut microbiota-dependent 24-hydroxycholesterol metabolism contributes to capsaicin-induced amelioration of Alzheimer’s disease-like pathology in mice
Dietary capsaicin alleviates Alzheimer’s disease-like pathologies in 5xFAD mice via reshaping gut bacteria and elevating the production of lipid metabolites 24-hydroxycholesterol.
- Yawen Li
- , Hui Wang
- & Jie Zheng
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Article
| Open AccessAI-based multiomics profiling reveals complementary omics contributions to personalized prediction of cardiovascular disease
Cardiovascular risk is driven by genes, proteins, and metabolites, yet their combined predictive value is unclear. Here, the authors develop CardiOmicScore to integrate genomics, proteomics and metabolomics and predict six cardiovascular diseases up to 15 years prior to disease onset.
- Yan Luo
- , Nan Zhang
- & Qingpeng Zhang
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Article
| Open AccessAn interpretable AI system reduces false-positive MRI diagnoses by stratifying high-risk breast lesions
Diagnosing breast cancer through MRI is limited by high false-positive rates and inter- reader variability, leading to unnecessary biopsies. In here, the authors find that the BI-RADS 4 Lesions Analysis System (BL4AS) model improves diagnostic accuracy and reduces unnecessary biopsies as well as inter-reader variability
- Yanting Liang
- , Zhitao Wei
- & Zhenwei Shi
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Article
| Open AccessCounteracting FOX proteins epigenetically control the herpesvirus lytic-latent balance
The herpes simplex virus lytic-latent balance is incompletely understood. In this study, the authors show that it is controlled by the relative abundance of host activating and repressive forkhead box (FOX) transcription factors that recruit epigenetic cofactors to the viral genome to remodel viral chromatin.
- Yuhang Xiang
- , Xiyuan Yang
- & Dongli Pan
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Article
| Open AccessEarly detection of aberrant cell fate and repair using circulating progenitor cells in patients with heterotopic ossification
Painful bone growth after injury or surgery often goes undetected until it is advanced and treatment options are limited. Here, authors demonstrate that a blood test detecting gene expression profiles in isolated circulating mesenchymal progenitor cells could detect early signs of this condition and track treatment success.
- Johanna Nunez
- , Matilda Holtz
- & N. Murat Karabacak
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Article
| Open AccessClonal expansion of cytotoxic CD8⁺ T cells in lecanemab-associated ARIA
Johnson et al. link ARIA, a complication of anti-amyloid therapy, to clonal expansion of cytotoxic CD8 + T cells with glycolytic reprogramming and vascular trafficking potential, with implications for biomarker development and risk mitigation.
- Lance A. Johnson
- , Kai Saito
- & Josh M. Morganti
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Article
| Open AccessAnti-TLR2 immunotherapy modulates neuron-to-oligodendrocyte propagation of α-synuclein in mouse and human models
The pathological mechanisms underlying multiple system atrophy (MSA) remain unclear. Here, the authors show in mouse and human MSA models that α-synuclein spreads from neurons to oligodendrocytes via TLR2 leading to myelination defects, and that blocking TLR2 prevents glial cytoplasmic inclusions and myelin damage.
- Eun-Jin Bae
- , Sangwoo Ham
- & Seung-Jae Lee
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Article
| Open AccessCircadian fluctuation of soluble CD26 dictates the impact of the timing of cord blood transplantation on acute graft-versus-host disease
It was shown that early-day stem cell infusions reduced the severity of acute graft-versus-host disease (aGVHD). Our result suggested early morning cord blood transplantation reduces aGVHD severity and correlated with circadian sCD26 fluctuations.
- Yue Wu
- , Yiwen Hou
- & Xiaoyu Zhu
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Article
| Open AccessElectrographic cue-reactivity co-localizes with accumbens deep brain stimulation in a case of opioid use disorder
Deep brain stimulation tuned to cue-reactivity within the nucleus accumbens region reduced drug cravings, heralding an evocation-based programming strategy for opioid use disorder.
- Liming Qiu
- , Young-Hoon Nho
- & Casey H. Halpern
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Article
| Open AccessCost-effectiveness of a smart pillbox intervention for adherence to oral HIV pre-exposure prophylaxis
A recent randomised controlled trial demonstrated effectiveness of a smart pillbox for oral HIV pre-exposure prophylaxis adherence in men who have sex with men in China. Here, the authors show that the intervention is cost effective, with greater benefits for more socially vulnerable groups.
- Zhen-Hao Wu
- , Zhen-Xing Chu
- & Qing-Hai Hu
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Article
| Open Access
Labor Market Outcomes of People with HIV Pre- and Post-Diagnosis in the Netherlands
The life expectancy of people living with HIV on antiretroviral therapy is close to that of the general population but wider impacts of living with HIV are not well described. Here, the authors investigate the causal effect of receiving an HIV diagnosis on labour market outcomes using data from the Netherlands.
- Andrei Tuiu
- , Esmée Zwiers
- & Marc van der Valk
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Article
| Open AccessA spatially resolved atlas of gastric cancer characterises a lymphocyte-aggregated region
The spatial organisation of the tumour microenvironment (TME) can affect immune responses that control tumour growth. Here, the authors use single-cell transcriptomics and spatial transcriptomics to identify a lymphocyte aggregated region (LAR) in gastric cancer and compare its cellular and molecular composition with the neighbouring TME.
- Sen Gao
- , Shishang Qin
- & Zemin Zhang
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Article
| Open AccessInterventional applications of a Stroke Heat Risk Prediction Model produce health benefits
Although heat is a major stroke risk factor, targeted intervention tools are lacking, so we developed and evaluated a Stroke Heat Risk Model for personalized prevention. Here, the authors show that it yields three times the preventable heat-attributable stroke deaths of current heat warning systems.
- Jingwei Zhang
- , Mengxue Zhang
- & Tiantian Li
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Article
| Open AccessMobility-driven synthetic contact matrices as a scalable solution for real-time pandemic response modeling
Contact matrices are used to describe social mixing patterns and inform mathematical models of disease transmission. Here, the authors evaluate the accuracy of synthetic contact matrices generated using mobility data compared to those derived empirically through surveys.
- Laura Di Domenico
- , Paolo Bosetti
- & Vittoria Colizza
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Article
| Open AccessGranzyme B-mimetic nanozyme for nanovesicle targeted anticancer applications
Granzyme B is an important factor in cytotoxic T lymphocytes anti-tumour immunity. Here, the authors report on a Pd-FTn granzyme B-mimicking nanozyme with a binuclear catalytic centre, delivered by functionalised nanovesicles to selectively trigger caspase-dependent apoptosis for a T cell-inspired cancer therapy.
- Xueyan Hu
- , Qiqi Liu
- & Xinglu Huang
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Article
| Open Access
CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting
CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.
- Ari Itoh-Nakadai
- , Minggao Liang
- & Fumihiko Ishikawa
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Article
| Open AccessComprehensive benchmarking single and multi ancestry polygenic score methods with the PGS-hub platform
Here the authors systematically benchmark 13 polygenic score (PGS) methods in UK Biobank European and African populations, revealing factors that affect prediction accuracy. They also introduce an automated platform for standardized and reproducible PGS computation.
- Xingyu Chen
- , Fei Wang
- & Minxian Wang
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Article
| Open AccessEssential role of NONO-HOXA1-Wnt axis in cardiomyocyte differentiation
Here they show that NONO collaborates with HOXA1 to modulate gene expression during early cardiomyocyte differentiation. This interaction facilitates activation of the Wnt signaling pathway, establishing the NONO-HOXA1-Wnt axis as a key mechanism in cardiac development.
- Zhiyu Feng
- , Yuan Gao
- & Guoying Huang
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Article
| Open AccessA stabilized tandem antigen chimera that elicits potent malaria transmission-reducing activity
Several transmission-blocking vaccine candidates based on Pfs230 and Pfs48/45 are in clinical development, but it remains unclear whether they will demonstrate high efficacy. Here, the authors develop a stabilized chimeric antigen presenting potent epitopes from Pfs230 and Pfs48/45 in a single construct and demonstrate induction of transmission-reducing antibodies when female mice are immunized with the antigen in a self-assembling protein nanoparticle formulation.
- Danton Ivanochko
- , Kazutoyo Miura
- & Jean-Philippe Julien
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Article
| Open AccessFunctional variants at 1p36.23 confer risk of schizophrenia through modulating RERE
Schizophrenia risk at 1p36.23 lacked functional insight. Here, the authors identify two enhancer variants that upregulate RERE, which disrupts neurogenesis and synaptic function by regulating Grin2a, linking genetic risk to neuronal development and excitatory signaling.
- Yixing Liu
- , Junyang Wang
- & Xiong-Jian Luo
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Article
| Open AccessDe novo variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders
This study reports that de novo germline missense variants in SF3B1, distinct from the somatic variants frequently observed in cancer, cause a neurodevelopmental disorder and disrupt global RNA splicing.
- Kevin Uguen
- , Tiffany Bergot
- & Delphine G. Bernard
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Article
| Open Access
Endothelial stem cells of the retinal vasculature reside in the optic nerve
This study finds stem-like endothelial cells in the optic nerve that supply and repair retinal blood vessels after injury, revealing a hierarchical repair system that may enable new treatments for blinding vascular eye diseases.
- Susumu Sakimoto
- , Toru Takigawa
- & Kohji Nishida
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Article
| Open AccessCamouflaged nanorobots target and regulate macrophage subcellular organelle crosstalk patterns to promote neural regeneration
Macrophages play an important role in repair and regeneration of damaged nerves in spinal cord injury (SCI). Here, Guo et al. investigate effects of endoplasmic reticulum-mitochondria crosstalk on macrophage phenotype and develop a targeted nanorobot inhibiting the Ero1α/MAMs/mtCa²⁺ axis, promoting M2 polarization and neural repair as a therapeutic strategy to treat SCI.
- Qiangqiang Guo
- , Wei Wang
- & Kun Xi
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Article
| Open AccessA common DNA deletion altering the 3’UTR of mdr1 is associated with reduced mefloquine susceptibility in P. vivax parasites from Cambodian patients
Plasmodium vivax is responsible for most malaria cases outside Africa and drug resistance is a concern. The authors use genomic approaches to identify a deletion near the MDR1 gene that affects its expression and is associated with lower mefloquine susceptibility.
- Katie Ko
- , Kieran Tebben
- & David Serre
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Article
| Open Access
Antibody-conjugated mesenchymal stromal cell drug delivery system for the treatment of autoimmune diseases in mice
Antibody-conjugated Mesenchymal stromal cells (Ac-MSC) carrying internalized therapeutic agents represent a promising therapeutic approach for the treatment of autoimmune disease. Here, an ac-MSC-based drug delivery system, consisting of anti-CD4 antibody-conjugated MSCs loaded with a RORγt inverse agonist, is engineered to achieve selective targeting of pathogenic CD4 T cells and to deliver therapeutic benefits in mouse models of psoriasis and arthritis.
- Qian Xie
- , Yanni Shen
- & Yan Wang
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Article
| Open Access
Longitudinal plasma proteomic signatures of elite and viremic spontaneous HIV controllers
Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.
- Nadira Vadaq
- , Albert L. Groenendijk
- & André J. A. M. van der Ven
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Article
| Open AccessWomen with polycystic ovary syndrome exhibit impaired endometrial receptivity with excessive ERα and histone lactylation
It remains unclear whether and how endometrial dysfunction leads to infertility in polycystic ovary syndrome (PCOS), independent of the ovary. Here, the authors show that elevated ERα and histone lactylation impair endometrial receptivity in PCOS and serve as potential therapeutic targets.
- Hongying Shan
- , Yue Wang
- & Heng Pan
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Article
| Open AccessEvolution of the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones
T cells contribute to protection and pathogenesis in tuberculosis. Here the authors sequence T cell receptor repertoires in human skin biopsies from the site of the tuberculin skin test and show enrichment of clonotypes reactive to Mycobacterium tuberculosis using a computational pipeline metaclonotypist to identify distinct TCRs predicted to share peptide-MHC reactivity across participants, as an approach to explore T cell correlates of tuberculosis disease-risk stratification and vaccine efficacy.
- Carolin T. Turner
- , Andreas Tiffeau-Mayer
- & Mahdad Noursadeghi
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Article
| Open AccessSerine inhibits granulosa cell ferroptosis to maintain ovarian function
This study demonstrates that the reduced serum serine in patients with chemotherapy or women with poor sleep, is linked to the decline of ovarian function. Serine supplementation prevented ovarian damage in mice by inhibiting ferroptosis in ovarian granulosa cells, without affecting chemotherapy efficacy.
- Hao-Cheng Gu
- , You-Qiong Zhuo
- & Hong-Bo Xin
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Article
| Open AccessImpact and cost-effectiveness of doxycycline post-exposure prophylaxis in Australian men who have sex with men
Doxycycline has been recommended as post-exposure prophylaxis for prevention of bacterial sexually-transmitted diseases. Here, the authors use mathematical modelling to investigate the potential disease, antimicrobial resistance, and economic implications of this intervention in gay, bisexual, and other men who have sex with men in Australia.
- Hao Lai
- , Jason J. Ong
- & Lei Zhang
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Article
| Open AccessMultimodal analysis disentangles the genetic and microbial associations between inflammatory bowel disease and other immune-mediated diseases across a harmonized population framework
Co-occurrence of immune-mediated inflammatory diseases (IMID) is common in patients with inflammatory bowel disease (IBD). However, to what extent genetic, immune, and microbial factors drive these associations remains elusive. Here, the authors present a multi-modal analysis, integrating genealogical data, genome-wide association data, and microbiota datasets, to disentangle the genetic and microbial contributions to disease co-occurrences.
- Marie Vibeke Vestergaard
- , Alonzo Alfaro-Núñez
- & Tine Jess
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Article
| Open AccessA fully degradable triboelectric vagus nerve stimulator for attenuating cardiac remodeling and heart failure at different stages
Heart failure affects millions worldwide with limited treatment options. Here, the authors develop a biodegradable, self-powered vagus nerve stimulator that attenuates cardiac damage at different disease stages without requiring battery replacement or surgical removal.
- Zhen Guo
- , Sheng-Yu Chao
- & Qi-Zhu Tang
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Article
| Open Access
Sero-genomic evidence for occult mpox exposure in healthy Nigerian adults
There are limited data on mpox immunity in West Africa. In this study, authors present serological and genomic evidence of residual smallpox vaccination immunity and possibly unrecognized mpox exposure among ostensibly healthy Nigerian adults.
- Adam Abdullahi
- , Ifeanyi Omah
- & Ravindra K. Gupta
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Article
| Open AccessGlycerol 3-phosphate acyltransferase exacerbates α-synuclein-induced toxicity by increasing lipid peroxidation
The role of lipid metabolism in Parkinson's disease is poorly understood. Here, Ren and co-authors identify a key enzyme in this process, mitochondrial glycerol 3-phosphate acyltransferase, as a critical driver of α-synuclein toxicity.
- Mengda Ren
- , Grace G. Y. Lim
- & Kah-Leong Lim
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Article
| Open AccessDouble-dose firmonertinib as first-line treatment in patients with locally advanced or metastatic non-small-cell lung cancer harboring EGFR L858R mutation: a prospective, multicenter, phase II study (FIRM)
Progression-free survival with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors remains suboptimal in EGFR L858R-mutated advanced non-small-cell lung cancer (NSCLC), highlighting the need for strategies to delay resistance. Here this group reports a single-arm, phase II study evaluating first-line double-dose firmonertinib in 33 patients with L858R-mutated locally advanced or metastatic NSCLC.
- Bo Shen
- , Chun Wang
- & Meiqi Shi
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Article
| Open AccessG9a-mediated H3K9me2 orchestrates intestinal epithelial regeneration through epigenetic silencing of cell cycle-related genes
Here they show that G9a-mediated H3K9me2 regulates intestinal homeostasis and injury repair through repression of cell cycle arrest genes in both mouse and human.
- Jingzhou Chen
- , Xiaoliang Shi
- & Jinghao Sheng
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Article
| Open AccessCentral amygdala single-nucleus atlas reveals chromatin and gene transcription dynamics in human alcohol use disorder
The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.
- Che Yu Lee
- , Ahyeon Hwang
- & Matthew J. Girgenti
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Article
| Open Access
The ratio of circulatory levels of sphingolipids to steroids predicts asthma exacerbations
Asthma exacerbations remain hard to predict with routine tests. Here, the authors show that simple blood sphingolipid-to-steroid ratios predict five-year exacerbation risk and can underpin a practical, low-cost assay that outperforms standard clinical measures.
- Yulu Chen
- , Pei Zhang
- & Jessica A. Lasky-Su
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Article
| Open Access
Site-saturation functional screens identify PALB2 missense variants associated with increased breast cancer risk
The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.
- Rick A.C.M. Boonen
- , Sabine C. Knaup
- & Haico van Attikum
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Article
| Open AccessNear-infrared light-driven nanomotors-based microneedles for the active therapy of bacterial infected acne
Acne is a common skin disease caused by the anaerobic Cutibacterium acnes. Here, the authors report a microneedles patch loaded with near infrared-driven self-oxygenating ZnO2@PDA-MnO2 nanomotors for photothermal therapy of acne.
- Ziwei Hu
- , Yuyang Gan
- & Yingfeng Tu
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Article
| Open AccessExcess mortality in Europe estimated by EuroMOMO during the COVID-19 pandemic and previous influenza seasons
This paper reports the excess mortality estimated during the evolving consecutive waves of COVID-19 in countries participating in the European Mortality Monitoring Network (EuroMOMO) in 2020-2023 and how they compare to recent influenza seasons.
- Sarah K. Nørgaard
- , Jens Nielsen
- & Lasse S. Vestergaard
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Article
| Open AccessMixed-model and transcriptome-wide association analyses identify transcription factors and genes associated with colorectal cancer susceptibility
This study applies generalized linear mixed models (GLMM) and advanced transcriptome wide association study (TWAS) methods to improve the discovery of colorectal cancer risk transcription factors and genes, including potential druggable targets.
- Zhishan Chen
- , Wenqiang Song
- & Xingyi Guo
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Article
| Open Access
Genetic insights and mechanistic parallels in gestational diabetes mellitus and type 2 diabetes
This study identifies shared genetic mechanisms between gestational diabetes mellitus (GDM) and type 2 diabetes (T2D), highlighting 5 genes linked to GDM and 97 genes associated with T2D. Four genes (COBLL1, NRBP1, IFT172, TRIM54) are shared, offering potential targets for treatment.
- Liwan Fu
- , Xiaodi Han
- & Yue-Qing Hu
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Article
| Open AccessVariations in the Natural History of High-Risk HPV Types Following HPV-16/18 Bivalent Vaccination in Females Aged 18-45 Years
A 10-year follow-up study of the HPV-16/18 bivalent vaccine shows that vaccination alters the natural history of high-risk HPV types, resulting in reduced HPV-16/18 infections while HPV-52 infections persist with decreased clearance and increased progression. The study shows that vaccinated populations have distinct HPV epidemiological profiles, indicating that current cervical cancer screening algorithms may be suboptimal.
- Qi Chen
- , Jiali Quan
- & Ningshao Xia
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