tbuckley/cabot-search huggingface dataset:
Autosomal dominant <i>SLURP1</i> variants cause palmoplantar keratoderma and progressive symmetric erythrokeratoderma
Authors: Xingyuan Jiang, Ryland D Mortlock, Ivan B Lomakin, Jing Zhou, Ronghua Hu, María Laura Cossio, Christopher G Bunick, Keith A Choate
Journal: British Journal of Dermatology (2025)

Epidermal differentiation disorders (EDDs, a.k.a. ichthyosis and palmoplantar keratoderma) are severe heritable skin conditions characterized by localized or generalized skin scaling and erythema. To identify novel genetic variants causing palmoplantar keratoderma (PPK) and progressive symmetric erythrokeratoderma (PSEK) phenotypes. We performed whole exome sequencing in a large EDD cohort including PPK and PSEK phenotypes to identify novel genetic variants. We investigated the variant consequence using in silico predictions, assays in patient keratinocytes, high-resolution spatial transcriptomics, and quantitative cytokine profiling. We identified three unrelated kindreds with autosomal dominant transmission of heterozygous SLURP1 variants affecting the same amino acid within the signal peptide (c.65C>A, p.A22D, and c.65C>T, p.A22V). One (p.A22V) had isolated PPK, and two others (p.A22D) had PSEK and PPK. In silico modeling suggested that both variants alter pro-SLURP1 cleavage, appending two amino acids to the secreted protein, which we subsequently confirmed with mass spectrometry. In patient keratinocytes we found increased differentiation-induced SLURP1 expression and secretion compared to healthy control cells. Spatial transcriptomics revealed increased NF-κB signaling and innate immune activity which may contribute to epidermal hyperproliferation in dominant SLURP1-PPK/PSEK. Our results expand the phenotypic spectrum of EDD due to SLURP1 pathogenic variants. While autosomal recessive Mal de Meleda is due to biallelic loss-of-function SLURP1 variants, our finding of autosomal dominant SLURP1 pathogenic variants in kindreds with PPK and PSEK suggests a novel mechanism of action. We found that heterozygous p.A22V and p.A22D SLURP1 variants append two amino acids to secreted SLURP1, increase differentiation-induced SLURP1 expression and secretion, and upregulate NF-κB signaling in PSEK cases.
Shared pathway of WDFY4-dependent cross-presentation of immune complexes by cDC1 and cDC2
Authors: Suin Jo, Ray A. Ohara, Derek J. Theisen, Sunkyung Kim, Tiantian Liu, Christopher B. Bullock, Michelle He, Feiya Ou, Jing Chen, Sytse J. Piersma, J. Luke Postoak, Wayne M. Yokoyama, Michael S. Diamond, Theresa L. Murphy, Kenneth M. Murphy
Journal: The Journal of Experimental Medicine (2025)

Priming CD8+ T cells against tumors or viral pathogens results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). Although monocyte-derived DCs and cDC2s can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to evaluate the role of cDC subsets in presentation of cell-associated and immune complex antigens to CD4+ and CD8+ T cells in vivo. For cell-associated antigens, cDC1s were necessary and sufficient to prime both CD4+ and CD8+ T cells. In contrast, for immune complex antigens, either cDC1 or cDC2, but not monocyte-derived DCs, could carry out cross-presentation to CD8+ T cells. Mice lacking cDC1 and vaccinated with immune complexes could cross-prime CD8+ T cells that were sufficient to mediate tumor rejection. Notably, this cross-presentation mediated by cDC2 was also WDFY4 dependent, similar to cross-presentation of cell-associated antigens by cDC1. These results demonstrate a previously unrecognized activity of WDFY4 in cDC2s and suggest a cross-presentation pathway shared by cDC subsets.
Impact of screening for HPV-positive oropharyngeal cancers: a microsimulation-based modeling study
Authors: Rebecca Landy, Gregory W Haber, Barry I Graubard, Carole Fakhry, Nicole G Campos, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi
Journal: JNCI Journal of the National Cancer Institute (2025)

We estimated the impact of screening on morbidity and mortality of HPV16-positive oropharyngeal cancer among US men aged 45-79 years. We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical-ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed four progression speeds across cancer stages (very-slow, slow, fast, and very-fast) and four screening frequencies. Among US men aged 45-79 years in 2021 (N = 54,881,311), 163,958 clinically diagnosed HPV-positive oropharyngeal cancers and 32,009 deaths would occur through age 84 in the absence of screening. Assuming very-fast progression, 4%, 20%, 31%, and 60% of these cancers would be detected by one-off, 5-yearly, 3-yearly, and annual screening. Annual screening (very-fast progression) could reduce the number of cancers diagnosed at advanced stages (AJCC 7, Stages III/IV: 90.0% with no screening vs 59.1%) and treated by multiple-modalities (80.6% with no screening vs 50.6%). Cancer mortality would also be reduced by 36.2%, with a gain of 106,000 life-years. Annual screening would have a number needed to screen (NNS) of 561 per screen-detected cancer, 1,118 per additional cancer treated by single-modality, 4,740 per death prevented, and 520 per life-year gained; such high NNS reflect potential inefficiency of population-level screening. If proven efficacious in randomized trials and cost-effective, screening for HPV-positive oropharyngeal cancers could provide considerable population-level reductions in advanced stage cancers, treatment-related morbidities, and mortality.
Selection increases mitonuclear DNA discordance but reconciles incompatibility in African cattle
Authors: Xian Shi, Cheng Ma, Ningbo Chen, Ming-Min Xu, Sumaya Kambal, Zheng-Fei Cai, Qiwen Yang, Adeniyi C Adeola, Li-Sheng Liu, Jun Wang, Wen-Fa Lu, Yan Li, George M Msalya, Chuzhao Lei, Joram M Mwacharo, Jian-Lin Han, Olivier Hanotte, Ya-Ping Zhang, Min-Sheng Peng
Journal: Molecular Biology and Evolution (2025)

Mitochondrial function relies on the coordinated interactions between genes in the mitochondrial (mtDNA) and nuclear genomes. Imperfect interactions following mitonuclear incompatibility may lead to reduced fitness. MtDNA introgressions across species and populations are common and well documented. Various strategies may be expected to reconcile mitonuclear incompatibility in hybrids or admixed individuals. African admixed cattle (Bos taurus × B. indicus) show sex-biased admixture, with taurine (B. taurus) mtDNA and a nuclear genome predominantly of humped zebu (B. indicus). Here, we leveraged local ancestry inference approaches to identify the ancestry and distribution patterns of nuclear functional genes associated with the mitochondrial oxidative phosphorylation process in the genomes of African admixed cattle. We show that most of the nuclear genes involved in mitonuclear interactions are under selection and of humped zebu ancestry. Variation in mtDNA copy number (mtDNA-CN) may have contributed to the recovery of optimal mitochondrial function following admixture with the regulation of gene expression, alleviating or nullifying mitochondrial dysfunction. Interestingly, some nuclear mitochondrial genes with enrichment in taurine ancestry may have originated from ancient African aurochs (B. primigenius africanus) introgression. They may have contributed to the local adaptation of African cattle to pathogen burdens. Our study provides further support and new evidence showing that the successful settlement of cattle across the continent was a complex mechanism involving adaptive introgression, mtDNA-CN variation, regulation of gene expression, and selection of ancestral mitochondria-related genes.
The transcription factor combination MEF2 and KLF7 promotes axonal sprouting in the injured spinal cord with functional improvement and regeneration-associated gene expression
Authors: Callan L. Attwell, Inés Maldonado-Lasunción, Ruben Eggers, Bastiaan A. Bijleveld, Ward M. Ellenbroek, Natascha Siersema, Lotte Razenberg, Dédé Lamme, Nitish D. Fagoe, Ronald E. van Kesteren, August B. Smit, Joost Verhaagen, Matthew R. J. Mason
Journal: Molecular Neurodegeneration (2025)

Axon regeneration after injury to the central nervous system (CNS) is limited by an inhibitory environment but also because injured neurons fail to initiate expression of regeneration associated genes (RAGs). The potential of strong RAG expression to promote regeneration in the CNS is exemplified by the conditioning lesion model, whereby peripheral nerve injury promotes regeneration of centrally projecting branches of the injured neurons. RAG expression could potentially be induced by delivery of the right set of transcription factors (TFs). We here aim to identify TF combinations that activate this program. We first analysed binding site motifs in promoters of the RAG program to identify nine candidate growth-promoting TFs. These were systematically screened in vitro to identify combinations that had potent neurite-growth promoting activity. Next, adeno-associated viral vectors were used to express these TF combinations in vivo in L4/L5 dorsal root ganglia to test whether they would promote regeneration in a spinal cord injury model (dorsal column lesion) in female rats. To determine whether they could activate the RAG program we carried out gene expression profiling on laser-dissected dorsal root ganglion neurons specifically expressing these TF combinations, and of DRG neurons that had been axotomized. Promoter analysis identified ATF3, Jun, CEBPD, KLF7, MEF2, SMAD1, SOX11, STAT3 and SRF as candidate RAG-activating TFs. In vitro screening identified two TF combinations, KLF7/MEF2 and ATF3/KLF7/MEF2, that had potent neurite-growth promoting activity, the latter being the more powerful. In vivo, KLF7/MEF2, but not ATF3/KLF7/MEF2 or KLF7 or MEF2 alone, promoted axonal sprouting into the dorsal column lesion site and led to improved functional recovery. Gene expression profiling revealed that unexpectedly, the MEF2-VP16 construct used had little transcriptional activity in vivo, suggesting additional steps may be required to achieve full MEF2 activity. All combinations except MEF2 alone induced RAG expression mirroring that induced by axotomy to significant extents, while ATF3/KLF7/MEF2, KLF7 and ATF3, but not KLF7/MEF2 also induced apoptosis-related genes which may hinder regeneration. The TF combination KLF7/MEF2 partially mimics the conditioning lesion effect, inducing axonal sprouting into a dorsal column lesion and driving significant RAG expression, and also promotes functional improvement.
The Impact of Pharmacotherapy for Premenstrual Dysphoric Disorder on Sleep
Authors: Elisa M S Meth, Diana A Nôga, Manon Dubol, Pei Xue, Inger Sundström-Poromaa, Christian Benedict
Journal: Sleep Medicine Reviews (2025)

Premenstrual dysphoric disorder (PMDD) affects a subset of women of reproductive age, characterized by severe mood disturbances and physical symptoms during the luteal phase of the menstrual cycle. Symptoms include mood swings, irritability, anxiety, fatigue, physical discomfort, and disruptions to sleep and circadian rhythms, such as altered melatonin secretion. Despite the prevalence of these symptoms, the impact of PMDD treatments on sleep and circadian markers, like melatonin, remains insufficiently understood. This review examines how dysregulated serotonin signaling, disrupted allopregnanolone activity (a neurosteroid derived from progesterone), and aberrant circadian rhythms contribute to PMDD. It also explores the effects of pharmacological treatments, including selective serotonin reuptake inhibitors, on sleep and melatonin regulation, and how these factors influence treatment outcomes. Additionally, the use of hypnotics and sedatives to manage sleep disturbances in PMDD is considered, weighing their potential benefits and risks. A deeper understanding of the interaction between PMDD symptoms, sleep, and circadian rhythms is crucial for developing more effective treatments. Further research is needed to explore the relationship between symptom management, sleep patterns, and circadian function in PMDD, and to determine how these factors can be optimized to improve clinical outcomes and quality of life for women affected by the disorder.
FDG PET/CT in a Case of Marjolin Ulcer of the Scalp Over a Long-standing Burn Scar
Authors: Mehul Dulet, Sameer Taywade, Vikrant Verma, Rajesh Kumar
Journal: Clinical Nuclear Medicine (2025)

Abstract Marjolin ulcer is a malignant degeneration of previously injured skin, long-established scars, and wounds. This malignant transformation is most implicated in full-thickness burns; however, it may be associated with vaccination sites, pressure sores, venous stasis, and many other conditions causing chronic scar or wound formation. These lesions are aggressive and carry a poor prognosis. FDG PET/CT is an excellent diagnostic aid to differentiate these lesions from benign inflammation, to evaluate the primary malignant site and its extent and depth, and to evaluate metastasis. Metabolic activity has been noted to be significantly higher in Marjolin ulcer than in benign conditions.
68Ga-FAPI PET/CT in a Patient With Multiple Aneurysms Due to Idiopathic Hypereosinophilic Syndrome
Authors: Puhao Li, Juan Liang, Yue Chen, Haoyuan Ding
Journal: Clinical Nuclear Medicine (2025)

Abstract Idiopathic hypereosinophilic syndrome is a group of unexplained diseases characterized by a persistent increase in eosinophils with multiple organs damage. Herein, we describe the 68 Ga-FAPI PET/CT findings of idiopathic hypereosinophilic syndrome in a 56-year-old woman. 68 Ga-FAPI PET/CT showed multiple aneurysms with increased FAPI uptake. In addition, myocardial uptake of FAPI was observed.
Comparison oPf 68Ga-FAPI and 18F-FDG PET/CT Findings in Oncocytic and Conventional Subtypes of Pediatric Adrenocortical Carcinoma
Authors: Elnaz Jenabi, Hamidreza Amini, Bababk Nikkholgh, Ghasemali Divband
Journal: Clinical Nuclear Medicine (2025)

Adrenocortical carcinoma, a poor prognosis cancer with a low survival rate, is a rare pediatric malignancy. We performed 18F-FDG PET/CT and 68Ga-FAPI PET/CT imaging in 2 children with different subtypes of adrenocortical carcinoma and compared the findings. FAPI PET/CT revealed superior performance in patient with conventional subtype and in detecting skeletal lesions. However, the recurrent lesions in the surgical bed had higher FDG uptake in both patients.
Patients with PSOriasis and Suppurative Hidradenitis (PSO-SH) share genetic risk factors and are at risk of increased morbidity.
Authors: Antonia Wiala, Kareem G Elhage, Andrea Leung, Albert T Young, Mark Gregory, Indra Adrianto, Li Zhou, Qing-Sheng Mi, Sugandh Kumar, Faye Orcales, Samuel Yeroushalmi, Kathryn Haran, Jared Liu, Haley B Naik, Wilson Liao, Christian Posch
Journal: Journal of the American Academy of Dermatology (2025)
Reply to: “Optimizing Antiviral Prophylaxis Strategies: Insights and Reflections on a Real-World Study” and “Optimal Timing To Initiate Antiviral Prophylaxis of MTCT: More Required to Be Done”
Authors: Mingwang Shen, Shihao He, Naijuan Yao, Li Xie, Lei Zhang, Tianyan Chen
Journal: Journal of Hepatology (2025)
Microalgae-carrying nanomedicine for bioadhesive drug delivery for treating chemotherapy-induced intestinal injury treatment
Authors: Jie Chen, Bing Wang, Lan Shen, Yongzhuo Huang
Journal: Asian Journal of Pharmaceutical Sciences (2025)

Gastrointestinal tract toxicity represents a serious adverse effect of chemotherapy, leading to reduced quality of life and survival. For instance, irinotecan (CPT-11) usually causes severe gastrointestinal toxicity, with a lack of effective therapeutic interventions, making treatment often unsustainable. Therefore, development of an effective and safe therapy is crucial for improving chemotherapy efficacy and the patients' quality of life. In this work, we developed a novel approach involving the helical-shaped cyanobacterium microalgae, Spirulina platensis (SP), to carry the bornyl acetate (BA)-loaded chitosan nanoparticles to enhance drug retention in the small intestine. We demonstrated the protection effect of BA against chemotherapy-induced intestinal injury using an epithelial cell model. In a mouse model, orally administered BA-ChNPs@SP accumulated in the small intestine and attenuated inflammation by reducing dsDNA release and oxidative stress. This was concomitant with the restoration of the intestinal barrier and modulation of the immune microenvironment. This work suggests the promise of the microalgae-carrying nanomedicine strategy for treatment of intestinal diseases, emphasizing its potential in addressing chemotherapy-induced gastrointestinal complications.
Implantable devices for resected glioblastoma therapy
Authors: Xiaoyu Chang, Hui Guo, Yunqian Li, Jianxun Ding
Journal: Asian Journal of Pharmaceutical Sciences (2025)

Glioblastoma (GBM) is a highly infiltrative brain tumor. The treatment of GBM is challenging due to the existence of blood brain barrier, its highly invasive nature, and its heterogeneity. Given the limitations of conventional therapies, this Perspective explores the development trajectory of implantable devices, highlighting the advantages of current models. With the progression in research, these implantable devices certainly hold promising potential for GBM therapy.
Senescence as a Molecular Target in Skin Aging and Disease
Authors: Henriette Thau, Bastian P Gerjol, Katharina Hahn, Rosalie Wolff von Gudenberg, Leonard Knoedler, Kenneth Stallcup, Maximilian Y Emmert, Timo Buhl, Saranya P Wyles, Tamar Tchkonia, Stefan G Tullius, Jasper Iske
Journal: Ageing Research Reviews (2025)
Is NEWS2 the optimal evidence-based surveillance tool for all respiratory patients or does it just represent the beginning of an iterative development process?
Authors: Dominick Shaw, Andrew W Fogarty
Journal: Thorax (2025)

Medical practice is built on the foundations of evidence-based medicine. Hence, the more common the clinical intervention, the more comprehensive the evidence on which that intervention should be based. Although the widespread adoption of a national early warning score in the UK has led to improvements in the delivery of care, it should be considered as providing a foundation that can be refined and developed, and there is still a need for critical reflection and evaluation of early warning scores, particularly for individuals with chronic respiratory disease, in order to optimise patient monitoring, predict deterioration and guide intervention.
Dietary nitrate supplementation enhances exercise capacity in WHO Group 3 pulmonary hypertension: a double-blind, placebo-controlled, randomised crossover study (EDEN-OX2)
Authors: Abdullah S Alsulayyim, Ali M Alasmari, Laura C Price, Colm McCabe, Saeed M Alghamdi, Keir Elmslie James Philip, Sara C Buttery, Matthew J Pavitt, Michael I Polkey, Matthew J Rickman, Blerina Ahmetaj-Shala, Jane A Mitchell, Rami A Alyami, Nicholas S Hopkinson
Journal: Thorax (2025)

Dietary nitrate supplementation, which improves skeletal muscle oxygen utilisation, vascular endothelial function and exercise capacity in people with chronic obstructive pulmonary disease, may benefit other lung conditions. In a double-blind, placebo-controlled, crossover study, in 19 adults with Group 3 pulmonary hypertension who desaturated during exercise, 140 mL of nitrate-rich beetroot juice improved endurance shuttle walk time compared with nitrate-depleted beetroot juice placebo (median (IQR) ESWT NR-BRJ 197 (140–273) s vs PL-BRJ 174 (107–229) s; median difference (MD) (95% CI) 30 (6.19 to 91.07) s, p=0.0281), endothelial function, flow-mediated dilatation (+3.40±5.47% vs −1.33±4.78; MD (95% CI) 4.73 (1.44 to 8.02), p=0.007) and lowered mean arterial blood pressure (−3.9 (−7.4 to −0.4) mm Hg, p=0.028).
Adult asthma hospitalisations decreased markedly in Finland and Sweden between 2006 and 2022
Authors: Juho E Kivistö, Jennifer L P Protudjer, Sandra Ekstrom, Jussi Karjalainen, Heini Huhtala, Lauri Lehtimäki, Inger Kull
Journal: Thorax (2025)

A decreasing trend in asthma hospitalisations among Finnish and Swedish children has been reported. However, possible changes in asthma hospitalisations among adults are incompletely characterised. We aimed to investigate the incidence of adult asthma hospitalisations in Finland and Sweden from 2006 to 2022 using Finland's National Hospital Discharge Register and Sweden's National Patient Register. During the study period, the incidence of asthma hospitalisations decreased by 65.8% in Finland (from 84.9 to 29.0 per 100 000 person-years) and by 52.5% in Sweden (from 31.4 to 14.9 per 100 000 person-years). The incidences of asthma hospitalisations were distinctly higher in Finland compared with Sweden at the start of the study period but approached parity among both sexes.
A microbial metabolite inhibits the HIF-2α-ceramide pathway to mediate the beneficial effects of time-restricted feeding on MASH
Authors: Yi Zhang, Xuemei Wang, Jun Lin, Jia Liu, Kai Wang, Qixing Nie, Chuan Ye, Lulu Sun, Yanpeng Ma, Ruize Qu, Yuejian Mao, Xuguang Zhang, Hua Lu, Pengyan Xia, Dongyu Zhao, Guang Wang, Zhipeng Zhang, Wei Fu, Changtao Jiang, Yanli Pang
Journal: Cell Metabolism (2025)
Manganese Dioxide Coupled Metal-Organic Framework as Mitophagy Regulator Alleviates Periodontitis through SIRT1-FOXO3-BNIP3 Signaling Axis
Authors: Cheng Zhu, Kai Huang, Tiancheng Li, Yixin Li, Yu Jin, Ruomei Li, Zhiyu Zhu, Shengbing Yang, Lunguo Xia, Bing Fang
Journal: Biomaterials (2025)
Molecular landscape and therapeutic strategies in pediatric differentiated thyroid carcinoma
Authors: Adeline T Yang, Sin-ting Tiffany Lai, Theodore W Laetsch, Tricia Bhatti, Zubair Baloch, Lea F Surrey, Aime T Franco, Julio C Marques Ricarte-Filho, Sogol Mostoufi-Moab, N Scott Adzick, Ken Kazahaya, Andrew J Bauer
Journal: Endocrine Reviews (2025)

There has been significant progress in understanding the molecular landscape of pediatric differentiated thyroid carcinoma over the past two decades. Classification of pediatric differentiated thyroid carcinoma into three-tiers, RAS-like mutant, BRAF-mutant, and kinase-fusions, accurately reflects an increasing risk for invasive behavior, including regional and distant metastasis. In clinical practice, somatic oncogene testing for nodules with indeterminate cytology per the Bethesda System for Reporting Thyroid Cytopathology provides objective data to optimize surgical planning. In addition, knowledge of the somatic oncogene for widely invasive carcinomas allows for incorporation of oncogene-specific inhibitory therapy both in the adjuvant and neoadjuvant setting. In the present review, we review the risk factors, clinical presentation, and evaluation of pediatric DTC, highlighting the correlation among ultrasound features, cytology, and oncogenic driver of the tumor. We subsequently propose an integrated, multi-modal approach that can be used to improve diagnostic accuracy and reliability for pre-operative planning as well as identify and discuss which pediatric patients may benefit from systemic oral targeted therapy.