tbuckley/cabot-search huggingface dataset:
Analyzing Lognormal Data: A Nonmathematical Practical Guide
Authors: Harvey J Motulsky, Trajen Head, Paul B S Clarke
Journal: Pharmacological Reviews (2025)

Lognormal distributions are pervasive in pharmacology and elsewhere in biomedical science, arising naturally when biological effects multiply rather than add. Despite their ubiquity in pharmacological parameters (eg, EC50, IC50, Kd, and Km), lognormal distributions are often overlooked or misunderstood, leading to flawed data analysis. This largely nonmathematical review explains why lognormal distributions are common, how to recognize them, and how to analyze them appropriately. We show that many measured variables are lognormal. So are many derived parameters, particularly those defined as ratios of lognormal variables. Through examples and simulations accessible to working scientists, we demonstrate how misidentifying lognormal distributions as normal leads to reduced statistical power, unnecessarily large sample sizes, false identification of outliers, and inappropriate reporting of effects as differences rather than ratios. We challenge the common practice of using normality tests to decide how to analyze data, showing that many data sets pass both normality and lognormality tests, especially with small sample sizes. Instead, we advocate for assuming lognormality based on the nature of the variable. This review provides practical guidance on recognizing and presenting lognormal data, and comparing data sets sampled from lognormal distributions. Based on Monte Carlo simulations, we recommend the lognormal Welch's t test or nonparametric Brunner-Munzel test for comparing 2 unpaired groups, the lognormal ratio paired t test for paired comparisons, and lognormal ANOVA for ≥3 groups. By recognizing and properly handling lognormal distributions, pharmacologists can design more efficient experiments, obtain more reliable statistical inferences, and communicate their results more effectively. SIGNIFICANCE STATEMENT: Lognormal distributions are common in pharmacology and many scientific fields, but they are often misunderstood or overlooked. This review provides a detailed guide to recognizing and analyzing lognormal data, aiming to help pharmacologists perform more appropriate and more powerful statistical analyses, draw more meaningful conclusions from their data, and communicate their results more effectively.
International Union of Basic and Clinical Pharmacology: Fundamental Insights and Clinical Relevance Regarding the Carnitine Palmitoyltransferase Family of Enzymes
Authors: Rosalía Rodríguez-Rodríguez, Miguel Baena, Sebastián Zagmutt, West Kristian Paraiso, Ana Cristina Reguera, Rut Fadó, Núria Casals
Journal: Pharmacological Reviews (2025)

The carnitine palmitoyltransferases (CPTs) play a key role in controlling the oxidation of long-chain fatty acids and are potential therapeutic targets for diseases with a strong metabolic component, such as obesity, diabetes, and cancer. Four distinct proteins are CPT1A, CPT1B, CPT1C, and CPT2, differing in tissue expression and catalytic activity. CPT1s are finely regulated by malonyl-CoA, a metabolite whose intracellular levels reflect the cell's nutritional state. Although CPT1C does not exhibit significant catalytic activity, it is capable of modulating the functioning of other neuronal proteins. Structurally, all CPTs share a Y-shaped catalytic tunnel that allows the entry of 2 substrates and accommodation of the acyl group in a hydrophobic pocket. Several molecules targeting these enzymes have been described, some showing potential in normalizing blood glucose levels in diabetic patients, and others that, through a central mechanism, are anorexigenic and enhance energy expenditure. However, given the critical roles that CPTs play in certain tissues, such as the heart, liver, and brain, it is essential to fully understand the differences between the various isoforms. We analyze in detail the structure of these proteins, their cellular and physiological functions, and their potential as therapeutic targets in diseases such as obesity, diabetes, and cancer. We also describe drugs identified to date as having inhibitory or activating capabilities for these proteins. This knowledge will support the design of new drugs specific to each isoform, and the development of nanomedicines that can selectively target particular tissues or cells. SIGNIFICANCE STATEMENT: Carnitine palmitoyltransferase (CPT) proteins, as gatekeepers of fatty acid oxidation, have great potential as pharmacological targets to treat metabolic diseases like obesity, diabetes, and cancer. In recent years, significant progress has been made in understanding the 3-dimensional structure of CPTs and their pathophysiological functions. A deeper understanding of the differences between the various CPT family members will enable the design of selective drugs and therapeutic approaches with fewer side effects.
Trastuzumab rezetecan, a HER2-directed antibody–drug conjugate, in patients with advanced HER2-mutant non-small-cell lung cancer (HORIZON-Lung): phase 2 results from a multicentre, single-arm study
Authors: Ziming Li, Yan Wang, Yuping Sun, Linlin Wang, Xingya Li, Longhua Sun, Zhiyi He, Haiyan Yang, Yongsheng Wang, Qiming Wang, Zhengbo Song, Wei Hong, Yong Wang, Guohao Xia, Yan Yu, Min Peng, Yong Song, Donglin Wang, Rui Meng, Jian Fang, Yongzhong Luo, Wenhua Liang, Sheng Hu, Zhihui Wang, Ke Song, You Li, Lulu Yang, Wei Shi, Shun Lu
Journal: The Lancet Oncology (2025)
FDG PET/CT in ALK-positive Histiocytosis of the Nasal Cavity in a Pediatric Patient
Authors: Qing Chen, Lilan Fu, Guangxiu Guo, Aisheng Dong, Jia Guo
Journal: Clinical Nuclear Medicine (2025)

Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare newly recognized subtype of histiocytic neoplasms. The disease can involve multiple systems or single system. We present FDG PET/CT findings in a pediatric patient with ALK-positive histiocytosis isolated to the left nasal cavity. The nasal cavity tumor invaded the nasal septum, left nasal bone, and left ethmoid sinus and showed intense FDG activity with an SUV max of 9.9.
Cerebral Echinococcosis Mimicking Malignancy on 68Ga-FAPI PET/MR
Authors: Zhangyongxue Zhou, Yuhu Lv, Danzha Zheng, Xiaoli Lan, Chunxia Qin
Journal: Clinical Nuclear Medicine (2025)

A 52-year-old man presented with headache and dizziness. An MRI revealed a space-occupying lesion suspicious of a glioma. Subsequent 68 Ga-FAPI PET/MR showed increased uptake in the lesion located in the right parieto-occipito-temporal lobe (SUVmax 6.0). The intracranial mass was surgically resected, and the pathology confirmed the presence of hydatid cysts. It is important to note that the clinical manifestations of cerebral echinococcosis closely mimic those of brain tumors, necessitating careful differentiation and diagnosis.
A five-drug class model using routinely available clinical features to optimise prescribing in type 2 diabetes: a prediction model development and validation study
Authors: John M Dennis, Katherine G Young, Pedro Cardoso, Laura M Güdemann, Andrew P McGovern, Andrew Farmer, Rury R Holman, Naveed Sattar, Trevelyan J McKinley, Ewan R Pearson, Angus G Jones, Beverley M Shields, Andrew T Hattersley
Journal: The Lancet (2025)
Letter to the Editor: Mean arterial pressure as a complex treatment target in patients with cirrhosis and acute kidney injury
Authors: Filipe S. Cardoso
Journal: Hepatology (2025)

Curry Cabral Hospital, Nova Medical School, Lisbon, Portugal Correspondence Filipe S. Cardoso, Transplant Unit, Curry Cabral Hospital, R Beneficiência 8 1069-166 Lisbon, Portugal. Email: [email protected]
Axillary Skin Fibroblast Activation Protein Uptake After Chemo-immunotherapy on PET/CT and SPET/CT
Authors: Elisabetta Perrone, Kriti Ghai, Aleksandr Eismant, Maurizio Podda, Richard P. Baum
Journal: Clinical Nuclear Medicine (2025)

Fibroblast activation protein (FAP) uptake can occur in benign conditions in addition to malignancies. This case series presents the first evidence of diffuse FAP uptake in axillary skin on PET/CT and SPET/CT of 33 patients with progressive solid tumors, referred to peptide-targeted radionuclide therapy after failing prior chemotherapy and/or immunotherapy. Upon physical examination, no significant findings were observed in the axillary regions. We hypothesize that fibroblastic activation may involve sweat glands consequently to systemic therapy, although the reason why the axillary site is favored is not known. Being common in this clinical setting, proper interpretation of this sign is needed.
Assessment of liver injury potential of investigational medicines in drug development
Authors: Naga Chalasani, Paul H. Hayashi, Debra Luffer-Atlas, Arie Regev, Paul B. Watkins
Journal: Hepatology (2025)

Drug-induced liver injury (DILI) is rare in clinical practice but when it occurs it can lead to acute liver failure and death. Drug developers and regulators undertake a series of steps to identify the DILI potential of a medication before it is approved for marketing. Preclinical testing by drug developers typically involves a multitude of in vitro assays and in vivo animal experiments before a compound is moved into first-in-human phase 1 testing. Over the last two decades, there have been a number of advances in preclinical screening for DILI potential of a new chemical entity, but these approaches tend to be overly sensitive with insufficient positive predictive value. Once in clinical trials, the DILI potential of an investigational agent and risks to a participant are carefully managed through patient selection, DILI monitoring paradigms, and drug interruption and discontinuation criteria, in close concert with the regulators. Recent developments in Quantitative Systems Toxicology offer promising and complementary in silico approaches to predict the compound’s risk for DILI via multifaceted systems biology. When a drug developer submits a New Drug Application (NDA) for marketing approval, regulators review the preclinical and clinical trial data in a structured fashion to assess the DILI risk. While these approaches have been successful in dramatically reducing the marketing approval of medications eventually associated with hepatotoxicity, many challenges remain in identifying the risk for DILI during preclinical and early-to-late clinical development stages for genetic medicines, biological agents, and immunotherapies. In this review, we discuss current preclinical, in-silico, and clinical development approaches to screen for DILI potential of an investigational agent and provide a high-level description of regulators’ approach for assessing DILI risk in an NDA.
Artificial intelligence-enhanced electrocardiography for the identification of a sex-related cardiovascular risk continuum: a retrospective cohort study
Authors: Arunashis Sau, Ewa Sieliwonczyk, Konstantinos Patlatzoglou, Libor Pastika, Kathryn A McGurk, Antônio H Ribeiro, Antonio Luiz P Ribeiro, Jennifer E Ho, Nicholas S Peters, James S Ware, Upasana Tayal, Daniel B Kramer, Jonathan W Waks, Fu Siong Ng
Journal: The Lancet Digital Health (2025)
β-Catenin regulates distinct pathways from YAP and suppresses ONECUT1 to drive hepatoblastoma development in mice and humans
Authors: Weiting Liao, Yi Zhang, Jingxiao Wang, Guofei Cui, Matthias Evert, Meng Xu, Yanhui Wu, Xue Wang, Shanshan Deng, Xinhua Song, Satdarshan P. Monga, Jinqiu Zhao, Qiu Li, Diego F. Calvisi, Xin Chen
Journal: Hepatology (2025)

Background &amp; aims: Hepatoblastoma (HB) is the predominant primary malignant liver tumor in childhood. Concomitant YAP and β-Catenin activation occurs in most HB. However, the signaling pathways distinctively regulated by YAP and β-Catenin protooncogenes in HB remain unexplored. Approach and results: We engineered an inducible HB murine model using hydrodynamic injection to deliver transposon plasmids encoding constitutive YAP and doxycycline (Dox)-inducible ΔN90-β-Catenin(YAP/TRE-β-Catenin). Gene expression patterns in mouse HB lesions upon short-term Dox withdrawal, i.e., tumors still existed, but ΔN90-β-Catenin was turned OFF, were analyzed. Mice rapidly developed aggressive HB lesions when fed doxycycline. However, upon Dox withdrawal, HB regressed, although tumors did not completely disappear over a long time. At the molecular level, YAP and β-Catenin were found to regulate distinct gene expression programs in HB. Specifically, YAP controls the Hippo and metabolism-related pathways, whereas β-Catenin modulates immune-related pathways contributing to immune exclusion in the tumor microenvironment. Furthermore, we identified the transcription factor ONECUT1 as a tumor suppressor gene downregulated by activated β-Catenin in HB. Low ONECUT1 expression also characterizes human HB, and co-expression of ONECUT1 strongly suppressed YAP/β-Catenin-driven HB formation in mice. Mechanistically, ONECUT1 functions downstream of activated β-Catenin and negatively regulates tumor cell glycolysis. Conclusions: We show that suppressing activated β-Catenin could hamper HB progression in vivo by affecting pathways distinct from those regulated by YAP in HB. Inhibition of ONECUT1 expression by β-Catenin might represent a critical molecular event leading to HB formation.
Feeding dystonia, chorea, psychosis, and self-mutilation in an African patient with neuroacanthocytosis syndrome
Authors: Maouly Fall, Moussa Seck, Alassane Mamadou Diop, Jamil Kahwagi, Grace Tsemo Yimta, Allé Guéye, Pedro Rodriguez Cruz, Mie Rizig
Journal: The Lancet (2025)
Spatial single-cell proteomics landscape decodes the tumor microenvironmental ecosystem of intrahepatic cholangiocarcinoma
Authors: Libing Hong, Jie Mei, Xuqi Sun, Yifan Wu, Zhen Dong, Yuzhi Jin, Liaoliao Gao, Jinlin Cheng, Weihong Tian, Chuan Liu, Bin Li, Pingping Hu, Lulu Liu, Shan Xin, Xiaomeng Dai, Peng Zhao, Rongping Guo, Minshan Chen, Jingping Yun, Bo Lin, Wei Wei, Weijia Fang, Xuanwen Bao
Journal: Hepatology (2025)

Background &amp; Aims The prognoses and therapeutic responses of patients with intrahepatic cholangiocarcinoma (iCCA) depend on spatial interactions among tumor microenvironment (TME) components. However, the spatial TME characteristics of iCCA remain poorly understood. The aim of this study was to generate a comprehensive spatial atlas of iCCA using artificial intelligence-assisted spatial multiomics patterns and to identify spatial features associated with prognosis and immunotherapy. Approach &amp; Results: Spatial multiomics, including imaging mass cytometry (IMC, n=155 in-house), spatial proteomics (n=155 in-house), spatial transcriptomics (n=4 in-house), multiplex immunofluorescence (mIF, n=20 in-house), single-cell RNA sequencing (scRNA-seq, n=9 in-house and n=34 public), bulk RNA-seq (n=244 public), and bulk proteomics (n=110 in-house and n=214 public), were employed to elucidate the spatial TME of iCCA. More than 1.06 million cells were resolved, and the findings revealed that spatial topology, including cellular deposition patterns, cellular communities, and intercellular communications, profoundly correlates with the prognosis of iCCA patients. Specifically, CD163hi M2-like resident-tissue macrophages suppress anti-tumor immunity by directly interacting with CD8+ T cells, resulting in poorer patient survival. Additionally, five spatial subtypes with distinct prognoses were identified, and potential therapeutic options were generated for these subtypes. Furthermore, a spatial TME deep learning system was developed to predict the prognosis of iCCA patients with high accuracy from a single 1-mm 2 tumor sample. Conclusions: This study offers preliminary insights into the spatial TME ecosystem of iCCA, providing valuable foundations for precise patient classification and the development of personalized treatment strategies.
Proteomic organ-specific ageing signatures and 20-year risk of age-related diseases: the Whitehall II observational cohort study
Authors: Mika Kivimäki, Philipp Frank, Jaana Pentti, Markus Jokela, Solja T Nyberg, Acer Blake, Joni V Lindbohm, Hamilton Se-Hwee Oh, Archana Singh-Manoux, Tony Wyss-Coray, Linda Partridge
Journal: The Lancet Digital Health (2025)
SRChing for new targets in HCC
Authors: Michael T. Dill, Jan S. Tchorz
Journal: Hepatology (2025)

1Department of Gastroenterology, Hepatology, Infectious Diseases & Intoxications, Heidelberg University Hospital, Heidelberg, Germany 2German Cancer Research Center (DKFZ) Heidelberg, Experimental Hepatology, Inflammation and Cancer, Heidelberg, Germany 3Novartis Biomedical Research, Novartis Pharma AG, Basel, Switzerland Editorial for Hepatology – MS HEP-24-1802: Phosphoproteomics delineates hepatocellular carcinoma subtypes and pinpoints therapeutic targets Correspondence Michael T. Dill, University Hospital Heidelberg, Department of Gastroenterology and Hepatology. Email: [email protected] Jan S. Tchorz, Novartis Institutes for BioMedical Research Basel, Developmental and Molecular Pathways. Email: [email protected]
De novo basecalling of RNA modifications at single molecule and nucleotide resolution
Authors: Sonia Cruciani, Anna Delgado-Tejedor, Leszek P. Pryszcz, Rebeca Medina, Laia Llovera, Eva Maria Novoa
Journal: Genome biology (2025)

Abstract RNA modifications influence RNA function and fate, but detecting them in individual molecules remains challenging for most modifications. Here we present a novel methodology to generate training sets and build modification-aware basecalling models. Using this approach, we develop the m 6 ABasecaller , a basecalling model that predicts m 6 A modifications from raw nanopore signals. We validate its accuracy in vitro and in vivo, revealing stable m 6 A modification stoichiometry across isoforms, m 6 A co-occurrence within RNA molecules, and m 6 A-dependent effects on poly(A) tails. Finally, we demonstrate that our method generalizes to other RNA and DNA modifications, paving the path towards future efforts detecting other modifications.
Reply to Huang <i>et al.</i>: Sowing Tailored Seeds: Gene-edited Basal Cells for Precision Regulation of Airway Phenotypes
Authors: Andrew C. Berical, Hirofumi Kiyokawa, Mary Lou Beermann, Daniel Wallman, Gabrielle Cherfane, Victoria Dunphy, Jiehong Pan, Andrew Tilston-Lunel, Xaralabos Varelas, Amjad Horani, Steven L Brody, Darrell N Kotton, Finn J. Hawkins
Journal: American Journal of Respiratory and Critical Care Medicine (2025)
Synapsin III promotes neuronal-like transdifferentiation of glioblastoma stem cells by disrupting JAG1-Notch1 interaction
Authors: Yilin Deng, Zheng Yuan, Xiong Jin, Zekun Wang, Rui Gong, Shuai Ren, Jong Bae Park, Bingyang Shi, Jinlong Yin
Journal: Neuro-Oncology (2025)

Glioblastoma (GBM), a formidable and highly aggressive form of brain cancer, is predominantly driven by GBM stem cells (GSCs), which are characterized by their ability for self-renewal and aberrant differentiation. Targeting the terminal differentiation of GSCs represents a promising therapeutic strategy. This study aimed to elucidate the role of synapsin III (SYN3) in driving the differentiation of GSCs into neuron-like cells and its effect on the tumor-suppressive pathways in GBM. Proliferation assays, limited dilution assays, immunocytochemistry, western blot, RT-qPCR, and GSC tumor models were used to determine gene function and assess the role of γ-secretase inhibitors. Co-immunoprecipitation and microscale thermophoresis were conducted to explore the underlying regulatory mechanisms. Intracranial orthotopic injection of adeno-associated virus (AAV) was performed to evaluate therapeutic potential. We demonstrate that SYN3, uniquely within the synapsin family, acts as a tumor suppressor by steering GSCs toward neuronal-like transdifferentiation. Mechanistically, SYN3 enhances the expression of Neuregulin 3 (NRG3), which serves as a non-canonical antagonist of Notch signaling by competitively binding to specific epitopes within the EGF-like domain of JAG1, a critical site for the canonical engagement of Notch receptors. This critical interaction disrupts the JAG1-Notch1 signaling pathway, a key mechanism driving GSCs toward neuronal-like transdifferentiation, thereby reducing their stemness. Furthermore, SYN3 demonstrated significant antineoplastic activity in a mouse model harboring GSCs. AAV-mediated overexpression of SYN3 markedly impeded GBM progression. Our research reveals the therapeutic potential of SYN3 in regulating GSC fate and offers a novel differentiation-based approach for GBM therapy.
Intermuscular Fat and Physical Activity Levels Relative to Exercise Capacity Change During Breast Cancer Treatment
Authors: Lauren Daniel, Moriah P Bellissimo, Ralph B D'Agostino, Kristine C Olson, Amy C Ladd, Kerryn W Reding, Kathryn E Weaver, Glenn J Lesser, Bonnie Ky, W Gregory Hundley
Journal: JACC CardioOncology (2025)
Increased Uptake of 68Ga-DOTA-IBA in Lymph Node Metastases of Prostate Cancer
Authors: Na Zhang, Linwei Li, Qiang Han, Yan Zhu, Yue Chen
Journal: Clinical Nuclear Medicine (2025)

A 61-year-old man with prostate cancer underwent 68 Ga-labeled DOTA-ibandronic acid ( 68 Ga-DOTA-IBA) PET/CT scan. The examination showed no bone metastases. Incidentally, uptake of 68 Ga-DOTA-IBA increased in the lymph node metastases of the left neck.
Publisher Correction: The glucose transporter 2 regulates CD8+ T cell function via environment sensing
Authors: Hongmei Fu, Juho Vuononvirta, Silvia Fanti, Fabrizia Bonacina, Antonio D’Amati, Guosu Wang, Thanushiyan Poobalasingam, Maria Fankhaenel, Davide Lucchesi, Rachel Coleby, David Tarussio, Bernard Thorens, Robert J. Hearnden, M. Paula Longhi, Paul Grevitt, Madeeha H. Sheikh, Egle Solito, Susana A. Godinho, Michele Bombardieri, David M. Smith, Dianne Cooper, Asif J. Iqbal, Jeffrey C. Rathmell, Samuel Schaefer, Valle Morales, Katiuscia Bianchi, Giuseppe Danilo Norata, Federica M. Marelli-Berg
Journal: Nature Metabolism (2025)
Indole derivatives ameliorated the methamphetamine-induced depression and anxiety via aryl hydrocarbon receptor along “microbiota-brain” axis
Authors: Xi Wang, Miaoyang Hu, Weilan Wu, Xinyu Lou, Rong Gao, Tengfei Ma, S Thameem Dheen, Jie Cheng, Jianping Xiong, Xufeng Chen, Jun Wang
Journal: Gut Microbes (2025)

In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.