tbuckley/cabot-search huggingface dataset:
How to approach a patient hospitalized for pneumonia who is not responding to treatment?
Authors: Pedro Povoa, Luís Coelho, Jordi Carratala, Kelly Cawcutt, Sara E Cosgrove, Ricard Ferrer, Carlos A Gomez, Michael Klompas, Thiago Lisboa, Ignacio Martin-Loeches, Saad Nseir, Jorge I F Salluh, Sias Scherger, Daniel A Sweeney, Andre C Kalil
Journal: Intensive Care Medicine (2025)

Pneumonia is a frequent cause of intensive care unit (ICU) admission and is the most common infection in ICU patients across all geographic regions. It takes 48-72h for most patients to respond to appropriate antibiotic therapy. Non-response is typically defined as the persistence/worsening of clinical signs-such as fever, respiratory distress, impaired oxygenation and/or radiographic abnormalities-with rates ranging 20-30%. Several factors can contribute to non-response. Host factors, including immunosuppression, chronic lung disease, or ongoing aspiration, may impair resolution. Additionally, incorrect antibiotic dosing, atypical or resistant pathogens (such as multidrug-resistant bacteria, Mycobacterium tuberculosis, or fungal infections) may be responsible, requiring alternative antimicrobial strategies. A septic complication related to pneumonia (e.g., empyema) or not (e.g., acalculous cholecystitis) may need to be excluded. Finally, non-infectious conditions (e.g., pulmonary embolism, malignancy, secondary ARDS or vasculitis) that can mimic or potentiate pneumonia must be considered. Although non-responding pneumonia is frequent, its management lacks strong evidence, and its approach is based mostly on the art of medicine and clinical judgement. Clinicians should continuously reassess the medical history and physical exam, review microbiological data, and consider imaging such as chest CT. Bronchoscopy or repeat sputum sampling may aid in identifying alternative pathogens or non-infectious causes. The management of a non-responding pneumonia depends on the findings of a structured reassessment. Herein, we provide guidance on how to identify and manage non-responding pneumonia. Ultimately, addressing pneumonia that does not respond to antibiotics is crucial for preventing complications, optimizing antimicrobial stewardship, and improving patient outcomes.
GBRAP: A Comprehensive Database and Tool for Exploring Genomic Diversity Across All Domains of Life
Authors: Sachithra Kalhari Yaddehige, Chiara Vischioni, Michele Berselli, Leonardo Alberghini, Massimo Mezzavilla, Tania Bobbo, Cristian Taccioli
Journal: Molecular Biology and Evolution (2025)

Abstract Evolutionary studies require extensive examination of genomic information across all domains of life. Despite the availability of a large number of genomes through GenBank, the effective visualisation or comparison of the information they contain is challenging due to many reasons, including their size. We introduce GBRAP, a comprehensive software tool to analyse genome files, and an online database housing an extensive collection of carefully curated, high-quality genome statistics for all the organisms available in the RefSeq database of NCBI. Users can either directly search, or select from pre-categorized groups, the organisms of their choice and retrieve data, the output is generated as tables containing more than 200 columns of useful genomic information (Base counts, GC content, Shannon Entropy, Codon Usage etc.) separately calculated for different genomic elements (eg. CDS, Introns, tRNA, rRNA, ncRNA, etc.). The data are independently displayed (if applicable) for each chromosomal, mitochondrial, plastid, or plasmid sequence. All the data can be visualised on the database or downloaded as CSV or Excel files. The GBRAP database is free to access without any registration and is publicly available at http://tacclab.org/gbrap/
The fire ant social chromosome exerts a major influence on genome regulation
Authors: Beryl M Jones, Alex H Waugh, Michael A Catto, Sasha Kay, Karl M Glastad, Michael A D Goodisman, Sarah D Kocher, Brendan G Hunt
Journal: Molecular Biology and Evolution (2025)

Abstract Supergenes underlying complex trait polymorphisms ensure sets of coadapted alleles remain genetically linked. Despite their prevalence in nature, the mechanisms of supergene effects on genome regulation are poorly understood. In the fire ant Solenopsis invicta, a supergene containing over 500 individual genes influences trait variation in multiple castes to collectively underpin a colony level social polymorphism. Here, we present results of an integrative investigation of supergene effects on gene regulation. We present analyses of ATAC-seq data to investigate variation in chromatin accessibility by supergene genotype and STARR-seq data to characterize enhancer activity by supergene haplotype. Integration with gene co-expression analyses, newly mapped intact transposable elements (TEs), and previously identified copy number variants (CNVs), collectively reveal widespread effects of the supergene on chromatin structure, gene transcription, and regulatory element activity, with a genome-wide bias for open chromatin and increased expression in the presence of the derived supergene haplotype, particularly in regions that harbor intact TEs. Integrated consideration of CNVs and regulatory element divergence suggests each evolved in concert to shape the expression of supergene encoded factors, including several transcription factors that may directly contribute to the trans-regulatory footprint of a heteromorphic social chromosome. Overall, we show how genome structure in the form of a supergene has wide-reaching effects on gene regulation and gene expression.
Genotype‐guided cardiac device intervention in <scp><i>LMNA</i></scp>‐related cardiac conduction disorder: The need for timely genetic testing
Authors: Shunsuke Inoue, Zhehao Dai, Tsukasa Oshima, Seitaro Nomura, Takashi Hiruma, Ryo Abe, Kanna Fujita, Manami Katoh, Toshiyuki Ko, Yu Shimizu, Masamichi Ito, Kenichiro Yamagata, Junichi Ishida, Eisuke Amiya, Masaru Hatano, Norifumi Takeda, Hiroyuki Morita, Katsuhito Fujiu, Norihiko Takeda, Issei Komuro
Journal: European Journal of Heart Failure (2025)

Sudden cardiac death is a catastrophic event, making its prevention important. However, patient selection for primary prevention remains controversial. We report two cases of cardiac conduction disorder initially treated with permanent pacemaker implantation. Genetic testing later revealed novel pathogenic variants in LMNA , leading to an upgrade to implantable cardioverter‐defibrillator for primary prevention of sudden cardiac death. These cases highlight the importance of early genetic analysis to guide optimal device therapy. The delay in obtaining genetic results necessitated reoperation, underscoring the need for preceding genomic sequencing and physician awareness to improve clinical decision‐making and patient outcomes.
Longitudinal blood pressure and cardiovascular outcomes in heart failure: An individual patient data pooling analysis of clinical trials
Authors: Jing‐Wei Li, Jiang Wang, Yunlong Chen, Hao Yang, Yi Wang, Xia Wang, Jingjng Xiao, Ying Wang, Dehui Qian, Shiyong Yu, Xiaohui Zhao, Hu Tan, Jun Jin, Xin Du, Craig S. Anderson
Journal: European Journal of Heart Failure (2025)
A Clinical Pharmacological Perspective on Intraperitoneal Chemotherapy
Authors: Pascale C S Rietveld, Niels A D Guchelaar, Sebastiaan D T Sassen, Birgit C P Koch, Ron H J Mathijssen, Stijn L W Koolen
Journal: Drugs (2025)

Peritoneal metastases (PM), frequently observed in malignancies such as ovarian, colorectal, pancreatic, and gastric cancers, present a significant therapeutic challenge due to poor prognosis and limited effectiveness to systemic chemotherapy. The peritoneal-plasma barrier reduces effective drug transfer from plasma to the peritoneal cavity, reducing cytotoxic effects on PM. Intraperitoneal (IP) chemotherapy offers a locoregional approach, enabling high local drug concentrations that can enhance therapeutic efficacy while limiting systemic toxicity. The three major methods for IP administration-hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), and catheter-based IP (CBIP) chemotherapy-each provide unique pharmacokinetic (PK) advantages for PM treatment. This review provides a comprehensive update on the pharmacological rationale of IP chemotherapy, focusing on drug characteristics that support extended IP retention and effective tumor targeting. The effects of administration variables are discussed, highlighting their role in optimizing IP drug exposure. Additionally, recent PK data on commonly used drugs in IP therapy, including platinum-based agents, taxanes, and novel nanoparticle formulations, will be evaluated. While PK rationale supports the administration of IP chemotherapy, further efficacy results from ongoing clinical trials are still awaited. Innovations in nanoparticle-based formulations and controlled-release systems offer substantial potential for improving both drug retention and targeted delivery, enhancing treatment precision and minimizing systemic toxicity. Continued exploration in these areas, along with optimization of IP administration protocols, is vital for advancing patient outcomes, refining therapeutic strategies, and maximizing the benefits of IP chemotherapy in clinical practice.
Enhanced staging of renal cell carcinoma using tumor morphology features: model development and multi-source validation
Authors: Enyu Yuan, Yuntian Chen, Lei Ye, Ben He, ChunLei He, Junchao Ma, Ting Yang, Hao Zeng, Ling Yang, Jin Yao, Bin Song
Journal: npj Digital Medicine (2025)

Preoperative detection of pT3a invasion in non-metastatic renal cell carcinoma (RCC) remains challenging with CT. This study developed and validated radiomic models using preoperative CT to identify pT3a invasions. Six models were trained and internally validated via nested cross-validation on 999 patients from one hospital. External validation included 313 patients from two hospitals and 204 patients from four TCIA datasets. A multi-reader multi-case study with seven radiologists evaluated the model's incremental value. The morphology model achieved the highest internal AUC (0.867, 95% CI: 0.866-0.869) and maintained performance in external validations (AUC = 0.895 and 0.842). When used as a second reader, it significantly improved junior radiologists' sensitivity and discrimination (AUC: 0.790 vs. 0.831, p < 0.001) without compromising specificity. This study demonstrates that CT-based radiomic models, particularly the morphology model, can reliably detect pT3a invasion and enhance diagnostic accuracy for junior radiologists, offering potential clinical utility in preoperative staging.
Multi-modality imaging for precise intra-arterial delivery of mRNA, AAVs, and antibodies to the head and neck area in mice
Authors: Chengyan Chu, Guanda Qiao, Shriya Madan, Lucia Fadon-Padilla, Jinghui Wang, Abdallah Salemdawod, Shalini Sharma, David Gulisashvili, Lorrisa McDougall, Yajie Liang, Miroslaw Janowski, Piotr Walczak
Journal: Journal of Controlled Release (2025)
Safety and Sample Adequacy for Comprehensive Biomarker Testing of Bronchoscopic Biopsies: An American Association of Bronchology and Interventional Pulmonology (AABIP) and International Association for the Study of Lung Cancer (IASLC) Clinical Practice Guideline
Authors: Udit Chaddha, Abhinav Agrawal, Uzair Ghori, Fayez Kheir, Labib Debiane, Annette McWilliams, George Cheng, Haval Balata, Kwun M Fong, Witold Rzyman, Anant Mohan, Natthaya Triphuridet, Stephen Lam, Junichi Soh, David Yankelevitz, David Cl Lam, Mary Beth Beasley, Marjolein Heuvelmans, Dawei Yang, Rudolf M Huber, Antoni Rosell Gratacos, Lucia Viola, Long Jiang, Septimiu Murgu
Journal: Journal of Thoracic Oncology (2025)
Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous Non–Small-Cell Lung Cancer: Phase 3 LEAP-006 Study
Authors: Roy S Herbst, Byoung Chul Cho, Caicun Zhou, Mauricio Burotto, Manuel Cobo Dols, Mehmet A N Sendur, Vladimir Moiseyenko, Ignacio Casarini, Makoto Nishio, Rina Hui, Elvire Pons-Tostivint, Julia Dudnik, Samreen Ahmed, Chinyere E Okpara, Corina Dutcus, Lina Yin, Yiwen Luo, Diana Chirovsky, Niyati Bhagwati, Delvys Rodriguez Abreu
Journal: Journal of Thoracic Oncology (2025)
Biomimetic Transformation of Inferior Parenchyma Cellulose into a Sustainable, Functional Medical Hydrogel Inspired by the Dermis
Authors: Ze Chen, Tian Si, Xin Gao, Keli Chen, Zhe Yu, Yuting Zhang, Lincai Peng, Jie Shang, Heng Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract Inevitable daily damage to skin necessitates advanced occlusive dressings to mitigate infections and accelerate regeneration. Biomacromolecule‐based hydrogels serve as sustainable alternatives to synthetic polymers, facing challenges in achieving multifunctional integration. To address this issue, a novel multifunctional biomass‐derived hydrogel is developed which exhibits characteristics such as stretchability, adhesiveness, moisture absorption capacity, drug loading/sustained release, and antibacterial properties. The gel is developed through synergistic interactions among bamboo‐derived regenerated cellulose (RC), carboxylated β‐cyclodextrin (Hβ‐CD), silanized liquid metal nanodroplets (SLM NDs), and pectin. This composite forms a 3D network stabilized by hydrogen, ionic, and amide bonds, exhibiting exceptional stretchability (247.7%), adhesiveness (7.81–23.97 kPa), and toughness (4.47 MJ m −3 ). Its microporous structure efficiently absorbs wound exudates; while, maintaining an optimal healing microenvironment. Host–guest interactions between Hβ‐CD and benzalkonium chloride (BKC) enhance drug‐loading capacity, achieving 78.8% sustained release. Antibacterial assays demonstrate inhibition zones against E. coli (20.07 ± 1.57 mm) and S. aureus (32.21 ± 0.34 mm). In vivo studies reveal 75% wound closure rate within 10 days. SLM NDs enable dynamic reversible bonds for mechanical adaptability; while, pectin reinforces bioadhesion and structural integrity. These properties make this hydrogel a promising candidate for clinical wound care, offering significant potential for medical applications.
Direct Surface Modification of the Epidermis Using Mussel‐Inspired Polydopamine with Multiple Anti‐Biofouling Functions
Authors: Su Eon Lee, Hanna Lee, Jang Hwan Kim, Sungwook Park, Young Taek Oh, Hayoung Choi, Jeong‐Min Kim, Hye‐Jun Jo, Jun Hyun Park, Ho Jun Jin, Kwan Hyi Lee, Seung Ho Han, Hojun Kim, Jun Kyun Oh, Bong Hoon Kim
Journal: Advanced Healthcare Materials (2025)

Abstract The surface properties of the epidermis are crucial in pathogen adhesion and proliferation. Moreover, damage to the epidermis caused by various physical and chemical attacks provides a favorable environment for pathogen penetration and proliferation through the exposed internal living tissue. Surface modification of the epidermis to impart anti‐biofouling properties can provide effective protection against infections. In this study, a facile method of imparting multiple anti‐biofouling functions by directly modifying the epidermal surface of an organism using dopamine, which is a mussel‐inspired substance, is introduced. Biocompatible polydopamine (PDA) is uniformly applied to organic surfaces with diverse morphological features and surface energies, indicating its versatility. In addition, the reliability of epidermal modification with PDA is confirmed via the PDA‐induced prevention of chronic changes in the impedance of the epidermis. Critically, the PDA‐modified epidermis exhibited various anti‐biofouling functions, including antibacterial and anti‐adsorption properties against bacteria and cellular/noncellular microorganisms, respectively. Improved antibacterial properties are successfully realized via integration with tobramycin, which is a representative antibiotic. Direct surface modification using PDA offers an innovative approach to safeguard biological surfaces, particularly the human epidermis, against various pathogens, with potential for application in medical patches and skin‐attached devices.
Membrane Intercalation of a Conjugated Oligoelectrolyte Photosensitizer Enables Efficient Anticancer Photodynamic Therapy
Authors: Samuel Jun Wei Chan, Zhaolin Xiao, Wilson Wee Mia Soh, Ji‐Yu Zhu, Fernando Lopez‐Garcia, Hui Deng, Guillermo Carlos Bazan
Journal: Advanced Healthcare Materials (2025)

Abstract Photodynamic therapy (PDT) complements traditional chemotherapeutic methods by leveraging an external optical stimulus to target and eradicate tumor cells. Photosensitizers with favorable photophysical properties are, however, often hampered by poor biodistribution and inadequate cellular uptake, highlighting the need for novel molecular design strategies. Conjugated oligoelectrolytes (COEs) are a class of optical reporters that readily incorporate within cells due to their lipid bilayer mimicking molecular topology. Herein, a COE‐derived photosensitizer, COE‐PP, which features a central porphyrin core flanked by ionic pendant groups is disclosed. COE‐PP has a solubility in aqueous media of &gt;20 m m , yet the membrane‐mimicking molecular topology enables high cellular uptake and prolonged retention of the COE in vitro and in vivo of up to 21 days. COE‐PP is an effective phototheranostic agent for simultaneous tumor imaging and eradication, with the generation of reactive oxygen species (ROS) upon illumination. The membrane localization of COE‐PP promotes cell death during PDT by ROS and through downstream pathways involving lysosomal membrane permeabilization. These synergistic effects enable effective treatment of COE‐containing tumors. From a broad design perspective, the molecular architecture of COE‐PP demonstrates the potential of utilizing lipid bilayer‐mimicking molecular topologies to design phototheranostic molecules that offer spatiotemporal control for therapeutic interventions.
A Handheld Saliva Analyzer Employing Homogeneous Nanogrid Film for Noninvasive on‐Site Detection Periodontitis and Salivary Gland Tumor
Authors: Heng Dong, Jing Zhang, Tao Liu, Xiaoye Li, Xueli Yuan, Ao He, Qiang Li, Yu Zhang, Weijun Xiu, Zhenyu Chu, Yongbin Mou, Wanqin Jin
Journal: Advanced Healthcare Materials (2025)

Abstract Saliva is a non‐invasive, easily collected fluid ideal for health monitoring, but its ultralow metabolite concentrations make accurate detection challenging for current analytical tools, limiting its clinical diagnostic use. Here, a homogeneous nanogrid film composed of Prussian blue/Au nanogrid (PB/AuNG) to fabricate salivary biosensors for diagnosing oral diseases is fabricated. The PB/AuNG nanogrid film allows for the uniform immobilization of oxidase enzymes or antibodies, thereby substantially enhancing the detection sensitivity for trace salivary biomarkers. Then it is designed biosensing chips modified with PB/AuNG to respectively detect the lactate (potential biomarkers of periodontitis) and interleukin (IL)‐6 (potential biomarkers of salivary gland tumor). The microchips have achieved the ultra‐low limit of 6.5 µM to lactate within 5 s and 0.14 fg mL −1 to IL‐6 within 20 min. After comprehensive performance evaluation and feasibility validation, a handheld saliva analyzer integrated with PB/AuNG‐based microchips for portable, non‐hospital‐based monitoring is developed. The device is subsequently employed to analyze real saliva samples from periodontitis and salivary gland tumor patients, successfully distinguishing between the two groups based on differences in lactate and IL‐6 concentrations. This study presents a diagnostic platform for early detection of saliva metabolites, aiming to promote proactive, personalized health management.
Silicon Nanowire Mats Enable Advanced Bioelectrical Recordings in Primary DRG Cell Cultures
Authors: Ivano Lucarini, Francesco Maita, Giorgia Conte, Emanuela Saracino, Francesco Formaggio, Elena Palmieri, Roberta Fabbri, Aikaterini Konstantoulaki, Chiara Lazzarini, Marco Caprini, Valentina Benfenati, Luca Maiolo, Annalisa Convertino
Journal: Advanced Healthcare Materials (2025)

Abstract Primary dorsal root ganglion (DRG) cell cultures provide a valuable model for studying in vitro sensory transduction, neuropathies, and chronic pain, as they replicate the in vivo heterogeneity of DRG neurons and non‐neuronal cells. However, traditional patch‐clamp techniques are invasive and cannot capture the collective cell dynamics. While planar multielectrode arrays (MEAs) offer a non‐invasive alternative, they suffer from poor cell‐electrode coupling and limited resolution for identifying specific DRG neuronal types like C‐fiber nociceptors, key targets in chronic pain research. This work demonstrates that silicon nanowire (SiNW) mat‐based MEAs, while maintaining their reduced invasiveness, enable continuous intracellular recordings from neurons in primary rat DRG cell cultures. Supported by a cortical astrocyte feeder layer, SiNW mats promote DRG neuron and glial cell growth preserving cells’ in vivo morphological and functional characteristics. Integrated into a compartmentalized MEA, they enable reliable recordings of drug‐modulated neuronal activity alongside a baseline related to the astrocyte layer. The recorded signals exhibit characteristics of intracellular action potentials, suggesting spontaneous intracellular access by SiNWs. Distinct electrophysiological signatures allow identifying C‐fiber nociceptors, as confirmed by patch‐clamp measurements. This platform represents a powerful tool for investigating in vitro pain mechanisms, with potential applications in preclinical pain research and pharmacological translational studies.
Nanocatalytic Therapy for Pneumonia by a Hetero‐Element‐Doped Carbon Nanozyme
Authors: Min Zhou, Minxuan Zhang, Jiayuan Feng, Fuying Zhu, Tong Li, Qi Mei, Gen Wei, Hui Wei
Journal: Advanced Healthcare Materials (2025)

Abstract Pneumonia continues to be complicated by its progression to acute lung injury (ALI). The onset of ALI is linked to an overproduction of reactive oxygen species (ROS) and a severe inflammatory response. Therefore, the rapid mitigation of ROS and inflammation is crucial in addressing ALI. Concurrently, prompt bacterial elimination is necessary for bacteria‐induced ALI. Here, a Co‐based carbon nanozyme (CN) with enhanced enzyme‐like activities is developed by co‐doping with a small amount of Mn (CoMn CN). Compared to cobalt CN without Mn co‐doping (Co CN), the active sites of Co and its coordination with N in CoMn CN are slightly altered, resulting in enhanced oxidase (OXD)‐, peroxidase (POD)‐, superoxide dismutase (SOD)‐, and catalase (CAT)‐like activities. Given the enhanced enzyme‐like activities, its applications for lipopolysaccharide (LPS)‐ and methicillin‐resistant Staphylococcus aureus (MRSA)‐induced ALI treatments are explored. CoMn CN demonstrates superior efficacy in both LPS‐ and MRSA‐induced ALI models, effectively combining rapid scavenging of ROS and inflammation with subsequently bacterial elimination. Consequently, a novel type of Co‐based CN by Mn co‐doping is developed to augment enzyme‐like activities, offering significant protective effects against ALI. This study not only broadens the application of Co‐based CNs but also shows a promising strategy for ALI therapy.