tbuckley/cabot-search huggingface dataset:
Nanomedicine for targeting brain Neurodegeneration: Critical barriers and circadian rhythm Considerations
Authors: Laura Pineiro-Alonso, Inés Rubio-Prego, Alexandra Lobyntseva, Eva González-Freire, Robert Langer, María José Alonso
Journal: Advanced Drug Delivery Reviews (2025)

The development of novel therapies for central nervous system (CNS) diseases, particularly neurodegenerative disorders like Alzheimer's disease (AD), is a critical global health priority. Biotherapeutics, such as monoclonal antibodies (mAbs) and RNA-based therapies, have shown potential for treating brain disorders. However, their clinical progress is limited by their difficult access to their brain targets. At the preclinical level, nanotechnology has been shown, to help these molecules overcome the biological barriers that imped their adequate brain delivery. This review highlights advances in this area and the challenges for the translation to the clinic. Key nanotechnology-based strategies, such as surface modifications utilizing endogenous protein corona, functionalization with targeting ligands, therapeutic ultrasound-mediated microbubble oscillation were particularly analyzed. Additionally, in line with the focus of the Special Issue, this review integrates the concept of chronotherapy, with a focus on AD treatment, highlighting the idea that, by aligning nanoparticle (NP)-based drug delivery with circadian rhythms, it may be possible to improve therapeutic outcomes. Finally, the article analyzes current strategies in CNS drug delivery in clinical trials and provides future directions within this frame, notably in the area of AD.
Enhanced metastatic risk stratification for Cutaneous Squamous Cell Carcinoma by combining clinical guidelines with the Erasmus MC model: Results from Two Nationwide Nested Case-Control Studies
Authors: O F M Steijlen, L Pozza, J J H Traets, B Rentroia-Pacheco, C J Eggermont, D Bellomo, S Alex, V A Patel, A L Mooyaart, L M Hollestein, M Wakkee
Journal: Journal of the American Academy of Dermatology (2025)

Reliably assessing metastatic risk in cutaneous squamous cell carcinoma (CSCC) remains clinically challenging despite established guidelines. To assess whether a clinicopathological risk prediction model (Erasmus MC model) can enhance the identification of high-risk metastatic patients within current European and National Comprehensive Cancer Network (NCCN) guidelines for CSCC. A Dutch nested case-control (NCC) cohort (n=390 derived from N=12,325), was first stratified by guideline-defined risk groups. Each high-risk group was further stratified using thresholds for the risk estimated by the Erasmus MC model. The performance was assessed in an independent English NCC cohort (n=696, derived from N=31,981). The European guideline-defined high-risk group had a 3-year metastatic risk of 3.8% (95% CI 2.4%-5.2%). Within this group, 18.2% of the patients were identified with a higher 3-year risk of 10.1% (95% CI 6.7%-13.5%). For the NCCN-defined very high-risk group, the overall 3-year risk was 7.4% (95% CI 2.0%-9.2%). Of these, 34.5% of the patients had an even greater risk, of 14.0% (95% CI 8.3%-19.6%) LIMITATIONS: Routinely collected healthcare data often lacks detailed clinical information. The Erasmus MC model improves metastatic risk stratification by identifying higher risk groups within the frameworks of current European and NCCN CSCC guidelines.
Cannabinoid WIN55,212-2 restores bronchial epithelium by regulating oxidative stress and STAT6 phosphorylation
Authors: Mario Pérez-Diego, Alba Angelina, Yağız Pat, Angel Maldonado, Carmen Sevilla-Ortega, Leticia Martín-Cruz, Duygu Yazici, Beate Rückert, Milena Sokolowska, Mar Martín-Fontecha, Mübeccel Akdis, Cezmi A Akdis, Oscar Palomares
Journal: Journal of Allergy and Clinical Immunology (2025)

Viral infections and type 2 immune responses perpetuate airway epithelial barrier dysfunction and inflammation, leading to the development and progression of asthma. The synthetic cannabinoid WIN55,212-2 displays anti-inflammatory properties by acting on different immune system cells. To investigate the capacity of WIN55,212-2 to restore bronchial epithelial barrier function in asthma in the context of viral infections or type 2-driven inflammation. Air-liquid-interface (ALI) cultures of human bronchial epithelial cells and human bronchial epithelial spheroids were generated to assess the capacity of WIN55,212-2 to restore airway epithelial barrier damage induced by human rhinovirus A16 (RV-A16) infection or type 2 inflammation. RT-PCR, cytokine quantification, permeability assays, metabolic studies, flow cytometry and western blot techniques were employed to assess the effects of WIN55,212-2 on the airway epithelium. The in vivo relevance of our findings was evaluated in a murine model of IL-13-induced airway inflammation. Prophylactic and therapeutic administration of WIN55,212-2 accelerated the recovery from RV-A16-induced bronchial epithelial barrier damage. WIN55,212-2 inhibited the acquisition of IL-13-induced type 2 asthma features in ALI cultures, self-assembled bronchial epithelial spheroids and in vivo asthma model of airway inflammation and epithelial dysfunction. Mechanistically, WIN55,212-2 impaired IL-13-induced oxidative stress in epithelial cells restoring the activity of protein tyrosine phosphatases, which in turn inhibits pSTAT6-mediated signaling pathways and asthma features. The cannabinoid WIN55,212-2 displays airway epithelial barrier protective effects during RV-A16 infection or type 2 inflammation by mechanisms associated to the modulation of oxidative metabolism and pSTAT6-mediated signaling.
One-Hour Plasma Glucose Predicts the Progression From Normal Glucose Tolerance to Prediabetes
Authors: Muhammad Abdul-Ghani, Mohamed Abu-Farha, Tamam Abdul-Ghani, Alberto Chavez-Velazquez, Auora Merovci, Ralph A. DeFronzo, Fahad Alajmi, Michael Stern, Fahd Al-Mulla
Journal: Diabetes Care (2025)

OBJECTIVE To examine the ability of the 1-h plasma glucose (PG) concentration during the oral glucose tolerance test (OGTT) to predict the risk of progression to prediabetes in individuals with normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS A total of 1,557 participants from the San Antonio Heart Study who were free of type 2 diabetes at baseline, had a baseline OGTT, and had a repeat OGTT after 7.5 years of follow-up were evaluated. The ability of 1-h PG concentration to predict the development of prediabetes, based on American Diabetes Association criteria, was evaluated. RESULTS Approximately one-quarter of participants with NGT (24.7%) progressed to prediabetes at 7.5 years (22.5% with 1-h PG &amp;lt;155 mg/dL and 42.5% with 1-h PG &amp;gt;155 mg/dL). The 1-h PG was the strongest predictor of developing prediabetes, and a 1-h cut point of 120 mg/dL had 61% sensitivity and 67% specificity in identifying individuals with NGT at high risk of developing prediabetes. Participants with a 1-h PG of 120–155 mg/dL and who experienced a deterioration in glucose tolerance (progression to prediabetes) at follow-up were characterized by severe insulin resistance and metabolic abnormalities characteristic of the insulin resistance syndrome. Therefore, we suggest the term pre-prediabetes for this group to emphasize their high future risk of deteriorating glucose tolerance. CONCLUSIONS An increase in 1-h PG concentration precedes the development of prediabetes and identifies individuals with a 1-h PG of 120–155 mg/dL who are at increased risk of developing prediabetes. Therefore, we suggest the term pre-prediabetes for this group with an elevated risk of deteriorating glucose tolerance.
The nasal microbiome in early infancy is primarily shaped by the maternal nasal microbiome
Authors: Bailey E Quinn, José Alejandro Reyes Rodríguez, Emmanuel Kweku Sam, Jasmina Duliman, Elizabeth Denn, Sandra Lee, Liang Shan, Christiana Kuti, Beatrice Irene Nyann, Nicolas Rosario-Matos, Leyao Wang
Journal: Journal of Allergy and Clinical Immunology (2025)

The infant nasal microbiota closely mediates the risks of developing childhood respiratory diseases. However, the primary sources of these early residing bacteria remain largely unknown, preventing the development of microbiome strategies for disease prevention. Identify the primary maternal source of bacteria found in the early infant nasal microbiome. We conducted a birth cohort study, named Mother Infant Microbiome International Cohort (MIMIC). We recruited 95 mother-newborn dyads from three sites (St. Louis, Missouri, United States; San Juan, Puerto Rico; and Accra, Ghana) and collected samples at two time points (at birth and around two months of age). We performed analyses on 16S ribosomal RNA gene sequencing data to evaluate the maternal microbiomes (nasal, saliva, breast milk, and areola skin) as sources seeding the infant nasal microbiome. The infant nasal microbiome underwent a major compositional change during the first two months of life. The maternal nasal microbiome was identified as the primary source of bacteria in the early nasal microbiome across the three regions. Corynebacterium was predominantly transferred from the maternal nasal microbiome. Infants were more likely to harbor a Corynebacterium-dominant nasal microbiome if their mother's nasal microbiome was Corynebacterium-dominant. The maternal nasal microbiome is an important source of bacteria in the early nasal microbiome. A large portion of transmitted bacteria from the maternal nasal microbiome was a generally beneficial bacterial genus, Corynebacterium. Results from this study will aid the development of early life intervention strategies that aim to reduce the incidence of childhood respiratory diseases and asthma.
Glycosylation-driven programs coordinate immunoregulatory and pro-angiogenic functions of myeloid-derived suppressor cells
Authors: Ada G Blidner, Camila A Bach, Pablo A García, Joaquín P Merlo, Alejandro J Cagnoni, Nadia Bannoud, Montana N Manselle Cocco, Juan M Pérez Sáez, Nicolás A Pinto, Nicolás I Torres, Luciana Sarrias, Tomás Dalotto-Moreno, Sabrina G Gatto, Rosa M Morales, M Laura Giribaldi, Juan C Stupirski, Juan P Cerliani, Susan L Bellis, Mariana Salatino, María F Troncoso, Karina V Mariño, Martín C Abba, Diego O Croci, Gabriel A Rabinovich
Journal: Immunity (2025)
Activity-dependent development of the body’s touch receptors
Authors: Celine Santiago, Julianna Siegrist, Nusrat Africawala, Annie Handler, Aniqa Tasnim, Rabia Anjum, Josef Turecek, Brendan P Lehnert, Sophia Renauld, Jinheon Choi, Michael Nolan-Tamariz, Michael Iskols, Alexandra R Magee, Suzanne Paradis, Nikhil Sharma, David D Ginty
Journal: Neuron (2025)

We report a role for activity in the development of the primary sensory neurons that detect touch. Genetic deletion of Piezo2, the principal mechanosensitive ion channel in somatosensory neurons, caused profound changes in the formation of mechanosensory end-organ structures. Peripheral-nervous-system-specific deletion of the voltage-gated sodium channel Nav1.6 (Scn8a), which resulted in altered electrophysiological responses to mechanical stimuli, also disrupted somatosensory neuron morphologies, supporting a role for neuronal activity in end-organ formation. Single-cell RNA sequencing of Piezo2 mutants revealed changes in gene expression in sensory neurons activated by light mechanical forces, whereas other neuronal classes were minimally affected, and genetic deletion of Piezo2-dependent genes partially reproduced the defects in mechanosensory neuron structures observed in Piezo2 mutants. These findings indicate that mechanically evoked neuronal activity acts early in life to shape the maturation of mechanosensory end-organs that underlie our sense of gentle touch.
Acetaminophen inhibits diacylglycerol lipase synthesis of 2-arachidonoyl glycerol: Implications for nociception
Authors: Michaela Dvorakova, Taryn Bosquez-Berger, Jenna Billingsley, Natalia Murataeva, Taylor Woodward, Emma Leishman, Anaëlle Zimmowitch, Anne Gibson, Jim Wager-Miller, Ruyi Cai, Shangxuan Cai, Tim Ware, Ku-Lung Hsu, Yulong Li, Heather Bradshaw, Ken Mackie, Alex Straiker
Journal: Cell Reports Medicine (2025)

Acetaminophen (paracetamol) is a common analgesic, but its mechanism of action remains unknown. Despite causing around 500 deaths annually in the US, safer alternatives have not been developed. Because endocannabinoids may have a role in acetaminophen action, we examine interactions between the two. We report that acetaminophen inhibits the activity of diacylglycerol lipase α (DAGLα), but not DAGLβ, decreasing the production of the endocannabinoid 2-arachidonoyl glycerol. This gives rise to the counterintuitive hypothesis that decreasing endocannabinoid production by DAGLα inhibition may be antinociceptive in certain settings. Supporting this hypothesis, we find that diacylglycerol lipase (DAGL) inhibition by RHC80267 is antinociceptive in wild-type but not CB1 knockout mice in the hot-plate test. We propose (1) that activation of DAGLα may exacerbate some forms of nociception and (2) a mechanism for the antinociceptive actions of acetaminophen, whereby acetaminophen inhibits a DAGLα/CB1-based circuit that plays a permissive role in at least one form of nociception.
Distinct systemic impacts of Aβ42 and Tau revealed by whole-organism snRNA-seq
Authors: Ye-Jin Park, Tzu-Chiao Lu, Tyler Jackson, Lindsey D Goodman, Lindsey Ran, Jiaye Chen, Chung-Yi Liang, Erin Harrison, Christina Ko, Xi Chen, Baiping Wang, Ao-Lin Hsu, Elizabeth Ochoa, Kevin F Bieniek, Shinya Yamamoto, Yi Zhu, Hui Zheng, Yanyan Qi, Hugo J Bellen, Hongjie Li
Journal: Neuron (2025)
Acetylated cellulose suppresses body mass gain through gut commensals consuming host-accessible carbohydrates
Authors: Tadashi Takeuchi, Eiji Miyauchi, Yumiko Nakanishi, Yusuke Ito, Tamotsu Kato, Katsuki Yaguchi, Masami Kawasumi, Naoko Tachibana, Ayumi Ito, Shu Shimamoto, Akinobu Matsuyama, Nobuo Sasaki, Ikuo Kimura, Hiroshi Ohno
Journal: Cell Metabolism (2025)

Effective approaches to preventing and treating obesity are urgently needed. Although current strategies primarily focus on direct modulation of host metabolism, another promising approach may involve limiting nutrient availability through regulation of the gut microbiota, which links diet and host physiology. Here, we report that acetylated cellulose (AceCel), which markedly alters gut bacterial composition and function, reduces body mass gain in both wild-type and obese mice. AceCel limits carbohydrate oxidation and promotes fatty acid oxidation in the host liver in a microbiota-dependent manner. We further show that acetate enhances carbohydrate fermentation by the gut commensal Bacteroides thetaiotaomicron, depleting host-accessible simple sugars in the gut of AceCel-fed mice. These findings highlight the potential of AceCel as a prebiotic that regulates carbohydrate metabolism in both bacteria and host, offering promise as a therapeutic strategy for obesity.
A pathological missense mutation in the deubiquitinase USP5 leads to insensitivity to pain
Authors: Flavia T.T. Antunes, Maria A. Gandini, Agustin Garcia-Caballero, Sun Huang, Md Yousof Ali, Eder Gambeta, Ivana A. Souza, Erika K. Harding, Laurent Ferron, Asbjorg Stray-Pedersen, Vinicius M. Gadotti, Gerald W. Zamponi
Journal: The Journal of Experimental Medicine (2025)

Cav3.2 T-type calcium channels and their dysregulation by the deubiquitinase USP5 contribute to development of inflammatory and neuropathic pain. We report on a pediatric patient with a de novo heterozygous missense mutation R24W in USP5 who exhibits pain insensitivity. We created a CRISPR knock-in mouse harboring this mutation and performed detailed behavioral analyses in acute and chronic pain models. Heterozygous R24W mice of both sexes are resistant to acute pain and to thermal hypersensitivity in chronic inflammatory and neuropathic pain models. In contrast, only male R24W mice confer resistance to development of mechanical hypersensitivity. R24W mice lack upregulation of Cav3.2 and USP5 that is normally observed with CFA-induced inflammation. Moreover, mutant USP5 exhibits a dramatic reduction in enzymatic activity but stronger interactions with Cav3.2. Hence, R24W mutant USP5 is a critical regulator of chronic and acute pain states in humans by acting as a dominant-negative regulator of Cav3.2. Our data validate USP5 as a potential therapeutic target for chronic pain in humans.
3D Bioprinting and Artificial Intelligence‐Assisted Biofabrication of Personalized Oral Soft Tissue Constructs (Adv. Healthcare Mater. 13/2025)
Authors: Yichen Dai, Peter Wang, Apurva Mishra, Kui You, Yuheng Zong, Wen Feng Lu, Edward Kai‐Hua Chow, Philip M Preshaw, Dejian Huang, Jacob Ren Jie Chew, Dean Ho, Gopu Sriram
Journal: Advanced Healthcare Materials (2025)
Ischemic Myocardium Targeting Peptide‐Guided Nanobubbles for Multimodal Imaging and Treatment of Coronary Microvascular Dysfunction (Adv. Healthcare Mater. 13/2025)
Authors: Bo Yu, Ziwei Pang, Jing Zhao, Jingyi Xue, Hsuan Lo, Tiancheng Gu, Ping Zhang, Jiawei Tian, Guo‐Qing Du
Journal: Advanced Healthcare Materials (2025)
Multifunctional Carbon Quantum Dots for Monitoring and Therapy of Bacterial Infected Wounds (Adv. Healthcare Mater. 13/2025)
Authors: Wenxin Qi, Yihao Liu, Naijun Dong, Mengting Li, Jianxin Zhou, Yijun Xie, Qing Chang, Benxiang Luo, Christian Celia, Jiao Wang, Robert Chunhua Zhao, Xiaoyong Deng
Journal: Advanced Healthcare Materials (2025)
<scp>IgG</scp> Removal Enhances the Sensitivity of Amoxicillin‐Specific <scp>IgE</scp> Detection in <scp>ImmunoCAP</scp> and Radioallergosorbent Test
Authors: Jose A. Céspedes, Ana M. Pérez‐Moreno, Raquel Jurado‐Escobar, Gador Bogas, María Salas, Adriana Ariza, Rosa Muñoz‐Cano, Cristobalina Mayorga, María Jose Torres, Juan L. Paris
Journal: Allergy (2025)
Clinical Factors Associated With Catheter‐Related <scp>VTE</scp> in Patients Undergoing Hematopoietic Cell Transplantation: A Multi‐Center Study
Authors: Navel Gopal Subramanian, Danielle Guffey, Jonathan Avery, David Garcia, Ryan Basom, Stephanie J. Lee, Katherine Klein, Partow Kebriaei, Gabriela Rondon, Elizabeth Shpall, Shida Jin, Elliana Young, Cristhiam Mauricio Rojas Hernandez, Ang Li
Journal: American Journal of Hematology (2025)
Bioprinting Perfusable and Vascularized Skeletal Muscle Flaps for the Treatment of Volumetric Muscle Loss (Adv. Healthcare Mater. 13/2025)
Authors: Eliana O. Fischer, Anna Tsukerman, Majd Machour, Margarita Shuhmaher, Asaf Silverstein, Maya Yaakov, Orit Bar‐Am, Lior Debbi, Shulamit Levenberg
Journal: Advanced Healthcare Materials (2025)
Non‐Surgical, In‐Stent Membrane Bioelectronics for Long‐Term Intracranial Pressure Monitoring (Adv. Healthcare Mater. 13/2025)
Authors: Jimin Lee, Allison Bateman, Mi Hyeon Kim, Bruno Rigo, Hodam Kim, Jaeho Lee, Yun Hyeok Choi, Robert Herbert, Deok Hee Lee, Woon‐Hong Yeo
Journal: Advanced Healthcare Materials (2025)
Two‐Year Data of Tapered Dupilumab Shows High Effectiveness in <scp>CRSwNP</scp> With <scp>NSAID</scp>‐Exacerbated Respiratory Disease
Authors: H. B. E. Elzinga, J. J. Otten, M. E. Cornet, A. B. Rinia, R. J. L. Van Der Lans, W. J. Fokkens, S. Reitsma
Journal: Allergy (2025)

ABSTRACT Background Patients with Non‐steroidal anti‐inflammatory drugs ( NSAID )‐Exacerbated Respiratory Disease (N‐ ERD ) can suffer from difficult‐to‐treat primary diffuse type 2 chronic rhinosinusitis with nasal polyps ( CRSwNP ). This study evaluates dupilumab effectiveness and dose tapering in CRSwNP patients with N‐ ERD compared to those without. Methods A real‐world prospective cohort with CRSwNP patients, with N‐ ERD or without ( CRSwNP ‐ NOS ; not otherwise specified), aged ≥ 18 treated with dupilumab 300 mg subcutaneously every 2 weeks. In case of clinical control, the interdose interval was prolonged every 6 months with steps of 2 weeks. (Clinical) data were collected at baseline, 24 weeks, and 2 years of treatment. Results Most baseline characteristics, including Nasal Polyp Score ( NPS ), Sino‐Nasal Outcome Test‐22 ( SNOT ‐22), and Sniffin′ sticks‐12 test ( SSIT ‐12) were comparable between groups (N‐ ERD n = 105, CRSwNP ‐ NOS n = 293). There was a higher prevalence (91.5% vs. 71.1%, p &lt; 0.001) but comparable control of asthma in N‐ ERD patients (asthma control test [ ACT] : N‐ ERD 66.7% less controlled/uncontrolled vs. CRSwNP ‐ NOS 58.3%, p = 0.21). All outcomes improved significantly with dupilumab treatment at 24 weeks and remained improved after 2 years, without intergroup differences (median scores at 24 weeks for N‐ ERD patients vs. CRSwNP ‐ NOS , respectively: NPS : 2 vs. 1, p = 0.65; SNOT ‐22: 18 vs. 19, p = 0.27; SSIT ‐12: 7 vs. 8, p = 0.02; ACT : 21 vs. 22, p = 0.11). Dose tapering was possible in the majority of patients, with almost half at an 8–12 weeks interval in both groups after 2 years. Conclusion Dupilumab shows comparable effectiveness and taper feasibility between CRSwNP N‐ ERD patients and CRSwNP ‐ NOS patients.
Direct Single‐Dose Drug‐Provocation Test Is Safe for Delabelling Penicillin Low‐Risk Reactions in Adults
Authors: Marina Labella, Julia Rodriguez de Guzmán, Patricia Diez‐Echave, María Salas, Rubén Fernández‐Santamaría, Cristobalina Mayorga, Inmaculada Doña, María José Torres
Journal: Allergy (2025)

ABSTRACT Background Penicillins (PENs) are the most frequent drug‐allergic reactions trigger. However, diagnostic work‐up is complex and time‐consuming: it requires skin testing (ST) and drug‐provocation test (DPT), needing faster delabelling strategies. Although direct DPT without previous STs has shown to be safe, most of the studies are performed in children or in North American, Asian, or Oceanian adults, with few studies in the European adult population. We explored its safety in European adult patients with low‐risk PEN allergy history and, additionally, analysed ST role and T‐cell involvement by lymphocyte transformation test (LTT). Methods We prospectively evaluated &gt; 16 years of PEN‐allergic labelled patients referred to Málaga Regional University Hospital during 2023. They reported non‐immediate reactions without alarm signs and unknown reactions. Direct‐single‐dose DPT was performed in all patients. If positive, ST and LTT were carried out after reaction resolution. Results We included 269 patients with the culprits being an unidentified PEN (36%), amoxicillin (AX) (32%), and AX‐clavulanic acid (AX‐CLV) (31%); and the symptoms maculopapular exanthema (MPE) (34%) and unknown reaction during childhood (23%). Only 16 (5.9%) had positive DPT, being 56% for AX and 44% for AX‐CLV, 81% developing MPE, none severe. Most DPT‐reacting patients reported cutaneous non‐immediate reactions in the index reaction, and only one had an unknown childhood reaction. The mean day interval between drug administration and symptom development was lower ( p = 0.002) in positive DPT than in the index reaction (2 vs 5 days). Moreover, ST was positive in only 19% and LTTs in 86.7% of positive DPT patients. Conclusions Direct‐single‐dose DPT is safe for delabelling PEN allergy in non‐immediate reactions without alarm signs and unknown reactions. ST had a poor diagnostic value and LTT had a high one, confirming a T‐cell involvement.