tbuckley/cabot-search huggingface dataset:
Protein Nanoparticles for Targeted SARS‐CoV‐2 Trapping and Neutralization (Adv. Healthcare Mater. 6/2025)
Authors: Marc Fornt‐Suñé, Maria C. Puertas, Javier Martinez‐Picado, Javier García‐Pardo, Salvador Ventura
Journal: Advanced Healthcare Materials (2025)
HPV vaccine impact: genotype-specific changes in cervical pre-cancer share similarities with changes in cervical screening cytology
Authors: Rachael Adcock, Cosette M Wheeler, William C Hunt, Norah E Torrez-Martinez, Michael Robertson, Ruth McDonald, Nancy E Joste, Mark H Stoler, Maurits N C de Koning, Wim G V Quint
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Following human papillomavirus (HPV) vaccine introduction, declines in the prevalence of HPV vaccine types have been observed in screening cytology, but data from the United States describing HPV type-specific changes in cervical intraepithelial neoplasia (CIN) grades 2-3 and adenocarcinoma in situ (CIN2/CIN3/AIS) are limited. Methods A state-wide sample of individuals with cervical biopsies was selected for broad-spectrum HPV genotyping. CIN2/CIN3/AIS incidence and prevalence were calculated for type-specific high-risk HPV (hrHPV) among individuals aged 15-29 years. Weighted incidence rate ratios (IRR) and relative differences in prevalence (RDP) were computed to compare three time periods: 2006-2009 (Cohort 1 [C1], n = 4121), 2012-2015 (C2, n = 2194) and 2015-2018 (C3, n = 1481). Results When comparing C1 vs C3 among those aged 21-25 years, significant reductions in hrHPV type-specific CIN2/CIN3/AIS incidence were observed for HPV16, HPV18, HPV31 and HPV33, with corresponding IRRs of 0.4 (95% Confidence Interval [95%CI]: 0.3 to 0.4), 0.3 (95%CI: 0.1 to 0.7), 0.6 (95%CI: 0.5 to 0.9) and 0.4 (95%CI: 0.1 to 0.8), respectively. The RDP comparing C1 vs C3 for HPV16/18 positive CIN2/CIN3/AIS was -43.8% (P &amp;lt; .001). When excluding HPV16/18 or HPV16/18/31/33 from all hrHPV types, the RDP was +56.6% and +92.5% (P &amp;lt; .001), respectively. Conclusions hrHPV type-specific CIN2/CIN3/AIS incidence decreased significantly for vaccine types HPV16/18 and for HPV31 and HPV33. While the HPV vaccine is highly beneficial and a top priority for preventing HPV-related cancer, the long-term vaccine impact in cohorts receiving the 4-valent HPV vaccine requires continued follow-up to assess genotype-specific distributions in the remaining CIN2+ lesions and cancers.
Minimally Invasive Syringe‐Injectable Hydrogel with Angiogenic Factors for Ischemic Stroke Treatment (Adv. Healthcare Mater. 6/2025)
Authors: Donggue Kim, Ji Woo Lee, Yang Tae Kim, Junhyeok Choe, Gaeun Kim, Chang Man Ha, Jae Geun Kim, Kwang Hoon Song, Sunggu Yang
Journal: Advanced Healthcare Materials (2025)
Injectable Glucose‐Releasing Microgels Enhance the Survival and Therapeutic Potential of Transplanted MSCs Under Ischemic Conditions (Adv. Healthcare Mater. 6/2025)
Authors: Chieh‐Cheng Huang, Chun‐Kai Chang, Pei‐Ching Yang, Han Chiu, Shih‐Heng Chen, Li‐Wen Hsu
Journal: Advanced Healthcare Materials (2025)
Actuating Extracellular Matrices Decouple the Mechanical and Biochemical Effects of Muscle Contraction on Motor Neurons (Adv. Healthcare Mater. 6/2025)
Authors: Angel Bu, Ferdows Afghah, Nicolas Castro, Maheera Bawa, Sonika Kohli, Karina Shah, Brandon Rios, Vincent Butty, Ritu Raman
Journal: Advanced Healthcare Materials (2025)
Linking Metastatic Potential and Viscoelastic Properties of Breast Cancer Spheroids via Dynamic Compression and Relaxation in Microfluidics (Adv. Healthcare Mater. 6/2025)
Authors: Margherita Tavasso, Ankur D. Bordoloi, Elsa Tanré, Sanne A. H. Dekker, Valeria Garbin, Pouyan E. Boukany
Journal: Advanced Healthcare Materials (2025)
Microbiota and metabolite-based prediction tool for colonic polyposis with and without a known genetic driver
Authors: Bryson W. Katona, Ashutosh Shukla, Weiming Hu, Thomas Nyul, Christina Dudzik, Alex Arvanitis, Daniel Clay, Michaela Dungan, Marina Weber, Vincent Tu, Fuhua Hao, Shuheng Gan, Lillian Chau, Anna M. Buchner, Gary W. Falk, David L. Jaffe, Gregory Ginsberg, Suzette N. Palmer, Xiaowei Zhan, Andrew D. Patterson, Kyle Bittinger, Josephine Ni
Journal: Gut Microbes (2025)

Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis (N = 9), Gene-neg adenomatous polyposis (N = 18), and serrated polyposis syndrome (SPS, N = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively. Stool metabolites were quantified via 1H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.
The microcirculation, the blood-brain barrier and the neurovascular unit in health and Alzheimer’s Disease. The aberrant pericyte is a central player.
Authors: Yasmin Amy Divecha, Sanketh Rampes, Sabine Tromp, Sevda T Boyanova, Alice Fleckney, Mehmet Fidanboylu, Sarah Ann Thomas
Journal: Pharmacological Reviews (2025)

High fidelity neuronal signaling is enabled by a stable local microenvironment. A high degree of homeostatic regulation of the brain microenvironment, and its separation from the variable and potentially neurotoxic contents of the blood, is brought about by the central nervous system barriers. Evidence from clinical and preclinical studies implicates brain microcirculation, cerebral hypoperfusion, blood-brain barrier dysfunction, and reduced amyloid clearance in Alzheimer pathophysiology. Studying this dysregulation is key to understanding Alzheimer disease (AD), identifying drug targets, developing treatment strategies, and improving prescribing to this vulnerable population. This review has 2 parts: part 1 describes the cerebral microcirculation, cerebral blood flow, extracellular fluid drainage, and the neurovascular unit components with an emphasis on the blood-brain barrier, and part 2 summarizes how each aspect is altered in AD. Discussing the neurovascular unit structures separately allows us to conclude that aberrant pericytes are an early contributor and central to understanding AD pathophysiology. Pericytes have multiple functions including maintenance of blood-brain barrier integrity and the control of capillary blood flow, capillary stalling, neurovascular coupling, intramural periarterial drainage, glia-lymphatic (glymphatic) drainage, and consequently amyloid and tau clearance. Pericytes are vasoactive, express cholinergic and adrenergic receptors, and exhibit apolipoprotein E isoform-specific transport pathways. Hypoperfusion in AD is linked to a pericyte-mediated response. Deficient endothelial cell-pericyte (PDGBB-PDGFRβ) signaling loops cause pericyte dysfunction, which contributes and even initiates AD degeneration. We conclude that pericytes are central to understanding AD pathophysiology, are an interesting therapeutic target in AD, and have an emerging role in regenerative therapy. SIGNIFICANCE STATEMENT: Dysregulation and dysfunction of the neurovascular unit and fluid circulation (including blood, cerebrospinal fluid, and interstitial fluid) occurs in Alzheimer disease. A central player is the aberrant pericyte. This has fundamental implications to understanding disease pathophysiology and the development of therapies.
An axonal brake on striatal dopamine output by cholinergic interneurons
Authors: Yan-Feng Zhang, Pengwei Luan, Qinbo Qiao, Yiran He, Peter Zatka-Haas, Guofeng Zhang, Michael Z. Lin, Armin Lak, Miao Jing, Edward O. Mann, Stephanie J. Cragg
Journal: Nature Neuroscience (2025)

Abstract Depolarization of axons is necessary for somatic action potentials to trigger axonal neurotransmitter release. Here we show that striatal cholinergic interneurons (ChIs) and nicotinic receptors (nAChRs) on mouse dopamine axons interrupt this relationship. After nAChR-mediated depolarization, dopamine release by subsequent depolarization events was suppressed for ~100 ms. This suppression was not due to depletion of dopamine or acetylcholine, but to a limited reactivation of dopamine axons after nAChR-mediated depolarization, and is more prominent in dorsal than in ventral striatum. In vivo, nAChRs predominantly depressed dopamine release, as nAChR antagonism in dorsal striatum elevated dopamine detected with optic-fiber photometry of dopamine sensor GRAB DA2m and promoted conditioned place preference. Our findings reveal that ChIs acting via nAChRs transiently limit the reactivation of dopamine axons for subsequent action potentials in dopamine neurons and therefore generate a dynamic inverse scaling of dopamine release according to ChI activity.
Short-term effects of high-protein, lower-carbohydrate ultra-processed foods on human energy balance
Authors: Franziska A. Hägele, Catrin Herpich, Jana Koop, Jonas Grübbel, Rebecca Dörner, Svenja Fedde, Oliver Götze, Yves Boirie, Manfred J. Müller, Kristina Norman, Anja Bosy-Westphal
Journal: Nature Metabolism (2025)

Abstract Protein-enriched ultra-processed foods (UPFs) are generally perceived as a healthy and favourable dietary choice for weight management. However, compared with low-processed foods, the consumption of UPFs has been demonstrated to result in overfeeding and gains in body weight and fat mass. Here we investigate the short-term effects of protein-enriched UPFs on energy intake and energy balance in a single-blind crossover trial involving 21 healthy young adults, who were randomly assigned to 2 UPF diets for 54 hours in a whole-room calorimeter. Participants received either a high-protein (30%) and lower-carbohydrate (29%) diet (HPLC-UPF) or a normal-protein (13%) and normal-carbohydrate (46%) diet (NPNC-UPF). Meals were equally palatable, matched for calories, fat and fibre, and consumed ad libitum. As primary outcomes, compared with NPNC-UPF consumption, the HPLC-UPF diet resulted in a higher energy expenditure (128 ± 98 kcal d −1 ) and lower energy intake (−196 ± 396 kcal d −1 ), leading to a less-positive energy balance (18% versus 32%) with gains in protein and carbohydrate balance only. Postprandial ghrelin levels were lower, whereas glucagon and peptide YY levels were higher with HPLC-UPF compared with NPNC-UPF (secondary outcomes). Despite a reduction in energy intake and increased energy expenditure, the short-term consumption of protein-enriched UPFs did not prevent overeating but did favourably affect energy partitioning. ClinicalTrials.gov registration: NCT05337007 .
Allogeneic Stem Cell Transplant for Myelofibrosis and Myelodysplastic Syndromes: A Contemporary Review
Authors: Nico Gagelmann, Nicolaus Kröger
Journal: American Journal of Hematology (2025)

ABSTRACT Allogeneic hematopoietic stem‐cell transplantation (HCT) remains the only potentially curative therapy for patients with myelodysplastic neoplasms (MDS) and myelofibrosis (MF) and is the standard care for eligible patients with higher‐risk disease. Despite significant advancements, both diseases pose unique challenges due to their clinical and molecular heterogeneity, necessitating personalized approaches to patient selection, timing, and transplant management. For MDS, genomic profiling has revolutionized prognostic frameworks such as IPSS‐M, enabling tailored therapeutic decisions. In MF, driver mutations (e.g., JAK2, CALR, MPL ) and additional high‐risk molecular markers provide critical insights into disease biology and transplant outcomes. Optimal timing of HCT is critical, and recent models might help personalize treatment approaches. Molecular measurable residual disease monitoring has demonstrated prognostic value in both diseases, guiding preemptive strategies to mitigate relapse risk. Harnessing molecular technologies, clinical expertise, patient‐centered decision‐making, and innovative pharmaceutical strategies offers an exciting opportunity to shape a transformative and curative treatment framework. Here, we provide a contemporary review on HCT for MDS and MF, highlighting up‐to‐date insights into disease biology, standard of care, and recommendations, as well as open avenues.
The Five Times Sit-to-Stand Test Predicts Achievable Exercise Intensity During Stress Echocardiography
Authors: Yasuhide Mochizuki, Yui Kuroki, Mina Shibakai, Ayaka Oda, Sakiko Gohbara, Yumi Yamamoto, Saaya Ichikawa-Ogura, Rumi Hachiya, Eiji Toyosaki, Hiroto Fukuoka, Toshiro Shinke
Journal:  (2025)

Exercise stress echocardiography (ESE) is becoming increasingly important in assessing heart failure and valvular diseases; however, determining optimal exercise intensity remains challenging, particularly in patients with physical disorders. A total of 94 patients scheduled for ESE were enrolled in the study. Physical capability was assessed using the five times sit-to-stand test (5-STS), Clinical Frailty Scale, acronyms of the five components, namely strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) questionnaire, grip strength test, and bioelectrical impedance analysis. In the derivation cohort (n = 43), we determined the 5-STS cut-off value to achieving a 25 W load. The effectiveness of this cut-off value was prospectively evaluated in a validation cohort (n = 51). In the derivation cohort, the 5-STS predicted achieving a 25 W load using a cut-off of 11.7 s with 91% sensitivity and 70% specificity. In the validation cohort, using 12.0 s as the cut-off demonstrated 98% sensitivity and 88% specificity. The multivariate analysis identified age, sex (female), brain natriuretic peptide, SARC-F, and 5-STS as independent predictors of maximum achieved load. In a multivariate model including bioelectrical impedance parameters, lower limb muscle mass independently influenced maximum achievable load, regardless of age. Patients with optimized 5-STS-based load selection achieved significantly higher peak heart rates and maximum loads than those without. Sarcopenia-related indices, particularly the 5-STS, effectively and simply predicted achievable exercise intensity during ESE, independent of age and sex. The use of these indices to determine the initial load may help optimize ESE protocols for individual patients.
Cardiac ischemia/reperfusion increases cardiomyocyte KLF5 in pigs and mice that aggravates tissue injury and remodeling
Authors: Nikolaos Mylonas, Georgios Siokatas, Effimia Zacharia, Christine Pol, Tyler Rolland, Ioannis D Kyriazis, Matthew Hoffman, Alycia Hildebrand, Thomas Bannister, Erhe Gao, Ira J Goldberg, Vincent W Yang, Agnieszka B Bialkowska, John Elrod, John M Canty, Ioanna Andreadou, Brian Weil, Konstantinos Drosatos
Journal: Cardiovascular Research (2025)

Abstract Aims Activation of the transcriptional factor Krüppel-like factor 5 (KLF5) is detrimental to chronic heart failure. We explored the involvement of KLF5 in myocardial ischemia/reperfusion injury. Methods and results Yorkshire pigs underwent 75΄ of ischemia, followed by 3h or 24h of reperfusion. C57BL/6J mice underwent 30΄ of ischemia, followed by 10’, 2h, 12h, 24h, or 4 weeks of reperfusion. Hearts and isolated cardiomyocytes were analyzed for gene expression. We assessed cardiac function, infarct size (IS), oxidative stress, and fibrosis in mice subjected to pharmacologic or genetic KLF5 inhibition, as well as pharmacologic inhibition of NADPH oxidases or Glucose Transporter (GLUT)1 and GLUT4. Bulk RNA sequencing, untargeted 1H-NMR metabolomics and LC-MS lipidomics were performed. Isolated primary murine cardiomyocytes were infected with recombinant adenovirus expressing KLF5. During reperfusion, cardiοmyocyte KLF5 expression was increased in porcine and murine hearts. Pharmacologic or cardiomyocyte-specific genetic inhibition of KLF5 reduced IS and improved cardiac function in mice. Importantly, acute KLF5 inhibition during early reperfusion suppressed fibrosis and preserved systolic cardiac function 4 weeks post-ischemia/reperfusion. This improvement was associated with lower NOX4 expression, less oxidative stress, and suppressed inflammation and cell apoptosis. Pharmacologic inhibition of NOX4 conferred the same benefit. Metabolomic analysis indicated that KLF5 inhibition lowered glucose-derived metabolites (UDP-Glucose and Lactate) at early reperfusion. Accordingly, cardiac GLUT1 and GLUT4 levels were increased with ischemia/reperfusion, which was reverted by KLF5 inhibition. Pharmacologic inhibition of both GLUT1/4 reduced IS. Finally, myocardial KLF5 overexpression increased GLUT1 mRNA levels and mouse mortality. Conclusions Ischemia/reperfusion increases cardiomyocyte KLF5 expression in pigs and mice. This constitutes a central element of myocardial injury pathophysiology and is associated with stimulation of GLUT1 and GLUT4 expression, activation of NOX4, oxidative stress, inflammation and apoptosis. Acute KLF5 inhibition during reperfusion constitutes a novel therapeutic approach against myocardial ischemia/reperfusion injury.
Redefining the Limits of Functional Continuity in the Early Evolution of P-Loop NTPases
Authors: Andrey O Demkiv, Saacnicteh Toledo-Patiño, Encarnación Medina-Carmona, Andrej Berg, Gaspar P Pinto, Antonietta Parracino, Jose M Sanchez-Ruiz, Alvan C Hengge, Paola Laurino, Liam M Longo, Shina Caroline Lynn Kamerlin
Journal: Molecular Biology and Evolution (2025)

At the heart of many nucleoside triphosphatases is a conserved phosphate-binding sequence motif. A current model of early enzyme evolution proposes that this 6-8 residue motif could have sparked the emergence of the very first nucleoside triphosphatases - a striking example of evolutionary continuity from simple beginnings, if true. To test this provocative model, seven disembodied Walker A-derived peptides were extensively computationally characterized. Although dynamic flickers of nest-like conformations were observed, significant structural similarity between the situated peptide and its disembodied counterpart was not detected. Simulations suggest that phosphate binding is non-specific, with a preference for GTP over orthophosphate. Control peptides with the same amino acid composition but different sequences and situated conformations behaved similarly to the Walker A peptides, revealing no indication that the Walker A sequence is privileged as a disembodied peptide. We conclude that the evolutionary history of the P-Loop NTPase family is unlikely to have started with a disembodied Walker A peptide in an aqueous environment. The limits of evolutionary continuity for this protein family must be reconsidered. Finally, we argue that motifs such as the Walker A motif may represent incomplete or fragmentary molecular fossils - the true nature of which have been eroded by time.
Enteric tuft cell inflammasome activation drives NKp46+ILC3 IL22 via PGD2 and inhibits <i>Salmonella</i>
Authors: Madeline J. Churchill, Ankit Pandeya, Renate Bauer, Tighe Christopher, Stefanie Krug, Roslyn Honodel, Shuchi Smita, Lindsey Warner, Bridget M. Mooney, Alexis R. Gibson, Patrick S. Mitchell, Elia D. Tait Wojno, Isabella Rauch
Journal: The Journal of Experimental Medicine (2025)

To distinguish pathogens from commensals, the intestinal epithelium employs cytosolic innate immune sensors. Activation of the NAIP–NLRC4 inflammasome initiates extrusion of infected intestinal epithelial cells (IEC) upon cytosolic bacterial sensing. We previously reported that activation of the inflammasome in tuft cells, which are primarily known for their role in parasitic infections, leads to the release of prostaglandin D2 (PGD2). We observe that NAIP–NLRC4 inflammasome activation in tuft cells leads to an antibacterial response with increased IL-22 and antimicrobial protein levels within the small intestine, which is dependent on PGD2 signaling. A NKp46+ subset of ILC3 expresses the PGD2 receptor CRTH2 and is the source of the increased IL-22. Inflammasome activation in tuft cells also leads to better control of Salmonella Typhimurium in the distal small intestine. However, tuft cells in the cecum and colon are dispensable for antibacterial immunity. These data support that intestinal tuft cells can also induce antibacterial responses, possibly in a tissue-specific manner.
Duodenal biopsy and drainage procedures via the hepaticogastrostomy route using a newly designed device delivery system
Authors: Koichi Soga, Takeshi Fujiwara, Fuki Hayakawa, Mayumi Yamaguchi, Ikuhiro Kobori, Masaya Tamano
Journal: Endoscopy (2025)

Assessing postoperative retroperitoneal malignant invasion with duodenal stenosis and obstructive jaundice is challenging. After surgical reconstruction, endoscopic access through the retroperitoneum becomes difficult, complicating efforts to improve these conditions. Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) is a highly effective treatment for obstructive jaundice [1]. However, deploying several devices through the needle tract remains considerably challenging.
Mutational Landscape of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Association with Immune Checkpoint Inhibitor Outcome
Authors: Patricia McCoon, Ying Wang, Zhongwu Lai, Qu Zhang, Weimin Li, Sophie Wildsmith, Nassim Morsli, Rajiv Raja, Nicholas Holoweckyj, Jill Walker, Melissa de los Reyes, Ricard Mesía, Lisa Licitra, Robert L. Ferris, Jérôme Fayette, Dan P. Zandberg, Lillian L. Siu, Robert Haddad
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Understanding the mutational landscape of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is important in identifying biomarkers to determine which patients may benefit from immune checkpoint inhibitors (ICIs). Patients and Methods: The HAWK (NCT02207530), CONDOR (NCT02319044), and EAGLE (NCT02369874) studies evaluated R/M HNSCC treatment with durvalumab or durvalumab-tremelimumab. Tumor tissue samples pooled from HAWK/CONDOR (n=153) and plasma cell-free DNA samples from EAGLE (n=285) were analyzed to identify somatic alterations and association with survival. Results: The mutational landscape was similar in tissue and plasma. Compared with wild-type, TP53 mutations were associated with significantly shorter OS (HR; 95% CI) with standard of care (SoC; 2.12; 1.20–3.78 EAGLE) and ICIs (1.49; 1.05–2.12; HAWK/CONDOR and 1.44; 0.99–2.10; EAGLE). In EAGLE, patients with TP53 mutations had significantly longer OS with durvalumab-tremelimumab versus SoC (P = 0.045). KMT2D mutations were associated with a trend towards longer OS (HR; 95% CI) versus wild-type in HAWK/CONDOR (0.81; 0.56–1.19), and a trend towards longer OS with ICIs versus SoC in EAGLE. For both mutations, an ECOG performance status of 1 was associated with worsened OS, and PD-L1 positivity was associated with improved OS. Conclusions: This is the first large-scale study to show the mutational landscape of R/M HNSCC and its association with clinical outcomes in patients treated with ICIs or SoC. TP53 mutation was a negative prognostic marker, however, treatment with durvalumab-tremelimumab significantly improved survival over SoC. Further investigation of KMT2D as a predictive biomarker for immunotherapy in R/M HNSCC is warranted.