tbuckley/cabot-search huggingface dataset:
Tri‐Layer Citrate‐Based Hydroxyapatite Composite Scaffold Promoting Osteogenesis and Gingival Tissue Regeneration for Periodontal Bone Defect Repair
Authors: Wei Qiu, Kaiying Zhang, Min Wu, Meimei Fu, Hongle Wu, Ruoshu Tang, Zehao Chen, Jinshan Guo, Fuchun Fang
Journal: Advanced Healthcare Materials (2025)

Periodontal bone defect (PBD) treatment involving oral soft and hard tissues is complicated and high requirements for regenerated materials. Besides osteogenic effects, the materials are also required to have the function of barrier soft tissues and promote wound healing. Citrate is reported to promote bone formation through enhanced osteoinductivity and facilitate wound healing by enabling phased angiogenesis. Herein, a novel tri-layered citrate-based hydroxyapatite (Ci-HA) composite scaffold that serves as a bone substitute is developed by "one-pot" method for PBD treatment. It is found that Ci-HA degradation products can promote the osteoblastic differentiation of rat bone mesenchymal stem cells and human periodontal ligament stem cells and upregulate angiogenesis-related gene expression in human gingival fibroblasts. Moreover, 3D remodeling in vitro shows that an intermediate layer of tri-layered Ci-HA composite scaffold acts as an optimal barrier. In vivo evaluation of Ci-HA in a rat periodontal intrabony three-wall defect model shows significantly increased bone formation with markedly enhanced osseointegration and better wound healing properties similarly with commercial Bio-Oss bone powder and Bio-Gide membrane. Thus, the novel tri-layered Ci-HA composite scaffold with high biocompatibility may represent a promising biomaterial with multi-effective bone regeneration, barrier effect, and wound healing capacity in the treatment of PBD.
New NIR‐Activated Organic Molecule‐Based Nanocomposite as an Efficient Sensitizer for Photothermal and Photodynamic Therapy of Cancer
Authors: Ming‐Hsin Liu, Zhen‐Jie Gao, Wei‐Yung Huang, Chi‐Hung Hsiao, Vincent Chen, Lee‐Jene Lai, Zi‐Jing Lin, Mo D.‐S. Hua, Chia‐Chun Hsieh, Er‐Yuan Chuang, Jiashing Yu, Ken‐Tsung Wong
Journal: Advanced Healthcare Materials (2025)

Acceptor-donor-acceptor (A-D-A)-configured molecules with coplanar dithieno[2,3-d:2',3'-d']thieno[3,2-b:3',2'-b']dipyrrole (DTPT) as the core are promising organic semiconductor materials utilized in organic photovoltaic devices owing to their efficient charge transportation capabilities. In addition to optoelectronic applications, they are potential in photothermal and photodynamic applications due to their light-absorption properties. This study evaluates the utilization of DTPT-based fused-ring-conjugated small molecules with strong near-infrared (NIR) absorption as stable organic photosensitizers for phototherapy by forming nanoparticles (NPs) with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS). Among them, NPs prepared from the 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene)malononitrile (TCF) end-capping DTPT-centered molecule, DTPTTCF, exhibit low cytotoxicity, enhance photothermal conversion efficiency and superior photodynamic activity. In vitro and in vivo experiments demonstrate the remarkable anticancer efficacy of DTPTTCF@TPGS NPs that can effectively suppress cancer cell proliferation under 808 nm laser treatment. Additionally, soft X-ray tomography (SXT) is employed as a high-resolution tool to observe intracellular variations that reveal distinct vacuolization in the NPs + Laser treated group. These observations highlight that the DTPTTCF@TPGS NPs cause significant damage to cancer cells under NIR irradiation. Furthermore, in vivo, experiments demonstrate the apoptosis of cancer cells within tumor tissues and the effective elimination of tumors upon NIR irradiation of DTPTTCF@TPGS NPs treated mice. This work manifests the potential application of the DTPT-cored A-D-A-type molecule as an advanced agent for tumor phototherapy with enhanced efficacy and selectivity.
The Tailored Biosimilar Approach: Expectations and Requirements
Authors: Elena Guillen, Sean Barry, Nils Jost, Niklas Ekman, Verena Knippel, Johanna Kuhlmann-Gottke, Julia Maier, Martina Weise, Andrea Laslop, René Anour, Ger van Zandbergen, Nadine Kirsch-Stefan
Journal: Drugs (2025)

Regulatory approval of biosimilar medicines currently requires a combination of physicochemical and functional testing, pharmacokinetic data, and clinical efficacy studies (CES). In this article, we discuss the tailored biosimilar approach, which represents an evolution in regulatory thinking by moving away from the default requirement for CES in biosimilar approval. We explore how physicochemical and functional data can be predictive for clinical performance and address the limitations of CES for regulatory decision-making. We argue that, in most cases, the combination of a robust package of physicochemical and functional testing, with appropriately designed pharmacokinetic studies provides sufficient evidence to establish biosimilarity. Additionally, we provide our perspective on the requirements, expectations, and exceptions for future biosimilar approvals, outlining specific scenarios where additional clinical evidence may be necessary. These include cases where the mechanism of action is unknown or poorly characterized, when product heterogeneity cannot be adequately characterized, or where relevant safety or immunogenicity concerns arise with the reference product or biosimilar candidate. Finally, we aim to clarify the remaining concerns surrounding the tailored biosimilar approach, providing insights into the potential to streamline biosimilar development and regulatory approval.
Renal Ghrelin-Family GPR39 Receptor and Urinary Concentrating Ability
Authors: Lingzhi Liu, Lena L. Rosenbaek, Mackenzie Kui, Samuel L. Svendsen, Annemette Overgaard Brethvad, Alexander Jakobsen, Laura V. Sparsoe, Aimi Hamilton, Mads V. Sørensen, Mathias Skov, Jacob R. Therkildsen, Jesper Kingo Andresen, Anna Laitakari, Thomas M. Frimurer, Boye Lagerbon Jensen, Jennifer Pluznick, Robert A. Fenton, Birgitte Holst, Helle Praetorius
Journal: Journal of the American Society of Nephrology (2025)

Low-calorie intake is associated with substantial changes in volume distribution and volume status in the body, resulting in reduced circulatory volume and a reduction in blood pressure. Activation of the orphan receptor GPR39 dampens food intake and causes weight loss in a GLP-1-dependent fashion. We speculated that appetite-regulating signaling might also be responsible for the circulatory volume contraction observed in response to anorectic states. To assess the effect of GPR39 fluid homeostasis, we combined in vivo, ex vivo, and in vitro studies to assess the effect of a selective GPR39 agonist (Cpd1324). Oral gavage of Cpd1324 dose-dependently increased the water intake of wild-type (WT) C57BL/6J mice only and was completely absent in global GPR39 knockout (KO) mice. GPR39 is expressed in the distal convoluted tubule and collecting duct of the kidney, and WT mice exclusively showed Cpd1324-induced increase in urine production, increased K+ excretion, and reduced urine concentrating capacity both at baseline and after an 8-hour water restriction compared to vehicle controls. Correspondingly, Cpd1324 reduced AVP-induced cAMP production and directly counteracted the AVP-induced water permeability in perfused cortical collecting ducts. Moreover, specific GPR39 activation reduced the baseline and AVP-stimulated abundance of phosphorylated pS256-AQP2 and pT58-NCC and diminished the AVP-stimulated pS269-AQP2 abundance in renal tubular suspensions. These effects were seen exclusively in GPR39 wild-type mice and not in KO mice. These data suggest that Cpd1324 directly targets renal GPR39 to induce increased diuresis and consequently stimulate drinking behavior. We conclude that activation of GPR39 causes diuresis by opposing AVP-induced Na+ and Cl- reabsorption in the distal convoluted tubule and water reabsorption in the collecting duct.
90-Day mortality prediction in elective visceral surgery using machine learning
Authors: Christoph Riepe, Robin van de Water, Axel Winter, Bjarne Pfitzner, Lara Faraj, Robert Ahlborn, Maximilian Schulze, Daniela Zuluaga, Christian Schineis, Katharina Beyer, Johann Pratschke, Bert Arnrich, Igor M. Sauer, Max M. Maurer
Journal: International Journal of Surgery (2025)

Machine Learning (ML) is increasingly being adopted in biomedical research, however, its potential for outcome prediction in visceral surgery remains uncertain. This study compares the potential of ML methods for preoperative 90-day mortality (90DM) prediction of an aggregated multi-organ approach to conventional scoring systems and individual organ models. This retrospective cohort study enrolled patients undergoing major elective visceral surgery between 2014 and 2022 across two tertiary centers. Multiple ML models for preoperative 90DM prediction were trained, externally validated and benchmarked against the American Society of Anesthesiologists (ASA) score and revised Charlson Comorbidity Index (rCCI). Areas under the receiver operating characteristic (AUROC) and precision recall curves (AUPRC) including standard deviations were calculated. Additionally, individual models for esophageal, gastric, intestinal, liver, and pancreatic surgery were developed and compared to an aggregated approach. 7,711 cases encompassing 78 features were included. Overall 90DM was 4% (n = 309). An XBoost classifier demonstrated the best performance and high robustness following external validation (AUROC: 0.86 [0.01]; AUPRC: 0.2 [0.04]). All models outperformed the ASA score (AUROC: 0.72; AUPRC: 0.08) and rCCI (AUROC: 0.81; AUPRC: 0.11). rCCI, patient age and C-reactive protein emerged as most decisive model weights. Models for gastric (AUROC: 0.88 [0.13]; AUPRC: 0.24 [0.26]) and intestinal surgery (AUROC: 0.87 [0.05]; AUPRC: 0.17 [0.09]) revealed the highest organ-specific performances, while pancreatic surgery yielded the lowest results (AUROC: 0.66 [0.08]; AUPRC: 0.22 [0.12]). A combined multi-organ approach (AUROC: 0.84 [0.04]; AUPRC: 0.21 [0.06]) demonstrated superiority over the weighted average across all organ-specific models (AUROC: 0.82 [0.07]; AUPRC: 0.2 [0.13]). ML offers robust preoperative risk stratification for 90DM in elective visceral surgery. Leveraging training across multi-organ cohorts may improve accuracy and robustness compared to organ-specific models. Prospective studies are needed to confirm the potential of ML in surgical outcome prediction.
Donor Optimizing to Boost Type I and Type II Photosensitization for Solid Tumor Therapy
Authors: Xingang Liu, Chuang Liu, Min Wu, Lei Cao, Chunhua Lu, Bin Liu
Journal: Advanced Healthcare Materials (2025)

Oxygen-less dependent Type I photosensitizers (PSs) have emerged as a crucial strategy for enhancing photodynamic therapy efficiency in treating hypoxic tumors. However, solid tumors have normoxia regions situated near functional blood vessels and hypoxia regions in their interiors. To maximize the utilization of oxygen within solid tumors, herein a viable donor optimizing approach is developed to enhance both Type I&II reactive oxygen species generation of PSs. At the same mole concentration, one optimized PS (named DE) generated 9 times more 1O2 than commercial Type II PS Chlorin e6 upon white light irradiation for 60 s. Compared to the commercial Type I PS Rose Bengal, •OH generation by DE is 2.9 times more under the hypoxia condition. With its optimized Type I&II pathway under normoxia and hypoxia conditions, DE is proven to be an efficient PS for solid tumor treatment, offering a promising approach for PS development.
Hypertensive Disorders of Pregnancy and Long-Term Risk of Dilated Cardiomyopathy
Authors: Upasana Tayal, Constantinos Kallis, Georgie M. Massen, Nora Rossberg, Emily L. Graul, Jennifer K. Quint
Journal: JAMA Cardiology (2025)

The impact of hypertensive disorders of pregnancy on developing dilated cardiomyopathy is unknown. To determine whether hypertensive disorders of pregnancy are associated with long-term risk of dilated cardiomyopathy. This population-based cohort study performed in England used the following linked electronic health records databases: Clinical Practice Research Datalink (CPRD) Pregnancy Register, CPRD Aurum (primary care), Hospital Episode Statistics Admitted Patient Care, and Office for National Statistics mortality data. Participants included an exposed cohort of 14 083 patients in their first pregnancy with hypertensive disorders of pregnancy (index date observed: January 1997 to December 2018; followed up until July 2023) and unexposed cohort of 70 415 with normotensive pregnancies randomly sampled from the Pregnancy Register (5:1 ratio). Hypertensive disorder of pregnancy (preeclampsia, gestational hypertension). Cox proportional hazards models were fitted to estimate hazard ratios (HRs) of developing dilated cardiomyopathy. The cohort included 14 083 individuals with a hypertensive disease of pregnancy during their first pregnancy and 70 415 individuals with normotensive first pregnancies. A first-time pregnancy complicated by a hypertensive disorder of pregnancy, compared with a normotensive first-time pregnancy, was associated with a 93% higher risk of developing dilated cardiomyopathy (adjusted HR, 1.93 [95% CI, 1.33-2.81]; P = .001; adjusted for maternal age). Dilated cardiomyopathy developed a median (IQR) of 5.1 (0.7-10.6) years post partum in those with HDP and 10.6 (4.2-15.8) years post partum in those with normotensive first pregnancies. The association remained significant after adjusting for maternal age, birth year, gestational diabetes, postpregnancy diabetes, postpregnancy hypertension, total parity, ethnicity, and socioeconomic status (adjusted HR, 1.55 [95% CI, 1.04-2.31]; P = .03). There was a dose response; there was a higher risk of DCM in those with preeclampsia (adjusted HR, 1.85 [95% CI, 1.24-2.76]; P = .002) and severe preeclampsia (adjusted HR, 4.29 [95% CI, 2.32-7.96]; P < .001). Maternal age (adjusted HR per year of age, 1.06 [95% CI, 1.03-1.08]; P < .001) and postpartum incident hypertension (adjusted HR, 1.68 [95% CI, 1.16-2.42]; P = .006) were independently associated with the development of DCM. Patients with hypertensive disorders of pregnancy had a greater risk of developing dilated cardiomyopathy. Older maternal age and postpartum hypertension were associated with higher risk of dilated cardiomyopathy after a hypertensive disorder of pregnancy. These findings support long-term clinical vigilance of patients with a history of hypertensive disorders of pregnancy.
Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19
Authors: Patrícia Brito Rodrigues, Vinícius de Rezende Rodovalho, Valentin Sencio, Nicolas Benech, Marybeth Creskey, Fabiola Silva Angulo, Lou Delval, Cyril Robil, Philippe Gosset, Arnaud Machelart, Joel Haas, Amandine Descat, Jean François Goosens, Delphine Beury, Florence Maurier, David Hot, Isabelle Wolowczuk, Harry Sokol, Xu Zhang, Marco Aurélio Ramirez Vinolo, François Trottein
Journal: Gut Microbes (2025)

Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.
Radiotherapy Utilization in Traditional Medicare and Medicare Advantage
Authors: Jacob Hogan, E. John Orav, Tianfeng Zhang, Alexander Spektor, Jie Zheng, Thomas C. Tsai, Miranda B. Lam
Journal: JAMA Network Open (2025)

As more than 50% of Medicare beneficiaries are enrolled in Medicare Advantage (MA), understanding whether the treatment covered by MA vs traditional Medicare (TM) is comparable can aid in providing high-value care. As the majority of patients with cancer undergo radiotherapy, it is important to quantify TM and MA utilization in oncology. To analyze the primary type of radiotherapy technology used, treatment length, and estimated spending for MA patients with cancer undergoing radiotherapy compared with TM patients with cancer. This retrospective cross-sectional study used 2018 Medicare claims data for TM and MA patients aged 65 years or older who received radiotherapy for 1 of 15 cancer types. Analyses were performed between May 1 and December 28, 2024. Insurance type (MA vs TM), cancer type, age, dual-eligibility status, medical comorbidities, county, and radiotherapy center type. Primary type of radiotherapy technology used, treatment length, and estimated spending for 90-day radiotherapy episodes. Adjusted rates and odds ratios (ORs) were calculated to compare technology types and rate ratios (RRs) to compare treatment length and estimated spending between TM and MA episodes. Of 31 563 treatment episodes among 30 941 patients, 22 594 (71.58%) were covered by TM (mean [SD] age, 74.76 [6.57] years; 50.76% among males) and 8969 (28.42%) were covered by MA (mean [SD] age, 74.51 [6.24] years; 51.78% among males). For radiotherapy episodes in patients with MA, adjusted analyses revealed lower odds of proton therapy use (52 [0.58% (95% CI, 0.34%-0.82%)] vs 373 [1.65% (95% CI, 1.50%-1.80%)]; OR, 0.36 [95% CI, 0.27-0.48]) and stereotactic radiotherapy use (1235 [13.77% (95% CI, 13.13%-14.41%)] vs 3391 [15.01% (95% CI, 14.61%-15.41%)]; OR, 0.87 [95% CI, 0.81-0.95]), higher odds of 2- or 3-dimensional radiotherapy use (3962 [44.17% (95% CI, 43.39%-44.96%)] vs 9584 [42.43% (95% CI, 41.93%-42.92%)]; OR, 1.13 [95% CI, 1.06-1.21]), greater mean treatment length (21.38 [95% CI, 21.14-21.61] vs 19.48 [95% CI, 19.33-19.62] treatments; RR, 1.10 [95% CI, 1.08-1.11]), and higher estimated radiotherapy spending ($8677.56 [95% CI, $8566.58-$8788.54] vs $8393.20 [95% CI, $8323.34-$8463.05]; RR, 1.04 [95% CI, 1.02-1.06]) compared with episodes in patients with TM. In this cross-sectional study, MA patients with cancer undergoing radiotherapy had higher estimated spending and greater mean treatment length than those covered by TM. Despite lower utilization of more expensive advanced treatment modalities, MA was not associated with cost savings. Whether MA meets the value proposition for radiation oncology requires further investigation.
MXene and Near‐Infrared Carbon Dots Co‐Encapsulated Hydrogel Facilitates Infected Bone Defect Reconstruction
Authors: Longfei Xiao, Yang Wang, Jinming Cai, Jinyan Hu, Hongjing Dou, Yu Zhu, Bijiang Geng, Dengyu Pan, Longxiang Shen
Journal: Advanced Healthcare Materials (2025)

Inadequate bone differentiation and intractable biofilm formation due to stubborn bacterial infection complicate infected bone defect repair. Adding harmful antibiotics into scaffolds not only promotes multidrug-resistant bacteria but also decreases bone repair effect. Furthermore, dynamic monitor of scaffolds' degradation is crucial for achieving visualized bone defect repair, however, currently reported biomaterials do not have imaging tracing capabilities. On this basis, this work develops a scaffold material with triple functionality for visualized therapy of infected bone defects: antibacterial, osteogenesis, and near-infrared (NIR) imaging capabilities. Single-layer Ti3C2Tx with broad-spectrumantibacterial activity and negatively charged carbon dots (CDs) with osteogenic activity are synthesized for infected bone defect repair. To validate antibacterial and osteogenic activities in vivo, 3D injectable hydrogels encapsulated with Ti3C2Tx and CDs (CD/Ti3C2Tx/GelMA) are constructed. NIR imaging is used to monitor the degradation process of CD/Ti3C2Tx/GelMA hydrogels in infected bone defect models, which indicated that CDs are completely released from hydrogels in about 30 days. Owing to the continuous release of Ti3C2Tx and CDs, the obtained CD/Ti3C2Tx/GelMA hydrogels can efficiently promote the repair of infected bone defects within 60 days. These findings develop a new biomaterial with great performance for visualized antibacterial and osteogenic therapy of infected bone defects.
Regenerating Family Protein 3α‐Loaded Responsive Hydrogel Accelerates Infected Diabetic Wound Healing
Authors: Qingyun Wu, Shenglong Jiang, Jia Liu, Lili Ren, Chen Luo, Guoguang Chen, Luting Yu
Journal: Advanced Healthcare Materials (2025)

Chronic diabetic wounds are characterized by a persistent inflammatory response, severe oxidative stress, and excessive proteolysis, creating an inhibitory microenvironment that impedes tissue regeneration. Recent findings indicate that regenerating family protein 3α (Reg3α) can promote keratinocyte proliferation and epidermal neogenesis, while also exhibiting antimicrobial properties. However, the low bioavailability significantly limits the clinical use of Reg3α in the treatment of chronic diabetic wounds. This study presents a glucose and ROS dual-responsive hydrogel loaded with Reg3α, which is synthesized by phenylboronic acid-modified hyaluronic acid (HAP) and polyvinyl alcohol (PVA). The Reg3α-loaded hydrogel (HAP-PVA/Reg3α), which exhibits favorable viscoelastic properties to adapt to wound application, promotes cell proliferation and demonstrates antibacterial and anti-inflammatory activities without inducing cytotoxicity or hemolysis in vitro. In diabetic mice, HAP-PVA/Reg3α effectively accelerates Staphylococcus aureus (S. aureus)-infected wound healing by alleviating bacterial infection, reducing inflammation, and facilitating collagen deposition. The result of RNA-seq suggests a negative regulation of M0 macrophages in the HAP-PVA/Reg3α group, which is presumably associated with their transformation into anti-inflammatory M2 macrophages. Meanwhile, serum pro-inflammatory IL-6 level is significantly decreased in Reg3α and HAP-PVA/Reg3α groups. In conclusion, HAP-PVA/Reg3α as a multifunctional hydrogel has significant potential for the treatment of chronic infected diabetic wounds.