tbuckley/cabot-search huggingface dataset:
Human Cell‐Derived Matrix Composite Hydrogels with Diverse Composition for Use in Vasculature‐on‐chip Models
Authors: Elizabeth L. Doherty, Grace Krohn, Emily C. Warren, Alexandra Patton, Chloe P. Whitworth, Mitesh Rathod, Andreea Biehl, Wen Yih Aw, Donald O. Freytes, William J. Polacheck
Journal: Advanced Healthcare Materials (2024)

Microphysiological and organ-on-chip platforms seek to address critical gaps in human disease models and drug development that underlie poor rates of clinical success for novel interventions. While the fabrication technology and model cells used to synthesize organs-on-chip have advanced considerably, most platforms rely on animal-derived or synthetic extracellular matrix as a cell substrate, limiting mimicry of human physiology and precluding use in modeling diseases in which matrix dynamics play a role in pathogenesis. Here, the development of human cell-derived matrix (hCDM) composite hydrogels for use in 3D microphysiologic models of the vasculature is reported. hCDM composite hydrogels are derived from human donor fibroblasts and maintain a complex milieu of basement membrane, proteoglycans, and nonfibrillar matrix components. The use of hCDM composite hydrogels as 2D and 3D cell culture substrates is demonstrated, and hCDM composite hydrogels are patterned to form engineered human microvessels. Interestingly, hCDM composite hydrogels are enriched in proteins associated with vascular morphogenesis as determined by mass spectrometry, and functional analysis demonstrates proangiogenic signatures in human endothelial cells cultured in these hydrogels. In conclusion, this study suggests that human donor-derived hCDM composite hydrogels could address technical gaps in human organs-on-chip development and serve as substrates to promote vascularization.
Optimizing Postneoadjuvant Treatment in Patients With Early Breast Cancer Achieving Pathologic Complete Response
Authors: Carmine Valenza, Dario Trapani, Sibylle Loibl, Stephen K.L. Chia, Harold J. Burstein, Giuseppe Curigliano
Journal: Journal of Clinical Oncology (2024)

pCR should be integrated with other prognostic factors to optimize postneoadjuvant treatments in BC.
Dapagliflozin and Timing of Prior Heart Failure Hospitalization
Authors: Jawad H. Butt, Pardeep S. Jhund, Kieran F. Docherty, Brian L. Claggett, Muthiah Vaduganathan, Erasmus Bachus, Adrian F. Hernandez, Carolyn S.P. Lam, Silvio E. Inzucchi, Felipe A. Martinez, Rudolf A. de Boer, Mikhail N. Kosiborod, Akshay S. Desai, Lars Køber, Piotr Ponikowski, Marc S. Sabatine, Scott D. Solomon, John J.V. McMurray
Journal: JACC Heart Failure (2024)

Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable." The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure). A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death. In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category. The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.
Navigating the landscape of RNA delivery systems in cardiovascular disease therapeutics
Authors: Paula Gil-Cabrerizo, Teresa Simon-Yarza, Elisa Garbayo, María J. Blanco-Prieto
Journal: Advanced Drug Delivery Reviews (2024)

Cardiovascular diseases (CVDs) stand as the leading cause of death worldwide, posing a significant global health challenge. Consequently, the development of innovative therapeutic strategies to enhance CVDs treatment is imperative. RNA-based therapies, encompassing non-coding RNAs, mRNA, aptamers, and CRISPR/Cas9 technology, have emerged as promising tools for addressing CVDs. However, inherent challenges associated with RNA, such as poor cellular uptake, susceptibility to RNase degradation, and capture by the reticuloendothelial system, underscore the necessity of combining these therapies with effective drug delivery systems. Various non-viral delivery systems, including extracellular vesicles, lipid-based carriers, polymeric and inorganic nanoparticles, as well as hydrogels, have shown promise in enhancing the efficacy of RNA therapeutics. In this review, we offer an overview of the most relevant RNA-based therapeutic strategies explored for addressing CVDs and emphasize the pivotal role of delivery systems in augmenting their effectiveness. Additionally, we discuss the current status of these therapies and the challenges that hinder their clinical translation.
Secondary Hypertrophic Osteoarthropathy
Authors: Margarida Lucas Rocha, Vitor Silvestre-Teixeira
Journal: New England Journal of Medicine (2024)

A 55-year-old woman with a 29-pack-year smoking history presented with a 1.5-year history of pain in her fingers, wrists, hips, knees, and ankles. Clubbing of the fingers and toes was seen on examination.
Endoscopic hand-suturing training model
Authors: Taku Morita, Ken Ohata, Toshihiro Araki, Makoto Koda, Kazuta Fukumori, Yohei Minato, Takumi Kawaguchi
Journal: Endoscopy (2024)

Endoscopic hand-suturing (EHS) is a novel suturing method that allows optimal and secure intraluminal suturing [1] [2]. On the other hand, the procedure is reported to be complicated, difficult, and time-consuming [3] [4]. At present, there is no appropriate training model for it and no established method for learning it.
Cholangioscopy-assisted endoscopic mucosal resection for gallbladder polyp and stone extraction for cholecystocholedocholithiasis.
Authors: Wengang Zhang, Ningli Chai, Yujie Feng, Jiafeng Wang, Qingzhen Wu, Zhenyu Liu, Enqiang Linghu
Journal: Endoscopy (2024)

A 58-year-old man with cholecystocholedocholithiasis was assessed in our hospital. Preoperative computerized tomography (CT) showed a 0.6-cm common bile duct (CBD) stone combined with sediment-like gallstones. Therefore, we performed cholangioscopy-assisted extraction through papillary stent [1] for him.
Endoscopic lithotripsy for an impacted biliary stone at the confluence of the cystic duct and common bile duct using a novel drill dilator
Authors: Yuichi Hirata, Yuichiro Aoyama, Ryosuke Mizukami, Mayumi Doi, Atsunori Maeda, Daisuke Orita, Yoshihiro Okabe
Journal: Endoscopy (2024)

Endoscopic retrograde cholangiopancreatography (ERCP) is widely performed for patients with common bile duct (CBD) stones. Many cases are successfully managed with endoscopic sphincterotomy and stone removal using balloon or basket catheters. However, for difficult or complex stones, ERCP with conventional techniques may fail to achieve biliary clearance in 10–15% of cases [1]. Peroral cholangioscopy-guided electrohydraulic lithotripsy (POCS-EHL) is effective in these cases; however, it is expensive and time-consuming. Herein, we report a case of endoscopic lithotripsy for an impacted stone at the confluence of the cystic duct (CD) and CBD using a novel drill dilator.
Freehand suturing to apply traction during endoscopic submucosal dissection
Authors: Jochen Weigt, Cosima Göring, Verena Keitel
Journal: Endoscopy (2024)

The technique of freehand suturing in gastrointestinal endoscopy has evolved through technical developments such as knotless barbed wire sutures and needle manipulators, with initial publications showing promising results [1] [2]. The main advantage of freehand suturing over currently used device-based suturing is the ease of the technique. The method of freehand suturing offers a variety of possible applications, but these are not yet well established. Besides closing of mucosal or complete wall defects of the gastrointestinal tract, one of our first thoughts was the use of the suture string to apply tension to the mucosa while performing resections such as endoscopic submucosal dissection (ESD) or submucosal tunnel preparation. We present the technique of freehand suture traction during ESD in a porcine stomach.
Conductive Hyaluronic Acid/Deep Eutectic Solvent Composite Hydrogel as a Wound Dressing for Promoting Skin Burn Healing Under Electrical Stimulation
Authors: Yu Tian, Fei Jiang, Haijiao Xie, Zhe Chi, Chenguang Liu
Journal: Advanced Healthcare Materials (2024)

Abstract Burns can cause severe damage to the skin due to bacterial infection and severe inflammation. Although conductive hydrogels as electroactive burn‐wound dressings achieve remarkable effects on accelerating wound healing, issues such as imbalance between their high conductivity and mechanical properties, easy dehydration, and low transparency must be addressed. Herein, a double‐network conductive eutectogel is fabricated by integrating polymerizable deep eutectic solvents (PDESs)including acrylamide/choline chloride/glycerol (acrylamide‐polymerization crosslink) and thiolated hyaluronic acid (disulfide‐bonding crosslink). The introduction of PDESs provides the eutectogel with a conductivity (up to 0.25 S·m −1 ) and mechanical strength (tensile strain of 59–77%) simulating those of natural human skin, as well as satisfactory tissue adhesiveness, self‐healing ability, and antibacterial properties. When combined with exogenous electrical stimulation, the conductive eutectogel exhibits the ability to reduce inflammation, stimulate cell proliferation and migration, promote collagen deposition and angiogenesis, and facilitate skin tissue remodeling. This conductive eutectogel shows great potential as a dressing for healing major burn wounds.
Precisely Self‐Cooperative Nanoassembly Enables Photothermal/Ferroptosis Synergistic Tumor Eradication
Authors: Xiaohong Yang, Chengcheng Feng, Pengfei Wang, Shishi Xie, Yuequan Wang, Haotian Zhang, Zhonggui He, Shenwu Zhang, Cong Luo
Journal: Advanced Healthcare Materials (2024)

Ferroptosis is identified as a potential target for anticancer therapy. However, most conventional ferroptosis inducers not only fail to trigger intracellular lipid peroxidation storm, but are also prone to cause ferroptosis-related toxicity through off-target destruction of intracellular antioxidant defense systems. Therefore, a potent and highly tumor-specific ferroptosis induction modality is desired. Herein, a self-cooperative nanomedicine for imaging-guided photothermal ferrotherapy, which is fabricated based on molecular nanoassembly (NA) of DiR (a photothermal probe) and ferrocene (Fc, a reactant of the Fenton reaction), is elaborately exploited. DiR-elicited hyperthermia induces both photothermal therapy (PTT) and a significant acceleration of the kinetics of the Fc-involved Fenton reaction, collaboratively causing a lipid peroxidation storm in tumor cells. In turn, plenty of lipid peroxides boost PTT through the downregulation of heat shock protein 90. As expected, such a self-cooperative NA demonstrates synergetic tumor eradication in the 4T1 breast tumor-bearing mice xenograft model. This study offers a novel nanotherapeutic paradigm for precise multimodal cancer therapy.
Merit of integrating in situ transcriptomics and anatomical information for cell annotation and lineage construction in single-cell analyses of Populus
Authors: Ying-Lan Chen, Jo-Wei Allison Hsieh, Shang-Che Kuo, Chung-Ting Kao, Chia-Chun Tung, Jhong-He Yu, Tien-Hsien Chang, Chuan Ku, Jianbo Xie, Deqiang Zhang, Quanzi Li, Ying-Chung Jimmy Lin
Journal: Genome biology (2024)

Abstract Cell type annotation and lineage construction are two of the most critical tasks conducted in the analyses of single-cell RNA sequencing (scRNA-seq). Four recent scRNA-seq studies of differentiating xylem propose four models on differentiating xylem development in Populus . The differences are mostly caused by the use of different strategies for cell type annotation and subsequent lineage interpretation. Here, we emphasize the necessity of using in situ transcriptomes and anatomical information to construct the most plausible xylem development model.
Development of an Injectable Biphasic Hyaluronic Acid‐Based Hydrogel With Stress Relaxation Properties for Cartilage Regeneration
Authors: Han‐Sem Kim, Cheng Ji Li, Sung‐Min Park, Kyung Wook Kim, Ji‐Hun Mo, Guang‐Zhen Jin, Hae‐Hyoung Lee, Hae‐Won Kim, Ueon Sang Shin, Jung‐Hwan Lee
Journal: Advanced Healthcare Materials (2024)

Biomimetic stress-relaxing hydrogels with reversible crosslinks attract significant attention for stem cell tissue regeneration compared with elastic hydrogels. However, stress-relaxing hyaluronic acid (HA)-based hydrogels fabricated using conventional technologies lack stability, biocompatibility, and mechanical tunability. Here, it is aimed to address these challenges by incorporating calcium or phosphate components into the HA backbone, which allows reversible crosslinking of HA with alginate to form interpenetrating networks, offering stability and mechanical tunability for mimicking cartilage. Diverse stress-relaxing hydrogels (τ1/2; SR50, 60-2000 s) are successfully prepared at ≈3 kPa stiffness with self-healing and shear-thinning abilities, favoring hydrogel injection. In vitro cell experiments with RNA sequencing analysis demonstrate that hydrogels tune chondrogenesis in a biphasic manner (hyaline or calcified) depending on the stress-relaxation properties and phosphate components. In vivo studies confirm the potential for biphasic chondrogenesis. These results indicate that the proposed stress-relaxing HA-based hydrogel with biphasic chondrogenesis (hyaline or calcified) is a promising material for cartilage regeneration.
Combined rituximab and belimumab to treat recalcitrant epidermolysis bullosa aquisita associated with systemic lupus erythematosus
Authors: Thomas J Tull, Emma C Benton, Kristina Semkova, Natalie A Watson, John B Mee, Begona Lopez, Jane Setterfield, Barbara Carey, Sajjad Ahmad, Scott J Robbie, Richard W Groves, Giovanni Sanna, David P D’Cruz
Journal: British Journal of Dermatology (2024)

We report two cases of recalcitrant epidermolysis bullosa aquisita with associated systemic lupus erythematosus treated with combination rituximab and belimumab therapy. This resulted in the complete resolution of cutaneous lesions and a partial response of the mucosal lesions. These cases support the use of combined rituximab and belimumab for the treatment of recalcitrant immunobullous disease.
Programming peptide-oligonucleotide nano-assembly for engineering of neoantigen vaccine with potent immunogenicity
Authors: Zhichu Xiang, Jianhua Lu, Shangrui Rao, Chenxing Fu, Yuying Yao, Yongdong Yi, Yang Ming, Weijian Sun, Weisheng Guo, Xiaoyuan Chen
Journal: Theranostics (2024)

Neoantigen nanovaccine has been recognized as a promising treatment modality for personalized cancer immunotherapy. However, most current nanovaccines are carrier-dependent and the manufacturing process is complicated, resulting in potential safety concerns and suboptimal codelivery of neoantigens and adjuvants to antigen-presenting cells (APCs).
Disturbed flow impairs MerTK-mediated efferocytosis in aortic endothelial cells during atherosclerosis
Authors: Jinzi Wu, Shijie Liu, Oishani Banerjee, Hang Shi, Bingzhong Xue, Zufeng Ding
Journal: Theranostics (2024)

Background: MER proto-oncogene tyrosine kinase (MerTK) is a key receptor for efferocytosis, a process for the clearance of apoptotic cells.MerTK is mainly expressed in macrophages and immature dendritic cells.There are very limited reports focused on MerTK biology in aortic endothelial cells (ECs).It remains unclear for the role of blood flow patterns in regulating MerTK-mediated efferocytosis in aortic ECs.This study was designed to investigate whether endothelial MerTK and EC efferocytosis respond to blood flow patterns during atherosclerosis.Methods: Big data analytics, RNA-seq and proteomics combined with our in vitro and in vivo studies were applied to reveal the potential molecular mechanisms.Partial carotid artery ligation combined with AAV-PCSK9 and high fat diet were used to set up acute atherosclerosis in 4 weeks.Results: Our data showed that MerTK is sensitive to blood flow patterns and is inhibited by disturbed flow and oscillatory shear stress in primary human aortic ECs (HAECs).The RNA-seq data in HAECs incubated with apoptotic cells showed that d-flow promotes pro-inflammatory pathway and senescence pathway.Our in vivo data of proteomics and immunostaining showed that, compared with WT group, MerTK -/-aggravates atherosclerosis in d-flow areas through upregulation of endothelial dysfunction markers (e.g.IL-1β, NF-κB, TLR4, MAPK signaling, vWF, VCAM-1 and p22 phox ) and mitochondrial dysfunction.Interestingly, MerTK -/-induces obvious abnormal endothelial thickening accompanied with decreased endothelial efferocytosis, promoting the development of atherosclerosis.Conclusions: Our data suggests that blood flow patterns play an important role in regulating MerTK-mediated efferocytosis in aortic ECs, revealing a new promising therapeutic strategy with EC efferocytosis restoration to against atherosclerosis.
Transglutaminase 2 in diabetes mellitus: Unraveling its multifaceted role and therapeutic implications for vascular complications
Authors: Kwon-Soo Ha
Journal: Theranostics (2024)

Diabetes, a severe metabolic disease characterized by chronic hypoglycemia, poses debilitating and life-threatening risks of microvascular and macrovascular complications, including blindness, kidney failure, heart attacks, and limb amputation.Addressing these complications is paramount, urging the development of interventions targeting diabetes-associated vascular dysfunctions.To effectively combat diabetes, a comprehensive understanding of the pathological mechanisms underlying complications and identification of precise therapeutic targets are imperative.Transglutaminase 2 (TGase2) is a multifunctional enzyme implicated in the pathogenesis of diverse diseases such as neurodegenerative disorders, fibrosis, and inflammatory conditions.TGase2 has recently emerged as a key player in both the pathogenesis and therapeutic intervention of diabetic complications.This review highlights TGase2 as a therapeutic target for diabetic complications and explores TGase2 inhibition as a promising therapeutic approach in their treatment.
Theranostics and artificial intelligence: new frontiers in personalized medicine
Authors: Gokce Belge Bilgin, Cem Bilgin, Brian J. Burkett, Jacob J. Orme, Daniel S. Childs, Matthew P. Thorpe, Thorvardur R Halfdanarson, Geoffrey B Johnson, Ayse Tuba Kendi, Oliver Sartor
Journal: Theranostics (2024)

The field of theranostics is rapidly advancing, driven by the goals of enhancing patient care. Recent breakthroughs in artificial intelligence (AI) and its innovative theranostic applications have marked a critical step forward in nuclear medicine, leading to a significant paradigm shift in precision oncology. For instance, AI-assisted tumor characterization, including automated image interpretation, tumor segmentation, feature identification, and prediction of high-risk lesions, improves diagnostic processes, offering a precise and detailed evaluation. With a comprehensive assessment tailored to an individual's unique clinical profile, AI algorithms promise to enhance patient risk classification, thereby benefiting the alignment of patient needs with the most appropriate treatment plans. By uncovering potential factors unseeable to the human eye, such as intrinsic variations in tumor radiosensitivity or molecular profile, AI software has the potential to revolutionize the prediction of response heterogeneity. For accurate and efficient dosimetry calculations, AI technology offers significant advantages by providing customized phantoms and streamlining complex mathematical algorithms, making personalized dosimetry feasible and accessible in busy clinical settings. AI tools have the potential to be leveraged to predict and mitigate treatment-related adverse events, allowing early interventions. Additionally, generative AI can be utilized to find new targets for developing novel radiopharmaceuticals and facilitate drug discovery. However, while there is immense potential and notable interest in the role of AI in theranostics, these technologies do not lack limitations and challenges. There remains still much to be explored and understood. In this study, we investigate the current applications of AI in theranostics and seek to broaden the horizons for future research and innovation.
HDAC6-dependent deacetylation of NGF dictates its ubiquitination and maintains primordial follicle dormancy
Authors: Tuo Zhang, Yuntong Tong, Rengguang Zhu, Yaoyun Liang, Jixian Zhang, Chujiao Hu, Meina He, Zhu Hu, Zhiyi Shen, Jin Niu, Jingjing Zhang, Yuanyuan Yu, Bangming Jin, Shan Lei, Zhirui Zeng, Yingmin Wu, Zengmei Cheng, Ziwen Xiao, Bing Guo, Shuyun Zhao, Guoqiang Xu, Wei Pan, Tengxiang Chen
Journal: Theranostics (2024)

Rationale: Primordial follicles are limited in number and cannot be regenerated, dormant primordial follicles cannot be reversed once they enter a growth state.Therefore, the length of the female reproductive lifespan depends on the orderly progression and selective activation of primordial follicles, the mechanism of which remains unclear.Methods: We used human ovarian cortical biopsy specimens, granulosa cells from diminished ovarian reserve (DOR) patients, Hdac6-overexpressing transgenic mouse model, and RNA sequencing to analyze the crucial roles of histone deacetylase 6 (HDAC6) in fertility preservation and primordial follicle activation.Results: In the present study, we found that HDAC6 was highly expressed in most dormant primordial follicles.The HDAC6 expression was reduced accompanying reproductive senescence in human and mouse ovaries.Overexpression of Hdac6 delayed the rate of primordial follicle activation, thereby prolonging the mouse reproductive lifespan.Short-term inhibition of HDAC6 promoted primordial follicle activation and follicular development in humans and mice.Mechanism studies revealed that HDAC6 directly interacted with NGF, reducing acetylation modification of NGF and thereby accelerating its ubiquitination degradation.Consequently, the reduced NGF protein level maintained the dormancy of primordial follicles. Conclusions:The physiological significance of the high expression of HDAC6 in most primordial follicles is to reduce NGF expression and prevent primordial follicle activation to maintain female fertility.Reduced HDAC6 expression increases NGF expression in primordial follicles, activating their development and contributing to reproduction.Our study provides a clinical reference value for fertility preservation.