tbuckley/cabot-search huggingface dataset:
3D Bioprinted Tissue‐Engineered Bone with Enhanced Mechanical Strength and Bioactivities: Accelerating Bone Defect Repair through Sequential Immunomodulatory Properties
Authors: Daqian Liu, Jingsong Liu, Pengcheng Zhao, Zhibin Peng, Zhibin Geng, Jingwei Zhang, Zhuoran Zhang, Ruifang Shen, Xiang Li, Xiaoyu Wang, Shuangzuo Li, Jiankai Wang, Xintao Wang
Journal: Advanced Healthcare Materials (2024)

In this study, a new-generation tissue-engineered bone capable of temporally regulating the immune response, balancing proinflammatory and anti-inflammatory activities, and facilitating bone regeneration and repair to address the challenges of delayed healing and nonunion in large-sized bone defects, is innovatively developed. Using the innovative techniques including multiphysics-assisted combined decellularization, side-chain biochemical modification, and sterile freeze-drying, a novel photocurable extracellular matrix hydrogel, methacrylated bone-derived decellularized extracellular matrix (bdECM-MA), is synthesized. After incorporating the bdECM-MA with silicon-substituted calcium phosphate and bone marrow mesenchymal stem cells, the tissue-engineered bone is fabricated through digital light processing 3D bioprinting. This study provides in vitro confirmation that the engineered bone maintains high cellular viability while achieving MPa-level mechanical strength. Moreover, this engineered bone exhibits excellent osteogenesis, angiogenesis, and immunomodulatory functions. One of the molecular mechanisms of the immunomodulatory function involves the inhibition of the p38-MAPK pathway. A pioneering in vivo discovery is that the natural biomaterial-based tissue-engineered bone demonstrates sequential immunomodulatory properties that activate proinflammatory and anti-inflammatory responses in succession, significantly accelerating the repair of bone defects. This study provides a new research basis and an effective method for developing autogenous bone substitute materials and treating large-sized bone defects.
Neural implicit surface reconstruction of freehand 3D ultrasound volume with geometric constraints
Authors: Hongbo Chen, Logiraj Kumaralingam, Shuhang Zhang, Sheng Song, Fayi Zhang, Haibin Zhang, Thanh-Tu Pham, Kumaradevan Punithakumar, Edmond H.M. Lou, Yuyao Zhang, Lawrence H. Le, Rui Zheng
Journal: Medical Image Analysis (2024)
Detection of Epstein‒Barr virus DNA methylation as tumor markers of nasopharyngeal carcinoma patients in saliva, oropharyngeal swab, oral swab, and mouthwash
Authors: Xiao‐Hui Zheng, Xi‐Zhao Li, Cao‐Li Tang, Yu‐Meng Zhang, Ting Zhou, Xiao‐Jing Yang, Ying Liao, Yong‐Qiao He, Tong‐Min Wang, Wen‐Qiong Xue, Wei‐Hua Jia
Journal: MedComm (2024)

Saliva biopsy of nasopharyngeal carcinoma (NPC) has been developed in our latest study, indicating the application of oral sampling in NPC detection. Further exploration of the potential for self-sampling from the oral cavity is necessary. A total of 907 various samples from oral cavity, including saliva (
Distinct active zone protein machineries mediate Ca2+ channel clustering and vesicle priming at hippocampal synapses
Authors: Javier Emperador-Melero, Jonathan W. Andersen, Sarah R. Metzbower, Aaron D. Levy, Poorna A. Dharmasri, Giovanni de Nola, Thomas A. Blanpied, Pascal S. Kaeser
Journal: Nature Neuroscience (2024)
Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo
Authors: Cristina Puy, Samantha A. Moellmer, Jiaqing Pang, Helen Vu, Alexander Melrose, Christina U. Lorentz, Erik I. Tucker, Joseph J Shatzel, Ravi Shankar Keshari, Florea Lupu, David Gailani, Owen J.T. McCarty
Journal: Blood (2024)
Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios
Authors: Dong-Jin Han, Sunmin Kim, Seo-Young Lee, Youngbeen Moon, Su Jung Kang, Jinseon Yoo, Hye Young Jeong, Hae Jin Cho, Jeong Yang Jeon, Byeong Chang Sim, Jaehoon Kim, Seungho Lee, Ruibin Xi, Tae-Min Kim
Journal: Genome Medicine (2024)

Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other.
An unbiased lncRNAs dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for Multiple Myeloma
Authors: Katia Grillone, Serena Ascrizzi, Paolo Cremaschi, Jussara Amato, Nicoletta Polerà, Ottavio Croci, Roberta Rocca, Caterina Riillo, Francesco Conforti, Raffaele Graziano, Diego Brancaccio, Daniele Caracciolo, Stefano Alcaro, Bruno Pagano, Antonio Randazzo, Pierosandro Tagliaferri, Francesco Iorio, Pierfrancesco Tassone
Journal: Blood (2024)
An in situ bioadhesive foam as a large intestinal delivery platform for antibody fragment to treat inflammatory bowel disease
Authors: Wunan Zhang, Fiona McCartney, Yining Xu, Cécilia Bohns Michalowski, Inês Domingues, Espoir K Kambale, Tom G Moreels, Léo Guilbaud, Cheng Chen, Valentina Marotti, David J Brayden, Ana Beloqui
Journal: Journal of Controlled Release (2024)

Biologics have been widely used as injectables in the treatment of inflammatory bowel disease (IBD). Different local treatment attempts have been developed in recent years. However, maintaining systemic levels of biologics is still crucial for achieving colitis remission. An equilibrium between systemic and local concentrations of biologics is therefore essential for treatment of colitis. Current formulations struggle to create optimal balance between drug concentrations in plasma and the colonic wall. Addressing this challenge, we developed a rectally delivered in situ foam that generates CO
An “Iron-phagy” nanoparticle inducing irreversible mitochondrial damages for antitumor therapy
Authors: Zixu Wang, Shanshan Xiang, Yihe Qiu, Fangying Yu, Sufen Li, Shufen Zhang, Guangtao Song, Yichong Xu, Tingting Meng, Hong Yuan, Fuqiang Hu
Journal: Journal of Controlled Release (2024)
Enhanced delivery of CRISPR/Cas9 system based on biomimetic nanoparticles for hepatitis B virus therapy
Authors: Kexin Wu, Miao He, Binli Mao, Yangchen Xing, Shiqi Wei, Dongjun Jiang, Shunyao Wang, Asma A Alkuhali, Jinjun Guo, Zongjie Gan, Man Li, Xiaosong Li, Huali Chen
Journal: Journal of Controlled Release (2024)
Prolonged release from lipid nanoemulsions by modification of drug lipophilicity
Authors: Nina Baumann, Janosch Baumgarten, Conrad Kunick, Heike Bunjes
Journal: Journal of Controlled Release (2024)

In addition to the solubilization of poorly water-soluble, highly lipophilic drugs, lipid nanoemulsions bear potential for drug targeting approaches. This requires that the drug remains within the emulsion droplets until they reach the site of action. Since drug release is rather controlled by the lipophilicity of the drug than by the formulation, this study systematically investigated the influence of drug lipophilicity on the course of drug transfer in (physiological) acceptor media. An increase in drug lipophilicity, according to ClogD/P values, was achieved by the formation of lipophilic prodrugs of 5-phenylanthranilic acid - a potential pathoblocker. The range of substances was supplemented by orlistat, lumefantrine and cholesteryl acetate as model drugs. Drug transfer from supercooled trimyristin nanodroplets was determined via differential scanning calorimetry by monitoring their onset crystallization temperature, which decreases linearly with increasing drug content. Release of the model (pro)drugs ranged from burst to hardly any release in the order of the ClogD/P values. Except for cholesteryl acetate, the results were in line with the lipophilicity of the model (pro)drugs estimated by their retention times on a reversed-phase HPLC column under isocratic conditions. An approximate prediction of drug release kinetics was, thus, possible by logP calculations and, to a limited extent, also by reversed-phase HPLC. A further finding was the increased drug loading capacity of the lipid nanoemulsion for lipophilic prodrugs, if the structural changes of the parent compound were accompanied by a lower melting point.
US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Locally Advanced or Metastatic Breast Cancer With <i>PIK3CA</i>/<i>AKT1</i>/<i>PTEN</i> Alterations
Authors: Asma Dilawari, James Buturla, Christy Osgood, Xin Gao, Wei Chen, Tiffany K. Ricks, Timothy Schaefer, Sreedevi Avasarala, Francisca Reyes Turcu, Anand Pathak, Shyam Kalavar, Vishal Bhatnagar, Justin Collazo, Nam Atiqur Rahman, Bronwyn Mixter, Shenghui Tang, Richard Pazdur, Paul Kluetz, Laleh Amiri-Kordestani
Journal: Journal of Clinical Oncology (2024)

PURPOSE The US Food and Drug Administration (FDA) approved capivasertib in combination with fulvestrant for adult patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, locally advanced, or metastatic breast cancer (MBC) who have received at least one previous endocrine therapy and whose tumors harbor one or more phosphatidylinositol 3-kinase ( PIK3CA )/AKT Serine/Threonine Kinase 1 ( AKT1 )/phosphatase and tensin homolog ( PTEN ) alterations, as detected by an FDA-approved test. PATIENTS AND METHODS Approval was based on CAPItello-291, a randomized, double-blind, multicenter trial of 708 patients with hormone receptor–positive, HER2-negative advanced or MBC, including 289 patients with PIK3CA/AKT1/PTEN tumor alterations. Patients were randomly assigned 1:1 to receive capivasertib 400 mg twice daily for 4 days per week with fulvestrant versus placebo with fulvestrant. Random assignment was stratified by presence of liver metastases, previous treatment with CDK4/6i, cyclin-dependent kinase four and six (CDK4/6) inhibitors, and geographical region. RESULTS A statistically significant progression-free survival (PFS) benefit was demonstrated in the overall population (hazard ratio [HR], 0.6 [95% CI, 0.51 to 0.71]); this result was driven by 289 patients in the biomarker-positive population (HR, 0.5 [95% CI, 0.37 to 0.68]). An exploratory analysis of investigator-assessed PFS in the 313 (44%) patients in the biomarker-negative population showed uncertain benefit (HR, 0.78 [95% CI, 0.60 to 1.01]). With capivasertib, more patients had Grade ≥3 toxicities. Key concerns included hyperglycemia (18% all-grade, 2.8% Grade ≥3), cutaneous toxicity (58% all-grade, 17% Grade ≥3), and diarrhea (72% all-grade, 9% Grade ≥3). CONCLUSION Capivasertib with fulvestrant was approved for patients whose tumors harbored PIK3CA/AKT1/ PTEN alterations. Benefit-risk assessment in this subgroup was favorable based on a statistically significant and clinically meaningful improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in overall survival. By contrast, the benefit-risk was unfavorable in the biomarker-negative population.
Bioprinted mesenchymal stem cell microfiber-derived extracellular vesicles alleviate unilateral renal ischemia-reperfusion injury and fibrosis by inhibiting tubular epithelial cells ferroptosis
Authors: Qiang Guo, Jianwei Chen, Jianjian Wu, Zijun Mo, Lei Ye, Wenwen Zhong, Yi Zhang, Huajian Lai, Yifei Zhang, Jianguang Qiu, Tao Xu, Dejuan Wang
Journal: Bioactive Materials (2024)
Indoor Allergen Exposure and its Association to Upper Respiratory Infections and Pulmonary Outcomes among Children with Asthma
Authors: Darlene Bhavnani, Travis Lilley, Paul J. Rathouz, Sylvie Beaudenon-Huibregtse, Meghan F. Davis, Meredith C. McCormack, Corinne A. Keet, Susan Balcer-Whaley, Michelle Newman, Elizabeth C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2024)
Central Centrifugal Cicatricial Alopecia is associated with Keloid Scarring in Black Women: A Retrospective Chart Review
Authors: Hailey Konisky, Raquel Klinger, Kateryna Karpoff, Eliza Balazic, Chesahna Kindred, Kseniya Kobets
Journal: Journal of the American Academy of Dermatology (2024)
Hydroxyethyl starch conjugates co-assembled nanoparticles promote photodynamic therapy and antitumor immunity by inhibiting antioxidant systems
Authors: Xiang Chen, Zhengtao Yong, Yuxuan Xiong, Hai Yang, Chen Xu, Xing Wang, Qingyuan Deng, Jiayuan Li, Xiangliang Yang, Zifu Li
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Photodynamic therapy (PDT) can produce high levels of reactive oxygen species (ROS) to kill tumor cells and induce antitumor immunity. However, intracellular antioxidant systems, including glutathione (GSH) system and thioredoxin (Trx) system, limit the accumulation of ROS, resulting in compromised PDT and insufficient immune stimulation. Herein, we designed a nanomedicine PtHPs co-loading photosensitizer pyropheophorbide a (PPa) and cisplatin prodrug Pt-COOH(IV) (Pt (IV)) based on hydroxyethyl starch (HES) to inhibit both GSH and Trx antioxidant systems and achieve potent PDT as well as antitumor immune responses. Specifically, HES-PPa and HES-Pt were obtained by coupling HES with PPa and Pt (IV), and assembled into nanoparticle PtHPs by emulsification method to achieve the purpose of co-delivery of PPa and Pt (IV). PtHPs improved PPa photostability while retaining PPa photodynamic properties.
Applying the dissemination and implementation sciences to allergy and immunology: A Work Group Report from the AAAAI Quality, Adherence, and Outcomes Committee
Authors: Sujani Kakumanu, Stanley Szefler, Andrea A. Pappalardo, Anne E. Sales, Alan P. Baptist, Jessica Stern, Sharmilee M. Nyenhuis
Journal: Journal of Allergy and Clinical Immunology (2024)
The Development and Performance of Alternative Criteria for Lung Cancer Screening
Authors: Lauren E. Kearney, Patrick Belancourt, Hormuzd A. Katki, Nichole T. Tanner, Renda Soylemez Wiener, Hilary A. Robbins, Rebecca Landy, Tanner J. Caverly
Journal: Annals of Internal Medicine (2024)

The recommendation for lung cancer screening (LCS) developed by the U.S. Preventive Services Task Force (USPSTF) may exclude some high-benefit people.
Effect of Starting Dialysis Versus Continuing Medical Management on Survival and Home Time in Older Adults With Kidney Failure
Authors: Maria E. Montez-Rath, I-Chun Thomas, Vivek Charu, Michelle C. Odden, Carolyn D. Seib, Shipra Arya, Enrica Fung, Ann M. O’Hare, Susan P.Y. Wong, Manjula Kurella Tamura
Journal: Annals of Internal Medicine (2024)

For older adults with kidney failure who are not referred for transplant, medical management is an alternative to dialysis.
Enhancing neuro-oncology care through equity-driven applications of artificial intelligence
Authors: Mulki Mehari, Youssef Sibih, Abraham Dada, Susan M Chang, Patrick Y Wen, Annette M Molinaro, Ugonma N Chukwueke, Joshua A Budhu, Sadhana Jackson, J Ricardo McFaline-Figueroa, Alyx Porter, Shawn L Hervey-Jumper
Journal: Neuro-Oncology (2024)

Abstract The disease course and clinical outcome for brain tumor patients depend not only on the molecular and histological features of the tumor but also on the patient’s demographics and social determinants of health. While current investigations in neuro-oncology have broadly utilized artificial intelligence (AI) to enrich tumor diagnosis and more accurately predict treatment response, postoperative complications, and survival, equity-driven applications of AI have been limited. However, AI applications to advance health equity in the broader medical field have the potential to serve as practical blueprints to address known disparities in neuro-oncologic care. In this consensus review, we will describe current applications of AI in neuro-oncology, postulate viable AI solutions for the most pressing inequities in neuro-oncology based on broader literature, propose a framework for the effective integration of equity into AI-based neuro-oncology research, and close with the limitations of AI.
Point-of-care C-reactive protein measurement by community health workers safely reduces antimicrobial use among children with respiratory illness in rural Uganda: A stepped wedge cluster randomized trial
Authors: Emily J. Ciccone, Di Hu, John S. Preisser, Caitlin A. Cassidy, Lydiah Kabugho, Baguma Emmanuel, Georget Kibaba, Fred Mwebembezi, Jonathan J. Juliano, Edgar M. Mulogo, Ross M. Boyce
Journal: PLoS Medicine (2024)

Acute respiratory illness (ARI) is one of the most common reasons children receive antibiotic treatment. Measurement of C-reaction protein (CRP) has been shown to reduce unnecessary antibiotic use among children with ARI in a range of clinical settings. In many resource-constrained contexts, patients seek care outside the formal health sector, often from lay community health workers (CHW). This study's objective was to determine the impact of CRP measurement on antibiotic use among children presenting with febrile ARI to CHW in Uganda.
Proton Pump Inhibitors May Cause a Decline in eGFR by Inhibiting Organic Cation Transporter 2–Dependent Creatinine Secretion
Authors: Navjot S. Pabla, Alex Sparreboom
Journal: Journal of the American Society of Nephrology (2024)

We read with great interest the recent investigation outlined in JASN by Pyne et al., which extends on previous observational findings by conducting a post hoc analysis of a clinical trial.1 Their results reveal a modest yet significant increase in the rate of decline in eGFR associated with the use of proton pump inhibitors (PPIs). We concur with the authors regarding the necessity for future investigations to establish causality in these associations. We wish to highlight that the potential involvement of tubular creatinine secretion in the eGFR decline observed with PPI usage has not been adequately considered. Tubular secretion plays a pivotal role in the elimination of endogenous metabolites and pharmaceutical agents. Notably, creatinine undergoes substantial tubular secretion, leading to an overestimation of GFR by 10%–20% when using creatinine clearance. Studies in both human subjects and rodent models have definitively elucidated the function of organic cation transporter 2 (OCT2, encoded by the SLC22A2 gene) in the basolateral tubular uptake and subsequent secretion of creatinine. OCT2 is a versatile transporter involved in the tubular secretion of commonly prescribed medications, such as metformin, cisplatin, and cimetidine. Inhibition of OCT2-mediated creatinine secretion can occur in the presence of either a drug that is a substrate, such as cimetidine, or a drug that inhibits OCT2 function, such as CDK4/6 kinase inhibitors. Several frequently used medications are recognized as OCT2 substrates and or inhibitors, and their administration is often associated with minor yet noteworthy elevations in plasma creatinine levels. Previously, we demonstrated that CDK4/6 kinase inhibitors employed in breast cancer therapy are potent inhibitors of OCT2,2 which was subsequently confirmed as the cause of elevated serum creatinine levels after abemaciclib administration in human subjects.3 It has been established for over a decade that PPIs, such as pantoprazole, are potent inhibitors of OCT2.4 This raises the possibility that the decline in eGFR associated with PPI usage may result from impaired tubular secretion rather than a true decrease in GFR or impaired renal function. In line with this perspective, we concur with the proposal that future investigations should explore alterations associated with PPI administration in other markers of GFR, such as cystatin C, in addition to creatinine.
Authors' Reply: Proton Pump Inhibitors May Cause a Decline in eGFR by Inhibiting Organic Cation Transporter 2–Dependent Creatinine Secretion
Authors: Lonnie Pyne, John Eikelboom, Jacqueline Bosch, Michael Walsh
Journal: Journal of the American Society of Nephrology (2024)

We thank Pabla and Sparreboom for their insightful comments1 highlighting the possibility that the excess eGFR decline seen with pantoprazole in our post hoc analysis2 of the COMPASS trial could be due to reduced creatinine secretion rather than causing kidney injury. The evidence that proton pump inhibitors inhibit organic cation transporter 2 comes primarily from in silico and in vitro experiments,3,4 and its existence/magnitude of the effect is uncertain in humans. Additional analyses of the COMPASS trial suggest that the effect of pantoprazole compared with placebo on rate of eGFR change was attenuated in patients who discontinued treatment before eGFR reassessment (−0.04 ml/min per 1.73 m2 per year, 95% confidence interval, −0.26 to 0.17) compared with those who remained on treatment (−0.60 ml/min per 1.73 m2 per year, 95% confidence interval, −0.85 to −0.34). We reported the mean effect across subgroups given the high risk of presenting biased treatment effects based on postrandomization subgroups,5 but this disparity could support a reversible effect of pantoprazole on eGFR, possibly due to inhibition of creatinine secretion. However, this finding could also be explained by lower total drug exposure, thereby suggesting a dose-response or threshold exposure effect (i.e., those who stopped treatment early avoided measurable pantoprazole-induced kidney injury because they had less drug exposure). These possibilities could be further explored in future proton pump inhibitor studies by serial measurements of kidney function beginning early after starting treatment to understand potential acute effects and continuing until after study drug discontinuation to understand reversibility of effects. In addition, the use of analytes that are less affected by organic cation transporter 2 inhibition, such as cystatin C, may be beneficial. The potential adverse effect of proton pump inhibitors on renal function remains relevant, particularly for those at higher risk for progressive kidney disease and/or who have weak indications for chronic proton pump inhibitor use.
Diagnosis of Brugada Syndrome With a Sodium-Channel-Blocker Test: Who Should Be Tested? Who Should Not?
Authors: Sami Viskin, Ehud Chorin, Raphael Rosso, Ahmad S. Amin, Arthur A. Wilde
Journal: Circulation (2024)

Intravenous infusion of sodium-channel blockers (SCB) with either ajmaline, flecainide, procainamide, or pilsicainide to unmask the ECG of Brugada syndrome is the drug challenge most commonly used for diagnostic purposes when investigating cases possibly related to inherited arrhythmia syndromes. For a patient undergoing an SCB challenge, the impact of a positive result goes well beyond its diagnostic implications. It is, therefore, appropriate to question who should undergo a SCB test to diagnose or exclude Brugada syndrome and, perhaps more importantly, who should not. We present a critical review of the benefits and drawbacks of the SCB challenge when performed in cardiac arrest survivors, patients presenting with syncope, family members of probands with confirmed Brugada syndrome, and asymptomatic patients with suspicious ECG.
Junctophilin-2 Regulates Mitochondrial Metabolism
Authors: Sasha Z. Prisco, Lynn M. Hartweck, Felipe Kazmirczak, Jenna B. Mendelson, Stephanie L. Deng, Madelyn Blake, Satadru K. Lahiri, Xander H.T. Wehrens, Kurt W. Prins
Journal: Circulation (2024)