tbuckley/cabot-search huggingface dataset:
Silencing siRNA microneedle patches versus silicone sheets in reducing post-surgical scars: a randomized single-blinded intra-individually controlled clinical trial
Authors: Delwyn Zhi Jie Lim, Yong Yao Chun, Amelia Yuting Monteiro, Hui Mei Cheng, Jia Yi Lee, Yingrou Tan, Timothy T Y Tan, Hong Liang Tey
Journal: British Journal of Dermatology (2024)

A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars.
Olfr2-positive macrophages originate from monocytes proliferate <i>in situ</i> and present a pro-inflammatory foamy-like phenotype
Authors: Sujit Silas Armstrong Suthahar, Felix Sebastian Nettersheim, Ahmad Alimadadi, Erpei Wang, Monica Billitti, Natalya Resto-Trujillo, Payel Roy, Catherine C Hedrick, Klaus Ley, Marco Orecchioni
Journal: Cardiovascular Research (2024)

Olfactory receptor 2 (Olfr2) has been identified in a minimum of 30% of vascular macrophages, and its depletion was shown to reduce atherosclerosis progression. Mononuclear phagocytes, including monocytes and macrophages within the vessel wall, are major players in atherosclerosis. Single-cell RNA sequencing studies revealed that atherosclerotic artery walls encompass several monocytes and vascular macrophages, defining at least nine distinct subsets potentially serving diverse functions in disease progression. This study investigates the functional phenotype and ontogeny of Olfr2-expressing vascular macrophages in atherosclerosis.
Intranasal delivery of imaging agents to the brain
Authors: Abdallah Almahmoud, Harendra S Parekh, Brett M Paterson, Karnaker Reddy Tupally, Viktor Vegh
Journal: Theranostics (2024)

The potential of intranasal administered imaging agents to altogether bypass the blood-brain barrier offers a promising non-invasive approach for delivery directly to the brain. This review provides a comprehensive analysis of the advancements and challenges of delivering neuroimaging agents to the brain by way of the intranasal route, focusing on the various imaging modalities and their applications in central nervous system diagnostics and therapeutics. The various imaging modalities provide distinct insights into the pharmacokinetics, biodistribution, and specific interactions of imaging agents within the brain, facilitated by the use of tailored tracers and contrast agents.
Theoretical basis, state and challenges of living cell-based drug delivery systems
Authors: Wei Liu, Guowang Cheng, Hao Cui, Zhen Tian, Bowen Li, Yanhua Han, Jia-Xin Wu, Jie Sun, Yuyue Zhao, Tongkai Chen, Guangtao Yu
Journal: Theranostics (2024)

The therapeutic efficacy of drugs is determined, to a certain extent, by the efficiency of drug delivery. The low efficiency of drug delivery systems (DDSs) is frequently associated with serious toxic side effects and can even prove fatal in certain cases. With the rapid development of technology, drug delivery has evolved from using traditional frameworks to using nano DDSs (NDDSs), endogenous biomaterials DDSs (EBDDSs), and living cell DDSs (LCDDSs). LCDDSs are receiving widespread attention from researchers at present owing to the unique advantages of living cells in targeted drug delivery, including their excellent biocompatibility properties, low immunogenicity, unique biological properties and functions, and role in the treatment of diseases. However, the theoretical basis and techniques involved in the application of LCDDSs have not been extensively summarized to date. Therefore, this review comprehensively summarizes the properties and applications of living cells, elaborates the various drug loading approaches and controlled drug release, and discusses the results of clinical trials. The review also discusses the current shortcomings and prospects for the future development of LCDDSs, which will serve as highly valuable insights for the development and clinical transformation of LCDDSs in the future.
Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice
Authors: Priyadarshani Nadeeshika Samarawickrama, Guiqin Zhang, Enfang Zhu, Xin Dong, Ayesha Nisar, Hong Zhu, Yuan Ma, Zheyan Zhou, Honglin Yang, Li Gui, Mei Cao, Wei Li, Yu Chang, Meiting Zi, Haoling Cui, Zhongping Duan, Xuan Zhang, Wen Li, Yonghan He
Journal: Theranostics (2024)

Diabetic foot ulcers (DFUs) pose a substantial healthcare challenge due to their high rates of morbidity, recurrence, disability, and mortality. Current DFU therapeutics continue to grapple with multiple limitations. Senescent cells (SnCs) have been found to have a beneficial effect on acute wound healing, however, their roles in chronic wounds, such as DFU, remain unclear.
Extrachromosomal circular DNA orchestrates genome heterogeneity in urothelial bladder carcinoma
Authors: Wei Lv, Xiaoguang Pan, Peng Han, Shuang Wu, Yuchen Zeng, Qingqing Wang, Lidong Guo, Mengyang Xu, Yanwei Qi, Li Deng, Zhe Xu, Conghui Li, Tianxi Yu, Xin Cui, Huajing Teng, Chongjun Xiang, Haotian Tan, Yue Li, Ning Liang, Huiying Tao, Qingqing Gao, Guohua Yu, Jia Mi, Fuyi Xu, Benjiao Gong, Lei Shi, Tao Wang, Huanming Yang, Wei Dong, Lars Bolund, Lin Lin, Wenting Wang, Hanbo Li, Jinrong Huang, Chunhua Lin, Yonglun Luo
Journal: Theranostics (2024)

Extrachromosomal circular DNA is a hallmark of cancer, but its role in shaping the genome heterogeneity of urothelial bladder carcinoma (UBC) remains poorly understood. Here, we comprehensively analyzed the features of extrachromosomal circular DNA in 80 UBC patients.
The biphasic role of Hspb1 on ferroptotic cell death in Parkinson's disease
Authors: Jieyi Meng, Jinyu Fang, Yutong Bao, Huizhu Chen, Xiaodan Hu, Ziyuan Wang, Man Li, Quancheng Cheng, Yaqiong Dong, Xiaoda Yang, Yushu Zou, Dongyu Zhao, Jiping Tang, Weiguang Zhang, Chunhua Chen
Journal: Theranostics (2024)

: Ferroptosis-driven loss of dopaminergic neurons plays a pivotal role in the pathogenesis of Parkinson's disease (PD). In PD patients, Hspb1 is commonly observed at abnormally high levels in the substantia nigra. The precise consequences of Hspb1 overexpression in PD, however, have yet to be fully elucidated.
A novel expression domain of <i>extradenticle</i> underlies the evolutionary developmental origin of the chelicerate patella
Authors: Benjamin C Klementz, Georg Brenneis, Isaac A Hinne, Ethan M Laumer, Sophie M Neu, Grace M Hareid, Guilherme Gainett, Emily V W Setton, Catalina Simian, David E Vrech, Isabella Joyce, Austen A Barnett, Nipam H Patel, Mark S Harvey, Alfredo V Peretti, Monika Gulia-Nuss, Prashant P Sharma
Journal: Molecular Biology and Evolution (2024)

Neofunctionalization of duplicated gene copies is thought to be an important process underlying the origin of evolutionary novelty and provides an elegant mechanism for the origin of new phenotypic traits. One putative case where a new gene copy has been linked to a novel morphological trait is the origin of the arachnid patella, a taxonomically restricted leg segment. In spiders, the origin of this segment has been linked to the origin of the paralog dachshund-2, suggesting that a new gene facilitated the expression of a new trait. However, various arachnid groups that possess patellae do not have a copy of dachshund-2, disfavoring the direct link between gene origin and trait origin. We investigated the developmental genetic basis for patellar patterning in the harvestman Phalangium opilio, which lacks dachshund-2. Here, we show that the harvestman patella is established by a novel expression domain of the transcription factor extradenticle. Leveraging this definition of patellar identity, we surveyed targeted groups across chelicerate phylogeny to assess when this trait evolved. We show that a patellar homolog is present in Pycnogonida (sea spiders) and various arachnid orders, suggesting a single origin of the patella in the ancestor of Chelicerata. A potential loss of the patella is observed in Ixodida. Our results suggest that the modification of an ancient gene, rather than the neofunctionalization of a new gene copy, underlies the origin of the patella. Broadly, this work underscores the value of comparative data and broad taxonomic sampling when testing hypotheses in evolutionary developmental biology.
Patterns of fitness and gene expression epistasis generated by beneficial mutations in the <i>rho</i> and <i>rpoB</i> genes of <i>Escherichia coli</i> during high-temperature adaptation
Authors: Andrea González-González, Tiffany N Batarseh, Alejandra Rodríguez-Verdugo, Brandon S Gaut
Journal: Molecular Biology and Evolution (2024)

Epistasis is caused by genetic interactions among mutations that affect fitness. To characterize properties and potential mechanisms of epistasis, we engineered eight double mutants that combined mutations from the rho and rpoB genes of Escherichia coli. The two genes encode essential functions for transcription, and the mutations in each gene were chosen because they were beneficial for adaptation to thermal stress (42.2 °C). The double mutants exhibited patterns of fitness epistasis that included diminishing returns epistasis at 42.2 °C, stronger diminishing returns between mutations with larger beneficial effects and both negative and positive (sign) epistasis across environments (20.0 °C and 37.0 °C). By assessing gene expression between single and double mutants, we detected hundreds of genes with gene expression epistasis. Previous work postulated that highly connected hub genes in coexpression networks have low epistasis, but we found the opposite: hub genes had high epistasis values in both coexpression and protein-protein interaction networks. We hypothesized that elevated epistasis in hub genes reflected that they were enriched for targets of Rho termination but that was not the case. Altogether, gene expression and coexpression analyses revealed that thermal adaptation occurred in modules, through modulation of ribonucleotide biosynthetic processes and ribosome assembly, the attenuation of expression in genes related to heat shock and stress responses, and with an overall trend toward restoring gene expression toward the unstressed state.
Tracking rare single donor and recipient immune and leukemia cells after allogeneic hematopoietic cell transplantation using mitochondrial DNA mutations
Authors: Livius Penter, Nicoletta Cieri, Katie Maurer, Marwan Kwok, Haoxiang Lyu, Wesley S. Lu, Giacomo Oliveira, Satyen H. Gohil, Ignaty Leshchiner, Caleb A. Lareau, Leif S. Ludwig, Donna S. Neuberg, Haesook T. Kim, Shuqiang Li, Lars Bullinger, Jerome Ritz, Gad Getz, Jacqueline S. Garcia, Robert J. Soiffer, Kenneth J. Livak, Catherine J. Wu
Journal: Blood Cancer Discovery (2024)

Abstract Combined tracking of clonal evolution and chimeric cell phenotypes could enable detection of the key cellular populations associated with response following therapy, including after allogeneic hematopoietic stem cell transplantation (HSCT). We demonstrate that mitochondrial DNA (mtDNA) mutations co-evolve with somatic nuclear DNA mutations at relapse post-HSCT and provide a sensitive means to monitor these cellular populations. Further, detection of mtDNA mutations via single-cell ATAC with select antigen profiling by sequencing (ASAP-seq) simultaneously determines not only donor and recipient cells, but also their phenotype, at frequencies of 0.1-1%. Finally, integration of mtDNA mutations, surface markers, and chromatin accessibility profiles enables the phenotypic resolution of leukemic populations from normal immune cells, thereby providing fresh insights into residual donor-derived engraftment and short-term clonal evolution following therapy for post-transplant leukemia relapse. As throughput evolves, we envision future development of single-cell sequencing-based post-transplant monitoring as a powerful approach for guiding clinical decision making.
Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-In-Human Trial
Authors: Jane C. Davies, Deepika Polineni, A Christopher Boyd, Scott Donaldson, Deborah R Gill, Uta Griesenbach, Stephen C Hyde, Raksha Jain, Gerry McLachlan, Marcus A Mall, Eric WFW Alton
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (
Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for <i>PIK3CA</i>-Mutated, Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced or Metastatic Breast Cancer
Authors: Komal L. Jhaveri, Melissa K. Accordino, Philippe L. Bedard, Andrés Cervantes, Valentina Gambardella, Erika Hamilton, Antoine Italiano, Kevin Kalinsky, Ian E. Krop, Mafalda Oliveira, Peter Schmid, Cristina Saura, Nicholas C. Turner, Andrea Varga, Sravanthi Cheeti, Stephanie Hilz, Katherine E. Hutchinson, Yanling Jin, Stephanie Royer-Joo, Ubong Peters, Noopur Shankar, Jennifer L. Schutzman, Dejan Juric
Journal: Journal of Clinical Oncology (2024)

PURPOSE To investigate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of inavolisib, a potent and selective small-molecule inhibitor of p110α that promotes the degradation of mutated p110α, in combination with palbociclib and endocrine therapy (ET), in a phase I/Ib study in patients with PIK3CA -mutated, hormone receptor–positive/human epidermal growth factor receptor 2–negative locally advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT03006172 ). METHODS Women ≥18 years of age received inavolisib, palbociclib, and letrozole (Inavo + Palbo + Letro arm) or fulvestrant (Inavo + Palbo + Fulv arm) until unacceptable toxicity or disease progression. The primary objective was to evaluate safety or tolerability. RESULTS Fifty-three patients were included, 33 in the Inavo + Palbo + Letro arm and 20 in the Inavo + Palbo + Fulv arm. Median duration of inavolisib treatment was 15.7 and 20.8 months (cutoff: March 27, 2023), respectively. Treatment-related adverse events (TRAEs) occurred in all patients; the most frequent were stomatitis, hyperglycemia, and diarrhea; grade ≥3 any TRAE rates were 87.9% and 85.0%; 6.1% and 10.0% discontinued any treatment due to TRAEs in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. No PK drug–drug interactions (DDIs) were observed among the study treatments when administered. Confirmed objective response rates were 52.0% and 40.0% in patients with measurable disease, and median progression-free survival was 23.3 and 35.0 months in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. Available paired pre- and on-treatment tumor tissue and circulating tumor DNA analyses confirmed the effects of study treatment on pharmacodynamic and pathophysiologic biomarkers of response. CONCLUSION Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity.
Diagnosis and Risk Stratification in Waldenström Macroglobulinemia
Authors: Saurabh Zanwar, Prashant Kapoor
Journal: Journal of the National Comprehensive Cancer Network (2024)

Waldenström macroglobulinemia (WM) is a B-cell lymphoma characterized by the presence of bone marrow lymphoplasmacytic infiltration and circulating monoclonal immunoglobulin M protein. The clinical presentation of WM is variable, ranging from gradually progressive cytopenias, organomegaly, fatigue, B symptoms, and peripheral neuropathy to the more emergent presentation with symptomatic hyperviscosity, cryoglobulinemia, hemolytic anemia–associated symptoms, acquired von Willebrand disease or acquired hemophilia–associated bleeding. Approximately 1 in 5 patients with WM are asymptomatic at diagnosis and classified as having smoldering WM, not requiring WM-directed therapy. Although WM typically has an indolent, relapsing-remitting course, the outcomes are heterogeneous. The prognosis of patients with WM is known to be impacted by certain clinical and laboratory features at initial presentation, with advanced age, elevated serum lactate dehydrogenase, and low serum albumin unfavorably affecting the outcome. Although complications such as histologic transformation or light and/or heavy chain (AL/ALH) amyloidosis are infrequent, their occurrence adversely influences the disease course. The International Prognostic Staging System for WM (IPSS-WM) is a validated model, often used in clinical practice, but needs to be reexamined in the current era. The discovery of the recurrent MYD88 L265P gain-of-function point mutation and the subclonal CXCR4 mutations has helped improve our understanding of the WM biology, and the prognostic impact of these mutations is under evaluation, with somewhat inconsistent findings thus far across studies. This review discusses the clinical presentation, diagnostic criteria, and prognostic markers of WM.
Cancer-Associated Venous Thromboembolic Disease, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology
Authors: Michael B. Streiff, Bjorn Holmstrom, Dana Angelini, Aneel Ashrani, Tyler Buckner, Robert Diep, Kleber Yotsumoto Fertrin, Annemarie E. Fogerty, Nicolas Gallastegui Crestani, Radhika Gangaraju, Cristhiam Rojas-Hernandez, Samuel Z. Goldhaber, Ibrahim Ibrahim, Timothy Kubal, Andrew D. Leavitt, Ming Lim, Janelle Mann, Simon Mantha, Colleen Morton, Alex Nester, Andrew O’Brien, Thomas L. Ortel, Alexander Pine, Allyson Pishko, Mona Ranade, Amirali Salmasi, Jordan Schaefer, Eliot Williams, Geoffrey Wool, Theodore Wun, Sarah Montgomery, Jamie Nguyen, Deborah Freedman-Cass, Bailee Sliker
Journal: Journal of the National Comprehensive Cancer Network (2024)

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.
NCCN Guidelines® Insights: Colorectal Cancer Screening, Version 1.2024
Authors: Reid M. Ness, Xavier Llor, Mohammad Ali Abbass, Shrinivas Bishu, Christopher T. Chen, Gregory Cooper, Dayna S. Early, Mark Friedman, David Fudman, Francis M. Giardiello, Kathryn Glaser, Surya Gurudu, Michael Hall, Lyen C. Huang, Rachel Issaka, Bryson Katona, Trilokesh Kidambi, Audrey J. Lazenby, Jennifer Maratt, Arnold J. Markowitz, Joseph Marsano, Folasade P. May, Robert J. Mayer, Kinga Olortegui, Swati Patel, Shajan Peter, Laura D. Porter, Mehnaz Shafi, Peter P. Stanich, Jonathan Terdiman, Peter Vu, Jennifer M. Weiss, Elizabeth Wood, Carly J. Cassara, Vaishnavi Sambandam
Journal: Journal of the National Comprehensive Cancer Network (2024)

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel’s recommendations regarding the age at which to initiate screening in average-risk individuals and those with increased risk based on personal history of childhood, adolescent, and young adult cancer.
Evaluation of Socioeconomic and Racial/Ethnic Disparities in All-Cause Mortality in Adolescents and Young Adults With Cancer
Authors: Scott Henderson, Mark Duggan, Chun Chao, Robert Cooper
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: Adolescent and young adult (AYA) patients with cancer have historically been understudied. Few studies have examined survival disparities associated with racial/ethnic and socioeconomic status (SES) and do not account for the influence of insurance status and access to care. We evaluated the association of SES and race/ethnicity with overall mortality for AYA patients who were members of an integrated health system with relatively equal access to care. Methods: AYA patients diagnosed with the 15 most common cancer types during 2010 through 2018 at Kaiser Permanente Southern California were included. Neighborhood Deprivation Index (NDI) quartile (Q1: least deprived; Q4: most deprived) was used as a measure of SES. Mortality rate per 1,000 person-years was calculated for each racial/ethnic and NDI subgroup. Multivariable Cox model was used to estimate hazard ratios (HRs) for all-cause mortality adjusting for sex, age and stage at diagnosis, cancer type, race/ethnicity, and NDI. Results: Data for 6,379 patients were tracked for a maximum of 10 years. Crude mortality rates were higher among non-White racial/ethnic patients compared with non-Hispanic (NH)–White patients. In the Cox model, Hispanic (HR, 1.31; P =.004) and NH-Black (HR, 1.34; P =.05) patients experienced significantly higher all-cause mortality risk compared with NH-White patients. Patients from more deprived neighborhoods had higher mortality risk. In the Cox model, there was no significant difference in all-cause mortality between Q1 and Q2 through Q4 (Q2: HR, 0.88; P =.26, Q3: HR, 0.94; P =.56, and Q4: HR, 0.95; P =.70). Conclusions: For AYAs with cancer with similar access to care, Hispanic and NH-Black patients have higher risk of all-cause mortality than NH-White patients, whereas no significant SES-associated survival disparities were observed. These findings warrant further investigation, awareness, and intervention to address inequities in cancer care among vulnerable populations.