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Recent UMass Chan Publications
Total:
30
results
Nuclear factor kappa B-dependent persistence of Salmonella Typhi and Paratyphi in human macrophages
Salmonella serovars Typhi and Paratyphi cause a prolonged illness known as enteric fever, whereas other serovars cause acute gastroenteritis. Mechanisms responsible for the divergent clinical manifestations of nontyphoidal and enteric fever Salmonella infections have remained elusive. Here, we show that S. Typhi and S. Paratyphi A can persist within human macrophages, whereas S. Typhimurium rapidl...
Preexisting antibody assays for gene therapy: Considerations on patient selection cutoffs and companion diagnostic requirements
Recombinant adeno-associated virus (AAV) vectors are the leading delivery vehicle used for in vivo gene therapies. Anti-AAV antibodies (AAV Abs) can interact with the viral capsid component of an AAV-based gene therapy (GT). Therefore, patients with preexisting AAV Abs (seropositive patients) are often excluded from GT trials to prevent treatment of patients who are unlikely to benefit¹ or may hav...
What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2023? Report of the Basic and Translational Research Committee of the International Liver Transplantation Society
The 2023 Joint Annual Congress of the International Liver Transplantation Society, European Liver and Intestine Transplant Association, and Liver Intensive Care Group of Europe were held in Rotterdam, the Netherlands, from May 3 to 6, 2023. This year, all speakers were invited to attend the Congress in person for the first time since the COVID-19 pandemic. The congress was attended by 1159 registe...
CKLF instigates a "cold" microenvironment to promote MYCN-mediated tumor aggressiveness
Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor (CKLF) is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN. Using the ...
Modular vector assembly enables rapid assessment of emerging CRISPR technologies
The diversity of CRISPR systems, coupled with scientific ingenuity, has led to an explosion of applications; however, to test newly described innovations in their model systems, researchers typically embark on cumbersome, one-off cloning projects to generate custom reagents that are optimized for their biological questions. Here, we leverage Golden Gate cloning to create the Fragmid toolkit, a mod...
Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics
Numerous nonantibiotic drugs have potent antibacterial activity and can adversely impact the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Netwo...
Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis
CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.
Standard Setting for the CGSO Qualifying Examination: A Structured Approach Setting a Meaningful Standard
No abstract
Machine Learning and Digital Biomarkers Can Detect Early Stages of Neurodegenerative Diseases
Neurodegenerative diseases (NDs) such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) are devastating conditions that can develop without noticeable symptoms, causing irreversible damage to neurons before any signs become clinically evident. NDs are a major cause of disability and mortality worldwide. Currently, there are no cures or treatments to halt their progression. Therefore, the de...
Contributions of Hyperactive Mutations in Mpro from SARS-CoV-2 to Drug Resistance
The appearance and spread of mutations that cause drug resistance in rapidly evolving diseases, including infections by the SARS-CoV-2 virus, are major concerns for human health. Many drugs target enzymes, and resistance-conferring mutations impact inhibitor binding or enzyme activity. Nirmatrelvir, the most widely used inhibitor currently used to treat SARS-CoV-2 infections, targets the main prot...
Enfortumab-vedotin use for urothelial carcinoma in two patients on hemodialysis
Enfortumab vedotin (EV) is a novel treatment option for patients with advanced/metastatic urothelial carcinoma who have progressed after chemotherapy and immunotherapy. Two patients at two different New England tertiary cancer care centers were treated with EV while concurrently receiving hemodialysis (HD), where a complete response to EV in both patients was noted. The use of EV in patients requi...
Neonatal respiratory care practice among level III and IV NICUs in New England
CONCLUSIONS: Results identify trends and areas of variation and suggest that the presence of guidelines alone is not predictive of outcome.
Beyond the Beat: A Cardiac Anesthesiologist's Perspective on Cardiovascular-Kidney-Metabolic Health in Perioperative Care
No abstract
Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis
CONCLUSIONS AND RELEVANCE: In this study, activated glial markers (in particular GFAP) and neurofilament heavy chain were associated specifically with nonrelapsing progressive disease outcomes (independent of acute inflammatory activity). Elevated CSF GFAP was associated with long-term MS disease progression.
cMPL-Based Purification and Depletion of Human Hematopoietic Stem Cells: Implications for Pre-Transplant Conditioning
The transplantation of gene-modified autologous hematopoietic stem and progenitor cells (HSPCs) offers a promising therapeutic approach for hematological and immunological disorders. However, this strategy is often limited by the toxicities associated with traditional conditioning regimens. Antibody-based conditioning strategies targeting cKIT and CD45 antigens have shown potential in mitigating t...
Survivin Mediates Mitotic Onset in HeLa Cells Through Activation of the Cdk1-Cdc25B Axis
The Survivin protein has roles in repairing incorrect microtubule-kinetochore attachments at prometaphase, and the faithful execution of cytokinesis, both as part of the chromosomal passenger complex (CPC) (1). In this context, errors frequently lead to aneuploidy, polyploidy and cancer (1). Adding to these well-known roles of this protein, this paper now shows for the first time that Survivin is ...
Safety and Outcomes in Multiplane Facial Rejuvenation with Tranexamic Acid: A Cohort Study
CONCLUSIONS: TXA improves the short- and long-term outcomes of patients who undergo multiplane facial rhytidectomy. It also decreases intraoperative bleeding by more than half and reduces the operative time by one third. Moreover, patients receiving TXA presented significantly less ecchymosis, edema, and time to drain removal.
Evaluating the Impact of a Pediatric Inpatient Social Care Program in a Community Hospital
CONCLUSIONS: The implementation of a stakeholder-informed social care program within a community hospital setting led to the increased identification of social risks and social work consultations and improved timeliness of social work consultations and written communication of social risks in discharge summaries for primary care providers.
The Sac Evolution Imaging Follow-Up after EVAR: an international expert opinion-based Delphi consensus study
CONCLUSIONS: Based on the elevated strength and high consistency of this international expert-based Delphi consensus, most of the statements might guide current clinical management of follow-up after EVAR according to the sac regression. Future studies are needed to clarify debated issues.
FGFR inhibitors in urothelial cancer: Contextualizing THOR within the new treatment landscape
As frontline treatment of advanced urothelial cancer (UC) evolves, optimal sequencing of subsequent therapies remains unclear. The phase 3 THOR trial compared the efficacy of erdafitinib to chemotherapy or immunotherapy in FGFR3/2-altered advanced UC. THOR offers valuable data informing sequencing strategies, reinforcing the need for molecular testing in UC.
Enhancing Osteosacoma Killing and CT Imaging Using Ultra High Drug Loading and NIR-Responsive Bismuth Sulfide @Mesoporous Silica Nanoparticles
No abstract
Trisomy silencing by XIST: translational prospects and challenges
XIST RNA is heavily studied for its role in fundamental epigenetics and X-chromosome inactivation; however, the translational potential of this singular RNA has been much less explored. This article combines elements of a review on XIST biology with our perspective on the translational prospects and challenges of XIST transgenics. We first briefly review aspects of XIST RNA basic biology that are ...
Examining racial/ethnic inequities in treatment participation among perinatal individuals with depression
CONCLUSIONS: Perinatal mental healthcare inequities are associated with disparities in treatment referrals. Interventions focusing on referral disparities across race and ethnicity are needed.
How persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease
T cells help orchestrate immune responses to pathogens, and their aberrant regulation can trigger autoimmunity. Recent studies highlight that a threshold number of T cells (a quorum) must be activated in a tissue to mount a functional immune response. These collective effects allow the T cell repertoire to respond to pathogens while suppressing autoimmunity due to circulating autoreactive T cells....
Biodistribution and safety of a single rAAV3B-AAT vector for silencing and replacement of alpha-1 antitrypsin in Cynomolgus macaques
Alpha-1 antitrypsin deficiency (AATD) is characterized by both chronic lung disease due to loss of wild-type AAT (M-AAT) antiprotease function and liver disease due to toxicity from delayed secretion, polymerization, and aggregation of misfolded mutant AAT (Z-AAT). The ideal gene therapy for AATD should therefore comprise both endogenous Z-AAT suppression and M-AAT overexpression. We designed a du...
Editorial: Quantification and prediction of T-cell cross-reactivity through experimental and computational methods
No abstract
Effect of Ergocalciferol on β-Cell Function in New-Onset Type 1 Diabetes: A Secondary Analysis of a Randomized Clinical Trial
No abstract
Complication Rates of Central Venous Catheters: A Systematic Review and Meta-Analysis
CONCLUSIONS AND RELEVANCE: Approximately 3% of CVC placements were associated with major complications. Use of ultrasonography guidance may reduce specific risks including arterial puncture and pneumothorax.
Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors
CONCLUSION: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially ...
The structure of Mycobacterium thermoresistibile MmpS5 reveals a conserved disulfide bond across mycobacteria
The tuberculosis (TB) emergency has been a pressing health threat for decades. With the emergence of drug-resistant TB and complications from the COVID-19 pandemic, the TB health crisis is more serious than ever. Mycobacterium tuberculosis (Mtb), the causative agent of TB, requires iron for its survival. Thus, Mtb has evolved several mechanisms to acquire iron from the host. Mtb produces two sider...
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