Hydration behavior of asparagine: an approach using time domain reflectometry at low temperatures.

The dielectric behavior of Asparagine (CHNO) in water over the frequency range of 10 MHz to 30 GHz in the temperature region of 278.15-303.15 K in a step of 5 K has been carried out using time domain reflectometry (TDR) at various concentrations of asparagine.

Endovascular Aneurysm Repair-First Strategy for Ruptured Abdominal Aortic Aneurysm Might Not Be Applicable to all Cases.

Background: We evaluate the relationship between the hospital case volume (HCV) and mortality outcomes after open aortic repair (OAR) and endovascular aortic repair (EVAR) of intact (iEVAR) and ruptured (rEVAR) abdominal aortic aneurysm (AAA) using a contemporary administrative database.

Methods: The Healthcare Cost and Utilization Project Database for New York (2016) and New Jersey/Maryland/Florida (2016-2017) were queried using International Classification of Disease-10th edition to identify patients who had undergone OAR and EVAR. The hospitals were categorized into quartiles (Q) per overall (EVAR + OAR) volume, OAR-alone volume and EVAR-alone volume.

Drug-Polymer Nanodroplet Formation and Morphology Drive Solubility Enhancement of GDC-0810.

Nanodroplet formation is important to achieve supersaturation of active pharmaceutical ingredients (APIs) in an amorphous solid dispersion. The aim of the current study was to explore how polymer composition, architecture, molar mass, and surfactant concentration affect polymer-drug nanodroplet morphology with the breast cancer API, GDC-0810. The impact of nanodroplet size and morphology on dissolution efficacy and drug loading capacity was explored using polarized light microscopy, dynamic light scattering, and cryogenic transmission electron microscopy.

Analytical Characterization of Heterogeneities in mRNA-Lipid Nanoparticles Using Sucrose Density Gradient Ultracentrifugation.

Rational design and robust formulation processes are critical for optimal delivery of mRNA by lipid nanoparticles (LNPs). Varying degrees of heterogeneity in mRNA-LNPs can affect their biophysical and functional properties. Given the profound complexity of mRNA-LNPs, it is critical to develop comprehensive and orthogonal analytical techniques for a better understanding of these formulations.

Neutrophils at the Crossroads: Unraveling the Multifaceted Role in the Tumor Microenvironment.

Over the past decade, research has prominently established neutrophils as key contributors to the intricate landscape of tumor immune biology. As polymorphonuclear granulocytes within the innate immune system, neutrophils play a pivotal and abundant role, constituting approximately ∼70% of all peripheral leukocytes in humans and ∼10-20% in mice. This substantial presence positions them as the frontline defense against potential threats.

Myotubularin-related protein-6 silencing protects mice from Leishmania donovani infection.

The protozoan parasite Leishmania donovani resides within mammalian macrophages and alters its antigen-presenting functions to negatively regulate host-protective T cell responses. This negative regulation of human T cell responses in vitro is attributed to myotubularin-related protein-6 (MTMR6), an ion channel-associated phosphatase. As mouse and human MTMR6 share homology, we studied whether MTMR6 silencing by lentivirally expressed MTMR6shRNA (Lv-MTMR6shRNA) reduced Leishmania growth in macrophages and whether MTMR6 silencing in Leishmania-susceptible BALB/c mice reduced the infection and reinstated host-protective T cell functions.

Interleukin-7 potentiates MAPK10-elicited host-protective vaccine against Leishmania donovani.

Leishmania donovani causes the potentially fatal disease visceral leishmaniasis for which neither a vaccine nor an adjuvant for human use exists. Although interleukin-7 (IL-7) is implicated in CD4 T-cell response stabilization, its anti-leishmanial function is uncertain. Therefore, we examined whether IL-7 would potentiate the efficacy of Leishmania major-expressed MAPK10 (LmjMAPK10; M10)-elicited anti-leishmanial host-protective response.

Noncoding mutations cause super-enhancer retargeting resulting in protein synthesis dysregulation during B cell lymphoma progression.

Whole-genome sequencing of longitudinal tumor pairs representing transformation of follicular lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) identified coding and noncoding genomic alterations acquired during lymphoma progression. Many of these transformation-associated alterations recurrently and focally occur at topologically associating domain resident regulatory DNA elements, including H3K4me3 promoter marks located within H3K27ac super-enhancer clusters in B cell non-Hodgkin lymphoma. One region found to undergo recurrent alteration upon transformation overlaps a super-enhancer affecting the expression of the PAX5/ZCCHC7 gene pair.

Speed kills? Quantifying the association between police traffic stops, types of stops, and motor vehicle collisions.

Background: Motor vehicle crashes (MVCs) are a leading cause of traumatic death and injury. Police traffic stops (PTS) are a common approach to enforcing motor vehicle laws intended to prevent MVCs. However, it is unclear which types of PTS are most effective.

Temperature-dependent hydration behavior of aqueous lysine: an approach towards protein binding through dielectric spectroscopy.

Present work reports interaction between water and amino acid lysine for understanding the physicochemical properties that will be useful in the structure formation of protein. The dielectric relaxation of aqueous lysine was systematically investigated over a temperature range spanning from 298.15 K to 278.

Direct oral anticoagulants over warfarin at discharge associated with improved survival and patency in infra-geniculate bypasses with prosthetic conduits.

Objective: There is no consensus on the optimal anticoagulant regimen following lower extremity bypass. Historically, warfarin has been utilized for prosthetic or compromised vein bypasses. Direct-acting oral anticoagulants (DOACs) are increasingly replacing warfarin in this context, but their efficacy in bypass preservation has not been well-studied.

Water dynamics on the structural properties of some NSAID's with leucine in the picosecond region using time domain spectroscopy.

Concentration-dependent dielectric response for non-steroidal anti-inflammatory drugs (NSAIDs): Aceclofenac (ACF) and Diclofenac (DCF) in the aqueous leucine solution have been reported at different concentrations and temperatures (298.15 K to 283.15 K).

Disparities in Clinical Trial Enrollment and Reporting in Rectal Cancer: A Systematic Review and Demographic Comparison to the National Cancer Database.

Background: Cancer care guidelines based on clinical trial data in homogenous populations may not be applicable to all rectal cancer patients. The aim of this study was to evaluate whether patients enrolled in rectal cancer clinical trials (CTs) are representative of United States (U.S.

Inhalable dry powder product (DPP) of mRNA lipid nanoparticles (LNPs) for pulmonary delivery.

Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated successful development of an mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes for the DPP were accomplished by varying the excipients, lipid composition, concentration of LNPs, and weight percentage of mRNA.

Process Robustness in Lipid Nanoparticle Production: A Comparison of Microfluidic and Turbulent Jet Mixing.

The recent clinical and commercial success of lipid nanoparticles (LNPs) for nucleic acid delivery has incentivized the development of new technologies to manufacture LNPs. As new technologies emerge, researchers must determine which technologies to assess and how to perform comparative evaluations. In this article, we use a quality-by-design approach to systematically investigate how the mixer technology used to form LNPs influences LNPstructure.

Primary Colorectal Tumor Location and Predictors for Metastasis to the Brain.

Introduction Although rectal cancer is thought to have a higher rate of metastasis to the brain compared with colon cancer, there is limited and contradictory data on the subject. This study aims to determine the prevalence of brain metastasis for colon and rectal cancers (CRC), and to explore associations and predictors of brain metastasis (BM). Methods The 2010-2016 National Cancer Database (NCDB) was queried for patients with stage IV CRC.

Correlating the Structure and Gene Silencing Activity of Oligonucleotide-Loaded Lipid Nanoparticles Using Small-Angle X-ray Scattering.

With three FDA-approved products, lipid nanoparticles (LNPs) are under intensive development for delivering wide-ranging nucleic acid therapeutics. A significant challenge for LNP development is insufficient understanding of structure-activity relationship (SAR). Small changes in chemical composition and process parameters can affect LNP structure, significantly impacting performance and .

Disparities and access to thoracic surgeons among esophagectomy patients in the United States.

Esophagectomy is a complex operation with significant morbidity and mortality. Previous studies have shown that sub-specialization is associated with improved esophagectomy outcomes. We hypothesized that disparities would exist among esophagectomy patients regarding access to thoracic surgeons based on demographic, geographic, and hospital factors.

Surgical subspecialization is associated with higher rate of rib fracture stabilization: a retrospective database analysis.

Background: Surgical stabilization of rib fractures (SSRF) is performed on only a small subset of patients who meet guideline-recommended indications for surgery. Although previous studies show that provider specialization was associated with SSRF procedural competency, little is known about the impact of provider specialization on SSRF performance frequency. We hypothesize that provider specialization would impact performance of SSRF.

Contemporary outcomes of surgical resection for chest wall chondrosarcoma.

Objective: Chondrosarcoma is the most common primary malignant chest wall tumor and is historically associated with poor prognosis. Recommendations regarding surgical excision are on the basis of small, single-institution studies. We used a large national database to assess outcomes of surgery for chest wall chondrosarcoma (CWC) hypothesizing that surgical excision remains standard of care.

Disparities in Access to Thoracic Surgeons among Patients Receiving Lung Lobectomy in the United States.

Objective: Lung lobectomy is the standard of care for early-stage lung cancer. Studies have suggested improved outcomes associated with lobectomy performed by specialized thoracic surgery providers. We hypothesized that disparities would exist regarding access to thoracic surgeons among patients receiving lung lobectomy for cancer.

Impact of non-ionizable lipids and phase mixing methods on structural properties of lipid nanoparticle formulations.

Lipid nanoparticles (LNPs) have been widely investigated for nucleic acid therapeutic delivery, and demonstrated their potential in enabling new mRNA vaccines. LNPs are usually formulated with multi-lipid components and the composition variables may impact their structural properties. Here, we investigated the impact of helper lipids on physicochemical properties of LNPs using a Design of Experiments (DoE) definitive screening design.

Nonspherical ultrasound microbubbles.

Surface tension provides microbubbles (MB) with a perfect spherical shape. Here, we demonstrate that MB can be engineered to be nonspherical, endowing them with unique features for biomedical applications. Anisotropic MB were generated via one-dimensionally stretching spherical poly(butyl cyanoacrylate) MB above their glass transition temperature.

Ultrasound-mediated delivery of flexibility-tunable polymer drug conjugates for treating glioblastoma.

Effective chemotherapy delivery for glioblastoma multiforme (GBM) is limited by drug transport across the blood-brain barrier and poor efficacy of single agents. Polymer-drug conjugates can be used to deliver drug combinations with a ratiometric dosing. However, the behaviors and effectiveness of this system have never been well investigated in GBM models.