Objectives: Pseudoaneurysm formation in connective tissue patients postoperatively can be a challenging and life-threatening problem to treat. Repair of an aorta to intercostal bypass graft pseudoaneurysm post open thoracoabdominal aortic aneurysm repair by percutaneous glue embolization utilizing Dyna CT Needle Guidance technology is a safe, minimally invasive method with low morbidity and short post-procedural recovery.
Methods: A 30-year-old male with suspected connective tissue disorder who developed a Type B aortic dissection complicated by limb threatening right lower extremity ischemia treated with left-to-right fem-fem bypass and RLE fasciotomies.
The ATP-driven bicarbonate transporter 1 (BCT1) from Synechococcus is a four-component complex in the cyanobacterial CO2-concentrating mechanism. BCT1 could enhance photosynthetic CO2 assimilation in plant chloroplasts. However, directing its subunits (CmpA, CmpB, CmpC, and CmpD) to three chloroplast sub-compartments is highly complex.
View Article and Find Full Text PDFPlants have many genes encoding both alpha and beta type carbonic anhydrases. Arabidopsis has eight alpha type and six beta type carbonic anhydrase genes. Individual carbonic anhydrases are localized to specific compartments within the plant cell.
View Article and Find Full Text PDFHollow fiber filter fouling is a common issue plaguing perfusion production process for biologics therapeutics, but the nature of filter foulant has been elusive. Here we studied cell culture materials especially Chinese hamster ovary (CHO) cell-derived extracellular vesicles in perfusion process to determine their role in filter fouling. We found that the decrease of CHO-derived small extracellular vesicles (sEVs) with 50-200 nm in diameter in perfusion permeates always preceded the increase in transmembrane pressure (TMP) and subsequent decrease in product sieving, suggesting that sEVs might have been retained inside filters and contributed to filter fouling.
View Article and Find Full Text PDFPurpose: This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer.
Methods: This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2.
Objective: Gynecologic cancers are traditionally managed according to their presumed site of origin, without regard to the underlying histologic subtype. Clear cell histology is associated with chemotherapy refractoriness and poor survival. Mutations in SWI/SNF chromatin remodeling complex member ARID1A, which encodes for BAF250a protein, are common in clear cell and endometriosis-associated endometrioid carcinomas.
View Article and Find Full Text PDFPrimary liver cancer is the sixth most common cancer worldwide and the third leading cause of cancer-related death. Conventional therapies offer limited survival benefit despite improvements in locoregional liver-directed therapies, which highlights the underlying complexity of liver cancers. This review explores the latest research in primary liver cancer therapies, focusing on developments in genomics, molecular biomarkers, and artificial intelligence.
View Article and Find Full Text PDFLCIA (low CO2-inducible protein A) is a chloroplast envelope protein associated with the CO2-concentrating mechanism of the green alga Chlamydomonas reinhardtii. LCIA is postulated to be a HCO3- channel, but previous studies were unable to show that LCIA was actively transporting bicarbonate in planta. Therefore, LCIA activity was investigated more directly in two heterologous systems: an Escherichia coli mutant (DCAKO) lacking both native carbonic anhydrases and an Arabidopsis mutant (βca5) missing the plastid carbonic anhydrase βCA5.
View Article and Find Full Text PDFChlamydomonas reinhardtii evolved a CO-concentrating mechanism (CCM) because of the limited CO in its natural environment. One critical component of the C. reinhardtii CCM is the limiting CO inducible B (LCIB) protein.
View Article and Find Full Text PDFCarbonic anhydrases (CAs) are zinc-metalloenzymes that catalyze the interconversion of CO2 and HCO3-. In heterotrophic organisms, CAs provide HCO3- for metabolic pathways requiring a carboxylation step. Arabidopsis (Arabidopsis thaliana) has 14 α- and β-type CAs, two of which are plastid CAs designated as βCA1 and βCA5.
View Article and Find Full Text PDFImportance: Although the activity of pembrolizumab and lenvatinib (the only US Food and Drug Administration-approved immunotherapy for mismatch repair proficient endometrial cancer [MMRP EC]) is compelling, there are no biomarkers of response and most patients do not tolerate, do not respond to, or develop resistance to this regimen, highlighting the need for additional, potentially biomarker-driven therapeutic approaches for patients with recurrent MMRP EC.
Objective: To assess the potential positive outcomes and safety of the combination of the polyadenosine diphosphate-ribose polymerase inhibitor talazoparib and the programmed cell death ligand 1 (PD-L1) inhibitor avelumab in recurrent MMRP EC.
Design, Settings, And Participants: This investigator-initiated, open-label, single-arm, 2-stage, phase 2 study nonrandomized controlled trial patients at 4 institutions in the US.
In recent years, researchers have attempted to improve photosynthesis by introducing components from cyanobacterial and algal CO2-concentrating mechanisms (CCMs) into terrestrial C3 plants. For these attempts to succeed, we need to understand the CCM components in more detail, especially carbonic anhydrase (CA) and bicarbonate (HCO3−) transporters. Heterologous complementation systems capable of detecting carbonic anhydrase activity (i.
View Article and Find Full Text PDFBackgroundImmune checkpoint inhibitors (ICIs) have modest activity in ovarian cancer (OC). To augment their activity, we used priming with the hypomethylating agent guadecitabine in a phase II study.MethodsEligible patients had platinum-resistant OC, normal organ function, measurable disease, and received up to 5 prior regimens.
View Article and Find Full Text PDFBackground: Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC).
Objective: In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC.
Study Design: This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC.
Chlamydomonas reinhardtii can grow photosynthetically using CO2 or in the dark using acetate as the carbon source. In the light in air, the CO2 concentrating mechanism (CCM) of C. reinhardtii accumulates CO2, enhancing photosynthesis.
View Article and Find Full Text PDFPurpose: CD137 agonism and CSF1R blockade augment stereotactic body radiotherapy (SBRT) and anti-programmed death-1 in preclinical models. We evaluated the safety and efficacy of SBRT with nivolumab+urelumab (CD137 agonist) or nivolumab+cabiralizumab (CSF1R inhibitor).
Patients And Methods: This phase I clinical trial enrolled patients with advanced solid tumors that had progressed on standard therapies.
B cell differentiation driven by microbial antigens leads to production of anti-microbial antibodies, such as those neutralizing viruses, bacteria or bacterial toxin, that are class-switched (IgG and IgA) and somatically hypermutated (maturation of the antibody response) as well as secreted in large volume by plasma cells. Similar features characterize pathogenic antibodies to self-antigens in autoimmunity, reflecting the critical role of class switch DNA recombination (CSR), somatic hypermutation (SHM) and plasma cell differentiation in the generation of antibodies to not only foreign antigens but also self-antigens (autoantibodies). Central to CSR/SHM and plasma cell differentiation are AID, a potent DNA cytidine deaminase encoded by Aicda, and Blimp-1, a transcription factor encoded by Prdm1.
View Article and Find Full Text PDFMemory B cells (MBCs) are long-lived and produce high-affinity, generally, class-switched antibodies. Here, we use a multiparameter approach involving CD27 to segregate naïve B cells (NBC), IgD unswitched (unsw)MBCs and IgG or IgA class-switched (sw)MBCs from humans of different age, sex and race. Conserved antibody variable gene expression indicates that MBCs emerge through unbiased selection from NBCs.
View Article and Find Full Text PDFPreterm birth is a major public health problem, occurring in more than half a million births per year in the United States. A number of maternal conditions have been recognized as risk factors for preterm birth, but for the majority of cases, the etiology is not completely understood. is one of the most prevalent sexually transmitted infections in the world.
View Article and Find Full Text PDFPurpose: Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced tumor gene expression, and overall survival (OS).
Patients And Methods: Patients with AST received SBRT (30-50 Gy in 3-5 fractions) to two to four metastases followed by pembrolizumab (200 mg i.