Sequencing by avidity enables high accuracy with low reagent consumption.

We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase-polymer-nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer.

Feasibility and safety values of activated clotting time-guided systemic heparinization in coil embolization for unruptured intracranial aneurysms.

OBJECTIVE: This study aimed to evaluate the feasibility and safety values of activated clotting time (ACT)-guided systemic heparinization in reducing periprocedural thrombosis and bleeding complications during coil embolization of unruptured intracranial aneurysms. METHODS: A total of 228 procedures performed on 213 patients between 2016 and 2021 were included in the retrospective analysis. The target ACT was set at 250 s. Logistic regression was performed to assess predictors for the occurrence of thrombosis and bleeding. Receiver operating characteristic (ROC) analyses were employed to determine the optimal cut-off values for ACT, heparinization, and procedure time. RESULTS: Most (85.1%) of procedures were stent-assisted embolization. The mean baseline ACT was 128.8 ± 45.7 s. The mean ACT at 20 min after the initial intravenous heparin loading of 78.2 ± 18.8 IU/kg was 185 ± 46.4 s. The mean peak ACT was 255.6 ± 63.8 s with 51.3% (117 cases) achieving the target ACT level. Peak ACT was associated with symptomatic thrombosis (OR per second, 1.008; 95% CI, 1.000-1.016; P = 0.035) (cut-off value, 275 s; area under ROC (AUROC), 0.7624). Total administered heparin dose per body weight was negatively associated with symptomatic thrombosis (OR per IU/kg, 0.972; 95% CI, 0.949-0995; P = 0.018) (cut-off value, 294 IU/kg; AUROC, 0.7426) but positively associated with significant bleeding (OR, 1.008 per IU/kg; 95% CI, 1.005-1.012; P <0 .001) (cut-off value, 242 IU/kg; AUROC, 0.7391). Procedure time was significantly associated with symptomatic thrombosis (OR per minute, 1.05; 95% CI, 1.017-1.084; P value = 0.002) (cut-off value, 158 min; area under ROC, 0.8338). CONCLUSION: This study demonstrated that ACT-guided systemic heparinization was feasible to achieve the target ACT value and proposes probable safety thresholds to prevent periprocedural complications through reducing procedure time during coil embolization of unruptured intracranial aneurysms in the stent era.

Double-barreled IMA-M2 and STA-MCA bypass in severe stenosis of terminal internal carotid artery: three case reports.

EC-IC bypasses have been performed to treat complex aneurysms or moyamoya disease or atherosclerotic steno-occlusive disease. We report the three cases that underwent EC-IC revascularization of the IMA-M2 bypass using the radial artery graft concurrently after the STA-MCA anastomosis to prevent potential ischemic damage during the operation and augment more flow in terminal internal carotid artery stenosis. All patients experienced neither perioperative complications nor further events for a 3-month follow-up. The double-barreled IMA-M2 and STA-MCA bypass is a good option for substantial amount of EC-IC revascularization with minimizing ischemic injury and maximizing flow amount in patients with severe hemodynamic compromise.

Alternate Simultaneous Bilateral Carotid Angiography in Y-stent-Assisted Coil Embolization for an Anterior Communicating Artery Aneurysm with Triplicate A2 Variant.

The triplicate A2 variant is one of several common anomalies of the anterior cerebral artery. An anterior communicating artery aneurysm with triplicate A2 variant in close proximity to the aneurysm neck is challenging to treat due to potential unilateral/bilateral corpus callosum or parietal lobe infarction. Alternate simultaneous bilateral carotid angiography can differentiate triplicate A2 branches through time-difference alternate injection of contrast into the carotid arteries bilaterally, which can enhance anatomic understanding of complex anterior communicating artery aneurysms during complex endovascular treatment. In this case, a complex aneurysm with an associated triplicate A2 variant was treated successfully with Y-stent-assisted coil embolization using alternate simultaneous bilateral carotid angiography.

Predictors for intracerebral hemorrhage after intravenous or intraarterial recanalization in acute major cerebral artery occlusion in Korean patients.

OBJECTIVE: To evaluate predictors for intracerebral hemorrhage (ICH) and 1-month mortality after intravenous (IV) or intraarterial (IA) recanalization therapy for major cerebral artery occlusion in Korean patients. METHODS: From 2011 to 2015, we prospectively gathered data from consecutive patients treated with IV/IA recanalization within 8 h of symptoms in a single center. The effects of demographic, clinical, laboratory, and radiological factors on ICH within 2 weeks were assessed, as well as 1-month mortality. RESULTS: From a total of 183 patients, symptomatic intracerebral hemorrhage (SICH) occurred in 32 patients (17.5%), and asymptomatic ICH occurred in 37 patients (20.2%). The mortality rate at 1 month in ICH patients was 37.7%. The international normalized ratio (INR) (OR, 4.9; 95% CI, 1.03-23.4; p = 0.046), glucose (OR, 1.119 per mmol/L; 95% CI, 1.015-1.233; p = 0.023), medium-volume infarct (15-69.9 mL) (OR, 2.62; 95% CI, 1.1-6.26; p = 0.03), large-volume infarct (≥70 mL) (OR, 5.54; 95% CI, 2.1-14.6; p = 0.001), and angioplasty or stenting (OR, 6.29; 95% CI, 1.71-23.22; p = 0.006) were predictors of any ICH. Hyperlipidemia or statin medication (OR, 4.17; 95% CI, 1.38-12.59; p = 0.011), INR (OR, 7.13; 95% CI, 0.94-54.22 p = 0.058), and large-volume infarct (≥70 mL) (OR, 7.96; 95% CI, 2.31-27.39; p = 0.001) were predictors of SICH. Hypertension (OR, 5.77; 95% CI, 1.43-23.3; p = 0.014), initial NIHSS score (OR, 1.09; 95% CI, 1.01-1.18; p = 0.27), and SICH (OR, 15.7; 95% CI, 4.04-61.08; p < 0.001) were predictors of 1-month mortality. CONCLUSION: INR and glucose may be strong modifiable predictors of critical ICH leading to death after IV/IA recanalization therapy in acute cerebral artery occlusion.

Nanophotonic Cell Lysis and Polymerase Chain Reaction with Gravity-Driven Cell Enrichment for Rapid Detection of Pathogens.

Rapid and precise detection of pathogens is a critical step in the prevention and identification of emergencies related to health and biosafety as well as the clinical management of community-acquired urinary tract infections or sexually transmitted diseases. However, a conventional culture-based pathogen diagnostic method is time-consuming, permitting physicians to use antibiotics without ample clinical data. Here, we present a nanophotonic Light-driven Integrated cell lysis and polymerase chain reaction (PCR) on a chip with Gravity-driven cell enrichment Health Technology (LIGHT) for rapid precision detection of pathogens (<20 min). We created the LIGHT, which has the three functions of (1) selective enrichment of pathogens, (2) photothermal cell lysis, and (3) photonic PCR on a chip. We designed the gravity-driven cell enrichment via a nanoporous membrane on a chip that allows an effective bacterial enrichment of 40 000-fold from a 1 mL sample in 2 min. We established a light-driven photothermal lysis of preconcentrated bacteria within 1 min by designing the network of nanoplasmonic optical antenna on a chip for ultrafast light-to-heat conversion, created the nanoplasmonic optical antenna network-based ultrafast photonic PCR on a chip, and identified Escherichia coli. Finally, we demonstrated the end-point detection of up to 103 CFU/mL of E. coli in 10 min. We believe that our nanophotonic LIGHT will provide rapid and precise identification of pathogens in both developing and developed countries.

Bubble-free rapid microfluidic PCR.

Microfluidic polymerase chain reaction (PCR) has been of great interest owing to its ability to perform rapid and specific nucleic acid amplification and analysis on small volumes of samples. One of the major drawbacks of microfluidic PCR is bubble generation and reagent evaporation, which can cause malfunctions. Here, through theoretical modeling and characterization of bubble behavior, we propose a bubble-free microfluidic PCR device via controlled fluid transfer. Our approach exploits a thin impermeable polyethylene (PE) top layer that minimizes the generation of bubbles by inhibiting mass transport along a vertical direction. Simulation results demonstrate that a calculated mass flow difference of approximately 370% can be obtained by utilizing an impermeable membrane as the vertical barrier layer. To demonstrate proof-of-concept, two nanoporous polymeric materials, poly(dimethylsiloxane) (PDMS) and PE, were used for stand-alone self-powered sample loading (approximately 70 s) and for use as a vertical barrier layer, respectively. Consequently, we demonstrate successful amplification of the cMET gene, a nucleic acid (NA) biomarker for lung cancer, and complete an ultrafast PCR test in less than 3 min using a high powered Peltier-based thermal cycler under bubble-free conditions. This approach will result in a new paradigm for ultrafast molecular diagnosis and can facilitate NA-based nearly instantaneous diagnostics for point-of-care testing and for personalized and preventive medicine.

Microphysiological Analysis Platform of Pancreatic Islet ß-Cell Spheroids.

The hallmarks of diabetics are insufficient secretion of insulin and dysregulation of glucagon. It is critical to understand release mechanisms of insulin, glucagon, and other hormones from the islets of Langerhans. In spite of remarkable advancements in diabetes research and practice, robust and reproducible models that can measure pancreatic ß-cell function are lacking. Here, a microphysiological analysis platform (MAP) that allows the uniform 3D spheroid formation of pancreatic ß-cell islets, large-scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development is reported. The MAP enables the scaffold-free formation of densely packed ß-cell spheroids (i.e., multiple array of 110 bioreactors) surrounded with a perfusion flow network inspired by physiologically relevant microenvironment. The MAP permits dynamic perturbations on the ß-cell spheroids and the precise controls of glycemia and lipidemia, which allow us to confirm that cellular apoptosis in the ß-cell spheroid under hyperglycemia and hyperlipidemia is mostly dependent to a reactive oxygen species-induced caspase-mediated pathway. The ß-cells' MAP might provide a potential new map in the pathophysiological mechanisms of ß cells.

Pulmonary metastases from benign calvarial meningioma: a case report.

The most common intracranial tumour is meningioma, which rarely presents with extracranial metastasis, especially in benign cases. We report a case of meningioma recurrence with multiple pulmonary metastases in a patient who had a benign meningioma removed 12 years prior.