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Introduction: Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts. Methods: Patients were eligible for this retrospective study if they had metastatic ALK-positive NSCLC with CNS relapse on alectinib 600 mg twice daily dosing and subsequently received escalated dosing (900 mg twice daily) of alectinib. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Results: Among 27 patients, median duration of dose-escalated alectinib was 7.7 months (95% confidence interval [CI]: 4.8-10.9), with median overall time-to-progression (TTP) of 7.1 months (95% CI: 4.4-9.6). Among 25 CNS response-assessable patients, CNS objective response rate was 12.0% (95% CI: 2.5-31.2) and CNS disease control rate was 92.0% (95% CI: 74.0-99.0), with median CNS duration of disease control of 5.3 months (95% CI: 3.4-8.3) and median CNS TTP of 7.1 months (95% CI: 4.4-9.6). Among four patients with measurable CNS disease at baseline, three experienced a best intracranial response of stable disease and one experienced intracranial partial response with CNS TTP ranging from 4.1 to 7.7 months. No patient required drug discontinuation due to treatment-related adverse event or experienced grade 3 or higher treatment-related adverse events. Conclusions: Dose-intensified alectinib was found to have tolerability and activity in patients with ALK-positive NSCLC who experienced CNS relapse on standard-dose alectinib and represents one clinically viable strategy for this population.

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Lung transplant is an established treatment for patients with end-stage lung disease. As a result, there is increased demand for transplants. Despite improvements in pretransplant evaluation, surgical techniques, and postsurgical care, the average posttransplant life expectancy is only around 6.5 years. Early recognition of complications on imaging and treatment can improve survival. Knowledge of surgical techniques and imaging findings of surgical and nonsurgical complications is essential. This review covers surgical techniques and imaging appearance of postsurgical and nonsurgical complications, including allograft dysfunction, infections, neoplasms, and recurrence of primary lung disease.

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Predicting the severity of acute chest syndrome is an important research priority in sickle cell disease. In this retrospective study of patients with acute chest syndrome, an enlarged pulmonary artery on computed tomography was associated with severe respiratory failure defined by the need for either noninvasive or mechanical ventilation.

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Speciated hourly measurements of fine aerosols were made for more than two years at an urban, an industrial and a port site in Busan, Korea. A Generalized Additive Model (GAM) was designed to deconvolve factors contributing to the pollutant concentrations at multiple scales. The model yields estimates of source contributions to pollution by separately identifying the signals in the time series due to meteorology, vertical mixing, horizontal wind transport and temporal variations such as diurnal, weekly, seasonal and annual trends. The GAM model was expanded to include FLEXPART back trajectory clusters generated using fuzzy c-means clustering. This made it possible to quantify the impact of long-range transport using the Trajectory Cluster Contribution Function (TCCF). TCCF provides a development of methods such as Concentration Field Analysis and Potential Source Contribution Function by providing numerical estimates of concentration changes associated with different air mass transport patterns while accounting for possible confounding factors from meteorology. The GAM simulations identified the importance of local transport for primary pollutants and long-range transport from China for secondary pollutants. Local factors accounted for up to 72% of the variance in concentrations of NO2 and elemental carbon whereas large-scale/seasonal factors accounted for up to 56% of PM2.5 and 80% of inorganic species. The algorithm further identified the importance of the weekend effect and the holiday effect at the different sites in Busan. The residual from the analysis was used to estimate the impact of the COVID-19 pandemic. The signature of the pandemic was different between the pollutants as well as from site to site. The model was able to distinguish small impacts from local pollutants at the residential site; short-lived acute impacts from industrial changes; and longer-term changes due to the early pandemic response in China.

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Purpose: Continuous monitoring of elevated intraocular pressure and timely drug delivery for successful treatment of glaucoma are necessary to reduce intraocular pressure (IOP), which shows wide variations across the circadian pattern and in response to medication. This in vivo study presents a new contact lens-based method of optical IOP measurement or temperature-triggered drug elution. Methods: A contact lens with moiré patterns of concentric circles measures the changes in eyeball diameter of a rabbit glaucoma model due to changes in IOP by superimposing a camera-captured image onto the micro pattern of the contact lens with a computer-assisted virtual reference image. Drug elution from the nanoporous bicontinuous microemulsion contact lens (BME-CL) into the eye of the rabbit was triggered by a temperature-responsive nanogel drug carrier. Results: The moiré pattern change on the contact lens was proportional to the IOP increase in the rabbit eye either ex vivo or in vivo and was also correlated with imaging-based alterations in the anterior chamber angle at a range of IOP values (3-40 mm Hg). The cumulative drug absorbed reached as high as 10.6 µg/mL aqueous humor until 7 days after wearing the BME-CL, and a 33% decrease in IOP was observed at 3 hours after drug elution. Conclusions: The results suggest that continuous measurement and treatment of elevated IOP are feasible using moiré pattern-inscribed and thermosensitive drug-eluting contact lenses, respectively. Translational Relevance: Pressure-sensing or thermosensitive contact lenses enable monitoring IOP or drug release triggered by body temperature for the treatment of glaucoma patients.

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2-Bromo-6-hydroxybenzofurans are potentially versatile intermediates for the divergent synthesis of numerous benzofuran-based natural products and their analogues. Herein we report the first one-pot strategy for the efficient synthesis of 2-bromo-6-hydroxybenzofurans. The present protocol provides shorter routes for the synthesis of moracins M, N, O and P; gramniphenols F and G; and morunigrol C using a protecting group-free approach.

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The isolation and characterization of circulating tumor cells (CTC) is of great importance in cancer diagnosis and prognosis. Highly sensitive detection of CTCs can be very difficult because they are extremely rare (i.e., 1-5 CTCs per 10(9) erythrocytes) in blood. Recently, various devices have been developed that exploit biochemical (affinity-based) and physical (size or density) methods. Antibody-based isolation has its own limitations, as the expression level of the epitopes for an antibody varies due to the heterogeneity of cancer cells. Harsh conditions associated with physical methods can cause the deformation and damage of CTCs during the isolation process. Here, we propose a microfluidic lateral flow filtration (µ-LaFF) chip in which lateral flow was combined with vertical flow into the filter to capture the CTCs gently. The CTCs experienced weak shear flow owing to the lateral flow and traveled alongside the filter channel until finally being captured. The vertical flow in the filter held the captured cells tightly and served as an exit for uncaptured hematological cells (white and red blood cells). From our µ-LaFF chip we obtained a high capture efficiency (95%) and purity (99%), minimizing any damage to the CTCs. Our µ-LaFF technology is expected to be useful in the diagnosis and prognosis of various cancers.

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Circulating tumor cells (CTCs) are defined as cells that have detached from a primary tumor and are circulating in the bloodstream. Their isolation and quantification is of great value for cancer prognoses and drug testing. Here, the development of a centrifugal affinity plate (CAP) system is described, in which centrifugal force and antibody-based capture are exploited to enrich CTCs on one plate and hematological cells on the other. The CAP is rotated to exert centrifugal force on the cells in a blood sample, quickly transporting them to the anti-epithelial adhesion molecule (EpCAM)-coated and anti-CD45-coated surface of the CAP to shorten the reaction time and increase the adhesion force between the tumor and blood cells and each antibody. The effect of a rotating process on cell capture was investigated, and the capture efficiency was demonstrated using blood samples from healthy donors spiked with human non-small cell lung cancer (NCI-H1650) and breast cancer (MCF-7) cells. The CAP system was capable of rapid isolation and identification of CTCs without the requirement for pretreatment of blood samples. Finally, the CAP system was tested to evaluate the detection efficiency of CTCs in the blood samples of breast cancer patients. The number of captured CTCs in only 1ml of blood varied from 6 to 10.

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A 50-year-old woman presented with drowsiness, severe dysarthria, left facial palsy, and left hemiparesis. Diffusion-weighted MRI showed cerebral infarction in the left pontine tegmentum and right cerebellum and angiography revealed basilar artery occlusion. Altered consciousness and hemiparesis fully resolved following successful recananlisation of the basilar artery by emergent intra-arterial thrombolysis. However, about 8 months later, obvious wasting of the left temporal and buccal area without sensory signs was detected. Electrophysiological evaluation revealed a chronic denervation process in the left masseter and temporalis muscles. We suggest that a small infarction in the trigeminal nucleus of the pontine tegmentum can cause an isolated trigeminal motor neuropathy with masticatory muscle atrophy.

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Mouse P19 embryonic carcinoma (EC) stem cells were xenotransplanted into the emptied chorion, the transparent envelope of a fertilized zebrafish egg (rather than mouse native zona pellucida) combined with a microfluidic device to study P19 EC cell differentiation in the chorion biomaterial. A distilled-water jet was used to remove the innate yolk and perivitelline inner mass from the chorion. P19 EC cells were injected into the emptied chorion using a micropipette, and they were subsequently cultured until the inner space of the chorion became completely occupied by cells. A simple microfluidic device was used for handling convenience and effective experiment. At d15, we found neural cells in the outer layer of the cell mass and beating cardiomyocytes in the inner layer of the large embryoid body. We propose that even though the species are different, the external innate membranes developed for embryo protection represent a useful type of ECM.

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