A dynamic approach to support outbreak management using reinforcement learning and semi-connected SEIQR models.

BACKGROUND: Containment measures slowed the spread of COVID-19 but led to a global economic crisis. We establish a reinforcement learning (RL) algorithm that balances disease control and economic activities. METHODS: To train the RL agent, we design an RL environment with 4 semi-connected regions to represent the COVID-19 epidemic in Tokyo, Osaka, Okinawa, and Hokkaido, Japan. Every region is governed by a Susceptible-Exposed-Infected-Quarantined-Removed (SEIQR) model and has a transport hub to connect with other regions. The allocation of the synthetic population and inter-regional traveling is determined by population-weighted density. The agent learns the best policy from interacting with the RL environment, which involves obtaining daily observations, performing actions on individual movement and screening, and receiving feedback from the reward function. After training, we implement the agent into RL environments describing the actual epidemic waves of the four regions to observe the agent's performance. RESULTS: For all epidemic waves covered by our study, the trained agent reduces the peak number of infectious cases and shortens the epidemics (from 165 to 35 cases and 148 to 131 days for the 5th wave). The agent is generally strict on screening but easy on movement, except for Okinawa, where the agent is easy on both actions. Action timing analyses indicate that restriction on movement is elevated when the number of exposed or infectious cases remains high or infectious cases increase rapidly, and stringency on screening is eased when the number of exposed or infectious cases drops quickly or to a regional low. For Okinawa, action on screening is tightened when the number of exposed or infectious cases increases rapidly. CONCLUSIONS: Our experiments exhibit the potential of the RL in assisting policy-making and how the semi-connected SEIQR models establish an interactive environment for imitating cross-regional human flows.

Measurement of Cancer-Related Fatigue Based on Heart Rate Variability: Observational Study.

BACKGROUND: Cancer-related fatigue is a serious side effect of cancer, and its treatment can disrupt the quality of life of patients. Clinically, the standard method for assessing cancer-related fatigue relies on subjective experience retrieved from patient self-reports, such as the Brief Fatigue Inventory (BFI). However, most patients do not self-report their fatigue levels. OBJECTIVE: In this study, we aim to develop an objective cancer-related fatigue assessment method to track and monitor fatigue in patients with cancer. METHODS: In total, 12 patients with lung cancer who were undergoing chemotherapy or targeted therapy were enrolled. We developed frequency-domain parameters of heart rate variability (HRV) and BFI based on a wearable-based HRV measurement system. All patients completed the BFI-Taiwan version questionnaire and wore the device for 7 consecutive days to record HRV parameters such as low frequency (LF), high frequency (HF), and LF-HF ratio (LF-HF). Statistical analysis was used to map the correlation between subjective fatigue and objective data. RESULTS: A moderate positive correlation was observed between the average LF-HF ratio and BFI in the sleep phase (ρ=0.86). The mapped BFI score derived by the BFI mapping method could approximate the BFI from the patient self-report. The mean absolute error rate between the subjective and objective BFI scores was 3%. CONCLUSIONS: LF-HF is highly correlated with the cancer-related fatigue experienced by patients with lung cancer undergoing chemotherapy or targeted therapy. Beyond revealing fatigue levels objectively, continuous HRV recordings through the photoplethysmography watch device and the defined parameters (LF-HF) can define the active phase and sleep phase in patients with lung cancer who undergo chemotherapy or targeted chemotherapy, allowing a deduction of their sleep patterns.

Home use of a compact, 12­lead ECG recording system for newborns.

BACKGROUND: An easy-to-operate ECG recorder should be useful for newborn screening for heart conditions, by health care workers - or parents. We developed a one-piece electrode strip and a compact, 12­lead ECG recorder for newborns. METHOD: We enrolled 2582 newborns in a trial to assess abilities of parents to record a 12­lead ECG on their infants (2-4 weeks-old). Newborns were randomized to recordings by parents (1290) or our staff (1292 controls). Educational backgrounds of parents varied, including 64% with no more than a high school diploma. RESULTS: For newborns randomized to parent recorded ECGs, 94% of parents completed a 10-minute recording. However, 42.6% asked for verbal help, and 12.7% needed physical help. ECG quality was the same for recordings by parents versus staff. CONCLUSIONS: By use of a one-piece electrode strip and a compact recorder, 87% of parents recorded diagnostic quality ECGs on their newborn infants, with minimal assistance.

Fibrocyte trafficking in patients with chronic obstructive asthma and during an acute asthma exacerbation.

BACKGROUND: Fibrocytes express several chemokine receptors (CCR7 and CXCR4) that regulate their recruitment and trafficking into tissue-damage sites in response to specific chemokine gradients (CCL19 and CXCL12). OBJECTIVE: We investigated whether these chemoattractants and S100A9, through the receptor for advanced glycation end-products (RAGE; ie, its receptor), are involved in fibrocyte trafficking in patients with chronic obstructive asthma (COA) and during an acute exacerbation (AE) in patients without airflow obstruction (Asthma AE group). METHODS: We collected peripheral blood from 14 asthmatic patients with normal pulmonary function, 14 patients with COA, 11 patients in the Asthma AE group, and 14 healthy subjects. Isolated circulating fibrocytes were used for migration assay. Expression of CCR7, CXCR4, S100A9, and RAGE in fibrocytes was measured by using flow cytometry. CCL19 and CXCL12 expression in bronchial tissues was determined by using immunohistochemistry and RT-PCR. RESULTS: There were higher numbers of circulating fibrocytes in patients in the Asthma AE group and patients with COA. The expression of CXCL12 in bronchial tissues and CXCR4 in circulating fibrocytes was higher in the Asthma AE group and, to a lesser extent, in patients with COA. The expression of CCL19 in bronchial tissues and CCR7 in fibrocytes was higher in patients with COA. CXCL12/CXCR4 and CCL19/CCR7 enhanced fibrocyte transmigration in the Asthma AE group and in patients with COA, respectively. The upregulated expression of S100A9 and RAGE in fibrocytes of patients in the Asthma AE group and those with COA contributes to the enhanced basal migratory motility of fibrocytes. CONCLUSION: The CXCR4/CXCL12 axis contributes to chemotaxis of fibrocytes in patients in the Asthma AE group, whereas the CCR7/CCL19 axis plays an important role in patients with COA. S100A9 enhances the basal migratory motility of fibrocytes from patients in the Asthma AE group and patients with COA.

Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the "alarmin" family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study.

BACKGROUND: Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients. METHODS: To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines. RESULTS: Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group. CONCLUSIONS: A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019).

Use of a wearable device to compare subjective and objective fatigue in lung cancer patients and cancer-free controls.

PURPOSE: The study evaluates the use of heart rate variability (HRV), a measure of autonomic nervous system (ANS) modulation via wearable smart bands, to objectively assess cancer-related fatigue (CRF) levels. It aims to enhance understanding of fatigue by distinguishing between LF/HF ratios and LF/HF disorder ratios through HRV and photoplethysmography (PPG), identifying them as potential biomarkers. METHODS: Seventy-one lung cancer patients and 75 non-cancer controls wore smart bands for one week. Fatigue was assessed using Brief Fatigue Inventory, alongside sleep quality and daily interference. HRV parameters were analyzed to compare groups. RESULTS: Cancer patients showed higher fatigue and interference levels than controls (64.8% vs. 54.7%). Those with mild fatigue had elevated LF/HF disorder ratios during sleep (40% vs. 20%, P = 0.01), similar to those with moderate to severe fatigue (50% vs. 20%, P = 0.01), indicating more significant autonomic dysregulation. Notably, mild fatigue patients had higher mean LF/HF ratios than controls (1.9 ± 1.34 vs. 1.2 ± 0.6, P = 0.01), underscoring the potential of disorder ratios in signaling fatigue severity. CONCLUSIONS: Utilizing wearable smart bands for HRV-based analysis is feasible for objectively assess CRF levels in cancer patients, especially during sleep. By distinguishing between LF/HF ratios and LF/HF disorder ratios, our findings suggest that wearable technology and detailed HRV analysis offer promising avenues for real-time fatigue monitoring. This approach has the potential to significantly improve cancer care by providing new methods for managing and intervening in CRF, particularly with a focus on autonomic dysregulation as a crucial factor.

Cancer-related fatigue classification based on heart rate variability signals from wearables.

Background: Cancer-related fatigue (CRF) is the most distressing side effect in cancer patients and affects the survival rate. However, most patients do not report their fatigue level. This study is aimed to develop an objective CRF assessment method based on heart rate variability (HRV). Methods: In this study, patients with lung cancer who received chemotherapy or target therapy were enrolled. Patients wore wearable devices with photoplethysmography that regularly recorded HRV parameters for seven consecutive days and completed the Brief Fatigue Inventory (BFI) questionnaire. The collected parameters were divided into the active and sleep phase parameters to allow tracking of fatigue variation. Statistical analysis was used to identify correlations between fatigue scores and HRV parameters. Findings: In this study, 60 patients with lung cancer were enrolled. The HRV parameters including the low-frequency/high-frequency (LF/HF) ratio and the LF/HF disorder ratio in the active phase and the sleep phase were extracted. A linear classifier with HRV-based cutoff points achieved correct classification rates of 73 and 88% for mild and moderate fatigue levels, respectively. Conclusion: Fatigue was effectively identified, and the data were effectively classified using a 24-h HRV device. This objective fatigue monitoring method may enable clinicians to effectively handle fatigue problems.

Antineutrophil Cytoplasmic Antibodies and Organ-Specific Manifestations in Eosinophilic Granulomatosis with Polyangiitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a rare and often severe systemic vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). EGPA can affect multiple organ systems, but the relationships between ANCA status and the organ-specific manifestations of EGPA in previous reports were inconsistent. OBJECTIVE: To investigate the association of the ANCA status with organ-specific manifestations in EGPA. METHODS: We performed a systematic review of studies published before March 16, 2020, in the PubMed, Embase, Web of Science, and Cochrane Library databases. The primary outcome was the association of ANCA status with organ-specific involvements of EGPA. Odds ratios (ORs) and 95% CIs were calculated using a random-effects model. RESULTS: A total of 24 cross-sectional studies with 2527 patients with EGPA, including 921 ANCA-positive patients and 1606 ANCA-negative patients, were included in the meta-analysis. The significant results of pooled analyses revealed that compared with patients with EGPA with negative ANCA status, patients with EGPA with positive ANCA status had higher risks of peripheral neuropathy (OR, 1.701), renal involvement (OR, 5.097), and cutaneous purpura (OR, 1.746) and lower risks of pulmonary infiltrates (OR, 0.589) and cardiac involvement (OR, 0.427). The pooled analysis also revealed no significant association of ANCA status with asthma and involvements of the central nervous system, gastrointestinal tract, or skin. CONCLUSIONS: This study provides more evidence that patients with EGPA may exhibit different features of disease based on their ANCA status.

Hypoxia-inducible factor 1alpha induces corticosteroid-insensitive inflammation via reduction of histone deacetylase-2 transcription.

Corticosteroids are potent anti-inflammatory agents, but corticosteroid insensitivity is a major barrier for the treatment of some chronic inflammatory diseases. Here, we show that hypoxia induces corticosteroid-insensitive inflammation via reduced transcription of histone deacetylase-2 (HDAC2) in lung epithelial and macrophage cells. HDAC2 mRNA and protein expression was reduced under hypoxic conditions (1% O(2)). Hypoxia enhanced interleukin-1beta-induced interleukin-8 (CXCL8) production in A549 cells and decreased the ability of dexamethasone to suppress the CXCL8 production. Deletion or point mutation studies revealed that binding of the transcription factor hypoxia-inducible factor (HIF) 1alpha to a HIF response element at position -320, but not HIF-1beta or HIF-2alpha, results in reduced polymerase II binding at the site, leading to reduced promoter activity of HDAC2. Our results suggest that activation of HIF-1alpha by hypoxia decreases HDAC2 levels, resulting in amplified inflammation and corticosteroid resistance.

Matrix metalloproteinase-7 (MMP-7) polymorphism is a risk factor for endometrial cancer susceptibility.

BACKGROUND: The goal of our study was to evaluate the influence of genetic polymorphisms of matrix metalloproteinases (MMP)-2, MMP-3 and MMP-7 on susceptibility to endometrial cancer. METHODS: In the present study, we enrolled a total of 118 patients with endometrial cancer confirmed by histopathology, and 229 unrelated healthy individuals. Polymorphism for the MMP-2 (rs2285053), MMP-3 (rs3025058) and MMP-7 (rs11568818) genes was genotyped by polymerase chain reaction-restriction enzyme length polymorphism. RESULTS: The frequencies of MMP-7 -181 G/G and A/G genotypes were found to be significantly higher in cancer patients compared with healthy controls (p = 0.017). Stratification showed that individuals with MMP-7 -181 G allele were at increased risk for endometrial cancer when >50 years of age [odds ratios (OR) = 2.03; 95% confidence interval (CI) 1.21-3.39], endometrioid (OR = 1.80; 95% CI 1.11-2.92), low (stage I-II) (OR = 1.73; 95% CI 1.05-2.83) or high stage (stage III-IV) (OR = 2.69; 95% CI 1.16-6.24). Compared with the A/A genotype, the A/G + G/G genotype modified the risk of developing endometrial carcinoma and significance was detected in patients over 50 years old, and those with endometrioid type and high stage endometrial cancer. However, no significant difference in MMP-2 (-735 C/T) and MMP-3 (6A/5A) genotypes was observed between endometrial carcinoma cases and controls. CONCLUSIONS: This is the first report on the association of MMP-2, MMP-3 and MMP-7 gene polymorphisms in endometrial cancer. Our results suggest that individuals with the MMP-7 -181 G/G and A/G genotype may have an increased risk of developing endometrial cancer.

Promoting formic acid oxidation performance of Pd nanoparticles via Pt and Ru atom mediated surface engineering.

The alteration of surface functional properties via incorporation of foreign atoms is supposed to be a key strategy for the enhanced catalytic performance of noble-metal based nanocatalysts (NCs). In the present study, carbon-supported palladium (Pd)-based NCs including Pd, PdPt and PdRuPt have been prepared via a polyol reduction method under the same reduction conditions as for formic acid oxidation reaction (FAOR) applications. By cross-referencing the results of the microscopic, spectroscopic and electrochemical analysis we demonstrated that adding a small amount of platinum (Pt) into Pd NCs (i.e. PdPt NCs) significantly promotes the FAOR performance as compared to that of Pd NCs via weakening the COads bond strength at a lower voltage (0.875 V vs. NHE) than Pd (0.891 V vs. NHE). Of special relevance, the PdPt NC shows a mass activity (MA) of 1.0 A mg-1 and 1.9 A mg-1, respectively, in the anodic and cathodic scan. These values are ∼1.7-fold (0.6 A mg-1) and ∼4.8-fold (0.4 A mg-1) higher than those of Pd NC. Moreover, PdPt NC retains a higher MA (54 mA mg-1) than that of Pd NC (9 mA mg-1) after chronoamperometric (CA) stability tests over 2000 s. Meanwhile, further addition of ruthenium (Ru) (i.e. PdRuPt NCs) outstandingly enhances the CO tolerance during the CA test via removal of adsorbed COads and thus shows the highest MA (62 mA mg-1) after CA testing, which is higher than that of PdPt (54 mA mg-1) and Pd (9 mA mg-1) NCs. The intriguing results obtained in this study have great significance to provide further strategic opportunities for tuning the surface electronic properties of Pd-based NCs to design Pd-based NCs with improved electrochemical performance.

Investigation of Morphological Variations of Photoplethysmography Signal in Human Epilepsy.

The purpose of this study is to analyse the ictal variations in peripheral blood flow using photoplethysmogram (PPG) and single lead Electrocardiogram (ECG) signals. 11 subjects with 56 partial seizures were recorded with the PPG sensor worn on their left ankles. 6 different features from PPG pulse morphology related to hemodynamics were derived. The seizures were divided into two groups based on the side of the seizure activity. The investigation of ictal variations in features did not show any significant difference between the seizures' lateralizations. The analysis of latencies of ictal changes in the PPG features revealed the PPG pulse amplitude precede the variations in other PPG features including ictal heart rate variability. In addition, analysis of the effect of seizure lengths on ictal variations showed the seizures' lengths have no significant effect on the feature variation rates.Clinical relevance- Analysis of the extracted PPG features and their timing suggest an increase in vascular resistance due to increase in sympathetic tone which occurs prior to the ictal tachycardia. These variations is independent of the seizures' lengths and lateralizations.

CO-Reductive and O2-Oxidative Annealing Assisted Surface Restructure and Corresponding Formic Acid Oxidation Performance of PdPt and PdRuPt Nanocatalysts.

Formic acid oxidation reaction (FAOR) at anode counterpart incurs at substantial high overpotential, limiting the power output efficiency of direct formic acid fuel cells (DFAFCs). Despite intense research, the lack of high-performance nanocatalysts (NCs) for FAOR remains a challenge in realizing DFAFC technologies. To surmount the overpotential losses, it is desirable to have NCs to trigger the FAOR as close to the reversible conditions (i.e. with over-potential loss as close to zero as possible). Herein, Pd-based binary and ternary NCs consisting of PdPt and PdRuPt have been synthesized via the polyol reduction method on the carbon support. As prepared PdPt and PdRuPt NCs were further subjected to heat treatment (annealed) in CO (namely PdPt-CO and PdRuPt-CO) and O2 (namely PdPt-O2 and PdRuPt-O2) atmosphere at 473 K temperature. By cross-referencing results of electron microscopy and X-ray spectroscopy together with electrochemical analysis, the effects of heat treatment under CO-reductive and O2-oxidative conditions towards FAOR were schematically elucidated. Of special relevance, the mass activity (MA) of PdPt-CO, PdPt-O2, PdRuPt-CO, and PdRuPt-O2 NCs is 1.7/2.0, 1.3/2.2, 1.1/5.5, and 0.9/4.7 Amg-1 in the anodic/cathodic scan, respectively, which is 2~4-folds improved comparative to of as-prepared PdPt (1.0/1.9 Amg-1 in anodic/cathodic scan, respectively) and PdRuPt (0.9/1.4 Amg-1 in anodic/cathodic scan, respectively) NCs. Meanwhile, after chronoamperometric (CA) stability test up to 2000 s, PdPt-CO (72 mAmg-1) and PdRuPt-CO (213 mAmg-1) NCs exhibit higher MA compared to as-prepared PdPt (54 mAmg-1) and PdRuPt (62 mAmg-1) NCs, which is attributed to the increase of surface Pt composition, especially for PdRuPt-CO NC. Besides, the stability of PdPt-O2 (15 mAmg-1) and PdRuPt-O2 (22 mAmg-1) NCs is deteriorated as compared to that of as-prepared NCs due to severe oxidation in O2 atmosphere. Of utmost importance, we developed a ternary PdRuPt catalyst with ultra-low Pt content (~2 wt.%) and significantly improved FAOR performance than pure Pt catalysts. Moreover, we demonstrated that the FAOR performance can be further enhanced by more than 30% via a unique CO annealing treatment.

Electrorheological Sensor Encapsulating Microsphere Media for Plague Diagnosis with Rapid Visualization.

Plague is a disease infected by an etiological agent, which is transmitted from fleas to a variety of wildlife rodents. Therefore, rapid diagnosis of plague on-site in the field is important. Polystyrene microspheres (SMs) of 2.2 µm diameter were synthesized by emulsion polymerization to adsorb magnetic nanoparticles (FNs), resulting in core-/shell-structured microspheres that generate a significant contrast in relative permittivities between SMs and FNs. Electrorheological displays (EDs) consisting of two indium tin oxide glasses with spacers were constructed to contain core-/shell-structured SM/FN (SM@FN) solutions for observing their transmittance change. The ED encapsulating dispersed SM@FN solution exhibited an opaque state because light was scattered significantly without the application of an alternating electric field (AEF). In the presence of an AEF, the particle chaining behavior results in enhancement of the transmittance of ED. At a specific frequency, the so-called characteristic frequency (Fc), the transmittance reaches a maximum. Fc could be used as an indicator to mark the shell materials. The antibody of Yersinia pestis (ab-Yp) was coated onto the SM@FN as a biosensing medium. The Fc of ab-Yp-modified microspheres shifted from 200 to 750 kHz with antigen coupling of Y. pestis antigen (ag-Yp). In the absence of fluorescence labeling, the large change in ED transmittance could be visualized during the Y. pestis detection. The limit of detection and the limit of quantification were ∼30 and ∼40 ng/µL, respectively, obtained within 30 s according to the highest transmittance of ED under the AEF at 750 kHz. Y. pestis detection was not affected by Escherichia coli and Staphylococcus aureus significantly. Compared with other common immunoassays, including the secondary immunochemical or enzyme-linked steps, this simple electrorheological sensor with high sensitivity and selectivity could be a candidate for on-site plague diagnosis.

Ex Vivo Expansion and Drug Sensitivity Profiling of Circulating Tumor Cells from Patients with Small Cell Lung Cancer.

Small cell lung cancer (SCLC) represents one of the most aggressive malignancies among cancer types. Not only tumor sample availability is limited, but also the ability for tumor cells to rapidly acquire drug resistance are the rate-limiting bottlenecks for overall survival in current clinical settings. A liquid biopsy capable of capturing and enriching circulating tumor cells (CTCs), together with the possibility of drug screening, is a promising solution. Here, we illustrate the development of a highly efficient ex vivo CTC expansion system based on binary colloidal crystals substrate. Clinical samples were enrolled from 22 patients with SCLC in the study. The CTCs were enriched and expanded from the collected peripheral blood samples. Expanded cells were analyzed for protein expression and observed for drug sensitivity with the use of immunofluorescence and ATP titer evaluation, respectively. Successful CTC spheroid proliferation was established after 4 weeks within 82% of all the collected peripheral blood samples from enrolled patients. Upon immunofluorescence analysis, the enriched cells showed positive markers for EpCAM, TTF-1, synaptophysin and negative for CD45. Additionally, the expanded CTCs demonstrated marked heterogeneity in the expression of E-cadherin and N-cadherin. In a preliminary case series, the drug sensitivity of patient-derived CTC to cisplatin and etoposide was studied to see the correlation with the corresponding therapeutic outcome. In conclusion, our study demonstrates that it is possible to efficiently expand CTCs from SCLC within a clinically relevant time frame; the biomarker information generated from enriched CTCs can assist the selection of effective drugs and improve disease outcome.

Overcoming steroid unresponsiveness in airways disease.

Most of the patients with asthma are found to be successfully treated with conventional therapy. However, there are a small proportion of asthmatic patients who fail to respond to corticosteroids even at high doses or with supplementary therapy. In addition, even high doses of corticosteroids have a minimal effect on the inexorable decline in lung function in COPD (chronic obstructive pulmonary disease) and only a small effect in reducing exacerbations. Corticosteroid-insensitivity therefore presents a profound management problem. Corticosteroids act through a cytosolic receptor [GR (glucocorticoid receptor)], which is activated and translocates to the nucleus. Once in the nucleus, it either binds to DNA and switches on the expression of anti-inflammatory genes or represses the activity of distinct signalling pathways such as NF-kappaB (nuclear factor kappaB), AP-1 (activator protein-1) or MAPKs (mitogen-activated protein kinases). This latter step requires the recruitment of co-repressor molecules. A failure to respond to corticosteroids may therefore result from lack of binding to GR, reduced GR expression, lack of co-repressor activity or enhanced activation of inflammatory pathways. These events can be modulated by oxidative stress or high levels of inflammatory cytokines, which may lead to a reduced clinical outcome. Understanding the molecular mechanisms of GR action, and inaction, may lead to the development of new anti-inflammatory drugs or reverse the relative corticosteroid-insensitivity that is characteristic of these diseases.

Design and testing of a miniature broadband frequency domain photon migration instrument.

A board-level broadband frequency domain photon migration (mini-FDPM) instrument has been constructed to replace a conventional network-analyzer-based FDPM instrument. The mini-FDPM instrument with four wavelengths (681, 783, 823, and 850 nm), matches conventional FDPM instrument in performance (-88 dBm noise level, 100 dB dynamic range) and bandwidth (1 GHz), and recovers the same optical properties within about 6% in absorption and 4% in reduced scattering for liquid phantoms covering a wide range of relevant optical properties. Compared to the conventional FDPM instrument, the mini-FDPM instrument is more than 5x faster (approximately 200 ms per 401 modulation frequencies) and several orders of magnitude less in size and cost. Standard fiber-optic-based probes can be used with the mini-FDPM instrument, which increases applications in a number of clinically relevant measurement scenarios. By drastically reducing size and cost, FDPM miniaturization lowers barriers to access and will help promote FDPM in clinical research problems. The mini-FDPM instrument forms the core of a modular broadband diffuse optical spectroscopy instrument that can be used for a variety of clinical problems in imaging and functional monitoring (i.e., breast/skin cancer, brain activation, and exercise physiology).

Characterizing the conservation effect of clear coatings on photodegradation of wood.

Photodiscoloration of clear-coated wood may be caused by the yellowing of both clear coating film and underlying wood, or either of them. Wood specimens covered with two types of free polyurethane films with/without light stabilizer were used to simulate the photodiscoloration of clear-coated wood. Percent UV transmission of aromatic polyurethane (PU) films decreased after irradiation, whereas aliphatic polyurethane (PUA) films significantly increased with irradiation time resulting in further photoyellowing of wood beneath the PUA film. A light reflection model was used to elucidate discoloration caused separately by the clear coating film and the underlying wood. After 24 days of light irradiation, clear coating and the underlying wood contributed respectively, 40.70% and 59.30% discoloration of PU-coated specimens, and the corresponding values for PUA-coated specimens were 5.15% and 94.85%. PU film with light stabilizer reduced lignin degradation and generation of carbonyl derivatives in the underlying wood.

Reducing the Computational Complexity of EEG Source Localization With Cortical Patch Decomposition and Optimal Electrode Selection.

OBJECTIVE: Real-time implementation of EEG source localization can be employed in a broad area of applications such as clinical diagnosis of neurologic diseases and brain-computer interface. However, a power-efficient, low-complexity, and real-time implementation of EEG source localization is still challenging due to extensive iterations in the solutions. In this study, two techniques are introduced to reduce the computational burden of the subspace-based MUltiple SIgnal Classification (MUSIC) algorithm. METHODS: To shrink the exhaustive search inherent in MUSIC, the cortex is parsed into cortical regions. A novel nomination procedure involving a dictionary learning step will pick a number of regions to be searched for the active sources. In addition, a new electrode selection algorithm based on the Cramer-Rao bound of the errors is introduced to pick the best set of an arbitrary number of electrodes out of the total. RESULTS: The performance of the proposed techniques were evaluated using simulated EEG signal under variation of different parameters such as the number of nominated regions, the signal to noise ratio, and the number of electrodes. The proposed techniques can reduce the computational complexity by up to $90\%$. Furthermore, the proposed techniques were tested on EEG data from an auditory oddball experiment. CONCLUSION: A good concordance was observed in the comparison of the topographies and the localization errors derived from the proposed technique and regular MUSIC. SIGNIFICANCE: Such reduction can be exploited in the real-time, long-run, and mobile monitoring of cortical activity for clinical diagnosis and research purposes.