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Despite the continuously increased requirement on automated synthesis of medicines for distributed manufacturing and personal care, it remains a challenge to realize automated synthesis which requires solid-liquid phase reactions. In this work, we demonstrated an automated solid-liquid synthesis for gadopentetate dimeglumine, the most widely used magnetic resonance imaging (MRI) contrast agent. The high-efficiency reaction was performed in a 3D microfluidic chip which was fabricated by femtosecond laser micromachining. The structure of the chip realized 3D shear flow which was essential for highly efficient mixing and movement of the solid-liquid mixtures. Ultraviolet visible (UV–vis) spectrometer was employed for in-line analysis to help automation of this system. Comparing with the round-bottom flask system, this synthetic system showed significantly higher reaction rate, indicating the advantage of the 3D microfluidic technology in micro chemical engineering.

Approximately 3 million United States military personnel and contractors were deployed to Southwest Asia and Afghanistan over the past two decades. After returning to the United States, many developed persistent respiratory symptoms, including those due to asthma, rhinosinusitis, bronchiolitis, and others, which we collectively refer to as deployment-related lung diseases (DRLD). The mechanisms of different DRLD have not been well defined. Limited studies from us and others suggest that multiple factors and biological signaling pathways contribute to the onset of DRLD. These include, but are not limited to, exposures to high levels of particulate matter (PM) from sandstorms, burn pit combustion products, improvised explosive devices, and diesel exhaust particles. Once inhaled, these hazardous substances can activate lung immune and structural cells to initiate numerous cell-signaling pathways such as oxidative stress, Toll-like receptors, and cytokine-driven cell injury (e.g., interleukin-33). These biological events may lead to a pro-inflammatory response and airway hyperresponsiveness. Additionally, exposures to PM and other environmental hazards may predispose military personnel and contractors to more severe disease due to the interactions of those hazardous materials with subsequent exposures to allergens and cigarette smoke. Understanding how airborne exposures during deployment contribute to DRLD may identify effective targets to alleviate respiratory diseases and improve quality of life in veterans and active duty military personnel.

Primary primitive neuroectodermal tumor (PNET) of the bladder is an extremely rare and highly aggressive neoplasm. We report a case of PNET of the urinary bladder associated with increased serum neuron-specific enolase (NSE) in the presence of relapse and metastasis. A 66-year-old male presented to our department due to painless gross hematuria. Computed tomographic urography (CTU) showed an intraluminal tumor in the anterior bladder wall. Biopsy revealed a malignant small round blue cell tumor. The patient denied radical cystectomy, and partial cystectomy was given together with resection of adjacent peritoneum. The patient was diagnosed with primary bladder PNET after pathological inspection with negative surgical margins. Additionally, he received 6 cycles of chemotherapy using etoposide and cisplatin (EP) regime, and showed recurrence and metastasis afterwards. Disease progression was seen after transurethral resection (TUR) of bladder tumor and radiotherapy. Pelvic and retroperitoneal metastasis triggered bilateral hydronephrosis, and then palliative treatment was given with bilateral percutaneous nephrostomy. Finally, he died 12 months after diagnosis. PNETs are highly aggressive tumors characterized by the expression of MIC2 and neural markers and the presence of EWS-FLI1 translocation. We recommend histologic, immunohistochemical, and cytogenetic analysis in all patients with small round blue cell bladder malignancy in order to rule out other small cell malignancies. Multimodal treatment, including surgery and adjuvant chemotherapy must be initiated. Patients aged ≤30 years underwent complete resection of tumor and standard chemotherapy showed a better prognosis, while those with metastasis, incomplete resection and inadequate response to chemotherapy showed poor prognosis. Moreover, an elevated NSE may indicate a poor prognosis.

IMPORTANCE Passive surveillance systems are susceptible to the under-reporting of adverse events (AE) and a lack of information pertaining to vaccinated populations. Conventional active surveillance focuses on predefined AEs. Advanced data mining tools could be used to identify unusual clusters of potential AEs after vaccination. OBJECTIVE To assess the feasibility of a novel tree-based statistical approach to the identification of AE clustering following the implementation of a varicella vaccination program among one-year-olds. SETTING AND PARTICIPANTS This nationwide safety surveillance was based on data from the Taiwan National Health Insurance database and National Immunization Information System for the period 2004 through 2014. The study population was children aged 12-35 months who received the varicella vaccine. EXPOSURE First-dose varicella vaccine. OUTCOMES AND MEASURES All incident ICD-9-CM diagnoses (emergency or inpatient departments) occurring 1-56 days after the varicella vaccination were classified within a hierarchical system of diagnosis categories using Multi-Level Clinical Classifications Software. A self-controlled tree-temporal data mining tool was then used to explore the incidence of AE clustering with a variety of potential risk intervals. The comparison interval consisted of days in the 56-day follow-up period that fell outside the risk interval. RESULTS Among 1,194,189 varicella vaccinees with no other same-day vaccinations, nine diagnoses with clustering features were categorized into four safety signals: fever on days 1-6 (attributable risk [AR] 38.5 per 100,000, p

BACKGROUND Most reproductive system studies suggest the protective effects of vitamin D, but vitamin D deficiency and insufficiency are growing global health issues. The present study investigates the association between vitamin D deficiency/insufficiency and gynecologic diseases to identify illness risks at different serum vitamin D levels in Taiwan. METHODS A total of 7699 female adults aged ≥20 years with results for both serum vitamin D and gynecologic-associated diseases were drawn from the Taiwan MJ cohort. We analyzed the correlation between serum vitamin D levels and results from reproductive system evaluations, including history of dysmenorrhea, results of Pap smear, high-risk human papillomavirus (HPV) infection of the cervix, mammography, and ultrasound of breast and pelvis. RESULTS Over 80% of participants showed vitamin D deficiency/insufficiency. Participants with abnormal Pap smear results, high-risk HPV infection, and history of dysmenorrhea showed significantly lower levels of serum vitamin D (p < 0.001-0.05). Serum vitamin D deficiency was significantly associated with positive high-risk HPV infection of the cervix (p < 0.05) and dysmenorrhea (p < 0.001). After controlling for age as a confounding variable for each gynecologic disease, level of serum vitamin D was significantly associated with abnormal breast ultrasound (odds ratio = 0.724) and uterus ultrasound (odds ratio = 0.673 - 0.8), and dysmenorrhea (odds ratio = 0.829). CONCLUSION Associations were found between vitamin D deficiency and endometriosis, uterine myoma, dysmenorrhea, abnormal Pap smear results, and high-risk HPV infection of the cervix. Therefore, vitamin D supplements may present a cost-effective benefit for the prevention and treatment of gynecologic diseases, and thus reduction of healthcare expenditures.

Upon returning from deployment to Afghanistan, a substantial number of U.S. military personnel report deployment-related lung disease (DRLD) symptoms, including those consistent with an asthma-like airways disease. DRLD is thought to be caused by prolonged inhalation of toxic desert particulate matter, which can persist in the postdeployment setting such as exposure to common household allergens. The goal of this study was to define the transcriptomic responses of lung leukocytes of mice exposed to Afghanistan desert particulate matter (APM) and house dust mite (HDM). C57BL/6 mice (n = 15/group) were exposed to filtered air or aerosolized APM for 12 days, followed by intranasal PBS or HDM allergen challenges for 24 h. Bronchoalveolar lavage (BAL) cells were collected for single-cell RNA sequencing (scRNAseq), and assessment of inflammation and airway hyper-responsiveness. Unsupervised clustering of BAL cell scRNAseq data revealed a unique monocyte population induced only by both APM and allergen treatments. This population of monocytes is characterized by the expression of genes involved in allergic asthma, including Alox15. We validated Alox15 expression in monocytes via immunostaining of lung tissue. APM pre-exposure, followed by the HDM challenge, led to significantly increased total respiratory system resistance compared with filtered air controls. Using this mouse model to mimic DRLD, we demonstrated that inhalation of airborne PM during deployment may prime airways to be more responsive to allergen exposure after returning home, which may be linked to dysregulated immune responses such as induction of a unique lung monocyte population.

Graphical abstract, Introduction A population-specific genomic reference is important for research and clinical practice, yet it remains unavailable for Han Chinese (HC) in Taiwan. Objectives We report the first whole genome sequencing (WGS) database of HC (1000 Taiwanese genome (1KTW-WGS)) and demonstrate several applications to cardiovascular medicine. Methods Whole genomes of 997 HC were sequenced to at least 30X depth. A total of 20,117 relatively healthy HC individuals were genotyped using a customized Axiom GWAS array. We performed a genome-wide genotype imputation technique using IMPUTE2. Results We identified 26.7 million single-nucleotide variants (SNVs) and 4.2 million insertions-deletions. Of the SNVs, 16.1% were novel relative to dbSNP (build 152), and 34.2% were novel relative to gnomAD. A total of 18,450 healthy HC individuals were genotyped using a customized Genome-Wide Association Study (GWAS) array. We identified hypertension-associated variants and developed a hypertension prediction model based on the correlation between the WGS data and GWAS data (combined clinical and genetic models, AUC 0.887), and also identified 3 novel hyperlipidemia-associated variants. Each individual carried an average of 16.42 (SD = 3.72) disease-causing variants. Additionally, we established an online SCN5A (an important cardiac gene) database that can be used to explore racial differences. Finally, pharmacogenetics studies identified HC population-specific SNVs in genes (CYP2C9 and VKORC1) involved in drug metabolism and blood clotting. Conclusion This research demonstrates the benefits of constructing a population-specific genomic reference database for precision medicine.

Despite the capacity to be alone has been considered as a sign of maturity and inner peace for human beings, the contextual factors underlying the relation between the capacity to be alone and psychological distress remain unclear. This study speculated that the direct effect of the capacity to be alone on psychological distress may vary with the levels of individuals’ personality characteristics, such as rumination and mindfulness. To test these hypotheses, 815 middle school students were recruited to complete the self-report questionnaires measuring their capacity to be alone, psychological distress, ruminative responses and mindfulness. The results indicated that the capacity to be alone was positively associated with psychological distress. This direct effect could be moderated by rumination and mindfulness as well as the combined effect of these two. The direct effect was stronger for adolescents with high rumination and low mindfulness than those with low rumination and high mindfulness. These findings enrich our understanding of when or for whom the capacity to be alone is correlated with psychological distress. Moreover, these findings highlight the need to take individuals’ personality characteristics into account to reveal the relation between the capacity to be alone and psychological distress more accurately.

Artificial intelligence in gastrointestinal radiology: A review with special focus on recent development of magnetic resonance and computed tomography

Dysphagia is present in 25-50% of patients with stroke. Therefore, studying the probability of nasogastric tube removal in such patients before discharge from the rehabilitation ward is crucial. In this study, we developed a model to predict the outcome of dysphagia in patients with stroke. A retrospective study was performed from May 2015 to December 2018. We reviewed the medical charts of all patients with a diagnosis of stroke receiving nasogastric tube feeding. Patients were divided into weaned and nonweaned groups to compare baseline characteristics and functional status. The weaned and nonweaned groups comprised 55 and 65 patients, respectively. In the final logistic regression analysis model, the Barthel index at admission, lip closing status, ability to answer simple questions and functional independence before stroke were used to develop a predictive model (Logit = 0.8942 × functional independence before this stroke + 1.1279 × ability to answer simple question + 0.5345 × lip-close status + 0.0546 × Barthel index at admission - 2.2805). The optimal cutoff point based on Youden's index was more than -0.8403 with a sensitivity and specificity of 85.45 and 73.85%, respectively. The positive predicted value was 73.44%. In patients with stroke and dysphagia, a high Barthel index, intact lip closing status, ability to answer simple questions and better functional status before stroke appeared to affect nasogastric tube removal before discharge from the rehabilitation ward. Based on the final regression model, the proposed equation will help physicians and speech pathologists in planning patient care.

To further advance assessment of patient-reported outcomes, the European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group has developed computerized adaptive test (CAT) versions of all EORTC Quality of Life Core Questionnaire (QLQ-C30) scales/items. The aim of this study was to develop and evaluate an item bank for CAT measurement of insomnia (CAT-SL). In line with the EORTC guidelines, the developmental process comprised four phases: (I) defining the concept insomnia and literature search, (II) selection and formulation of new items, (III) pre-testing and (IV) field-testing, including psychometric analyses of the final item bank. In phase I, the literature search identified 155 items that were compatible with our conceptualisation of insomnia, including both quantity and quality of sleep. In phase II, following a multistep-approach, this number was reduced to 15 candidate items. Pre-testing of these items in cancer patients (phase III) resulted in an item list of 14 items, which were field-tested among 1094 patients in phase IV. Psychometric evaluations showed that eight items could be retained in a unidimensional model. The final item bank yielded greater measurement precision than the original QLQ-C30 insomnia item. It was estimated that administering two or more items from the insomnia item bank with CAT results in a saving in sample size between approximately 15–25%. The 8-item EORTC CAT-SL item bank facilitates precise and efficient measurement of insomnia as part of the EORTC CAT system of health-related quality life assessment in both clinical research and practice.

Size-controlled flow synthesis of nanoporous particles are of considerable interest for future industrial applications, however, is facing challenges due to lack of in-situ method for size-characterization in fluidic environment. We present that ultraviolet-visible (UV–vis) absorption spectroscopy can be integrated into a flow-synthesis system which was produced by femtosecond laser micromachining. The shift of the absorption peak position of the ex-situ and in-situ UV–vis spectra correlates to variation of size of porous metal-organic frameworks crystals. ZIF-67 crystals with a size in the range from 200 nm to 1025 nm are fabricated with the assistance of tri-ethylamine under monitoring of in-situ UV–vis spectra. The ZIF-67 crystals are converted into nanoporous carbons particles with controlled sizes. These materials show size-dependent performance in Na-ion battery and size-independent performance in metal/H2O seawater battery.

We have demonstrated that alginate with negligible anticoagulant activity can be converted into carbonized nanogels with potent anticoagulant activity through a solid-state heating process. The conversion of alginate into graphene-like nanosheet (GNS)-embedded polyphenolic-alginate nanogels (GNS/Alg-NGs) has been carried out through condensation and carbonization processes. The GNS/Alg-NGs exhibit much stronger anticoagulant activity (>520-fold) compared to untreated alginate, mainly because their polyphenolic structures have a high binding affinity [dissociation constant (Kd) = 2.1 × 10-10 M] toward thrombin. In addition, the thrombin clotting time delay caused by the GNS/Alg-NGs is 10-fold longer than that of natural polyphenolic compounds, such as quercetin, catechin, naringenin, caffeic acid, and ferulic acid. The thrombin- or kaolin-activated thromboelastography of whole-blood coagulation reveals that the GNS/Alg-NGs display a much stronger anticoagulant ability than that of untreated alginate and naturally sulfated polysaccharides (fucoidan). The GNS/Alg-NGs exhibit superior biocompatibility and anticoagulant activity, as observed with an in vivo rat model, revealing their potential as a blood thinner for the treatment of thrombotic disorders.

Purpose The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. Methods In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. Results From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r| Conclusions For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.

Methotrexate (MTX) is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world. The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing concern due to its potential to induce water pollution. In the present study, the degradation of MTX in aqueous medium was investigated by UV-activated peroxymonosulfate (PMS). A significant improvement in degradation rate by increasing UV intensity and PMS concentration while the decrease in degradation efficiency with the increase of solution pH and initial concentration of MTX was observed. The proposed UV/PMS process could achieve more than 90% MTX degradation in 30 min with a good mineralization degree (65%). A pseudo-first order kinetic model was employed and successfully predicted the degradation of MTX. The effect of other operational parameters such as the initial concentration of the targeted compound, dosage of oxidant (PMS), solution pH and UV intensity on the degradation rate were investigated. At the last, the main transform intermediates were identified using LC–MS and possible degradation pathways were proposed. The results show that UV/PMS can be used as an efficient technology to treat pharmaceuticals such as methotrexate containing water and wastewater.

BACKGROUND AND PURPOSE To assess a 3D high-resolution IR-prepped fast SPGR high-resolution MRI sequence for evaluating hypoglossal nerve lesions. METHODS The clinical data of 8 patients with hypoglossal nerve lesions admitted from December 2011 to February 2016 were retrospectively analyzed. MRI included contrast-enhanced conventional sequences and a 3D IR-prepped fast SPGR high-resolution T1-weighted (BRAVO) MRI sequence at 3T. RESULTS Eight patients had hypoglossal lesions detected by MRI. Conventional enhanced scanning could not clearly display the hypoglossal nerve and canal, while the enhanced 3D high-resolution sequence could. In addition, multiple planar reconstruction clearly displayed the hypoglossal nerve, hypoglossal canal, and lesions in multiple planes. CONCLUSIONS Compared with conventional MRI, we show superior results from an advanced sequence to improve image quality in characterizing hypoglossal nerve lesions.

IntroductionParkin (Park2), an E3 ubiquitin ligase, is critical to maintain mitochondrial function by regulating mitochondrial biogenesis and degradation (mitophagy), but recent evidence suggests the involvement of Parkin in promoting inflammation. In the present study, we determined if Parkin regulates airway mitochondrial DNA (mtDNA) release and inflammatory responses to type 2 cytokine interleukin (IL)-13 and allergens.MethodsWe measured Parkin mRNA expression in brushed bronchial epithelial cells and mtDNA release in the paired bronchoalveolar lavage fluid (BALF) from normal subjects and asthmatics. Parkin-deficient primary human tracheobronchial epithelial (HTBE) cells generated using the CRISPR-Cas9 system were stimulated with IL-13. To determine the in vivo function of Parkin, Parkin knockout (PKO) and wild-type (WT) mice were treated with IL-13 or allergen (house dust mite, HDM) in the presence or absence of mtDNA isolated from normal mouse lungs.ResultsParkin mRNA expression in asthmatic airway epithelium was upregulated, which positively correlated with the levels of released mtDNA in BALF. IL-13-stimulated HTBE cells increased Parkin expression. Moreover, IL-13 induced mtDNA release in Parkin-sufficient, but not in Parkin-deficient HTBE cells. PKO (vs WT) mice attenuated airway mtDNA release and inflammation following IL-13 or HDM treatments. mtDNA amplified airway inflammation in mice treated with IL-13 or HDM. Notably, Parkin also mediated mtDNA-induced exacerbation of airway inflammation.ConclusionOur research findings suggest that Parkin promotes mtDNA release and inflammation in airways, thus improving our understanding of the complex role of Parkin and mitochondrial dysfunction in asthma pathogenesis.

Background Nab-paclitaxel has been widely used in treating breast cancer and pancreatic patients for its low toxicity and high efficiency. However, its role in gastric cancer (GC) remains ambiguous. The aim of our study was to test the anti-tumor activity of nab-paclitaxel using GC patient-derived organoids. Methods By using the organoid culture system, we describe the establishment of human gastric cancer organoid lines from surgical samples of three patients with gastric cancer. The consistency of these organoids with original cancer tissues was evaluated by histopathological examination. The characteristics of the cancer organoids were tested using immunofluorescence (IF) staining. Using organoids, the anti-tumor efficiencies of nab-paclitaxel, 5-Fu and epirubicin were compared by CCK8 assay and Annexin V-FITC/PI staining. Results Three organoids were successfully established and passaged. The morphology of the established GC organoids was consistent with original cancer tissues. The IC50 of nab-paclitaxel was 3.68 μmol/L in hGCO1, 2.41 μmol/L in hGCO2 and 2.91 μmol/L in hGCO3, which was significantly lower than those of 5-FU (72.99 μmol/L in hGCO1, 28.32 μmol/L in hGCO2 and 2.91 μmol/L in hGCO3) and epirubicin (25.85μmol/L in hGCO1, 15.15 μmol/L in hGCO2 and 7.60 μmol/L in hGCO3). When each organoid lines were treated with nab-paclitaxel for increasing period of time, the percentage of the apoptotic cells in each organoid increased accordingly. Conclusion Nab-paclitaxel showed strong anti-tumor activity and had the potential to become front-line drug for treating GC patients. Gastric cancer organoid may be a good tool to predict in vivo response to drugs.

Background: Immune reaction is the most important defense mechanism for destroying invading pathogens in our body, and the epitope is the position of the antigen–antibody interaction on pathogenic proteins. Objective: The majority of epitopes are structural; however, the existing sequence-based predicting websites still have several methods to improve the predicting performance. Therefore, in this study, we used SVM as a machine learning tool to predict the epitope-based on protein sequences. Methods: Firstly, we built five SVM models in the first layer according to five features, including binary composition, position-specific scoring matrix, secondary structure, accessible surface area, and association rule, and then chose the patterns that exhibited the best performance in each model. Secondly, using the confidence score of the first-layer models as the input value for the SVM model in the second layer, that SVM model was integrated into the first-layer SVM models for improving the predicting accuracy. Results: The final prediction model was able to achieve up to 63% accuracy in predicting epitope results, and the predicting performance was better than that achieved by the existing predicting websites. Conclusion: Finally, a case study using a two-subunit cytochrome c oxidase of Paracoccus denitrificans was tested, achieving an accuracy of up to 66%.

Purpose Electronic cigarettes (e-cigs) are relatively new devices that allow the user to inhale a heated and aerosolized solution. At present, little is known about their health effects in the human lung, particularly in the small airways (

The Michael addition reaction is a spontaneous and quick chemical reaction that is widely applied in various fields. This reaction is performed by conjugating an addition of nucleophiles with α, β-unsaturated carbonyl compounds, resulting in the bond formation of C-N, C-S, C-O, and so on. In the development of molecular materials, the Michael addition is not only used to synthesize chemical compounds but is also involved in the mechanism of drug action. Several covalent drugs that bond via Michael addition are regarded as anticarcinogens and anti-inflammatory drugs. Although drug development is mainly focused on pharmaceutical drug discovery, target-based discovery can provide a different perspective for drug usage. However, considerable time and labor are required to define a molecular target through molecular biological experiments. In this review, we systematically examine the chemical structures of current FDA-approved antiviral drugs for potential Michael addition moieties with α, β-unsaturated carbonyl groups, which may exert an unidentified broad-spectrum inhibitory mechanism to target viral or host factors. We thus propose that profiling the targets of antiviral agents, such as Michael addition products, can be achieved by employing a high-throughput LC-MS approach to comprehensively analyze the interaction between drugs and targets, and the subsequent drug responses in the cellular environment to facilitate drug repurposing and/or identify potential adverse effects, with a particular emphasis on the pros and cons of this shotgun proteomic approach.

Emerging and resurging mosquito-borne flaviviruses are an important public health challenge. The increased prevalence of dengue virus (DENV) infection has had a significant socioeconomic impact on epidemic countries. The recent outbreak of Zika virus (ZIKV) has created an international public health emergency because ZIKV infection has been linked to congenital defects and Guillain-Barre syndrome. To develop potentially prophylactic antiviral drugs for combating these acute infectious diseases, we have targeted the host calcium/calmodulin-dependent kinase II (CaMKII) for inhibition. By using CaMKII structure-guided inhibitor design, we generated four families of benzenesulfonamide (BSA) derivatives for SAR analysis. Among these substances, N-(4-cycloheptyl-4-oxobutyl)-4-methoxy-N-phenylbenzenesulfonamide (9) showed superior properties as a lead CaMKII inhibitor and antiviral agent. BSA 9 inhibited CaMKII activity with an IC50 value of 0.79 μM and displayed EC50 values of 1.52 μM and 1.91 μM against DENV and ZIKV infections of human neuronal BE(2)C cells, respectively. Notably, 9 significantly reduced the viremia level and increased animal survival time in mouse-challenge models.

Background: Wearable and unobtrusive sensing devices are rapidly evolving for long-term cardiovascular monitoring. However, most of the cardiovascular device requires multi-channel physiological signals acquisition, especially in continuous blood pressure (BP) measurement using pulse transition time (PTT) based methods. The multi-devices implementation could impede wearable applications. Objective: This study developed a wearable neck patch device using single-channel impedance plethysmography (IPG) sensing for cardiovascular monitoring, including continuous BP and heart rate (HR) measurement. Methods: IPG-based BP model was derived based on the Bramwell-Hill equation. A patch IPG device was designed and installed above the carotid artery of the subject neck. To validate the BP and HR functions of our device, the Bland-Altman plots were performed to evaluate the estimation error between the reference and the proposed devices within 20 healthy subjects. Results: The BP performance indicates that systolic BP (SBP) estimation error was -0.16 ± 2.97 mmHg and 2.43 ± 1.71 mmHg in terms of mean error (ME) and mean absolute error (MAE), and 0.09 ± 3.30 mmHg and 2.83 ± 1.68 mmHg for diastolic BP (DBP) estimation. Moreover, the HR accuracy has the ME and MAE of 0.02 ± 0.17 bpm and 0.14 ± 0.08 bpm; mean percentage error (MPE) and mean absolute percentage error (MAPE) obtained 0.04 ± 0.23 % and 0.19 ± 0.12 %. Based on statistical results, the BP and HR function of our device satisfied with AAMI/ANSI criteria below 5 ± 8 mmHg and ± 5 bpm or ± 10%. Conclusion: This study implemented a wearable neck patch device with single-channel IPG acquisition that provided two significant cardiovascular parameters of continuous BP and HR, and its performance agreed with standard criteria based on validation with reference sensors. Significance: The proposed proof-of-concept IPG neck patch device has a high potential for wearable applications and low-cost manufacturing in cardiovascular monitoring.

Summary All-optical physiology (AOP) manipulates and reports neuronal activities with light, allowing for interrogation of neuronal functional connections with high spatiotemporal resolution. However, contemporary high-speed AOP platforms are limited to single-depth or discrete multi-plane recordings that are not suitable for studying functional connections among densely packed small neurons, such as neurons in Drosophila brains. Here, we constructed a 3D AOP platform by incorporating single-photon point stimulation and two-photon high-speed volumetric recordings with a tunable acoustic gradient-index (TAG) lens. We demonstrated the platform effectiveness by studying the anterior visual pathway (AVP) of Drosophila. We achieved functional observation of spatiotemporal coding and the strengths of calcium-sensitive connections between anterior optic tubercle (AOTU) sub-compartments and >70 tightly assembled 2-μm bulb (BU) microglomeruli in 3D coordinates with a single trial. Our work aids the establishment of in vivo 3D functional connectomes in neuron-dense brain areas., Graphical Abstract, Highlights • All-optical volumetric physiology = precise stimulation + fast volumetric recording • Precise single-photon point stimulation among genetically defined neurons • 3D two-photon imaging by an acoustic gradient-index lens for dense neural structures • Observation of 3D functional connectivity in Drosophila anterior visual pathway, Neuroscience; Techniques in Neuroscience; Biological Sciences Research Methodologies; Biological Sciences Tools

Nephrolithiasis is a common disease affecting almost all populations, with an increasing prevalence over the past decades. Previous studies revealed several functional polymorphisms associated with the pathogenesis of nephrolithiasis. However, data on Asian populations are limited. In this study, three candidate polymorphisms were selected from previous studies to investigate the correlations with nephrolithiasis in a Taiwanese population. In total, 454 nephrolithiasis patients were recruited from Kaohsiung Medical University Hospital, with SNP frequency for 1513 subjects of general population from the Taiwan Biobank (TWB) as a genotypic reference. Results revealed that subjects with minor TT genotype at rs1256328 (alkaline phosphatase, liver/bone/kidney (ALPL)) have higher susceptibility to nephrolithiasis (odds ratio (OR) = 2.03, p = 0.0013). In addition, subjects carrying the minor AA genotype at rs12654812 (regulator of G protein signaling 14 (RGS14)) have higher susceptibility to nephrolithiasis (OR = 1.91, p = 0.0017). Among nephrolithiasis patients, subjects with GG at rs7627468 (calcium-sensing receptor (CASR)) have lower pH level in urine (p = 0.0088). Importantly, rs7627468 is associated with the expressions of IQCB1 and EAF2. rs12654812 could influence the expression of RGS14 itself, MXD3, and FGFR4. In summary, this study successfully validated the genetic roles of rs1256328 and rs12654812 in human nephrolithiasis.

The spectrum and evolution of proliferation rates in stage IV lung carcinoids is poorly defined. In particular, there are limited data on the prevalence and characteristics of tumors exceeding the standard upper proliferative criteria—as defined largely based on early-stage carcinoids—in metastatic setting. Sixty-six patients with stage IV lung carcinoids were identified, and all evaluable samples (n = 132; mean 2 samples per patient) were analyzed for mitotic counts and Ki-67 rate. Clinicopathologic and genomic features associated with elevated proliferation rates (>10 mitoses per 2 mm2 and/or >20% hot-spot Ki-67), and evolution of proliferation rates in serial specimens were analyzed. We found that mitoses and/or Ki-67 exceeded the standard criteria in 35 of 132 (27%) samples, primarily (31/35 cases) at metastatic sites. Although neuroendocrine neoplasms with >10 mitoses per 2 mm2 are currently regarded as de facto neuroendocrine carcinomas, the notion that these cases are part of the spectrum of carcinoids was supported by (1) well-differentiated morphology, (2) conventional proliferation rates in other samples from same patient, (3) genetic characteristics, including the lack of RB1/TP53 alterations in all tested samples (n = 19), and (4) median overall survival of 2.7 years, compared to

CeO2 nanorods supported nickel catalysts were prepared by wetness impregnation method, using nickel nitrate and nickel chloride as nickel sources. The dried catalyst precursors were decomposed either by thermal calcination or glow discharge plasma technique. The effects of precursor decomposition methods and nickel sources on the catalytic performance of glycerol steam reforming were then investigated. Characterization and catalytic results showed that glow discharge plasma treatment instead of thermal calcination enhanced the nickel dispersion, improved the Ni-Ce interaction and led to the formation of Ni-O-Ce composite, which could both enhance the H2 selectivity and restrain the coke deposition during reaction. Thus, no deactivation was observed on the two plasma treated catalysts throughout the tests. Nickel source may influence both rate of particle sintering and carbonaceous deposition during reaction; fast nickel sintering but slower coke deposition was found on the catalysts prepared from nickel chloride, and coke deposition was more detrimental to active sites decrease than nickel sintering.

Background: We validated the new European Organisation for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN43). Methods: We enrolled 812 patients with head and neck cancer from 18 countries. Group 1 completed the questionnaire before therapy, and 3 and 6 months later. In group 2 (survivors), we determined test–retest reliability using intraclass correlation coefficients (ICC). Internal consistency was assessed using Cronbach's Alpha, the scale structure with confirmatory factor analysis, and discriminant validity with known-group comparisons. Results: Cronbach's alpha was >0.70 in 10 of the 12 multi-item scales. All standardized factor loadings exceeded 0.40. The ICC was >0.70 in all but two scales. Differences in scale scores between known-groups were >10 points in 17 of the 19 scales. Sensitivity to change was found to be sufficient in 18 scales. Conclusions: Evidence supports the reliability and validity of the EORTC QLQ-HN43 as a measure of quality of life.

This study aimed to compare the accuracy of gated-SPECT (GSPECT) and gated-PET (GPET) in the assessment of left ventricular (LV) end-diastolic volumes (EDVs), end-systolic volumes (ESVs) and LV ejection fractions (LVEFs) among patients with prior myocardial infarction (MI). One hundred and sixty-eight consecutive patients with MI who underwent GSPECT and GPET were included. Of them, 76 patients underwent CMR in addition to the two imaging modalities. The measurements of LV volumes and LVEF were performed using Quantitative Gated SPECT (QGS), Emory Cardiac Toolbox (ECTB), and 4D-MSPECT (4DM). The correlation between GPET, GSPECT, and CMR were excellent for LV EDV (r = 0.855 to 0.914), ESV (r = 0.852 to 0.949), and LVEF (r = 0.618 to 0.820), as calculated from QGS, ECTB, and 4DM. In addition, subgroup analysis revealed that EDV, ESV, and LVEF measured by GPET were accurate in patients with different extents of total perfusion defect (TPD), viable myocardium, and perfusion/metabolic mismatch. Furthermore, multivariate regression analysis identified that mismatch score was associated with the difference in EDV (P