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Although COVID-19 coagulopathy typically manifests with thrombotic complications, hemorrhagic complications also occur and must be considered when making decisions about anticoagulation in these patients. Here, we report a case of massive hemoptysis occurring in a recently post-partum woman via Cesarean section with COVID-19 who was managed via bronchial artery embolization while on extracorporeal membrane oxygenation.

There is growing interest in the implementation of microsampling approaches for the quantitation of circulating concentrations of analytes in biological samples derived from nonclinical and clinical studies involved in drug development. This interest is partly due to the ethical advantages of taking smaller blood volumes, particularly for studies in rodents, children and the critically ill. In addition, these technologies facilitate sampling to be performed in previously intractable locations and occasions. Further, they enable the collection of samples for additional purposes (extra time points, biomarkers, sampling during a clinical event, etc). This article gives a comprehensive insight to the utilization of these approaches in drug discovery and development, and provides recommendations for best practice for nonclinical, clinical and bioanalytical aspects.

Objective(s): Subglottic stenosis (SGS) represents a constellation of diverse pathologic processes that ultimately lead to narrowing of the subglottic region and can produce significant morbidity. Existing endoscopic and radiographic assessments may not be consistent in practice. Methods: Severity of stenosis was evaluated and reported using the Cotton-Myer classification system from 33 endoscopic procedures from 32 unique subjects. Radiographic imaging within the preceding 3 month period was subsequently reviewed and narrowing was measured by a blinded radiologist. Degree of stenosis was reported as a percentage in 30 out of 33 endoscopic evaluations and subsequently compared to radiographically determined percentage of stenosis. Statistical analyzes were conducted to evaluate concordance between endoscopic and radiographic assessments. Results: About 45.5% (15/33) of the evaluations were in agreement using Cotton-Myer scoring, while 27.3% (9/33) were discrepant by 1 grade and 27.3% (9/33) by 2 grades. Correlation of degree of stenosis as a percentage using Spearman (coefficient: 0.233, P-value: .214) and Pearson (coefficient: 0.138, P-value: .466) methods demonstrated very weak relationships. Radiographic scoring did not predict endoscopic classification to a significant degree using mixed effects regression. Conclusions: Radiographic and endoscopic grading of subglottic stenosis may not be reliably concordant in practice.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been reported to mediate both tumorigenic and anti-tumor effects in vivo. Blockade of the CEACAM1 signaling pathway has recently been implicated as a novel mechanism for cancer immunotherapy. CC1, a mouse anti-CEACAM1 monoclonal antibody (mAb), has been widely used as a pharmacological tool in preclinical studies to inform on CEACAM1 pathway biology although limited data are available on its CEACAM1 blocking characteristics or pharmacodynamic-pharmacokinetic profiles. We sought to investigate CEACAM1 expression on mouse tumor and immune cells, characterize CC1 mAb binding, and evaluate CC1 in syngeneic mouse oncology models as a monotherapy and in combination with an anti-PD-1 mAb. CEACAM1 expression was observed at high levels on neutrophils, NK cells and myeloid-derived suppressor cells (MDSCs), while the expression on tumor-infiltrating CD8+ T cells was low. Unexpectedly, rather than blocking, CC1 facilitated binding of soluble CEACAM1 to CEACAM1 expressing cells. No anti-tumor effects were observed in CT26, MBT2 or A20 models when tested up to 30 mg/kg dose, a dose that was estimated to achieve >90% target engagement in vivo. Taken together, tumor infiltrating CD8+ T cells express low levels of CEACAM1 and CC1 Ab mediates no or minimal anti-tumor effects in vivo, as a monotherapy or in combination with anti-PD-1 treatment.

bit is a collection of small scripts and programs that facilitate many common tasks in bioinformatics. It operates in a Unix-like command-line environment and is comprised of bash and python code. bit is openly available on GitHub, archived with Zenodo, and is conda installable. The package is useful for users who want to do things such as manipulate fasta files, calculate GC content, quickly summarize nucleotide assemblies, easily download assemblies from NCBI just based on accessions, pull amino-acid sequences from GenBank files, calculate Shannon uncertainty for columns in multiple sequence alignments, and more. The source code is hosted on GitHub: github.com/AstrobioMike/bit

The 8th Annual Shanghai Symposium on Clinical and Pharmaceutical Solutions through Analysis (CPSA): Clinical and Pharmaceutical Success from Discovery to Regulatory Approval: Biomarkers, Modeling and Analytical Technologies (CPSA Shanghai 2017); Renaissance Shanghai Pudong Hotel, Shanghai, China, 12–14 April 2017 was held on 12–14 April 2017 in Shanghai, China. The meeting was featured with highly interactive events including diversified symposia, workshops, roundtable discussions, conference awards and poster sessions. There were over 220 participants with 61 oral presentations and 20 posters presented. In addition, the meeting included a preconference workshop with an inaugural session on the evaluation of quality and efficacy for generic drugs in China.

This study proposes a gradient-boosting-based machine learning approach for predicting the PM2.5 concentration in Taiwan. The proposed mechanism is evaluated on a large-scale database built by the Environmental Protection Administration, and Central Weather Bureau, Taiwan, which includes data from 77 air monitoring stations and 580 weather stations performing hourly measurements over 1 year. By learning from past records of PM2.5 and neighboring weather stations’ climatic information, the forecasting model works well for 24-h prediction at most air stations. This study also investigates the geographical and meteorological divergence for the forecasting results of seven regional monitoring areas. We also compare the prediction performance between Taiwan, Taipei, and London; analyze the impact of industrial pollution; and propose an enhanced version of the prediction model to improve the prediction accuracy. The results indicate that Taipei and London have similar prediction results because these two cities have similar topography (basin) and are financial centers without domestic pollution sources. The results also suggest that after considering industrial impacts by incorporating additional features from the Taichung and Thong-Siau power plants, the proposed method achieves significant improvement in the coefficient of determination (R2) from 0.58 to 0.71. Moreover, for Taichung City the root-mean-square error decreases from 8.56 for the conventional approach to 7.06 for the proposed method.

Department of Defense (DoD) military systems designed to attack, protect, and provide tactical advantages to the warfighter increasingly push technological advances. Systems and subsystems share data at high rates to make quick decisions. Because of the rapid advancements in technology, the DoD Family of Testers (FoT) are unable to validate units under test (UUT) that use high-speed digital buses. Current and developing solutions to solve this problem are done in a closed architecture designed specifically for one DoD automatic test system (ATS). Technology Service Corporation's Automatic Test System (TSCATS) is being developed as a high-speed digital bus augmentation capability to the DoD FoTs leveraging IEEE standards to provide an open architecture framework. The discrete system can be remotely triggered and applicable to a wide range of DoD FoTs. The TSCATS utilizes a commercial off-the-shelf (COTS) PXIe hardware platform and a software Test Executive (TE) capable of parsing an automatic test mark-up language (ATML IEEE Std. 1671) test description (TD) document and using synthetic instruments to deliver and test high-speed communication protocols. Benefits to this approach include reduced life-cycle, TPS development, and re-host costs while providing DoD an augmented test capability for their ATS environment. The DoD is increasingly incorporating ATML as its standard language in describing all aspects of automated test systems and automatic testing. The sub-standard for IEEE Std. 1671, IEEE Std. 1671.1 - Standard for Automatic Test Markup Language Test Description, identifies and documents the necessary components for describing the testing procedure for a UUT. For a Test Program Set (TPS) developer, the test description provides important test information in developing software to validate a DoD UUT. The TSCATS hardware platform TE, Test Forge, provides test sequencing, parameter validation, data reporting, error handling, and UUT and ATE monitoring solutions. Test Forge is designed independently of specific underlying requirements of UUTs or test station capabilities. It is designed to provide a flexible architecture that allows developers to add or extend functionality. The Test Forge ATML TD tools provide an interface for test developers to load ATML test descriptions and automatically generate software test shells for development, parameter files, test sequences, and executable build specifications for the TPS software. The TSCATS hardware platform will incorporate a synthetic high-speed instrumentation module capable of exchanging test signals with the UUT controlled by Test Forge and can be connected to any ATE, DoD or commercial. The reconfigurable instrumentation module currently provides speeds up to 12.5 Gbps data rates, meeting signal requirements for high-speed communication protocols such as 10 GbE, SATA, USB, and Serial RapidIO. The platform uses COTS hardware based on industry standard practices for low-cost and easier upgrades. The TSCATS is designed to provide DoD a low-cost, open architecture, high-speed bus tester with ease of UUT re-hosting.

7th Annual Symposium on Clinical & Pharmaceutical Solutions through Analysis, Renaissance Shanghai Pudong Hotel, Shanghai, China, 20–23 April 2016 The 7th Annual Shanghai Symposium on Innovative Approaches to Reduce Attrition and Predict Clinical Outcomes (CPSA Shanghai 2016) was held on 20–23 April 2016 in Renaissance Shanghai Pudong Hotel, Shanghai, China. The meeting was featured with highly interactive events including diversified symposia, round table discussions, workshops, poster sessions and conference awards. There were over 220 participants from more than ten countries, with 61 oral presentations and 29 posters presented. In addition, the meeting included one preconference workshop and three joint sessions held with bioanalytical experts from local communities.

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine protein kinase that transmits calcium signals in various cellular processes. CaMKII is activated by calcium-bound calmodulin (Ca

The vitamin A metabolite retinoic acid (RA) regulates adaptive immunity in the intestines, with well-characterized effects on IgA responses, Treg induction, and gut trafficking of T- and B-effector cells. It also controls the generation of conventional dendritic cell (cDC) precursors in the bone marrow and regulates cDC subset representation, but its roles in the specialization of intestinal cDC subsets are understudied. Here we show that RA acts cell intrinsically in developing gut-tropic pre-mucosal dendritic cell (pre-μDC) to effect the differentiation and drive the specialization of intestinal CD103(+)CD11b(-) (cDC1) and of CD103(+)CD11b(+) (cDC2). Systemic deficiency or DC-restricted antagonism of RA signaling resulted in altered phenotypes of intestinal cDC1 and cDC2, and reduced numbers of cDC2. Effects of dietary deficiency were most apparent in the proximal small intestine and were rapidly reversed by reintroducing vitamin A. In cultures of pre-μDC with Flt3L and granulocyte-macrophage colony-stimulating factor (GM-CSF), RA induced cDC with characteristic phenotypes of intestinal cDC1 and cDC2 by controlling subset-defining cell surface receptors, regulating subset-specific transcriptional programs, and suppressing proinflammatory nuclear factor-κB-dependent gene expression. Thus, RA is required for transcriptional programming and maturation of intestinal cDC, and with GM-CSF and Flt3L provides a minimal environment for in vitro generation of intestinal cDC1- and cDC2-like cDC from specialized precursors.

The recent design of ultra-broadband, multi-frequency ultrasound transducers has enabled high sensitivity, high-resolution contrast imaging, with very efficient suppression of tissue background using a technique called acoustic angiography. Here we perform the first application of acoustic angiography to evolving tumors in mice predisposed to develop mammary carcinoma, with the intent of visualizing and quantifying angiogenesis progression associated with tumor growth. Metrics compared include vascular density and two measures of vessel tortuosity quantified from segmentations of vessels traversing and surrounding 24 tumors and abdominal vessels from control mice. Quantitative morphological analysis of tumor vessels demonstrated significantly increased vascular tortuosity abnormalities associated with tumor growth with the distance metric elevated approximately 14% and the sum of angles metric increased 60% in tumor vessels versus controls. Future applications of this imaging approach may provide clinicians a new tool in tumor detection, differentiation, or evaluation, though with limited depth of penetration using the current configuration.

The 17th Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis (CPSA) 29 September–2 October 2014, was held at the Sheraton Bucks County Hotel, Langhorne, PA, USA. The CPSA USA 2014 brought the various analytical fields defining the challenges of the modern analytical laboratory. Ongoing discussions focused on the future application of bioanalysis and other disciplines to support investigational new drugs (INDs) and new drug application (NDA) submissions, clinical diagnostics and pathology laboratory personnel that support patient sample analysis, and the clinical researchers that provide insights into new biomarkers within the context of the modern laboratory and personalized medicine.

Although the homing of lymphocytes to GALT has been extensively studied, little is known about how high endothelial venules (HEVs) within Peyer’s patches (PPs) are patterned to display dominantly mucosal addressin cell adhesion molecule 1 (MAdCAM-1). In this study, we report that Nkx2-3–deficient mice show gradual loss of MAdCAM-1 in PPs postnatally and increased levels of mRNA for peripheral lymph node addressin (PNAd) backbone proteins as well as enhanced expression of MECA79 sulfated glycoepitope at the luminal aspect of HEVs, thus replacing MAdCAM-1 with PNAd. Induction of PNAd in mutant PPs requires lymphotoxin β receptor activity, and its upregulation needs the presence of mature T and B cells. Furthermore, treatment with MECA-79 anti-PNAd mAb in vivo effectively blocks lymphocyte homing to mutant PPs. Despite the replacement of MAdCAM-1 by PNAd in HEV endothelia, lymphocytes could efficiently home to PPs in mutant mice. We conclude that although Nkx2-3 activity controls the addressin balance of HEVs in GALT, the general HEV functionality is preserved independently from Nkx2-3, indicating a substantial plasticity in the specification of GALT HEV endothelium.

The 5th Annual Shanghai Symposium on Clinical & Pharmaceutical Solutions through Analysis (CPSA Shanghai 2014) was held on 16–19 April 2014 in Shanghai, China. The meeting featured highly interactive events including diversified symposia, roundtable discussions, workshops, poster sessions and conference awards. There were over 220 participants from more than 10 countries, with 45 oral presentations and 42 posters presented. In addition, the meeting included one preconference workshop and a joint session with local bioanalytical and drug metabolism discussion groups.

The 16th Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis (CPSA) 7–10 October 2013, Sheraton Bucks County Hotel, Langhorne, PA, USA. The 2013 CPSA brought together the various US FDA regulated analytical fields affecting a ‘patient’ for the first time – bioanalysts supporting IND and NDAs, clinical diagnostic and pathology laboratory personnel, and clinical researchers that provide insights into new biomarkers. Although the regulatory requirements are different for each of the above disciplines, the unique analytical perspectives that affect the patient were shared – and the goal of the 2013 CPSA – ‘Connecting Patients and Subject Numbers Through Analysis’ was achieved.

Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterized human gut DC populations and defined their relationship to previously studied human and mouse DCs. CD103(+)Sirpα(-) DCs were related to human blood CD141(+) DCs and to mouse intestinal CD103(+)CD11b(-) DCs and expressed markers of cross-presenting DCs. CD103(+)Sirpα(+) DCs aligned with human blood CD1c(+) DCs and mouse intestinal CD103(+)CD11b(+) DCs and supported the induction of regulatory T cells. Both CD103(+) DC subsets induced the TH17 subset of helper T cells, while CD103(-)Sirpα(+) DCs induced the TH1 subset of helper T cells. Comparative analysis of transcriptomes revealed conserved transcriptional programs among CD103(+) DC subsets and identified a selective role for the transcriptional repressors Bcl-6 and Blimp-1 in the specification of CD103(+)CD11b(-) DCs and intestinal CD103(+)CD11b(+) DCs, respectively. Our results highlight evolutionarily conserved and divergent programming of intestinal DCs.

The 4th Annual Shanghai Symposium on Clinical & Pharmaceutical Solutions through Analysis (CPSA Shanghai 2013) was held on 24–27 April 2013 in Shanghai, China. The meeting provided an educational forum for scientists from pharmaceutical industry, academia, CROs and instrument vendors to share experience and ideas, and discuss current challenges, issues and innovative solutions associated with pharmaceutical R&D. The meeting featured highly interactive events, including diversified symposia, roundtable discussions, workshops, poster sessions and conference awards. Education and specialized training are the foundation of CPSA events. The CPSA Shanghai 2013 meeting also featured an inaugural satellite workshop event in Beijing, as well as joint sessions traditionally held with local bioanalytical and drug metabolism discussion groups.

Cartilaginous fishes are the oldest group in which an adaptive immune system based on immunoglobulin-superfamily members is found. This manuscript compares humoral immune function in small-spotted catshark (Scyliorhinus canicula) with that described for spiny dogfish (Squalus acanthias), another member of the Squalomorphi superorder, and nurse shark, the model for humoral immunity in elasmobranchs and a member of the Galeomorphi superorder. Although small-spotted catshark and nurse shark are separated by over 200 million years we found that immunoglobulin isoforms are well conserved between the two species. However, the plasma protein profile of small-spotted catshark was most similar to that of spiny dogfish, with low levels of pentameric IgM, and IgNAR present as a multimer in plasma rather than a monomer. We show that an antigen-specific monomeric IgM response, with a profile similar to that described previously for nurse sharks, can be raised in small-spotted catshark. Lacking polyclonal or monoclonal antibody reagents for detecting catshark IgNAR we investigated phage-display and recombinant Fc-fusion protein expression as alternative methods to look for an antigen-specific response for this isotype. However, we could find no evidence of an antigen-specific IgNAR in the animals tested using either of these techniques. Thus, unlike nurse sharks where antigen-specific monomeric IgM and IgNAR appear together, it seems there may be a temporal or complete 'uncoupling' of these isotypes during a humoral response in the small-spotted catshark.

This annual meeting began in 1998 and was the first industry-led event to focus on the specific needs of industry researchers. The goal of Clinical and Pharmaceutical Solutions Through Analysis (CPSA) is to provide an in-depth review of innovative technology and industry practices through open discussion of industry-related issues and needs. Education and specialized training are the foundation of all CPSA events. As the industry has evolved so has CPSA. Thus, the year the name was changed from Chemical and Pharmaceutical Structural Analysis to CPSA was to reflect the growing focus on clinical applications and the emergence of personalized medicine. Most importantly, the CPSA annual meeting has retained the same high-quality scientific content, open interaction from industry opinion leaders and a collegial environment.

This paper aims to discuss an exploratory study that a student teacher carried out on applying the “flipped classroom” approach in his information and communication technology (ICT) class. The study examined student perceptions of the new teaching approach and investigated whether it can help promote higher-order thinking. This study involved 28 students in a public secondary school in Hong Kong. They were attending an ICT class on 3D modelling. A mixed methods approach was adopted. Both quantitative and qualitative data were collected through surveys, online quizzes and focus group interview. The students’ assignments were also examined and analysed. The findings show that students are inclined to accept the new teaching model. We can conclude that it is possible to improve students’ higher-order thinking capability using the flipped classroom approach to teaching.

Circulating factor VIII (FVIII) is derived from liver and from extrahepatic sources probably of endothelial origin, but the vascular sites of FVIII production remain unclear. Among organs profiled, only liver and lymph nodes (LNs) show abundant expression of F8 messenger RNA (mRNA). Transcriptomic profiling of subsets of stromal cells, including endothelial cells (ECs) from mouse LNs and other tissues, showed that F8 mRNA is expressed by lymphatic ECs (LECs) but not by capillary ECs (capECs), fibroblastic reticular cells, or hematopoietic cells. Among blood ECs profiled, F8 expression was seen only in fenestrated ECs (liver sinusoidal and renal glomerular ECs) and some high endothelial venules. In contrast, von Willebrand factor mRNA was expressed in capECs but not in LECs; it was coexpressed with F8 mRNA in postcapillary high endothelial venules. Purified LECs and liver sinusoidal ECs but not capECs from LNs secrete active FVIII in culture, and human and mouse lymph contained substantial FVIII:C activity. Our results revealed localized vascular expression of FVIII and von Willebrand factor and identified LECs as a major cellular source of FVIII in extrahepatic tissues.

The 3rd Annual Symposium on Chemical and Pharmaceutical Structure Analysis was once again held in Shanghai, where a rich history of ‘East meets West’ continued. This meeting is dedicated to bringing together scientists from pharmaceutical companies, academic institutes, CROs and instrument vendors to discuss current challenges and opportunities on the forefront of pharmaceutical research and development. The diversified symposia and roundtables are highly interactive events where scientists share their experiences and visions in a collegial setting. The symposium highlighted speakers and sessions that provided first-hand experiences as well as the latest guidance and industrial/regulatory thinking, which was reflected by the theme of this year’s meeting ‘From Bench to Decision Making – from Basics to Application.’ In addition to the highly successful Young Scientist Excellence Award, new events were featured at this year’s meeting, such as the Executive Roundtable and the inaugural Innovator Award.

This annual meeting began in 1998 and was the first industry-led event to focus on the specific needs of industry researchers. The goal of Chemical and Pharmaceutical Structure Analysis is to provide an in-depth review of innovative technology and industry practices through open discussion of industry-related issues and needs. Education and specialized training are the foundation of all Chemical and Pharmaceutical Structure Analysis events – where technology and solutions meet.

This annual meeting began in 1998 and was the first industry-led event to focus on the specific needs of industry researchers. The goal of the Chemical and Pharmaceutical Structure Analysis is to provide an in-depth review of innovative technology and industry practices through open discussion of industry-related issues and needs. Education and specialized training are the foundation of all CPSA events: ‘Where Technology and Solutions Meet’.

With recent advances in animal models of disease, there has been great interest in capabilities for high-resolution contrast-enhanced ultrasound imaging. Microbubble contrast agents are unique in that they scatter broadband ultrasound energy because of their nonlinear behavior. For optimal response, it is desirable to excite the microbubbles near their resonant frequency. To date, this has been challenging with high-frequency imaging systems because most contrast agents are resonant at frequencies in the order of several megahertz. Our team has developed a unique dual-frequency confocal transducer which enables low-frequency excitation of bubbles near their resonance with one element, and detection of their emitted high-frequency content with the second element. Using this imaging approach, we have attained an average 12.3 dB improvement in contrast-to-tissue ratios over fundamental mode imaging, with spatial resolution near that of the high-frequency element. Because this detection method does not rely on signal decorrelation, it is not susceptible to corruption by tissue motion. This probe demonstrates contrast imaging capability with significant tissue suppression, enabling high-resolution contrast-enhanced images of microvascular blood flow. Additionally, this probe can readily produce radiation force on flowing contrast agents, which may be beneficial for targeted imaging or therapy.