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Article ; Online: Microprobe-Capture In-Emitter Elution: An Affinity Capture Technique to Directly Couple a Label-Free Optical Sensing Technology with Mass Spectrometry for Protein Analysis.

Luo, Ruben Yiqi / Yang, Samuel

2023 Volume 95, Issue 13, Page(s) 5494–5499

Abstract: Affinity capture of an analyte by a capture agent is one of the most effective sample preparation approaches in mass spectrometry (MS), especially top-down MS. We describe a new affinity capture technique for protein targets, called microprobe-capture in- ...

Abstract	Affinity capture of an analyte by a capture agent is one of the most effective sample preparation approaches in mass spectrometry (MS), especially top-down MS. We describe a new affinity capture technique for protein targets, called microprobe-capture in-emitter elution (MPIE), which can directly couple a label-free optical sensing technology (next-generation biolayer interferometry, BLI) with MS. To implement MPIE, an analyte is first captured on the surface of a microprobe and subsequently eluted from the microprobe inside an electrospray emitter. The capture process is monitored in real-time via BLI. When electrospray is established from the emitter to a mass spectrometer, the analyte is immediately ionized via electrospray ionization (ESI) for MS analysis. By this means, BLI and MS are directly coupled in the form of MPIE-ESI-MS. The performance of MPIE-ESI-MS was demonstrated by the analysis of β-amyloid 1-40 and transferrin using both standard samples and human specimens. In comparison to conventional affinity capture techniques such as bead-based immunoprecipitation, MPIE innovates the affinity capture methodology by introducing real-time process monitoring and providing binding characteristics of analytes, offering more information-rich experiment results. Thus, MPIE is a valuable addition to the top-down MS sample preparation toolbox, and MPIE-ESI-MS can be useful for identification and characterization of targets of interest.
MeSH term(s)	Humans ; Spectrometry, Mass, Electrospray Ionization/methods ; Technology
Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.2c04727
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Article ; Online: Microprobe-Capture In-Emitter Elution: An Affinity Capture Technique to Directly Couple a Label-Free Optical Sensing Technology with Mass Spectrometry for Protein Analysis

Luo, Ruben Yiqi / Yang, Samuel

Analytical Chemistry. 2023 Mar. 23, v. 95, no. 13 p.5494-5499

2023

Abstract	Affinity capture of an analyte by a capture agent is one of the most effective sample preparation approaches in mass spectrometry (MS), especially top-down MS. We describe a new affinity capture technique for protein targets, called microprobe-capture in-emitter elution (MPIE), which can directly couple a label-free optical sensing technology (next-generation biolayer interferometry, BLI) with MS. To implement MPIE, an analyte is first captured on the surface of a microprobe and subsequently eluted from the microprobe inside an electrospray emitter. The capture process is monitored in real-time via BLI. When electrospray is established from the emitter to a mass spectrometer, the analyte is immediately ionized via electrospray ionization (ESI) for MS analysis. By this means, BLI and MS are directly coupled in the form of MPIE-ESI-MS. The performance of MPIE-ESI-MS was demonstrated by the analysis of β-amyloid 1–40 and transferrin using both standard samples and human specimens. In comparison to conventional affinity capture techniques such as bead-based immunoprecipitation, MPIE innovates the affinity capture methodology by introducing real-time process monitoring and providing binding characteristics of analytes, offering more information-rich experiment results. Thus, MPIE is a valuable addition to the top-down MS sample preparation toolbox, and MPIE-ESI-MS can be useful for identification and characterization of targets of interest.
Keywords	analytical chemistry ; chemical species ; electrospray ionization mass spectrometry ; humans ; interferometry ; precipitin tests ; spectrometers ; transferrin
Language	English
Dates of publication	2023-0323
Size	p. 5494-5499.
Publishing place	American Chemical Society
Document type	Article ; Online
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.2c04727
Database	NAL-Catalogue (AGRICOLA)

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Article: COVID-19 Vaccine: A Common Suspect but Rare Culprit in Drug Rash With Eosinophilia and Systemic Symptoms (DRESS) Syndrome.

Hanna, Mary / Yang, Samuel

Cureus

2022 Volume 14, Issue 11, Page(s) e31310

Abstract: Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare drug reaction that commonly presents with rash, fever, lymphadenopathy, eosinophilia, and multiorgan involvement. We present a case of this syndrome in a 31-year-old male who ... ...

Abstract	Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare drug reaction that commonly presents with rash, fever, lymphadenopathy, eosinophilia, and multiorgan involvement. We present a case of this syndrome in a 31-year-old male who presented with a diffuse erythematous morbilliform rash with high fever and elevated liver enzymes. Upon history taking, the patient reported acute onset of multiple seizures that required intubation and ICU admission six weeks prior, which started 24 hours after receiving the Johnson and Johnson Janssen coronavirus disease 2019 (COVID-19) vaccine. During that hospitalization, he was given antiseizure medications Keppra (levetiracetam) and Dilantin (phenytoin), which he was eventually discharged home with. During our encounter with the patient, Dermatology was consulted and recommended punch skin biopsy, which revealed spongiotic dermatitis with subcorneal pustules along with superficial perivascular and mixed lymphocytic and neutrophilic infiltrate with dermal edema and rare eosinophils. Given these findings in conjunction with the patient's fever, elevated liver function, and cervical lymphadenopathy, the rash was consistent with DRESS syndrome or a pustular drug eruption likely secondary to phenytoin or levetiracetam. This case was eventually resolved with treatment with oral and topical corticosteroids and close outpatient follow-up with Dermatology. Prompt diagnosis and treatment of DRESS syndrome are therefore critical as the mortality rate can be as high as 10% in the setting of liver failure.
Language	English
Publishing date	2022-11-09
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.31310
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Re-visiting humoral constitutive antibacterial heterogeneity in bloodstream infections.

Abe, Ryuichiro / Ram-Mohan, Nikhil / Yang, Samuel

The Lancet. Infectious diseases

2023 Volume 24, Issue 4, Page(s) e245–e251

Abstract: Although cellular immunity has garnered much attention in the era of single-cell technologies, humoral innate immunity has receded in priority due to its presumed limited roles. Hence, despite the long-recognised bactericidal activity of serum-a ... ...

Abstract	Although cellular immunity has garnered much attention in the era of single-cell technologies, humoral innate immunity has receded in priority due to its presumed limited roles. Hence, despite the long-recognised bactericidal activity of serum-a functional characteristic of constitutive humoral immunity-much remains unclear regarding mechanisms underlying its inter-individual heterogeneity and clinical implications in bloodstream infections. Recent work suggests that the immediate antimicrobial effect of humoral innate immunity contributes to suppression of the excessive inflammatory responses to infection by reducing the amount of pathogen-associated molecular patterns. In this Personal View, we propose the need to re-explore factors underlying the inter-individual heterogeneity in serum antibacterial competence as a new approach to better understand humoral innate immunity and revisit the clinical use of measuring serum antibacterial activity in the management of bacterial bloodstream infections. Given the current emphasis on subtyping sepsis, a serum bactericidal assay might prove useful in defining a distinct sepsis endotype, to enable more personalised management.
MeSH term(s)	Humans ; Sepsis/drug therapy ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacterial Infections ; Bacteria ; Immunity, Innate
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2023-11-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(23)00494-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A strategic approach towards mass balance investigations in pharmaceutical drug substance release testing: A peculiar out of specification case study encountered during API manufacture.

Scott, Brandon S / Zhang, Kelly / Yehl, Peter M / Yang, Samuel H

Journal of pharmaceutical and biomedical analysis

2023 Volume 238, Page(s) 115773

Abstract: Mass balance in drug substances release testing is a critical quality attribute in pharmaceutical manufacturing that continues to challenge modern analytical characterization. This specific perspective of mass balance is lacking in literature, and the ... ...

Abstract	Mass balance in drug substances release testing is a critical quality attribute in pharmaceutical manufacturing that continues to challenge modern analytical characterization. This specific perspective of mass balance is lacking in literature, and the following work addresses the knowledge gap related to this topic by examining an in-depth case study and detailing the systematic investigation into mass imbalance observed during release testing of a small molecule API. The process followed a logical stepwise progression beginning with most probable causes and expanded to more obscure causes that require a deeper examination of the API in question until the undetected impurity in question was finally identified. The discovered impurity was eventually found to be formed from a unique side reaction that led to the formation of API-related oligomer impurities, which had eluded conventional small molecule release testing strategies. Ultimately, the characterization gap was traced back to deficiency in the LC results of the developed API purity methods. More importantly, this gap provides an ideal opportunity to highlight common oversights and pitfalls encountered in early phase pharmaceutical development especially as it relates to the method development of truly representative chromatography methods in the API characterization. The work reflects on the key lessons learned from the highlighted pitfalls that were encountered in this case study and offers strategic insights to guide and to improve the development workflow for drug substance characterization strategies.
MeSH term(s)	Chemistry, Pharmaceutical/methods ; Drug Contamination ; Chromatography, High Pressure Liquid/methods ; Pharmaceutical Preparations
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2023-10-10
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2023.115773
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Book ; Online: Masked Autoencoders As The Unified Learners For Pre-Trained Sentence Representation

Liu, Alexander / Yang, Samuel

2022

Abstract: Despite the progresses on pre-trained language models, there is a lack of unified frameworks for pre-trained sentence representation. As such, it calls for different pre-training methods for specific scenarios, and the pre-trained models are likely to be ...

Abstract	Despite the progresses on pre-trained language models, there is a lack of unified frameworks for pre-trained sentence representation. As such, it calls for different pre-training methods for specific scenarios, and the pre-trained models are likely to be limited by their universality and representation quality. In this work, we extend the recently proposed MAE style pre-training strategy, RetroMAE, such that it may effectively support a wide variety of sentence representation tasks. The extended framework consists of two stages, with RetroMAE conducted throughout the process. The first stage performs RetroMAE over generic corpora, like Wikipedia, BookCorpus, etc., from which the base model is learned. The second stage takes place on domain-specific data, e.g., MS MARCO and NLI, where the base model is continuingly trained based on RetroMAE and contrastive learning. The pre-training outputs at the two stages may serve different applications, whose effectiveness are verified with comprehensive experiments. Concretely, the base model are proved to be effective for zero-shot retrieval, with remarkable performances achieved on BEIR benchmark. The continuingly pre-trained models further benefit more downstream tasks, including the domain-specific dense retrieval on MS MARCO, Natural Questions, and the sentence embeddings' quality for standard STS and transfer tasks in SentEval. The empirical insights of this work may inspire the future design of sentence representation pre-training. Our pre-trained models and source code will be released to the public communities.
Keywords	Computer Science - Computation and Language
Subject code	330
Publishing date	2022-07-30
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interpretable deep learning for automatic diagnosis of 12-lead electrocardiogram.

Zhang, Dongdong / Yang, Samuel / Yuan, Xiaohui / Zhang, Ping

iScience

2021 Volume 24, Issue 4, Page(s) 102373

Abstract: Electrocardiogram (ECG) is a widely used reliable, non-invasive approach for cardiovascular disease diagnosis. With the rapid growth of ECG examinations and the insufficiency of cardiologists, accurate and automatic diagnosis of ECG signals has become a ... ...

Abstract	Electrocardiogram (ECG) is a widely used reliable, non-invasive approach for cardiovascular disease diagnosis. With the rapid growth of ECG examinations and the insufficiency of cardiologists, accurate and automatic diagnosis of ECG signals has become a hot research topic. In this paper, we developed a deep neural network for automatic classification of cardiac arrhythmias from 12-lead ECG recordings. Experiments on a public 12-lead ECG dataset showed the effectiveness of our method. The proposed model achieved an average F1 score of 0.813. The deep model showed superior performance than 4 machine learning methods learned from extracted expert features. Besides, the deep models trained on single-lead ECGs produce lower performance than using all 12 leads simultaneously. The best-performing leads are lead I, aVR, and V5 among 12 leads. Finally, we employed the SHapley Additive exPlanations method to interpret the model's behavior at both the patient level and population level.
Language	English
Publishing date	2021-03-29
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2021.102373
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Validity of Psychiatric Evaluation of Asylum Seekers through Telephone.

Yang, Samuel / Baronia, Regina / Ibrahim, Yasin

Case reports in psychiatry

2021 Volume 2021, Page(s) 8856352

Abstract: The goal of the psychiatric assessment of asylum seekers is to evaluate the asylum seeker's mental health and credibility. The shortage of mental health providers trained in this particular type of evaluation makes in-person evaluation not always ... ...

Abstract	The goal of the psychiatric assessment of asylum seekers is to evaluate the asylum seeker's mental health and credibility. The shortage of mental health providers trained in this particular type of evaluation makes in-person evaluation not always feasible. Telephonic interview has been occasionally utilized to fill this void. The validity of such evaluations in assessing credibility has yet to be fully established. In the case of telephonic interviews, evaluators are limited with no access to facial or body language cues that can indicate deception or honesty. We will present a case of a client evaluated via telephone that was deemed credible and eventually released to pursue asylum in the US. Assessment of credibility relied solely on cues obtained from the client's narrative, reported symptoms, and their style of interaction with the evaluator. We will highlight the findings from the client's interview that supported credibility in the case and discuss the challenges of assessing asylum seeker's credibility via telephonic interview. Telephonic evaluation of credibility can be considered a valid method despite major challenges, but psychiatric evaluators should be aware of the limitations of telephonic evaluations given the high possibility of secondary gains and deception.
Language	English
Publishing date	2021-02-10
Publishing country	United States
Document type	Case Reports
ZDB-ID	2629914-8
ISSN	2090-6838 ; 2090-682X
ISSN (online)	2090-6838
ISSN	2090-682X
DOI	10.1155/2021/8856352
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Neutrophil Extracellular Traps have DNAzyme activity that drives bactericidal potential.

Ku, Ti-Hsuan / Ram-Mohan, Nikhil / Zudock, Elizabeth J / Abe, Ryuichiro / Yang, Samuel

bioRxiv : the preprint server for biology

2023

Abstract: The mechanisms of bacterial killing by neutrophil extracellular traps (NETs) are unclear. DNA, the largest component of NETs is believed to merely be a scaffold with minimal antimicrobial activity through the charge of the backbone. Here, we report that ... ...

Abstract	The mechanisms of bacterial killing by neutrophil extracellular traps (NETs) are unclear. DNA, the largest component of NETs is believed to merely be a scaffold with minimal antimicrobial activity through the charge of the backbone. Here, we report that NETs DNA is beyond a scaffold and produces hydroxyl free radicals through the spatially concentrated G-quadruplex/hemin DNAzyme complexes, driving bactericidal effects. Immunofluorescence staining showed colocalization of G-quadruplex and hemin in extruded NETs DNA, and Amplex UltraRed assay portrayed its peroxidase activity. Proximity labeling of bacteria revealed localized concentration of radicals resulting from NETs bacterial trapping.
Language	English
Publishing date	2023-10-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.23.563618
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Article: Rapid molecular phenotypic antimicrobial susceptibility test for

Tjandra, Kristel C / Ram-Mohan, Nikhil / Abe, Ryuichiro / Wang, Tza-Huei / Yang, Samuel

bioRxiv : the preprint server for biology

2023

Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.01.530513
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