Proteo-SAFARI: An R Application for Identification of Fragment Ions in Top-Down MS/MS Spectra of Proteins.

Proteo-SAFARI is a shiny application for fragment assignment by relative isotopes, an R-based software application designed for identification of protein fragment ions directly in the / domain. This program provides an open-source, user-friendly application for identification of fragment ions from a candidate protein sequence with support for custom covalent modifications and various visualizations of identified fragments. Additionally, Proteo-SAFARI includes a nonnegative least-squares fitting approach to determine the contributions of various hydrogen shifted fragment ions ( + 1, + 1, - 1, - 2) observed in UVPD mass spectra which exhibit overlapping isotopic distributions.

resensitization of multidrug-resistant clinical isolates of and through phage-antibiotic synergy.

Bacteriophages are an increasingly attractive option for the treatment of antibiotic-resistant infections, but their efficacy is difficult to discern due to the confounding effects of antibiotics. Phages are generally delivered in conjunction with antibiotics, and thus, when patients improve, it is unclear whether the phages, antibiotics, or both are responsible. This question is particularly relevant for enterococcus infections, as limited data suggest phages might restore antibiotic efficacy against resistant strains.

Design, Testing, and Validation of a Soft Robotic Sensor Array Integrated with Flexible Electronics for Mapping Cardiac Arrhythmias.

Cardiac mapping is a crucial procedure for diagnosing and treating cardiac arrhythmias. Still, current clinical techniques face limitations including insufficient electrode coverage, poor conformability to complex heart chamber geometries, and high costs. This study explores the design, testing, and validation of a 64-electrode soft robotic catheter that addresses these challenges in cardiac mapping.

An unusual presentation of Herpes zoster and associated differentials.

This case study documents the case of a 27-year-old female who presented with a complaint of left anterolateral thigh numbness, initially diagnosed as meralgia paresthetica with a differential diagnosis of lumbar radiculopathy. Over a span of two weeks, the patient endured emotional trauma and subsequently developed lesions in the area of complaint. The patient was diagnosed at a medical clinic with herpes zoster and was prescribed anti-viral medication which resulted in complete resolution.

Hydrophilic Interaction Chromatography Coupled to Ultraviolet Photodissociation Affords Identification, Localization, and Relative Quantitation of Glycans on Intact Glycoproteins.

Protein glycosylation is implicated in a wide array of diseases, yet glycoprotein analysis remains elusive owing to the extreme heterogeneity of glycans, including microheterogeneity of some of the glycosites (amino acid residues). Various mass spectrometry (MS) strategies have proven tremendously successful for localizing and identifying glycans, typically utilizing a bottom-up workflow in which glycoproteins are digested to create glycopeptides to facilitate analysis. An emerging alternative is top-down MS that aims to characterize intact glycoproteins to allow precise identification and localization of glycans.

Bivalirudin in Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality used in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk.

Enhanced Characterization of Lysine-Linked Antibody Drug Conjugates Enabled by Middle-Down Mass Spectrometry and Higher-Energy Collisional Dissociation-Triggered Electron-Transfer/Higher-Energy Collisional Dissociation and Ultraviolet Photodissociation.

As the development of new biotherapeutics advances, increasingly sophisticated tandem mass spectrometry methods are needed to characterize the most complex molecules, including antibody drug conjugates (ADCs). Lysine-linked ADCs, such as trastuzumab-emtansine (T-DM1), are among the most heterogeneous biotherapeutics. Here, we implement a workflow that combines limited proteolysis with HCD-triggered EThcD and UVPD mass spectrometry for the characterization of the resulting middle-down large-sized peptides of T-DM1.

Sex-specific associations between AD genotype and the microbiome of human amyloid beta knock-in (hAβ-KI) mice.

Introduction: Emerging evidence links changes in the gut microbiome to late-onset Alzheimer's disease (LOAD), necessitating examination of AD mouse models with consideration of the microbiome.

Methods: We used shotgun metagenomics and untargeted metabolomics to study the human amyloid beta knock-in (hAβ-KI) murine model for LOAD compared to both wild-type (WT) mice and a model for early-onset AD (3xTg-AD).

Results: Eighteen-month female (but not male) hAβ-KI microbiomes were distinct from WT microbiomes, with AD genotype accounting for 18% of the variance by permutational multivariate analysis of variance (PERMANOVA).

A simple solid media assay for detection of synergy between bacteriophages and antibiotics.

The emergence of antibiotic-resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. Although phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation, and purification have enabled a reevaluation of their utility in contemporary clinical medicine.

Development of Virus-like Particle Plant-Based Vaccines against Avian H5 and H9 Influenza A Viruses.

Avian influenza A virus (AIV) is a significant cause of mortality in poultry, causing substantial economic loss, particularly in developing countries, and has zoonotic potential. For example, highly pathogenic avian influenza (HPAI) viruses of the H5 subtype have been circulating in Egypt for around two decades. In the last decade, H5N1 viruses of clade 2.

Highly parallelizable electronic transport calculations in periodic rhodium and copper nanostructures.

We extend the highly-parallelizable open-source electronic transport code TRANSEC (Feldman2014B035445;https://gitlab.com/computational-physics2/transec/) to perform real-space atomic-scale electronic transport calculations with periodic boundary conditions in the lateral dimensions. We demonstrate the use of TRANSEC in periodic Cu and Rh bulk structures and in large periodic Rh point contacts, in preparation to perform calculations of reflection probability across Rh grain boundaries.

Veterinarians' knowledge and experience of avian influenza and perspectives on control measures in the UK.

Background: The scale of the outbreak of highly pathogenic avian influenza (HPAI) in 2021-23 due to the influenza A/H5N1 virus is unprecedented.

Methods: An online survey was designed to explore veterinarians' experiences of and confidence in treating avian species, experiences of dealing with suspected HPAI and perspectives on control measures in the UK. The survey ran between December 2021 and March 2022.

Enhancing Top-Down Analysis of Proteins by Combining Ultraviolet Photodissociation (UVPD), Proton-Transfer Charge Reduction (PTCR), and Gas-Phase Fractionation to Alleviate the Impact of Nondissociated Precursor Ions.

Recent advances in top-down mass spectrometry strategies continue to improve the analysis of intact proteins. 193 nm ultraviolet photodissociation (UVPD) is one method well-suited for top-down analysis. UVPD is often performed using relatively low photon flux in order to limit multiple-generation dissociation of fragment ions and maximize sequence coverage.

Characterization of Unbranched Ubiquitin Tetramers by Combining Ultraviolet Photodissociation with Proton Transfer Charge Reduction Reactions.

Polyubiquitination is an important post-translational modification (PTM) that regulates various biological functions. The linkage sites and topologies of polyubiquitination chains are important factors in determining the fate of polyubiquitinated proteins. Characterization of polyubiquitin chains is the first step in understanding the biological functions of protein ubiquitination, but it is challenging owing to the repeating nature of the ubiquitin chains and the difficulty in deciphering linkage positions.

Exploring the responses of smallscale poultry keepers to avian influenza regulations and guidance in the United Kingdom, with recommendations for improved biosecurity messaging.

Understanding how smallscale ('backyard') poultry keepers interpret and respond to governmental directives designed to reduce the transmission of highly pathogenic avian influenza (HPAI) is of paramount importance in preparing for future HPAI outbreaks. Qualitative insights from open questions in an online survey conducted during the 2021-22 HPAI season (1,559 responses) shed light on smallscale poultry keepers' understanding of, and responses to, governmental directives to control HPAI exposure and onwards transmission. A follow-up participatory workshop (21 participants) explored the HPAI-related information sources used by smallscale poultry keepers, their trust in these sources, perceptions of HPAI-related risk, and interpretation of, opinions on and adherence to government regulations and communications regarding biosecurity and housing measures.

A simple solid media assay for detection of synergy between bacteriophages and antibiotics.

The emergence of antibiotic resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. While phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation and purification have enabled a reevaluation of their utility in contemporary clinical medicine.

Empathize with the well patient.

The role of empathy in Doctor-Patient interactions with those with MS is explored through a candid account from both sides of the relationship. As "well patients" with MS become more common, the practice of humanistic medicine and intentional displays of empathy become essential for positive interactions.

Creating Stretchable Electronics from Dual Layer Flex-PCB for Soft Robotic Cardiac Mapping Catheters.

The authors present in this study the development of a novel method for creating stretchable electronics from dual-layer flex printed circuit boards (flex-PCBs) as a platform for soft robotic sensor arrays (SRSAs) for cardiac voltage mapping applications. There is a crucial need for devices that utilize multiple sensors and provide high performance signal acquisition for cardiac mapping. Previously, our group demonstrated how single-layer flex-PCB can be postprocessed to create a stretchable electronic sensing array.