Peptide ligands for the universal purification of exosomes by affinity chromatography.

Exosomes are gaining prominence as vectors for drug delivery, vaccination, and regenerative medicine. Owing to their surface biochemistry, which reflects the parent cell membrane, these nanoscale biologics feature low immunogenicity, tunable tissue tropism, and the ability to carry a variety of payloads across biological barriers. The heterogeneity of exosomes' size and composition, however, makes their purification challenging.

Advances and opportunities in process analytical technologies for viral vector manufacturing.

Viral vectors are an emerging, exciting class of biologics whose application in vaccines, oncology, and gene therapy has grown exponentially in recent years. Following first regulatory approval, this class of therapeutics has been vigorously pursued to treat monogenic disorders including orphan diseases, entering hundreds of new products into pipelines. Viral vector manufacturing supporting clinical efforts has spurred the introduction of a broad swath of analytical techniques dedicated to assessing the diverse and evolving panel of Critical Quality Attributes (CQAs) of these products.

Multiangle Light Scattering as a Lentivirus Purification Process Analytical Technology.

The limited biomolecular and functional stability of lentiviral vectors (LVVs) for cell therapy poses the need for analytical tools that can monitor their titers and activity throughout the various steps of expression and purification. In this study, we describe a rapid (25 min) and reproducible (coefficient of variance ∼0.5-2%) method that leverages size exclusion chromatography coupled with multiangle light scattering detection (SEC-MALS) to determine size, purity, and particle count of LVVs purified from bioreactor harvests.

Causal functional connectivity in Alzheimer's disease computed from time series fMRI data.

between brain regions is known to be altered in Alzheimer's disease and promises to be a biomarker for early diagnosis. Several approaches for functional connectivity obtain an un-directed network representing stochastic associations (correlations) between brain regions. However, association does not necessarily imply causation.

Peptide ligands targeting the vesicular stomatitis virus G (VSV-G) protein for the affinity purification of lentivirus particles.

The recent uptick in the approval of ex vivo cell therapies highlights the relevance of lentivirus (LV) as an enabling viral vector of modern medicine. As labile biologics, however, LVs pose critical challenges to industrial biomanufacturing. In particular, LV purification-currently reliant on filtration and anion-exchange or size-exclusion chromatography-suffers from long process times and low yield of transducing particles, which translate into high waiting time and cost to patients.

Identification and characterization of CHO host-cell proteins in monoclonal antibody bioprocessing.

Host-cell proteins (HCPs) are the foremost class of process-related impurities to be controlled and removed in downstream processing steps in monoclonal antibody (mAb) manufacturing. However, some HCPs may evade clearance in multiple purification steps and reach the final drug product, potentially threatening drug stability and patient safety. This study extends prior work on HCP characterization and persistence in mAb process streams by using mass spectrometry (MS)-based methods to track HCPs through downstream processing steps for seven mAbs that were generated by five different cell lines.

Predictive modeling of single pass tangential flow filtration for continuous biomanufacturing.

Opportunities for process intensification have made continuous biomanufacturing an area of active research. While tangential flow filtration (TFF) is typically employed within the biologics purification train to increase drug substance concentration, single-pass TFF (SPTFF) modifies its format by enabling continuity of this process and achieving a multifold concentration factor through a single-pass over the filtration membranes. In continuous processes feed concentration and flow rate are determined by the preceding unit operations.

Digital by design approach to develop a universal deep learning AI architecture for automatic chromatographic peak integration.

Chromatographic data processing has garnered attention due to multiple Food and Drug Administration 483 citations and warning letters, highlighting the need for a robust technological solution. The healthcare industry has the potential to greatly benefit from the adoption of digital technologies, but the process of implementing these technologies can be slow and complex. This article presents a "Digital by Design" managerial approach, adapted from pharmaceutical quality by design principles, for designing and implementing an artificial intelligence (AI)-based solution for chromatography peak integration process in the healthcare industry.

"Black Esophagus" or Gurvits Syndrome: A Rare Cause of Upper Gastrointestinal Bleeding in Diabetic Ketoacidosis.

Black esophagus, also called Gurvits syndrome or acute esophageal necrosis (AEN), is a rare, life-threatening condition characterized by necrosis of the esophageal mucosa. We present a 36-year-old man who presented with hematemesis and was admitted for diabetic ketoacidosis (DKA) management. He then had a further episode of hematemesis with hemodynamic instability.

The Health-Related Quality of Life of Patients Waiting for Anterior Cruciate Ligament Reconstruction Is Worse Than an Age- and Sex-Matched Population: Increasing Time on Waiting List for Surgery Was Independently Associated with a Worse Quality of Life.

Background: The aims of this study were to assess the health-related quality of life (HRQoL) of patients awaiting anterior cruciate ligament (ACL) reconstruction compared to the population at risk: whether knee-specific function was predictive of HRQoL and to identify factors associated with a worse HRQoL.

Methods: Sixty-seven patients (male,  = 50; female,  = 17; mean age, 29) identified from the surgical waiting list completed a questionnaire that included demographics, BMI, time of injury, EuroQol 5-dimension (EQ-5D), Short-Form (SF-36), and International Knee Documentation Committee (IKDC) scores. Age- and sex-matched HRQoL data were obtained from population level data.

Efficient removal of 2,6-xylidine precipitate using different agitation protocols: An field emission scanning electron microscopic study.

Background: Any solution of chemical nature when combined will result in the formation of a precipitate, which in the root canal system will interfere with the hermetic seal. In clinical practice presence of any precipitate, especially carcinogenic in nature, should be eliminated.

Aim: To evaluate whether final irrigation with different agitation protocols will remove the precipitate formed following lidocaine hydrochloride and sodium hypochlorite combination at the coronal, middle, and apical-root thirds.

In-silico neuro musculoskeletal model reproduces the movement types obtained by spinal micro stimulation.

Background And Objectives: Virtual patients and physiologies allow experimentation, design, and early-stage clinical trials in-silico. Virtual patient technology for human movement systems that encompasses musculoskeleton and its neural control are few and far in between. Our major goal is to create a neuro- musculoskeletal upper limb in-silico model, which is modular in architecture and generates movement as an emergent phenomenon out of a multiscale co-simulation of spinal cord neural control and musculoskeletal dynamics.

Towards continuous mAb purification: Clearance of host cell proteins from CHO cell culture harvests via "flow-through affinity chromatography" using peptide-based adsorbents.

The growth of advanced analytics in manufacturing monoclonal antibodies (mAbs) has highlighted the challenges associated with the clearance of host cell proteins (HCPs). Of special concern is the removal of "persistent" HCPs, including immunogenic and mAb-degrading proteins, that co-elute from the Protein A resin and can escape the polishing steps. Responding to this challenge, we introduced an ensemble of peptide ligands that target the HCPs in Chinese hamster ovary (CHO) cell culture fluids and enable mAb purification via flow-through affinity chromatography.

Seasonal and annual variations of CO and CH at Shadnagar, a semi-urban site.

Carbon dioxide (CO) and methane (CH) are the most important greenhouse gases (GHGs) due to their significant role in anthropogenic global climate change. The spatio-temporal variations of their concentration are characterized by the terrestrial biosphere, seasonal weather patterns and anthropogenic emissions. Hence, to understand the variability in regional surface GHG fluxes, high precision GHGs measurements were initiated by the National Remote Sensing Center (NRSC) of India.

Longitudinal monitoring of cell metabolism in biopharmaceutical production using label-free fluorescence lifetime imaging microscopy.

Chinese hamster ovary (CHO) cells are routinely used in the biopharmaceutical industry for production of therapeutic monoclonal antibodies (mAbs). Although multiple offline and time-consuming measurements of spent media composition and cell viability assays are used to monitor the status of culture in biopharmaceutical manufacturing, the day-to-day changes in the cellular microenvironment need further in-depth characterization. In this study, two-photon fluorescence lifetime imaging microscopy (2P-FLIM) was used as a tool to directly probe into the health of CHO cells from a bioreactor, exploiting the autofluorescence of intracellular nicotinamide adenine dinucleotide phosphate (NAD(P)H), an enzymatic cofactor that determines the redox state of the cells.

On the merits and pitfalls of introducing a digital platform to aid conservation management: Volunteer data submission and the mediating role of volunteer coordinators.

Against a backdrop of accelerating digital innovation in nature conservation and environmental management, a real-world experiment was conducted with the research aims of assessing: 1) the effects of introducing a digital data-entry platform on volunteer data submission; and 2) the extent to which coordinators influence digital platform use by their volunteers. We focussed on a large-scale volunteer-based initiative aimed at eradicating the non-native American mink (Neovison vison) from northern Scotland. This geographically dispersed conservation initiative adopted a digital platform that allowed volunteers to submit records to a central database.

Towards more effective online environmental information provision through tailored Natural Language Generation: Profiles of Scottish river user groups and an evaluative online experiment.

As a result of societal transformations, political governance shifts, and advances in ICT, online information has become crucial in efforts by public authorities to make citizens better stewards of the environment. Yet, their environmental information provision may not always be attuned to end users' rationales, behaviours and appreciations. This study revolves around dynamic river level information provided by an environmental regulator - updated once a day or more, and collected by a sensor network of 333 gauging stations along 232 Scottish rivers.

Outcomes of Magnetic Resonance Imaging Detected Occult Neck of Femur Fractures: Do They Represent a Less Severe Injury with Improved Outcomes?

Purpose: Occult hip fractures in the elderly can be missed on standard radiographs and are a known cause of morbidity. These are generally diagnosed on either magnetic resonance imaging (MRI) or computed tomography scan, depending upon local hospital policy. While there is an abundance of literature on hip fractures in general, little is known about the clinical outcome of patients with occult hip fractures.

A prospective cohort study investigating the use of a surgical planning tool to improve patient fasting times in orthopaedic trauma.

Objectives: To improve surgical planning and reduce fasting times with a tool designed to predict average surgical times for the commonest orthopaedic trauma operations.

Methods: A prospective cohort study comprising two 2-week periods before and after introduction of a surgical planning tool. The tool was used in the post-intervention group to predict surgical times for each patient and the predicted end-time for each list.

Cemented total hip replacement in patients under 55 years.

Background and purpose - About 86,000 total hip replacements (THR) have been registered in patients under 55 years in the National Joint Registry of England and Wales (NJR). The use of uncemented implants has increased, despite their outcomes not having been proven to be significantly better than cemented implants in this registry. We determined the implant survivorship and functional outcomes of cemented THR in patients under 55 years at a minimum follow-up of 22 years.

A simple, one pot synthesis of furo[3,2-c]chromenes and evaluation of antimicrobial activity.

Synthesis of a number of 2-cyano-4-oxo-3-phenyl-3,4-dihydro-2H-furo[3,2-c]chromene-2-carboxylate compounds (5) have been accomplished by a simple, multicomponent one pot reaction and evaluated for in vitro antimicrobial activity against different Gram-positive and Gram-negative bacterial strains. The outcome of the screening study showed that compound 5c exhibited promising activity against Micrococcus luteus MTCC 2470 and Klebsiella planticola MTCC 530. Whereas, compound 5g exhibited excellent activity against Bacillus subtilis MTCC 121, Micrococcus luteus MTCC 2470, Klebsiella planticola MTCC 530, Escherichia coli MTCC 739 and displayed a moderate activity against Staphylococcus aureus MTCC 96 and Candida albicans MTCC 3017 when compared with Ciprofloxacin (standard control).

Total hip replacement for neck of femur fracture: Comparing outcomes with matched elective cohort.

Introduction: Current literature suggests that total hip replacement (THR) is superior to hemiarthroplasty (HA) for neck of femur fracture in selected group of patients. The outcomes of THR undertaken for trauma setting remain unclear when comparing with elective THR. We compared the outcomes of THR trauma cohort with best-matched elective cohort.

How well do contoured superior midshaft clavicle plates fit the clavicle? A cadaveric study.

Background: Given the degree of variation in clavicular morphology, 4 clavicle plating systems were examined for their congruity as superior, midshaft, anatomic clavicle (SMAC) plates in a cadaveric study.

Methods: SMAC plates from 4 manufacturers were applied to 79 dry right human clavicles. Two systems offered multiple (4) variations of plates (MP), 1 offered two variations (TP), and 1 had a single plate (SP).

Extraction of incarcerated medial epicondyle from the elbow joint using conventional nerve stimulator: a case report.

Introduction: Incarceration of the medial epicondyle is a well-recognised sequelae following closed reduction of the elbow. Manipulation for extraction is not usually successful and hence an incarcerated medial epicondyle is usually an indication for open reduction and fixation.

Case Presentation: We describe a simple technique of closed reduction using a conventional nerve stimulator to extract an incarcerated medial epicondyle in a 13-year-old Caucasian boy.

Automatic generation of natural language nursing shift summaries in neonatal intensive care: BT-Nurse.

Introduction: Our objective was to determine whether and how a computer system could automatically generate helpful natural language nursing shift summaries solely from an electronic patient record system, in a neonatal intensive care unit (NICU).

Methods: A system was developed which automatically generates partial NICU shift summaries (for the respiratory and cardiovascular systems), using data-to-text technology. It was evaluated for 2 months in the NICU at the Royal Infirmary of Edinburgh, under supervision.