A Novel Machine Learning Model to Predict Revision ACL Reconstruction Failure in the MARS Cohort.

Background: As machine learning becomes increasingly utilized in orthopaedic clinical research, the application of machine learning methodology to cohort data from the Multicenter ACL Revision Study (MARS) presents a valuable opportunity to translate data into patient-specific insights.

Purpose: To apply novel machine learning methodology to MARS cohort data to determine a predictive model of revision anterior cruciate ligament reconstruction (rACLR) graft failure and features most predictive of failure.

Study Design: Cohort study; Level of evidence, 3.

Surgical Predictors of Clinical Outcome 6 Years After Revision ACL Reconstruction.

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown.

Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient's outcome at 6-year follow-up.

Eumelanin and Pheomelanin Modelling in Optical Oximetry Using Pulse Oximetry (for 540 nm and 660 nm): DC Component.

Oximetry is used to quantify the presence of oxygen in soft tissues. It can be expressed as, for example, tissue oxygen saturation (StO), arterial oxygen saturation (SaO) and pulsatile oxygen saturation (SpO), among others. Non-invasive medical devices are used to estimate (SaO).

Detection of foot-and-mouth disease virus RNA using a closed loop-mediated isothermal amplification system.

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals responsible for economic losses that amount to >$20 billion annually. Rapid recognition of FMD cases provides vital information to guide control programmes. A range of point-of-need amplification technologies have been developed which allow sensitive detection of the causative virus (FMDV) in the field at locations remote from laboratories.

Status and future prospects for mobile phone-enabled diagnostics in Tanzania.

Introduction: Diagnosis is a key step towards the provision of medical intervention and saving lives. However, in low- and middle-income countries, diagnostic services are mainly centralized in large cities and are costly. Point of care (POC) diagnostic technologies have been developed to fill the diagnostic gap for remote areas.

Investigating Communication Dynamics in Neuronal Network using 3D Gold Microelectrode Arrays.

Although neuronal network models hold great potential for advancing neuroscience research, with the capacity to provide fundamental insights into mechanisms underlying neuronal functions, the dynamics of cell communication within such networks remain poorly understood. Here, we develop a customizable, polymer modified three-dimensional gold microelectrode array with sufficient stability for high signal-to-noise, long-term, neuronal recording of cultured networks. By using directed spatial and temporal patterns of electrical stimulation of cells to explore synaptic-based communication, we monitored cell network dynamics over 3 weeks, quantifying communication capability using correlation heatmaps and mutual information networks.

Single-Cell Sequencing Reveals Functional Alterations in Tuberculosis.

Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single-cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single-cell analysis of 23 990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell-cell signaling.

Alignment-free construction of double emulsion droplet generation devices incorporating surface wettability contrast.

Although polydimethylsiloxane (PDMS) is a versatile and easy-to-use material for microfluidics, its inherent hydrophobicity often necessitates specific hydrophilic treatment to fabricate microchip architectures for generating double emulsions. These additional processing steps frequently lead to increased complexity, potentially creating barriers to the wider use of promising microfluidic techniques. Here we describe an alignment-free spatial hydrophilic PDMS patterning technique to produce devices for the creation of double emulsions using combinations of PDMS and PDMS/surfactant bilayers.

LoCKAmp: lab-on-PCB technology for <3 minute virus genetic detection.

The recent COVID-19 outbreak highlighted the need for lab-on-chip diagnostic technology fit for real-life deployment in the field. Existing bottlenecks in multistep analytical microsystem integration and upscalable, standardized fabrication techniques delayed the large-scale deployment of lab-on-chip solutions during the outbreak, throughout a global diagnostic test shortage. This study presents a technology that has the potential to address these issues by redeploying and repurposing the ubiquitous printed circuit board (PCB) technology and manufacturing infrastructure.

Phage-Inducible Chromosomal Islands as a Diagnostic Platform to Capture and Detect Bacterial Pathogens.

Phage-inducible chromosomal islands (PICIs) are a family of phage satellites that hijack phage components to facilitate their mobility and spread. Recently, these genetic constructs are repurposed as antibacterial drones, enabling a new toolbox for unorthodox applications in biotechnology. To illustrate a new suite of functions, the authors have developed a user-friendly diagnostic system, based upon PICI transduction to selectively enrich bacteria, allowing the detection and sequential recovery of Escherichia coli and Staphylococcus aureus.

Sequence terminus dependent PCR for site-specific mutation and modification detection.

The detection of changes in nucleic acid sequences at specific sites remains a critical challenge in epigenetics, diagnostics and therapeutics. To date, such assays often require extensive time, expertise and infrastructure for their implementation, limiting their application in clinical settings. Here we demonstrate a generalizable method, named Specific Terminal Mediated Polymerase Chain Reaction (STEM-PCR) for the detection of DNA modifications at specific sites, in a similar way as DNA sequencing techniques, but using simple and widely accessible PCR-based workflows.

Mobile Health Access and Utilisation in Uganda: Knowledge, Attitudes and Perceptions of Health and Veterinary Workers.

Despite its strong growth in many parts of the world, mobile health access is still limited in low- and middle-income countries. Among the many factors restricting implementation are the lack of information security, insufficient evidence base, low sensitization, and user acceptance. Limited evidence has been obtained on current practices, perceptions, and user acceptability in such settings.

Meniscal and Articular Cartilage Predictors of Outcome After Revision ACL Reconstruction: A 6-Year Follow-up Cohort Study.

Background: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction.

Purpose: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patient's outcome at 6-year follow-up.

Study Design: Cohort study; Level of evidence, 3.

Changes in Oxygenation Levels During Moderate Altitude Simulation (Hypoxia-Induced): A Pilot Study Investigating the Impact of Skin Pigmentation in Pulse Oximetry.

The current COVID-19 pandemic has shown us that the pulse oximeter is a key medical device for monitoring blood-oxygen levels non-invasively in patients with chronic or acute illness. It has also emphasised limitations in accuracy for individuals with darker skin pigmentation, calling for new methods to provide better measurements. The aim of our study is to identify the impact of skin pigmentation on pulse oximeter measurements.

Descriptive Characteristics and Outcomes of Patients Undergoing Revision Anterior Cruciate Ligament Reconstruction With and Without Tunnel Bone Grafting.

Background: Lytic or malpositioned tunnels may require bone grafting during revision anterior cruciate ligament reconstruction (rACLR) surgery. Patient characteristics and effects of grafting on outcomes after rACLR are not well described.

Purpose: To describe preoperative characteristics, intraoperative findings, and 2-year outcomes for patients with rACLR undergoing bone grafting procedures compared with patients with rACLR without grafting.

Tracking Molecular Diffusion across Biomaterials' Interfaces Using Stimulated Raman Scattering.

The determination of molecular diffusion across biomaterial interfaces, including those involving hydrogels and tissues remains important, underpinning the understanding of a broad range of processes including, for example, drug delivery. Current techniques using Raman spectroscopy have previously been established as a method to quantify diffusion coefficients, although when using spontaneous Raman spectroscopy, the signal can be weak and dominated by interferences such as background fluorescence (including biological autofluoresence). To overcome these issues, we demonstrate the use of the stimulated Raman scattering technique to obtain measurements in soft tissue samples that have good signal-to-noise ratios and are largely free from fluorescence interference.

Returning to Activity After Anterior Cruciate Ligament Revision Surgery: An Analysis of the Multicenter Anterior Cruciate Ligament Revision Study (MARS) Cohort at 2 Years Postoperative.

Background: Patients with anterior cruciate ligament (ACL) revision report lower outcome scores on validated knee questionnaires postoperatively compared to cohorts with primary ACL reconstruction. In a previously active population, it is unclear if patient-reported outcomes (PROs) are associated with a return to activity (RTA) or vary by sports participation level (higher level vs. recreational athletes).

Reprogrammed tracrRNAs enable repurposing of RNAs as crRNAs and sequence-specific RNA biosensors.

In type II CRISPR systems, the guide RNA (gRNA) comprises a CRISPR RNA (crRNA) and a hybridized trans-acting CRISPR RNA (tracrRNA), both being essential in guided DNA targeting functions. Although tracrRNAs are diverse in sequence and structure across type II CRISPR systems, the programmability of crRNA-tracrRNA hybridization for Cas9 is not fully understood. Here, we reveal the programmability of crRNA-tracrRNA hybridization for Streptococcus pyogenes Cas9, and in doing so, redefine the capabilities of Cas9 proteins and the sources of crRNAs, providing new biosensing applications for type II CRISPR systems.

Programmable design of isothermal nucleic acid diagnostic assays through abstraction-based models.

Accelerating the design of nucleic acid amplification methods remains a critical challenge in the development of molecular tools to identify biomarkers to diagnose both infectious and non-communicable diseases. Many of the principles that underpin these mechanisms are often complex and can require iterative optimisation. Here we focus on creating a generalisable isothermal nucleic acid amplification methodology, describing the systematic implementation of abstraction-based models for the algorithmic design and application of assays.

Multiplex, Real-Time, Point-of-care RT-LAMP for SARS-CoV-2 Detection Using the HFman Probe.

Viral evolution impacts diagnostic test performance through the emergence of variants with sequences affecting the efficiency of primer binding. Such variants that evade detection by nucleic acid-based tests are subject to selective pressure, enabling them to spread more efficiently. Here, we report a variant-tolerant diagnostic test for SARS-CoV-2 using a loop-mediated isothermal nucleic acid-based amplification (LAMP) assay containing high-fidelity DNA polymerase and a high-fidelity DNA polymerase-medicated probe (HFman probe).

High-Speed Diagnosis of Bacterial Pathogens at the Single Cell Level by Raman Microspectroscopy with Machine Learning Filters and Denoising Autoencoders.

Accurate and rapid identification of infectious bacteria is important in medicine. Raman microspectroscopy holds great promise in performing label-free identification at the single-cell level. However, due to the naturally weak Raman signal, it is a challenge to build extensive databases and achieve both accurate and fast identification.