Transcription factor prediction using protein 3D secondary structures.

Motivation: Transcription factors (TFs) are DNA-binding proteins that regulate gene expression. Traditional methods predict a protein as a TF if the protein contains any DNA-binding domains (DBDs) of known TFs. However, this approach fails to identify a novel TF that does not contain any known DBDs.

Tibial Baseplate Microstructure Governs High Cycle Fatigue Fracture In Vivo.

Previous studies report rare occurrences of tibial baseplate fractures following primary total knee arthroplasty (TKA). However, at a microstructural scale, it remains unclear how fatigue models developed in vitro apply to fractures in vivo. In this study, we asked: (1) do any clinical factors differentiate fracture patients from a broader revision sample; and (2) in vivo, how does microstructure influence fatigue crack propagation? We identified three fractured tibial baseplates from an institutional review board exempt implant retrieval program.

Wear, Material Transfer, and Electrocautery Damage Are Ubiquitous on CoCrMo Femoral Knee Retrievals.

Despite high total knee arthroplasty (TKA) survivorship after 10 years (92%-99%), a gap persists where patient satisfaction lags clinical success. Additionally, while cobalt chrome molybdenum (CoCrMo) use decreases in primary total hip arthroplasty, the alloy continues to be widely used in TKA femoral components. In vivo, CoCrMo degradation may be associated with adverse local tissue reactions (ALTR) and compared with the hip, the damage mechanisms that may release metal in the knee and the potential biological effects remain poorly understood.

The value of long-duration energy storage under various grid conditions in a zero-emissions future.

Long-duration energy storage (LDES) is a key resource in enabling zero-emissions electricity grids but its role within different types of grids is not well understood. Using the Switch capacity expansion model, we model a zero-emissions Western Interconnect with high geographical resolution to understand the value of LDES under 39 scenarios with different generation mixes, transmission expansion, storage costs, and storage mandates. We find that a) LDES is particularly valuable in majority wind-powered regions and regions with diminishing hydropower generation, b) seasonal operation of storage becomes cost-effective if storage capital costs fall below US$5 kWh, and c) mandating the installation of enough LDES to enable year-long storage cycles would reduce electricity prices during times of high demand by over 70%.

Isotopic labeling of nanoparticles for the evaluation of their environmental fate in mesocosm experiments.

Mesocosm systems simulating floodplain areas are essential for the understanding of the environmental fate and effects of engineered nanoparticles (ENPs). In such mesocosm studies, the quantification of different types of nanoparticles coexisting in natural systems and containing the same element is often challenging. Such coexistence is expected e.

Titanium-Titanium Junctions in the Knee Corrode, Generating Damage Similar to the Hip.

Background: Previous studies identified corrosion between the modular tibial components of total knee arthroplasty devices. However, gaps persist. Compared to the hip, damage modes that occur within taper junctions in the knee remain poorly understood.

Retrieval Analysis of Titanium Nitride Coatings for Orthopaedic Implants.

Background: The first generation of titanium nitride (TiN) coatings for orthopaedic implants was clinically introduced in the 1990s because of their promising biocompatibility, wear resistance, and corrosion resistance. This study evaluated the in vivo performance of early TiN-coated knee and hip implants, focusing on the bearing surfaces and mechanisms of in vivo damage.

Methods: There were 13 TiN-coated implants (5 knee and 8 hip) retrieved from 8 patients as part of a multi-institutional implant retrieval program.

Clinical management of bone loss in cervical total disc arthroplasty: literature review and treatment recommendations.

Purpose: Cervical total disc replacement (cTDR) has been established as an alternative treatment for degenerative cervical radiculopathy and myelopathy. While the rate of complications for cTDR is reasonably low, recent studies have focused on bone loss after cTDR. The purpose of this work is to develop a clinical management plan for cTDR patients with evidence of bone loss.

Investigating the Feasibility and Performance of Hybrid Overmolded UHMWPE 3D-Printed PEEK Structural Composites for Orthopedic Implant Applications: A Pilot Study.

Ultra-high-molecular-weight polyethylene (UHMWPE) components for orthopedic implants have historically been integrated into metal backings by direct-compression molding (DCM). However, metal backings are costly, stiffer than cortical bone, and may be associated with medical imaging distortion and metal release. Hybrid-manufactured DCM UHMWPE overmolded additively manufactured polyetheretherketone (PEEK) structural components could offer an alternative solution, but are yet to be explored.

Bridging gaps in ophthalmology residency programs: the link between practice, training and confidence in ocular examination and gonioscopy for diagnosing glaucoma, a blinding disease.

Background: To evaluate real-world utilization of gonioscopy for diagnosing glaucoma among ophthalmologists with diverse subspecialties, and understand current perceptions of teaching, training, and confidence in gonioscopy.

Methods: A nationwide anonymous online survey was conducted among practicing ophthalmologists, querying about demographics, professional experience, practice of routine ocular examination for glaucoma and perceptions of confidence in performing them.

Results: 136 ophthalmologists participated in the survey, with various levels of experience from residency to over twenty years of ophthalmology practice.

Oxidation and Damage Mechanisms of Second-Generation Highly Cross-Linked Polyethylene Tibial Inserts.

Background: After clinical introduction in 2005, sequentially annealed, highly cross-linked polyethylene (SA HXLPE) was studied for retrievals with short implantation times; however, long-term follow-ups are lacking. The objective of this study was to examine and compare the revision reasons, damage mechanisms, and oxidation indices of SA HXLPE and conventional gamma inert-sterilized (Gamma Inert) ultra-high-molecular-weight polyethylene tibial inserts implanted for >5 years.

Methods: There were 74 total knee arthroplasty tibial inserts (46 SA HXLPEs, 28 Gamma Inerts) implanted for >5 years (mean 7 ± 2 years) retrieved as part of a multicenter retrieval program.

Detection of the benzodiazepine bromazolam by liquid chromatography with quadrupole time of flight mass spectrometry in postmortem toxicology casework and prevalence in Indiana (2023).

For the past 60 years, benzodiazepines such as chlordiazepoxide, diazepam, and alprazolam have been used as pharmaceutical medications for the treatment of myriad conditions including anxiety, seizures, and insomnia. In more recent years, novel benzodiazepine derivatives have emerged as illicit substances in powders and counterfeit tablets on the illicit drug market. In 2016, bromazolam, a brominated derivative of alprazolam, emerged on the illicit drug market in Europe, but the substance was not reported in the USA until 2019-2020.

Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice.

Mycobacterium tuberculosis infects two billion people across the globe, and results in 8-9 million new tuberculosis (TB) cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease.

Femoral Head Penetration Rates and Oxidation of Highly Cross-Linked Polyethylene Hip Liners Implanted More Than 10 Years.

Background: Highly cross-linked polyethylene (HXLPE) was introduced to improve wear in total hip arthroplasty, with manufacturers implementing different thermal treatments to reduce oxidation. It is important to understand how long-term time in vivo affects the wear of these materials. The purpose of this study was to investigate the wear and oxidative performance of first-generation HXLPE hip inserts implanted for greater than 10 years and compare annealed and remelted HXLPE formulations.

Loss of copy numbers of retrotransposons (HERVK) on chromosome 7p11.2 impacts EGFR (Epidermal Growth Factor Receptor)-induced phenotypes for platinum sensitivity and long-term survival in ovarian cancer-A study from the OVCAD consortium.

We analyzed variations in the epidermal growth factor receptor (EGFR) gene and 5'-upstream region to identify potential molecular predictors of treatment response in primary epithelial ovarian cancer. Tumor tissues collected during debulking surgery from the prospective multicenter OVCAD study were investigated. Copy number variations in the human endogenous retrovirus sequence human endogenous retrovirus K9 (HERVK9) and EGFR Exons 7 and 9, as well as repeat length and loss of heterozygosity of polymorphic CA-SSR I and relative EGFR mRNA expression were determined quantitatively.

Ubiquitin-specific protease 7 inhibitors reveal a differentiated mechanism of p53-driven anti-cancer activity.

The USP7 deubiquitinase regulates proteins involved in the cell cycle, DNA repair, and epigenetics and has been implicated in cancer progression. USP7 inhibition has been pursued for the development of anti-cancer therapies. Here, we describe the discovery of potent and specific USP7 inhibitors exemplified by FX1-5303.

Presentation and management of infection in total disc replacement: A review.

Background: Total disc replacement (TDR) is widely used in the treatment of cervical and lumbar spine pathologies. Although TDR infection, particularly delayed infection, is uncommon, the results can be devastating, and consensus on clinical management remains elusive. In this review of the literature, we asked: (1) What are the reported rates of TDR infection; (2) What are the clinical characteristics of TDR infection; and (3) How has infection been managed for TDR patients?

Methods: We performed a search of the literature using PubMed and Embase to identify studies that reported TDR infection rates, the identification and management of TDR infection, or TDR failures with positive cultures.

Proposal for a classification system of radiographic bone changes after cervical disc replacement.

Background: The goal of this study is to propose a classification system with a common nomenclature for radiographic observations of periprosthetic bone changes following cTDR.

Methods: Aided by serial plain radiographs from recent cTDR cases (34 patients; 44 devices), a panel of experts assembled for the purpose of creating a classification system to aid in reproducibly and accurately identifying bony changes and assessing cTDR radiographic appearance. Subdividing the superior and inferior vertebral bodies into 3 equal sections, observed bone loss such as endplate rounding, cystic erosion adjacent to the endplate, and cystic erosion not adjacent to the endplate, is recorded.

Host Genetic Background Influences BCG-Induced Antibodies Cross-Reactive to SARS-CoV-2 Spike Protein.

Bacillus Calmette-Guérin (BCG) protects against childhood tuberculosis; and unlike most vaccines, BCG broadly impacts immunity to other pathogens and even some cancers. Early in the COVID-19 pandemic, epidemiological studies identified a protective association between BCG vaccination and outcomes of SARS-CoV-2, but the associations in later studies were inconsistent. We sought possible reasons and noticed the study populations often lived in the same country.

Multiple genetic loci influence vaccine-induced protection against Mycobacterium tuberculosis in genetically diverse mice.

Mycobacterium tuberculosis (M.tb.) infection leads to over 1.

Magnetic resonance elastography captures a transient benefit of exercise intervention on forebrain stiffness in a rat model of fetal alcohol spectrum disorders.

Background: Fetal alcohol spectrum disorders (FASD), a group of prevalent conditions resulting from prenatal alcohol exposure, affect the maturation of cerebral white matter as first identified with neuroimaging. However, traditional methods are unable to track subtle microstructural alterations to white matter. This preliminary study uses a highly sensitive and clinically translatable magnetic resonance elastography (MRE) protocol to assess brain tissue microstructure through its mechanical properties following an exercise intervention in a rat model of FASD.

Systems genetics uncover new loci containing functional gene candidates in -infected Diversity Outbred mice.

the bacillus that causes tuberculosis (TB), infects 2 billion people across the globe, and results in 8-9 million new TB cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease.

Are Corrosion and Material Loss a Threat for Titanium-Titanium Tapers in Total Hip Arthroplasty Modular Acetabular Components?

Background: Extensive research has reported on fretting corrosion and material loss for a variety of metal taper interfaces in orthopedic devices. For modular acetabular shell-liner constructs, the interfaces studied thus far have consisted of mixed-metal pairings, and the risk of fretting corrosion and material loss for the all-titanium (Ti) shell-liner taper junction in one ceramic-on-ceramic (COC) design remains poorly understood. We asked: do Ti shell-liner taper interfaces in COC total hip arthroplasty devices show in vivo evidence of (1) fretting and/or corrosion, and (2) quantifiable potential material loss?

Methods: We examined 22 shell-liner pairs and 22 single liners from retrieved COC components.