MAGPIE: A Machine Learning Approach to Decipher Protein-Protein Interactions in Human Plasma.

Immunoprecipitation coupled to tandem mass spectrometry (IP-MS/MS) methods is often used to identify protein-protein interactions (PPIs). While these approaches are prone to false positive identifications through contamination and antibody nonspecific binding, their results can be filtered using negative controls and computational modeling. However, such filtering does not effectively detect false-positive interactions when IP-MS/MS is performed on human plasma samples.

Evaluation and Treatment of Baseball Pitchers: There's More to Assess than the Arm.

Injuries are commonplace in the overhead athlete, with many occurring to the shoulder and elbow. The increasing prevalence of injuries to the shoulder and elbow has been discussed at length in recent years, with increased research focus being placed on arm care for rehabilitation and prevention strategies. Even though the pitching motion is well-established as a whole-body kinetic chain movement, most attention in rehabilitation and prevention efforts is often placed on the upper extremity.

[When should a gluteus medius tendon rupture be operated on ?].

The gluteus medius allows hip abduction and stabilization of the pelvis when walking. A rupture of the gluteus medius tendon is associated with lateral hip pain, weakness, a positive Trendelenburg sign, and a limp. Diagnosis is confirmed by ultrasound or MRI.

[Platypnea-orthodeoxia syndrome in a patient with heart failure: A case report].

Introduction: The platypnea orthodeoxia syndrome is a rare clinical entity combining positional dyspnea and arterial oxygen desaturation during the transition to orthostatism, reversible on return to decubitus. The most frequent etiology of this syndrome is the presence of a patent foramen ovale (PFO) responsible for a right-to-left intracardiac shunt, the severity of which results in significant functional disability and a risk of death from hypoxia.

Case Report: We report the case of a 93-year old patient on long-term oxygen, initially hospitalized for acute heart failure following a community-acquired urinary tract infection.

Type 1 Immune Responses Related to Viral Infection Influence Corticosteroid Response in Asthma.

Rationale: Corticosteroid-responsive type 2 (T2) inflammation underlies the T2-high asthma endotype. However, we hypothesized that type 1 (T1) inflammation, possibly related to viral infection, may also influence corticosteroid response.

Objectives: To determine the frequency and within-patient variability of T1-high, T2-high, and T1/T2-high asthma endotypes and whether virally influenced T1-high disease influences corticosteroid response in asthma.

Biologic Medications for Severe Asthma: Implications for Understanding Pathogenic Heterogeneity and Endotypes.

Asthma is a chronic inflammatory disease of the airways long known for phenotypic heterogeneity. Phenotyping studies in asthma have led to a better characterization of disease pathogenesis, yet further work is needed to pair available treatments with disease endotypes. In this review, the biology of targeted pathways is discussed along with the efficacy of biologic therapies targeting those pathways.

Novel potent SOS1 inhibitors containing a tricyclic quinazoline scaffold: A joint view of experiments and simulations.

Small molecules that possess the ability to regulate the interactions between Son of Sevenless 1 (SOS1) and Kristen rat sarcoma (KRAS) offer immense potential in the realm of cancer therapy. In this study, we present a novel series of SOS1 inhibitors featuring a tricyclic quinazoline scaffold. Notably, we have identified compound 8d, which demonstrates the highest potency with an IC value of 5.

[Arthrogryposis Multiplex Congenita in pediatric age: Correlation between Muscle MRI and functional assessment].

Arthrogryposis multiplex congenita (AMC) is a group of diseases with joint limitations at two or more distinct joint levels at birth. Joint limitations are not progressive, but the functional consequences have a lifelong impact on patients. In this article we will present the results of our study aimed at evaluating the correlation between muscle fat infiltration on MRI and activity deficiencies and limitations in children with AMC.

Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke.

The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions.

Indoor radon trends with building code change in two Canadian cities.

Radon studies were conducted in two Canadian cities, in Halifax, Nova Scotia, and Winnipeg, Manitoba, to evaluate trends in indoor radon before and after the 2010 National Building Code of Canada was adopted into the legally binding provincial building codes in 2011. Participants were recruited in neighbourhoods characterized by newer housing developments. A postcard campaign in each city offered free radon testing to every house in the target areas, and free testing kits were mailed to study participants.

Origin of dedifferentiated adipocyte-derived cells (DFAT) during ceiling culture in an Adiponectin Cre-Recombinase mouse model.

DFAT cells represent an attractive source of stem cells in tissue engineering and in the potential treatment of several clinical conditions. Our objective was to determine whether DFAT cells originate from mature adipocytes and address whether contamination from the stromal vascular fraction (SVF) could be as a source for these cells. A murine adiponectin-creERT;mT/mG model was used with the excision of the cassette induced by tamoxifen injection for the cells expressing adiponectin (adipoq).

Real-time impedance-activated dielectrophoretic actuation for reconfigurable manipulation of single flowing particles.

This work presents an innovative all-electrical platform for selective single-particle manipulation. The platform combines microfluidic impedance cytometry for label-free particle characterization and dielectrophoresis for contactless multi-way particle separation. The microfluidic chip has a straightforward coplanar electrode layout and no particle pre-focusing mechanism is required.

Rapid Systematic Screening of Bispecific Antibody Surrogate Geometries for T-Cell Engagement Using DNA Nanotechnology.

Bispecific antibodies (bsAbs) are emerging immune-therapeutics, and many formats exist that differ considerably in structure. However, little systematic data exist about how the spatial organization of their components influences activity, requiring innovative approaches combining empirical and quantitative frameworks. This study presents a modular DNA nanotechnology platform to generate numerous bsAbs with surrogate geometries that span the structural features of the BiTE, IgG-like, and IgG-conjugate platforms to screen for T-cell engagement.

Sustained improvements in brain health and metabolic markers 24 months following bariatric surgery.

Obesity and its metabolic complications are associated with lower grey matter and white matter densities, whereas weight loss after bariatric surgery leads to an increase in both measures. These increases in grey and white matter density are significantly associated with post-operative weight loss and improvement of the metabolic/inflammatory profiles. While our recent studies demonstrated widespread increases in white matter density 4 and 12 months after bariatric surgery, it is not clear if these changes persist over time.

Catheter removal after interstitial brachytherapy for breast cancer: Feasibility study for task delegation.

Purpose: This study aims to assess the impact of delegating brachytherapy device removal to radiation therapists (RTTs) in the treatment of breast cancer, in terms of safety and efficacy of treatment.

Material And Methods: A retrospective, observational study was conducted to analyze breast cancer brachytherapy patients. Standardized protocols were drawn up and the RTTs were gradually trained to remove brachytherapy devices under medical supervision.

Thrombotic Microangiopathy After Long-Lasting Treatment by Gemcitabine: Description, Evolution and Treatment of a Rare Case.

Thrombotic microangiopathy (TMA) is an uncommon but severe complication that may occur in cancer patients under gemcitabine chemotherapy. Gemcitabine-induced thrombotic microangiopathy (G-TMA) can clinically and biologically present as atypical hemolytic uremic syndrome, with activation of the complement pathway asking the question of the use of eculizumab. We describe here the case of a patient suffering from metastatic cholangiocarcinoma treated by gemcitabine for 4 years leading to the remission of the underlying neoplasia.

Cascading Macrocycle and Helix Motions in a Foldarotaxane Molecular Shuttle.

The design of a dynamically assembled foldarotaxane was envisioned with the aim of operating as a two cascading trigger-based molecular shuttle. Under acidic conditions, both the macrocycle and helix were localized around their respective best molecular stations because they are far enough from each other not to alter the stability of complexes. The pH-dependent localization of the macrocycle along the encircled axle allowed us to modulate the association between the helical foldamer and its sites of interaction on the axle.

Stability of a Multiresponsive Sulfonium Vinyl Sulfide Linker toward Nucleophilic/Radical Thiols, Reactive Nitrogen Species, and in Cells under Pro-inflammatory Stimulation.

Chemical linkages that respond to biological stimuli are important for many pharmaceutical and biotechnological applications, making it relevant to explore new variants with different responsivity profiles. This work explores the responsiveness of a TAT peptide-based sulfonium vinyl sulfide probe that responds to nucleophilic thiols, radical thiol species (RTS), and reactive nitrogen species (RNS). Under model conditions, response to nucleophilic thiols was very slow (hours/days), though fast with down to molar equivalents of either RTS or RNS (minutes).

A population of Insula neurons encodes for social preference only after acute social isolation in mice.

The Insula functions as a multisensory relay involved in socio-emotional processing with projections to sensory, cognitive, emotional, and motivational regions. Notably, the interhemispheric projection from the Insula to the contralateral Insula is a robust yet underexplored connection. Using viral-based tracing neuroanatomy, ex vivo and in vivo electrophysiology, in vivo fiber photometry along with targeted circuit manipulation, we elucidated the nature and role of Insula communication in social and anxiety processing in mice.

Harnessing Water Competition to Drive Enzyme Crosstalk.

In nature, enzymatic pathways often involve compartmentalization effects that can modify the intrinsic activity and specificity of the different enzymes involved. Consequently, extensive research has focused on replicating and studying the compartmentalization effects on individual enzymes and on multistep enzyme "cascade" reactions. This study explores the influence of compartmentalization achieved using molecular crowding on the glucose oxidase/horseradish peroxidase (GOx/HRP) cascade reaction.

Hunting for a viral proxy in bioaerosols of swine buildings using molecular detection and metagenomics.

There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine. The effectiveness of dust mitigation strategies such as oil sprinkling, to decrease risk of airborne virus transmission are unknown. Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents.

Deciphering Natural Killer Cell Cytotoxicity Against Medulloblastoma in vitro and in vivo: Implications for Immunotherapy.

Purpose: Medulloblastoma (MB) is the most prevalent paediatric brain tumour. Despite improvements in patient survival with current treatment strategies, the quality of life of these patients remains poor owing to the sequelae and relapse risk. An alternative, or, in addition to the current standard treatment, could be considered immunotherapy, such as Natural Killer cells (NK).