Low-energy differential target multiplexed SCS derivative reduces pain and improves quality of life through 12 months in patients with chronic back and/or leg pain.

Introduction: Energy-reducing spinal cord stimulation (SCS) approaches have the potential to impact patient experience with rechargeable and non-rechargeable SCS devices through reducing device recharge time or enhancing device longevity. This prospective, multi-center study evaluated the safety, effectiveness, and actual energy usage of differential target multiplexed (DTM) endurance therapy, a reduced energy DTM SCS derivative.

Methods: Subjects who reported an overall pain visual analog score (VAS) of ≥6/10 cm and an Oswestry Disability Index score of 21-80 out of 100 at baseline with moderate to severe chronic, intractable back and/or leg pain were eligible.

Echocardiographic Strain Abnormalities Precede Left Ventricular Hypertrophy Development in Hypertrophic Cardiomyopathy Mutation Carriers.

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen-) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen-.

Safety and Efficacy of Combined Coronary and Peripheral Percutaneous Revascularization: A Proof-of-Concept Study.

. Lower extremity peripheral artery disease (LEPAD) frequently coexists with coronary artery disease (CAD) in patients with multisite vascular disease (MVD). While percutaneous revascularization is well-established for both LEPAD and CAD, limited evidence exists for patients eligible for both procedures.

Inhibition of asparagine synthetase effectively retards polycystic kidney disease progression.

Polycystic kidney disease (PKD) is a genetic disorder characterized by bilateral cyst formation. We showed that PKD cells and kidneys display metabolic alterations, including the Warburg effect and glutaminolysis, sustained in vitro by the enzyme asparagine synthetase (ASNS). Here, we used antisense oligonucleotides (ASO) against Asns in orthologous and slowly progressive PKD murine models and show that treatment leads to a drastic reduction of total kidney volume (measured by MRI) and a prominent rescue of renal function in the mouse.

Intranasal administration of Escherichia coli Nissle expressing the spike protein of SARS-CoV-2 induces long-term immunization and prevents spike protein-mediated lung injury in mice.

While current anti-Spike protein (SP) vaccines have been pivotal in managing the pandemic, their limitations in delivery, storage, and the inability to provide mucosal immunization (preventing infections) highlight the ongoing necessity for research and innovation. To tackle these constraints, our research group developed a bacterial-based vaccine using a non-pathogenic E. coli Nissle 1917 (EcN) strain genetically modified to express the SARS-CoV-2 spike protein on its surface (EcN-pAIDA1-SP).

Short peripheral blood leukocyte telomere length in rheumatoid arthritis-interstitial lung disease.

Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.

The lived experience of depression: a bottom-up review co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of depression, co-written by experts by experience and academics. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of depression, family members and carers, representing a global network of organizations. The material was enriched by phenomenologically informed perspectives and shared with all collaborators in a cloud-based system.

Antithrombotic Therapy in Peripheral Artery Disease: Current Evidence and Future Directions.

Patients with peripheral artery disease (PAD) are at an increased risk of major adverse cardiovascular events, and those with disease in the lower extremities are at risk of major adverse limb events primarily driven by atherothrombosis. Traditionally, PAD refers to diseases of the arteries outside of the coronary circulation, including carotid, visceral and lower extremity peripheral artery disease, and the heterogeneity of PAD patients is represented by different atherothrombotic pathophysiology, clinical features and related antithrombotic strategies. The risk in this diverse population includes systemic risk of cardiovascular events as well as risk related to the diseased territory (e.

Which Patients Receive Diagnostic Angiography? An EAST Multicenter Study Analysis of Internal Carotid Artery Blunt Cerebrovascular Injury.

Background: Digital subtraction angiography (DSA) is the gold standard radiologic modality in blunt cerebrovascular injury (BCVI). However, computerized tomography angiography (CTA) is primarily used in modern practice with CTA's widespread availability and the decreased stroke rate with CTA use. The frequency and indications for DSA in BCVI is undefined.

Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes.

The diffusion of next-generation sequencing (NGS)-based approaches allows for the identification of pathogenic mutations of cardiomyopathies and channelopathies in more than 200 different genes. Since genes considered uncommon for a clinical phenotype are also now included in molecular testing, the detection rate of disease-causing variants has increased. Here, we report the prevalence of genetic variants detected by using a NGS custom panel in a cohort of 133 patients with inherited cardiomyopathies (n = 77) or channelopathies (n = 56).

BMS-986158, a Small Molecule Inhibitor of the Bromodomain and Extraterminal Domain Proteins, in Patients with Selected Advanced Solid Tumors: Results from a Phase 1/2a Trial.

This phase 1/2a, open-label study (NCT02419417) evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of BMS-986158, a selective bromodomain and extraterminal domain (BET) inhibitor. Dose escalation was performed with 3 BMS-986158 dosing schedules: A (5 days on, 2 days off; range, 0.75-4.

USP13 modulates the stability of the APC/C adaptor CDH1.

Background: The cell division cycle is a process that is exquisitely controlled by a complex interplay between E3 ubiquitin ligases and deubiquitinating enzymes (DUBs). We have previously reported that the DUB USP13 regulates Aurora B levels along the cell cycle. That observation prompted us to explore any possible connection between USP13 and the APC/C, the major E3 controlling Aurora B levels in cells.

Intrinsic factor autoantibodies by luminescent immuno-precipitation system in patients with corpus atrophic gastritis.

Background: Corpus atrophic gastritis (CAG) may lead to intrinsic factor (IF) deficiency and vitamin B malabsorption. Intrinsic factor autoantibodies (IFA) are considered markers of pernicious anemia, but their clinical utility in CAG has not been evaluated. This study aimed to assess IFA in CAG patients and controls using a luciferase immunoprecipitation system (LIPS).

Dataset for the reporting of carcinoma of the exocrine pancreas: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Aims: Current guidelines for pathology reporting on pancreatic cancer differ in certain aspects, resulting in divergent reporting practices and a lack of comparability of data. Here, we report on a new international dataset for pathology reporting on resection specimens with cancer of the exocrine pancreas (ductal adenocarcinoma and acinar cell carcinoma). The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), which is a global alliance of major (inter)national pathology and cancer organisations.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

Background: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis.

Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.

Survey of spiking in the mouse visual system reveals functional hierarchy.

The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset-part of the Allen Brain Observatory-that surveys spiking from tens of thousands of units in six cortical and two thalamic regions in the brains of mice responding to a battery of visual stimuli.

Amsterdam International Consensus Meeting: tumor response scoring in the pathology assessment of resected pancreatic cancer after neoadjuvant therapy.

Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands.

USP13 controls the stability of Aurora B impacting progression through the cell cycle.

Aurora B kinase plays essential roles in mitosis. Its protein levels increase before the onset of mitosis and sharply decrease during mitosis exit. The latter decrease is due to a balance between the actions of the E3 ubiquitin ligase anaphase-promoting complex or cyclosome (activated by the Cdh1 adapter), and the deubiquitinating enzyme USP35.

Further insights into testicular germ cell tumor oncogenesis: potential therapeutic targets.

: Testicular germ cell tumors (TGCTs) are the most common neoplasia in the young male population, and the incidence has been constantly increasing in many parts of the world. These tumors are classified into seminomas and non-seminomas, and those divided, in turn, into yolk sac tumors, embryonal cell carcinomas, choriocarcinomas, and teratomas. Although therapeutic approaches have improved, approximately 25% of the patients relapse or, in a small number of cases, show platinum-resistant disease.

The application of unsupervised deep learning in predictive models using electronic health records.

Background: The main goal of this study is to explore the use of features representing patient-level electronic health record (EHR) data, generated by the unsupervised deep learning algorithm autoencoder, in predictive modeling. Since autoencoder features are unsupervised, this paper focuses on their general lower-dimensional representation of EHR information in a wide variety of predictive tasks.

Methods: We compare the model with autoencoder features to traditional models: logistic model with least absolute shrinkage and selection operator (LASSO) and Random Forest algorithm.

IgA Antibodies Directed Against Citrullinated Protein Antigens Are Elevated in Patients With Idiopathic Pulmonary Fibrosis.

Background: The etiology of idiopathic pulmonary fibrosis (IPF) is unknown. Because it shares genetic, histopathologic, and radiographic features with the fibrosing interstitial lung disease seen in rheumatoid arthritis (RA), the goal of this study was to investigate RA-related autoantibodies in IPF.

Methods: The study included patients with IPF from two separate cohorts at National Jewish Health and Brigham Women's Hospital (n = 181), general population control subjects (n = 160), and control subjects with disease (n = 86 [40 with RA-usual interstitial pneumonia and 46 with hypersensitivity pneumonitis]).

Discovery of dihydroxyindole-2-carboxylic acid derivatives as dual allosteric HIV-1 Integrase and Reverse Transcriptase associated Ribonuclease H inhibitors.

The management of Human Immunodeficiency Virus type 1 (HIV-1) infection requires life-long treatment that is associated with chronic toxicity and possible selection of drug-resistant strains. A new opportunity for drug intervention is offered by antivirals that act as allosteric inhibitors targeting two viral functions (dual inhibitors). In this work, we investigated the effects of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) derivatives on both HIV-1 Integrase (IN) and Reverse Transcriptase associated Ribonuclease H (RNase H) activities.

Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis.

Background: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity.

Objectives: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect.