Value and Kinetics of Virological Markers in the Natural Course of Chronic Hepatitis D Virus Infection.

Background And Aims: Chronic hepatitis D virus (HDV) infection can cause severe liver disease. With new treatment options available, it is important to identify patients at risk for liver-related complications. We aimed to investigate kinetics and predictive values of novel virological and immunological markers in the natural course of chronic HDV infection.

Rat as a Predictive Model for Human Clearance and Bioavailability of Monoclonal Antibodies.

Background: The prediction of human clearance (CL) and subcutaneous (SC) bioavailability is a critical aspect of monoclonal antibody (mAb) selection for clinical development. While monkeys are a well-accepted model for predicting human CL, other preclinical species have been less-thoroughly explored. Unlike CL, predicting the bioavailability of SC administered mAbs in humans remains challenging as contributing factors are not well understood, and preclinical models have not been systematically evaluated.

AntiCD30-Conjugated Antibody Plus Standard BEAM as Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Systemic Anaplastic Large Cell Lymphoma.

The outcome of refractory/relapsed systemic Anaplastic Large Cell Lymphoma (R/R-sALCL), especially for anaplastic lymphoma kinase-1 (ALK-1)-negative disease, remains dismal even after autologous hematopoietic stem cell transplantation (AHSCT). The intensification of both salvage and conditioning regimens, without increasing the toxicity, could improve the outcome of AHSCT in R/R-sALCL. Based on the successful experience of the incorporation of antiD20 monoclonal antibodies in the treatment of B-Cell Lymphomas, we designed a salvage and conditioning regimen incorporating the antiCD30-conjugated antibody (Brentuximab Vedotin, BV) to standard chemotherapy regimens, and we describe herein the clinical course of a patient with AKL-ve, R/R-sALCL, who received salvage regimen BV + DHAP, followed by AHSCT with preparative regimen consisted of BV plus standard BEAM.

Exploring Context Allows Us to Better Understand Physical Activity in People with and Without Parkinson's Who Have Fallen: A Mixed Methods Study.

Falls are a frequent and serious problem for older adults, especially for those living with Parkinson's. The relationship between falls and physical activity is complex, and people often restrict activity following a fall. Exercise is an important aspect of reducing further risk of a fall and a key component of the management of Parkinson's.

Lateral Atrial Expression Patterns Provide Insights into Local Transcription Disequilibrium Contributing to Disease Susceptibility.

Background: Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease development. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrial (LA) and right atrial (RA) may provide insight into diseases such as atrial fibrillation.

Methods: Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design.

Advanced electrocardiography heart age: a prognostic, explainable machine learning approach applicable to sinus and non-sinus rhythms.

Aims: An explainable advanced electrocardiography (A-ECG) Heart Age gap is the difference between A-ECG Heart Age and chronological age. This gap is an estimate of accelerated cardiovascular aging expressed in years of healthy human aging, and can intuitively communicate cardiovascular risk to the general population. However, existing A-ECG Heart Age requires sinus rhythm.

Coexisting patterns and significance of serum HBV RNA and HBV DNA in patients with treatment-naïve chronic hepatitis B virus infection.

Aim: The study aimed to explore the coexisting patterns and assess the significance of serum hepatitis B virus (HBV) RNA and traditional virological biomarkers in patients with antiviral treatment-naïve chronic hepatitis B virus (HBV) infection.

Methods: Serum HBV RNA, HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B envelope antigen (HBeAg) levels were measured and compared in patients with chronic hepatitis B virus infection. The HBV RNA levels were determined using a simultaneous amplification and testing assay.

Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay.

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau, p-tau and p-tau) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field.

Amyloid-β and tau deposition in traumatic brain injury: a study of Vietnam War veterans.

Traumatic brain injury is widely viewed as a risk factor for dementia, but the biological mechanisms underlying this association are still unclear. In previous studies, traumatic brain injury has been associated with the hallmark pathologies of Alzheimer's disease, i.e.

Nutraceutical and low energy shockwave treatments improved sexual function recovery in a rat pelvic neurovascular injury model.

Background: Pelvic trauma can have long-lasting debilitating effects, including severe erectile dysfunction (ED) in men. While there are effective treatments for ED, these treat the symptoms not the cause. Those who suffer from an acute traumatic injury to the neurovascular supply of penis, may benefit from regenerative therapy.

Nanoparticles in gynecologic cancers: a bibliometric and visualization analysis.

Background: Gynecological cancers are characterized by uncontrolled cell proliferation within the female reproductive organs. These cancers pose a significant threat to women's health, impacting life expectancy, quality of life, and fertility. Nanoparticles, with their small size, large surface area, and high permeability, have become a key focus in targeted cancer therapy.

[Determination of three metabolites of thromboxane A and 8-iso-prostaglandin F in urine by ultra performance liquid chromatography-tandem mass spectrometry].

Thromboxane A (TXA), a prothrombotic factor that induces platelet aggregation and thrombosis, acts as a vasoconstrictor by activating TXA receptors (TP receptors). TXA is extremely unstable and metabolizes into three major metabolites: 2,3-dinor thromboxane B (2,3-dinor-TXB), 11-dehydro TXB(11-dh-TXB), and 11-dehydro-2,3-dinor TXB(11-dh-2,3-dinor-TXB). 8-Iso-prostaglandin F(8-iso-PGF), a prostaglandin-like compound widely considered the best biomarker of oxidative stress, can also activate TP receptors.

Know Your ABCs: Discovery, Differentiation, and Targeting of T-Bet+ B Cells.

Since their first description in 2008, T-bet+ B cells have emerged as a clinically important B cell subset. Now commonly known as ABCs (Age-associated B Cells), they are uniquely characterized by their expression of the transcription factor T-bet. Indeed, this singular factor defines this B cell subset.

Knockout IL4I1 affects macrophages to improve poor efficacy of CD19 CAR-T combined with PD-1 inhibitor in relapsed/refractory diffuse large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy plays a critical role in the treatment of B-cell hematologic malignancies. The combination of PD-1 inhibitors and CAR-T has shown encouraging results in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, there are still cases where treatment is ineffective.

How to combine multiple tools for the genetic diagnosis work-up of pediatric B-cell acute lymphoblastic leukemia.

This study investigated the importance of comprehensive genetic diagnosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We analyzed 175 B-ALL employing karyotyping, FISH, MLPA, targeted next-generation sequencing (t-NGS), and Optical Genome Mapping (OGM). This approach achieved an 83% classification rate, identifying 17 distinct genetic subtypes.

Multidisciplinary treatment is necessary in glioblastoma with extracerebral metastases.

Purpose: While glioblastoma is the most common malignant brain tumor in adults, extracerebral manifestations are very rare in this highly aggressive disease with poor prognosis.

Methods: We conducted a systematic literature review in the PubMed database and complemented the data by inclusion of a case treated in our clinic. In this context, we report on a 60-year-old woman with a right frontal glioblastoma, IDH wildtype, MGMT methylated.

Policy options for sustainable access to off-patent antibiotics in Europe.

Securing sustainable access to existing antibiotics optimises agent choice for individual treatments and is crucial to curb antibiotic resistance. Access to antibiotics is often restricted in many countries, due to general market unavailability or episodic shortages. This article outlines key policy options to maintain availability of existing antibiotics and enhance antibiotic supply chain resilience focusing on the perspectives of European Union (EU) and European Economic Area (EEA) institutions and member states.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Classification of Molecular Subtypes of Breast Cancer Using Radiomic Features of Preoperative Ultrasound Images.

Radiomics has been used as a non-invasive medical image analysis technique for diagnosis and prognosis prediction of breast cancer. This study intended to use radiomics based on preoperative Doppler ultrasound images to classify four molecular subtypes of breast cancer. A total of 565 female breast cancer patients diagnosed by postoperative pathology in a hospital between 2014 and 2022 were included in this study.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Proximal protection devices for carotid artery stenting - A benchtop assessment of flow reversal performance.

Background And Purpose: Proximal protection devices, such as TransCarotid Artery Revascularization (TCAR, SilkRoad Medical, Sunnyvale), aim to yield better outcomes in carotid artery stenting (CAS) than distal protection devices by preventing plaque embolization to the brain. However, transfemoral catheters may not fully reverse flow from the external carotid artery (ECA) to the internal carotid artery (ICA). We assess a new balloon-sheath device, Femoral Flow Reversal Access for Carotid Artery Stenting (FFRACAS), for this purpose.

GABA receptors regulate the neural stem cell potential of Pkd2l1 cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway.

Cerebrospinal fluid-contacting neurons (CSF-cNs) exhibit neural stem cell (NSC) properties both in vitro and in vivo, and they may play a critical role in recovery after spinal cord injury (SCI). GABA receptors (GABABRs) are expressed in Pkd2l1 CSF-cNs. However, their role in Pkd2l1 CSF-cNs still needs to be discovered.

Development of compounds for targeted degradation of mammalian cryptochrome proteins.

The mammalian cryptochrome proteins (CRY1 and CRY2) are transcriptional repressors most notable for their role in circadian transcriptional feedback. Not all circadian rhythms depend on CRY proteins, however, and the CRY proteins are promiscuous interactors that also regulate many other processes. In cells with chronic CRY deficiency, protein homeostasis is highly perturbed, with a basal increase in cellular stress and activation of key inflammatory signalling pathways.

Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation.

Background: Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown.

Methods: Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion.

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.