Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study.

Objectives: Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX).

Methods: In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks (BEL/ST; reference arm) was included.

Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM). Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV). In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.

Exploring the Darkverse: A Multi-Perspective Analysis of the Negative Societal Impacts of the Metaverse.

The Metaverse has the potential to form the next pervasive computing archetype that can transform many aspects of work and life at a societal level. Despite the many forecasted benefits from the metaverse, its negative outcomes have remained relatively unexplored with the majority of views grounded on logical thoughts derived from prior data points linked with similar technologies, somewhat lacking academic and expert perspective. This study responds to the dark side perspectives through informed and multifaceted narratives provided by invited leading academics and experts from diverse disciplinary backgrounds.

Uncovering transcriptomic landscape alterations of CAN-2409 in and glioma models.

Rationale: CAN-2409 is a locally delivered oncolytic therapy, which results in vaccination against the injected tumor. CAN-2409 consists of a non-replicating adenovirus armed with the Herpes virus thymidine kinase, which metabolizes ganciclovir into a phosphorylated nucleotide that is incorporated into the tumor cell's genome, thereby inflicting immunogenic cancer cell death. While CAN-2409's immunological impact has been well characterized, its effects on the tumor cells transcriptome remains unknown.

Mammalian Glycosylation Patterns Protect Citrullinated Chemokine MCP-1/CCL2 from Partial Degradation.

Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a potent chemotactic agent for monocytes, primarily produced by macrophages and endothelial cells. Significantly elevated levels of MCP-1/CCL2 were found in synovial fluids of patients with rheumatoid arthritis (RA), compared to osteoarthritis or other arthritis patients. Several studies suggested an important role for MCP-1 in the massive inflammation at the damaged joint, in part due to its chemotactic and angiogenic effects.

A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome.

BACKGROUNDPrimary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g.

Synovial gene signatures associated with the development of rheumatoid arthritis in at risk individuals: A prospective study.

Objective: To identify molecular changes in synovium before arthritis development in individuals at risk of developing rheumatoid arthritis (RA).

Materials And Methods: We included 67 IgM rheumatoid factor and/or anti-citrullinated protein antibody positive individuals with arthralgia but without arthritis. Synovial biopsies were collected after which individuals were prospectively followed for at least 2 years during which 17 developed arthritis.

A model for (Karnal bunt)- (Wheat) system under changing environmental conditions.

Unlabelled: Karnal bunt (KB) of wheat incited by  Mitra is now gaining importance from the last few years due to its increasing incidence. Regular surveys are conducted to collect wheat grains samples from different grain markets of Punjab, India. Since weather plays a significant role in the initiation as well as the development of Karnal bunt.

Increased Frequency of CD4 Follicular Helper T and CD8 Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis.

Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody-positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Subsequently, we confirmed their presence in lymph nodes and synovial tissue of RA patients using immunofluorescence microscopy.

Systemic high-dose dexamethasone treatment may modulate the efficacy of intratumoral viral oncolytic immunotherapy in glioblastoma models.

Background: Intratumoral viral oncolytic immunotherapy is a promising new approach for the treatment of a variety of solid cancers. CAN-2409 is a replication-deficient adenovirus that delivers herpes simplex virus thymidine kinase to cancer cells, resulting in local conversion of ganciclovir or valacyclovir into a toxic metabolite. This leads to highly immunogenic cell death, followed by a local immune response against a variety of cancer neoantigens and, next, a systemic immune response against the injected tumor and uninjected distant metastases.

Toward Individualized Prediction of Response to Methotrexate in Early Rheumatoid Arthritis: A Pharmacogenomics-Driven Machine Learning Approach.

Objective: To test the ability of machine learning (ML) approaches with clinical and genomic biomarkers to predict methotrexate treatment response in patients with early rheumatoid arthritis (RA).

Methods: Demographic, clinical, and genomic data from 643 patients of European ancestry with early RA (mean age 54 years; 70% female) subdivided into a training (n = 336) and validation cohort (n = 307) were used. The genomic data comprised 160 single-nucleotide polymorphisms (SNPs) previously associated with RA or methotrexate metabolism.

A study comparing depression, anxiety, and coping styles between high school students attending and not attending coaching class for medical entrance examination.

Background: Various kinds of stressors and psychological problems have been reported in the adolescent student population. This study assessed and compared depression, anxiety, and various coping styles among high school students attending coaching classes for medical entrance examination (MEE) and those not.

Materials And Methods: Systemic random sampling technique was used to recruit 400 high school students with equal number of those attending (Group 1) and those not attending any coaching class for MEE (Group 2).

A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis.

Objective: Tumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). This phase IIa, randomised, double-blind experimental medicine study investigated the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of the RIPK1 inhibitor GSK2982772 in patients with active UC.

Design: In part A, prior to a protocol amendment, one patient was randomised to receive GSK2982772 60 mg twice daily for 42 days.

Increased concentration of serum gamma-glutamyl transferase in ischemic stroke patients.

Background: Stroke is responsible for the largest proportion of neurological disorders causing a significant morbidity. Gamma-glutamyl transferase (GGT) enzyme has an active involvement in atherosclerosis through its role in oxidative and inflammatory mechanisms. Recent evidence suggests that serum GGT is related to the risk and prognosis of cerebrovascular diseases.

Comparison of two screening instruments to detect dementia in Indian elderly subjects in a clinical setting.

Objective: Cognitive screening in elderly patients receiving treatment for chronic medical conditions in a busy outpatient clinical setting is crucial to detect dementia at an earlier stage. Although Hindi Mini-Mental State Examination (HMSE) is an established screening tool for the geriatric population in India, but cannot be administered with the informant. Our study aims to compare two screening instruments, Informant based - Eight-item Interview to Differentiate Aging and Dementia (AD8) and HMSE among elderly patients attending medical outpatient service (OPD) in a tertiary care hospital.

Novel Insights Into Rheumatoid Arthritis Through Characterization of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients With Differing Numbers of Swollen Joints.

In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies and patients with established rheumatoid arthritis (RA), by applying an integrative multi-omics approach where we investigated differences at the level of DNA methylation and gene expression in relation to disease pathogenesis. We performed concurrent whole-genome bisulphite sequencing and RNA-Sequencing on synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66), with patients with SJC66 of 9 or more displaying separation from the rest.

Health anxiety among medical students: A comparison between preclinical and clinical years of training.

Objective: It is common among medical students to falsely attribute bodily sensations/symptoms and holds a belief of having a medical illness with varying level of conviction. We studied and compared this condition known as "medical student syndrome", a type of hypochondriasis, between preclinical and clinical years students.

Methodology: This research was a descriptive study where a total of 100 students were approached and were asked to complete a short form of health anxiety inventory (SHAI) which has Cronbach's alpha 0.

A Comparative Study of Yoga with Paroxetine for the Treatment of Premature Ejaculation: A Pilot Study.

Context: Premature ejaculation (PME) is a common sexual disorder. Drugs used commonly used for its treatment have various side effects and disadvantages. Yoga is being increasingly studied in a variety of medical disorders with positive results.

COVID-19 contact tracing in a tertiary care hospital: A retrospective chart review.

Background: Contact tracing is one of the strategies used to control COVID-19 pandemic. It played an important role in the beginning to identify all contacts and minimise the spread of the infection.

Methods: A retrospective chart review was carried out of contact tracing records during the one-month period, starting from the onset of the first lockdown in India.