Sliding Window INteraction Grammar (SWING): a generalized interaction language model for peptide and protein interactions.

The explosion of sequence data has allowed the rapid growth of protein language models (pLMs). pLMs have now been employed in many frameworks including variant-effect and peptide-specificity prediction. Traditionally, for protein-protein or peptide-protein interactions (PPIs), corresponding sequences are either co-embedded followed by post-hoc integration or the sequences are concatenated prior to embedding.

De novo identification of CD4 T cell epitopes.

CD4 T cells recognize peptide antigens presented on class II major histocompatibility complex (MHC-II) molecules to carry out their function. The remarkable diversity of T cell receptor sequences and lack of antigen discovery approaches for MHC-II make profiling the specificities of CD4 T cells challenging. We have expanded our platform of signaling and antigen-presenting bifunctional receptors to encode MHC-II molecules presenting covalently linked peptides (SABR-IIs) for CD4 T cell antigen discovery.

Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial.

Overcoming intrinsic resistance to immune checkpoint blockade for microsatellite stable (MSS) colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) remains challenging. We conducted a single-arm, non-randomized, phase II trial (NCT03104439) combining radiation, ipilimumab and nivolumab to treat patients with metastatic MSS CRC (n = 40) and PDAC (n = 25) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The primary endpoint was disease control rate (DCR) by intention to treat.

Revealing and IgG4 analysis to factor VIII in haemophilia-A patients with and without inhibitors.

Introduction: The acquisition of factor VIII inhibitors poses major management challenges for haemophilia A (HA) patients. Most (Factor VIII) inhibitors are immunoglobulin G4 (IgG4) and G1 (IgG1) subclasses, with IgG4 being the most prevalent. The Nijmegen Bethesda Assay (NBA) was used to quantify inhibitors.

Mixing-based inhibitor screening in haemophilia A: challenges in interpretation.

: Inhibitor development in haemophilia A patients is a dreaded complication of factor VIII (FVIII) replacement therapy. With increasing use of FVIII replacement therapy, there is an imperative need for cost-effective and standardized screening. To evaluate the efficacy of mixing-based inhibitor screening (MBIS) in the detection of FVIII inhibitors and to assess the best cut-off values for MBIS.

Clinicopathological parameters influencing inhibitor development in patients with hemophilia A receiving on-demand therapy.

Background: Development of inhibitors to transfused factor VIII in patients with hemophilia A continues to be a challenge for professionals involved in hemophilia care. The majority of patients in India receive 'on-demand' rather than prophylactic therapy. The present study was done to assess the prevalence of factor VIII inhibitors in patients with hemophilia A (PWHA) receiving 'on-demand' therapy in a North Indian population and to study the clinicopathological parameters influencing the development of inhibitors.

Clinical relevance of PD-L1 expression in gallbladder cancer: a potential target for therapy.

Aims: Programmed death-ligand 1 (PD-L1), a potential target for immune checkpoint inhibitors in various solid neoplasms, has been studied in very few cases of Gall Bladder Carcinoma (GBC). The current study aimed to evaluate PD-L1 expression at primary and metastatic sites of GBC, and its associations with standard prognostic clinicopathological parameters, as well as with overall survival.

Methods And Results: One hundred and seventy-four cases of GBC were evaluated for PD-L1 expression by the use of the SP263 clone in tissue microarrays.