A Comprehensive ddPCR Strategy for Sensitive and Reliable Monitoring of CAR-T Cell Kinetics in Clinical Applications.

In this study, we present the design, implementation, and successful use of digital droplet PCR (ddPCR) for the monitoring of chimeric antigen receptor T-cell (CAR-T) expansion in patients with B-cell malignancies treated with different CAR-T products at our clinical center. Initially, we designed a specific and highly sensitive ddPCR assay targeting the junction between the 4-1BB and CD3ζ domains of tisa-cel, normalized with , and validated it using blood samples from the first tisa-cel-treated patient in Switzerland. We further compared this assay with a published qPCR (quantitative real-time PCR) design.

PARPi, BRCA, and gaps: controversies and future research.

In recent years, various poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have been approved for the treatment of several cancers to target the vulnerability of homologous recombination (HR) deficiency (e.g., due to BRCA1/2 dysfunction).

Selective haematological cancer eradication with preserved haematopoiesis.

Haematopoietic stem cell (HSC) transplantation (HSCT) is the only curative treatment for a broad range of haematological malignancies, but the standard of care relies on untargeted chemotherapies and limited possibilities to treat malignant cells after HSCT without affecting the transplanted healthy cells. Antigen-specific cell-depleting therapies hold the promise of much more targeted elimination of diseased cells, as witnessed in the past decade by the revolution of clinical practice for B cell malignancies. However, target selection is complex and limited to antigens expressed on subsets of haematopoietic cells, resulting in a fragmented therapy landscape with high development costs.

Camera trap surveys of Atlantic Forest mammals: A data set for analyses considering imperfect detection (2004-2020).

Camera traps became the main observational method of a myriad of species over large areas. Data sets from camera traps can be used to describe the patterns and monitor the occupancy, abundance, and richness of wildlife, essential information for conservation in times of rapid climate and land-cover changes. Habitat loss and poaching are responsible for historical population losses of mammals in the Atlantic Forest biodiversity hotspot, especially for medium to large-sized species.

Mutational patterns in therapy-related acute lymphoblastic leukemia subgroups: one step closer to unveiling the genetic odyssey.

There is increasing evidence that therapy-related acute lymphoblastic leukemia (trALL) resulting from chemo- and/or radiotherapy represents a distinct entity. However, apart from rearrangements, which have been repeatedly reported in this subgroup, the relevance of other aberrations remains controversial due to divergent study results and sparse molecular analyses. Within our ALL patient cohort, 15% ( = 19/131) met the criteria for trALL with a high proportion of Ph + and rearrangements.

Temporomandibular joint surgery: the past, present, and future.

Temporomandibular joint surgery for various pathological conditions and diseases affecting the integrity, mobility, and function of the joint has a long history. However, the greatest explosion of knowledge regarding the diagnosis and management of temporomandibular joint pain, pathology, and rehabilitation has occurred in the last 50 years. This review focuses on the incremental expansion of knowledge over time that led to the development of concepts that support our current surgical decisions and techniques, with the aim of identifying gaps in knowledge that require well-designed studies to move the field forward.

Methodological approaches and competence areas of nursing students in virtual reality simulation research - A scoping review.

Objectives: To analyze methodological approaches (theoretical frameworks, study designs, methods) and competence areas of nursing students in research on virtual reality simulations (VRS) with a high level of immersion.

Methods: A scoping review was performed. A systematic search of the literature was conducted on MEDLINE, CINAHL and ERIC databases on 30/11/22.

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates.

Background And Objectives: Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates.

Methods: We identified patients with acetylcholine receptor antibody-positive (AChR) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses.

Loss of the volume-regulated anion channel components LRRC8A and LRRC8D limits platinum drug efficacy.

In recent years platinum (Pt) drugs have been found to be especially efficient to treat patients with cancers that lack a proper DNA damage response, . due to dysfunctional BRCA1. Despite this knowledge, we are still missing helpful markers to predict Pt response in the clinic.

Azathioprine therapy induces selective NK cell depletion and IFN-γ deficiency predisposing to herpesvirus reactivation.

Background: Azathioprine is a widely prescribed drug for patients with chronic inflammatory diseases such as myasthenia gravis or organ transplant recipients. Azathioprine exerts immunosuppressive effects by inhibiting intracellular purine synthesis and reducing the numbers of circulating B and T lymphocytes. Case reports indicate increased risk for serious infections that can occur despite regular measurements of lymphocyte counts during azathioprine therapy.

Framing cognitive offloading in terms of gains or losses: achieving a more optimal use of reminders.

Nowadays individuals can readily set reminders to offload intentions onto external resources, such as smartphone alerts, rather than using internal memory. Individuals tend to be biased, setting more reminders than would be optimal. We address the question whether the reminder bias depends on offloading scenarios being framed as either gains or losses, both between-participants (Experiment 1) and within-participants (Experiment 2).

Introducing innovative cellular therapies into the clinic: a 2-year retrospective experience of a chimeric antigen receptor T-cell programme at a single centre in Switzerland.

Aim Of The Study: Chimeric antigen receptor T (CAR-T) cells are a powerful form of immune-cell therapy for patients with relapsed/refractory B-cell lymphoma and acute B lymphoblastic leukaemia. CAR-T cells have been commercially available in Switzerland since 2018. Because of the complexity and costs of this treatment it is critical to review patient outcomes in real-world settings, to examine whether the promising results from pivotal trials can be reproduced and to identify clinical parameters that determine their efficacy.

Comprehensive Validation of Diagnostic Next-Generation Sequencing Panels for Acute Myeloid Leukemia Patients.

Next-generation sequencing has greatly advanced the molecular diagnostics of malignant hematological diseases and provides useful information for clinical decision making. Studies have shown that certain mutations are associated with prognosis and have a direct impact on treatment of affected patients. Therefore, reliable detection of pathogenic variants is critically important.

SMARCE1 deficiency generates a targetable mSWI/SNF dependency in clear cell meningioma.

Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes establish and maintain chromatin accessibility and gene expression, and are frequently perturbed in cancer. Clear cell meningioma (CCM), an aggressive tumor of the central nervous system, is uniformly driven by loss of SMARCE1, an integral subunit of the mSWI/SNF core. Here, we identify a structural role for SMARCE1 in selectively stabilizing the canonical BAF (cBAF) complex core-ATPase module interaction.

Real-world outcomes in elderly ALL patients with and without allogeneic hematopoietic stem cell transplantation: a single-center evaluation over 10 years.

Elderly patients (EP) of 60 years and above with acute lymphoblastic leukemia (ALL) have a dismal prognosis, but pediatric-inspired chemotherapy and allogeneic stem cell transplantation (allo HCT) are used reluctantly due to limited data and historical reports of high treatment-related mortality in EP. We analyzed 130 adult ALL patients treated at our center between 2009 and 2019, of which 26 were EP (range 60-76 years). Induction with pediatric-inspired protocols was feasible in 65.

Density and habitat use of one of the last jaguar populations of the Brazilian Atlantic Forest: Is there still hope?

The jaguar () plays an important role in maintaining biodiversity and ecological processes. We evaluated the status of a jaguar population in one of the last stronghold habitats for its conservation in the Atlantic Forest, the Rio Doce State Park (RDSP). We used a random survey design from 2016/17 to estimate jaguar abundance and density as well as its occupancy and detection probabilities in the entire Park's area.

Clinical, laboratory and ultrasonographic findings in 38 calves with type-4 abomasal ulcer.

Background: Type-4 abomasal ulcers (U4) are perforated ulcers causing diffuse peritonitis. This retrospective study describes the clinical, laboratory and ultrasonographic findings in 38 calves with U4. The medical records of 38 calves aged three days to 20 weeks with U4 were scrutinised.

Effects of Choice Restriction on Accuracy and User Experience in an Internet-Based Geopolitical Forecasting Task.

Large-scale geopolitical forecasting tournaments have emerged in recent years as effective testbeds for conducting research into novel forecasting tools and methods. A challenge of such tournaments involves the distribution of forecasting load across forecasters, since there are often more forecasting questions than an individual forecaster can answer. Intelligent load distribution, or triage, may therefore be helpful in ensuring that all questions have sufficient numbers of forecasts to benefit from crowd-based aggregation and that individual forecasters are matched to the questions for which they are best suited.

Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature.

Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG.