Investigation of crystalline lens overshooting: experiment and optomechanical simulation results.

Crystalline lens overshooting refers to a situation in which the lens momentarily shifts too much from its typical location immediately after stopping the rotational movement of the eye globe. This movement can be observed using an optical technique called Purkinje imaging. In this work, an experimental setup was designed to reproduce this effect using a fresh porcine eye.

An integrated model of the human cornea as a linear biaxial birefringent medium.

A novel model of human corneal birefringence is presented. The cornea is treated as a homogeneous biaxial linear birefringent medium in which the values of the binormal axes angle and organization of the main refractive indices vary continuously from the apex to the limbus. In its central part, the angle between binormal axes is 35°, and para centrally, it smoothly increases to 83.

Complexity of crystalline lens wobbling investigated by means of combined mechanical and optical simulations.

Crystalline lens wobbling is a phenomenon when the lens oscillates briefly from its normal position immediately after stopping the rotational movement of the eye globe. It can be observed by means of Purkinje imaging. The aim of this research is to present the data and computation workflow that involve both biomechanical and optical simulations that can mimic this effect, aimed to better understanding of lens wobbling.

Opto-mechanical self-adjustment model of the human eye.

The eye has specific optical and biomechanical properties that jointly regulate the eye's quality of vision, shape, and elasticity. These two characteristics are interdependent and correlated. Contrary to most currently available computational models of the human eye that only focus on biomechanical or optical aspects, the current study explores the inter-relationships between biomechanics, structure, and optical properties.

Clinical Pharmacology and Determinants of Response to UCART19, an Allogeneic Anti-CD19 CAR-T Cell Product, in Adult B-cell Acute Lymphoblastic Leukemia.

Background: UCART19 is an "off-the-shelf" genome-edited anti-CD19 chimeric antigen receptor (CAR)-T cell product, manufactured from unrelated healthy donor cells.

Methods: UCART19 was administered to 25 adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) in the CALM trial. All patients underwent lymphodepletion with fludarabine and cyclophosphamide ± alemtuzumab and received one of three ascending doses of UCART19.

Selected Predictors of COVID-19 Mortality in the Hospitalised Patient Population in a Single-Centre Study in Poland.

: The correct analysis of COVID-19 predictors could substantially improve the clinical decision-making process and enable emergency department patients at higher mortality risk to be identified. : We retrospectively explored the relationship between some demographic and clinical factors, such as age and sex, as well as the levels of ten selected factors, namely, CRP, D-dimer, ferritin, LDH, RDW-CV, RDW-SD, procalcitonin, blood oxygen saturation, lymphocytes, and leukocytes, and COVID-19 mortality risk in 150 adult patients diagnosed with COVID-19 at Provincial Specialist Hospital in Zgierz, Poland (this hospital was transformed, in March 2020, into a hospital admitting COVID-19 cases only). All blood samples for testing were collected in the emergency room before admission.

Allogeneic Anti-BCMA CAR T Cells Are Superior to Multiple Myeloma-derived CAR T Cells in Preclinical Studies and May Be Combined with Gamma Secretase Inhibitors.

Unlabelled: Multiple myeloma remains an incurable plasma cell malignancy despite the rapidly evolving treatment landscape. Chimeric antigen receptor T cells targeted against BCMA have recently shown great promise in relapsed refractory multiple myeloma; however, all patients ultimately still progress from their disease. Lack of CAR T-cell persistence, impaired T-cell fitness in autologous CAR T-cell products and the presence of an immunosuppressive bone marrow (BM) microenvironment are contributory factors to treatment failure.

UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial.

Background: The prognosis for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia remains poor. UCART19, an allogeneic genome-edited anti-CD19 chimeric antigen receptor (CAR) T-cell product derived from healthy donors and available for immediate clinical use, offers a potential therapeutic option for such patients. The CALM trial is a first-in-human study evaluating the safety and antileukaemic activity of UCART19 in adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia.

Corneal Behavior during Tonometer Measurement during the Water Drinking Test in Eyes with XEN GelStent in Comparison to Non-Implanted Eyes.

Biomechanics of the cornea have significant influences on the non-contact measurement of the intraocular pressure. The corneal behaviour during tonometry is a fundamental factor in estimating its value. The aim of the study was to analyse the behaviour of the cornea during tonometric measurement with the forced change in intraocular pressure during the water drinking test.

Short-Time Changes of Intraocular Pressure and Biomechanics of the Anterior Segment of the Eye during Water Drinking Test in Patients with XEN GelStent.

Purpose: Little is known about short-term changes in intraocular pressure (IOP) following minimally invasive glaucoma surgeries, such as post-XEN GelStent implantation. Although the importance of corneal biomechanics in glaucoma diagnostics has been reported, little work has been conducted on postoperative description of changes when the structure of the anterior segment is altered. The aim of presented study was to evaluate the changes in the biomechanical parameters of the anterior segment of the post-XEN GelStent implantation eyes.

Innate-like Gene Expression of Lung-Resident Memory CD8 T Cells during Experimental Human Influenza: A Clinical Study.

Suboptimal vaccine immunogenicity and antigenic mismatch, compounded by poor uptake, means that influenza remains a major global disease. T cells recognizing peptides derived from conserved viral proteins could enhance vaccine-induced cross-strain protection. To investigate the kinetics, phenotypes, and function of influenza virus-specific CD8 resident memory T (Trm) cells in the lower airway and infer the molecular pathways associated with their response to infection .

How a dynamic optical system maintains image quality: Self-adjustment of the human eye.

The eyeball is continually subjected to forces that cause alterations to its shape and dimensions, as well as to its optical components. Forces that induce accommodation result in an intentional change in focus; others, such as the effect of intraocular pressure fluctuations, are more subtle. Although the mechanical properties of the eyeball and its components permit mediation of such subtle forces, the concomitant optical changes are not detected by the visual system.

Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies.

Background: Genome-edited donor-derived allogeneic anti-CD19 chimeric antigen receptor (CAR) T cells offer a novel form of CAR-T-cell product that is available for immediate clinical use, thereby broadening access and applicability. UCART19 is one such product investigated in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Two multicentre phase 1 studies aimed to investigate the feasibility, safety, and antileukaemic activity of UCART19 in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia.

Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection.

The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease.

Impact of Blood Loss and Intraoperative Blood Transfusion During Liver Transplantation on the Incidence of Early Biliary Complications and Mortality.

Biliary complications are one of the most serious and dangerous complications following liver transplantation. Factors that may determine their occurrence are still being assessed. The retrospective analysis of 239 consecutive liver transplantations (LT) performed between January 2013 and December 2018 was conducted in compliance with the Helsinki Congress and the Istanbul Declaration.

Organ Donation in Intensive Care Units of Hospitals in Warsaw.

Background: In recent years a systematic decrease in donation activity in Poland (15.4 vs 13.0) has been observed.

Epitope-specific airway-resident CD4+ T cell dynamics during experimental human RSV infection.

BACKGROUNDRespiratory syncytial virus (RSV) is an important cause of acute pulmonary disease and one of the last remaining major infections of childhood for which there is no vaccine. CD4+ T cells play a key role in antiviral immunity, but they have been little studied in the human lung.METHODSHealthy adult volunteers were inoculated i.

Monitoring Allogeneic CAR-T Cells Using Flow Cytometry.

Chimeric antigen receptor T cell (CAR-T) therapies have now entered mainstream clinical practice with two approved autologous CAR-T products targeting CD19 and numerous other products in early and late phase clinical trials. This has led to a demand for highly sensitive, specific, and easily reproducible methods to monitor CAR-T cells in patients. Here we describe a flow cytometry based protocol for detection of allogeneic CAR-T cells and for monitoring their phenotype and numbers in blood and bone marrow of patients following CAR-T treatment.

Corneal Buckling during Applanation and Its Effect on the Air Pressure Curve in Ocular Response Analyzer.

The paper presents, for the first time, corneal buckling, during the air puff applanation, recorded with use of Ocular Response Analyzer (ORA), when the cornea is deeper deformed after its applanation. Precise numerical analysis of the air pressure curve from the raw data, distinct local disturbances of the curve, which appear almost exactly at the time of the first and the second applanations. Thirty measurements taken on six eyes show clear dependencies between times of both applanations and appearances of local wave disturbances on the air pressure curve as well as between the amplitude of pressure wave disturbances and the respective height of applanation curve.

Data analysis of the ocular response analyzer for improved distinction and detection of glaucoma.

The purpose of this study was to evaluate the clinical utility of the output parameters of the ocular response analyzer (ORA) and those calculated from the raw ORA in subjects with healthy eyes and those with suspected glaucoma, and in patients with two types of glaucoma. The raw ORA data were analyzed using a custom software that included the Gaussian filtering of applanation curves for three different window sizes. To the best of our knowledge, these findings present a novel means of optimizing the use of measurements from the ORA, which can refine the characteristics of corneal biomechanics, enabling a distinction between the types of glaucoma and leading to an improvement in diagnosing and early detection.

Emerging Cellular Therapies: T Cells and Beyond.

Cellular therapies, including those based on T cells, are becoming approved options for clinicians treating a range of diseases. Cytotoxic T lymphocytes (CTLs) can be modified ex vivo to express receptors such as chimeric antigen receptors (CARs) or T cell receptors, allowing them to target tumour cells when infused back into patients with particular cancers. CTLs specific for viruses can be purified ex vivo and reinfused into patients transplanted with haematopoietic stem cells to help combat viral reactivation.

Allogeneic CAR-T Cells: More than Ease of Access?

Patient derived anti-CD19 chimeric antigen receptor-T (CAR-T) cells are a powerful tool in achieving a complete remission in a range of B-cell malignancies, most notably B-acute lymphoblastic leukaemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). However, there are limitations, including inability to manufacture CAR-T cells from the patient's own T cells, disease progression and death prior to return of engineered cells. T cell dysfunction is known to occur in cancer patients, and several groups have recently described differences in CAR-T cells generated from chronic lymphocytic leukaemia (CLL) patients compared with those from a healthy donor.