Distal Triceps Tendon Rupture-First Retrospective Study in Central Europe.

This retrospective study is the only one in the last 10 years from central Europe and provides a current picture of prevalence, new diagnostic modalities, new methods of surgical treatment, and also offers new insights into post-operative care. Triceps tendon rupture is the least reported among all the tendon injuries in the literature. In general, effective treatments for tendon injuries are lacking because the understanding of tendon biology lags behind that of the other components of the musculoskeletal system.

Rational engineering of minimally immunogenic nucleases for gene therapy.

Genome editing using CRISPR-Cas systems is a promising avenue for the treatment of genetic diseases. However, cellular and humoral immunogenicity of genome editing tools, which originate from bacteria, complicates their clinical use. Here we report reduced immunogenicity (Red)(i)-variants of two clinically relevant nucleases, SaCas9 and AsCas12a.

The effect of lengthening of the percutaneous implant in the surgical treatment of Th-L ankylosed spine fractures: 4 segment fixation versus 5 to 8 segment fixation.

Background: Fractures of thoracolumbar spine in the field of ankylosing diseases such as ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) can by surgically treated with miniinvasive posterior transpedicular fixation. The exact length of implant is the subject of several studies. In our study, we retrospectively evaluated the treatment of B3 fractures of the ankylosed thoracolumbar spine with use a shorter versus longer implant, always with 8 screws.

Maternal Streptococcus agalactiae colonization in Europe: data from the multi-center DEVANI study.

Introduction: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD).

Methods: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study.

Role of IgA1 protease-producing bacteria in SARS-CoV-2 infection and transmission: a hypothesis.

Secretory (S) IgA antibodies against severe acute respiratory syndrome (SARS)-CoV-2 are induced in saliva and upper respiratory tract (URT) secretions by natural infection and may be critical in determining the outcome of initial infection. Secretory IgA1 (SIgA1) is the predominant isotype of antibodies in these secretions. Neutralization of SARS-CoV-2 is most effectively accomplished by polymeric antibodies such as SIgA.

Establishing African genomics and bioinformatics programs through annual regional workshops.

The African BioGenome Project (AfricaBP) Open Institute for Genomics and Bioinformatics aims to overcome barriers to capacity building through its distributed African regional workshops and prioritizes the exchange of grassroots knowledge and innovation in biodiversity genomics and bioinformatics. In 2023, we implemented 28 workshops on biodiversity genomics and bioinformatics, covering 11 African countries across the 5 African geographical regions. These regional workshops trained 408 African scientists in hands-on molecular biology, genomics and bioinformatics techniques as well as the ethical, legal and social issues associated with acquiring genetic resources.

The immunoglobulin superfamily ligand B7H6 subjects T cell responses to NK cell surveillance.

Understanding the mechanisms that regulate T cell immunity is critical for the development of effective therapies for diseases associated with T cell dysfunction, including autoimmune diseases, chronic infections, and cancer. Co-inhibitory "checkpoint molecules," such as programmed cell death protein-1, balance excessive or prolonged immune activation by T cell-intrinsic signaling. Here, by screening for mediators of natural killer (NK) cell recognition on T cells, we identified the immunoglobulin superfamily ligand B7H6 to be highly expressed by activated T cells, including patient-infused CD19-targeting chimeric antigen receptor (CAR) T cells.

nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma.

Intrinsic brain tumors, such as gliomas are largely resistant to immunotherapies including immune checkpoint blockade. Adoptive cell therapies (ACT) including chimeric antigen receptor (CAR) or T cell receptor (TCR)-transgenic T cell therapy targeting glioma-associated antigens are an emerging field in glioma immunotherapy. However, imaging techniques for non-invasive monitoring of adoptively transferred T cells homing to the glioma microenvironment are currently lacking.

Tumor-reactive T helper cells in the context of vaccination against glioma.

With the advances in immunogenomics, the majority of tumor-specific antigens were found to be recognized by T helper cells (TCs). This observation led to the development of long epitope vaccines in various cancers. Mechanistically, we are still gaining a deeper understanding of the mode of action of TCs as precision antitumor agonists.

Co-evolution at protein-protein interfaces guides inference of stoichiometry of oligomeric protein complexes by de novo structure prediction.

The quaternary structure with specific stoichiometry is pivotal to the specific function of protein complexes. However, determining the structure of many protein complexes experimentally remains a major bottleneck. Structural bioinformatics approaches, such as the deep learning algorithm Alphafold2-multimer (AF2-multimer), leverage the co-evolution of amino acids and sequence-structure relationships for accurate de novo structure and contact prediction.

NLGN4X TCR transgenic T cells to treat gliomas.

Background: Neuroligin 4 X-linked (NLGN4X) harbors a human leukocyte antigen (HLA)-A*02-restricted tumor-associated antigen, overexpressed in human gliomas, that was found to induce specific cytotoxic T cell responses following multi-peptide vaccination in patients with newly diagnosed glioblastoma.

Methods: T cell receptor (TCR) discovery was performed using droplet-based single-cell TCR sequencing of NLGN4X-tetramer-sorted T cells postvaccination. The identified TCR was delivered to Jurkat T cells and primary human T cells (NLGN4X-TCR-T).

Do depressed patients really over-report cognitive impairment?

Background: Depressed patients report more severe cognitive impairment than is detectable by neuropsychological tests because they may underestimate their cognitive performance. Alternatively, it is possible that cognitive impairment primarily occurs under everyday life conditions as referred to in most questionnaires. The aim of the present study is to investigate the validity of self-reports in patients with major depression in order to better understand the pronounced impairment in self-reports.

Evidence-Based Practice: Implementing REIS Findings in South African Aged Care Facilities.

Background: Older adults living in Residential Aged Care Facilities (RACFs) in South Africa are often exposed to environments that fail to provide adequate occupational opportunities. Practitioners in developing economies are challenged to provide therapeutic services in environments that emphasize occupational deprivation.

Objectives: This study investigated barriers and enablers to implementing recommendations derived from the findings generated by the Residential Environment Impact Scale (REIS).

Smooth and Discrete Cone-Nets.

Cone-nets are conjugate nets on a surface such that along each individual curve of one family of parameter curves there is a cone in tangential contact with the surface. The corresponding conjugate curve network is projectively invariant and is characterized by the existence of particular transformations. We study properties of that transformation theory and illustrate how several known surface classes appear within our framework.

The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients.

Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical response.

Assessing the Mental Condition of Paramedics and Nurses during the SARS-CoV-2 Pandemic.

Background: The COVID-19 pandemic has significantly affected many aspects of life. The aim of this study was to assess the mental state of medical personnel most involved with patients affected by SARS-CoV-2.

Methods: The survey research was conducted between October 2021 and March 2022.

MHC class II-restricted antigen presentation is required to prevent dysfunction of cytotoxic T cells by blood-borne myeloids in brain tumors.

Cancer immunotherapy critically depends on fitness of cytotoxic and helper T cell responses. Dysfunctional cytotoxic T cell states in the tumor microenvironment (TME) are a major cause of resistance to immunotherapy. Intratumoral myeloid cells, particularly blood-borne myeloids (bbm), are key drivers of T cell dysfunction in the TME.

Neonatal invasive disease caused by Streptococcus agalactiae in Europe: the DEVANI multi-center study.

Purpose: Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants < 3 months of age and of mortality among neonates. This study, a major component of the European DEVANI project (Design of a Vaccine Against Neonatal Infections) describes clinical and important microbiological characteristics of neonatal GBS diseases. It quantifies the rate of antenatal screening and intrapartum antibiotic prophylaxis among cases and identifies risk factors associated with an adverse outcome.

IgE type multiple myeloma exhibits hypermutated phenotype and tumor reactive T cells.

Multiple myeloma (MM) is a hematological malignancy originating from malignant and clonally expanding plasma cells. MM can be molecularly stratified, and its clonal evolution deciphered based on the Ig heavy and light chains of the respective malignant plasma cell clone. Of all MM subtypes, IgE type MM accounts for only <0.

T cell receptor dynamic and transcriptional determinants of T cell expansion in glioma-infiltrating T cells.

Background: Glioblastoma (GBM) is characterized by low numbers of glioma-infiltrating lymphocytes (GIL) with a dysfunctional phenotype. Whether this dysfunctional phenotype is fixed or can be reversed upon culturing is poorly understood. The aim of this study was to assess T cell receptor (TCR)-dynamics and -specificities as well as determinants of GIL expansion by sequencing-based technologies and functional assays to explore the use of GIL for cell therapy.

Dysfunctional dendritic cells limit antigen-specific T cell response in glioma.

Background: Dendritic cells (DC), the most potent professional antigen presenting cells capable of effective cross-presentation, have been demonstrated to license T helper cells to induce antitumor immunity in solid tumors. Specific DC subtypes are recruited to the injured brain by microglial chemokines, locally adapting to distinct transcriptional profiles. In isocitrate dehydrogenase (IDH) type 1 mutant gliomas, monocyte-derived macrophages have recently been shown to display an attenuated intratumoral antigen presentation capacity as consequence of the local accumulation of the oncometabolite R-2-hydroxyglutarate.

Induction of Susceptibility to Disseminated Infection with IgA1 Protease-Producing Encapsulated Pathogens Streptococcus pneumoniae, Haemophilus influenzae Type b, and Neisseria meningitidis.

Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae are the principal causes of bacterial meningitis. It is unexplained why only occasional individuals develop invasive infection, while the vast majority remain healthy and develop immunity when encountering these pathogens. A capsular polysaccharide and an IgA1 protease are common to these pathogens.