Human stem cell-based retina on chip as new translational model for validation of AAV retinal gene therapy vectors.

Gene therapies using adeno-associated viruses (AAVs) are among the most promising strategies to treat or even cure hereditary and acquired retinal diseases. However, the development of new efficient AAV vectors is slow and costly, largely because of the lack of suitable non-clinical models. By faithfully recreating structure and function of human tissues, human induced pluripotent stem cell (iPSC)-derived retinal organoids could become an essential part of the test cascade addressing translational aspects.

Influence of Nutrition and Maternal Bonding on Postnatal Lung Development in the Newborn Pig.

Background: Microbial colonization and immune cell maturation coincide at mucosal sites and are decisive for postnatal lung development. How external factors influence neonatal pulmonary immune development is poorly understood.

Objective: To elucidate the impact of key determinants in early life, nutrition, and maternal bonding, on postnatal lung maturation in a human-relevant animal model.

The Impact of the COVID-19 Pandemic on Spine Surgery in Central Europe: A Questionnaire-Based Study.

Objective: The severe acute respiratory coronavirus 2 (SARS-CoV2) crisis led to many restrictions in daily life and protective health care actions in all hospitals to ensure basic medical supply. This questionnaire-based study among spinal surgeons in central Europe was generated to investigate the impact of coronavirus disease 2019 (COVID-19) and consecutively the differences in restrictions in spinal surgery units.

Methods: An online survey consisting of 32 questions on the impact of the COVID-19 pandemic and the related restrictions on spinal surgery units was created.

Lectin-Mediated Bacterial Modulation by the Intestinal Nematode .

Ascariasis is a global health problem for humans and animals. Adult nematodes are long-lived in the host intestine where they interact with host cells as well as members of the microbiota resulting in chronic infections. Nematode interactions with host cells and the microbial environment are prominently mediated by parasite-secreted proteins and peptides possessing immunomodulatory and antimicrobial activities.

The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13.

B-cell acute lymphoblastic leukemia (B-ALL) occurs most commonly in children, whereas chronic myeloid leukemia is more frequent in adults. The myeloid bias of hematopoiesis in elderly individuals has been considered causative, but the age of the bone marrow microenvironment (BMM) may be contributory. Using various murine models of B-ALL in young vs old mice, we recapitulated B-ALL preponderance in children vs adults.

Histopathological growth patterns in patients with advanced nodular lymphocyte-predominant Hodgkin lymphoma treated within the randomized HD18 study: a report from the German Hodgkin Study Group.

We retrospectively investigated histopathological growth patterns in individuals with advanced nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated within the randomized HD18 study. In all, 35/60 patients (58%) presented with atypical growth patterns. Patients with atypical growth patterns more often had stage IV disease (P = 0·0354) and splenic involvement (P = 0·0048) than patients with typical growth patterns; a positive positron emission tomography after two cycles of chemotherapy (PET-2) tended to be more common (P = 0·1078).

The Building Blocks of Child Bilingual Code-Mixing: A Cross-Corpus Traceback Approach.

This paper offers an inductive, exploratory study on the role of input and individual differences in the early code-mixing of bilingual children. Drawing on data from two German-English bilingual children, aged 2-4, we use the traceback method to check whether their code-mixed utterances can be accounted for with the help of constructional patterns that can be found in their monolingual data and/or in their caregivers' input. In addition, we apply the traceback method to check whether the patterns used by one child can also be found in the input of the other child.

The gating pore blocker 1-(2,4-xylyl)guanidinium selectively inhibits pacemaking of midbrain dopaminergic neurons.

Although several ionic mechanisms are known to control rate and regularity of the slow pacemaker in dopamine (DA) neurons, the core mechanism of pacing is controversial. Here we tested the hypothesis that pacemaking of SNc DA neurons is enabled by an unconventional conductance. We found that 1-(2,4-xylyl)guanidinium (XG), an established blocker of gating pore currents, selectively inhibits pacemaking of DA neurons.

Validation of the German-language version of the Liverpool Oral Rehabilitation Questionnaire version 3 and evaluation of oral-health-related quality of life among patients with squamous cell carcinoma of the head and neck.

The aim of this study was to translate the Liverpool Oral Rehabilitation Questionnaire version 3 (LORQv3) into German and validate this version in order to assess oral-health-related quality of life (OHRQoL) among head and neck cancer patients. This study was conducted at a German university clinic among patients who had completed therapy for squamous cell carcinoma of the head and neck (HNSCC). The original English-language LORQv3 was translated into German according to the forward-backward approach.

Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma.

A hallmark of classical Hodgkin lymphoma (cHL) is the attenuation of B-cell transcription factors leading to global transcriptional reprogramming. The role of miRNAs (microRNAs) involved in this process is poorly studied. Therefore, we performed global miRNA expression profiling using RNA-seq on commonly used cHL cell lines, non-Hodgkin lymphoma cell lines and sorted normal CD77 germinal centre B-cells as controls and characterized the cHL miRNome (microRNome).

Collision risk of bats with small wind turbines: Worst-case scenarios near roosts, commuting and hunting structures.

Small wind turbines (SWTs) have become increasingly common within the last decade, but their impact on wildlife, especially bats, is largely unknown. We conducted an operational experiment by sequentially placing a mobile SWT with five different operational modes at six sites of high bat activity, including roosts, commuting structures, and highly frequented hunting areas. Bat flight trajectories around the SWT were documented at each site during five consecutive nights using a specifically designed high-spatial-resolution 3D camera.

Pericardial disease in patients treated with immune checkpoint inhibitors.

Background: There are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis on or after treatment with immune checkpoint inhibitors (ICIs).

Methods: This was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI. A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion.

High-resolution asymmetric structure of a Fab-virus complex reveals overlap with the receptor binding site.

Canine parvovirus is an important pathogen causing severe diseases in dogs, including acute hemorrhagic enteritis, myocarditis, and cerebellar disease. Overlap on the surface of parvovirus capsids between the antigenic epitope and the receptor binding site has contributed to cross-species transmission, giving rise to closely related variants. It has been shown that Mab 14 strongly binds and neutralizes canine but not feline parvovirus, suggesting this antigenic site also controls species-specific receptor binding.

The Clinical Relevance of Target Lymph Node Biopsy after Primary Systemic Therapy in Initially Node-Positive Breast Cancer Patients.

Purpose: To assess the impact of the removal of the target lymph node (TLN) on therapy after the completion of primary systemic therapy (PST) in initially node-positive breast cancer patients.

Methods: Pooled data analysis of participants of the prospective CLIP- and TATTOO-study at the University of Rostock was performed.

Results: A total of 75 patients were included; 63 of them (84.

Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [F]FDG PET/CT and MRI.

Purpose: While [F]-fluorodeoxyglucose ([F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT.

Methods: Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [F]FDG and [Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection.

Flexing a standard hinge-powered operating table for lumbosacral three-column osteotomy (3-CO) site closure in 84 consecutive patients.

Three-column osteotomy (3-CO) is a powerful technique in adult deformity surgery, and pedicle subtraction osteotomy (PSO) is the workhorse to correct severe kyphotic spinal deformities. Aging of the population, increasing cases of iatrogenic flat back deformities and understanding the importance of sagittal balance have led to a dramatic increase of this surgical technique. Surgery, however, is demanding and associated with high complication rates so that every step of the procedure requires meticulous technique.

Lost clips after targeted lymph node biopsy in breast cancer patients: Follow-up of the CLIP-study.

Introduction: Clipping and selective removal of axillary lymph nodes in breast cancer patients presenting with initially node-positive disease and achieving a nodal downstaging after primary systemic therapy is a less invasive method for axillary staging. An imaging guided localization and successful extirpation of these clipped lymph nodes is not possible in all patients. To date no follow-up data regarding patients with lost clips are available.

ε-Phages Are Naturally Bred and Have a Vastly Improved Host Range in over Wild Type Phages.

Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 strains (MRSA/MSSA) composed to reflect the prevalence of clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%.

Insight into the introduction of domestic cattle and the process of Neolithization to the Spanish region Galicia by genetic evidence.

Domestic cattle were brought to Spain by early settlers and agricultural societies. Due to missing Neolithic sites in the Spanish region of Galicia, very little is known about this process in this region. We sampled 18 cattle subfossils from different ages and different mountain caves in Galicia, of which 11 were subject to sequencing of the mitochondrial genome and phylogenetic analysis, to provide insight into the introduction of cattle to this region.

Surgical nuances and construct patterns influence construct stiffness in C1-2 stabilizations: a biomechanical study of C1-2 gapping and advanced C1-2 fixation.

Purpose: Stabilization of C1-2 using a Harms-Goel construct with 3.5 mm titanium (Ti) rods has been established as a standard of reference (SOR). A reduction in craniocervical deformities can indicate increased construct stiffness at C1-2.

Evolutionary clonal trajectories in nodular lymphocyte-predominant Hodgkin lymphoma with high risk of transformation.

The B-cell architecture of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is complex since it is composed of malignant lymphocyte-predominant cells along with a rich B-cell bystander environment. To gain insight into molecular determinants of disease transformation, we studied B-cell evolutionary trajectories in lymphoma tissue from diagnosis to relapse or transformation to non- Hodgkin lymphoma by next-generation sequencing of immunoglobulin heavy chains. Patients with NLPHL that later transformed were older and showed IgD negativity, absence of the characteristic IGHV3/IGHD3/IGHJ6 lymphocyte-predominant rearrangement and high repertoire clonality.

Accuracy of 18-F Fluorodeoxyglucose Positron Emission Tomographic/Computed Tomographic Imaging in Primary Staging of Squamous Cell Carcinoma of the Oral Cavity.

Importance: Squamous cell carcinoma (SCC) of the oral cavity is one of the most common tumor entities worldwide. Precise initial staging is necessary to determine a diagnosis, treatment, and prognosis.

Objective: To examine the diagnostic accuracy of preoperative 18-F fluorodeoxyglucose (FDG) positron emission tomographic/computed tomographic (PET/CT) imaging in detecting cervical lymph node metastases.