Neuropathologic Features of Antemortem Atrophy-Based Subtypes of Alzheimer Disease.

Background And Objectives: To investigate whether antemortem MRI-based atrophy subtypes of Alzheimer disease (AD) differ in neuropathologic features and comorbid non-AD pathologies at postmortem.

Methods: From the Alzheimer's Disease Neuroimaging Initiative cohort, we included individuals with antemortem MRI evaluating brain atrophy within 2 years before death, antemortem diagnosis of AD dementia/mild cognitive impairment, and postmortem-confirmed AD neuropathologic change. Antemortem atrophy subtypes were modeled as continuous phenomena based on a recent conceptual framework: typicality (spanning limbic-predominant AD to hippocampal-sparing AD) and severity (spanning typical AD to minimal atrophy AD).

A cross-kingdom view on the immunomodulatory role of MIF/D-DT proteins in mammalian and plant Pseudomonas infections.

Gram-negative Pseudomonas bacteria are largely harmless saprotrophs, but some species can be potent pathogens of both plants and mammals. Macrophage migration-inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (D-DT, also referred to as MIF-2) are multifunctional proteins that in addition to their intracellular functions also serve as extracellular signalling molecules (cytokines) in orchestrating mammalian immune responses. It recently emerged that plants also possess MIF-like proteins, termed MIF/D-DT-like (MDL) proteins.

Histone post-translational modifications - cause and consequence of genome function.

Much has been learned since the early 1960s about histone post-translational modifications (PTMs) and how they affect DNA-templated processes at the molecular level. This understanding has been bolstered in the past decade by the identification of new types of histone PTM, the advent of new genome-wide mapping approaches and methods to deposit or remove PTMs in a locally and temporally controlled manner. Now, with the availability of vast amounts of data across various biological systems, the functional role of PTMs in important processes (such as transcription, recombination, replication, DNA repair and the modulation of genomic architecture) is slowly emerging.

Dynamically disordered hydrogen bonds in the hureaulite-type phosphatic oxyhydroxide Mn[(PO)(PO(OH))](HOH).

We report the temperature evolution of hydrogen bond (HB) chains and rings in Mn[(PO)(PO(OH))](HOH) to reveal conduction pathways based on difference Fourier maps with neutron- and synchrotron x-ray diffraction data. Localized proton dynamics for the five distinct hydrogen sites were observed and identified in this study. Their temperature evaluation over ten orders of magnitude in time was followed by means of quasielastic neutron scattering, dielectric spectroscopy, and ab initio molecular dynamics.

Patient-dependent risk factors for wound infection after skin surgery: A systematic review and meta-analysis.

Postoperative wound infection in dermatologic surgery causes impaired wound healing, poor cosmetic outcome and increased morbidity. Patients with a high-risk profile may benefit from perioperative antibiotic prophylaxis. The objective of this systematic review was to identify risk factors for surgical site infection after dermatologic surgery.

Dental and Orthopaedic Implant Loosening: Overlap in Gene Expression Regulation.

Objectives: Endoprosthetic loosening still plays a major role in orthopaedic and dental surgery and includes various cellular immune processes within peri-implant tissues. Although the dental and orthopaedic processes vary in certain parts, the clinical question arises whether there are common immune regulators of implant loosening. Analyzing the key gene expressions common to both processes reveals the mechanisms of osteoclastogenesis within periprosthetic tissues of orthopaedic and dental origin.

Enhanced Chimeric Antigen Receptor T Cell Therapy through Co-Application of Synergistic Combination Partners.

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable response rates and revolutionized the treatment of patients suffering from defined hematological malignancies. However, many patients still do not respond to this therapy or relapse after an initial remission, underscoring the need for improved efficacy. Insufficient in vivo activity, persistence, trafficking, and tumor infiltration of CAR T cells, as well as antigen escape and treatment-associated adverse events, limit the therapeutic success.

A Spontaneous Model of Experimental Autoimmune Encephalomyelitis Provides Evidence of MOG-Specific B Cell Recruitment and Clonal Expansion.

The key role of B cells in the pathophysiology of multiple sclerosis (MS) is supported by the presence of oligoclonal bands in the cerebrospinal fluid, by the association of meningeal ectopic B cell follicles with demyelination, axonal loss and reduction of astrocytes, as well as by the high efficacy of B lymphocyte depletion in controlling inflammatory parameters of MS. Here, we use a spontaneous model of experimental autoimmune encephalomyelitis (EAE) to study the clonality of the B cell response targeting myelin oligodendrocyte glycoprotein (MOG). In particular, 94% of SJL/j mice expressing an I-A: MOG specific transgenic T cell receptor (TCR) spontaneously develop a chronic paralytic EAE between the age of 60-500 days.

Duodenal tropism of SARS-CoV-2 and clinical findings in critically ill COVID-19 patients.

Purpose: Duodenal involvement in COVID-19 is poorly studied. Aim was to describe clinical and histopathological characteristics of critically ill COVID-19 patients suffering from severe duodenitis that causes a significant bleeding and/or gastrointestinal dysmotility.

Methods: In 51 critically ill patients suffering from SARS-CoV-2 pneumonia, severe upper intestinal bleeding and/or gastric feeding intolerance were indications for upper gastrointestinal endoscopy.

Relationship Between Circadian Strain, Light Exposure, and Body Mass Index in Rural and Urban Quilombola Communities.

Industrialization has greatly changed human lifestyle; work and leisure activities have been moved indoors, and artificial light has been used to illuminate the night. As cyclic environmental cues such as light and feeding become weak and/or irregular, endogenous circadian systems are increasingly being disrupted. These disruptions are associated with metabolic dysfunction, possibly contributing to increased rates of overweight and obesity worldwide.

Efficacy, safety and quality-of-life data from patients with pre-treated metastatic colorectal cancer receiving trifluridine/tipiracil: results of the TALLISUR trial.

Introduction: Trifluridine/tipiracil (FTD/TPI) improved both overall and progression-free survival (OS, PFS) of patients with pre-treated metastatic colorectal cancer (mCRC) in the pivotal phase III RECOURSE trial. However, health-related quality of life (HRQoL) was not assessed directly. To this end and to generate post-authorisation data, the TALLISUR trial was conducted.

Twenty Years On: RECIST as a Biomarker of Response in Solid Tumours an EORTC Imaging Group - ESOI Joint Paper.

Response evaluation criteria in solid tumours (RECIST) v1.1 are currently the reference standard for evaluating efficacy of therapies in patients with solid tumours who are included in clinical trials, and they are widely used and accepted by regulatory agencies. This expert statement discusses the principles underlying RECIST, as well as their reproducibility and limitations.

Seventh BHD international symposium: recent scientific and clinical advancement.

The 7th Birt-Hogg-Dubé (BHD) International Symposium convened virtually in October 2021. The meeting attracted more than 200 participants internationally and highlighted recent findings in a variety of areas, including genetic insight and molecular understanding of BHD syndrome, structure and function of the tumor suppressor Folliculin (FLCN), therapeutic and clinical advances as well as patients' experiences living with this malady.

Are Specific Body Sites Prone for Wound Infection After Skin Surgery? A Systematic Review and Meta-Analysis.

Introduction: Identifying risk factors for wound infection may guide clinical practice for optimal use of perioperative antibiotic prophylaxis in dermatologic surgery.

Objective: To summarize the current evidence whether specific body sites have higher risks for surgical site infections (SSI).

Methods: The systematic literature search included MEDLINE, Embase, CENTRAL, and trial registers.

Riboflavin and Its Effect on Dentin Bond Strength: Considerations for Clinical Applicability-An In Vitro Study.

Bioactive collagen crosslinkers propose to render the dentin hybrid layer less perceptive to hydrolytic challenge. This study aims to evaluate whether bond strength of dental resin composite to dentin benefits from riboflavin (RB)-sensitized crosslinking when used in a clinically applicable protocol. A total of 300 human dentin specimens were prepared consistent with the requirements for a macro-shear bond test.

Transmission dynamics and successful control measures of SARS-CoV-2 in the mega-size city of Guangzhou, China.

The severe acute respiratory syndrome coronavirus 2 has caused a worldwide pandemic. Control measures differ among countries and have a varying degree of effectiveness, which requires assessment. To evaluate the effectiveness of public health interventions of the coronavirus disease 2019 (COVID-19) in Guangzhou by 3 periods according to interventions: January 7 to 22 (no intervention), January 23 to February 23 (implemented intensive interventions), and February 24 to May 17 (the normalization mode of COVID-19 prevention and control).

Neurofilament light chain serum levels correlate with the severity of neurotoxicity after CAR T-cell treatment.

Antitumor therapy with CD19-targeted chimeric antigen receptor (CAR) modified T cells is highly efficient. However, treatment is often complicated by a unique profile of unpredictable neurotoxic adverse effects of varying degrees known as immune effector cell-associated neurotoxicity syndrome (ICANS). We examined 96 patients receiving CAR T cells for refractory B-cell malignancies at 2 major CAR T-cell treatment centers to determine whether serum levels of neurofilament light chain (NfL), a marker of neuroaxonal injury, correlate with the severity of ICANS.

Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups.

Background: Special AT-rich sequence-binding protein 2 (SATB2) has emerged as an alternative immunohistochemical marker to CDX2 for colorectal differentiation. However, the distribution and prognostic relevance of SATB2 expression in colorectal carcinoma (CRC) have to be further elucidated.

Methods: SATB2 expression was analysed in 1039 CRCs and correlated with clinicopathological and morphological factors, CDX2 expression as well as survival parameters within the overall cohort and in clinicopathological subgroups.

KRAS signaling in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes.

Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients.

Background: The inflammatory response to results in variable degrees of lung pathology during active TB (ATB) with central involvement of neutrophils. Little is known about neutrophil-derived mediators and their role in disease severity at baseline and recovery upon TB treatment initiation.

Methods: 107 adults with confirmed pulmonary TB were categorised based on lung pathology at baseline and following successful therapy using chest X-ray scores (Ralph scores) and GeneXpert bacterial load (Ct values).

Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents.

Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8 T cells, albeit restricted production of neutralizing antibodies.

Novel Multimodal Management of Post-Partum Synchronous Metastatic Pulmonary EBV-Associated Lymphoepithelioma-Like Carcinoma (LELC)-A Case Report.

Primary Epstein-Barr-Virus (EBV)-associated pulmonary lymphoepithelioma-like carcinoma (LELC) is an aggressive rare cancer. Higher incidences have been observed in Asian sub-populations. Multimodal treatment paradigms have emerged as promising novel strategies in the management of advanced NSCLC.

Lipid metabolism in cancer progression and therapeutic strategies.

Dysregulated lipid metabolism represents an important metabolic alteration in cancer. Fatty acids, cholesterol, and phospholipid are the three most prevalent lipids that act as energy producers, signaling molecules, and source material for the biogenesis of cell membranes. The enhanced synthesis, storage, and uptake of lipids contribute to cancer progression.