The combined use of scRNA-seq and network propagation highlights key features of pan-cancer Tumor-Infiltrating T cells.

Improving the selectivity and effectiveness of drugs represents a crucial issue for future therapeutic developments in immuno-oncology. Traditional bulk transcriptomics faces limitations in this context for the early phase of target discovery as resulting gene expression levels represent the average measure from multiple cell populations. Alternatively, single cell RNA sequencing can dive into unique cell populations transcriptome, facilitating the identification of specific targets.

Microbiological Profiles of Patients with Spondylodiscitis.

Spondylodiscitis is a severe spinal infection that requires an effective antibiotic treatment. Therefore, we sought to analyse the causative pathogens from intraoperative specimen in patients with spondylodiscitis and a need for surgery. To this end, we performed a retrospective study of all patients with spondylodiscitis and a need for operative treatment admitted to our hospital between January 2020 and December 2022.

Panton-Valentine Leukocidin-Positive Staphylococcus aureus in Family and Pet Cat.

Continued detection of Panton-Valentine leukocidin-positive Staphylococcus aureus in samples from a family with severe repeated skin infections and their pet cat suggests transmission between the family and the cat. Decolonizing the pet led to successful elimination of the bacteria from the household. Clinicians should consider pet cats as possible reinfection sources.

Chagas Disease: Comparison of Therapy with Nifurtimox and Benznidazole in Indigenous Communities in Colombia.

: For indigenous people in Colombia, high infection rates with Chagas disease (CD) are known. : In 2018 and 2020, nine villages were screened for CD. CD-positive patients could enter a drug observed treatment.

Impaired Hepatic Very Low-Density Lipoprotein Secretion Promotes Tumorigenesis and Is Accelerated with Fabp1 Deletion.

Genetic polymorphisms that impair very low-density lipoprotein (VLDL) secretion are linked to hepatic steatosis, fibrosis, and hepatocellular cancer. Liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) impairs VLDL assembly, promoting hepatic steatosis and fibrosis, which are attenuated in Mttp-LKO X Fabp1-null [Fabp1/Mttp double knockout (DKO)] mice. The current study examined the impact of impaired VLDL secretion in Mttp-LKO mice on hepatocellular cancer incidence and progression in comparison to Fabp1/Mttp DKO mice.

Gastrointestinal Pathogens in Multi-Infected Individuals: A Cluster Analysis of Interaction.

Indigenous people live in remote areas of Colombia. Multiple infections with bacteria, protozoa and/or helminths are common, as well as colonization in various forms. This study focused on the question of whether and to what extent various pathogens interact with each other.

CHROMAgar™ LIN-R as an efficient screening tool to assess the prevalence of linezolid-resistant enterococci in German hospital patients-a multicentre study approach, 2021-2022.

Background: In recent years, an increasing number of linezolid-resistant enterococci (LRE) was recognized at the German National Reference Centre (NRC) for Enterococci. National guidelines on infection prevention recommend screening for LRE in epidemiologically linked hospital settings without referring to a reliable and rapid diagnostic method. Since 2020, CHROMAgar™ provide a chromogenic linezolid screening agar, LIN-R, suitable to simultaneously screen for linezolid-resistant staphylococci and enterococci.

Protocol to isolate RBP-mRNA complexes using RNA-CLIP and examine target mRNAs.

RNA-binding proteins (RBPs) regulate diverse functions by interacting with target transcripts. Here we present a protocol to isolate RBP-mRNA complexes using RNA-CLIP and examine target mRNAs in association with ribosomal populations. We describe steps to identify specific RBPs and RNA targets reflecting a variety of developmental, physiological, and pathological states.

RBM47 regulates intestinal injury and tumorigenesis by modifying proliferation, oxidative response, and inflammatory pathways.

RNA-binding protein 47 (RBM47) is required for embryonic endoderm development, but a role in adult intestine is unknown. We studied intestine-specific Rbm47-knockout mice (Rbm47-IKO) following intestinal injury and made crosses into ApcMin/+ mice to examine alterations in intestinal proliferation, response to injury, and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue.

Periprosthetic joint infection caused by kytococcus schroeteri: The first reported case and a review of the literature.

Oftentimes, Gram-positive cocci are the cause for periprosthetic joint infections (PJI). Most of these infections include bacteria such as Staphylococcus aureus, Staphylococcus epidermidis or other coagulase-negative staphylococci. We here present the first case of a PJI caused by Kytococcus schroeteri.

Microbiological Trends and Antibiotic Susceptibility Patterns in Patients with Periprosthetic Joint Infection of the Hip or Knee over 6 Years.

We sought to analyze trends of the causative pathogens and their antibiotic susceptibility patterns in patients with periprosthetic joint infections (PJI) of the hip and knee to get better insights and improve treatment. Retrospective evaluation of all consecutive patients with microbiological detection of a causative pathogen at a tertiary endoprothetic referral center between January 2016 and December 2021 in Germany was performed. Overall, 612 different microorganisms could be detected in 493 patients (hip: n = 293; knee: n = 200).

Microbiological Profiles of Patients with Periprosthetic Joint Infection of the Hip or Knee.

Periprosthetic joint infections (PJI) are one of the most devastating consequences after total joint arthroplasty. We sought to analyze the causative pathogens of patients with PJI to get better insights and improve treatment. We performed a retrospective study of all patients with PJI of the hip and knee with microbiological detection of a causative pathogen at a tertiary endoprothetic referral center between January 2016 and March 2021.

German Multicenter Study Analyzing Antimicrobial Activity of Ceftazidime-Avibactam of Clinical Meropenem-Resistant Isolates Using a Commercially Available Broth Microdilution Assay.

Multidrug resistance is an emerging healthcare issue, especially concerning Pseudomonas aeruginosa. In this multicenter study, P. aeruginosa isolates with resistance against meropenem detected by routine methods were collected and tested for carbapenemase production and susceptibility against ceftazidime-avibactam.

Comparison of Empiric Antibiotic Escalation Therapy with Vancomycin (VAN) versus Linezolid (LIN) in Patients with Febrile Neutropenia.

Background: In febrile neutropenia, either linezolid (LIN) or vancomycin (VAN) can be used if a gram-positive infection is suspected. Interestingly there is no literature in which both are compared in the setting of febrile neutropenia. Therefore, we provide here the results of a retrospective analysis of adding VAN versus LIN in patients with febrile neutropenia.

Liver-Specific Deletion of Mouse Tm6sf2 Promotes Steatosis, Fibrosis, and Hepatocellular Cancer.

Background And Aims: Human transmembrane 6 superfamily 2 (TM6SF2) variant rs58542926 is associated with NAFLD and HCC. However, conflicting reports in germline Tm6sf2 knockout mice suggest no change or decreased very low density lipoprotein (VLDL) secretion and either unchanged or increased hepatic steatosis, with no increased fibrosis. We generated liver-specific Tm6Sf2 knockout mice (Tm6 LKO) to study VLDL secretion and the impact on development and progression of NAFLD.

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer.

The RNA-binding protein Apobec1 complementation factor (A1CF) regulates posttranscriptional ApoB mRNA editing, but the range of RNA targets and the long-term effect of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf-transgenic (A1cf+/Tg), A1cf+/Tg Apobec1-/-, and A1cf-/- mice fed chow or high-fat/high-fructose diets using RNA-Seq, RNA CLIP-Seq, and tissue microarrays from human hepatocellular cancer (HCC). A1cf+/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution.

The Performance of a Dithiothreitol-Based Diagnostic System in Diagnosing Periprosthetic Joint Infection Compared to Sonication Fluid Cultures and Tissue Biopsies.

Purpose: The aim of this study was to evaluate the performance of a commercially available dithiothreitol (DTT) kit for routine use in diagnosing periprosthetic joint infections (PJIs) in comparison to conventional microbiological tissue specimens and sonication procedures in a maximal care hospital.

Methods: We applied the DTT system in 40 consecutive cases of revision arthroplasty (23 PJIs and 17 aseptic revisions), with an exchange or a removal of components. The hardware components were split between the DTT system and the conventional sonication procedure.

2-Hydroxypropyl-β-cyclodextrin is the active component in a triple combination formulation for treatment of Niemann-Pick C1 disease.

Niemann-Pick type C1 (NPC1) disease is a fatal neurovisceral disease for which there are no FDA approved treatments, though cyclodextrin (HPβCD) slows disease progression in preclinical models and in an early phase clinical trial. Our goal was to evaluate the mechanism of action of a previously described combination-therapy, Triple Combination Formulation (TCF) - comprised of the histone deacetylase inhibitor (HDACi) vorinostat/HPβCD/PEG - shown to prolong survival in Npc1 mice. In these studies, TCF's benefit was attributed to enhanced vorinostat pharmacokinetics (PK).

An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo.

The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube-based optical reporter that noninvasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission.