Chemotherapy drives tertiary lymphoid structures that correlate with ICI-responsive TCF1+CD8+ T cells in metastatic ovarian cancer.

Purpose: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICIs) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication.

Experimental Design: We harnessed a variety of transcriptomic, spatial and functional assays to characterize the differential impact of neo-adjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to NACT-naïve HGSOC samples from 5 independent patient cohorts.

High incidence of occult familial cases amongst Czech patients with head and neck paragangliomas.

Introduction: Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors, which are mostly benign in nature. Amongst all genes, Succinate Dehydrogenase Subunit D () is the most commonly mutated in familial HNPGLs. In about 30% of HNPGLs, germline mutations in can also occur in the absence of positive family history, thus giving rise to "occult familial" cases.

Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities.

Purpose: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsufficiency.

Methods: Three individuals with intellectual disability and iris anomalies and truncating de novo PRR12 variants were described previously.

Otorhinolaryngology in the COVID-19 era: Are there significant differences between hospital-based and private practices?

Objectives: The COVID-19 disease has an incredible impact on both hospital-based and private practices in the field of otorhinolaryngology and head and neck surgery. Practical issues faced by both types of practices have not been well addressed in most studies. A national survey was conducted in April 2020 to identify the challenges faced by otorhinolaryngologists practicing in the Czech Republic.

Extremely wicked, shockingly evil and undoubtedly COVID-19: the silent serial killer.

Background: The SARS-COV-2 virus has more than just an infectious role to play in the society. The rapid spread has also led to significant personal, professional, financial and economic recession globally. Health care professionals are getting seriously compromised due to these issues.

Face to face with COVID-19: highlights of challenges encountered in various ENT practices across the Czech Republic (a national survey).

The SARS-CoV-2 virus causing the COVID-19 disease created considerable complications and disruptions due to it's pandemic spread. The nature of the disease left certain clinical specialties more vulnerable than others, causing serious problems with organization of care of patients. Most studies concentrated on protocols and strategies to control the situation and reduce further spread amongst medical fields.

Cancer Microenvironment: What Can We Learn from the Stem Cell Niche.

Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle-also known as the bulge region.

Glucocerebrosidase gene has an alternative upstream promoter, which has features and expression characteristic of housekeeping genes.

Database searches have shown that a part of glucocerebrosidase (GBA) transcripts may originate at an alternative upstream promoter (P2) located 2.6 kb upstream of the known (P1) GBA promoter. The putative alternative transcripts contained one or two extra exons (exon -2 or exons -2, -1, respectively), but the first ATG codon and predicted amino-acid sequence are the same as in the transcript from P1.

Glucosylceramide transfer from lysosomes--the missing link in molecular pathology of glucosylceramidase deficiency: a hypothesis based on existing data.

Gaucher disease (GD), deficiency of acid glucosylceramidase (GlcCer-ase) is characterized by deficient degradation of beta-glucosylceramide (GlcCer). It is well known that, in GD, the lysosomal accumulation of uncleaved GlcCer is limited to macrophages, which are gradually converted to storage cells with well known cytology--Gaucher cells (GCs). On the basis of previous studies of the disorder and of a comparison with other lysosomal enzymopathies affecting degradation of the GlcCer-based glycosphingolipid series, it is hypothesized that in other cell types (i.

Sequelae of storage in Fabry disease--pathology and comparison with other lysosomal storage diseases.

Aim: To evaluate the sequelae of the lysosomal storage of globotriaosylceramide (Gb3) in a series of patients with Fabry disease.

Methods: Biopsy and post-mortem samples from 12 patients with Fabry disease were examined microscopically, including, in some cases, immunohistochemistry and electron microscopy. Where possible, comparisons were made with other lysosomal storage disorders.

Advanced glycation end products in clinical nephrology.

As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis.

Mucolipidosis type II with evidence of a novel storage site.

In a case of infantile mucolipidosis type II (I-cell disease), storage was identified at autopsy in serous-type secretory cells in exocrine pancreas, in the tracheal and sublingual salivary glands and in the chief (zymogenic) cells of the gastric oxyntic glands, suggesting a systemic involvement of this type of secretory cells. The content of specific secretory granules was inversely proportional to the intensity of the storage process. The mucus-producing cells were not affected.

Incidence of neuronal perikaryal spheroids in neuronal ceroid lipofuscinoses (Batten disease).

The stored material in neuronal ceroid lipofuscinosis (NCL) undergoes, irrespective of the disease type, a uniform modification, altering profoundly its physical and histochemical properties. The process is accompanied by loss of immunodetectable epitopes of subunit c of mitochondrial ATP synthase (SCMAS) in the transformed storage material in NCL2 and NCL6 and of sphingolipid activator proteins (SAPs) A and D in NCL1, NCL2, and NCL6. It is restricted to certain subcortical brain nuclei, typically nucleus niger, dentatus, lentiformis, and thalamus.