RNAscope

Lung transplantation for coronavirus disease 2019 associated severe acute respiratory distress syndrome

The purpose of this review is to analyze the most recent and relevant literature involving lung transplantation for coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS), the pathological mechanisms of lung injury, selection criteria and outcomes.Pathological analysis of lungs after COVID-19 ARDS has shown architectural distortion similar to that observed in explanted lungs from patients undergoing lung transplantation for end-stage lung diseases such as emphysema.

Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma (ATC) are highly aggressive malignant tumors with poor overall prognosis despite multimodal therapy. As ATC are extremely rare, no randomized controlled study has been published for metastatic disease. Thyrosine kinase inhibitors, especially lenvatinib and immune checkpoint inhibitors such as pembrolizumab, are emerging drugs for ATC. Few studies have reported the efficacity of pembrolizumab and lenvatinib association, resulting in its frequent off-label use.

CDON contributes to Hedgehog-dependent patterning and growth of the developing limb

Hedgehog (HH) signaling is a major driver of tissue patterning during embryonic development through the regulation of a multitude of cell behaviors including cell fate specification, proliferation, migration, and survival. HH ligands signal through the canonical receptor PTCH1 and three co-receptors, GAS1, CDON and BOC.

The PD-1/PD-L1 Pathway: A Perspective on Comparative Immuno-Oncology

The programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway mainly attracted attention in immuno-oncology, leading to the development of immune checkpoint therapy. It has, however, much broader importance for tissue physiology and pathology. It mediates basic processes of immune tolerance and tissue homeostasis. In addition, it is involved in the pathogenesis of chronic infectious diseases, autoimmunity, and cancer. It is also an important paradigm for comparative pathology as well as the "one health one medicine" concept.

TP53 positivity combined with high fibrinogen expression defines a subtype of oral squamous cell carcinoma with an unfavorable prognosis

The number of deaths due to oral squamous carcinoma (OSCC), a malignant tumor of the oral cavity, is on the increase. We examined fibrinogen (FIB) expression in patients with OSCC and developed novel immunoprofile classification methods that include FIB. The plasma FIB level in patients with OSCC was elevated compared with that in patients with non-tumor oral disease (non-T); using a cut-off point of 342 mg/dL, we found the area under the curve-receiver operating characteristic level for OSCC was 0.745.

Glutamatergic PPT neurons control wakefulness and locomotion via distinct axonal projections

The pedunculopontine tegmental nucleus (PPT) is implicated in many brain functions, ranging from sleep/wake control and locomotion, to reward mechanisms and learning. The PPT contains cholinergic, GABAergic and glutamatergic neurons with extensive ascending and descending axonal projections. Glutamatergic PPT (PPT vGlut2) neurons are thought to promote wakefulness, but the mechanisms through which this occurs are unknown.

CRISPR-Cas9-mediated functional dissection of the foxc1 genomic region in zebrafish identifies critical conserved cis-regulatory elements

FOXC1 encodes a forkhead-domain transcription factor associated with several ocular disorders. Correct FOXC1 dosage is critical to normal development, yet the mechanisms controlling its expression remain unknown. Together with FOXQ1 and FOXF2, FOXC1 is part of a cluster of FOX genes conserved in vertebrates. CRISPR-Cas9-mediated dissection of genomic sequences surrounding two zebrafish orthologs of FOXC1 was performed.

ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma

Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk.

Noradrenergic consolidation of social recognition memory is mediated by β-arrestin-biased signaling in the mouse prefrontal cortex

Social recognition memory (SRM) is critical for maintaining social relationships and increasing the survival rate. The medial prefrontal cortex (mPFC) is an important brain area associated with SRM storage. Norepinephrine (NE) release regulates mPFC neuronal intrinsic excitability and excitatory synaptic transmission, however, the roles of NE signaling in the circuitry of the locus coeruleus (LC) pathway to the mPFC during SRM storage are unknown. Here we found that LC-mPFC NE projections bidirectionally regulated SRM consolidation.

Towards a definition of microglia heterogeneity

High dimensional single-cell analysis such as single cell and single nucleus RNA sequencing (sc/snRNAseq) are currently being widely applied to explore microglia diversity. The use of sc/snRNAseq provides a powerful and unbiased approach to deconvolve heterogeneous cellular populations. However, sc/snRNAseq and analyses pipelines are designed to find heterogeneity. Indeed, cellular heterogeneity is often the most frequently reported finding.

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