Spatial transcriptomics in breast cancer reveals tumour microenvironment-driven drug responses and clonal therapeutic heterogeneity.

Breast cancer patients are categorized into three subtypes with distinct treatment approaches. Precision oncology has increased patient outcomes by targeting the specific molecular alterations of tumours, yet challenges remain. Treatment failure persists due to the coexistence of several malignant subpopulations with different drug sensitivities within the same tumour, a phenomenon known as intratumour heterogeneity (ITH).

PanDrugs2: prioritizing cancer therapies using integrated individual multi-omics data.

Genomics studies routinely confront researchers with long lists of tumor alterations detected in patients. Such lists are difficult to interpret since only a minority of the alterations are relevant biomarkers for diagnosis and for designing therapeutic strategies. PanDrugs is a methodology that facilitates the interpretation of tumor molecular alterations and guides the selection of personalized treatments.

RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein expression in more than 2,000 breast tumors (777 estrogen receptor-negative, ER ) from four independent cohorts. RANK protein expression was more frequent in ER tumors, where it associated with poor outcome and poor response to chemotherapy.

CALR-mutated cells are vulnerable to combined inhibition of the proteasome and the endoplasmic reticulum stress response.

Cancer is driven by somatic mutations that provide a fitness advantage. While targeted therapies often focus on the mutated gene or its direct downstream effectors, imbalances brought on by cell-state alterations may also confer unique vulnerabilities. In myeloproliferative neoplasms (MPN), somatic mutations in the calreticulin (CALR) gene are disease-initiating through aberrant binding of mutant CALR to the thrombopoietin receptor MPL and ligand-independent activation of JAK-STAT signaling.

Bioinformatics roadmap for therapy selection in cancer genomics.

Tumour heterogeneity is one of the main characteristics of cancer and can be categorised into inter- or intratumour heterogeneity. This heterogeneity has been revealed as one of the key causes of treatment failure and relapse. Precision oncology is an emerging field that seeks to design tailored treatments for each cancer patient according to epidemiological, clinical and omics data.

Whole-genome CRISPR screening identifies N-glycosylation as a genetic and therapeutic vulnerability in CALR-mutant MPNs.

Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPNs). Although the biological mechanism by which CALR mutations cause MPNs has been elucidated, there currently are no clonally selective therapies for CALR-mutant MPNs. To identify unique genetic dependencies in CALR-mutant MPNs, we performed a whole-genome clustered regularly interspaced short palindromic repeats (CRISPR) knockout depletion screen in mutant CALR-transformed hematopoietic cells.

Beyondcell: targeting cancer therapeutic heterogeneity in single-cell RNA-seq data.

We present Beyondcell, a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calculates an enrichment score in a collection of drug signatures, delineating therapeutic clusters (TCs) within cellular populations. Additionally, Beyondcell determines the therapeutic differences among cell populations and generates a prioritised sensitivity-based ranking in order to guide drug selection.

bollito: a flexible pipeline for comprehensive single-cell RNA-seq analyses.

Summary: bollito is an automated, flexible and parallelizable computational pipeline for the comprehensive analysis of single-cell RNA-seq data. Starting from FASTQ files or preprocessed expression matrices, bollito performs both basic and advanced tasks in single-cell analysis integrating >30 state-of-the-art tools. This includes quality control, read alignment, dimensionality reduction, clustering, cell-marker detection, differential expression, functional analysis, trajectory inference and RNA velocity.

Subfoveal choroidal thickness as a potential predictor of treatment response after intravitreal ranibizumab injections for polypoidal choroidal vasculopathy.

Objective: To evaluate the impact of subfoveal choroidal thickness (SFCT) and other clinical biomarkers in intravitreal anti-vascular endothelial growth factor response in treatment-naive Caucasian patients diagnosed with polypoidal choroidal vasculopathy (PCV/AT1).

Design: Cross-sectional study.

Participants: Treatment-naive patients diagnosed with PCV/AT1 recruited in a single centre from January 2013 to December 2020.

Spontaneous resolution of inflammatory epiretinal membrane: Case series and review of the literature.

Epiretinal membrane (ERM) represents a common complication of uveitis that may contribute independently to vision loss in patients with uveitis. Although spontaneous idiopathic ERM separation has been previously reported, to the best of our knowledge there are only two case reports in the scientific literature that depicts spontaneous regression of an inflammation-associated ERM. Spontaneous ERM separation is a rare but possible event, which occurs most often subsequent to posterior vitreous detachment.

Synergic effect of corneal hysteresis and central corneal thickness in the risk of early-stage primary open-angle glaucoma progression.

Purpose: To evaluate corneal hysteresis (CH), acquired with ocular response analyzer (ORA), as a risk factor for glaucoma progression in early-stage primary open-angle glaucoma (POAG).

Methods: In a historical cohort study, patients diagnosed in 2011 with early-stage POAG according to the Hodapp, Parrish and Anderson classification modified for Octopus perimetry and followed up until glaucomatous progression development; otherwise, observations were censored in October 2018. Cox regression was used to obtain hazard ratios (HR) to evaluate baseline variables (CH, central corneal thickness, gender, age IOP and glaucoma family history) as risk factors for perimetric glaucoma progression.

Delayed Onset of Retinal Embolism After Coronary Angioplasty.

Although rare, retinal artery cholesterol emboli (Hollenhorst plaques) post angioplasty can be a severe event that can cause irreversible visual disturbances, usually taking place during or following the procedure. However, as the number of procedures continues to increase, interventional radiologists or cardiologists who perform coronary catheterization should be cognizant of its possible delayed occurrence, as in the case presented herein.

Impact of ocular dominance on circumpapillary and macular retinal nerve fibre layer thickness and ganglion cell layer thickness in a healthy pediatric population.

Objective: This study was designed to evaluate potential differences in circumpapillary retinal nerve fibre layer (cpRNFL) thickness and segmented macular retinal layers between dominant and nondominant eyes on spectral-domain optical coherence tomography in a pediatric population.

Design: Cross-sectional study.

Participants: 89 healthy children attending a general pediatric clinic.

Reproducibility of macular retinal nerve fiber layer and ganglion cell layer thickness measurements in a healthy pediatric population.

Purpose: To evaluate the reproducibility of Spectralis spectral domain-OCT segmented ganglion cell layer (GCL) and macular retinal nerve fiber layer (mRNFL) measurements in a healthy children population.

Methods: An observational, cross-sectional study was carried out on 79 children to measure the intraobserver reproducibility and the repeatability between a novel and an experienced operator of the segmented macular GCL and mRNFL. Interobserver and intraobserver reproducibility were defined by the intraclass correlation coefficient (ICC) and coefficients of variation (COV).

Atypical perifoveal exudative vascular anomalous complex (PEVAC) with multifocal and bilateral presentation.

Purpose: To report an unusual case of multifocal and bilateral perifoveal exudative vascular anomalous complex (PEVAC) lesions in an otherwise healthy patient.

Observations: A 62-year-old male with complaints of long-term progressive blurred vision in both eyes. There was no history of diabetes, arterial hypertension or inflammatory disease.

In Silico Drug Prescription for Targeting Cancer Patient Heterogeneity and Prediction of Clinical Outcome.

In silico drug prescription tools for precision cancer medicine can match molecular alterations with tailored candidate treatments. These methodologies require large and well-annotated datasets to systematically evaluate their performance, but this is currently constrained by the lack of complete patient clinicopathological data. Moreover, in silico drug prescription performance could be improved by integrating additional tumour information layers like intra-tumour heterogeneity (ITH) which has been related to drug response and tumour progression.

Influence of mutation bias and hydrophobicity on the substitution rates and sequence entropies of protein evolution.

The number of amino acids that occupy a given protein site during evolution reflects the selective constraints operating on the site. This evolutionary variability is strongly influenced by the structural properties of the site in the native structure, and it is quantified either through sequence entropy or through substitution rates. However, while the sequence entropy only depends on the equilibrium frequencies of the amino acids, the substitution rate also depends on the exchangeability matrix that describes mutations in the mathematical model of the substitution process.

Diagnostic capacity of SD-OCT segmented ganglion cell complex versus retinal nerve fiber layer analysis for congenital glaucoma.

Purpose: To compare the diagnostic performance of circumpapillary retinal nerve fiber layer (cpRNFL) analysis versus segmented ganglion cell complex analysis both by spectral-domain optical coherence tomography (SD-OCT) in children with primary congenital glaucoma (PCG).

Methods: Participants were 40 children diagnosed with PCG and 60 healthy children. Ophthalmological data collected (for one eye per child) were cup-disc ratio (C/D) and axial length (AL).

[Prevalence and gravity of depression and anxiety in patients with obesity and type 2 diabetes: a study in the population of Tabasco, Mexico].

Aims: The aim of this study was to assess the prevalence of anxiety and depression in groups of obese and normal-weight individuals with type 2 diabetes. Also, to analyze the severity of depression in type 2 diabetics by taking into account the body mass index in people with this condition.

Methods: This study included 702 patients with type 2 diabetes, 236 with normal weight, and 231 with obesity.

Interferon-associated retinopathy in a patient with metastatic melanoma.

We present the unusual case of a 35 year-old woman with stage IV melanoma and widespread metastases, who was undergoing treatment with interferon alpha-2b and who presented with interferon-associated retinopathy. The patient, who had been taking interferon treatment for three months, complained of a sudden loss of visual acuity in the left eye. An ocular examination revealed multiple cotton wool spots along the retina and macular involvement.

Performance of the rebound, noncontact and Goldmann applanation tonometers in routine clinical practice.

Purpose: To compare rebound tonometry (RBT) and noncontact tonometry (NCT) using Goldmann applanation tonometry (GAT) as reference.

Methods: The study sample was comprised of 108 eyes of 108 subjects consecutively examined at a general ophthalmology clinic. The order of use of the three tonometers was randomized at the study outset.