α-tubulin detyrosination fine-tunes kinetochore-microtubule attachments.

Post-translational cycles of α-tubulin detyrosination and tyrosination generate microtubule diversity, the cellular functions of which remain largely unknown. Here we show that α-tubulin detyrosination regulates kinetochore-microtubule attachments to ensure normal chromosome oscillations and timely anaphase onset during mitosis. Remarkably, detyrosinated α-tubulin levels near kinetochore microtubule plus-ends depend on the direction of chromosome motion during metaphase.

Easy to use tools for retrieving non-published data from clinically relevant subgroups.

Published trials sometimes report data for the overall population and selected subgroups, but not for the remaining population. Shenoy reports two methods able to extract data from the remaining subgroup using data for the overall population and a given subgroup.

Outpatient Palliative Care Program: Impact on Home Death Rate in Brazil.

While the positive impact of early palliative care on the quality of life of cancer patients is well established, there is a noticeable research gap in developing countries. This study sought to determine the impact of an outpatient palliative care (OPC) program on the location of death among patients in Brazil. This was a retrospective study including patients with cancer who died between January 2022 and December 2022 in 32 private cancer centers in Brazil.

Pediatric Asthma Therapy Assessment Questionnaire for the Brazilian population: Cross-cultural adaptation and measurement properties.

Objective: To cross-culturally adapt the Pediatric Asthma Therapy Assessment Questionnaire (ATAQ) into Brazilian Portuguese and analyze its measurement properties.

Methods: This exploratory methodological study included eight experts and 30 caregivers in the translation and cross-cultural adaptation steps. Thereafter, 118 caregivers of pediatric patients with asthma aged between 5 and 17 years were involved in the analysis of measurement properties.

Association of G12C Status with Age at Onset of Metastatic Colorectal Cancer.

The association of age at the onset of CRC and the prevalence of a G12C mutation is unclear. A retrospective, multicenter study evaluating metastatic CRC patients from January 2019 to July 2023, treated at the Oncoclinicas units and tested for tissue based / and mutations in a centralized genomics lab. A mismatch repair (MMR) status was retrieved from different labs and electronic medical records, as were patient demographics (age, gender) and tumor sidedness.

Claudin 18.2 as a New Biomarker in Gastric Cancer-What Should We Know?

Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive.

Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure.

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer-related mortality, and it is expected to play an even bigger part in cancer burden in the years to come. Despite concerted efforts from scientists and physicians, patients have experienced little improvement in survival over the past decades, possibly because of the non-specific nature of the tested treatment modalities. Recently, the discovery of potentially targetable molecular alterations has paved the way for the personalized treatment of PDAC.

Accuracy of ultrasound and visual inspection in antral follicular count in crossbred Holstein cows raised under grazing systems at high altitude.

The objective of this research was to investigate the diagnostic accuracy of post-mortem ultrasound in antral follicle count (AFC) determination and compare it with visual AFC in grazing crossbred Holstein cows, at high altitude in Ecuador. Pre-mortem blood from 80 cows was collected, and AFC and ovarian characteristics were analysed post-mortem by ultrasound and visual techniques. AFC counts were stratified as high, medium or low by terciles.

PD-L1 testing in advanced gastric cancer-what physicians who treat this disease must know-a literature review.

Background And Objective: Immune checkpoint inhibition has shed light on a new era in cancer therapy, and randomized clinical trials have demonstrated that a meaningful portion of the overall population of metastatic gastric cancer (GC) patients may derive clinical benefit from immunotherapy, which raises the relevance in identifying predictive biomarkers. Programmed cell death-ligand 1 (PD-L1) expression has demonstrated a significant association between level of expression and the magnitude of benefit derived from immune checkpoint inhibition in GC. Nevertheless, this biomarker shows several pitfalls that must be considered in the therapeutic decision to incorporate immune checkpoint inhibition as the standard of care of GC, such as spatial and temporal heterogeneity, interobserver variability, immunohistochemistry (IHC) assay, and influence by chemotherapy or radiation therapy.

Barriers to and facilitators of populational adherence to prevention and control measures of COVID-19 and other respiratory infectious diseases: a qualitative evidence synthesis.

Aims: To summarise the evidence on barriers to and facilitators of population adherence to prevention and control measures for coronavirus disease 2019 (COVID-19) and other respiratory infectious diseases.

Methods: A qualitative synthesis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and the Cochrane Effective Practice and Organization of Care: Qualitative Evidence Synthesis. We performed an electronic search on MEDLINE, Embase and PsycINFO from their inception to March 2023.

Sensitive, High-Throughput HLA-I and HLA-II Immunopeptidomics Using Parallel Accumulation-Serial Fragmentation Mass Spectrometry.

Comprehensive and in-depth identification of the human leukocyte antigen class I (HLA-I) and class II (HLA-II) tumor immunopeptidome can inform the development of cancer immunotherapies. Mass spectrometry (MS) is a powerful technology for direct identification of HLA peptides from patient-derived tumor samples or cell lines. However, achieving sufficient coverage to detect rare and clinically relevant antigens requires highly sensitive MS-based acquisition methods and large amounts of sample.

Minimal Residual Disease in Colorectal Cancer: Are We Finding the Needle in a Haystack?

Despite significant advances in the surgical and systemic therapy of colorectal cancer (CRC) in recent decades, recurrence rates remain high. Apart from microsatellite instability status, the decision to offer adjuvant chemotherapy to patients with CRC is solely based on clinicopathologic factors, which offer an inaccurate risk stratification of patients who derive benefit from adjuvant therapy. Owing to the recent improvements of molecular techniques, it has been possible to detect small allelic fractions of circulating tumor DNA (ctDNA), and therefore, to identify patients with minimal residual disease (MRD) after curative-intent therapies.

Understanding the Consequences of Moment-by-Moment Fluctuations in Mood and Social Experience for Paranoid Ideation in Psychotic Disorders.

Among individuals with psychotic disorders, paranoid ideation is common and associated with increased impairment, decreased quality of life, and a more pessimistic prognosis. Although accumulating research indicates negative affect is a key precipitant of paranoid ideation, the possible protective role of positive affect has not been examined. Further, despite the interpersonal nature of paranoid ideation, there are limited and inconsistent findings regarding how social context, perceptions, and motivation influence paranoid ideation in real-world contexts.

Calcineurin dephosphorylates topoisomerase IIβ and regulates the formation of neuronal-activity-induced DNA breaks.

Neuronal activity induces topoisomerase IIβ (Top2B) to generate DNA double-strand breaks (DSBs) within the promoters of neuronal early response genes (ERGs) and facilitate their transcription, and yet, the mechanisms that control Top2B-mediated DSB formation are unknown. Here, we report that stimulus-dependent calcium influx through NMDA receptors activates the phosphatase calcineurin to dephosphorylate Top2B at residues S1509 and S1511, which stimulates its DNA cleavage activity and induces it to form DSBs. Exposing mice to a fear conditioning paradigm also triggers Top2B dephosphorylation at S1509 and S1511 in the hippocampus, indicating that calcineurin also regulates Top2B-mediated DSB formation following physiological neuronal activity.

Biomarkers in Anal Cancer: Current Status in Diagnosis, Disease Progression and Therapeutic Strategies.

Squamous cell carcinoma of the anal canal (SCCA) is a rare neoplasm, but with rising incidence rates in the past few decades; it is etiologically linked with the human papillomavirus (HPV) infection and is especially prevalent in immunocompromised patients, mainly those infected with HIV. Fluoropyrimidine-based chemoradiotherapy remains the cornerstone of the treatment of non-metastatic disease, but the locally advanced disease still presents high rates of disease recurrence and systemic therapy of SCCA is an unmet clinical need. Despite sharing common molecular aspects with other HPV-related malignancies, such as cervical and head and neck cancers, SCCA presents specific epigenomic, genomic, and transcriptomic abnormalities, which suggest that genome-guided personalized therapies should be specifically designed for this disease.

Vitamin D and colorectal cancer - A practical review of the literature.

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States and the second cause worldwide. Its incidence rates have been decreasing in the overall population in the US in the past few decades, but with increasing rates in the population younger than 50 years old. Environmental factors are supposed to be involved in the development of the disease, with strong evidence favoring an influence of the diet and lifestyle.

Biologics in rectal cancer.

Introduction: Despite the use of multimodality therapy, locally advanced rectal cancer (LARC) still presents high rates of disease recurrence. Fluoropyrimidine-based chemotherapy concurrently with radiation therapy (RT) remains the cornerstone of neoadjuvant therapy of LARC, and novel therapies are urgently needed in order to improve the clinical outcomes.

Areas Covered: We aim to summarize data from completed and ongoing clinical trials addressing the role of biological therapies, including monoclonal antibodies, immune checkpoint inhibitors (ICIs), antibody-drug conjugates, bispecific antibodies, and gene therapies in the systemic therapy of rectal cancer.

The Role of Immunotherapy in the Treatment of Anal Cancer and Future Strategies.

Despite being markedly sensitive to chemoradiotherapy, patients with locally advanced (T3-4 and/or node-positive) squamous cell carcinoma of the anal canal (SCCA) still present high rates of disease recurrence, which is characterized by meaningful morbidity and mortality. Abdominoperineal resection as salvage surgery may be considered for patients with local recurrence, but with an important negative impact in the quality of life. Systemic therapy of advanced SCCA is an unmet clinical need.

Anal Cancer: Emerging Standards in a Rare Disease.

The social stigma surrounding an anal cancer diagnosis has traditionally prevented open discussions about this disease. However, as recent treatment options and an increasing rate of diagnoses are made worldwide, awareness is growing. In the United States alone, 9,090 individuals were expected to be diagnosed with anal cancer in 2021.

Pulmonary Inflammatory Response in Lethal COVID-19 Reveals Potential Therapeutic Targets and Drugs in Phases III/IV Clinical Trials.

It is imperative to identify drugs that allow treating symptoms of severe COVID-19. Respiratory failure is the main cause of death in severe COVID-19 patients, and the host inflammatory response at the lungs remains poorly understood. Therefore, we retrieved data from post-mortem lungs from COVID-19 patients and performed in-depth analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, and shortest pathways to physiological phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials.

Risk of Cancer in Inflammatory Bowel Disease and Pitfalls in Oncologic Therapy.

Background: Inflammatory bowel disease (IBD), represented by ulcerative colitis and Crohn's disease, is an idiopathic condition caused by a dysregulated immune response to host intestinal microflora, leading to chronic relapsing intestinal inflammation. Individuals with IBD are more prone to die from several diseases, including cancer.

Methods: An extensive search was conducted of PubMed using the following medical subject heading-"inflammatory bowel disease" OR "Crohn's disease" OR "ulcerative colitis" AND "cancer.

A comprehensive framework for early-onset colorectal cancer research.

Sporadic colorectal cancer has traditionally been viewed as a malignancy of older individuals. However, as the global prevalence of the disease diagnosed in younger individuals (<50 years) is expected to increase within the next decade, greater recognition is now being given to early-onset colorectal cancer. The cause of the predicted rise in prevalence is largely unknown and probably multifactorial.

Can the Synergic Contribution of Multigenic Variants Explain the Clinical and Cellular Phenotypes of a Neurodevelopmental Disorder?

We describe an infant female with a syndromic neurodevelopmental clinical phenotype and increased chromosome instability as cellular phenotype. Genotype characterization revealed heterozygous variants in genes directly or indirectly linked to DNA repair: a de novo X-linked pathogenic variant, a paternally inherited pathogenic variant and a maternally inherited variant of uncertain significance. The full spectrum of the phenotype cannot be explained by any of the heterozygous variants on their own; thus, a synergic contribution is proposed.