Comprehensive analysis and ACMG-based classification of CHEK2 variants in hereditary cancer patients.

CHEK2 variants are associated with intermediate breast cancer risk, among other cancers. We aimed to comprehensively describe CHEK2 variants in a Spanish hereditary cancer (HC) cohort and adjust the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for their classification. First, three CHEK2 frequent variants were screened in a retrospective Hereditary Breast and Ovarian Cancer cohort of 516 patients.

Netting and pan traps fail to identify the pollinator guild of an agricultural crop.

Pollinator decline is expected to cause significant reductions in food production and plant reproduction. Quantifying the impact of pollinator decline on food production requires survey methods that can identify insect and bee species responsible for pollination of specific crops. To address this issue, we compared the effectiveness of two survey methods, netting and pan traps, at capturing the pollinators of alfalfa, Medicago sativa.

A perfect storm and patient-provider breakdown in communication: two mechanisms underlying practice gaps in cancer-related fatigue guidelines implementation.

Purpose: Cancer-related fatigue (CRF) is a debilitating symptom experienced by many cancer patients. Although guidelines provide evidence-based recommendations for screening, assessing, and managing CRF, there is limited evidence of their implementation in practice. This study aimed to explore patients', healthcare providers' (HCPs), community support providers' (CSPs) experiences and opinions on CRF guidelines and the underlying causes of CRF treatment gaps following the Knowledge-to-Action model.

Role of POLE and POLD1 in familial cancer.

Purpose: Germline pathogenic variants in the exonuclease domain (ED) of polymerases POLE and POLD1 predispose to adenomatous polyps, colorectal cancer (CRC), endometrial tumors, and other malignancies, and exhibit increased mutation rate and highly specific associated mutational signatures. The tumor spectrum and prevalence of POLE and POLD1 variants in hereditary cancer are evaluated in this study.

Methods: POLE and POLD1 were sequenced in 2813 unrelated probands referred for genetic counseling (2309 hereditary cancer patients subjected to a multigene panel, and 504 patients selected based on phenotypic characteristics).

Thrombin generation abnormalities in Quebec platelet disorder.

Introduction: Calibrated automated thrombograms (CAT) with platelet-poor (PPP) and platelet-rich plasma (PRP) have provided useful insights on bleeding disorders. We used CAT to assess thrombin generation (TG) in Quebec platelet disorder (QPD)-a bleeding disorder caused by a PLAU duplication mutation that increases platelet (but not plasma) urokinase plasminogen activator (uPA), leading to intraplatelet (but not systemic) plasmin generation that degrades α-granule proteins and causes platelet (but not plasma) factor V (FV) deficiency.

Methods: Calibrated automated thrombograms was used to test QPD (n = 7) and control (n = 22) PPP and PRP, with or without added tranexamic acid (TXA).

Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients.

The SARS-Cov-2 pandemic significantly impacted on oncology practice across the globe. There is uncertainty as to the contribution of patients' demographics and oncological features on severity and mortality from Covid-19 and little guidance as to the role of anti-cancer and anti-Covid-19 therapy in this population. In a multi-center study of 890 cancer patients with confirmed Covid-19 we demonstrated a worsening gradient of mortality from breast cancer to haematological malignancies and showed that male gender, older age, and number of co-morbidities identifies a subset of patients with significantly worse mortality rates from Covid-19.

Study protocol of the Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial: a two-arm, two-centre randomized controlled trial.

Background: Up to 75% of women diagnosed with breast cancer report chemotherapy-related cognitive changes (CRCC) during treatment, including decreased memory, attention, and processing speed. Though CRCC negatively impacts everyday functioning and reduces overall quality of life in women diagnosed with breast cancer, effective interventions to prevent and/or manage CRCC are elusive. Consequently, women seldom receive advice on how to prevent or manage CRCC.

The association between REM sleep and decision-making: Supporting evidences.

Studies suggest that REM sleep is important for the maintenance of prefrontal cortex functioning. Therefore, reducing REM sleep may have an impact on cognitive functions such as impulse control and decision-making processes. This study examined the association between impulsiveness and sensation seeking personality traits, REM sleep and performance on a decision-making computer task following a habitual night of sleep and a partial sleep deprivation (PSD) condition with advanced wake-up time.

Bleeding risks for uncharacterized platelet function disorders.

Background: The bleeding risks for nonsyndromic platelet function disorders (PFDs) that impair aggregation responses and/or cause dense granule deficiency (DGD) are uncertain.

Objectives: Our goal was to quantify bleeding risks for a cohort of consecutive cases with uncharacterized PFD.

Methods: Sequential cases with uncharacterized PFDs that had reduced maximal aggregation (MA) with multiple agonists and/or nonsyndromic DGD were invited to participate along with additional family members to reduce bias.

Presenting Features and Early Mortality from SARS-CoV-2 Infection in Cancer Patients during the Initial Stage of the COVID-19 Pandemic in Europe.

We describe the outcomes in cancer patients during the initial outbreak of the COVID-19 in Europe from the retrospective, multi-center observational OnCovid study. We identified 204 cancer patients from eight centers in the United Kingdom, Italy, and Spain aged > 18 (mean = 69) and diagnosed with COVID-19 between February 26th and April 1st, 2020. A total of 127 (62%) were male, 184 (91%) had a diagnosis of solid malignancy, and 103 (51%) had non-metastatic disease.

Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals.

The causal mechanism for cancer predisposition in Lynch-like syndrome (LLS) remains unknown. Our aim was to elucidate the constitutional basis of mismatch repair (MMR) deficiency in LLS patients throughout a comprehensive (epi)genetic analysis. One hundred and fifteen LLS patients harboring MMR-deficient tumors and no germline MMR mutations were included.

Immune Cell Associations with Cancer Risk.

Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in immune and/or stromal cell contents in the corresponding tissue. Predicted target genes show expression and regulatory associations with immune features.

Earlier onset of flowering and increased reproductive allocation of an annual invasive plant in the north of its novel range.

Background And Aims: It remains unclear whether invasive species can maintain both high biomass and reproductive output across their invaded range. Along latitudinal gradients, allocation theory predicts that faster flowering onset at high latitudes results in maturation at smaller size and thus reduced reproductive output. For annual invasive plants, more favourable environmental conditions at low latitudes probably result in stronger competition of co-occurring species, potentially driving selection for higher investment in vegetative biomass, while harsher climatic conditions and associated reproductive uncertainty at higher latitudes could reduce selection for vegetative biomass and increased selection for high reproductive investment (stress-gradient hypothesis).

Evaluation of CNV detection tools for NGS panel data in genetic diagnostics.

Although germline copy-number variants (CNVs) are the genetic cause of multiple hereditary diseases, detecting them from targeted next-generation sequencing data (NGS) remains a challenge. Existing tools perform well for large CNVs but struggle with single and multi-exon alterations. The aim of this work is to evaluate CNV calling tools working on gene panel NGS data and their suitability as a screening step before orthogonal confirmation in genetic diagnostics strategies.

Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients.

COVID-19, the illness caused by infection with the novel coronavirus SARS-CoV-2, is a rapidly spreading global pandemic in urgent need of effective treatments. Here we present a comprehensive examination of the host- and virus-targeted functions of the flavonolignan silibinin, a potential drug candidate against COVID-19/SARS-CoV-2. As a direct inhibitor of STAT3-a master checkpoint regulator of inflammatory cytokine signaling and immune response-silibinin might be expected to phenotypically integrate the mechanisms of action of IL-6-targeted monoclonal antibodies and pan-JAK1/2 inhibitors to limit the cytokine storm and T-cell lymphopenia in the clinical setting of severe COVID-19.

Translating guidelines to practice: a training session about cancer-related fatigue.

Background: Cancer-related fatigue (crf) is the highest unmet need in cancer survivors. The Canadian Association of Psychosocial Oncology (capo) has developed guidelines for screening, assessment, and intervention in crf; however, those guidelines are not consistently applied in practice because of patient, health care provider (hcp), and systemic barriers. Notably, previous studies have identified a lack of knowledge of crf guidelines as an impediment to implementation.

An investigation into socio-demographic-, health-, and cancer-related factors associated with cortisol and C-reactive protein levels in breast cancer survivors: a longitudinal study.

Background: Breast cancer survivors (BCS) may exhibit dysregulated patterns of cortisol and C-reactive protein (CRP). The aims of this study were to describe BCS' cortisol and CRP levels over a 1-year period after treatment, and assess how levels relate to socio-demographic- (age, education level, marital status), health- (body mass index [BMI] category, menopausal status), and cancer-related factors (cancer stage, chemotherapy exposure, time since diagnosis).

Methods: Participants (N = 201) provided data at 3 months post-treatment (T1) and again 3, 6, 9, and 12 months later (T2-T5).

Forest microclimate dynamics drive plant responses to warming.

Climate warming is causing a shift in biological communities in favor of warm-affinity species (i.e., thermophilization).

Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors.

Mitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. How genomic instability influences the metabolic capacity of cancer cells is nevertheless poorly understood. Here, we show that homologous recombination-defective (HRD) cancers rely on oxidative metabolism to supply NAD and ATP for poly(ADP-ribose) polymerase (PARP)-dependent DNA repair mechanisms.

Health beliefs and engagement in moderate-to-vigorous-intensity physical activity among cancer survivors: a cross-sectional study.

Purpose: Moderate-to-vigorous-intensity physical activity (PA) can alleviate many adverse side effects and symptoms caused by cancer treatments; yet, most cancer survivors are insufficiently active. Evidence shows that theory-based PA behavior change interventions are more effective than non-theory-based interventions; thus, it is necessary to ascertain modifiable theoretical factors associated with moderate-to-vigorous-intensity PA among cancer survivors. Drawing on the health belief model (HBM), the associations between moderate-to-vigorous-intensity PA and (1) perceived susceptibility to cancer recurrence and health problems, (2) perceived severity of cancer recurrence and health problems, (3) perceived benefits of PA for reducing risk of cancer recurrence and health problems, (4) perceived barriers to PA, and (5) PA barrier self-efficacy among cancer survivors were examined.

Primary breast cancer and health related quality of life in Spanish women: The EpiGEICAM case-control study.

This study evaluates the impact of breast cancer (BC) in health related quality of life (HRQL) and in psychological distress (PD) during the initial phases of the disease and looks for contributing factors. A multicentric case-control study, EpiGEICAM, was carried out. Incident BC cases and age- and residence- matched controls were included.

Weight cycling is associated with adverse cardiometabolic markers in a cross-sectional representative US sample.

Background: Whether weight cycling (repeated weight loss and regain) is associated with cardiometabolic health is unclear. Study objective was to examine whether weight cycling since young adulthood (ie, 25 years of age) was associated with cardiometabolic markers.

Methods: Data from a nationally representative cross-sectional US sample (National Health and Nutrition Examination Survey, 1999-2014) were used.

Association of premenopausal risk-reducing salpingo-oophorectomy with breast cancer risk in BRCA1/2 mutation carriers: Maximising bias-reduction.

Background: Whether risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers reduces the breast cancer (BC) risk is conflicting, potentially due to methodological issues of prior analysis. We analysed the association between premenopausal RRSO and BC risk in BRCA1/2 carriers after adjusting for potential biases.

Methods: We analysed data from 444 BRCA1 and 409 BRCA2 carriers under age 51 with no cancer prior to genetic testing or during first 6 months of surveillance (to avoid cancer-induced testing bias and prevalent-cancer bias).