Final Results for Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma.

Background: The 5-year results of this trial showed that adjuvant therapy with dabrafenib plus trametinib resulted in longer relapse-free survival and distant metastasis-free survival than placebo among patients with V600-mutated stage III melanoma. Longer-term data were needed, including data regarding overall survival.

Methods: We randomly assigned 870 patients with resected stage III melanoma with V600 mutations to receive 12 months of dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos.

Orthodontic treatment in children and adolescent patients with X-linked hypophosphatemia: A case-control study.

Objectives: X-linked hypophosphatemia (XLH) is a rare genetic disease that disturbs bone and teeth mineralization. It also affects craniofacial growth and patients with XLH often require orthodontic treatment. The aim of this study was to describe changes in the dental health of XLH children during orthodontic treatment compared with those in matched controls undergoing similar orthodontic procedures.

ForCenS-LGM: a dataset of planktonic foraminifera species assemblage composition for the Last Glacial Maximum.

Species assemblage composition of marine microfossils offers the possibility to investigate ecological and climatological change on time scales inaccessible using conventional observations. Planktonic foraminifera - calcareous zooplankton - have an excellent fossil record and are used extensively in palaeoecology and palaeoceanography. During the Last Glacial Maximum (LGM; 19,000 - 23,000 years ago), the climate was in a radically different state.

Effectiveness of topical sodium thiosulfate for ectopic calcifications and ossifications. Results of the CATSS-O study.

Introduction: Ectopic calcifications (ECs) and heterotopic ossifications (HOs) form in non-mineralized tissues, most often in subcutaneous and muscular areas. Local and systemic complications can cause severe disability. Systemic administration of sodium thiosulfate (STS) gives promising results but is difficult to use in clinical practice.

Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.

Background: Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis.

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures.

Background: In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment.

Materials And Methods: Organ doses were calculated for treatment of a diffuse midline glioma (50.

Multi-Morbidity and Risk of Breast Cancer among Women in the UK Biobank Cohort.

(Multi-)Morbidity shares common biological mechanisms or risk factors with breast cancer. This study aimed to investigate the association between the number of morbidities and patterns of morbidity and the risk of female breast cancer. Among 239,436 women (40-69 years) enrolled in the UK Biobank cohort who had no cancer history at baseline, we identified 35 self-reported chronic diseases at baseline.

The effect of thyroid dysfunction on breast cancer risk: an updated meta-analysis.

In a previous systematic review and meta-analysis of studies reporting associations between hyper-/hypothyroidism and breast cancer incidence published through 29 January 2019, we identified a higher risk with diagnosed hyperthyroidism compared to euthyroidism, but no association with diagnosed hypothyroidism. This 2-year updated meta-analysis aims to investigate the role of menopause in this association and the dose-response relationship with blood levels of thyroid-stimulating hormone (TSH) and thyroid hormones. After the exclusion of studies with only mortality follow-up, with thyroid dysfunction evaluated as a cancer biomarker or after prior breast cancer diagnosis, we reviewed 25 studies that were published up to 01 December 2021 and identified in MEDLINE, the COCHRANE library, Embase, or Web of Science; of these, 9 were included in the previous meta-analysis.

The role of stereotactic radiotherapy in addition to immunotherapy in the management of melanoma brain metastases: results of a systematic review.

Aim of this study was to systematically review the literature to assess efficacy and safety of stereotactic radiotherapy (SRT) in combination with immunotherapy for the treatment of melanoma brain metastases (MBM). The literature was searched using PubMed, Scopus, and Embase. Studies comparing SRT plus immunotherapy versus SRT or immunotherapy alone were deemed eligible for inclusion.

SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties.

Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells.

EBV+ tumors exploit tumor cell-intrinsic and -extrinsic mechanisms to produce regulatory T cell-recruiting chemokines CCL17 and CCL22.

The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV+ tumors employ multiple immune escape mechanisms, including the recruitment of immunosuppressive regulatory T cells (Treg). Here, we show some EBV+ tumor cells express high levels of the chemokines CCL17 and CCL22 both in vitro and in vivo and that this expression mirrors the expression levels of expression of the EBV LMP1 gene in vitro.

Hereditary Xerocytosis: Differential Behavior of PIEZO1 Mutations in the N-Terminal Extracellular Domain Between Red Blood Cells and HEK Cells.

Hereditary Xerocytosis, a rare hemolytic anemia, is due to gain of function mutations in PIEZO1, a non-selective cation channel activated by mechanical stress. How these PIEZO1 mutations impair channel function and alter red blood cell (RBC) physiology, is not completely understood. Here, we report the characterization of mutations in the N-terminal part of the protein (V598M, F681S and the double mutation G782S/R808Q), a part of the channel that was subject of many investigations to decipher its role in channel gating.

[Artificial intelligence, radiomics and pathomics to predict response and survival of patients treated with radiations].

Artificial intelligence approaches in medicine are more and more used and are extremely promising due to the growing number of data produced and the variety of data they allow to exploit. Thus, the computational analysis of medical images in particular, radiological (radiomics), or anatomopathological (pathomics), has shown many very interesting results for the prediction of the prognosis and the response of cancer patients. Radiotherapy is a discipline that particularly benefits from these new approaches based on computer science and imaging.

[Towards freedom to claim the right to die].

current evolution of society makes it possible to debate the issue of the end of life for people suffering from pathologies in which the vital prognosis is not involved; this concerns psychiatric situations in particular. This debate, which bears the seeds of a real desire to die as a personal choice, is likely to profoundly modify the doctor-patient relationship in the particular field of psychiatry.

Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib.

Purpose: Although patients with unresectable or metastatic melanoma can experience long-term survival with BRAF- and MEK-targeted agents or immune checkpoint inhibitors over 5 years, resistance develops in most patients. There is a distinct lack of pretherapeutic biomarkers to identify which patients are likely to benefit from each therapy type. Most research has focused on the predictive role of T cells in antitumor responses as opposed to B cells.

Thyroid dysfunction and breast cancer risk among women in the UK Biobank cohort.

This study aimed to evaluate the association between thyroid dysfunction and breast cancer risk. We included 239,436 females of the UK Biobank cohort. Information on thyroid dysfunction, personal and family medical history, medications, reproductive factors, lifestyle, and socioeconomic characteristics was retrieved from baseline self-reported data and hospital inpatient databases.

Heparin-induced thrombocytopenia: Construction of a pretest diagnostic score derived from the analysis of a prospective multinational database, with internal validation.

Background: Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays.

Objective: To develop a pretest score for HIT.

Design: Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.

Associations of Physical Activity Level and Variability With 6-Month Weight Change Among 26,935 Users of Connected Devices: Observational Real-Life Study.

Background: Physical activity (PA) is a modifiable lifestyle factor that can be targeted to increase energy expenditure and promote weight loss. However, the amount of PA required for weight loss remains inconsistent. Wearable activity trackers constitute a valuable opportunity to obtain objective measurements of PA and study large populations in real-life settings.

Measuring Topological Invariants in a Polaritonic Analog of Graphene.

Topological materials rely on engineering global properties of their bulk energy bands called topological invariants. These invariants, usually defined over the entire Brillouin zone, are related to the existence of protected edge states. However, for an important class of Hamiltonians corresponding to 2D lattices with time-reversal and chiral symmetry (e.