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Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients with ERBB2-Positive Breast Cancer : A Phase 2 Randomized Clinical Trial

Importance: Trastuzumab emtansine (T-DM1) is presently approved for treatment of advanced breast cancer and after incomplete response to neoadjuvant therapy, but the potential of T-DM1 as monotherapy is so far unknown. Objective: To assess pathologic complete response (pCR) to standard neoadjuvant therapy of combination docetaxel, trastuzumab, and pertuzumab (DTP) vs T-DM1 monotherapy in patients

Glucagon Counter-Regulation to Hypoglycemia During Incretin-Based Therapy

Incretin-based therapy is associated with low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) possibly due to its glucose-dependency in stimulating insulin secretion and a sustained glucagon response during hypoglycemia. This is of special relevance when it is combined with insulin or given to elderly patients since both insulin therapy and high age are associated with impaired glucagon co

Human Leukocyte Antigen-Based Risk Stratification in Heart Transplant Recipients-Implications for Targeted Surveillance

Background Human leukocyte antigen (HLA) matching isn't routinely performed in heart transplantation. Novel allograft perfusion methods may make HLA matching feasible. The purpose of this study is to reexamine whether HLA mismatch may be used in risk stratification to improve outcomes in heart transplantation. Methods and Results We analyzed 34 681 recipients undergoing heart transplantation betwe

Most gene fusions in cancer are stochastic events

Cancer-associated gene fusions resulting in chimeric proteins or aberrant expression of one or both partner genes are pathogenetically and clinically important in several hematologic malignancies and solid tumors. Since the advent of different types of massively parallel sequencing (MPS), the number of identified gene fusions has increased dramatically, prompting the question whether they all have

Older people's occupations. A life with and without work. : A life with and without work

Introduction: The demographic changes with population ageing and a rapidly growing share of very old peoplewill put an increasing pressure on the health and social care system. In order to both restrict early retirement and force people to extend their working life reforms are changing pension systems in many European countries. Besides that older people have to extend their working life it is imp

Discriminative accuracy of [18F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders

IMPORTANCE The positron emission tomography (PET) tracer [18F]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear. OBJECTIVE To examine the discriminative accuracy of [18F]flortaucipir for AD vs non-AD neurodegenerative disorders. DESIGN, SETTING, AND PARTICIPANTS In this cross-

Endogenous expression mapping of malignant melanoma by mass spectrometry imaging

BACKGROUND: Currently, only a limited number of molecular biomarkers for malignant melanoma exist. This is the case for both diagnosing the disease, staging, and efficiently measuring the response to therapy by tracing the progression of disease development and drug impact. There is a great need to identify novel landmarks of disease progression and alterations.METHODS: Matrix-assisted laser desor

Cardiovascular organ damage in type 2 diabetes mellitus : The role of lipids and inflammation

Background: The relationship between dyslipidemia, inflammation and CV organ damage in type 2 diabetes mellitus (T2DM) is complex. Insulin resistance and inflammatory cytokines interleukins (ILs) increase plasma triglycerides (TG). ILs also up-regulate expression of matrix-metalloproteinases (MMPs) that, together with TG, decrease high density lipoprotein cholesterol (HDL) levels. High TG, low HDL

Abnormal cerebral hemodynamics and blood-brain barrier permeability detected with perfusion MRI in systemic lupus erythematosus patients

Objective: Dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) has previously shown alterations in cerebral perfusion in patients with systemic lupus erythematosus (SLE). However, the results have been inconsistent, in particular regarding neuropsychiatric (NP) SLE. Thus, we investigated perfusion-based measures in different brain regions in SLE patients with and without NP invo

Incidence of pre-eclampsia : effect of deprivation

Objectives: To examine the relationship between the English index of multiple deprivation (IMD) and the incidence of pre-eclampsia (PE), evaluate the distribution of IMD in a cohort of ethnically diverse pregnant women in South East England and assess whether IMD improves the prediction of PE compared with that provided by the ‘history-only’ competing-risks model (based on maternal characteristics

Towards sustainable plastics : Microbial production of aromatic and aliphatic building blocks from biobased feedstock and plastic hydrolysate

The current plastic system is unsustainable and needs to change. Plastics are mainly produced from fossil feedstock, contributing to greenhouse gas emissions, and low rate of post-consumer recycling results in pollution on land and in oceans with high ecological impact, and huge loss of valuable material. There is an urgent need to find solutions for shifting the raw material base to renewable res

Use of flutemetamol F18-labeled positron emission tomography and other biomarkers to assess risk of clinical progression in patients with amnestic mild cognitive impairment

Importance: Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessmen

Associations and gastrointestinal symptoms in women with endometriosis in comparison to women with irritable bowel syndrome : a study based on a population cohort

Background: Endometriosis and irritable bowel syndrome (IBS) have similar symptoms, pathogenesis, and risk factors. These diagnoses often coexist and are frequently misdiagnosed leading to diagnostic delays. This study of a population-based cohort aimed to investigate associations relating to endometriosis and IBS and to compare gastrointestinal symptoms between endometriosis and IBS. Method: The

Normalization of puberty and adult height in girls with Turner syndrome : results of the Swedish Growth Hormone trials initiating transition into adulthood

Objective: To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities. Methods: National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3–16 years at GH start during year 1987–1998

Atrial Fibrillation and Clonal Hematopoiesis in TET2 and ASXL1

Importance: Clonal hematopoiesis of indeterminate potential (CHIP) may contribute to the risk of atrial fibrillation (AF) through its association with inflammation and cardiac remodeling. Objective: To determine whether CHIP was associated with AF, inflammatory and cardiac biomarkers, and cardiac structural changes. Design, Setting, and Participants: This was a population-based, prospective cohort

Adverse pregnancy outcomes and long term risk of ischemic heart disease in mothers : national cohort and co-sibling study

Objective: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers. Design: National cohort study. Setting: Sweden. Participants: All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015. Main outcome measures: The main outcome measure was incidence of ischemic heart disease from delivery to 2018, iden

Large Eddy Simulation of a model jet-engine swirl-stabilized flame using sustainable aviation fuels

Sustainable Aviation Fuels (SAF) typically exhibit a composition that differs significantly from conventional jet fuels. These variations in chemical makeup influence the thermophysical and reactive properties of these propellants. In this study, Finite-Rate Chemistry (FRC) Large Eddy Simulations (LES) are employed to investigate turbulent spray flames from a Triple Annular Research Swirler (TARS)

Association Between Preoperative Opioid and Benzodiazepine Prescription Patterns and Mortality After Noncardiac Surgery

IMPORTANCE: The number of patients prescribed long-term opioids and benzodiazepines and complications from their long-term use have increased. Information regarding the perioperative outcomes of patients prescribed these medications before surgery is limited.OBJECTIVE: To determine whether patients prescribed opioids and/or benzodiazepines within 6 months preoperatively would have greater short- a