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Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells

Neuroblastoma is the most commonly diagnosed extracranial tumor in the first year of life. Approximately 9% of neuroblastoma patients present germline or somatic aberrations in the gene encoding for anaplastic lymphoma kinase (ALK). This increases in high-risk neuroblastomas, which have a 14% frequency of ALK aberrations at the time of diagnosis and show increasing numbers at relapse. Abrogating A

Reprogramming Cancer Cells to Antigen-presenting Cells

Cancer cells evade the immune system by downregulating antigen presentation. Although immune checkpoint inhibitors (ICI) and adoptive T-cell therapies revolutionized cancer treatment, their efficacy relies on the intrinsic immunogenicity of tumor cells and antigen presentation by dendritic cells. Here, we describe a protocol to directly reprogram murine and human cancer cells into tumor-antigen-pr

Discordance Between Creatinine-Based and Cystatin C–Based Estimated GFR : Interpretation According to Performance Compared to Measured GFR

Rationale & Objective: Use of cystatin C in addition to creatinine to estimate glomerular filtration rate (estimated glomerular filtration rate based on cystatin C [eGFRcys] and estimated glomerular filtration rate based on creatinine [eGFRcr], respectively) is increasing. When eGFRcr and eGFRcys are discordant, it is not known which is more accurate, leading to uncertainty in clinical decisio

Averaging bias in environmental impact estimates : Evidence from the negative footprint illusion

In this paper we argue that unsustainable behaviors often stem from a common averaging bias when people estimate the environmental impact of a set of environmentally friendly and less friendly objects or actions. In Experiment 1, we show that people believe that the total carbon footprint of a category of items (a community of buildings in this case) is lower, rather than higher, when environmenta

Preterm or early term birth and risk of attention-deficit/hyperactivity disorder : a national cohort and co-sibling study

Purpose: To examine risks of attention-deficit/hyperactivity disorder (ADHD) in preterm and early term birth survivors, and potential sex-specific differences. Methods: A national cohort study was conducted of all 4061,795 singletons born in Sweden in 1973–2013 who survived infancy, followed up for ADHD identified from nationwide diagnoses and medications through 2018. Poisson regression was used

The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer

Objective: The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. Methods: We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were trea

The importance of business travel for trade : Evidence from the liberalization of the Soviet airspace

The strong negative relationship between geographical distance and trade is not well understood. I use the liberalization of the Soviet airspace to estimate the causal impact of business travel cost on trade. The liberalization radically reduced travel time between Europe and East Asia and was followed by a significant increase in trade. I find that the cost of business travel can account for a la

M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection

Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A d restricted and critically protected against infectio

Activated Peyer′s patch B cells sample antigen directly from M cells in the subepithelial dome

The germinal center (GC) reaction in Peyer′s patches (PP) requires continuous access to antigens, but how this is achieved is not known. Here we show that activated antigen-specific CCR6+CCR1+GL7− B cells make close contact with M cells in the subepithelial dome (SED). Using in situ photoactivation analysis of antigen-specific SED B cells, we find migration of cells towards the GC. Following antig

Executive Summary : Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

BACKGROUND Numerous laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. An expert committee compiled evidence-based recommendations for laboratory analysis in patients with diabetes. The overall quality of the evidence and the strength of the recommendations wer

Early screening outcomes before, during, and after a randomized controlled trial with digital breast tomosynthesis

Purpose: To describe and compare early screening outcomes before, during and after a randomized controlled trial with digital breast tomosynthesis (DBT) including synthetic 2D mammography versus standard digital mammography (DM) (To-Be 1) and a follow-up cohort study using DBT (To-Be 2). Methods: Retrospective results of 125,020 screening examinations from four consecutive screening rounds perform

Two-year MRI-defined structural damage and patient-reported outcomes following surgery or exercise for meniscal tears in young adults

Objective: To investigate potential differences in structural knee joint damage assessed by MRI and patient-reported outcomes (PROMs) at 2-year follow-up between young adults randomised to early surgery or exercise and education with optional delayed surgery for a meniscal tear. Methods: A secondary analysis of a multicentre randomised controlled trial including 121 patients (18-40 years) with an

Refining the Definition of Stage 1 Type 1 Diabetes : An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity

OBJECTIVE To estimate the risk of progression to stage 3 type 1 diabetes based on varying definitions of multiple islet autoantibody positivity (mIA). RESEARCH DESIGN AND METHODS Type 1 Diabetes Intelligence (T1DI) is a combined prospective data set of children from Finland, Germany, Sweden, and the U.S. who have an increased genetic risk for type 1 diabetes. Analysis included 16,709 infants-toddl

Entinostat Enhances the Efficacy of Chemotherapy in Small Cell Lung Cancer Through S-phase Arrest and Decreased Base Excision Repair

PURPOSE: Acquired chemoresistance is a frequent event in small cell lung cancer (SCLC), one of the deadliest human malignancies. Histone deacetylase inhibitors (HDACi) have been shown to synergize with different chemotherapeutic agents including cisplatin. Accordingly, we aimed to investigate the dual targeting of HDAC inhibition and chemotherapy in SCLC.EXPERIMENTAL DESIGN: The efficacy of HDACi

Pivotal advance : CD45RB glycosylation is specifically regulated during human peripheral B cell differentiation

A screen of cell surface markers differentially expressed during peripheral B cell differentiation identified that the CD45RB epitope detected by the mAb MEM-55 was highly expressed on CD27+ memory B cells and absent on CD27- naïve B cells. IgG+CD27- memory and a previously unacknowledged CD27- population in blood also expressed high levels of CD45RBMEM55. Naïve and memory B cells from tonsils fol