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Hypoxia attenuates trastuzumab uptake and trastuzumab-emtansine (T-DM1) cytotoxicity through redistribution of phosphorylated caveolin-1

The antibody drug conjugate trastuzumab-emtansine (T-DM1) offers an additional treatment option for patients with HER2-amplified tumors. However, primary and acquired resistance is a limiting factor in a significant subset of patients. Hypoxia, a hallmark of cancer, regulates the trafficking of several receptor proteins with potential implications for tumor targeting. Here, we have investigated ho

Novel insights into the emerging roles of tRNA-derived fragments in mammalian development

ABTRACT: tRNA-derived fragments or tRFs were long considered merely degradation intermediates of full-length tRNAs; however, emerging research is highlighting unanticipated new and highly distinct functions in epigenetic control, metabolism, immune activity and stem cell fate commitment. Importantly, recent studies suggest that RNA epitranscriptomic modifications may provide an additional regulato

Development of Humanized Ossicles : Bridging the Hematopoietic Gap

Ectopic 'humanized ossicles' (hOss) are miniaturized, engineered human bone organs in mice displaying a similar structure and function to native mouse bones. However, they are composed of human mesenchymal derived cells forming a humanized bone marrow niche. This in vivo reconstitution of human skeletal and hematopoietic compartments provides an opportunity to investigate the cellular and molecula

Risk of hernia formation after radical prostatectomy : a comparison between open and robot-assisted laparoscopic radical prostatectomy within the prospectively controlled LAPPRO trial

Purpose: In addition to incisional hernia, inguinal hernia is a recognized complication to radical retropubic prostatectomy. To compare the risk of developing inguinal and incisional hernias after open radical prostatectomy compared to robot-assisted laparoscopic prostatectomy. Method: Patients planned for prostatectomy were enrolled in the prospective, controlled LAPPRO trial between September 20

Ice-nucleating ability of particulate emissions from solid-biomass-fired cookstoves : An experimental study

This research was part of the Salutary Umeå Study of Aerosols in Biomass Cookstove Emissions (SUSTAINE) laboratory experiment campaign. We studied ice-nucleating abilities of particulate emissions from solid-fuel-burning cookstoves, using a portable ice nuclei counter, Spectrometer Ice Nuclei (SPIN). These emissions were generated from two traditional cookstove types commonly used for household co

Outcome and characteristics of non-measurable myeloma : A cohort study with population-based data from the Swedish Myeloma Registry

Objective: We describe survival in patients with oligo- and non-secretory multiple myeloma (MM). We refer to the whole group as non-measurable MM and compare it with secretory MM. Methods: Oligo-secretory MM was defined as M protein in serum <10 g/L and M protein in urine <200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M protein, they were defined as non-secretory. The

Label-free processing of stem cell preparations by acoustophoresis

The first bone marrow transplant in a human was performed in 1959, providing evidence that cells can be used for transplantation and treatment, revealing that healing capacities lie within the human body that ought to be understood. Since then hematopoietic stem cell transplantation has developed as a standard treatment for many cancers besides other malignancies. Much research is done to understa

The Association Between Cancer and Dementia : A National Cohort Study in Sweden

Background: Previous studies have found that the incidence of dementia is lower in patients with cancer. However, the impact of survival bias, as well as the confounding by medical treatment, have not been fully addressed. We aimed to explore the subsequent risk of dementia in different follow-up intervals among patients with cancer, as well as the risk before the diagnosis of cancer. Methods: By

3d phase-contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects

Background: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility. Material and methods: Four

Numerical and experimental investigation of tool geometry effect on residual stresses in orthogonal machining of Inconel 718

Residual stress has become more important than ever with the increasing performance requirement of components especially for those applied in safety-critical areas. As the machining process is fundamentally correlated with the acquired component properties, it is essential to fully understand the formation mechanism of residual stresses in the cutting process and its influence on the performance o

Substrate and plant genotype strongly influence the growth and gene expression response to trichoderma afroharzianum T22 in sugar beet

Many strains of Trichoderma fungi have beneficial effects on plant growth and pathogen control, but little is known about the importance of plant genotype, nor the underlying mechanisms. We aimed to determine the effect of sugar beet genotypic variation on Trichoderma biostimulation. The effect of Trichoderma afroharzianum T22 on sugar beet inbred genotypes were investigated in soil and on sterile

Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction

Plasma concentrations of many cardiovascular and inflammatory proteins are altered after ST-elevation myocardial infarction (STEMI) and may provide prognostic information. We conducted a large-scale proteomic analysis in patients with STEMI, correlating protein levels to infarct size and left ventricular ejection fraction (LVEF) determined with cardiac magnetic resonance imaging. We analysed 131 c

Cardiovascular risk assessment in south and middle-east asians living in the western countries

Nearly a quarter of the world population lives in the South Asian region (India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and the Maldives). Due to rapid demographic and epidemiological transition in these countries, the burden of non-communicable diseases is growing, which is a serious public health concern. Particularly, the prevalence of pre-diabetes, diabetes and atherosclerotic cardiov

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of thes

Lung regeneration : implications of the diseased niche and ageing

Most chronic and acute lung diseases have no cure, leaving lung transplantation as the only option. Recent work has improved our understanding of the endogenous regenerative capacity of the lung and has helped identification of different progenitor cell populations, as well as exploration into inducing endogenous regeneration through pharmaceutical or biological therapies. Additionally, alternativ

Oligodendroglial (dys)function in alpha-synucleinopathies

Komplexiteten hos a-synukleinopatier, som inkluderar multipel systematrofi (MSA) och Parkinsons sjukdom (PS), är inte helt klarlagd. Det är känt att patologisk ansamling av a-synuclein (a-syn) till fiberlika proteinaggregat är ett cellulärt kännetecken för dessa sjukdomar. a-Syn-positiva aggregat förekommer i nervceller i PS och Lewy body demens (LBD) och i oligodendrocyter i MSA. Mycket forskningThe complexity of a-synucleinopathies, which include multiple system atrophy (MSA) and Parkinson’s disease (PD), is not entirely understood. It is known that pathological accumulation of a-synuclein (a-syn) into proteinaceous aggregates is a cellular hallmark of these diseases. a-Syn positive aggregates appear in neurons in PD and dementia with Lewy bodies (DLB), and in oligodendrocytes in MSA. Mu

Pregnancy Complication History in 10-Year Cardiovascular Disease Risk Prediction: a Review of Recent Evidence

Purpose of ReviewWomen with prevalent pregnancy complications (including preterm birth and preeclampsia) have twice the risk of later cardiovascular disease (CVD) compared to unaffected women. Current prevention guidelines recommend that reproductive history should be part of a woman’s CVD risk assessment. This review synthesizes recent findings on the value of history of pregnancy complications i

Photofunctionality of iron(III) N-heterocyclic carbenes and related d5 transition metal complexes

Despite a few reports of photoluminescent and strongly photo-oxidizing transition metal complexes with a d5 electronic configuration, the photophysics and photochemistry of this class of transition metal complexes have largely remained unexplored. Recent investigations of earth-abundant iron(III) N-heterocyclic carbene (NHC) complexes have demonstrated promising photophysical and photochemical pro

A Stable Homoleptic Organometallic Iron(IV) Complex

A homoleptic organometallic FeIV complex that is stable in both solution and in the solid state at ambient conditions has been synthesized and isolated as [Fe(phtmeimb)2](PF6)2 (phtmeimb=[phenyl(tris(3-methylimidazolin-2-ylidene))borate]−). This FeIV N-heterocyclic carbene (NHC) complex was characterized by 1H NMR, HR-MS, elemental analysis, scXRD analysis, electrochemistry, Mößbauer spectroscopy,