A rigorous multi-laboratory study of known PDAC biomarkers identifies increased sensitivity and specificity over CA19-9 alone.

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs.

Multiplexed Glycan Immunofluorescence Identification of Pancreatic Cancer Cell Subpopulations in Both Tumor and Blood Samples.

Pancreatic ductal adenocarcinoma (PDAC) tumor heterogeneity impedes the development of biomarker assays suitable for early disease detection that would improve patient outcomes. The CA19-9 glycan is currently used as a standalone biomarker for PDAC. Furthermore, previous studies have shown that cancer cells may display aberrant membrane-associated glycans.

A Rigorous Multi-Laboratory Study of Known PDAC Biomarkers Identifies Increased Sensitivity and Specificity Over CA19-9 Alone.

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs.

Principles and potential of solvent gradient size-exclusion chromatography for polymer analysis.

The properties of a polymeric material are influenced by its underlying molecular distributions, including the molecular-weight (MWD), chemical-composition (CCD), and/or block-length (BLD) distributions. Gradient-elution liquid chromatography (LC) is commonly used to determine the CCD. Due to the limited solubility of polymers, samples are often dissolved in strong solvents.

Feasibility of Virtual Reality Exercises at Home for Post-COVID-19 Condition: Cohort Study.

Background: Between 30% to 76% of COVID-19 patients have persistent physical and mental symptoms, sometimes up to 9 months after acute COVID-19. Current rehabilitation is mostly focused on the physical symptoms, whereas experts have agreed on the need for a biopsychosocial approach. A novel approach such as virtual reality (VR) rehabilitation at home might benefit patients and therapists, especially considering the expected rush of patients with post-COVID-19 condition needing rehabilitation.

Using beat frequency in music to adjust running cadence in recreational runners: A randomized multiple baseline design.

Running with music has been shown to acutely change cadence. However, it is unclear if the increased cadence remains long-term when running without music in an in-field situation. The aim of this 12-week study was to investigate the effect of a 4-week music running program on cadence, speed and heartrate during and after the music running program.

The Framing Preference for Large and Increasing Components in Static and Dynamic Descriptions.

Describing sets in terms of a two-valued variable, either value can be chosen: exam results may be referred to by pass rates or fail rates. What determines such framing choices? Building on work by McKenzie and colleagues on reference points in the production and interpretation of framed information, we investigate two determinants of frame choice. One is that speakers tend to focus on the component that has increased vis-à-vis a previous state, the other is the tendency to choose the component larger than 50%.

Thermal modulation to enhance two-dimensional liquid chromatography separations of polymers.

Many materials used in a wide range of fields consist of polymers that feature great structural complexity. One particularly suitable technique for characterising these complex polymers, that often feature correlated distributions in e.g.

Detection of Chemotherapy-resistant Pancreatic Cancer Using a Glycan Biomarker, sTRA.

Purpose: A subset of pancreatic ductal adenocarcinomas (PDACs) is highly resistant to systemic chemotherapy, but no markers are available in clinical settings to identify this subset. We hypothesized that a glycan biomarker for PDACs called sialylated tumor-related antigen (sTRA) could be used for this purpose.

Experimental Design: We tested for differences between PDACs classified by glycan expression in multiple systems: sets of cell lines, organoids, and isogenic cell lines; primary tumors; and blood plasma from human subjects.

Iterative RAFT-Mediated Copolymerization of Styrene and Maleic Anhydride toward Sequence- and Length-Controlled Copolymers and Their Applications for Solubilizing Lipid Membranes.

The use of poly(styrene--maleic acid) (SMA) for the solubilization of lipid membranes and membrane proteins is becoming more widespread, and with this, the need increases to better understand the chemical properties of the copolymer and how these translate into membrane solubilization properties. SMA comes in many different flavors that include the ratio of styrene to maleic acid, comonomer sequence distribution, average chain length, dispersity, and potential chemical modifications. In this work, the synthesis and membrane active properties are described for 2:1 (periodic) SMA copolymers with varying from ∼1.

Overexpression of HGF/MET axis along with p53 inhibition induces de novo glioma formation in mice.

Background: Aberrant MET receptor tyrosine kinase (RTK) activation leads to invasive tumor growth in different types of cancer. Overexpression of MET and its ligand hepatocyte growth factor (HGF) occurs more frequently in glioblastoma (GBM) than in low-grade gliomas. Although we have shown previously that HGF-autocrine activation predicts sensitivity to MET tyrosine kinase inhibitors (TKIs) in GBM, whether it initiates tumorigenesis remains elusive.

Simultaneous characterization of poly(acrylic acid) and polysaccharide polymers and copolymers.

Copolymer products that result from grafting acrylic acid and other hydrophilic monomers onto polysaccharides have recently gained significant interest in research and industry. Originating from renewable sources, these biodegradable, low toxicity, and polar copolymer products exhibit potential to replace polymers from fossil sources in several applications and industries. The methods usually employed to characterize these copolymers are, however, quite limited, especially for the measurement of bulk properties.

Reasons for continuing physiotherapy treatment after a high-intensity physyiotherapy program in patients after total knee arthroplasty: a mixed-methods study.

: Patients after total knee arthroplasty treated with a 10-day high-intensity physiotherapy program in a resort were expected to recover fast without need for a longer physiotherapy treatment period.: To explore the expectations and experiences of patients with total knee arthroplasty following the high-intensity physiotherapy program, including the perceived recovery level at discharge, and reasons for (not) adhering to the given advice at discharge (being either continuing with or refraining from further physiotherapy treatment).: A mixed-methods approach: semi-structured interviews were held and were then used to develop items and answer categories for a survey.

The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy Over CA19-9 in Pancreatic Cancer Diagnosis.

Purpose: The CA19-9 biomarker is elevated in a substantial group of patients with pancreatic ductal adenocarcinoma (PDAC), but not enough to be reliable for the detection or diagnosis of the disease. We hypothesized that a glycan called sTRA (sialylated tumor-related antigen) is a biomarker for PDAC that improves upon CA19-9.

Experimental Design: We examined sTRA and CA19-9 expression and secretion in panels of cell lines, patient-derived xenografts, and primary tumors.

Differential responses of MET activations to MET kinase inhibitor and neutralizing antibody.

Background: Aberrant MET tyrosine kinase signaling is known to cause cancer initiation and progression. While MET inhibitors are in clinical trials against several cancer types, the clinical efficacies are controversial and the molecular mechanisms toward sensitivity remain elusive.

Methods: With the goal to investigate the molecular basis of MET amplification (MET) and hepatocyte growth factor (HGF) autocrine-driven tumors in response to MET tyrosine kinase inhibitors (TKI) and neutralizing antibodies, we compared cancer cells harboring MET (MKN45 and MHCCH97H) or HGF-autocrine (JHH5 and U87) for their sensitivity and downstream biological responses to a MET-TKI (INC280) and an anti-MET monoclonal antibody (MetMab) in vitro, and for tumor inhibition in vivo.

Two-Dimensional Liquid Chromatography Analysis of Polystyrene/Polybutadiene Block Copolymers.

A detailed characterization of a commercial polystyrene/polybutadiene block copolymer material (Styrolux) was carried out using two-dimensional liquid chromatography (2D-LC). The Styrolux is prepared by statistical linking reaction of two different polystyrene- block-polybutadienyl anion precursors with a multivalent linking agent. Therefore, it is a mixture of a number of branched block copolymers different in molecular weight, composition, and chain architecture.

Mining High-Complexity Motifs in Glycans: A New Language To Uncover the Fine Specificities of Lectins and Glycosidases.

Knowledge of lectin and glycosidase specificities is fundamental to the study of glycobiology. The primary specificities of such molecules can be uncovered using well-established tools, but the complex details of their specificities are difficult to determine and describe. Here we present a language and algorithm for the analysis and description of glycan motifs with high complexity.

Shoulder Dynamic Control Ratio and Rotation Range of Motion in Female Junior Elite Handball Players and Controls.

Objective: To compare glenohumeral range of motion and shoulder rotator muscle strength in healthy female junior elite handball players and controls.

Design: Cross-sectional case-control study.

Setting: Sports medical center.

Cartilage-specific deletion of Mig-6 results in osteoarthritis-like disorder with excessive articular chondrocyte proliferation.

A deficiency of mitogen-inducible gene-6 (Mig-6) in mice leads to the development of an early-onset, osteoarthritis (OA)-like disorder in multiple synovial joints, underlying its importance in maintaining joint homeostasis. Here we determined what joint tissues Mig-6 is expressed in and what role chondrocytes play in the Mig-6-deficient OA-like disorder. A Mig-6/lacZ reporter mouse strain expressing β-galactosidase under the control of the Mig-6 gene promoter was generated to determine Mig-6 expression in joint tissues.

Strengthening context-dependent anticancer effects on non-small cell lung carcinoma by inhibition of both MET and EGFR.

The MET and EGFR receptor tyrosine kinases (RTK) are often coexpressed and may cross-talk in driving the development and progression of non-small cell lung carcinoma (NSCLC). In addition, MET amplification is an alternative resistance mechanism for escaping EGFR-targeted therapy. To assess the benefits of combined targeting of MET and EGFR for treating NSCLCs, we investigated the activities of these two RTK pathways in NSCLC cell lines and evaluated their responses to SGX523 and erlotinib, the small-molecule kinase inhibitors of MET and EGFR, respectively.

Cancer-type regulation of MIG-6 expression by inhibitors of methylation and histone deacetylation.

Epigenetic silencing is one of the mechanisms leading to inactivation of a tumor suppressor gene, either by DNA methylation or histone modification in a promoter regulatory region. Mitogen inducible gene 6 (MIG-6), mainly known as a negative feedback inhibitor of the epidermal growth factor receptor (EGFR) family, is a tumor suppressor gene that is associated with many human cancers. To determine if MIG-6 is inactivated by epigenetic alteration, we identified a group of human lung cancer and melanoma cell lines in which its expression is either low or undetectable and studied the effects of methylation and of histone deacetylation on its expression.

Effects of leg muscle botulinum toxin A injections on walking in children with spasticity-related cerebral palsy: a systematic review.

Aim: To assess treatment effects of botulinum toxin type A (BoNT-A) on walking of children with leg spasticity due to cerebral palsy (CP) compared with usual care.

Method: We systematically searched the databases CINAHL, Cochrane, PEDro, EMBASE, and PubMed from July 1993 until July 2009 and additionally screened reference lists. Randomized controlled trials assessing functional outcomes on walking of children with CP were included.

Can a fatigue test of the isolated lumbar extensor muscles of untrained young men predict strength progression in a resistance exercise program?

Aim: The aim of this exploratory study was to investigate the predictive value of a fatigue test of the lumbar extensor muscles for training progression in a group of 28 healthy but predominantly sedentary male students, in an 8-week resistance exercise program.

Methods: A three-phased fatigue test of the lumbar extensor muscles was designed, consisting of two consecutive measurements of full-range isometric back strength on a lumbar measurement device, separated by a dynamic back extension set to volitional fatigue. Differences between the strength values of the 1st and 3rd step is thought to reflect individual back muscle fatigue characteristics.

MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor-dependent fashion to suppress carcinoma growth.

The hepatocyte growth factor (HGF)-MET pathway supports several hallmark cancer traits, and it is frequently activated in a broad spectrum of human cancers (http://www.vai.org/met/).