Polymeric antibubbles with strong ultrasound imaging capabilities.

Antibubbles are liquid droplets encapsulated by a gas film that have recently been explored for on-demand ultrasound-triggered drug release. However, their ultrasound imaging capabilities are limited by their stiff shells stabilized with silica nanoparticles. Here, we develop polymeric antibubbles that generate greater ultrasound contrast than silica-based antibubbles, while showing better stability than conventional polymeric microbubbles.

Polymeric Microbubble Shell Engineering: Microporosity as a Key Factor to Enhance Ultrasound Imaging and Drug Delivery Performance.

Microbubbles (MB) are widely used as contrast agents for ultrasound (US) imaging and US-enhanced drug delivery. Polymeric MB are highly suitable for these applications because of their acoustic responsiveness, high drug loading capability, and ease of surface functionalization. While many studies have focused on using polymeric MB for diagnostic and therapeutic purposes, relatively little attention has thus far been paid to improving their inherent imaging and drug delivery features.

Liquid biopsy based HER2 amplification status in gastric cancer patients indicates clinical response.

Gastric carcinomas are among the most common cancers in Germany, with approximately 18,000 new cases per year. About 10 years ago, based on results of the Trastuzumab for gastric cancer (ToGA) trial, the addition of the monoclonal antibody trastuzumab to a platinum-fluoropyrimidine chemotherapy backbone became the standard-of-care 1st-line therapy for human epidermal growth factor receptor 2 ()-positive gastric cancers. Only patients with primary gene amplification benefit from this therapy.

Tunable polymeric micelles for taxane and corticosteroid co-delivery.

Nanomedicine holds promise for potentiating drug combination therapies. Increasing (pre)clinical evidence is available exemplifying the value of co-formulating and co-delivering different drugs in modular nanocarriers. Taxanes like paclitaxel (PTX) are widely used anticancer agents, and commonly combined with corticosteroids like dexamethasone (DEX), which besides for suppressing inflammation and infusion reactions, are increasingly explored for modulating the tumor microenvironment towards enhanced nano-chemotherapy delivery and efficacy.

Coinhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancer via readthrough transcription.

Pancreatic carcinoma lacks effective therapeutic strategies resulting in poor prognosis. Transcriptional dysregulation due to alterations in KRAS and MYC affects initiation, development, and survival of this tumor type. Using patient-derived xenografts of KRAS- and MYC-driven pancreatic carcinoma, we show that coinhibition of topoisomerase 1 (TOP1) and bromodomain-containing protein 4 (BRD4) synergistically induces tumor regression by targeting promoter pause release.

Lasting response by vertical inhibition with cetuximab and trametinib in KRAS-mutated colorectal cancer patient-derived xenografts.

Although approximately half of all metastatic colorectal cancers (mCRCs) harbour mutations in KRAS or NRAS, hardly any progress has been made regarding targeted treatment for this group over the last few years. Here, we investigated the efficacy of vertical inhibition of the RAS-pathway by targeting epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase kinase (MEK) in patient-derived xenograft (PDX) tumours with primary KRAS mutation. In total, 19 different PDX models comprising 127 tumours were tested.

Lower extremity kinematics during running and hip abductor strength in iliotibial band syndrome: A systematic review and meta-analysis.

Background: Iliotibial band syndrome is a common overuse injury that is twice as likely to affect female runners compared to male runners. It is unclear if there is a consistent running pattern and strength profile exhibited by female and male runners with iliotibial band syndrome.

Research Question: The purpose of this systematic review and meta-analysis was to determine if any differences existed in lower-extremity kinematics and hip strength between runners who retrospectively, currently, or prospectively had iliotibial band syndrome.

DMA of TPU Films and the Modelling of Their Viscoelastic Properties for Noise Reduction in Jet Engines.

Due to current developments in jet engine design, the acoustic performance of conventional acoustic liners needs to be improved with respect to lower frequency spectrums and broadband absorption. In this context, the present study aimed to determine the viscoelastic material properties of a thermoplastic polyurethane (TPU) film for targeted application in novel acoustic liners with integrated film material for enhanced noise reduction. Therefore, a dynamic mechanical analysis (DMA) was performed to determine these viscoelastic material properties.

Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients-a CERTAIN registry analysis.

Background: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients.

Optical genome mapping reveals additional prognostic information compared to conventional cytogenetics in AML/MDS patients.

Cytogenetic diagnostics play a crucial role in risk stratification and classification of myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), thus influencing treatment decisions. Optical genome mapping (OGM) is a novel whole genome method for the detection of cytogenetic abnormalities. Our study assessed the applicability and practicality of OGM as diagnostic tool in AML and MDS patients.

Secondary resistance to anti-EGFR therapy by transcriptional reprogramming in patient-derived colorectal cancer models.

Background: The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the molecular level. Here we tested in vivo selection of anti-EGFR SR tumors in CRC patient-derived xenograft (PDX) models as a strategy for a molecular dissection of SR mechanisms.

Methods: We analyzed 21 KRAS, NRAS, BRAF, and PI3K wildtype CRC patient-derived xenograft (PDX) models for their anti-EGFR sensitivity.

Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group.

Perioperative chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) is a mainstay in the treatment of esophagogastric adenocarcinomas (EGA). Trastuzumab improved survival when added to chemotherapy in patients with HER-2-positive metastatic EGA. We investigated the combination of trastuzumab and FLOT as perioperative treatment in patients with locally advanced EGA.

Precise variant interpretation, phenotype ascertainment, and genotype-phenotype correlation of children in the EARLY PRO-TECT Alport trial.

Early initiation of therapy in patients with Alport syndrome (AS) slows down renal failure by many years. Genotype-phenotype correlations propose that the location and character of the individual's variant correlate with the renal outcome and any extra renal manifestations. In-depth clinical and genetic data of 60/62 children who participated in the EARLY PRO-TECT Alport trial were analyzed.

Evolution of RAS Mutational Status in Liquid Biopsies During First-Line Chemotherapy for Metastatic Colorectal Cancer.

Treatment options for patients with metastatic colorectal cancer (mCRC) are limited. This particularly affects the largest group of patients with RAS mutations, who are considered ineligible for therapy with antiEGFR antibodies. In this liquid biopsy-based study, we performed the first in-depth analysis of the RAS mutational status in initially RAS-mutated patients during first-line therapy.

The Effect of Tactical Tasks and Gear on Muscle Activation of SWAT Officers.

Keeler, JM, Pohl, MB, Bergstrom, HC, Thomas, JM, and Abel, MG. The effect of tactical tasks and gear on muscle activation of SWAT officers. J Strength Cond Res 36(1): 238-244, 2022-Special Weapons and Tactics (SWAT) officers perform a variety of tactical operations while wearing tactical gear.

Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.

Background: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours.

Methods: In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m epirubicin and 60 mg/m cisplatin on day 1 plus either 200 mg/m fluorouracil as continuous intravenous infusion or 1250 mg/m capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m docetaxel, 85 mg/m oxaliplatin, 200 mg/m leucovorin and 2600 mg/m fluorouracil as 24-h infusion on day 1 (FLOT; experimental group).

Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in -Mutant Pancreatic and Colorectal Cancer.

Aberrations within the PI3K/AKT signaling axis are frequently observed in numerous cancer types, highlighting the relevance of these pathways in cancer physiology and pathology. However, therapeutic interventions employing AKT inhibitors often suffer from limitations associated with target selectivity, efficacy, or dose-limiting effects. Here we present the first crystal structure of autoinhibited AKT1 in complex with the covalent-allosteric inhibitor borussertib, providing critical insights into the structural basis of AKT1 inhibition by this unique class of compounds.

Proteinuria in children with autosomal dominant polycystic kidney disease.

Background: Proteinuria is a common complication in adults with autosomal dominant polycystic kidney disease (ADPKD) and serves as a risk factor for progression. However, proteinuria has rarely been examined in children with ADPKD and the type of proteinuria has not yet been investigated. The aim of the study was to assess the prevalence and to analyse the types of proteinuria in children with ADPKD.

MODIFYING STANCE ALTERS THE PEAK KNEE ADDUCTION MOMENT DURING A GOLF SWING.

Background: The knee joint is one of the most frequently injured regions in the game of golf, and the loads experienced by the knee during the golf swing are typically greater than during other activities of daily living. Altering movement patterns is a common strategy that can be used to reduce loading on the knee joint but has received little attention during studies of the golf swing. The primary aim of this study was to examine the effect altering golf stance has on the lead limb peak external knee adduction moment.

Reducing Impact Loading in Runners: A One-Year Follow-up.

Unlabelled: Increased vertical impact loading during running has been associated with a variety of running related injuries including stress fractures, patellofemoral pain, and plantar fasciitis.

Purpose: The purpose of this study was to examine the acute and long-term effect of a gait retraining program aimed at teaching runners with high impact loading to run softer.

Methods: Nineteen runners with high tibial shock (TS) first underwent a control period of eight sessions of treadmill running over 2 wk, progressing from 15 to 30 min.

Effects of a Hip Flexor Stretching Program on Running Kinematics in Individuals With Limited Passive Hip Extension.

Mettler, JH, Shapiro, R, and Pohl, MB. Effects of a hip flexor stretching program on running kinematics in individuals with limited passive hip extension. J Strength Cond Res 33(12): 3338-3344, 2019-Tightness of the hip flexor muscle group may theoretically contribute to altered kinematics of the lumbo-pelvic-hip (LPH) complex during dynamic movements.

Hypomagnesaemia is absent in children with autosomal dominant polycystic kidney disease.

Background: Hypomagnesaemia is present in 40-50% of children with autosomal dominant renal cysts and diabetes syndrome (RCAD). On the contrary, the prevalence of hypomagnesaemia in children with autosomal dominant polycystic kidney disease (ADPKD) has never been examined. We aimed to investigate whether hypomagnesaemia is present in children with polycystic kidney diseases.

Midtarsal locking, the windlass mechanism, and running strike pattern: A kinematic and kinetic assessment.

Changes in running strike pattern affect ankle and knee mechanics, but little is known about the influence of strike pattern on the joints distal to the ankle. The purpose of this study was to explore the effects of forefoot strike (FFS) and rearfoot strike (RFS) running patterns on foot kinematics and kinetics, from the perspectives of the midtarsal locking theory and the windlass mechanism. Per the midtarsal locking theory, we hypothesized that the ankle would be more inverted in early stance when using a FFS, resulting in decreased midtarsal joint excursions and increased dynamic stiffness.