Molecular Profiling Identifies CD49d and CD79b as Predictive Markers for Acquired Acalabrutinib Resistance in Patients With Chronic Lymphocytic Leukemia.

Contemporary studies of Bruton tyrosine kinase inhibitor (BTKi) resistance focus on mutations in the B-cell receptor (BCR) pathway, but alternative mechanisms of resistance remain undefined. Here, we sought to identify novel predictive markers of acquired resistance to acalabrutinib, a second-generation BTKi, in patients with chronic lymphocytic leukemia (CLL). Clinical samples from 41 patients with relapsed/refractory or treatment-naive CLL receiving acalabrutinib as part of a clinical trial (NCT02029443) were divided into two groups: those who continued to respond to treatment (NP, n = 23) and those who developed progressive disease on acalabrutinib therapy (PD, n = 18).

An Evaluation of Zebrafish, an Emerging Model Analyzing the Effects of Toxicants on Cognitive and Neuromuscular Function.

An emerging alternative to conventional animal models in toxicology research is the zebrafish. Their accelerated development, regenerative capacity, transparent physical appearance, ability to be genetically manipulated, and ease of housing and care make them feasible and efficient experimental models. Nonetheless, their most esteemed asset is their 70% (+) genetic similarity with the human genome, which allows the model to be used in a variety of clinically relevant studies.

A phase 1/2 study of the combination of acalabrutinib and vistusertib in patients with relapsed/refractory B-cell malignancies.

In a phase 1b study of acalabrutinib (a covalent Bruton tyrosine kinase (BTK) inhibitor) in combination with vistusertib (a dual mTORC1/2 inhibitor) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), multiple ascending doses of the combination as intermittent or continuous schedules of vistusertib were evaluated. The overall response rate was 12% (3/25). The pharmacodynamic (PD) profile for acalabrutinib showed that BTK occupancy in all patients was >95%.

Adipose Stem Cells Incorporated in Fibrin Clot Modulate Expression of Growth Factors.

Purpose: To evaluate the platelet capture rate of whole blood fibrin clots and the expression, secretion, and retention of the growth factors vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) from fibrin clots and to determine how these levels may be modulated by allogeneic adipose-derived stem cells (ASCs).

Methods: Whole blood from 10 human volunteers was transferred to a clotting device and the platelet capture rate determined. Two experimental conditions and 1 control were evaluated over 2 weeks in vitro.

Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells.

One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation.

Strategies for bioengineered scaffolds that support adipose stem cells in regenerative therapies.

Regenerative medicine possesses the potential to ameliorate damage to tissue that results from a vast range of conditions, including traumatic injury, tumor resection and inherited tissue defects. Adult stem cells, while more limited in their potential than pluripotent stem cells, are still capable of differentiating into numerous lineages and provide feasible allogeneic and autologous treatment options for many conditions. Adipose stem cells are one of the most abundant types of stem cell in the adult human.

Induced Pluripotent Stem Cell-Derived Retinal Pigmented Epithelium: A Comparative Study Between Cell Lines and Differentiation Methods.

Purpose: The application of induced pluripotent stem cell-derived retinal pigmented epithelium (iPSC-RPE) in patients with retinal degenerative disease is making headway toward the clinic, with clinical trials already underway. Multiple groups have developed methods for RPE differentiation from pluripotent cells, but previous studies have shown variability in iPSC propensity to differentiate into RPE.

Methods: This study provides a comparison between 2 different methods for RPE differentiation: (1) a commonly used spontaneous continuously adherent culture (SCAC) protocol and (2) a more rapid, directed differentiation using growth factors.

Vitronectin-Based, Biomimetic Encapsulating Hydrogel Scaffolds Support Adipogenesis of Adipose Stem Cells.

Soft tissue defects are relatively common, yet currently used reconstructive treatments have varying success rates, and serious potential complications such as unpredictable volume loss and reabsorption. Human adipose-derived stem cells (ASCs), isolated from liposuction aspirate have great potential for use in soft tissue regeneration, especially when combined with a supportive scaffold. To design scaffolds that promote differentiation of these cells down an adipogenic lineage, we characterized changes in the surrounding extracellular environment during adipogenic differentiation.

The effect of insertion angle on the pullout strength of threaded suture anchors: a validation of the deadman theory.

Purpose: To determine the effect of insertion angle, from 45° to 135° in 15° increments, on the number of cycles withstood, the ultimate pullout strength, and the stiffness of threaded suture anchors subjected to load.

Methods: Threaded anchors were inserted into polyurethane foam at angles from 45° to 135°, in 15° increments, relative to the direction of pull. Five anchors were tested at each angle.

X-ray pump optical probe cross-correlation study of GaAs.

Ultrafast dynamics in atomic, molecular and condensed-matter systems are increasingly being studied using optical-pump, X-ray probe techniques where subpicosecond laser pulses excite the system and X-rays detect changes in absorption spectra and local atomic structure(1-3). New opportunities are appearing as a result of improved synchrotron capabilities and the advent of X-ray free-electron lasers(4,5). These source improvements also allow for the reverse measurement: X-ray pump followed by optical probe.

Biomechanical evaluation of graft fixation techniques for acromioclavicular joint reconstructions using coracoclavicular tendon grafts.

Background: This study compared the initial strength of acromioclavicular joint reconstructions using coracoclavicular tendon grafts using interference screws, a tendon square knot, or side-to-side suturing for graft fixation.

Materials And Methods: An acromioclavicular joint reconstruction was performed using a hamstring allograft looped under the coracoid and then fixed using interference screws, a square knot in the graft, and side-to-side graft suturing in each of 8 cadaveric shoulders. Each reconstruction was cycled in a superior direction, and displacements were recorded.

Biomechanical comparison of acromioclavicular joint reconstructions using coracoclavicular tendon grafts with and without coracoacromial ligament transfer.

Purpose: The purpose of this study was to compare the initial strength of acromioclavicular joint reconstructions using coracoclavicular (CC) tendon grafts with and without coracoacromial (CA) ligament transfers.

Methods: Two different acromioclavicular joint reconstructions were performed in 7 matched pairs of cadaveric shoulders. Paired shoulders were repaired with either a hamstring allograft CC reconstruction (group 1) or a hamstring allograft CC reconstruction plus a CA ligament transfer (group 2).

Role of sulfide and ligand strength in controlling nanosilver toxicity.

Nanosilver has been used broadly in nanotechnology enhanced consumer products because of its strong antimicrobial properties. Silver nanoparticles (AgNPs) released from these products will likely enter wastewater collection and treatment systems. This research evaluated the role of sulfide and ligand strength in controlling nanosilver toxicity to nitrifying bacteria that are important in wastewater treatment.

Comparison of the inactivation of Bacillus subtilis spores and MS2 bacteriophage by MIOX, ClorTec and hypochlorite.

Aims: To compare the disinfection ability of two widely used electrolytic generation systems (ClorTec and MIOX) and the conventional chlorine disinfectant (sodium hypochlorite) using three strains of Bacillus subtilis spores and MS2 bacteriophage.

Methods And Results: Three B. subtilis aerobic spore strains (ATCC1A1, 35021 and 35946) and the bacteriophage MS2 (ATCC 15597-B1) were propagated and sporulated.

Prediction of N-nitrosodimethylamine (NDMA) formation as a disinfection by-product.

This study investigated the possibility of a statistical model application for the prediction of N-nitrosodimethylamine (NDMA) formation. The NDMA formation was studied as a function of monochloramine concentration (0.001-5mM) at fixed dimethylamine (DMA) concentrations of 0.

Element concentrations of dry-grind corn-processing streams.

The dry-grind corn process is one of two technologies used to convert corn into ethanol. In this process, all kernel components are processed through several sequential steps, including fermentation. Only one coproduct (distillers' dried grains with solubles [DDGS]) is available for marketing.

Assessing object-to-picture and picture-to-object matching as prerequisite skills for pictorial preference assessments.

Tangible and pictorial paired-stimulus (PPS) preference assessments were compared for 6 individuals with developmental disabilities. During tangible and PPS assessments, two edible items or photographs were presented on each trial, respectively, and approach responses were recorded. Both assessments yielded similar preference hierarchies for 3 participants who could match pictures and objects but different hierarchies for 3 participants who could not.

Impacts of goethite particles on UV disinfection of drinking water.

A unique association between bacterial cells and small goethite particles (approximately 0.2 by 2 microm) protected Escherichia coli and Pseudomonas putida from UV inactivation. The protection increased with the particle concentration in the turbidity range of 1 to 50 nephelometric turbidity units and with the bacterium-particle attachment time prior to UV irradiation.

Effects of alum coagulation on speciation and distribution of trihalomethanes (THMs) and haloacetic acids (HAAs).

The impacts of alum coagulation on the distribution of disinfection by-products (DBPs), trihalomethanes (THMs), and haloacetic acids (HAAs) were evaluated under controlled chlorination conditions using four surface waters. Among the nine HAAs found in waters, dihaloacetic acids (X2AAs) have been found to be the dominant species in all of the raw and alum treated waters. Alum coagulation tends to remove more monohaloacetic acids (XAAs) and trihaloacetic acids (X3AAs) precursors than that of dihaloacetic acids (X2AAs).

Environmental factors influencing microcystin distribution and concentration in the Midwestern United States.

During May-September 2000-2001, physicochemical data were collected from 241 lakes in Missouri, Iowa, northeastern Kansas, and southern Minnesota U.S.A.

Characterization of gluten processing streams.

Corn gluten meal (CGM) is a major coproduct of corn wet milling; it has value because of high protein. However, variation in composition and high P content reduce market value. Data that characterize gluten streams would be helpful in identifying key processing steps that could be modified to improve the quality of CGM and increase processing efficiency.

Relationship of chlorine decay and THMs formation to NOM size.

Because of increasing concern about balancing health risks for pathogen control and disinfection by-product (DBP) formation in water supplies, utilities are forced to closely examine and optimize their disinfection practices. A better understanding of the relationship between the molecular weights of the natural organic matter (NOM), chlorine decay kinetics and THMs formation can help the utilities to minimize the DBP concentrations, providing healthier and microbially safer water. The authors present data on chlorine decay kinetics and total trihalomethanes (TTHM) formation kinetics and modeling with different molecular weights NOM fractions of Mississippi River water.

Short communication: effects of X-rays on growth and germinal tissue of calves.

A study was carried out to measure the growth and germinal tissue responses of young bull calf whose testicles were exposed to different levels of high energy, pulsed beams (X rays). Treatments (absorbed doses) were 0, 1530, 1980, 3060, or 6300 rads. Body weights were measured monthly for 10 mo; testosterone concentrations were measured in mo 2 and 5.