Exploring Orodispersible Films Containing the Proteolysis Targeting Chimera ARV-110 in Hot Melt Extrusion and Solvent Casting Using Polyvinyl Alcohol.

Background/objectives: This project aims to provide valuable insights into the formulation of orodispersible films (ODFs) for the delivery of PROTAC ARV-110. The primary objective of this drug delivery formulation is to enhance the solubility of PROTAC ARV-110, which faces significant challenges due to the low solubility of this active pharmaceutical ingredient, as it belongs to a molecular class that is considered to exceed the "Rule of Five".

Methods: We employed the concept of developing a rapidly disintegrating ODF to enhance the solubility of PROTAC ARV-110, utilizing polyvinyl alcohol as the polymer of choice.

Pan-phylum genomes of hornworts reveal conserved autosomes but dynamic accessory and sex chromosomes.

Hornworts, one of the three bryophyte phyla, show some of the deepest divergences in extant land plants, with some families separated by more than 300 million years. Previous hornwort genomes represented only one genus, limiting the ability to infer evolution within hornworts and their early land plant ancestors. Here we report ten new chromosome-scale genomes representing all hornwort families and most of the genera.

Diaci v3.0: chromosome-level assembly, de novo transcriptome, and manual annotation of Diaphorina citri, insect vector of Huanglongbing.

Background: Diaphorina citri is an insect vector of "Candidatus Liberibacter asiaticus" (CLas), the gram-negative bacterial pathogen associated with citrus greening disease. Control measures rely on pesticides with negative impacts on the environment, natural ecosystems, and human and animal health. In contrast, gene-targeting methods have the potential to specifically target the vector species and/or reduce pathogen transmission.

Outlier detection in cardiac diffusion tensor imaging: Shot rejection or robust fitting?

Cardiac diffusion tensor imaging (cDTI) is highly prone to image corruption, yet robust-fitting methods are rarely used. Single voxel outlier detection (SVOD) can overlook corruptions that are visually obvious, perhaps causing reluctance to replace whole-image shot-rejection (SR) despite its own deficiencies. SVOD's deficiencies may be relatively unimportant: corrupted signals that are not statistical outliers may not be detrimental.

Teneurin C-Terminal Associated Peptide (TCAP)-1 Attenuates Restraint Stress-Induced Corticosterone Increases in Male Mice and Rats.

Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis response can result in anxiety and other neuropsychiatric disorders and effective therapeutics are needed to mitigate this maladaptive response. Here we examined the effects of Teneurin C-terminal Associated Peptide (TCAP)-1, a peptide known to inhibit corticotropin releasing factor (CRF)-mediated stress, on the physiological expression of stress, and whether the effects of TCAP-1 were dependent on the route of administration. We first examined whether subcutaneous administration of TCAP-1 influenced tube restraint stress-induced corticosterone (CORT) increases in both male mice and rats.

Social Determinants of Health and Language and Academic Outcomes in Pediatric Cochlear Implantation: A Systematic Review and Meta-Analysis.

Importance: Cochlear implants can restore sound and enable speech and language development for children with severe to profound sensorineural hearing loss. Long-term outcomes of pediatric cochlear implant recipients are variable. Although the association between social determinants of health (SDH) and pediatric cochlear implant outcomes has been explored, the strength of this association has not been quantitatively synthesized in the literature.

Reducing Learning and Psychosocial Disparities in Latino Children with Cancer: A Randomized Intervention Trial.

Background: We developed a high-intensity parenting intervention (HIP) to help parents support the academic success of childhood cancer survivors (CCSs), who often face post-treatment challenges affecting their school-related functioning. This randomized controlled trial (NCT03178617) evaluated HIP's efficacy compared to lower-intensity, single-session, treatment-as-usual services (LIP) in Latino families. Primary outcomes were parenting efficacy and CCSs' school functioning; secondary outcomes included parenting knowledge and measures of CCSs' academic performance, attention, and functioning outside of school.

Resuscitative endovascular balloon occlusion of the aorta in the patient with obesity.

Background: Palpation of anatomic landmarks is difficult in patients with obesity, which could increase difficulty of achieving femoral access and resuscitative endovascular balloon occlusion of the aorta (REBOA) placement. The primary aim of this study was to examine the association between obesity and successful REBOA placement. We hypothesized that higher body mass index (BMI) would decrease first-attempt success and increase time to successful aortic occlusion (AO).

Uniform chi-squared model probabilities in NMR crystallography.

A nearly universal component of NMR crystallography is the ranking of candidate structures based on how well their first-principles-predicted NMR parameters align with the results of solid-state NMR experiments. Here, a novel approach for assigning probabilities to candidate models is proposed that quantifies the likelihood that each model is the correct experimental structure. This method employs hierarchical Bayesian inference and leverages explicit prior probabilities derived from a uniform distribution of potential candidate structures with respect to chi-squared values.

The interplay of density functional selection and crystal structure for accurate NMR chemical shift predictions.

chemical shift prediction plays a central role in nuclear magnetic resonance (NMR) crystallography, and the accuracy with which chemical shifts can be predicted relative to experiment impacts the confidence with which structures can be assigned. For organic crystals, periodic density functional theory calculations with the gauge-including projector augmented wave (GIPAW) approximation and the PBE functional are widely used at present. Many previous studies have examined how using more advanced density functionals can increase the accuracy of predicted chemical shifts relative to experiment, but nearly all of those studies employed crystal structures that were optimized with generalized-gradient approximation (GGA) functionals.

Cannabis Use, Use Disorder, and Workplace Absenteeism in the U.S., 2021-2022.

Introduction: Cannabis use and cannabis use disorder (CUD) are associated with adverse psychosocial outcomes, but their impact on workplace absenteeism remains poorly understood. Moreover, few studies have examined the role of CUD severity. This study aims to address these gaps by examining the associations between cannabis use recency, frequency, CUD severity, and workplace absenteeism.

NCI SEER-Linked Virtual Tissue Repository Pilot.

Background: The Surveillance, Epidemiology, and End Results (SEER) Program with the National Cancer Institute tested whether population-based cancer registries can serve as honest brokers to acquire tissue and data in the SEER-Linked Virtual Tissue Repository (VTR) Pilot.

Methods: We collected formalin-fixed, paraffin-embedded tissue and clinical data from patients with pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC) for two studies comparing cancer cases with highly unusual survival (≥5 years for PDAC and ≤30 months for BC) to pair-matched controls with usual survival (≤2 years for PDAC and ≥5 years for BC). Success was defined as the ability for registries to acquire tissue and data on cancer cases with highly unusual outcomes.

Predictors of Response to Cognitive Behavioral Therapy in Patients With Tinnitus.

Importance: Clinical guidelines recommend cognitive behavioral therapy (CBT) as a treatment for tinnitus. However, patient response to CBT is variable, and currently, there are no known predictors of response to CBT treatment for tinnitus.

Objective: To identify the clinical predictors of patient response to CBT for treatment of tinnitus.

Use of Poly(vinyl alcohol) in Spray-Dried Dispersions: Enhancing Solubility and Stability of Proteolysis Targeting Chimeras.

PROTACs, proteolysis targeting chimeras, are bifunctional molecules inducing protein degradation through a unique proximity-based mode of action. While offering several advantages unachievable by classical drugs, PROTACs have unfavorable physicochemical properties that pose challenges in application and formulation. In this study, we show the solubility enhancement of two PROTACs, ARV-110 and SelDeg51, using Poly(vinyl alcohol).

Chromosome-scale genome assembly and annotation of the tetraploid potato cultivar Diacol Capiro adapted to the Andean region.

Potato (Solanum tuberosum) is an essential crop for food security and is ranked as the third most important crop worldwide for human consumption. The Diacol Capiro cultivar holds the dominant position in Colombian cultivation, primarily catering to the food processing industry. This highly heterozygous, autotetraploid cultivar belongs to the Andigenum group and it stands out for its adaptation to a wide variety of environments spanning altitudes from 1,800 to 3,200 meters above sea level.

Improved restoration of biomechanical factors using a narrow-box shaped reconstruction compared to a wide one in superior capsular reconstruction for irreparable supraspinatus tendon tears: a biomechanical study using a static shoulder simulator.

Hypothesis And/or Background: Extensive, irreparable rotator cuff tears remain a surgical challenge and multiple treatment options are proposed and currently in use. To biomechanically compare superior glenohumeral translation, subacromial contact pressures, and area in a box-shaped reconstruction using the long head of the biceps tendon (LHBT) in an irreparable supraspinatus tendon tear model.

Methods: Seven cadaveric shoulders (mean age 61 years; range 32-84 years; standard deviation 22.

Sedimentation of large, soluble proteins up to 140 kDa for H-detected MAS NMR and C DNP NMR - practical aspects.

Solution NMR is typically applied to biological systems with molecular weights < 40 kDa whereas magic-angle-spinning (MAS) solid-state NMR traditionally targets very large, oligomeric proteins and complexes exceeding 500 kDa in mass, including fibrils and crystalline protein preparations. Here, we propose that the gap between these size regimes can be filled by the approach presented that enables investigation of large, soluble and fully protonated proteins in the range of 40-140 kDa. As a key step, ultracentrifugation produces a highly concentrated, gel-like state, resembling a dense phase in spontaneous liquid-liquid phase separation (LLPS).