Identification of potent biparatopic antibodies targeting FGFR2 fusion driven cholangiocarcinoma.

Unlabelled: Translocations involving FGFR2 gene fusions are common in cholangiocarcinoma and predict response to FGFR kinase inhibitors. However, the rate and durability of response are limited due to the emergence of resistance, typically involving acquired FGFR2 kinase domain mutations, and to sub-optimal dosing, relating to drug adverse effects. Here, we report the development of biparatopic antibodies targeting the FGFR2 extracellular domain (ECD), as candidate therapeutics.

Recycling and 3D-Printing Biodegradable Membranes for Gas Separation-toward a Membrane Circular Economy.

Polymer membranes employed in gas separation play a pivotal role in advancing environmental sustainability, energy production, and gas purification technologies. Despite their significance, the current design and manufacturing of these membranes lack cradle-to-cradle approaches, contributing to plastic waste pollution. This study explores emerging solutions, including the use of biodegradable biopolymers such as polyhydroxybutyrate (PHB) and membrane recycling, with a focus on the specific impact of mechanical recycling on the performance of biodegradable gas separation membranes.

Non-destructive methods to assess pesticide exposure in free-living bats.

Bat populations are dwindling worldwide due to anthropogenic activities like agriculture, however the role that pesticide exposure plays on these declines is unclear. To address these research gaps, we first need to develop reliable methods to detect and monitor exposure to environmental pollutants and its effects on free-living bats. The use of biomarkers is a sensitive and informative tool to study sublethal effects in wildlife, however it requires laboratory validation and integrative approaches to be applicable to free-living species.

Recent Developments in Islet Biology: A Review With Patient Perspectives.

Navigating the coronavirus disease-2019 (COVID-19, now COVID) pandemic has required resilience and creativity worldwide. Despite early challenges to productivity, more than 2,000 peer-reviewed articles on islet biology were published in 2021. Herein, we highlight noteworthy advances in islet research between January 2021 and April 2022, focussing on 5 areas.

Systematic profiling of conditional degron tag technologies for target validation studies.

Conditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, successful design of a CDT fusion protein often requires a prolonged, ad hoc cycle of construct design, failure, and re-design. To address this limitation, we report here a system to rapidly compare the activity of five unique CDTs: AID/AID2, IKZF3d, dTAG, HaloTag, and SMASh.

Microtentacle Formation in Ovarian Carcinoma.

Background: The development of chemoresistance to paclitaxel and carboplatin represents a major therapeutic challenge in ovarian cancer, a disease frequently characterized by malignant ascites and extrapelvic metastasis. Microtentacles (McTNs) are tubulin-based projections observed in detached breast cancer cells. In this study, we investigated whether ovarian cancers exhibit McTNs and characterized McTN biology.

Preoperative photography improves patient satisfaction following hallux valgus surgery.

Background: Patient satisfaction is variable following hallux valgus (HV) surgery. This prospective, blinded, randomized trial endeavored to determine whether showing patients a preoperative photograph would improve satisfaction following HV corrective surgery.

Methods: Adult patients undergoing HV surgery were randomized to a picture group (P) or a no picture group (NP).

Cosmetic "Gold Thread Therapy": A Nuisance That Decreases the Diagnostic Quality of a Dental Panoramic Image.

During routine imaging of the craniofacial region, it is recognised that some "cosmetic" procedures with metallic insertions can be revealed radiographically. These objects however make it difficult to obtain a good interpretation of anatomical structures for management of diseases. A 58-year-old female patient visited a private dental facility in Kuala Lumpur for prosthodontic replacement of missing teeth.

Impact of pharmacist insulin injection re-education on glycemic control among type II diabetic patients in primary health clinics.

Background: Insulin injection technique re-education and diabetes knowledge empowerment has led to improved glycemic control.

Objectives: To evaluate the impact of pharmacist's monthly re-education on insulin injection technique (IT), lipohypertrophy, patients' perception on insulin therapy and its effect on glycaemic control.

Methods: This randomized controlled, multi-centered study was conducted among type 2 diabetics from 15 government health clinics.

Impaction fractures of the anterior tibial plafond: Outcomes after fractures around the ankle: Is the anterior impaction plafond fracture a problem?

Objectives: To determine whether patients with AO/OTA 43-B anterior impaction tibial plafond fractures have worse clinical outcomes, and an increased risk of progression to ankle arthrodesis.

Design: Retrospective cohort study.

Setting: Level 1 academic trauma center.

The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain.

Objective: To assess the analgesic efficacy and safety of single-dose oral cannabidiol (CBD) as an adjunct to standard care for patients presenting to an emergency department with acute low back pain.

Design: Randomised, double blinded, placebo-controlled clinical trial.

Setting: The tertiary emergency department of Austin Hospital, Melbourne.

Biomechanical Consequences of Nail Insertion Point and Anterior Cortical Perforation for Antegrade Femoral Nailing.

This biomechanical study assessed the influence of changing antegrade cephalomedullary nail insertion point from anterior to neutral to posterior locations relative to the tip of the greater trochanter with or without anterior cortical perforation in the distal femur. Artificial osteoporotic femurs and cephalomedullary nails were used to create 5 test groups each with 8 specimens: intact femur without a nail or perforation, anterior nail insertion point without perforation, neutral nail insertion point without perforation, posterior nail insertion point without perforation, and posterior nail insertion point with perforation. Nondestructive biomechanical tests were done at 250 N in axial, coronal 3-point bending, sagittal 3-point bending, and torsional loading in order to measure overall stiffness and bone stress.

Characterization of a novel yeast phase-specific antigen expressed during in vitro thermal phase transition of Talaromyces marneffei.

Talaromyces marneffei is a dimorphic fungus that has emerged as an opportunistic pathogen particularly in individuals with HIV/AIDS. Since its dimorphism has been associated with its virulence, the transition from mold to yeast-like cells might be important for fungal pathogenesis, including its survival inside of phagocytic host cells. We investigated the expression of yeast antigen of T.

The Role of Eicosanoids in Gynecological Malignancies.

Eicosanoids, bio-active lipid molecules, evoke a multitude of biological effects that directly affect cancer cells and indirectly affect tumor microenvironment. An emerging role has been shown for eicosanoids in the pathogenesis of gynecological malignancies which include cancers of the vulva, vagina, cervix, uterine, and ovary. Eicosanoid biosynthesis pathways start at the metabolism of phospholipids by phospholipase A2 then proceeding to one of three pathways: the cyclooxygenase (COX), lipoxygenase (LOX), or P450 epoxygenase pathways.

Efficacy of Clopidogrel for Prevention of Stroke Based on Allele Status in the POINT Trial.

Background And Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone.

Eicosanoids in Cancer: Prostaglandin E Receptor 4 in Cancer Therapeutics and Immunotherapy.

The cyclooxygenase-2 (COX-2) enzyme is frequently overexpressed in epithelial malignancies including those of the breast, prostate, lung, kidney, ovary, and liver and elevated expression is associated with worse outcomes. COX-2 catalyzes the metabolism of arachidonic acid to prostaglandins. The COX-2 product prostaglandin E (PGE) binds to four G-protein-coupled EP receptors designated EP1-EP4.

Ultrasound-guided in Utero Transplantation of Placental Stem Cells into the Liver of Crigler-Najjar Syndrome Model Rat.

Background: Advances in prenatal screening and early diagnosis of genetic disease will potentially allow for preemptive treatment of anticipated postnatal disease by in utero cell transplantation (IUCT). This strategy carries potential benefits over postnatal treatment, which might allow for improved engraftment and function of the transplanted cells. Congenital metabolic disorders may be an ideal target for this type of therapy, as in most cases, they require replacement of a single deficient hepatic enzyme, and multiple small-animal models exist for preclinical testing.

Metastatic Profile of Colorectal Cancer: Interplay Between Primary Tumor Location and KRAS Status.

Background: Mutant KRAS tumors are purported to metastasize differently than wild-type KRAS tumors. The biological heterogeneity of tumors from different parts of the colon are also reported to affect metastasis. This study aims to characterize the metastatic profile by evaluating these factors in unison.

Randomized Controlled Trial of Melatonin for Sleep Disturbance in Dravet Syndrome: The DREAMS Study.

Study Objectives: Dravet syndrome is a severe developmental and epileptic encephalopathy, in which 75% of patients have sleep disturbance. Melatonin is often used for sleep problems in childhood; however, there is no quality evidence supporting its use in Dravet syndrome. We hypothesized that melatonin would increase total sleep and quality of life for patients with Dravet syndrome.

Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial.

Objective: There is increasing recognition that, in men, some biological actions attributed to testosterone (TS) are mediated by estradiol (E2). This study used two low doses of daily transdermal E2 gel to assess the effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen deprivation therapy (ADT). Secondarily, we aimed to assess short-term biological effects of E2 add-back without increasing circulating TS.

Precision therapy for epilepsy due to mutations: A randomized trial of oral quinidine.

Objective: To evaluate quinidine as a precision therapy for severe epilepsy due to gain of function mutations in the potassium channel gene .

Methods: A single-center, inpatient, order-randomized, blinded, placebo-controlled, crossover trial of oral quinidine included 6 patients with severe autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) due to mutation. Order was block randomized and blinded.

Automated Bone Age Analysis with Lossy Image Files.

Background: In our U.S. Department of Defense hospital system, pediatric endocrinology and radiology resources to evaluate bone age radiographs are limited.