Engineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis.

Blood transfusion plays a vital role in modern medicine, but frequent shortages occur. Ex vivo manufacturing of red blood cells (RBCs) from universal donor cells offers a potential solution, yet the high cost of recombinant cytokines remains a barrier. Erythropoietin (EPO) signaling is crucial for RBC development, and EPO is among the most expensive media components.

Comparison between AI and human expert performance in acute pain assessment in sheep.

This study explores the question whether Artificial Intelligence (AI) can outperform human experts in animal pain recognition using sheep as a case study. It uses a dataset of N = 48 sheep undergoing surgery with video recordings taken before (no pain) and after (pain) surgery. Four veterinary experts used two types of pain scoring scales: the sheep facial expression scale (SFPES) and the Unesp-Botucatu composite behavioral scale (USAPS), which is the 'golden standard' in sheep pain assessment.

Automated landmark-based cat facial analysis and its applications.

Facial landmarks, widely studied in human affective computing, are beginning to gain interest in the animal domain. Specifically, landmark-based geometric morphometric methods have been used to objectively assess facial expressions in cats, focusing on pain recognition and the impact of breed-specific morphology on facial signaling. These methods employed a 48-landmark scheme grounded in cat facial anatomy.

Behavioral red flags for optimizing castration-induced acute pain diagnosis in cattle.

Unesp-Botucatu Cattle Pain Scale (UCAPS) is widely used in experimental settings, however the high number of UCAPS behaviors might represent a barrier to its implementation in the farm's or hospital's routine. We aimed to identify a smaller combination of UCAPS behaviors that could be used as behavioral red flags for optimizing the acute pain diagnosis in cattle. We hypothesize that a specific set of UCAPS behaviors might be used as behavioral red flags for pain.

Unripe Plantain Peel Biohydrogel for Methylene Blue Removal from Aqueous Solution.

Dye contamination is a serious environmental issue, particularly affecting water bodies, driving efforts to synthesize adsorbent materials with high dye-removal capacities. In this context, eco-friendly and cost-effective materials derived from bioresidues are being explored to recycle and valorize waste. This study investigates the synthesis, characterization, and application of a biohydrogel made from unripe plantain peel (PP), modified with carboxymethyl groups and crosslinked using varying concentrations of citric acid (CA), an eco-friendly and economical organic acid.

Attitudes and opinions of Brazilian veterinarians towards the assessment and management of acute avian pain.

Background: Veterinarians' approaches to the management of avian pain have been poorly documented despite the rising number of pet birds seen in clinical settings.

Methods: An online survey was advertised nationwide to recruit Brazilian veterinarians who had treated traumatic and surgical conditions in birds within the previous year. The survey comprised 25 closed or semi-closed questions divided into four sections (demographics, routinely performed medical procedures and pain recognition, drug choices for analgesia and challenges to pain treatment, and attitudes towards pain relief in birds).

Automated video-based pain recognition in cats using facial landmarks.

Affective states are reflected in the facial expressions of all mammals. Facial behaviors linked to pain have attracted most of the attention so far in non-human animals, leading to the development of numerous instruments for evaluating pain through facial expressions for various animal species. Nevertheless, manual facial expression analysis is susceptible to subjectivity and bias, is labor-intensive and often necessitates specialized expertise and training.

The dual-specificity kinase DYRK1A interacts with the Hepatitis B virus genome and regulates the production of viral RNA.

The genome of Hepatitis B virus (HBV) persists in infected hepatocytes as a nuclear episome (cccDNA) that is responsible for the transcription of viral genes and viral rebound, following antiviral treatment arrest in chronically infected patients. There is currently no clinically approved therapeutic strategy able to efficiently target cccDNA (Lucifora J 2016). The development of alternative strategies aiming at permanently abrogating HBV RNA production requires a thorough understanding of cccDNA transcriptional and post-transcriptional regulation.

The diverging role of O-GlcNAc transferase in corticotroph and somatotroph adenomas.

Purpose: Molecular mechanisms involved in the pathogenesis and tumor progression of pituitary adenomas (PA) remain incompletely understood. Corticotroph and somatotroph PA are associated with a high clinical burden, and despite improved surgical outcomes and medical treatment options, they sometimes require multiple surgeries and radiation. Preliminary data suggested a role for O-GlcNAc Transferase (OGT), the enzyme responsible for the O-GlcNAcylation of proteins.

The impact of using pain scales by untrained students on the decision to provide analgesia to multiple species.

Objective: To evaluate if students without training assess pain similarly to an expert, and to compare indications for analgesic intervention based on student opinions versus scale scoring.

Study Design: Prospective, blind, randomized, cross-sectional study.

Animals: Video recordings of a bull, horse, cat, pig and sheep.

Real-time and video-recorded pain assessment in beef cattle: clinical application and reliability in young, adult bulls undergoing surgical castration.

Bovine pain assessment relies on validated behavioral scales related to normal and pain-related behaviors. This study investigated the reliability and applicability of real-time and video-recorded pain assessment, and their agreement, in young, adult bulls undergoing surgical castration. Ten Nelore and nine Angus bulls underwent general anesthesia and surgical castration.

Enhancement of erythropoietic output by Cas9-mediated insertion of a natural variant in haematopoietic stem and progenitor cells.

Some gene polymorphisms can lead to monogenic diseases, whereas other polymorphisms may confer beneficial traits. A well-characterized example is congenital erythrocytosis-the non-pathogenic hyper-production of red blood cells-that is caused by a truncated erythropoietin receptor. Here we show that Cas9-mediated genome editing in CD34 human haematopoietic stem and progenitor cells (HSPCs) can recreate the truncated form of the erythropoietin receptor, leading to substantial increases in erythropoietic output.

CHMP2A regulates broad immune cell-mediated antitumor activity in an immunocompetent in vivo head and neck squamous cell carcinoma model.

Background: Natural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us to define approaches to improve immune-mediate antitumor activity.

A simultaneous knockout knockin genome editing strategy in HSPCs potently inhibits CCR5- and CXCR4-tropic HIV-1 infection.

Allogeneic hematopoietic stem and progenitor cell transplant (HSCT) of CCR5 null (CCR5Δ32) cells can be curative for HIV-1-infected patients. However, because allogeneic HSCT poses significant risk, CCR5Δ32 matched bone marrow donors are rare, and CCR5Δ32 transplant does not confer resistance to the CXCR4-tropic virus, it is not a viable option for most patients. We describe a targeted Cas9/AAV6-based genome editing strategy for autologous HSCT resulting in both CCR5- and CXCR4-tropic HIV-1 resistance.

Age-related increase in the expression of 11β-hydroxysteroid dehydrogenase type 1 in the hippocampus of male rhesus macaques.

Introduction: The hippocampus is especially susceptible to age-associated neuronal pathologies, and there is concern that the age-associated rise in cortisol secretion from the adrenal gland may contribute to their etiology. Furthermore, because 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) catalyzes the reduction of cortisone to the active hormone cortisol, it is plausible that an increase in the expression of this enzyme enhances the deleterious impact of cortisol in the hippocampus and contributes to the neuronal pathologies that underlie cognitive decline in the elderly.

Methods: Rhesus macaques were used as a translational animal model of human aging, to examine age-related changes in gene and protein expressions of (/HSD11B1) in the hippocampus, a region of the brain that plays a crucial role in learning and memory.

Validation of the Portuguese Version of the Short-Form Glasgow Composite Measure Pain Scale (CMPS-SF) According to COSMIN and GRADE Guidelines.

We aimed to validate the CMPS-SF according to COSMIN and GRADE guidelines. Four trained evaluators assessed 208 videos (pre-operative-M1, peak of pain-M2, 1 h after the peak of pain and analgesia (rescue)-M3, and 24 h post-extubation-M4) of 52 dogs, divided into negative controls (n = 10), soft tissue surgeries (n = 22), and orthopedic surgeries (n = 20). The videos were randomized and blinded as to when they were filmed, and were evaluated in two stages, 21 days apart.

Combining Cell-Intrinsic and -Extrinsic Resistance to HIV-1 By Engineering Hematopoietic Stem Cells for CCR5 Knockout and B Cell Secretion of Therapeutic Antibodies.

Autologous transplantation of null hematopoietic stem and progenitor cells (HSPCs) is the only known cure for HIV-1 infection. However, this treatment is limited because of the rarity of -null matched donors, the morbidities associated with allogeneic transplantation, and the prevalence of HIV-1 strains resistant to CCR5 knockout (KO) alone. Here, we propose a one-time therapy through autologous transplantation of HSPCs genetically engineered to produce both CCR5 KO cells and long-term secretion of potent HIV-1 inhibiting antibodies from B cell progeny.

Factors Influencing Parental Willingness to Consent to a Survey Study for Patients in the Pediatric Emergency Department.

Objective: To identify factors that impact parental willingness to consent to research studies conducted for their children during visits to pediatric emergency departments (EDs).

Methods: Parents and guardians of children receiving care in our pediatric ED were approached and asked if they would be willing to let their child participate in a research study requiring the child to complete an electronic questionnaire. No such questionnaire existed, however, because the primary purpose was to ascertain the parent's willingness to let their child participate.

Loss of the DYRK1A Protein Kinase Results in the Reduction in Ribosomal Protein Gene Expression, Ribosome Mass and Reduced Translation.

Ribosomal proteins (RPs) are evolutionary conserved proteins that are essential for protein translation. RP expression must be tightly regulated to ensure the appropriate assembly of ribosomes and to respond to the growth demands of cells. The elements regulating the transcription of RP genes (RPGs) have been characterized in yeast and , yet how cells regulate the production of RPs in mammals is less well understood.