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CONTEXT.—: Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and β-thalassemia. OBJECTIVE.—: To assess a comprehensive approach for the screening and diagnosis of rare thalassemia. DESIGN.—: The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing...

INTRODUCTION: The specific physiological background induced by pregnancy leads to significant changes in maternal pharmacokinetics, suggesting potential variability in plasma concentrations of antiretrovirals. Pregnant HIV patients exposed to subtherapeutic doses, particularly in the last trimester of the pregnancy, have higher chances to transmit the infection to their children. Therefore, the therapeutic drug monitoring of antiretrovirals in HIV pregnant patients would be of great value...

Aversive caregiving in early life is a risk factor for aberrant brain and behavioral development. This outcome is related to epigenetic dysregulation of the brain-derived neurotrophic factor (Bdnf) gene. The Bdnf gene encodes for BDNF, a neurotrophin involved in early brain development, neural plasticity, learning, and memory. Recent work suggests that exercise may be neuroprotective in part by supporting BDNF protein and gene expression, making it an exciting target for therapeutic interventions. To our knowledge, exercise has never been studied as a therapeutic intervention in preclinical rodent models of caregiver maltreatment...


Brain-Computer Interfaces (BCIs) have the potential to reinstate lost communication faculties. Results from speech decoding studies indicate that a usable speech BCI based on activity in the sensorimotor cortex (SMC) can be achieved using subdurally implanted electrodes. However, the optimal characteristics for a successful speech implant are largely unknown. We address this topic in a high field blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) study, by assessing the decodability of spoken words as a function of hemisphere, gyrus, sulcal depth, and position along the ventral/dorsal-axis...

Temporal control is central to deploy and coordinate genetic programs during development. At present, there is limited understanding of the molecular mechanisms that govern the duration and speed of developmental processes. Timing mechanisms may run in parallel and/or interact with each other to integrate temporal signals throughout the organism. In this piece, we consider findings on the extrinsic control of developmental tempo and discuss the intrinsic roles of cell cycle, metabolic rates, protein turnover, and post-transcriptional mechanisms in the regulation of tempo during neural development...

A recent article in Perspectives on Psychological Science (Webb & Tangney, 2022) reported a study in which just 2.6% of participants recruited on Amazon's Mechanical Turk (MTurk) were deemed "valid." The authors highlighted some well-established limitations of MTurk, but their central claims-that MTurk is "too good to be true" and that it captured "only 14 human beings . . . [out of] N = 529"-are radically misleading, yet have been repeated widely. This commentary aims to (a) correct the record (i.e., by showing that Webb and Tangney's approach to data collection led to unusually low data quality) and (b) offer a shift in perspective for running high-quality studies online...

Poisonous mushrooms containing α-amatoxin can be lethal, making it imperative to develop a rapid and sensitive detection method for α-amatoxin. Utilizing the DNA tetrahedral structure as its foundation, the aptamer allows controlled density and orientation. Consequently, we designed aptamer tetrahedral functionalized magnetic beads that specifically target α-amanitin to release complementary DNA (C-DNA) strands. These strands were then employed as primers to initiate rolling circle amplification (RCA) with fluorescent dyes...

PURPOSE: Student study behaviours that prioritise the UKMLA content map over the local curriculum are a significant risk for UK medical education. To mitigate this, we describe a student-centred faculty process to improve local curriculum guidance based on an evaluation of student study behaviours, concerns and needs. Responses informed the build of an online curriculum map. METHODS: A mixed methods approach was adopted, including an online anonymous survey exploring student study behaviours and preferences for curricular guidance...

The underlying mechanism(s) by which the PML::RARA fusion protein initiates acute promyelocytic leukemia is not yet clear. We defined the genomic binding sites of PML::RARA in primary mouse and human hematopoietic progenitor cells with V5-tagged PML::RARA, using anti-V5-PML::RARA chromatin immunoprecipitation sequencing and CUT&RUN approaches. Most genomic PML::RARA binding sites were found in regions that were already chromatin-accessible (defined by ATAC-seq) in unmanipulated, wild-type promyelocytes, suggesting that these regions are "open" prior to PML::RARA expression...

The failures of individual agents can significantly impact the functionality of associated groups in interconnected systems. To reveal these impacts, we develop a threshold model to investigate cascading failures in double-layer hypergraphs with interlayer interdependence. We hypothesize that a hyperedge disintegrates when the proportion of failed nodes within it exceeds a threshold. Due to the interdependence between a node and its replica in the other layer, the disintegrations of these hyperedges could trigger a cascade of events, leading to an iterative collapse across these two layers...

INTRODUCTION: A specialized service for antifungal blood level determination is not available in Colombia. This service is essential for the proper follow-up of antifungal therapies. OBJECTIVE: To standardize and validate a simple, sensitive, and specific protocol based on high-performance liquid chromatography with a diode array detector for voriconazole blood level quantification. MATERIALS AND METHODS: We used an Agilent HPLC™ series-1200 equipment with a UVdiode array detector with an analytical column Eclipse XDB-C18 and pre-column Eclipse- XDB-C18 (Agilent)...

Functional lipids, primarily derived through the modification of natural lipids by various processes, are widely acknowledged for their potential to impart health benefits. In contrast to chemical methods for lipid modification, enzymatic catalysis offers distinct advantages, including high selectivity, mild operating conditions, and reduced byproduct formation. Nevertheless, enzymes face challenges in industrial applications, such as low activity, stability, and undesired selectivity. To address these challenges, protein engineering techniques have been implemented to enhance enzyme performance in functional lipid synthesis...

Tannases are valuable industrial enzymes used in food, pharmaceutical, cosmetic, leather manufacture and in environmental biotechnology. In this study, 15 fungal isolates were obtained from Egyptian cultivated soil and marine samples. The isolated fungi were qualitatively and quantitatively screened for their abilities to produce tannase. The selected fungal isolate NRC8 giving highest tannase activity was identified by molecular technique (18S rRNA) as Aspergillus glaucus. Among different tannin-containing wastes tested, the black tea waste was the best substrate for tannase production by Aspergillus glaucus in solid-state fermentation (SSF)...

Advances in machine learning have enabled sufficiently accurate predictions of protein structure to be used in macromolecular structure determination with crystallography and cryo-electron microscopy data. The Phenix software suite has AlphaFold predictions integrated into an automated pipeline that can start with an amino acid sequence and data, and automatically perform model-building and refinement to return a protein model fitted into the data. Due to the steep technical requirements of running AlphaFold efficiently, we have implemented a Phenix-AlphaFold webservice that enables all Phenix users to run AlphaFold predictions remotely from the Phenix GUI starting with the official 1...

Neural tracing proteins like horseradish peroxidase-conjugated wheat germ agglutinin (WGA-HRP) can target the central nervous system (CNS) through anatomic retrograde transport without crossing the blood-brain barrier (BBB). Conjugating WGA-HRP to nanoparticles may enable the creation of BBB-bypassing nanomedicine. Microfluidics and two-photon confocal microscopy is applied to screen nanocarriers for transport efficacy and gain mechanistic insights into their interactions with neurons. Protein modification of gold nanoparticles alters their cellular uptake at the axonal terminal and activates fast retrograde transport...

The developmental origins of health and disease concept highlights the impact of early environments on chronic non-communicable diseases like diabetes, cardiovascular disease, and cancer. Studies using animal models have investigated how maternal factors such as undernutrition, overnutrition, obesity, and exposure to chemicals or hypoxia affect fetal development and offspring health, leading to issues like low birth weight, high blood pressure, dyslipidemia, and insulin resistance. Given the increasing prevalence of overweight and obesity among reproductive-age women, effective interventions are critical...

Occupations including first responders and military require manual tasks; therefore changes in hand strength and dexterity could affect performance. We hypothesised that pinch strength, grip strength, and dexterity will change after unloaded and loaded exercise. Twenty-four male (25 ± 4.0 yrs; 86.3 ± 9.3 kg) and 10 female (25 ± 6.0 yrs; 62.1 ± 5.9 kg) participants completed 3 conditions for 5 minutes: (1) no exercise (2) run with no load at 3...

One of the prerequisites for successful organ xenotransplantation is a reasonable size match between the porcine organ and the recipient's organ to be replaced. Therefore, the selection of a suitable genetic background of source pigs is important. In this study, we investigated body and organ growth, cardiac function, and genetic diversity of a colony of Auckland Island pigs established at the Center for Innovative Medical Models (CiMM), LMU Munich. Male and female Auckland Island pig kidney cells (selected to be free of porcine endogenous retrovirus C) were imported from New Zealand, and founder animals were established by somatic cell nuclear transfer (SCNT)...

Endoscopic endonasal skull base surgery is increasingly prevalent, with its scope expanding from pathogens in the midline region to those in the paramedian region. Maximizing anterior sphenoidectomy is important for the median approach, and lateralizing the pterygopalatine fossa is crucial for the paramedian approach. Maximizing the surgical corridor in the nasal cavity and minimizing damage to neurovascular structures are vital for establishing a surgical field with minimal bleeding, ensuring safe, precise, and gentle procedures...

We summarize the 10th Competition on Legal Information Extraction and Entailment. In this tenth edition, the competition included four tasks on case law and statute law. The case law component includes an information retrieval task (Task 1), and the confirmation of an entailment relation between an existing case and a selected unseen case (Task 2). The statute law component includes an information retrieval task (Task 3), and an entailment/question-answering task based on retrieved civil code statutes (Task 4)...