Loss of DOT1L function disrupts neuronal transcription, animal behavior, and leads to a novel neurodevelopmental disorder.

Individuals with monoallelic pathogenic variants in the histone lysine methyltransferase DOT1L display global developmental delay and varying congenital anomalies. However, the impact of monoallelic loss of remains unclear. Here, we present a largely female cohort of 11 individuals with variants with developmental delays and dysmorphic facial features.

Important Crop Pollinators Respond Less Negatively to Anthropogenic Land Use Than Other Animals.

Animal-mediated pollination is a key ecosystem service required to some extent by almost three-quarters of the leading human food crops in global food production. Anthropogenic pressures such as habitat loss and land-use intensification are causing shifts in ecological community composition, potentially resulting in declines in pollination services and impacting crop production. Previous research has often overlooked interspecific differences in pollination contribution, yet such differences mean that biodiversity declines will not necessarily negatively impact pollination.

Framing the future: Ensuring vulnerable island communities are engaged.

Objective: Statements such as the Bridgetown Declaration serve as a wake-up call for action to address the significant mental health needs in small island developing states. Overarching frameworks and action plans have been developed to support nations to promote mental health and build resilience for their populations in the region, and while these frameworks and action plans provide direction, translating them into grassroots change can be a challenge. At the Creating Futures 23 conference, delegates from the Oceania region were invited to participate in a plenary workshop entitled Framing the Future.

Geometric morphometric analysis of the brainstem and cerebellum in Chiari I malformation.

Background: Chiari I malformation (CMI) is characterized by inferior descent of the cerebellar tonsils through the foramen magnum and is associated with headache and neck pain. Many morphometric research efforts have aimed to describe CMI anatomy in the midsagittal plane using classical measurement techniques such as linear dimensions and angles. These methods are less frequently applied to parasagittal features and may fall short in quantifying more intricate anatomy with fewer distinct homologous landmarks.

Rare case of divided phrenic nerve variation: a cadaveric case report.

The phrenic nerve innervates the respiratory diaphragm, the primary muscle active during ventilation. The canonical path of the phrenic nerve originates from the cervical spine at C3-C5 spinal nerves and travels inferiorly through the neck and thoracic cavity to reach the diaphragm. During a cadaver dissection, a variation of the phrenic nerve was discovered in a 93-year-old male specimen.

Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi-ascending dose study with a bioequivalence arm in healthy volunteers.

PF614, a trypsin-activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs) of plasma oxycodone following oral administration. This study was a two-part design including a multi-ascending dose (part A) and a bioequivalence (BE) study (part B) in healthy volunteers. In part A, 24 subjects were randomized 3:1 to receive PF614 (50, 100, or 200 mg, n = 6/cohort) or OxyContin (20, 40, or 80 mg; n = 2/cohort) in ascending cohorts, delivered every 12 h for a total of nine doses.

Acetic Acid Enables Molecular Enumeration of Mycobacterium tuberculosis from Sputum and Eliminates the Need for a Biosafety Level 3 Laboratory.

Background: Improved monitoring of Mycobacterium tuberculosis response to treatment is urgently required. We previously developed the molecular bacterial load assay (MBLA), but it is challenging to integrate into the clinical diagnostic laboratory due to a labor-intensive protocol required at biosafety level 3 (BSL-3). A modified assay was needed.

Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis.

Background: Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug.

Treatment Failure in a UK Malaria Patient Harboring Genetically Variant Plasmodium falciparum From Uganda With Reduced In Vitro Susceptibility to Artemisinin and Lumefantrine.

Background: Recent cases of clinical failure in malaria patients in the United Kingdom (UK) treated with artemether-lumefantrine have implications for malaria chemotherapy worldwide.

Methods: Parasites were isolated from an index case of confirmed Plasmodium falciparum treatment failure after standard treatment, and from comparable travel-acquired UK malaria cases. Drug susceptibility in vitro and genotypes at 6 resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor.

Key tropical crops at risk from pollinator loss due to climate change and land use.

Insect pollinator biodiversity is changing rapidly, with potential consequences for the provision of crop pollination. However, the role of land use-climate interactions in pollinator biodiversity changes, as well as consequent economic effects via changes in crop pollination, remains poorly understood. We present a global assessment of the interactive effects of climate change and land use on pollinator abundance and richness and predictions of the risk to crop pollination from the inferred changes.

Rare discovery of sacral "ribs": a cadaveric case report.

Supernumerary ribs are a well-documented congenital anomaly that can occur at any point of the vertebral column, most commonly in the cervical or lumbar region. However, accessory ribs found in the sacrococcygeal region are exceptionally rare and may be difficult to distinguish from other bony manifestations of the pelvic girdle. During cadaveric dissection, a pair of sacral "ribs" were found projecting from the left posterolateral sacral region.

Fermentation Gone Wild: A Biochemistry Laboratory Experiment.

An experiment for the upper-level biochemistry laboratory is described in which students isolate a wild yeast from environmental sources and characterize the strain for its potential in the brewing industry. In addition to providing valuable experience in important biochemical techniques, this study also illustrates key principles of bioprospecting, the search for new biological sources with potential commercial or scientific value. By foraging for yeast in the wild, students explore the microbial diversity of their local environment and potentially find untapped sources of yeast that produce novel flavors and aromas.

Endogenous CRISPR/Cas systems for genome engineering in the acetogens and .

Acetogenic bacteria can play a major role in achieving Net Zero through their ability to convert CO into industrially relevant chemicals and fuels. Full exploitation of this potential will be reliant on effective metabolic engineering tools, such as those based on the CRISPR/Cas9 system. However, attempts to introduce -containing vectors into were unsuccessful, most likely as a consequence of Cas9 nuclease toxicity and the presence of a recognition site for an endogenous restriction-modification (R-M) system in the gene.

Exploitation of a Type 1 Toxin-Antitoxin System as an Inducible Counter-Selective Marker for Genome Editing in the Acetogen .

Targeted mutations in the anaerobic methylotroph have previously been obtained using CRISPR-based mutagenesis methods. In this study, a RelB-family toxin from was placed under the control of an anhydrotetracycline-sensitive promoter, forming an inducible counter-selective system. This inducible system was coupled with a non-replicative integrating mutagenesis vector to create precise gene deletions in B2.

A Standardized Protocol for Opioid Prescribing After Surgery Decreases Total Morphine Equivalents Prescribed.

Introduction: Perioperative opioid analgesia has been extensively reexamined during the opioid epidemic. Multiple studies have demonstrated over prescription of opioids, demonstrating the need for change in prescribing practices. A standard opioid prescribing protocol was implemented to evaluate opioid prescribing trends and practices.

An Unusual Variant of Anomalous Pancreaticobiliary Junction.

A 27-year-old previously healthy African American female presented to the Emergency Department with an acute onset of epigastric abdominal pain and nausea. Laboratory studies proved unremarkable. CT scan demonstrated intrahepatic and extrahepatic biliary ductal dilation with possible stones within the common bile duct.

Achieving a real-time online monitoring system for conservation culturomics.

Environmental monitoring is increasingly shifting toward a set of systems that describe changes in real time. In ecology specifically, a series of challenges have prevented the rollout of real-time monitoring for features such as biodiversity change or ecosystem service provision. Conservation culturomics, a field concerned with interactions between people and nature, is well placed to demonstrate how monitoring might move toward a network of real-time platforms, given its existence exclusively in the digital realm.

The role of social innovation in tackling global poverty and vulnerability.

Tackling the rapid rise in global poverty is one of the most pressing challenges the world faces today, especially in this new age of turbulence. On top of the ongoing environmental crisis, the last fifteen years has been rocked by the financial crisis of 2007-8, compounded by the 2020 Covid-pandemic and then by the 2022 war in Ukraine, each of which has negatively impacted all aspects of sustainable development. Although in practice many development organizations have been using the methods and processes of social innovation to tackle poverty and vulnerability for many years, it is only recently that they have specifically begun to analyse and codify its contribution to these and other SDGs.

Morphology and morphometry of the human obturator nerve in males and females.

Peripheral nerve injury and the nerves' subsequent repair and regeneration continues to be marked clinically by poor functional recovery. The analysis of nerve morphology is an aspect which may provide an impact on successful clinical outcomes through better prediction of donor and recipient matching. In this study, we evaluated the morphological aspects of the human obturator nerve for a better understanding of its potential in nerve transplantation.

Evolution of drug resistance in the genomic era.

has acquired drug resistance to all drugs that have been used against it, including those only recently introduced into clinical practice. Compared to other bacteria, it has a well conserved genome due to its role as an obligate human pathogen that has adapted to a niche over five to ten thousand years. These features facilitate reconstruction and dating of phylogenies, giving key insights into how resistance has been acquired and spread globally.

European household spending and socio-economic impacts on food behavior during the first wave of COVID-19.

This paper provides a European-level analysis using a large-scale survey of 13 countries to examine the power of relevant economic and socio-demographic characteristics to account for changes in food consumption and purchasing behavior during COVID-19. This was done by focusing on a two-level analysis of subject-related predictors highlighted in many existing country-level studies to test the generality of their significance. The Level 1 predictors relate to the individual households participating in the survey consisting of household composition, education, and location, as well as three types of perceived COVID-19 risks of infection, severity, and anxiety.

Setting Preconception Care Priorities in Australia Using a Delphi Technique.

Preconception health affects fertility, pregnancy, and future health outcomes but public awareness of this is low. Our aims were to rank priorities for preconception care (PCC), develop strategies to address these priorities, and establish values to guide future work in preconception healthcare in Australia. A Delphi technique involved two rounds of online voting and mid-round workshops.

Design, Analysis, and Implementation of a Novel Biochemical Pathway for Ethylene Glycol Production in .

The platform chemical ethylene glycol (EG) is used to manufacture various commodity chemicals of industrial importance, but largely remains synthesized from fossil fuels. Although several novel metabolic pathways have been reported for its bioproduction in model organisms, none has been reported for gas-fermenting, non-model acetogenic chassis organisms. Here, we describe a novel, synthetic biochemical pathway to convert acetate into EG in the industrially important gas-fermenting acetogen,.