ONC213: a novel strategy to resensitize resistant AML cells to venetoclax through induction of mitochondrial stress.

Background: Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and a salvage therapy for relapsed/refractory patients who have been treated with intensive chemotherapy. While this is an important treatment option, many patients fail to achieve complete remission and of those that do, majority relapse. Leukemia stem cells (LSCs) are believed to be responsible for AML relapse and can be targeted through oxidative phosphorylation reduction.

Aspergillus nidulans cell wall integrity kinase, MpkA, impacts cellular phenotypes that alter mycelial-material mechanical properties.

Mycelial materials are an emerging, natural material made from filamentous fungi that have the potential to replace unsustainable materials used in numerous commercial applications (e.g., packaging, textiles, construction).

Autism Spectrum Social Stories in Schools Trial 2 (ASSSIST-2): a pragmatic randomised controlled trial of the Social Stories™ intervention to address the social and emotional health of autistic children in UK primary schools.

Background: Autistic children can experience mental health, social and emotional difficulties. Carol Gray's Social Stories™ are a highly personalised intervention that provide social information in a short individually tailored story.

Methods: A multi-site pragmatic cluster randomised controlled trial to evaluate the clinical and cost-effectiveness of Social Stories™ alongside care as usual in autistic children aged 4-11 years.

Protein kinases MpkA and SepH transduce crosstalk between CWI and SIN pathways to activate protective hyphal septation under echinocandin cell wall stress.

Unlabelled: This study investigates a previously unreported stress signal transduced as crosstalk between the cell wall integrity (CWI) pathway and the septation initiation network (SIN). Echinocandins, which target cell wall synthesis, are widely used to treat mycoses. Their efficacy, however, is species specific.

Haploinsufficiency of lysosomal enzyme genes in Alzheimer's disease.

There is growing evidence suggesting that the lysosome or lysosome dysfunction is associated with Alzheimer's disease (AD). Pathway analysis of post mortem brain-derived proteomic data from AD patients shows that the lysosomal system is perturbed relative to similarly aged unaffected controls. However, it is unclear if these changes contributed to the pathogenesis or are a response to the disease.

M1 muscarinic receptor activation reverses age-related memory updating impairment in mice.

Previously consolidated memories can become temporarily labile upon reactivation. Reactivation-based memory updating is chiefly studied in young subjects, so we aimed to assess this process across the lifespan. To do this, we developed a behavioural paradigm wherein a reactivated object memory is updated with contextual information; 3-month-old and 6-month-old male C57BL/6 mice displayed object memory updating, but 12-month-old mice did not.

Cluster randomized trial of a team communication training implementation strategy for depression screening in a pediatric healthcare system: a study protocol.

Background: Pediatric depression is a global concern that has fueled efforts for enhanced detection and treatment engagement. As one example, the US Preventive Services Task Force recommends depression screening for adolescents ages 12-18 years. While many health systems have implemented components of depression screening protocols, there is limited evidence of effective follow-up for pediatric depression.

Diversity in U.S. Clinical Trials for Head and Neck Cancer: Are We Improving?

Background: This study assesses whether national initiatives undertaken to improve diversity in clinical trial enrollment have been successful within head and neck cancer (HNC) trials.

Methods: A retrospective analysis was conducted of HNC trials published on clinicaltrials.gov with start dates between 2000 and 2023.

Incremental Inverse Design of Desired Soybean Phenotypes.

We present an application of computational inverse design, which reverses the conventional trial-and-error forward design paradigm, optimizes biological phenotype by directly modifying genotype. The limitations of inverse design in genotype-to-bulk phenotype (G-BP) mapping can be addressed via an established design paradigm: "design, build, test, learn" (DBTL), where computational inverse design automates both the design and learn phases. In any context, inverse design is limited by the fundamental "one-to-many" nature of the inverse function.

Using flux theory in dynamic omics data sets to identify differentially changing signals using DPoP.

Background: Derivative profiling is a novel approach to identify differential signals from dynamic omics data sets. This approach applies variable step-size differentiation to time dynamic omics data. This work assumes that there is a general omics derivative that is a useful and descriptive feature of dynamic omics experiments.

Exogenous oxytocin administered to induce or augment labour is positively associated with quality of observed mother-infant bonding.

Oxytocin is a key hormone in the transition to motherhood. The maternal endogenous oxytocin system facilitates many physiological and biological adaptations, including breastfeeding, maternal wellbeing, and brain plasticity. Additionally, maternal endogenous oxytocin works as a finetuned orchestrator prior to, during, and after the birth of a child to support birth progression and mother-infant bonding.

The use of audio-biographical cues in dementia care: a four-year evaluation in Swiss hospitals, care, and domestic homes.

Introduction: In dementia care, the integration of innovative interventions is essential to enhancing the wellbeing and quality of life of people with dementia. Among these interventions, the Music Mirror intervention has emerged as a promising tool to provide personalized audio-biographical cues aimed at soothing, motivating, and engaging people with dementia. This study examined the effects of a Music Mirror intervention on the (a) wellbeing, emotions, and behavioral and psychological symptoms of 155 individuals with dementia, (b) perceived burden, relationship quality, and gains of their informal/formal caregivers, and (c) momentary closeness, wellbeing and stress of caregivers.

Impact of Social Stories on social and emotional health of autism spectrum primary school children: the ASSSIST2 RCT with economic evaluation.

Background: Differences in the way autistic children experience the world can contribute to anxiety and stress. Carol Gray's Social Stories™ are a highly personalised intervention to support children by providing social information about specific situations in an individual story.

Objectives: This randomised controlled trial aimed to establish whether Social Stories are clinically effective and cost-effective in improving social responsiveness and social and emotional health in children on the autism spectrum in schools.

Metabolic adaptation and related biomechanics in an ankle-based exoskeleton system during six sessions of steady state walking.

Ankle-based exoskeletons have demonstrated metabolic benefits during steady-state walking; however, variability exists in individual adaptation timelines necessary to achieve those benefits. This study assessed timelines for metabolic and gait-related adaptation while wearing an ankle-based exoskeleton while powered (EXOP) compared to unpowered (EXNP) and no device worn (NOEX). Metabolic (VO) and biomechanics data were collected while 14 participants walked on a treadmill at 1.

The evolution and history of Vinca alkaloids: From the Big Bang to the treatment of pediatric acute leukemia.

An attractive flower from the island of Madagascar has in part saved the lives of thousands of children with acute lymphoblastic leukemia (ALL). Random mutations and alterations to the genome led to the evolution of genes encoding enzymes, which would provide the periwinkle flower an arsenal of secondary metabolites to survive within the Madagascar ecosystem. Of the over 200 alkaloid compounds synthesized by the periwinkle, vincristine and vinblastine are the two most well-known being used for chemotherapy treatments, including for children with ALL.

Constitutional mismatch repair deficiency: a case on a commonly misinterpreted mutation in colon cancer.

It is estimated that 153,020 cases of CRC per year, with an increase in diagnoses in younger patients. We present a case of a female with an early presentation of Lynch Syndrome and CRC, who, on her third malignant presentation, was re-diagnosed as a constitutional mismatch repair deficiency.

"Who's watching?": Exploring patients' acceptance of having their consultations livestreamed for educational purposes.

Shortages of clinical placements are an ever-increasing global challenge. Livestreaming clinical experiences to remotely-located learners shows promise in addressing this challenge. However, little is known about the acceptability of livestreamed clinical experiences for patients.

Combining the novel FLT3 and MERTK dual inhibitor MRX-2843 with venetoclax results in promising antileukemic activity against FLT3-ITD AML.

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately one third of acute myeloid leukemia (AML) patients. FLT3-Internal tandem duplication (FLT3-ITD) mutations are the most common FLT3 mutations and are associated with a poor prognosis. Gilteritinib is a FLT3 inhibitor that is US FDA approved for treating adult patients with relapsed/refractory AML and a FLT3 mutation.

Pharmacotherapeutic potential of malvidin to cure imidacloprid induced hepatotoxicity via regulating PI3K/AKT, Nrf-2/Keap-1 and NF-κB pathway.

Imidacloprid (IMI) is one of the top-notch insecticides that adversely affects the body organs including the liver. Malvidin (MAL) is a natural flavonoid which exhibits a wide range of pharmacological properties. This research was designed to evaluate the protective ability of MAL to counteract IMI instigated liver toxicity in rats.

Therapeutic potential of salvigenin to combat atrazine induced liver toxicity in rats via regulating Nrf-2/Keap-1 and NF-κB pathway.

Atrazine (ATR) is the second most extensively used herbicide which adversely affects the body organs including liver. Salvigenin (SGN) is a flavonoid which demonstrates a wide range of biological and pharmacological abilities. This study was planned to assess the protective ability of SGN to avert ATR induced liver damage in rats.

Ultrasound assessment of acute Achilles tendon rupture and measurement of the tendon gap.

Achilles tendon rupture is a common sports-related injury which can carry significant morbidity to patients. Ultrasound remains the workhorse of imaging as it can confirm and localise the extent of Achilles tendon injury. The sonographic anatomy, both normal and ruptured sonographic appearances, as well as sonographic technique must be appreciated to accurately image and report findings, critical to patient management.