Single-cell DNA and surface protein characterization of high hyperdiploid acute lymphoblastic leukemia at diagnosis and during treatment.

High hyperdiploid (HeH) B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent subtype of childhood ALL. This leukemia is characterized by trisomies and tetrasomies of specific chromosomes and additional point mutations. Here, we used single-cell targeted DNA and antibody sequencing to determine the clonal evolution of HeH B-ALL during development and chemotherapy treatment.

Loss of mitochondrial amidoxime-reducing component 1 (mARC1) prevents disease progression by reducing fibrosis in multiple mouse models of chronic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease is a prevalent disease that affects nearly one-third of the global population. Recent genome-wide association studies revealed that a common missense variant in the gene encoding mitochondrial amidoxime reducing component 1 (mARC1) is associated with protection from metabolic dysfunction-associated steatotic liver disease, all-cause cirrhosis, and liver-related mortality suggesting a role for mARC1 in liver pathophysiology; however, little is known about its function in the liver. In this study, we aimed to evaluate the impact of mARC1 hepatoprotective variants on protein function, the effect of loss of mARC1 on cellular lipotoxic stress response, and the effect of global or hepatocyte-specific loss of mARC1 in various mouse models of metabolic dysfunction-associated steatohepatitis and liver fibrosis.

Improving Adherence to the Lead Exposure Protocol at Boston Medical Center's Pediatric Clinic.

Introduction: Using plan-do-study-act cycles, our team aimed to increase mean provider adherence to the Lead Exposure Protocol at the Boston Medical Center Pediatric Primary Care Clinic from 16% (baseline global mean provider adherence) to 80% from April 1, 2021, to February 1, 2023, thereby curbing the secondary effects of lead exposure.

Methods: Our team performed a chart review of patients 6 months to 5 years of age with blood lead levels (BLLs) ≥2 µg/dL (n = 853) to track provider adherence to Boston Medical Center's Lead Exposure Protocol. We created p charts to track the efficacy of interventions to improve adherence.

Migraine Genetic Susceptibility Does Not Strongly Influence Migraine Characteristics and Outcomes in a Treated, Real-World, Community Cohort.

: Migraine is a common neurological disorder with highly variable characteristics. While genome-wide association studies have identified genetic risk factors that implicate underlying pathways, the influence of genetic susceptibility on disease characteristics or treatment response is incompletely understood. We examined the relationships between a previously developed standardized integrative migraine polygenic genetic risk score (PRS) and migraine characteristics in a real-world, treated patient cohort.

An Integrative Migraine Polygenic Risk Score Is Associated with Age at Onset But Not Chronification.

: Genome-wide association studies (GWASs) demonstrate a complex genetic landscape for migraine risk. Migraine polygenic risk scores (PRSs) developed from GWAS data may have utility for predicting disease course. We analyzed the strength of association between an integrative migraine PRS and age at onset and chronification.

IVF with frozen-thawed sperm after prolonged capacitation yields comparable results to ICSI in horses: A morphokinetics study.

Intracytoplasmic sperm injection (ICSI) is the current clinical practice for the in vitro production of equine embryos. The use of conventional fertilization methods such as in vitro fertilization (IVF), has historically been associated with poor success in horses. However, recent improvements have led to better outcomes with IVF, though only when using fresh semen, which limits its use in clinical practice.

A 650-Myr history of Earth's axial precession frequency and the evolution of the Earth-Moon system derived from cyclostratigraphy.

The preservation of Milankovitch cycles in the stratigraphic record provides independent geological information to study our ancient solar system and can be leveraged to constrain existing theoretical models. Here, we identify 34 high-quality cyclostratigraphic records spanning the past 650 million years and use them to infer the evolution of the Earth-Moon system through a Bayesian inversion method. We reconstruct the time evolution of Earth's axial precession frequency, lunar distance, length of day, and the periods of obliquity and climatic precession cycles.

The existence of manual mode increases human blame for AI mistakes.

People are offloading many tasks to artificial intelligence (AI)-including driving, investing decisions, and medical choices-but it is human nature to want to maintain ultimate control. So even when using autonomous machines, people want a "manual mode", an option that shifts control back to themselves. Unfortunately, the mere existence of manual mode leads to more human blame when AI makes mistakes.

Unlocking the Complexity: Exploration of Acute Lymphoblastic Leukemia at the Single Cell Level.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. ALL originates from precursor lymphocytes that acquire multiple genomic changes over time, including chromosomal rearrangements and point mutations. While a large variety of genomic defects was identified and characterized in ALL over the past 30 years, it was only in recent years that the clonal heterogeneity was recognized.

Improving 3D dose prediction for breast radiotherapy using novel glowing masks and gradient-weighted loss functions.

Background: The quality of treatment plans for breast cancer can vary greatly. This variation could be reduced by using dose prediction to automate treatment planning. Our work investigates novel methods for training deep-learning models that are capable of producing high-quality dose predictions for breast cancer treatment planning.

Effects of substrate availability and mitochondrial disruption on oxidative metabolism and sperm motility in fertile dogs.

In several mammalian species, the measurement of mitochondrial oxygen consumption (MITOX) under different metabolic conditions has demonstrated a positive correlation with sperm motility and may be a sensitive indicator of mitochondrial health. In general, the maintenance of sperm motility and many key sperm functions and fertilizing events are heavily energy-dependent processes, and some species-specific substrate preferences exist. Although canine sperm have been known to undergo capacitation and maintain motility with supplementation of a wide range of energy substrates, the relationship between mitochondrial function, and the maintenance of oxidative metabolism and sperm motility remain unclear.

Strain concentration drives the anatomical distribution of injury in acute and chronic traumatic brain injury.

Brain tissue injury caused by mild traumatic brain injury (mTBI) disproportionately concentrates in the midbrain, cerebellum, mesial temporal lobe, and the interface between cortex and white matter at sulcal depths . The bio-mechanical principles that explain why physical impacts to different parts of the skull translate to common foci of injury concentrated in specific brain structures are unknown. A general and longstanding idea, which has not to date been directly tested in humans, is that different brain regions are differentially susceptible to strain loading.

Neural network dose prediction for cervical brachytherapy: Overcoming data scarcity for applicator-specific models.

Background: 3D neural network dose predictions are useful for automating brachytherapy (BT) treatment planning for cervical cancer. Cervical BT can be delivered with numerous applicators, which necessitates developing models that generalize to multiple applicator types. The variability and scarcity of data for any given applicator type poses challenges for deep learning.

Single-cell CRISPR screening characterizes transcriptional deregulation in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of leukemia caused by accumulation of multiple genetic alterations in T-cell progenitors. However, for many genes it remains unknown how their mutations contribute to disease development. We therefore performed two single-cell CRISPR screens in primary pro-T cells ex vivo to study the transcriptional impact of loss-of-function alterations in T-ALL and correlate this with effects on cell fitness.

On the Difference in Mechanical Behavior of Glass Bead-Filled Polyamide 12 Specimens Produced by Laser Sintering and Injection Molding.

An increasing demand for additively manufactured polymer composites with optimized mechanical properties is manifesting in different industries such as aerospace, biomedical, and automotive. Laser sintering (LS) is an additive manufacturing method that has the potential to produce reinforced polymers, which can meet the stringent requirements of these industries. For the development of a commercially viable LS nylon-based composite material, previous research studies worldwide have focused on adding glass beads to the powder material with the goal to produce fully dense parts with properties more representative of injection molded (IM) thermoplastic composites.

Psychoactive and other ceremonial plants from a 2,000-year-old Maya ritual deposit at Yaxnohcah, Mexico.

For millennia, healing and psychoactive plants have been part of the medicinal and ceremonial fabric of elaborate rituals and everyday religious practices throughout Mesoamerica. Despite the essential nature of these ritual practices to the societal framework of past cultures, a clear understanding of the ceremonial life of the ancient Maya remains stubbornly elusive. Here we record the discovery of a special ritual deposit, likely wrapped in a bundle, located beneath the end field of a Late Preclassic ballcourt in the Helena complex of the Maya city of Yaxnohcah.

Assessment of education in a community hospital on healthcare providers' knowledge of and attitudes toward medical marijuana.

Introduction: Although medical marijuana usage continues to become more socially acceptable and is increasingly regarded as a legitimate treatment alternative for certain medical conditions such as cancer and epilepsy, stigma remains.

Methods: This study examined whether offering an educational session addressing several key aspects of medical marijuana (e.g.

Involvement of peptidylarginine deiminase 4 in eosinophil extracellular trap formation and contribution to citrullinated histone signal in thrombi.

Background: Extracellular traps formed by neutrophils (NETs) and eosinophils (EETs) have been described in coronary thrombi, contributing to thrombus stability. A key mechanism during NET formation is histone modification by the enzyme PAD4. Citrullinated histones, the product of PAD4 activity, are often attributed to neutrophils.

Clinical performance of a multiparametric MRI-based post concussive syndrome index.

Introduction: Diffusion Tensor Imaging (DTI) has revealed measurable changes in the brains of patients with persistent post-concussive syndrome (PCS). Because of inconsistent results in univariate DTI metrics among patients with mild traumatic brain injury (mTBI), there is currently no single objective and reliable MRI index for clinical decision-making in patients with PCS.

Purpose: This study aimed to evaluate the performance of a newly developed PCS Index (PCSI) derived from machine learning of multiparametric magnetic resonance imaging (MRI) data to classify and differentiate subjects with mTBI and PCS history from those without a history of mTBI.

Facile Fabrication of Flexible and High-Performing Thermoelectrics by Direct Laser Printing on Plastic Foil.

The emerging fields of wearables and the Internet of Things introduce the need for electronics and power sources with unconventional form factors: large area, customizable shape, and flexibility. Thermoelectric (TE) generators can power those systems by converting abundant waste heat into electricity, whereas the versatility of additive manufacturing suits heterogeneous form factors. Here, additive manufacturing of high-performing flexible TEs is proposed.

Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent in Mice.

In addition to its potent antiplatelet activity, ticagrelor possesses antibacterial properties against gram-positive bacteria. We wondered whether the typical clinical dosage of ticagrelor could prevent the development of infective endocarditis caused by highly virulent . Ticagrelor prevented vegetation formation in a mouse model of inflammation-induced endocarditis.

Characteristics associated with response to subcutaneously administered anti-CGRP monoclonal antibody medications in a real-world community cohort of persons living with migraine: A retrospective clinical and genetic study.

Objective: To evaluate response to anti-calcitonin gene-related peptide (CGRP) migraine preventives in a real-world community cohort of persons living with migraine and to identify clinical and genetic characteristics associated with efficacious response.

Background: Erenumab-aooeb, fremanezumab-vrfm, and galcanezumab-gnlm target CGRP or its receptor; however, many patients are non-responsive.

Methods: In this retrospective clinical and genetic study, we identified 1077 adult patients who satisfied the International Classification of Headache Disorders, 3rd edition, criteria for migraine without aura, migraine with aura, or chronic migraine and who were prescribed an anti-CGRP migraine preventive between May 2018 and May 2021.

Leukotriene B4 receptor 1 (BLT1) does not mediate disease progression in a mouse model of liver fibrosis.

MASH is a prevalent liver disease that can progress to fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and ultimately death, but there are no approved therapies. Leukotriene B4 (LTB4) is a potent pro-inflammatory chemoattractant that drives macrophage and neutrophil chemotaxis, and genetic loss or inhibition of its high affinity receptor, leukotriene B4 receptor 1 (BLT1), results in improved insulin sensitivity and decreased hepatic steatosis. To validate the therapeutic efficacy of BLT1 inhibition in an inflammatory and pro-fibrotic mouse model of MASH and fibrosis, mice were challenged with a choline-deficient, L-amino acid defined high fat diet and treated with a BLT1 antagonist at 30 or 90 mg/kg for 8 weeks.

A feasibility study of adaptive radiation therapy for postprostatectomy prostate cancer.

Postoperative prostate radiotherapy requires large planning target volume (PTV) margins to account for motion and deformation of the prostate bed. Adaptive radiation therapy (ART) can incorporate image-guidance data to personalize PTVs that maintain coverage while reducing toxicity. We present feasibility and dosimetry results of a prospective study of postprostatectomy ART.