Adoptive T cell therapy targeting an inducible and broadly shared product of aberrant mRNA translation.

Prolonged exposure to interferon-gamma (IFNγ) and the associated increased expression of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) create an intracellular shortage of tryptophan in the cancer cells, which stimulates ribosomal frameshifting and tryptophan to phenylalanine (W>F) codon reassignments during protein synthesis. Here, we investigated whether such neoepitopes can be useful targets of adoptive T cell therapy. Immunopeptidomic analyses uncovered hundreds of W>F neoepitopes mainly presented by the HLA-A24:02 allele.

Predicting preterm birth using electronic medical records from multiple prenatal visits.

This study aimed to predict preterm birth in nulliparous women using machine learning and easily accessible variables from prenatal visits. Elastic net regularized logistic regression models were developed and evaluated using 5-fold cross-validation on data from 8,830 women in the Nulliparous Pregnancy Outcomes Study: New Mothers-to-Be (nuMoM2b) dataset at three prenatal visits: - , - , and - weeks of gestational age (GA). The models' performance, assessed using Area Under the Curve (AUC), sensitivity, specificity, and accuracy, consistently improved with the incorporation of data from later prenatal visits.

Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors.

Malignant rhabdoid tumor (MRT) is one of the most aggressive childhood cancers for which no effective treatment options are available. Reprogramming of cellular metabolism is an important hallmark of cancer, with various metabolism-based drugs being approved as a cancer treatment. In this study, we use patient-derived tumor organoids (tumoroids) to map the metabolic landscape of several pediatric cancers.

How hidden is hidden hearing loss? Self-reported listening problems in charcot Marie tooth disease.

Introduction: Laboratory studies have revealed hidden hearing loss in patients with Charcot-Marie-Tooth (CMT) disease, the most prevalent inherited neuropathy, which may impact their quality of life. The current study distinguished between CMT type 1, which involves demyelination of the peripheral nerves, and type 2, which concerns dysfunction of peripheral nerves due to axonopathy. The self-reported effects were investigated of CMT1 and CMT2 on listening problems and related social and attentional problems in everyday communicative situations.

The oestrous cycle stage affects mammary tumour sensitivity to chemotherapy.

The response of breast cancer to neoadjuvant chemotherapy (NAC) varies substantially, even when tumours belong to the same molecular or histological subtype. Here we identify the oestrous cycle as an important contributor to this heterogeneity. In three mouse models of breast cancer, we show reduced responses to NAC when treatment is initiated during the dioestrus stage, when compared with initiation during the oestrus stage.

Compound-dependent fetal toxicity after in utero exposure to chemotherapy in a pregnant mouse model.

Although chemotherapy is integrated in the treatment of second-trimester pregnant cancer patients, its potential cyto- and genotoxicity to fetal tissue remains unknown. To investigate any causal relation between in utero chemotherapy exposure and fetal toxicity, late-gestation pregnant BL6 mice were exposed to vehicle, or one of six chemotherapeutic compounds, used to treat pregnant cases: cyclophosphamide, carboplatin, cisplatin (alkylating agents), epirubicin, doxorubicin (anthracyclines) or paclitaxel (taxane). fetuses were euthanized at gestational day 18.

Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancer.

Messenger RNA (mRNA) translation is a tightly controlled process frequently deregulated in cancer. Key to this deregulation are transfer RNAs (tRNAs), whose expression, processing and post-transcriptional modifications are often altered in cancer to support cellular transformation. In conditions of limiting levels of amino acids, this deregulated control of protein synthesis leads to aberrant protein production in the form of ribosomal frameshifting or misincorporation of non-cognate amino acids.

Two-dimensional fetal speckle tracking; a learning curve study for offline strain analysis.

Objectives: Two-dimensional speckle tracking (2D-STE) strain analysis holds promise for assessing fetal cardiac function. Understand the learning curve before introducing 2D-STE into obstetrics is crucial. This study examined the learning curve for offline analysis of fetal left (LV) and right ventricular (RV) global longitudinal strain (GLS) using 2D-STE.

Selective inhibition of HDAC class IIA as therapeutic intervention for KMT2A-rearranged acute lymphoblastic leukemia.

KMT2A-rearranged acute lymphoblastic leukemia (ALL) is characterized by deregulation of the epigenome and shows susceptibility towards histone deacetylase (HDAC) inhibition. Most broad-spectrum HDAC inhibitors simultaneously target multiple human HDAC isoforms. Consequently, they often induce toxicity and especially in combination with other therapeutic agents.

Do erupting maxillary canines resorb adjacent teeth? A study focusing both on the ipsilateral and contralateral sides among individuals with unilaterally impacted canines.

Objectives: To determine the prevalence of root resorption of teeth adjacent to permanent maxillary canines on both sides, by cone-beam computed tomography (CBCT), in pretreatment adolescent subjects with unilaterally impacted maxillary canines, and to define predictive factors for the root resorption.

Materials And Methods: This retrospective sample included 76 adolescents (38 boys, 38 girls, mean age 12.3 ± 2.

ADARp150 counteracts whole genome duplication.

Impaired control of the G1/S checkpoint allows initiation of DNA replication under non-permissive conditions. Unscheduled S-phase entry is associated with DNA replication stress, demanding for other checkpoints or cellular pathways to maintain proliferation. Here, we uncovered a requirement for ADARp150 to sustain proliferation of G1/S-checkpoint-defective cells under growth-restricting conditions.

OBSERVE: guidelines for the refinement of rodent cancer models.

Existing guidelines on the preparation (Planning Research and Experimental Procedures on Animals: Recommendations for Excellence (PREPARE)) and reporting (Animal Research: Reporting of In Vivo Experiments (ARRIVE)) of animal experiments do not provide a clear and standardized approach for refinement during in vivo cancer studies, resulting in the publication of generic methodological sections that poorly reflect the attempts made at accurately monitoring different pathologies. Compliance with the 3Rs guidelines has mainly focused on reduction and replacement; however, refinement has been harder to implement. The Oncology Best-practices: Signs, Endpoints and Refinements for in Vivo Experiments (OBSERVE) guidelines are the result of a European initiative supported by EurOPDX and INFRAFRONTIER, and aim to facilitate the refinement of studies using in vivo cancer models by offering robust and practical recommendations on approaches to research scientists and animal care staff.

Elevated heart rate and decreased muscle endothelial nitric oxide synthase in early development of insulin resistance.

Insulin resistance (IR) is a risk factor for the development of several major metabolic diseases. Muscle fiber composition is established early in life and is associated with insulin sensitivity. Hence, muscle fiber composition was used to identify early defects in the development of IR in healthy young individuals in the absence of clinical manifestations.

Feasibility and reliability of fetal two dimensional speckle tracking echocardiography at 16 weeks gestational age: A pilot study.

Background: Fetal two-dimensional speckle tracking echocardiography (2D-STE) is an emerging technique for assessing fetal cardiac function by measuring global longitudinal strain. Alterations in global longitudinal strain may serve as early indicator of pregnancy complications, making 2D-STE a potentially valuable tool for early detection. Early detection can facilitate timely interventions to reduce fetal and maternal morbidity and mortality.

Early prediction of gestational diabetes mellitus using maternal demographic and clinical risk factors.

Objective: To build and validate an early risk prediction model for gestational diabetes mellitus (GDM) based on first-trimester electronic medical records including maternal demographic and clinical risk factors.

Methods: To develop and validate a GDM prediction model, two datasets were used in this retrospective study. One included data of 14,015 pregnant women from Máxima Medical Center (MMC) in the Netherlands.

What's the point? Infants' and adults' perception of different pointing gestures.

Adults and infants as young as 4 months old orient to pointing gestures. Although adults are shown to orient faster to index-finger pointing than other hand shapes, it is unknown whether hand shapes influence infants' perception of pointing. In this study, we used a spatial cueing paradigm on an eye tracker to investigate whether and to what extent adults and 12-month-old infants orient their attention in the direction of pointing gestures with different hand shapes: index finger, whole hand, and pinky finger.

Association Between Intermediate End Points, Progression-free Survival, and Overall Survival in First-line Advanced or Recurrent Endometrial Cancer.

Purpose: Advanced/recurrent endometrial cancer is associated with poor long-term outcomes. Clinical studies of novel regimens are ongoing, but given that data on overall survival (OS) take a long time to mature, surrogate end points are often used to support clinical-research interpretation. The aim of this study was to explore the correlation between progression-free survival (PFS)/time to progression (TTP) and OS across multiple time points in the first-line treatment of advanced/recurrent endometrial cancer.

MYC is a clinically significant driver of mTOR inhibitor resistance in breast cancer.

Targeting the PI3K-AKT-mTOR pathway is a promising therapeutic strategy for breast cancer treatment. However, low response rates and development of resistance to PI3K-AKT-mTOR inhibitors remain major clinical challenges. Here, we show that MYC activation drives resistance to mTOR inhibitors (mTORi) in breast cancer.

The impact of angles of insonation on left and right ventricular global longitudinal strain estimation in fetal speckle tracking echocardiography.

Objectives: Two-dimensional speckle tracking echocardiography has been considered an angle-independent modality. However, current literature is limited and inconclusive on the actual impact of angle of insonation on strain values. Therefore, the primary objective of this study was to assess the impact of angles of insonation on the estimation of fetal left ventricular and right ventricular global longitudinal strain.

Evidence and clinical relevance of maternal-fetal cardiac coupling: A scoping review.

Background: Researchers have long suspected a mutual interaction between maternal and fetal heart rhythms, referred to as maternal-fetal cardiac coupling (MFCC). While several studies have been published on this phenomenon, they vary in terms of methodologies, populations assessed, and definitions of coupling. Moreover, a clear discussion of the potential clinical implications is often lacking.

Long-Term Weight Changes After Starting Anti-IL-5/5Ra Biologics in Severe Asthma: The Role of Oral Corticosteroids.

Background: Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics significantly reduce OCS use, but their long-term effects on weight are unknown.

Objectives: To examine (1) weight change up to 2 years after anti-IL-5/5Ra initiation in subgroups on the basis of maintenance OCS use at start of treatment and (2) whether cumulative OCS exposure before or changes in OCS exposure during treatment are related to weight change.

The effect of functional calibration methods on gait kinematics in adolescents with idiopathic rotational deformity of the femur.

Background: Due to anatomical deviations, assumptions of the conventional calibration method for gait analysis may be violated in individuals with rotational deformities of the femur. Functional calibration methods were compared with conventional methods in this group for 1) localization of the hip joint center and orientation of the knee axis, and 2) gait kinematics.

Methods: Twenty-four adolescents with idiopathic rotational deformity of the femur underwent gait analysis and a CT scan.

Multi-omics analysis reveals distinct non-reversion mechanisms of PARPi resistance in BRCA1- versus BRCA2-deficient mammary tumors.

BRCA1 and BRCA2 both function in DNA double-strand break repair by homologous recombination (HR). Due to their HR defect, BRCA1/2-deficient cancers are sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis), but they eventually acquire resistance. Preclinical studies yielded several PARPi resistance mechanisms that do not involve BRCA1/2 reactivation, but their relevance in the clinic remains elusive.