Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.

Prognostic value of CHA2DS2-VASc score for in-hospital outcomes in patients with Takotsubo syndrome.

Background: There is uncertainty about the use of the CHA2DS2-VASc score to predict clinical events in patients with Takotsubo syndrome (TTS). This study aimed to assess the short-term prognostic role of CHA2DS2-VASc score in this population.

Methods: All admissions with a primary diagnosis of TTS were included using data from the National Inpatient Sample database during 2016-2019.

Updated, detailed scoring of the activities measure for upper limb amputation (AM-ULA).

Background: The Activities Measure for Upper Limb Amputation (AM-ULA), an activity measure for prosthesis users, uses a complex grading rubric to assign a single score to task performance which may limit responsiveness.

Purpose: To enhance AM-ULA responsiveness by exploring a scoring that uses multiple grading elements.

Study Design: Cross-sectional study.

Impact of high maternal body mass index on fetal cerebral cortical and cerebellar volumes.

Objectives: Maternal obesity increases a child's risk of neurodevelopmental impairment. However, little is known about the impact of maternal obesity on fetal brain development.

Methods: We prospectively recruited 20 healthy pregnant women across the range of pre-pregnancy or first-trimester body mass index (BMI) and performed fetal brain magnetic resonance imaging (MRI) of their healthy singleton fetuses.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Association of cardiometabolic index with all-cause and cardiovascular mortality among middle-aged and elderly populations.

The Cardiometabolic Index (CMI) is a well-recognized risk factor for a range of cardiovascular diseases and diabetes mellitus. However, the population-level characteristics of CMI and its potential association with mortality risk among individuals over 40 years of age have not been investigated. This study aims to assess the association between CMI and both all-cause and cardiovascular mortality among the middle-aged and elderly population.

3D-printed aberration-free terahertz metalens for ultra-broadband achromatic super-resolution wide-angle imaging with high numerical aperture.

Terahertz (THz) lens constitutes a vital component in the THz system. Metasurfaces-based THz metalenses and classical bulky lenses are severely constrained by chromatic/ spherical aberration and the diffraction limit. Consequently, achromatic super-resolution THz lenses are urgently needed.

Epigenetics in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the fourth leading cause of end-stage renal disease, contributing substantially to patient morbidity, mortality, and healthcare system strain. Emerging research highlights a pivotal role of epigenetics in ADPKD's pathophysiology, where mechanisms like DNA methylation, histone modifications, and non-coding RNA regulation significantly impact disease onset and progression. These epigenetic factors influence gene expression and regulate key processes involved in cyst formation and expansion, fibrosis, and inflammatory infiltration, thus accelerating ADPKD progression.

Disclosing sample bias fails to fully correct judgments of partisan extremity.

How do we infer the beliefs of an entire group (e.g., Democrats) after being exposed to the beliefs of only a handful of group members? What if we know that the beliefs we encountered were selected in a biased manner? Across two experiments, we recruited 640 U.

Neural regulation of pain anticipation is associated with mindful behavior change in patients with anxiety or depression: A pilot study.

Behavior change often requires overcoming discomfort or difficult emotions. Emotional dysregulation associated with anxiety or depression may prevent behavior change initiation among people managing chronic illness. Mindfulness training may catalyze chronic disease self-management by reducing experiential avoidance of aversive experiences that act as barriers to change initiation.

The Pelvic Floor Disorders Network: Evolution Over Two Decades of Female Pelvic Floor Research.

Importance: This review aimed to describe research initiatives, evolution, and processes of the Eunice Kennedy Shriver National Institute of Child Health and Human Development-supported Pelvic Floor Disorders Network (PFDN). This may be of interest and inform researchers wishing to conduct multisite coordinated research initiatives as well as to provide perspective to all urogynecologists regarding how the PFDN has evolved and functions.

Study Design: Principal investigators of several PFDN clinical sites and Data Coordinating Center describe more than 20 years of development and maturation of the PFDN.

Prediction of Retention Indices in LC-HRMS for Enhanced Structural Identification of Organic Micropollutants in Water: Selectivity-Based Filtration.

Addressing the global challenge of ensuring access to safe drinking water, especially in developing countries, demands cost-effective, eco-friendly, and readily available technologies. The persistence, toxicity, and bioaccumulation potential of organic pollutants arising from various human activities pose substantial hurdles. While high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-HRMS) is a widely utilized technique for identifying pollutants in water, the multitude of structures for a single elemental composition complicates structural identification.

Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.

Basic Science and Pathogenesis.

Background: Currently, it is unclear to what extent late-onset Alzheimer's disease (AD) risk variants contribute to early-onset AD (EOAD). One method to clarify the contribution of late-onset AD genetic risk to EOAD is to investigate the association of AD polygenic risk scores (PRS) with EOAD. We hypothesize that in the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS), EOAD participants will have greater PRS than early-onset amyloid-negative cognitively-impaired participants (EOnonAD) and controls, and investigate the association of AD PRS with age of disease onset (AoO) and cognitive performance.

Basic Science and Pathogenesis.

Background: Chitinase-3-like protein 1 (CHI3L1, or YKL-40) is an important regulator of immunity and, in the brain, is primarily secreted by activated astrocytes and heralds a neurotoxic inflammatory state. While it has been well known as a high-profile biomarker for Alzheimer's disease (AD) and inflammatory brain conditions (e.g.

Basic Science and Pathogenesis.

Background: TBI is the 3rd greatest risk factor for developing AD, behind genetics and aging. TBI is associated with a 3-4 year earlier onset of cognitive impairment, and increased cortical thinning and amyloid plaques in people with AD. The underlying mechanisms of this relationship are not understood, and as a result there are no treatments that protect patients from accelerated AD after TBI.

Tissue-resident NK cells do their own glandscaping.

In this issue of JEM, Sparano et al. (https://doi.org/10.

Basic Science and Pathogenesis.

Background: Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset.

Basic Science and Pathogenesis.

ARIA-E/H (amyloid-related imaging abnormalities-Edema/Hemorrhage) is an umbrella term that defines the radiographic appearance of MRI images abnormality during treatments with Aβ-lowering monoclonal antibodies (mAbs) for Alzheimer's disease immunotherapy. Today, it is well-recognized that ARIA-E events can also occur spontaneously in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with raised cerebrospinal fluid (CSF) concentrations of spontaneous auto-antibodies against Aβ (aAbs). In this framework, the last years of research and experience of the iCAB international Network generated an increased consensus that therapy-induced ARIA is the iatrogenic manifestation of CAA-ri.

Basic Science and Pathogenesis.

Background: The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is analyzing the genetic etiology of early onset (40-64 years) cognitive impairment, including amyloid-positive early-onset Alzheimer's disease (EOAD) and amyloid-negative early-onset Alzheimer's disease (EOnonAD). One goal of this investigation is to identify novel or under-characterized genetic variants.

Methods: Cognitively impaired (CI) LEADS participants, including amyloid-positive and amyloid-negative early-onset cases, were whole exome or genome sequenced (N = 361).

Clinical Manifestations.

Background: Frontotemporal dementia (FTD) presents with heterogeneous neuropsychiatric symptoms (NPS). These symptoms often begin prior to the onset of FTD, and progress throughout the prodromal stages of FTD. Particularly, familial FTD due to autosomal dominant genetic mutations might display mutation-specific NPS profiles.