Needed: Clear definition and hierarchical integration of motivation constructs.

Murayama and Jach offer a thoughtful and timely critique of motivation constructs. We largely concur with their basic premises, but offer additional input and clarification regarding the importance of carefully considering the energization and direction components of motivation, and fully attending to the hierarchical aspect of motivation rather than prioritizing particular levels of analysis.

The unboxing has already begun: One motivation construct at a time.

Murayama and Jach argue that it is not clearly specified how motivation constructs produce behavior and that this black box should be unpacked. We argue that the authors overlook important classic theory and highlight recent research programs that already started unboxing. We feel that without relying on the mechanisms that such programs uncover, the proposed computational approach will be fruitless.

Long-Term Prognostic Implications of Non-Culprit Lesions in Patients Presenting With an Acute Myocardial Infarction: Is It the Angiographic Stenosis Severity or the Underlying High-Risk Morphology?

Background: Patients with acute myocardial infarction and angiographically obstructive non-culprit lesions are at high risk for recurrent major adverse cardiac events (MACEs). However, it remains largely unknown whether events are due to stenosis severity or due to the underlying high-risk lesion morphology.

Methods: Between January 2017 and December 2021, 1312 patients with acute myocardial infarction underwent optical coherence tomography of all the 3 main epicardial arteries after successful percutaneous coronary intervention.

Remote Ischemic Conditioning Attenuates Transneuronal Degeneration and Promotes Stroke Recovery via CD36-Mediated Efferocytosis.

Background: Remote ischemic conditioning (RIC) has been implicated in cross-organ protection in cerebrovascular disease, including stroke. However, the lack of a consensus protocol and controversy over the clinical therapeutic outcomes of RIC suggest an inadequate mechanistic understanding of RIC. The current study identifies RIC-induced molecular and cellular events in the blood, which enhance long-term functional recovery in experimental cerebral ischemia.

Enhanced detection of circulating tumor cells using a MUC1 promoter-driven recombinant adenovirus.

Introduction: Circulating tumor cells (CTCs) have attracted significant interest as a biomarker for cancer diagnosis. In this study, we judiciously constructed a recombinant MUC1-dependent adenovirus (rAdF35-MUC1) that can selectively replicate and overexpress copepod super green fluorescent proteins (copGFP) in MUC1-positive tumor cells to investigate its role in the detection of CTCs.

Methods: We conducted a comparative study between rAdF35-MUC1 and the existing hTERT-dependent adenovirus (rAdF35-hTERT).

AI-driven multi-omics integration for multi-scale predictive modeling of genotype-environment-phenotype relationships.

Despite the wealth of single-cell multi-omics data, it remains challenging to predict the consequences of novel genetic and chemical perturbations in the human body. It requires knowledge of molecular interactions at all biological levels, encompassing disease models and humans. Current machine learning methods primarily establish statistical correlations between genotypes and phenotypes but struggle to identify physiologically significant causal factors, limiting their predictive power.

Data-Driven Maturity Level Evaluation for Cardiomyocytes Derived from Human Pluripotent Stem Cells (Invited Paper).

Cardiovascular disease is a leading cause of death worldwide. The differentiation of human pluripotent stem cells (hPSCs) into functional cardiomyocytes offers significant potential for disease modeling and cell-based cardiac therapies. However, hPSC-derived cardiomyocytes (hPSC-CMs) remain largely immature, limiting their experimental and clinical applications.

Integrated multiplex analysis of cell death regulators in stage II colorectal cancer suggests patients with 'persister' cell profiles fail to benefit from adjuvant chemotherapy.

Objective: Inducing tumour cell apoptosis is a primary objective of chemotherapy but, to date, there are no validated biomarkers of apoptosis sensitivity or resistance. Our objective was to image multiple apoptosis pathway proteins at single cell level and determine multi-protein associations with recurrence risk and chemotherapy response in patients with stage II colorectal cancer (CRC).

Methods And Analysis: Multiplexed imaging of 16 proteins in the intrinsic and extrinsic apoptosis pathways at single cell resolution on resected tissue from 194 patients with stage II CRC who either received adjuvant chemotherapy (n108) or were treated with surgery only (n=86).

MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps.

Introduction: Alzheimer's disease (AD) is a phenotypically and pathologically heterogenous neurodegenerative disorder. This heterogeneity can be studied and disentangled using data-driven clustering techniques.

Methods: We implemented a self-organizing map clustering algorithm on baseline volumetric MRI measures from nine brain regions of interest (ROIs) to cluster 1041 individuals enrolled in the placebo arm of the EXPEDITION3 trial.

Trans-ancestry genome wide association study of childhood body mass index identifies novel loci and age-specific effects.

Over the past 30 years, obesity prevalence has markedly increased globally, including among children. Although genome-wide association studies (GWAS) have identified over 1,000 genetic loci associated with obesity-related traits in adults, the genetic architecture of childhood obesity is less well-characterized. Moreover, most childhood obesity GWAS have been restricted to severely obese children, in relatively small sample sizes, and in primarily European ancestry populations.

HIV Pre-Exposure Prophylaxis (PrEP) awareness and use among Rakai Community Cohort Study youth aged 15-24.

Background: Preventing HIV infections among adolescents and young adults (AYA) is crucial for curtailing the epidemic. Oral pre-exposure prophylaxis (PrEP) is a highly effective prevention method increasingly available to this age group in sub-Saharan Africa but population-based data on awareness and use of PrEP among AYA remains limited.

Methods: Analyzing survey data from two rounds of the Rakai Community Cohort Study, an open, population-based cohort, we estimated prevalence ratios associating various sociodemographic characteristics with PrEP awareness and ever-use among 15- to 24-year-olds in south-central Uganda between 2018 and 2023.

Uropygial gland microbiota of nearctic-neotropical migrants vary with season and migration distance.

Symbiotic microbiota are important drivers of host behaviour, health, and fitness. While most studies focus on humans, model organisms, and domestic or economically important species, research investigating the role of host microbiota in wild populations is rapidly accumulating. Most studies focus on the gut microbiota; however, skin and other glandular microbiota also play an important role in shaping traits that may impact host fitness.

Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone.

Background: Klebsiella pneumoniae is one of the most prevalent pathogens responsible for multiple infections in healthcare settings and the community. K. pneumoniae CG147, primarily including ST147 (the founder ST), ST273, and ST392, is one of the most globally successful MDR clone linked to various carbapenemases.

A community-based approach to address lung cancer screening disparities in the black community using the Witness Project framework: development and pilot trial.

Background: Disparities in lung cancer outcomes persist among Black Americans, necessitating targeted interventions to address screening inequities. This paper reports the development and refinement of Witness Project Lung, a community-based initiative tailored to the specific needs of the Black community, aiming to improve awareness and engagement with lung cancer screening.

Methods: Utilizing a user-centered design and guided by the original Witness Project framework - an evidence-based lay health advisor intervention program originally developed to increase knowledge and awareness about breast cancer risk and screening in the Black community and later trans-created to the cervical and colorectal cancer screening contexts - Witness Project Lung was developed and refined through qualitative input from key stakeholders in the Black faith community.

Comprehensive transcriptomic analysis reveals turnip mosaic virus infection and its aphid vector Myzus persicae cause large changes in gene regulatory networks and co-transcription of alternative spliced mRNAs in Arabidopsis thaliana.

Background: Virus infection and herbivory can alter the expression of stress-responsive genes in plants. This study employed high-throughput transcriptomic and alternative splicing analysis to understand the separate and combined impacts on host gene expression in Arabidopsis thaliana by Myzus persicae (green peach aphid), and turnip mosaic virus (TuMV).

Results: By investigating changes in transcript abundance, the data shows that aphids feeding on virus infected plants intensify the number of differentially expressed stress responsive genes compared to challenge by individual stressors.

Resistance mechanisms and therapeutic strategies of CDK4 and CDK6 kinase targeting in cancer.

Cyclin-dependent kinases (CDKs) 4 and 6 (CDK4/6) are important regulators of the cell cycle. Selective CDK4/6 small-molecule inhibitors have shown clinical activity in hormonal receptor-positive (HR) metastatic breast cancer, but their effectiveness remains limited in other cancer types. CDK4/6 degradation and improved selectivity across CDK paralogs are approaches that could expand the effectiveness of CDK4/6 targeting.

Neuroactive steroid biosynthesis during pregnancy predicts future postpartum depression: a role for the 3α and/or 3β-HSD neurosteroidogenic enzymes?

Postpartum depression (PPD) affects ~10-15% of childbearing individuals, with deleterious consequences for two generations. Recent research has explored the biological mechanisms of PPD, particularly neuroactive steroids (NAS). We sought here to investigate associations between NAS levels and ratios during pregnancy and the subsequent development of depressive symptoms with postpartum onset.

Toward a biological definition of neuronal and glial synucleinopathies.

Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms.

Risk-directed management of chronic kidney disease.

The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data.

A comparative review of murine models of repeated low-dose cisplatin-induced chronic kidney disease.

This Review evaluates various mouse and rat models of chronic kidney disease (CKD) that result from repeated low-dose cisplatin (RLDC) treatment while also discussing ethical considerations on the topic. Cisplatin can cause nephrotoxicity, and high doses of cisplatin can cause acute kidney injury. The RLDC regimen has been used in the treatment of solid organ cancers and has shown efficacy in reducing the occurrence of acute kidney injury in patients.

Valley charge-transfer insulator in twisted double bilayer WSe.

In flat-band systems, emergent physics can be substantially modified by the presence of another nearby electronic band. For example, a Mott˘Hubbard insulator can turn into a charge transfer insulator if other electronic states enter between the upper and lower Hubbard bands. Here, we introduce twisted double bilayer (TDB) WSe, with twist angles near 60°, as a controllable platform in which the K-valley band can be tuned to close vicinity of the Γ-valley moiré flat band.

Stress landscape of folding brain serves as a map for axonal pathfinding.

Understanding the mechanics linking cortical folding and brain connectivity is crucial for both healthy and abnormal brain development. Despite the importance of this relationship, existing models fail to explain how growing axon bundles navigate the stress field within a folding brain or how this bidirectional and dynamic interaction shapes the resulting surface morphologies and connectivity patterns. Here, we propose the concept of "axon reorientation" and formulate a mechanical model to uncover the dynamic multiscale mechanics of the linkages between cortical folding and connectivity development.

Phase separation of a microtubule plus-end tracking protein into a fluid fractal network.

Microtubule plus-end tracking proteins (+TIPs) participate in nearly all microtubule-based cellular processes and have recently been proposed to function as liquid condensates. However, their formation and internal organization remain poorly understood. Here, we have study the phase separation of Bik1, a CLIP-170 family member and key +TIP involved in budding yeast cell division.