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Correction: Cultural framing of giftedness in recent US fictional texts
Improved gated recurrent unit-based osteosarcoma prediction on histology images: a meta-heuristic-oriented optimization concept
Transanal TME noninferior to the laparoscopic approach
Matrix degradation enhances stress relaxation, regulating cell adhesion and spreading
In native extracellular matrices (ECM), cells utilize matrix metalloproteinases (MMPs) to degrade and remodel their microenvironment. Accordingly, synthetic matrices have been engineered to permit MMP-mediated cleavage, facilitating cell spreading, migration, and interactions. However, the interplay between matrix degradability and mechanical properties remains underexplored. We hypothesized that MMP activity induces immediate mechanical alterations in the ECM, which are subsequently detected by cells. We observed that both fibrillar collagen and synthetic degradable matrices exhibit enhanced stress relaxation following MMP exposure. Cells responded to these variations in relaxation by modulating their spreading and focal adhesions. Furthermore, we demonstrated that stress relaxation and cell spreading can be precisely controlled through the rational design of matrix degradability. These findings establish a fundamental link between matrix degradability and stress relaxation, with potential implications for a broad spectrum of biological applications.
African Youth in Mind – Protocol of a Pilot feasibility trial of a brief psychological Intervention for older adolescents with depression delivered through senior high schools in Navrongo, Ghana
In Ghana, one in three adolescents are at risk of experiencing depression. However, access to treatment is limited due to the poor integration of mental health services into primary healthcare systems. Evidence-based interventions, especially psychological therapies and antidepressant medication, can restore health and functioning for depressed youth. Ghana currently runs a policy of free Senior High Secondary Education and aims to implement a national adolescent health policy. However, the mental health component is poorly developed. Our formative research informed the adaptation of a 6-session psychological intervention for depression, suitable for school-going youth aged 15-18 in Ghana. The aim of this study is to conduct a pilot trial of this ‘African Youth in Mind’ (Y-MIND) intervention, to answer questions of feasibility and acceptability before evaluating the intervention in a larger definitive trial. The Y-MIND intervention blends evidence-based problem-solving therapy with behavioural activation and psychoeducation. The intervention will be delivered by trained and supervised guidance and counselling coordinators. The study is a parallel arm cluster randomised controlled pilot trial. Six senior high schools will each be randomly allocated 2:1 to either the intervention condition or enhanced usual care (EUC). 60 adolescents aged 15 to 18 years in senior high schools who have scored have scored 10 or more on the locally validated Patient Health Questionnaire-9 (PHQ-9) will be randomised. The feasibility, acceptability and appropriateness of the intervention will be assessed using short quantitative measures, and qualitative interviews with adolescents and guidance and counselling coordinators. Symptoms of depression will be measured at 5 months post baseline assessment. Outcomes for anxiety, fidelity to the intervention, and cost effectiveness evaluation will also be collected. This will be the first feasibility trial of a task-shifted psychological treatment (Y-MIND) for adolescents with depression delivered by Guidance and Counselling Coordinators in high schools in any African country. Clinicaltrials.gov NCT06740084.
Lysyl-tRNA synthetase 1 promotes atherogenesis via autophagy-related secretion and inflammation
International approvals of cilta-cel: a lens on CAR T cell regulation
Most Christian American religious leaders silently believe in climate change, and informing their congregation can help open dialogue
Religious leaders shape the attitudes and beliefs of their congregations. In a nationally representative sample of U.S. religious leaders ( N = 1,600), the majority of which were of a Christian faith, we find that nearly 90% believe in anthropogenic climate change to some degree. From this 90%, a total of 60% believe humans play a major role and an additional 30% believe they play a role, but a more minor one. Yet roughly half have never discussed it with their congregation, and only a quarter have mentioned it more than once or twice. In a sample of Christian Americans representative of the proportions of major national denominations ( N = 987), we find that Christians underestimate the prevalence of their leaders who believe in climate change by 39 to 45 percentage points. Conversely, having a religious leader who talks about climate change predicts greater willingness to discuss it with fellow churchgoers and attend climate events. In an experimental intervention on another sample matching major Christian American denomination ( N = 959), we find that providing the actual consensus level of religious leaders’ belief in climate change reduces congregants’ misperception of religious leaders, increases their perception that other church members believe in and are open to discussing climate change, and leads Christians to believe that taking climate action is consistent with their church’s values while voting for politicians who will not take climate action is not.
Experimental study of pore-scale flow mechanism of immiscible CO2 flooding under in-situ temperature-pressure coupling conditions
The flow mechanism of CO2 flooding serves as the theoretical foundation for examining the synergic integration of oil recovery and CO2 storage. Immiscible CO2 flooding has attracted considerable research attention due to its simplicity and cost-efficiency. However, minimal studies are available regarding the flow characteristics and EOR mechanism of immiscible CO2 flooding in in-situ temperature-pressure coupling conditions at the pore scale. Therefore, this study employed a modified high-temperature, high-pressure microfluidic system to simulate the in-situ CO2 and water injection processes in a combined temperature-pressure environment and analyze the multiphase flow characteristics in the pores. The injection rate, displacement pressure difference, displacement efficiency, and residual oil distribution were quantitatively analyzed at different pressures. The results indicated higher residual oil clustering after water flooding at the same injection rate. CO2 flooding significantly reduced residual oil clustering and enhanced the oil flooding effect. The multiphase flow dynamics, type of remaining oil in different injection conditions, and flow characteristics of immiscible CO2 flooding were determined. A higher confining pressure interrupted the CO2 flow, which destabilized the displacement front increased the recovery efficiency by 12.9%. Furthermore, a higher injection rate and displacement pressure increased the recovery efficiency by 24.9% and 6.1%, respectively.
Author Correction: Association between ACTN3 (R577X), BDKRB2 (−9/+9) and AGT (M235T) polymorphisms and physical performance in Brazilian junior handball players
Hiding in plain sight: NUT carcinoma is an unrecognized subtype of squamous cell carcinoma of the lungs and head and neck
Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination
We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the Trem2 gene in mice impairs remyelination. Here, we blocked TREM2 function acutely with an antibody during both the demyelination and remyelination phases of the CPZ model and analyzed the impact of the antibody treatment on myelination and gene expression in single cells. We found that blocking TREM2 depleted a distinct population of microglia with high expression of the transcription factor MAFB during remyelination. The loss of these MAFB-high microglia was linked to impaired generation of myelinating oligodendrocytes. Importantly, we identified MAFB + microglia in acute and acute-chronic brain lesions from individuals with multiple sclerosis (MS), but not in inactive lesions. We conclude that TREM2 is essential for maintaining a population of MAFB-high microglia that is associated with myelin repair. This finding has significant implications for understanding demyelinating diseases like MS and suggests that stimulating TREM2 could be a promising therapeutic approach for myelin repair.
Correction: Biomechanical effects of saddle height changes in leisure cycling with unilateral transtibial prostheses: A simulated study
Optimizing sintering air volume for enhanced lean gas recovery and environmental performance
Perioperative chemotherapy superior to preoperative chemoradiotherapy for locally advanced EAC
De novo discovery of a molecular glue–like macrocyclic peptide that induces MCL1 homodimerization
Macrocyclic peptides have emerged as promising drug candidates, filling the gap between small molecules and large biomolecules in drug discovery. The antiapoptotic protein myeloid cell leukemia 1 (MCL1) is crucial for numerous cancers, yet it presents challenges for selective targeting by traditional inhibitors. In this study, we identified a macrocyclic peptide, 5L1, that strongly binds to MCL1, with a dissociation constant ( K D ) of 7.1 nM. This peptide shows the potential to specifically inhibit the function of MCL1, and demonstrates effective antitumor activity against several blood tumor cell lines with the half maximal inhibitory concentration (IC 50 ) values for cell-penetrating peptide-conjugated 5L1 in the range of 0.6 to 3 μM. Structural analysis revealed that it functions similarly to molecular glue, capable of binding to two MCL1 molecules simultaneously and inducing their homodimerization. This unique mechanism of action distinguishes it from traditional small-molecule MCL1 inhibitors, underscoring the potential of macrocyclic peptides functioning as molecular glues. Moreover, it inspires the development of highly selective inhibitors targeting MCL1 and other related targets with this glue-like mechanism.
Correction: From tradition to progressiveness: Analyzing Thailand’s image on youtube amid post-cannabis legalization
Performance of vertical steel plate anchor in layered cohesionless soil
Prediction of phase-separation propensities of disordered proteins from sequence
Phase separation is one possible mechanism governing the selective cellular enrichment of biomolecular constituents for processes such as transcriptional activation, mRNA regulation, and immune signaling. Phase separation is mediated by multivalent interactions of macromolecules including intrinsically disordered proteins and regions (IDRs). Despite considerable advances in experiments, theory, and simulations, the prediction of the thermodynamics of IDR phase behavior remains challenging. We combined coarse-grained molecular dynamics simulations and active learning to develop a fast and accurate machine learning model to predict the free energy and saturation concentration for phase separation directly from sequence. We validate the model using computational and previously measured experimental data, as well as new experimental data for six proteins. We apply our model to all 27,663 IDRs of chain length up to 800 residues in the human proteome and find that 1,420 of these (5%) are predicted to undergo homotypic phase separation with transfer free energies < −2 k B T . We use our model to understand the relationship between single-chain compaction and phase separation and find that changes from charge- to hydrophobicity-mediated interactions can break the symmetry between intra- and intermolecular interactions. We also provide proof of principle for how the model can be used in force field refinement. Our work refines and quantifies the established rules governing the connection between sequence features and phase-separation propensities, and our prediction models will be useful for interpreting and designing cellular experiments on the role of phase separation, and for the design of IDRs with specific phase-separation propensities.