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DNA motif discovery and, particularly, computational modeling of transcription factor binding motifs, has been a mecca of algorithmic bioinformatics for several decades. Here, we report the results of the largest open community challenge in Inferring BInding Specificities (IBIS), where participants all over the world were invited to construct binding specificity models from multi-assay experimental data for poorly studied human transcription factors. The submissions were rigorously tested...

This Letter presents a combination of searches for Higgs boson pair (HH) production performed by the ATLAS and CMS Collaborations using proton-proton collision datasets recorded at sqrt[s]=13 TeV during the Large Hadron Collider Run 2, corresponding to integrated luminosities ranging between 126 and 140 fb^{-1}. The upper limit at the 95% confidence level on the total HH signal strength, defined as the ratio of the measured cross section to the standard model (SM) prediction, corresponds to 2.5,...

Mass-spectrometry-based proteomics is rapidly advancing, becoming fast, affordable, and increasingly accessible to environmental scientists. This perspective outlines how proteomics can illuminate biotransformation processes and sublethal organism-level effects, and highlights future opportunities enabled by emerging technologies. Our goal is to give a concise overview on realistic expectations of current capabilities while inspiring scientists to adapt and develop novel proteomic approaches...

Whole-genome sequencing has revealed hundreds of cancer driver mutations in protein-coding genes, while our knowledge of how non-coding mutations contribute to tumorigenesis remains limited. Here, we develop and perform large-scale functional screens to identify non-coding regulatory elements whose mutations drive cancer development in non-transformed human breast epithelial cells and mouse models of breast and skin cancer. We identify 12 frequently mutated regulatory elements associated with 16...

Machine learning models have seen a lot of success in medical image segmentation domain. However, one of the challenges that they face are confounders or shortcuts: spurious correlations or biases in the training data that affect the resulting models. One example of such confounders for surgical machine learning is the setup of surgical equipment, including tools and lighting. Using the task of identification of safe and dangerous zones of dissection in laparoscopic cholecystectomy images and...

N⁶-methyladenosine (m6A) is the most abundant mRNA modification, regulating gene expression through binding of reader proteins, such as YTHDF2, which promote mRNA decay. Previous studies indicate YTHDF2 has relatively weak intrinsic RNA-binding affinity, suggesting additional factors may facilitate RNA binding. Here, we show that the C2H2-Zinc Finger protein, ZNF121, binds mRNA in cells and physically interacts with YTHDF2 in the cytoplasm. We demonstrate that ∼80% of ZNF121-bound mRNAs are also...

Subclass cell types are strongly conserved across mammalian brains, making the systemic absence of a caudal ganglionic eminence (CGE) Pax6 interneuron subclass in mouse transcriptional atlases unexpected. Through cross-species transcriptomic analysis, we identify a Pax6 subclass homolog in mouse and uncover primate-specific divergence in the Sncg subclass. Analyses of electrophysiological and spatial datasets reveal limited subclass-specific structure in either modality, emphasizing the superior...

Tremendous maturation in brain structure and function, underlying very rapid cognitive development, occurs in the early years of life, yet it has been difficult to obtain reliable measures of brain function over this period. A major challenge has been the difficulty of acquiring reliable neuroimaging data from awake young children, who often struggle to tolerate conventional imaging environments or remain still during scanning. Existing approaches each involves important compromises between...

CONCLUSIONS: The results support the need for, and perceived value of, specialized clinics for adults with complex healthcare needs and their caregivers.

This Letter presents a measurement of prompt charged-particle production in proton-oxygen interactions at sqrt[s_{NN}]=9.62 TeV center-of-mass energy with the ATLAS detector, corresponding to 634 μb^{-1} of integrated luminosity. A total of 246×10^{6} selected events have at least one track with transverse momentum p_{T}>500 MeV and pseudorapidity |η|<2.5. The measured fiducial proton-oxygen cross section is σ_{fid.}^{pO}=396±6(exp.)±9(lumi.) mb and the extrapolated inelastic proton-air cross...

MOTIVATION: Dose-response metrics such as the half-maximal inhibitory concentration, high-dose-response, and slope are central to drug discovery, yet standard Levenberg-Marquardt fits often produce biased or unsupported values for incomplete curves and lack uncertainty measures. In practice, this forces experimenters to visually inspect each curve fit to judge its reliability, a tedious, subjective, and non-scalable process.

CONCLUSIONS: Patients with severe ACLF who underwent LT showed markedly better survival outcomes than those who were declined. Patients with five or six organ failures had high risk of post-LT death cautioning against routine LT in this population.

CONCLUSIONS AND RELEVANCE: Heart failure is a significant global public health burden, and the impact is likely to increase as populations age. However, most HF etiologies can be prevented by interventions that reduce exposure to modifiable risk factors, such as elevated blood pressure, excessive alcohol consumption, and tobacco use. Etiology- and location-specific estimates can provide necessary information for public health officials to determine how best to prioritize interventions to reduce...

Surface frustrated Lewis pairs (SFLPs) have been widely studied as active sites for light-assisted CO(2) hydrogenation, while most efforts have focused on cation engineering to tune the Lewis acidity of metal centers, leaving the Lewis-basic component less directly controlled. Here, we report an anion engineering strategy based on nitridation to prepare nitrogen-doped, non-stoichiometric spinel zinc gallium oxide catalysts for CO(2) hydrogenation to methanol. Nitrogen incorporation modifies the...

As machine learning (ML) becomes increasingly important in protein engineering, synthetic biology, and bioprocess optimisation, the lack of consistent, complete, and standardised experimental reporting remains a major barrier to building effective models. EXPERT (EXpression and Purification Experimental Reporting Template) defines a structured framework for capturing protein expression and purification data across the community, to increase reproducibility across laboratories and support...

Oral squamous cell carcinoma (OSCC) often arises from oral epithelial dysplasia (OED); however, the gene expression changes during OED progression and its microenvironment are not fully understood. This study used spatial transcriptomics to identify differentially expressed genes and microenvironmental alterations associated with malignant transformation of OED. A retrospective analysis of paired OSCC and OED samples was conducted at the Faculty of Dentistry, University of Toronto. A total of 24...

During the Drosophila maternal-to-zygotic transition, maternally deposited RNAs are cleared in a temporally controlled manner. The RNA-binding protein Smaug is a major regulator of maternal mRNA decay and its expression at both the RNA and protein level is limited to a narrow temporal window during the MZT. Here we show that the Pumilio RNA-binding protein promotes degradation of smaug mRNA at the end of the MZT through Pumilio-binding cis-elements in the smaug 3´ untranslated region, and that...

Cancer genomics and precision oncology are increasingly central to cancer care, but many health systems struggle to implement them equitably, effectively, and sustainably. This Commission defines the current global precision oncology landscape and analyses the scientific, structural, and health-system challenges shaping its delivery and impact. Findings indicate that access to cancer genomics and precision oncology remains profoundly unequal across and within countries, leaving millions of...

Cancer genomic data sharing is a core pillar of precision oncology, underpinning reproducibility, scalability, and equity. The ability to discover, access, integrate, interpret, and reuse cancer 'omics data is a key determinant of precision oncology's value and benefit at scale. This work has been conducted as part of The Lancet Oncology Commission on Cancer Genomics and Precision Oncology to examine the practical data architecture required to support cancer genomics in research, clinical care,...

The integration of copy number variant (CNV) workflows into genome sequencing (GS) analysis pipelines allows for the identification of CNVs implicated in disease. Here, we generated a novel resource of CNVs identified in the HostSeq population cohort from Canada, identified the prevalence of recurrent CNVs associated with neurodevelopmental disorders, and determined CNVs of potential clinical relevance for reproductive planning and personal disease risk. GS data and CNV calls were generated for...