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A Local Structure Analysis of Defects in UiO-66: Insights from Solid-State Nuclear Magnetic Resonance and X-ray Absorption Fine Structure
Programmable Helicity and Macrocycle Symmetry in β-Peptides via Site-Selective Thioamide Substitution
PixlMap: A generalisable pixel classifier for cellular phenotyping in multiplex immunofluorescence images
Multiplexed methods for the detection of protein expression generate extremely data-rich images of intact tissue sections. These images are invaluable for the quantification and analysis of complex biology and biomarker development. However, their interpretation presents a considerable analytical challenge. Cell segmentation from images is a key bottleneck and a major focus of research activity in artificial intelligence. Most current methods depend initially on the use of a nuclear counterstain to identify nuclear boundaries, which is a relatively straightforward task. The cellular boundary is then assigned either by expansion of the nuclear outline, or by the use of membrane or cytoplasm-specific stains to delineate cell boundaries, or by some combination of the two. The task is critical, as inaccurate segmentation leads to information loss and data contamination from neighbouring cells. Increasingly sophisticated methods are being developed to address these issues, but each has its own shortcomings. We present an alternative method which is inspired by the fact that the assignation of a cellular phenotype ‘by eye’ does not depend upon the accurate identification of cell boundaries. We present an easy-to-use deep learning-based cellular phenotyping method which leverages this human capacity to assign phenotypes without segmenting the entire cell, and which can accurately phenotype cells based on nuclear segmentation alone. Using human ground truth annotations of entire cellular regions, we developed a classifier leveraging the U-Net architecture within a commercially available deep learning image analysis platform, but the principle is transferrable to any deep-learning framework. Crucially, training requires only a single example of each compartmental stain (nuclear/cytoplasmic/membranous). The resulting algorithm assigns class identities to cells with nuclear labelling alone, without the need for whole cell expansion. The method is highly novel, broadly generalisable, and comparable in accuracy to intensity-based phenotyping methods, bridging the gap between inaccurate cellular segmentation and accurate phenotype generation.
Testing the taxonomy of Dmanisi hominin fossils through dental crown area
The Dmanisi paleoanthropological assemblage from Georgia is among the most debated collections of hominin fossils due to its early age and extreme morphological diversity relative to other Homo assemblages. This variability has been interpreted as a result of sexual dimorphism in the Homo erectus clade, in which Dmanisi hominins were traditionally classified. However, this hypothesis has been challenged by the proposal that the Dmanisi fossils represent more than one Homo species. Taxonomic assessments of the Pleistocene Georgian hominins have focused primarily on craniometric analyses, with fewer studies addressing dental morphology through metric approaches. Considering the value of dental crown area in reconstructing evolutionary relationships, a comparative sample of fossil hominins, consisting of 51 maxillary and 71 mandibular specimens (583 teeth in total), was analyzed using Linear Discriminant Analysis (LDA) to evaluate the diversity in the Dmanisi fossil assemblage. Morphological affinities were examined visually through the first two discriminant functions, and taxonomic relationships were tested via classification analyses based on posterior probabilities. The analyses show a strong association of the D4500-D2600 specimen with australopiths, and of the D2282-D211 and D2700-D2735 specimens with Homo species. The sexual dimorphism hypothesis was tested by comparing the ratios of mandibular postcanine dentition of Dmanisi specimens with male and female gorillas and chimpanzees, which suggests that dental crown area of the Pleistocene Georgian hominins could be the product of sexual dimorphism only if they came from species with similar levels of dimorphism than these great apes. We conclude that differences in crown dimensions support the hypothesis of two distinct taxa coexistent at the Dmanisi site, previously proposed to be Homo georgicus and Homo caucasi . This proposal has important implications for the dispersal of Homo out of Africa at the beginning of Pleistocene.
Nonmetallic Modified Atomically Precise Octagold Nanoclusters for Electrocatalytic Nitrate Reduction to Ammonia
Robotic versus electromagnetic bronchoscopy for pulmonary leslon assessment using integrated intraprocedural imaging: Study protocol for the reliant 2 trial
Background Robotic assisted bronchoscopy (RAB) and electromagnetic navigational bronchoscopy (ENB) are two approaches to biopsy peripheral pulmonary lesions (PPLs). A recently completed cluster randomized controlled trial, RELIANT (NCT05705544), showed no difference in diagnostic yield between these two modalities. The ENB platform used in RELIANT included integrated digital tomosynthesis, allowing for real-time assessment of PPL location for more precise targeting at the time of biopsy. RAB has since been integrated with cone beam computed tomography (CBCT) to accomplish the same intraprocedural correction. It is unclear if the diagnostic yield of RAB with integrated CBCT (RAB-CBCT) is superior to ENB with integrated digital tomosynthesis (ENB-DT). Methods R obotic versus E lectromagnetic Bronchoscopy for Pulmonary L es I on A ssessme NT using integrated intraprocedural imaging (RELIANT 2) is an investigator-initiated, multicenter, open label, superiority, cluster randomized trial. At each participating institution, procedural rooms are randomly assigned to either RAB-CBCT or ENB-DT, with each procedure room-day considered a cluster. All adult patients undergoing navigational bronchoscopy for evaluation of PPL(s) are eligible. Allocation is concealed from schedulers, proceduralists, and patients until the morning of procedure when each room is randomized to a platform. The primary endpoint is the diagnostic yield, defined as the proportion of cases yielding a specific benign or malignant diagnosis per current ATS/ACCP definition. Secondary and safety endpoints include procedure duration and procedural complications. Enrollment began on November 11, 2024 and is expected to enroll approximately 440 patients in 220 clusters. Discussion RELIANT 2 is an ongoing cluster randomized trial comparing the diagnostic yield of RAB-CBCT to that of ENB-DT in patients undergoing bronchoscopy to biopsy PPLs. This trial will help address some of the limitations of the recently published RELIANT trial. Trial registration The trial was registered in ClinicalTrials.gov (NCT06654271) on October 21, 2024, prior to patient enrollment.
Sieving for Gold─An Efficient Method for Generating <i>N</i> -Heterocyclic Carbene Self-Assembled Monolayers on Nanostructured Gold Surfaces
“I’d probably trip over it because it’s bumpy”: A qualitative exploration of the lived experiences of ambulatory children with cerebral palsy walking in challenging environments
Background Children with cerebral palsy experience regular falls, but their lived experiences of falls in the real-world are unknown. Understanding the perspectives of children and parents is important to gain deeper insight into how falls happen in real-world environments, especially since typical walking analyses are carried out over level-ground and may overlook everyday challenges to balance (e.g., uneven pavements when walking to school). Walk-along interviews can generate rich insights into children’s everyday life by discussing experiences while walking. Aim The Walk-Along Project aimed to explore lived experiences of ambulatory children with cerebral palsy to determine challenging walking environments that increase fall risk day-to-day, using walk-along interviews. Methods Twelve ambulatory children with cerebral palsy (12 ± 3 years old, 6 hemiplegia, 6 diplegia) and their parents took part in an outdoor walk-along interview. Previous fall experiences and everyday challenging environments that may increase fall risk were discussed. Action cameras and microphones captured walking environments and conversations, which were later synchronised, transcribed and analysed in NVivo using interpretive description. Results Two themes were generated (‘places where trips and falls occur’ and ‘things children do to control falls and manage consequences’) plus five subthemes (‘walking on bumpy and unstable ground’, ‘taking care, walking slower and avoiding places’, ‘distracting environments are dangerous environments’, ‘close calls and falls’, and ‘managing consequences and concerns’). The most common environment suggested to increase fall risk was uneven surfaces (e.g., grass potholes) with distractions (e.g., dogs barking). Conclusions The Walk-Along Project reveals novel insights about places that increase fall risk in ambulatory children with cerebral palsy, beyond what is currently known. The importance of considering both environmental challenges (e.g., uneven surfaces) and sensory challenges (e.g., distractions) is highlighted through children’s lived experiences. Future work should consider how interacting factors (e.g., distractions in uneven environments) increase fall-risk in ambulatory children with cerebral palsy, in order to understand mechanisms of falls for potential fall prevention programmes.
Unraveling the General Trend of the Reaction of Nitrite with Diiron(II)-polychalcogenides
Navigating public, semi-public, and private drug use environments: A qualitative examination of unsheltered homelessness and drug use in Baltimore City
Unsheltered people experiencing homelessness (PEH) in the United States (US) have a disproportionately high burden of illegal drug use and overdose. Due to their economic and social marginalization, unsheltered PEH who use drugs are often constrained in where they use drugs, and this can hinder their engagement in harm reduction practices and increase their overdose risk. Using interpretative phenomenological analysis, this study investigates how unsheltered PEH who use drugs in Baltimore City perceive and engage with their drug use environment and how public, semi-public, and private features of their environment influence drug use practices and overdose risk. Public settings (e.g., street) are accessible to the general public, while semi-public settings (e.g., library restrooms) provide public access with some restrictions. In contrast, private settings (e.g., private residence) are under private ownership with no public access. Participants were recruited from the AIDS Linked to Intravenous Experience (ALIVE) Study. Data was analyzed from interviews conducted with nine participants. Participants described complex experiences managing their drug use in public, semi-public, and private spaces. In public and semi-public spaces, participants engaged in varied strategies to seek privacy. Privacy in these spaces provided participants a sense of refuge from policing and interference, but in some instances, at the expense of drug use safety. To access private spaces for drug use and shelter, participants reported engaging in an informal economy of sharing drugs and other resources. Using in private spaces enhanced participants’ sense of comfort and enabled safer drug use practices, though access to these spaces was inconsistent. A building where people can use drugs safely and privately with supervision from peers and medical staff was commonly described as an ideal drug use space across participants. Findings highlight the need to identify resources and interventions to facilitate safer drug use for unsheltered PEH who use drugs in the US. Future interventions should take a multi-level, harm reduction approach, targeting contextual and individual factors to promote safer drug use and minimize the risk of drug use-related harms among unsheltered PEH.
Selective Chiral Diamine-bisoxazoline Iron(II) Catalysts for Pyrrolidine Formation via Intramolecular C(sp <sup>3</sup> )–H Amination of Aliphatic Azides
Post-vaccination SARS-CoV-2 neutralizing antibodies in pregnant women receiving biologics for inflammatory bowel disease
Inflammatory bowel disease (IBD) treatments and pregnancy can independently modulate immune responses, but the combined impacts on SARS-CoV-2 vaccine-induced immunity are poorly understood. This study explores the efficacy of SARS-CoV-2 vaccination and placental antibody transfer among pregnant women with IBD on biologic therapies. This observational study included pregnant women with and without IBD from the PIANO and PREVENT-COVID studies and their neonates. We assessed anti-SARS-CoV-2 neutralizing antibody titers (NT50) in maternal and cord blood post-vaccination using a pseudotype neutralization assay and calculated placental transfer ratios. A total of 32 pregnant women participated, and 27 were exposed to a biologic medication during pregnancy. Neutralizing antibody titers were similar between biologic-treated and non-treated groups, and biologic-exposed women demonstrated robust placental transfer of neutralizing antibodies. Corticosteroid use during pregnancy was significantly associated with reduced placental transfer efficiency, although this effect was not significant in a sensitivity analysis excluding patients treated with immunomodulators. Vaccination timing and SARS-CoV-2 infection impacted maternal and cord antibody levels, with higher titers observed in those vaccinated before pregnancy or infected during pregnancy. Overall, our findings suggest that upon vaccination, pregnant women with IBD on biologic therapies mount effective SARS-CoV-2 neutralizing antibody responses similar to their non-biologic-exposed counterparts, with efficient placental transfer. These findings support the efficacy of SARS-CoV-2 vaccination in this population, though further research with larger cohorts is needed for validation and to explore the long-term protective effects of transferred antibodies in neonates. Furthermore, corticosteroid use, immunomodulator use, and vaccination timing may influence antibody dynamics, underscoring the need for tailored clinical management in this vulnerable population.
Driving style diversity in highway weaving areas: A drone-based analysis of population distribution patterns and operational parameter relationships
Driving style heterogeneity significantly influences traffic safety and efficiency in highway weaving areas, yet how operational parameters systematically shape population-level behavioral patterns remains unclear. This study examines the relationships between weaving area operational characteristics and driving style population distribution patterns using drone-collected trajectory data from seven highway weaving areas, obtaining 12,707 complete vehicle trajectories. Six driving style features incorporating speed and acceleration metrics were extracted, and Gaussian Mixture Model clustering identified three distinct driving style types: aggressive (23.5%), moderate (58.9%), and conservative (17.6%). Population distribution characteristics were quantified using Shannon entropy, Gini coefficient, and dominance index, revealing significant variations across weaving areas with Shannon entropy values ranging from 0.376 to 0.703. Statistical analysis demonstrated that weaving complexity exhibited strong positive correlation with Shannon entropy (r = 0.909, p = 0.005), while headway time showed significant negative correlation (r = −0.760, p = 0.047). A critical threshold of 300m was identified for weaving length effects on population distributions. Machine learning-based driving style classification models incorporating 17-dimensional features achieved 95.4% identification accuracy, with lateral acceleration contributing the highest feature importance (35.5%) and operational parameters accounting for 31.4% of total feature significance. The findings reveal that operational parameters correlate with driving style distributions through hierarchical patterns where geometric parameters are associated with spatial constraints, traffic flow parameters provide dynamic regulation, and weaving task parameters create behavioral differentiation. This research contributes to understanding how infrastructure and traffic conditions systematically shape collective driver behavior patterns, offering new approaches for traffic management optimization in intelligent transportation environments.
A Sterically Open Ruthenium-Based Photocage Activated by Red and Far-Red Light for a Wide Range of Drugs
Mapping the climate and agronomic digital advisory services landscape in West and Central Africa: A step towards making food systems productive and climate resilient
This study explores and examines the availability of digital agricultural solutions (DAGs) to enhance agricultural resilience in the face of climate change. The countries under study—Burundi, Ivory coast, Democratic Republic of Congo (DRC), Ghana, Nigeria, and Rwanda—display varying levels of vulnerability, suffering from low adaptive capacity to address climate impacts. The study examines available DAGs to support farmers, including mobile-based platforms providing weather and agronomic advice, market information, and financial services. We highlight the diverse needs and challenges faced by three key user groups of digital agro-climatic services: farmers, service providers, and policymakers. All stakeholders require tailored approaches to improve adoption and impact. We employed a mixed-method approach that combined literature review with semi-structured interviews to identify existing digital solutions in agriculture. Next, we produced country-specific reports to assess the current state of agronomic digital advisory services, their users, and challenges. Ghana, Nigeria, and Rwanda have made notable strides in delivering these services, though challenges such as inadequate infrastructure, high internet costs, and gender disparities hinder their wider adoption. Additionally, data fragmentation and lack of harmonization across platforms pose significant barriers to optimizing these digital solutions. We discuss the role of public extension services and policy frameworks in fostering digital transformation in agriculture, with an emphasis on the need for better data harmonization to improve decision-making. The study underscores the importance of integrating digital technologies with stronger policies, improved infrastructure, and greater inclusivity to support climate-resilient agricultural practices in the region.
Multisite Proton-Coupled Electron Transfer Enables Iodanyl Radical Catalysis
Lesion volume and location can be estimated by analysis of the new NIH Stroke Scale picture description
In January 2024, the picture stimuli used to elicit language on the NIH Stroke Scale were updated. Descriptions elicited using the now-retired Cookie Theft picture are informative regarding the size and location of stroke. An important dimension of validation for the new stimuli is to demonstrate that the language patients produce when describing the new Precarious Painter picture that is now part of the NIH Stroke Scale is similarly informative. Participants included 62 patients with acute ischemic stroke (24 left and 38 right) compared with 10 control participants hospitalized following transient ischemic attack. Descriptions of the Precarious Painter image were analyzed for content and structure. Bilateral regions of interest were selected based on their role in language processing, and lesion volume and location were measured on diffusion-weighted imaging. Analyses of variance were used to contrast discourse performance across groups, and correlations between discourse characteristics and proportion of region lesioned were calculated. Patients with left hemisphere strokes included less content from the right side of the picture, F(2) = 7.4, p = 0.001, η 2 P = 0.19, than those in the other groups. Informational efficiency had a strong inverse relationship with extent of lesion to the left, but not right, IFG. Correlations between discourse variables and lesion locations were grossly consistent with those previously reported and evidenced relationships between discourse variables and the bilateral extended language network. Features of picture description that may be appraised without specialized training in communication, such as how many things a patient includes, their location, and the inclusion of inferences or summarizing statements in the description, provide insight into stroke location and severity. The samples elicited using the new Precarious Painter stimulus perform similarly to those elicited using the retired Cookie Theft stimulus.