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Background: Handheld cameras may increase access to teleretinal diabetic retinopathy screenings (TDRS), as they are more economical and nimbler than traditional desktop cameras. However, their use in safety net clinical settings is less understood. Methods: The Los Angeles County Department of Public Health collaborated with the Los Angeles County Department of Health Services (DHS) to pilot the use of handheld cameras in DHS’s TDRS program. This study assessed screening metrics and interviewed TDRS coordinators and photographers about their experiences using these cameras. Results: Handheld cameras were harder to operate and performed less optimally on key screening metrics (e.g., image quality) compared to desktop cameras. However, this challenge appeared to be linked to the selected model rather than to all handheld cameras. The adoption of handheld cameras in DHS was aided by their integration into an existing agency infrastructure that already supported the use of desktop cameras; these operational supports included an established workflow, a data platform, and experienced photographers. Conclusions: The use of handheld cameras for TDRS is a promising practice for assuring equitable access to screenings. Handheld cameras are portable, smaller in size, and lower in cost than desktop cameras. Future projects should invest in and assess the performance of higher-quality models of these cameras, especially their use in safety net clinical settings.

Abstract Climate change's effect on agriculture is a severe problem in every society, particularly in West Africa. The rising temperatures and extreme weather events have significant implications for food security. In this study, we examine the effects of CO2 emissions, agricultural advancements, and food availability on economic growth in West Africa from 1990 to 2020, using a panel ARDL approach with data from 14 countries. The analysis evaluates both long- and short-term effects, with the Dynamic Fixed Effects (DFE) estimator chosen as the most robust model. Results show no significant link between CO2 emissions and economic growth, while agriculture plays a key role, and food availability has mixed effects. The findings underscore the importance of sustainable agriculture and food security in promoting economic resilience in West Africa, offering insights for policymakers.

Abstract Laboratory automation technologies have revolutionized biomedical research. However, the availability of automation solutions at the single-cell level remains scarce, primarily owing to the inherent challenges of handling cells with such small dimensions in a precise, biocompatible manner. Here, we present a single-cell-level laboratory automation solution that configures various experiments onto standardized, microscale test-tube matrices via our precise ultrasonic liquid sample ejection technology, known as PULSE. PULSE enables the transformation of titer plates into microdroplet arrays by printing nanodrops and single cells acoustically in a programmable, scalable, and biocompatible manner. Unlike pipetting robots, PULSE enables researchers to conduct biological experiments using single cells as anchoring points (e.g., 1 cell vs. 1000 cells per “tube”), achieving higher resolution and potentially more relevant data for modeling and downstream analyses. We demonstrate the ability of PULSE to perform biofabrication, precision gating, and deterministic array barcoding via preallocated droplet-addressable primers. Single cells can be gently printed at a speed range of 5–20 cell⋅s−1 with an accuracy of 90.5–97.7%, which can then adhere to the substrate and grow for up to 72 h while preserving cell integrity. In the deterministic barcoding experiment, 95.6% barcoding accuracy and 2.7% barcode hopping were observed by comparing the phenotypic data with known genotypic data from two types of single cells. Our PULSE platform allows for precise and dynamic analyses by automating experiments at the single-cell level, offering researchers a powerful tool in biomedical research.

Abstract Advanced biofabrication techniques can create tissue-like constructs that can be applied for reconstructive surgery or as in vitro three-dimensional (3D) models for disease modeling and drug screening. While various biofabrication techniques have recently been widely reviewed in the literature, acoustics-based technologies still need to be explored. The rapidly increasing number of publications in the past two decades exploring the application of acoustic technologies highlights the tremendous potential of these technologies. In this review, we contend that acoustics-based methods can address many limitations inherent in other biofabrication techniques due to their unique advantages: noncontact manipulation, biocompatibility, deep tissue penetrability, versatility, precision in-scaffold control, high-throughput capabilities, and the ability to assemble multilayered structures. We discuss the mechanisms by which acoustics directly dictate cell assembly across various biostructures and examine how the advent of novel acoustic technologies, along with their integration with traditional methods, offers innovative solutions for enhancing the functionality of organoids. Acoustic technologies are poised to address fundamental challenges in biofabrication and tissue engineering and show promise for advancing the field in the coming years.

Abstract Objectives Gout is caused by the response of the innate immune system to monosodium urate (MSU) crystals. A recent gout GWAS identified a signal of genetic association at a locus encompassing IL1RN-IL1F10. Colocalisation analysis using Genotype Tissue Expression Database (GTEx) eQTL data showed that the signal overlaps with genetic control of IL1RN/IL1F10 gene expression. We assess the functional implications of IL1RN rs9973741, the lead gout-associated variant. Methods We conducted functional validation of IL1RN rs9973741 in patients with gout and controls. The transcription level of IL1RN/IL1F10 was investigated in unstimulated or MSU-crystal co-stimulated PBMCs. Ex vivo functional assays were performed in PBMCs stimulated with C16 + MSU crystals or LPS for 24 h. Cytokine levels were assessed by ELISA. Results In unstimulated PBMCs, no association of IL1RN rs9973741 (gout risk allele G) to IL1RN expression was observed while IL-1F10 was hindered by low expression at both transcriptional and protein levels. However, G allele carriers showed lower IL1RN expression in PBMCs stimulated with C16/MSU crystal and lower concentrations of circulating IL-1Ra in both controls and gout patients. PBMCs depicted less spontaneous IL-1Ra release in GG homozygous controls and lower IL-1Ra production in response to C16 + MSU crystal costimulation in patients with gout. The G allele was associated with elevated IL-1β cytokine production in response to C16 + MSU crystal stimulation in controls. Conclusions The gout risk allele G associates with lower circulating IL-1Ra, lower IL-1Ra production in PBMC assays and elevated IL-1β production in PBMCs challenged with C16 + MSU crystals but not in unchallenged cells. Our data indicate that the genetic signal that associates with gout at IL1RN-IL1F10 region functions to alter expression of IL-1Ra when stimulated by MSU crystals.

The objective of this observational study was to estimate partial direct costs of dry cow antibiotic therapy (DCT) protocols used on 37 large dairy herds in Wisconsin and to estimate the potential monetary savings and reduction in antimicrobial usage (AMU) if selective DCT was used. Partial direct costs of DCT were calculated using costs of intramammary (IMM) antimicrobials and teat sealants. Data were retrospectively collected on 37 large dairy farms for a period of 1 yr and included the total number of cows dried off, types of IMM antimicrobial used, and product prices (obtained from farm invoices). A single farm visit was performed to verify data. Clinical mastitis (CM) and SCC history across lactation were used as the criteria to identify cows eligible to receive only teat sealants (no antibiotic DCT) based on adoption of a hypothetical selective DCT program. Descriptive statistics were performed using PROC MEANS to summarize continuous herd and cow characteristics. Differences in costs among IMM antibiotic products and eligibility to not receive antibiotics at dry-off by parity were analyzed using ANOVA. Differences in milk yield at the last test-day and DIM at dry-off based on eligibility for selective DCT were analyzed using PROC MIXED. A total of 35,691 cows were dried off across all herds (n = 37) and most of the herds used IMM antibiotic DCT at dry-off in most of the cows. Teat sealant was used as part of the dry-off protocol in all but 3 herds. Of the enrolled farms, 30 used blanket antibiotic DCT in all quarters of all cows and 7 herds used selective DCT with no administration of antibiotics given to 0.8% to 58% of the dry cows within the herd. Across all farms, the average cost of products given per dried cow was $19.57 ± 0.64 (mean ± SE) and ranged from $8.72 to $24.04. As expected, the cost per dried cow was greater ($23.45 ± $0.38) in herds that used higher cost IMM antibiotics as compared with herds that used lower cost IMM antibiotics ($16.64 ± $0.40). When using an algorithm based on udder health records to hypothetically select cows that would be eligible to receive teat sealants only (no antibiotic DCT), eligibility ranged from 27.3% to 93.3% within-herds and varied by parity, milk yield at last test-day, and DIM at dry-off. If a selective DCT program based on udder health records was used, an overall reduction of $5.37 (27% of total costs) per dry cow would be expected. Likewise, adoption of selective DCT based on udder health records would reduce AMU at dry-off by approximately 51%. However, neither of these estimates included potential adverse health complications (such as increased CM) that can occur if selective DCT programs are not effectively performed. Variations in partial direct costs at dry-off were observed among herds based on treatment protocols. In herds that have good udder health management and contagious mastitis pathogens controlled, adoption of selective DCT based on SCC and history of CM can reduce AMU and partial direct costs of dry cow management.

Abstract We present theoretical predictions for μ → e conversion rates using a tower of effective field theories connecting the UV to nuclear physics scales. The interactions in nuclei are described using a recently developed nonrelativistic effective theory (NRET) that organizes contributions according to bound nucleon and muon velocities, v → N $$ {\overrightarrow{v}}_N $$ and v → μ $$ {\overrightarrow{v}}_{\mu } $$ , with v → N $$ \left|{\overrightarrow{v}}_N\right| $$ > v → μ $$ \left|{\overrightarrow{v}}_{\mu}\right| $$ . To facilitate the top-down matching, we enlarge the set of Lorentz covariant nucleon-level interactions mapped onto the NRET operators to include those mediated by tensor interactions, in addition to the scalar and vector interactions already considered previously, and then match NRET nonperturbatively onto the Weak Effective Theory (WET). At the scale μ ≈ 2 GeV WET is formulated in terms of u, d, s quarks, gluons and photons as the light degrees of freedom, along with the flavor-violating leptonic current. We retain contributions from WET operators up to dimension 7, which requires the full set of 26 NRET operators. The results are encoded in the open-source Python- and Mathematica-based software suite MuonBridge, which we make available to the theoretical and experimental communities interested in μ → e conversion.

Abstract Background Routine childhood immunization against varicella-zoster virus has led to a dramatic reduction in the incidence of primary varicella. However, there are rare, yet significant cases reported of reactivated Oka-strain varicella, primarily in immunocompromised hosts. Case presentation A 16-year-old female with Hodgkin’s lymphoma developed a vesicular rash shortly after completing all chemotherapy treatment. Swabs obtained from the vesicles were positive for varicella-zoster virus. By the time of hospitalization, the patient developed a disseminated rash involving multiple dermatomes. Subsequent polymerase chain reaction confirmed Oka vaccine-strain varicella-zoster virus. The patient had previously received a primary series of immunizations against varicella in 2008 and 2012, with her 2nd dose given 11 years prior to her development of vaccine-strain herpes zoster and 10 years prior to her diagnosis of Hodgkin’s lymphoma, respectively. The patient was treated with parenteral acyclovir upon hospitalization and monitored clinically for cutaneous disease progression as well as sequelae. After 8 days of inpatient treatment, her rash had stopped spreading with no new lesions. All earlier lesions had crusted over. No serious sequelae of disease such as pneumonitis, hepatitis, encephalitis, or meningitis occurred, and she made a complete recovery. Conclusions There are individual and community-wide benefits to childhood immunization against varicella. This case highlights an unusual presentation of disseminated vaccine-strain herpes zoster in an adolescent with secondary immunodeficiency 11 years after completing primary immunization. In addition, this case informs pediatricians of complications that can arise in immunized subjects if they become immunosuppressed years later. The only way to distinguish between wild-type and vaccine-strain herpes zoster was by viral genotyping. Providers should be cognizant of potential vaccine virus reactivation in their differential. Considerations for work-up and management should include infection control and viral resistance in refractory cases.

Abstract Increasing biological nitrogen (N) fixation (BNF) in maize production could reduce the environmental impacts of N fertilizer use, but reactive N in the rhizosphere of maize limits the BNF process. Using non-transgenic methods, we developed gene-edited strains of Klebsiella variicola (Kv137-2253) and Kosakonia sacchari (Ks6-5687) bacteria optimized for root-associated BNF and ammonium excretion in N-rich conditions. The aim of this research was to elucidate the mechanism of action of these strains. We present evidence from in vitro, in planta and field experiments that confirms that our genetic remodeling strategy derepresses BNF activity in N-rich systems and increases ammonium excretion by orders of magnitude above the respective wildtype strains. BNF is demonstrated in controlled environments by the transfer of labeled 15N2 gas from the rhizosphere to the chlorophyll of inoculated maize plants. This was corroborated in several 15N isotope tracer field experiments where inoculation with the formulated, commercial-grade product derived from the gene-edited strains (PIVOT BIO PROVEN® 40) provided on average 21 kg N ha-1 to the plant by the VT-R1 growth stages. Data from small-plot and on-farm trials suggest that this technology can improve crop N status pre-flowering and has potential to mitigate the risk of yield loss associated with a reduction in synthetic N fertilizer inputs.

Abstract Background With the next generation of Human Epidermal Growth Factor Receptor 2 (HER2) -targeting therapies, such as antibody–drug conjugates, showing benefit in “HER2 low” and even “HER2 ultralow” patients, the need for novel methods to quantify HER2 expression accurately becomes even more important for clinical decision making. A HER2 PET/CT imaging assessment could evaluate HER2 positive disease locations while improving patient care, reducing the need for invasive biopsies. A single-domain antibody (sdAb)-based PET tracer could combine the high specificity of sdAbs with short-lived radionuclides such as fluorine-18 (18F) and gallium-68 (68Ga). SdAb-based PET tracers have clinically been used via a 68Ga-chelator approach. However, the distribution of 68Ga-labelled pharmaceuticals to peripheral PET centres is more challenging to organize due to the short half-life of 68Ga, most certainly when the available activity is limited by a generator. Cyclotron produced 68Ga has removed this limitation. Distribution of 18F-labelled pharmaceuticals remains less challenging due to its slightly longer half-life, and radiofluorination of sdAbs via N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) has shown to be a promising strategy for developing sdAb-based PET tracers. Although [18F]SFB automation has been reported, automating protein conjugation proves challenging. Herein we report the fully automated, cartridge-based production of [18F]FB-HER2 sdAb on a single synthesis module. Results [18F]FB-HER2 sdAb (> 6 GBq) was obtained after a fully automated production (95 min), with a RCP > 95%, apparent molar activity > 20 GBq/µmol and decay-corrected radiochemical yield (RCY d.c.) of 14 ± 2% (n = 4). Further upscaling amounted to production batches of 16 GBq with an apparent molar activity > 40 GBq/µmol and RCY d.c. of 8 ± 1% (n = 4). Ex vivo biodistribution and PET imaging showed specific HER2-positive tumour targeting and low kidney retention. Conclusion The [18F]FB-HER2 sdAb tracer was produced with clinically relevant activities using a fully automated production method. The automated production method was designed to ease the translation to the clinic and has the potential to be used not only in mono-centre but also multi-centre clinical trials with one central production site. [18F]FB-HER2 sdAb showed a favourable biodistribution pattern and could be a valuable alternative to 68Ga-labelled sdAb-based PET tracers in the clinic.

Abstract Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was eliminated from New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of SARS-CoV-2. However, in 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five-times higher than typical seasonal patterns. We generated 1470 viral genomes of both RSV-A and RSV-B sampled between 2015–2022 from across New Zealand. Using a phylodynamics approach, we used these data to better understand RSV transmission patterns in New Zealand prior to 2020, and how RSV became re-established in the community following the relaxation of COVID-19 restrictions. We found that in 2021, there was a large epidemic of RSV due to an increase in importations, leading to several large genomic clusters of both RSV-A ON1 and RSV-B BA9 genotypes. However, while a number of viral importations were detected, there was also a major reduction in RSV genetic diversity compared to pre-pandemic years. These data reveal the impact of NPI used during the COVID-19 pandemic on other respiratory infections and highlight the important insights that can be gained from viral genomes.

Abstract We study generative diffusion models in the regime where both the data dimension and the sample size are large, and the score function is trained optimally. Using statistical physics methods, we identify three distinct dynamical regimes during the generative diffusion process. The generative dynamics, starting from pure noise, first encounters a speciation transition, where the broad structure of the data emerges, akin to symmetry breaking in phase transitions. This is followed by a collapse phase, where the dynamics is attracted to a specific training point through a mechanism similar to condensation in a glass phase. The speciation time can be obtained from a spectral analysis of the data’s correlation matrix, while the collapse time relates to an excess entropy measure, and reveals the existence of a curse of dimensionality for diffusion models. These theoretical findings are supported by analytical solutions for Gaussian mixtures and confirmed by numerical experiments on real datasets.

Abstract Monitoring water uptake in cementitious systems is crucial to assess their durability against corrosion, salt attack, and freeze-thaw damage. However, gauging absorption currently relies on labor-intensive and infrequent weight measurements, as outlined in ASTM C1585. To address this issue, we introduce a custom computer vision model trained on 6234 images, consisting of 4000 real and 2234 synthetic, that automatically detects the water level in prismatic samples absorbing water. This model provides accurate and frequent estimations of water penetration values every minute. After training the model on 1440 unique data points, including 15 paste mixtures with varying water-to-cement ratios from 0.4 to 0.8 and curing periods of 1 to 7 days, we can now predict initial and secondary sorptivities in real time with high confidence, achieving R² > 0.9. Finally, we demonstrate its application on mortar and concrete systems, opening a pathway toward low-cost and automated durability assessment of construction materials.

Abstract Background A dementia diagnosis can lead to a decline in cognitive, social, and physical health, but people with dementia can live meaningful lives and participate actively in society with psychosocial support. This single-arm, non-randomised feasibility study explored the feasibility and acceptability of a Comprehensive REsilience-building psychoSocial intervenTion (CREST) for people with dementia, their caregivers, General Practitioners (GPs), and the public. Methods Nine people with dementia and their primary caregivers living in the community (n = 9 dyads) completed the CREST intervention which had three components (cognitive stimulation therapy [CST], physical exercise, and dementia education). Quantitative secondary outcomes were assessed at baseline and following the 15-week intervention; qualitative interviews were conducted during and post-intervention. All study components were assessed against pre-defined criteria, to determine the feasibility of conducting a future definitive trial. Results Recruitment of people with dementia and their caregiver was a significant challenge and led to considerable delays to the onset and conduct of the intervention. Only 13% of eligible GP practices agreed to assist in recruitment and achieved a 6% enrolment rate; a community-based recruitment strategy proved more effective, yielding a 29% enrolment rate. However, once recruited, participants maintained high attendance and adherence to the content of each component with average adherence rates of 98% for CST, exercise sessions and caregiver education. Adherence to secondary exercise measures was lower, with home exercise diary completion at 37% and Fitbit wear adherence at 80% during the day and 67% at night. The people with dementia felt their concentration and fitness had improved over the 15-week intervention and particularly enjoyed the social aspects (e.g. group classes, exercising with partners from the community). Caregivers felt they had better knowledge and understanding following their education component and reported that the social aspects (interacting and sharing experiences with each other) were important. Overall, participants reported that the three components of the intervention were feasible and acceptable. In addition, the quantitative measures and health economic tools employed were feasible. However, the secondary elements of the exercise component (recording home exercise diaries and Fitbit use) were not considered feasible. Overall, pre-defined criteria for progression to a definitive intervention were fulfilled in terms of acceptability, retention and fidelity but not recruitment. Conclusion While overall, the CREST intervention was feasible and acceptable to participants, significant difficulties with recruitment of people with dementia and their caregiver through GP practices impacted the viability of delivering the intervention. Recruitment through community-based groups proved a more feasible option and further work is needed to overcome barriers to recruiting this cohort before a larger-scale trial can be conducted. Trial registration ISRCTN25294519.

Abstract In this study, available large ensemble datasets in the Coupled Model Intercomparison Phase 6 (CMIP6) archive were used to provide the first multi-variate overview of the evolution of extreme seasons over Antarctica and the Southern Ocean during the 20th and 21st centuries following medium-to-high radiative forcing scenarios. The results show significant differences between simulated changes in background mean climate and changes in low (10th percentile) and high (90th percentile) extreme seasons. Regional winter warming is most pronounced for cold extremes. In summer, there are more pronounced increases in high extremes in precipitation and westerly wind during the ozone hole formation period (late 20th century), affecting coastal regions and, in particular, the Antarctic Peninsula. At midlatitudes, there is a reduction in the range of summer season wind extremes. Suggested mechanisms for these differences are provided relating to sea ice retreat and westerly jet position.

Abstract This untargeted metabolomics study investigated the synergistic antibacterial activity of polymyxin B and Leu10-teixobactin, a depsipeptide inhibitor of cell wall biosynthesis. Checkerboard microdilution assays revealed a significant synergy against polymyxin-susceptible and -resistant A. baumannii, excluding lipopolysaccharide-deficient variants. Time-kill assays confirmed bactericidal synergy, reducing bacterial burden by approximately 4-6-log10CFU/mL. The combination (2xMIC polymyxin B and 0.5xMIC Leu10-teixobactin) prevented bacterial regrowth after 24 h, indicating sustained efficacy against the emergence of resistant mutants. The analysis of A. baumannii ATCC™ 19606 metabolome demonstrated that the polymyxin B–Leu10-teixobactin combination produced more pronounced perturbation compared to the individual antibiotics across all time points (1, 3 and 6 h). Pathway analysis revealed that lipid metabolism, cell envelope biogenesis, and cellular respiration were predominantly impacted by the combination, and to a lesser extent by polymyxin B monotherapy. Leu10-teixobactin treatment alone had only a minor impact on the metabolome, primarily at the 6 h time point. Peptidoglycan assays confirmed the combination’s concerted deleterious effects on bacterial cell envelope integrity. Electron microscopy further substantiated these findings, revealing pronounced cell envelope damage, membrane blebbing, and vacuole formation. These findings highlight the potential of the polymyxin B–Leu10-teixobactin combination as an effective treatment in preventing resistance in A. baumannii.

Abstract Background Dynamic transmission models are often used to provide epidemiological guidance for pandemic policy decisions. However, how economic evaluation is typically incorporated into this technique to generate cost-effectiveness estimates of pandemic policy responses has not previously been reviewed. Methods We systematically searched the Embase, PubMed and Scopus databases for dynamic epidemiological modelling studies that incorporated economic evaluation of public health and social measures (PHSMs), with no date restrictions, on 7 July 2024. Results Of the 2,719 screened studies, 51 met the inclusion criteria. Most studies (n = 42, 82%) modelled SARS-CoV-2. A range of PHSMs were examined, including school closures, testing/screening, social distancing and mask use. Half of the studies utilised an extension of a Susceptible-Exposed-Infectious-Recovered (SEIR) compartmental model. The most common type of economic evaluation was cost-effectiveness analysis (n = 24, 47%), followed by cost-utility analysis (n = 17, 33%) and cost–benefit analysis (n = 17, 33%). Conclusions Economic evaluation is infrequently incorporated into dynamic epidemiological modelling studies of PHSMs. The scope of this research should be expanded, given the substantial cost implications of pandemic PHSM policy responses.

Cyclodextrins (CDs) are host systems with inherent capability for inclusion complex formation with various molecular entities, mostly hydrophobic substances. Host CDs are highly accommodative to water molecules as well and usually contain water in the native state. There is still an ongoing discussion on both the total number of water molecules and their preferred binding position inside the cavities of the CDs. To understand the hydration/dehydration properties of γ-CD (the largest of the three most abundant native CDs), the main experimental methods applied in this study were differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). By coupling these techniques with density functional theory (DFT) calculations we try to shed some light on the mechanism of the γ-CD hydration and to address some unanswered questions: (i) what are the preferable locations for water molecules in the macrocyclic cavity (“hot spots”); (ii) what are the major factors contributing to the stability of the water cluster in the CD interior; (iii) what type of interactions (i.e., water–water and/or water–CD walls) contribute to the stability of the water assemble; (iv) how does the mechanism of the γ-CD hydration compare with those of its α-CD and β-CD counterparts.

Abstract Staphylococcus aureus (S. aureus) is a significant Gram-positive opportunistic pathogen behind many debilitating infections. β-lactam antibiotics are conventionally prescribed for treating S. aureus infections. However, the adaptability of S. aureus in evolving resistance to multiple β-lactams contributed to the persistence and spread of infections, exemplified in the emergence of methicillin-resistant S. aureus (MRSA). In the present study, we investigated the efficacies of the synthetic teixobactin analogue, Leu10-teixobactin, combined with the penicillinase-resistant cephalosporin cefepime against MRSA strains. The Leu10-teixobactin and cefepime combination exerted synergism against most strains tested in broth microdilution assay. Time-kill profiles showed that both Leu10-teixobactin and cefepime predominantly exhibited synergistic activity, with > 2.0-log10CFU decrease compared to monotherapy at 24 h. Moreover, biofilm assays revealed a significant inhibition of biofilm production in ATCC™43300 cells treated with sub-MICs of Leu10-teixobactin and cefepime. Subsequent electron microscopy studies showed more extensive damage with the combination therapy compared to monotherapies, including aberrant bacterial morphology, vesicle formation and substantial lysis, indicating combined damage to the cell wall. Quantitative real-time PCR revealed marked perturbation of genes mecA, sarA, atlA, and icaA, substantiating the apparent mode of combined antibacterial action of both antibiotics against peptidoglycan synthesis and initial biofilm production. Hence, the study highlights the prospective utility of the Leu10-teixobactin-cefepime combination in treating MRSA infections via β-lactam potentiation.

Abstract Coronary artery disease (CAD) remains a leading cause of death worldwide and imposes a substantial socioeconomic burden on healthcare. Improving risk stratification in clinical practice could help to combat this burden. As amino acids are biologically active metabolites whose involvement in CAD remains largely unknown, this study investigated associations between circulating amino acid levels and CAD phenotypes. A high-coverage quantitative liquid chromatography-mass spectrometry approach was applied to acquire the serum amino acids profile of age- and sex-coarsened-matched patients with CAD (n = 46, 66.9 years, 74.7% male) and healthy individuals (n = 120, 67.4 years, 74.7% male) from the COmPLETE study. Multiple linear regressions were performed to investigate associations between amino acid levels and (a) the health status (CAD vs. healthy), (b) the number of affected coronary arteries, or (c) the left ventricular ejection fraction. Regressions were adjusted for age, sex, daily physical activity, sampling, and fasting time. Urea cycle amino acids (ornithine, citrulline, homocitrulline, aspartate, and arginine) were significantly and negatively associated with CAD, the number of affected coronary arteries, and the left ventricular ejection fraction. Lysine, histidine, and the glutamine/glutamate ratio were also significantly and negatively associated with the CAD phenotypes. Overall, patients with CAD displayed lower levels of urea cycle amino acids, highlighting a potential role for urea cycle amino acid profiling in cardiovascular risk stratification. Trial registration The study was registered on https://www.clinicaltrials.gov (NCT03986892) on June 5, 2019.

Abstract Bitcoin adoption as a legal tender threatens a financial crisis because of the lack of regulatory frameworks and systems for exchanging Bitcoin into local currencies. This study analyzes monthly data from 2010 to 2022 using a structural vector autoregressive model, estimating Bitcoin’s pass-through into remittance, money multiplier, the US Dollar index, and gold price. The results show that Bitcoin prices decrease the money multiplier and gold prices in both the short and long run, while remittances moderately increase in the long run. The implication of these results suggests the potential for international business opportunities to stimulate the credit, savings, and investment monetary policy channel. The results are robust to alternative SVAR identification strategies.

Abstract Hyperdimensional Computing (HDC), also known as Vector Symbolic Architectures (VSA), is a neuro-inspired computing framework that exploits high-dimensional random vector spaces. HDC uses extremely parallelizable arithmetic to provide computational solutions that balance accuracy, efficiency and robustness. The majority of current HDC research focuses on the learning capabilities of these high-dimensional spaces. However, a tangential research direction investigates the properties of these high-dimensional spaces more generally as a probabilistic model for computation. In this manuscript, we provide an approachable, yet thorough, survey of the components of HDC. To highlight the dual use of HDC, we provide an in-depth analysis of two vastly different applications. The first uses HDC in a learning setting to classify graphs. Graphs are among the most important forms of information representation, and graph learning in IoT and sensor networks introduces challenges because of the limited compute capabilities. Compared to the state-of-the-art Graph Neural Networks, our proposed method achieves comparable accuracy, while training and inference times are on average 14.6× and 2.0× faster, respectively. Secondly, we analyse a dynamic hash table that uses a novel hypervector type called circular-hypervectors to map requests to a dynamic set of resources. The proposed hyperdimensional hashing method has the efficiency to be deployed in large systems. Moreover, our approach remains unaffected by a realistic level of memory errors which causes significant mismatches for existing methods.

Abstract Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically rely on prior identification of tumor-specific mutations. Here, we develop a tumor-independent and mutation-independent approach (DELFI-tumor fraction, DELFI-TF) using low-coverage whole genome sequencing to determine the cfDNA tumor fraction and validate the method in two independent cohorts of patients with colorectal or lung cancer. DELFI-TF scores strongly correlate with circulating tumor DNA levels (ctDNA) (r = 0.90, p

Abstract Background Most children with developmental disabilities (DD) live in low- and middle-income countries, but access to services is limited, impacting their ability to thrive. Pilot study findings of the World Health Organization’s Caregiver Skills Training (WHO CST) intervention, which equips caregivers with strategies to facilitate learning and adaptive behaviours in children with DD, are promising but evidence from an appropriately powered trial delivered by non-specialist facilitators is lacking. This study will investigate the effectiveness and the resource impacts and costs and consequences of the WHO CST intervention in four sites in rural and urban Kenya and Ethiopia. Methods This is a 2-arm multi-site hybrid type-1 effectiveness implementation cluster randomised controlled superiority trial. After baseline assessments (T0) are completed by participants in clusters comprising 7 to 10 caregiver-child dyads, the clusters will be randomised to either the WHO CST intervention arm or a waitlist enhanced care as usual control arm. Further assessments will be completed at endpoint (T1, 18 ± 2 weeks after randomisation) and follow-up (T2, 44 ± 2 weeks after randomisation). The intervention comprises three individualised home visits and nine group sessions with trained non-specialist facilitators. Participants in the control arm will receive the intervention after completing follow-up assessments. We aim to recruit 544 child-caregiver dyads, evenly distributed across the two arms and countries. The co-primary outcomes are the child-focused Child Behavior Checklist (assessing emotional and behavioural problems) and the caregiver-focused Pediatric Quality of Life Inventory (assessing caregiver quality of life), both assessed at endpoint. Secondary outcome measures comprise the two co-primary outcomes at follow-up and ten additional outcome measures at endpoint, assessing stigma-based experiences, depressive symptoms, household food insecurity, child disciplinary strategies and beliefs, CST knowledge and skill competencies, caregiver and child quality of life, social support, and children’s communication modes and functions. After quantitative follow-up assessments are completed, a mixed-methods evaluation approach will be used to investigate implementation processes and acceptability, feasibility, and potential sustainability of the intervention. Discussion The study’s findings will provide evidence of the effectiveness and resource impacts and costs and consequences of a non-specialist-delivered intervention in under-resourced contexts in one low-income and one middle-income country in East Africa. Findings will inform future research, intervention, and policy efforts to support children with DD and their families in under-resourced majority world contexts. Trial registration Pan African Clinical Trial Registry PACTR202310908063134. Registered on October 16, 2023.

Abstract In this paper, we discuss how gauging one-form symmetries in Chern-Simons theories is implemented in an A-twisted topological open string theory. For example, the contribution from a fixed H/Z bundle on a three-manifold M, arising in a BZ gauging of H Chern-Simons, for Z a finite subgroup of the center of H, is described by an open string worldsheet theory whose bulk is a sigma model with target a Z-gerbe (a bundle of one-form symmetries) over T ∗ M, of characteristic class determined by the H/Z bundle. We give a worldsheet picture of the decomposition of one-form-symmetry-gauged Chern-Simons in three dimensions, and we describe how a target-space constraint on bundles arising in the gauged Chern-Simons theory has a natural worldsheet realization. Our proposal provides examples of the expected correspondence between worldsheet global higher-form symmetries, and target-space gauged higher-form symmetries.

Abstract Larval cryopreservation techniques have been established in Pacific oysters and Mediterranean mussels. Although initial cryopreservation protocols for both species differed slightly in Ficoll PM 70 (FIC) concentration, better post-thaw larval survivability was produced in mussels than oysters. Furthermore, the post-thaw survivability in the latter could be improved significantly by the addition of lipids and antioxidants to the cryoprotectant agent. These findings have generated a unique opportunity to investigate the cryo-functions of both endogenous and exogenous fatty acids (FAs) in bivalves as mammalian studies indicated that lipid compositions could contribute the interspecific difference in gamete and embryo cryopreservation. Our study showed that the higher survivability of post-thaw larvae in mussels (65% vs. 34% in oysters) could be attributed to their higher proportion of total polyunsaturated fatty acids (PUFAs), especially C22:6, and higher resistance of FA profiles to cryopreservation. In oysters, on the other hand, their FA profiles were very sensitive to cryopreservation, with saturated FAs and PUFAs being significantly increased (from 37 to 41%) and decreased (from 35% to ~ 32%), respectively. Although exogenous lipids could significantly improve the survivability of post-thaw oyster larvae from 34 to 51%, their supplementation did not alter the response pattern of endogenous FA profiles to cryopreservation.

Abstract Background Children with Neurofibromatosis 1 (NF1) show cognitive, behavioural and social differences compared to their peers. However, the age and sequence at which these differences begin to emerge is not fully understood. This prospective cohort study examines the cognitive, behavioural, ADHD trait and autism symptom development in infant and pre-school children with NF1 compared with typically developing (TD) children without a family history of neurodevelopmental conditions. Methods Data from standardised tests was gathered at 5, 10, 14, 24 and 36 months of age (NF1 n = 35, TD n = 29). Developmental trajectories of cognitive (Mullen Scales of Early Learning, MSEL) and adaptive behavioural (Vineland Adaptive Behavior Scales, VABS) development from 5 to 36 months were analysed using linear mixed modelling. Measures of ADHD (Child Behavior Checklist) and autism traits (ADOS-2, BOSA-MV and ADI-R) were assessed at 24 and 36 months. Results The developmental trajectory of cognitive skills (all domains of the MSEL) and behavioural skills (four domains of the VABS) differed significantly between NF1 and TD groups. Post-hoc tests demonstrated that the NF1 participants scored significantly lower than TD participants at 24 months on all MSEL and VABS domains. The NF1 cohort demonstrated higher mean autism and ADHD traits at 24 months and 14% of the NF1 cohort met a research diagnostic classification for autism at 36 months. Limitations The study has a relatively small sample size due to variable retention and rolling recruitment. Due to limitations imposed by the COVID-19 pandemic, we utilised the Brief Observation of Symptoms of Autism for Minimally Verbal children (BOSA-MV) for some participants, which was administered online and may not gather as accurate a picture of traits as ADOS-2. The BOSA-MV was utilised for 41% of participants with NF1 at 36 months compared to 11% at 24 months. This may explain the reduction in the percentage of children with NF1 that met autism criteria at 36 months. Conclusions By 24 months of age, the NF1 cohort show lower cognitive skills and adaptive behaviour and higher levels of autism and ADHD traits as compared to TD children. This has implications for developmental monitoring and referral for early interventions. Trial registration Not applicable.

Abstract Contactless microscale tweezers are highly effective tools for manipulating, patterning, and assembling bioparticles. However, current tweezers are limited in their ability to comprehensively manipulate bioparticles, providing only partial control over the six fundamental motions (three translational and three rotational motions). This study presents a joint subarray acoustic tweezers platform that leverages acoustic radiation force and viscous torque to control the six fundamental motions of single bioparticles. This breakthrough is significant as our manipulation mechanism allows for controlling the three translational and three rotational motions of single cells, as well as enabling complex manipulation that combines controlled translational and rotational motions. Moreover, our tweezers can gradually increase the load on an acoustically trapped cell to achieve controllable cell deformation critical for characterizing cell mechanical properties. Furthermore, our platform allows for three-dimensional (3D) imaging of bioparticles without using complex confocal microscopy by rotating bioparticles with acoustic tweezers and taking images of each orientation using a standard microscope. With these capabilities, we anticipate the JSAT platform to play a pivotal role in various applications, including 3D imaging, tissue engineering, disease diagnostics, and drug testing.

Abstract The seismic‐electromagnetic phenomenon entails the generation of transient electromagnetic signals, which can be observed both simultaneously (co‐seismic) and preceding (pre‐seismic) a seismic wave arrival. Following the most accredited hypothesis, these signals are mainly due to electrokinetic effects, generated on microscopic scale in porous media containing electrolytic fluids. Thus, the seismic‐electromagnetic signals are expected to be suitable for the detection and tracking of crustal fluids. Despite the growing interest in this phenomenon, there is a lack of freely available observational database of earthquake‐related electromagnetic signals recorded at co‐located seismic and magnetotelluric stations. To fill this gap, we set up two multicomponent monitoring stations in two seismically active areas of Southern Italy: the Gargano Promontory and the High Agri Valley. This work is both aimed to systematically analyse earthquake‐generated seismic‐electromagnetic recordings and to make the collected database accessible to the scientific community.

Abstract We investigate the emergence, mutation profile, and dissemination of SARS-CoV-2 lineage B.1.214.2, first identified in Belgium in January 2021. This variant, featuring a 3-amino acid insertion in the spike protein similar to the Omicron variant, was speculated to enhance transmissibility or immune evasion. Initially detected in international travelers, it substantially transmitted in Central Africa, Belgium, Switzerland, and France, peaking in April 2021. Our travel-aware phylogeographic analysis, incorporating travel history, estimated the origin to the Republic of the Congo, with primary European entry through France and Belgium, and multiple smaller introductions during the epidemic. We correlate its spread with human travel patterns and air passenger data. Further, upon reviewing national reports of SARS-CoV-2 outbreaks in Belgian nursing homes, we found this strain caused moderately severe outcomes (8.7% case fatality ratio). A distinct nasopharyngeal immune response was observed in elderly patients, characterized by 80% unique signatures, higher B- and T-cell activation, increased type I IFN signaling, and reduced NK, Th17, and complement system activation, compared to similar outbreaks. This unique immune response may explain the variant's epidemiological behavior and underscores the need for nasal vaccine strategies against emerging variants.

Abstract Introduction Gram-negative bacteremia is a life-threatening infection with high morbidity and mortality. Its incidence is rising worldwide, and treatment has become more challenging due to emerging bacterial resistance. Little data is available on the burden and outcome of such infections in Lebanon. Methods We conducted this retrospective study in four Lebanese hospitals. Data on medical conditions and demographics of 2400 patients diagnosed with a bloodstream infection based on a positive blood culture were collected between January 2014 and December 2020. Results Most bacteremias were caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, with the more resistant organisms being hospital-acquired. Third-generation cephalosporin and quinolone resistance was steady throughout the study, but carbapenem resistance increased. Mortality with such infections is high, but carbapenem resistance or infection with Pseudomonas or Acinetobacter species were significant risk factors for poor outcomes. Conclusion This is the first multi-center study from Lebanon on gram-negative bacteremia, resistance patterns, and factors associated with a poor outcome. More surveillance is needed to provide data to guide empirical treatment for bacteremia in Lebanon.

Abstract Microplastic pollution, an emerging environmental issue, poses significant threats to aquatic ecosystems and human health. In tackling microplastic pollution and advancing green hydrogen production, this study reveals a tandem catalytic microplastic degradation-hydrogen evolution reaction (MPD-HER) process using hierarchical porous carbon nitride-supported single-atom iron catalysts (FeSA-hCN). Through hydrothermal-assisted Fenton-like reactions, we accomplish near-total ultrahigh-molecular-weight-polyethylene degradation into C3-C20 organics with 64% selectivity of carboxylic acid under neutral pH, a leap beyond current capabilities in efficiency, selectivity, eco-friendliness, and stability over six cycles. The system demonstrates versatility by degrading various daily-use plastics across different aquatic settings. The mixture of FeSA-hCN and plastic degradation products further achieves a hydrogen evolution of 42 μmol h‒1 under illumination, outperforming most existing plastic photoreforming methods. This tandem MPD-HER process not only provides a scalable and economically feasible strategy to combat plastic pollution but also contributes to the hydrogen economy, with far-reaching implications for global sustainability initiatives.

Abstract Pediatric obesity rates have quadrupled in the United States, and deficits in higher-order cognition have been linked to obesity, though it remains poorly understood how deviations from normal body mass are related to the neural dynamics serving cognition in youth. Herein, we determine how age- and sex-adjusted measures of body mass index (zBMI) scale with neural activity in brain regions underlying fluid intelligence. Seventy-two youth aged 9–16 years underwent high-density magnetoencephalography while performing an abstract reasoning task. The resulting data were transformed into the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Whole-brain correlations with zBMI were subsequently conducted to quantify relationships between zBMI and neural activity serving abstract reasoning. Our results reveal that participants with higher zBMI exhibit attenuated theta (4–8 Hz) responses in both the left dorsolateral prefrontal cortex and left temporoparietal junction, and that weaker temporoparietal responses scale with slower reaction times. These findings suggest that higher zBMI values are associated with weaker theta oscillations in key brain regions and altered performance during an abstract reasoning task. Thus, future investigations should evaluate neurobehavioral function during abstract reasoning in youth with more severe obesity to identify the potential impact.

ABSTRACT: Negative associations of health disorders with reproductive performance, often measured with pregnancy per AI or the risk of pregnancy loss, have been demonstrated extensively. Most studies investigated common clinical diseases but did not include subclinical disorders comprehensively. They often evaluated cows subjected to hormonal synchronization protocols for timed AI, limiting the ability to understand how disease may affect spontaneous reproductive function, which is essential for targeted management programs with selective hormonal intervention. It is plausible that metabolic and inflammatory disorders have short- and long-term detrimental effects on different features of reproductive function that result in or contribute to reduced fertility. These may include: (1) re-establishment of endocrine function to promote follicular growth and first ovulation postpartum, (2) corpus luteum (CL) function, (3) estrus expression, and (4) uterine environment, fertilization, and embryonic development. In this narrative literature review, we discuss insights and knowledge gaps linking health disorders with these processes of reproductive function. A growing set of observational studies with adequate internal validity suggest that these outcomes may be affected by metabolic and inflammatory disorders that are common in the early postpartum period. A better characterization of these risk factors in multisite studies with greater external validity is warranted to develop decision-support tools to identify subgroups of cows that are more or less likely to be successful in targeted reproductive management programs.

Abstract Background setting Domestic violence (DV) perpetrated against male victims has received little attention in the literature, since men are generally the perpetrators rather than victims of DV. This study examines the characteristics of adult male victims and female Persons of Interest (POIs) suspected and/or charged with perpetrating a DV offence in an intimate relationship. Methods We analyzed the results from a text mining study on half a million (492,393) police-attended DV events from 2005 to 2016 in New South Wales (Australia). 7.3% (13,896) events involving an adult male victim and a female POI in an intimate relationship were included. Results Over three-quarters (77.5%; 10,775) of DV events had at least one abuse type recorded, with the most common being “unspecified assault” (57.3%), followed by verbal abuse (34.1%), and punching (29.1%). Half of events (51.2%; 7,128) had an injury recorded by the police, with “cut/abrasion(s)” the most common (41.6%), followed by “red mark/sign” (25.4%), and “bruising” (15.8%). A total of 2,196 (15.8%) DV events had a mention of a mental illness for the POIs and 570 (4.1%) for the victims. Mood disorders had the most mentions for both POIs (37.0%) and victims (32.8%). Among victims, anxiety related disorders saw the largest increase (14.0%) in mentions from 2005 to 2016, followed by depression (8.0%). Conclusion Our findings represent population level data insights from DV events involving an adult male victim in an intimate relationship with a female POI. Our findings align with existing studies suggesting that female POIs are more likely than male POIs to use objects/weapons, employ verbal abuse, and perform minor acts of physical violence. Female POIs had 4 times the number of mental illness mentions than male victims indicating that mental illness could be a risk factor for DV, while the increase in anxiety disorders and depression for male victims corresponds with research that associates mental illnesses and DV victimhood. This study highlights the need for a greater awareness and support for male victims of DV.

Abstract The evolution of the COVID-19 pandemic has been associated with variations in clinical presentation and severity. Similarly, prediction scores may suffer changes in their diagnostic accuracy. The aim of this study was to test the 30-day mortality predictive validity of the 4C and SEIMC scores during the sixth wave of the pandemic and to compare them with those of validation studies. This was a longitudinal retrospective observational study. COVID-19 patients who were admitted to the Emergency Department of a Spanish hospital from December 15, 2021, to January 31, 2022, were selected. A side-by-side comparison with the pivotal validation studies was subsequently performed. The main measures were 30-day mortality and the 4C and SEIMC scores. A total of 27,614 patients were considered in the study, including 22,361 from the 4C, 4,627 from the SEIMC and 626 from our hospital. The 30-day mortality rate was significantly lower than that reported in the validation studies. The AUCs were 0.931 (95% CI: 0.90–0.95) for 4C and 0.903 (95% CI: 086–0.93) for SEIMC, which were significantly greater than those obtained in the first wave. Despite the changes that have occurred during the coronavirus disease 2019 (COVID-19) pandemic, with a reduction in lethality, scorecard systems are currently still useful tools for detecting patients with poor disease risk, with better prognostic capacity.

Abstract Background Electronic Prospective Surveillance Models (ePSMs) remotely monitor the rehabilitation needs of people with cancer via patient-reported outcomes at pre-defined time points during cancer care and deliver support, including links to self-management education and community programs, and recommendations for further clinical screening and rehabilitation referrals. Previous guidance on implementing ePSMs lacks sufficient detail on approaches to select implementation strategies for these systems. The purpose of this article is to describe how we developed an implementation plan for REACH, an ePSM system designed for breast, colorectal, lymphoma, and head and neck cancers. Methods Implementation Mapping guided the process of developing the implementation plan. We integrated findings from a scoping review and qualitative study our team conducted to identify determinants to implementation, implementation actors and actions, and relevant outcomes. Determinants were categorized using the Consolidated Framework for Implementation Research (CFIR), and the implementation outcomes taxonomy guided the identification of outcomes. Next, determinants were mapped to the Expert Recommendations for Implementing Change (ERIC) taxonomy of strategies using the CFIR-ERIC Matching Tool. The list of strategies produced was refined through discussion amongst our team and feedback from knowledge users considering each strategy’s feasibility and importance rating via the Go-Zone plot, feasibility and applicability to the clinical contexts, and use among other ePSMs reported in our scoping review. Results Of the 39 CFIR constructs, 22 were identified as relevant determinants. Clinic managers, information technology teams, and healthcare providers with key roles in patient education were identified as important actors. The CFIR-ERIC Matching Tool resulted in 50 strategies with Level 1 endorsement and 13 strategies with Level 2 endorsement. The final list of strategies included 1) purposefully re-examine the implementation, 2) tailor strategies, 3) change record systems, 4) conduct educational meetings, 5) distribute educational materials, 6) intervene with patients to enhance uptake and adherence, 7) centralize technical assistance, and 8) use advisory boards and workgroups. Conclusion We present a generalizable method that incorporates steps from Implementation Mapping, engages various knowledge users, and leverages implementation science frameworks to facilitate the development of an implementation strategy. An evaluation of implementation success using the implementation outcomes framework is underway.

Abstract We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia.

Abstract Forests and woodlands are critical terrestrial carbon stores. Tree aboveground biomass (AGB) can be estimated using allometric models and terrestrial laser scanning (TLS). However, internal tree stem damage from biotic decay is an unresolved source of error for both TLS and allometries, with implications for accurate carbon assessment. We destructively harvested 63 TLS‐scanned trees in an Australian savanna, quantified internal damage in each tree by sampling cross sections at multiple heights, and modelled the effect of damage on AGB estimation for individual trees and total estimated biomass. We tested the performance of TLS AGB modelling against five allometries, applying both database and field‐measured wood specific gravity. For TLS‐modelled and allometric AGB estimates, we tested if tree size and level of internal stem damage contributed to AGB deviations. Approximately half of the trees in the study sustained 1–10% damage by volume, which was most extensive in the base and main trunk, decreasing into the crown. On average, damaged trees had 5% internal stem damage (by volume, SD = 6.65%), with some as high as 30%. We found TLS‐derived quantitative structural models (TLS‐QSMs) using field‐measured wood specific gravity to be most accurate in estimating total biomass (R2 = 0.99, +0.59% bias). TLS‐QSMs tended to overpredict AGB of large, damaged trees, and AGB estimates from allometric models were largely unaffected by internal damage. For individual trees, all methods were effective for predicting field‐measured AGB (R2 > 0.84) and several ASMs performed well (± ~10% bias). In the absence of local wood specific gravity calibration, a pantropical ASM was most accurate. For systems where internal stem damage is low (10%) are likely to produce inflated biomass estimates if TLS is used without calibration for damage. Internal stem damage should be quantified in ASMs and incorporated into TLS‐modelled AGB calibration to avoid biomass overestimation and maintain high standards of precision in forest carbon accounting.

This study aims to identify the main barriers in implementing business process innovation in government organizations using the Systematic Literature Review (SLR) method. The barriers were categorized into four aspects: people, technology, structure, and process, in accordance with the Socio-Technical Theory approach. The results show that a lack of knowledge and training related to innovation, limited funding, and inadequate technological infrastructure are the dominant barriers. In addition, complex bureaucracy and lack of structured processes are also significant barriers. The research recommends a holistic approach that includes improved communication, training, technology investment, as well as bureaucratic reform to foster more effective innovation. The findings provide a basis for better policy-making and emphasize the importance of further research to understand and address barriers to innovation in different countries.

BACKGROUND: Tirofiban has been shown to be superior to aspirin in achieving functional independence at 3 months for acute ischemic stroke of atheromatous or microatheromatous origin. As intravenous thrombolysis (IVT) has previously been shown to be nonsuperior to aspirin in achieving functional independence at 3 months for anterior choroidal or paramedian pontine infarction (ACI/PPI), we aimed to compare the outcomes of Caucasian patients receiving IVT plus tirofiban (IVT + T) with those receiving tirofiban alone for acute ACI/PPI. METHODS: A retrospective study was conducted in patients aged ≥ 18 years with ACI/PPI treated in our stroke unit between December 1, 2020, and April 30, 2023, who received therapeutic intervention within 9 hours of symptom onset or after awakening with stroke symptoms. Modified Rankin Scale (mRS) ≤ 1 at 3 months was the primary endpoint. Secondary endpoints were National Institutes of Health Stroke Scale (NIHSS) ≤ 2 at day 7 or discharge and post-procedural neurological deterioration (PPND) within 72 hours. Symptomatic intracranial hemorrhage (SICH) and major systemic bleeding (MSB) were the safety measures of the study. RESULTS: A total of 24 patients were enrolled in the tirofiban group and 43 patients in the IVT + T group. Compared to tirofiban alone, IVT + T was associated with a higher probability of achieving mRS ≤1 at 3 months (adjusted odds ratio [aOR], 8.79; 95% confidence interval [CI], 2.06–37.52; P = 0.003) and National Institutes of Health Stroke Scale ≤2 at day 7 or discharge (aOR, 3.70; 95% CI, 1.05–12.99; P = 0.041). No significant difference was seen between the two groups in preventing postprocedural neurological deterioration. One case of SICH and two cases of MSB occurred in the IVT + T group and no cases in the tirofiban group. One case of inhospital mortality was recorded in the IVT + T group. CONCLUSIONS: Our results showed that IVT + T may be safe and effective in Caucasian patients with acute ACI/PPI.

Abstract We study the cosmological evolution of a light QCD axion and identify the parameter space to obtain the correct relic dark matter abundance. The axion potential is flattened at the origin, corresponding to the only minimum, while it is unsuppressed at π. These potential features arise by assuming a mirror sector with the strong CP phase θ ¯ $$ \overline{\theta} $$ shifted by π compared to the SM sector, which allows the mirror axion potential to be tuned against the usual QCD axion potential. Before the QCD phase transition, assuming the mirror sector is decoupled and much colder than the SM thermal bath, the mirror sector potential dominates, causing the axion to initially roll to a temporary minimum at π. However, after the QCD phase transition, the potential minimum changes, and the axion relaxes from the newly created “hilltop” near π to the CP-conserving minimum at the origin. As the axion adiabatically tracks this shift in the potential minimum through the QCD phase transition, with non-adiabatic evolution near π and 0, it alters the usual prediction of the dark matter abundance. Consequently, this “hilltop” misalignment mechanism opens new regions of axion parameter space, with the correct relic abundance while still solving the strong CP problem, that could be explored in future experiments.

Abstract Biochar, produced from the thermochemical conversion of biomass waste, has various applications owing to its broad utility and advantageous properties. This study employs a scientometric approach to comprehensively assess the advancements in biochar application from 2022 to 2023. Utilizing 13,357 bibliographic records sourced from the Web of Science Core Collection with the search term “biochar”, the analysis focuses on authorship, national contributions, and keyword trends. Findings demonstrate a continual rise in annual publications since 2009, albeit with a moderated growth rate in 2023. China leads in publication outputs, followed by USA and India, with Hailong Wang emerging as a prominent figure in biochar research. Keyword co-occurrence analyses identify key research themes such as biochar’s role in climate change mitigation, easing salinity and drought stress, immobilizing toxic metals, degrading organic pollutants, serving as additives in anaerobic digestion, and functioning as electrodes in microbial fuel cells. Among these, biochar’s application for global climate change mitigation gains significant attention, while its utilization as electrodes in microbial fuel cells emerges as a promising research frontier, indicating the growing need for sustainable energy sources. The study also outlines critical research gaps and future priorities for enhancing biochar application. Overall, it highlights the diverse applicability of biochar and offers valuable insight into research progression and forthcoming directions in biochar studies. Graphical Abstract

Abstract Background Tuberculous peritonitis often presents with nonspecific symptoms that can lead to diagnostic challenges, particularly when manifesting as peritoneal pseudocysts. This study highlights the clinical complexity and diagnostic approach of tuberculous peritonitis presented as a pseudocyst in an immunocompetent adult, an atypical scenario that is rarely documented. Case presentation We report a detailed case of a 41-year-old man presenting with abdominal distension, pain, and significant weight loss over four months. Abdominal CT showed a peritoneal pseudocyst, initially misdiagnosed due to its resemblance to more common abdominal pathologies. The diagnosis of tuberculous peritonitis was confirmed through histopathological analysis. Additionally, a systematic literature review was conducted to identify and analyse similar cases, focusing on clinical presentations, diagnostic methods, and patient outcomes. Our patient exhibited classic symptoms of abdominal TB but was unique due to the absence of prior ventriculoperitoneal shunting, a common factor in similar cases. Our literature review found that such presentations typically result in diagnostic delays averaging five months, complicating patient management and outcomes. This review also underscores the importance of considering tuberculosis in the differential diagnosis of peritoneal pseudocysts, particularly in TB-endemic regions. Conclusion This case and review emphasize the need for high clinical suspicion and prompt investigation of tuberculosis in patients presenting with atypical abdominal symptoms and pseudocysts. Improved diagnostic strategies, including early use of imaging and pathological evaluations, are essential for timely diagnosis and management, thereby improving patient outcomes in suspected cases of extrapulmonary tuberculosis.

ChatGPT is a chatbot with potential educational benefits, particularly in enhancing computational thinking (CT) proficiencies such as programming, debugging, and algorithmic thinking for students. Despite its promise, there is limited research on how ChatGPT can specifically support the integration of CT into mathematics education using tools like GeoGebra. The researchers implemented plugged-computational thinking in mathematics (Math+CT) lessons by means of the utilization of GeoGebra, an application that requires students to input commands in order to generate mathematical objects. The present investigation employed an educational design research (EDR) methodology in which the researchers incorporate ChatGPT into our Math+CT lessons to assist students in accomplishing the task. We purposely selected the participants who are mainly postgraduate students and collected data from the participants’ conversation with ChatGPT and recorded their screens while interacting with ChatGPT and our Math+CT task. We analyzed the data through descriptive qualitative method on the participants’ prompts, the final codes and the number of iterations. The researchers examined how ChatGPT could be utilized to assist the participants in writing GeoGebra commands in terms of its benefits and limitations. ChatGPT assisted most participants in completing the task successfully, with only a basic need for proficiency in GeoGebra commands, mathematics, and critical thinking. However, it revealed that participants did not yet utilize an affective prompt to ChatGPT. Furthermore, ChatGPT has the potential to be utilized for differentiated instruction due to the fact that its responses to individual users vary significantly based on the input prompts. Limited understanding of basic GeoGebra commands, and mathematical concepts could hinder the participants from training ChatGPT or prevent them from arguing with ChatGPT. This study enhances the existing literature by illustrating that ChatGPT can facilitate critical CT aspects, including programming and debugging, in a mathematics education context. This suggests that AI tools such as ChatGPT can contribute to the development of independent problem-solving skills, provide tailored support based on the needs of individual students, and enhance personalized learning experiences. Additional research involving students in school is required in order to gain a deeper understanding of the integration of ChatGPT into Math+CT lessons.

Abstract Androgen receptor (AR) overexpression has been identified in gliomas and its stem cells, suggesting that AR plays an important role in tumor carcinogenesis. The prognostic significance of AR overexpression in gliomas remains unknown. AR mRNA expression in gliomas and relevant clinical data were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. AR expression levels were compared across gliomas of different histopathologic grades and molecular subtypes. Kaplan–Meier analyses in patients with different AR expression levels were investigated for the potential prognostic values of AR. Compared with normal brain tissue, gliomas show significantly higher AR mRNA expression (p

Abstract This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1–7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.

Abstract Background Understanding the aetiological organisms causing maternal infections is crucial to inform antibiotic treatment guidelines, but such data are scarce from Sub-Saharan Africa (SSA). We performed this systematic review and meta-analysis to address this gap. Methods Microbiologically confirmed maternal infection data were collected from PubMed, Embase, and African Journals online databases. The search strategy combined terms related to bacterial infection, pregnancy, postnatal period, observational studies, SSA. Exclusion criteria included colonization, asymptomatic infection, and screening studies. Pooled proportions for bacterial isolates and antimicrobial resistance (AMR) were calculated. Quality and completeness of reporting were assessed using the Newcastle–Ottawa and STROBE checklists. Findings We included 14 papers comprising data from 2,575 women from four sources (blood, urine, surgical wound and endocervical). Mixed-growth was commonly reported at 17% (95% CI: 12%-23%), E. coli from 11%(CI:10%-12%), S. aureus from 5%(CI: 5%-6%), Klebsiella spp. at 5%(CI: 4%- 5%) and Streptococcus spp. at 2%(CI: 1%-2%). We observed intra-sample and inter-sample heterogeneity between 88–92% in all meta-analyses. AMR rates were between 19% -77%, the highest with first-line beta-lactam antibiotics. Convenience sampling, and limited reporting of laboratory techniques were areas of concern. Interpretation We provide a comprehensive summary of microbial aetiology of maternal infections in SSA and demonstrate the paucity of data available for this region. We flag the need to review the current local and international empirical treatment guidelines for maternal bacterial infections in SSA because there is high prevalence of AMR among common causative bacteria. Funding This research was supported by the NIHR-Professorship/NIHR300808 and the Wellcome-Strategic-award /206545/Z/17/Z. Trial registration Prospero ID CRD42021238515.

Abstract Background Metagenomics is a powerful approach for the detection of unknown and novel pathogens. Workflows based on Illumina short-read sequencing are becoming established in diagnostic laboratories. However, high sequencing depth requirements, long turnaround times, and limited sensitivity hinder broader adoption. We investigated whether we could overcome these limitations using protocols based on untargeted sequencing with Oxford Nanopore Technologies (ONT), which offers real-time data acquisition and analysis, or a targeted panel approach, which allows the selective sequencing of known pathogens and could improve sensitivity. Methods We evaluated detection of viruses with readily available untargeted metagenomic workflows using Illumina and ONT, and an Illumina-based enrichment approach using the Twist Bioscience Comprehensive Viral Research Panel (CVRP), which targets 3153 viruses. We tested samples consisting of a dilution series of a six-virus mock community in a human DNA/RNA background, designed to resemble clinical specimens with low microbial abundance and high host content. Protocols were designed to retain the host transcriptome, since this could help confirm the absence of infectious agents. We further compared the performance of commonly used taxonomic classifiers. Results Capture with the Twist CVRP increased sensitivity by at least 10–100-fold over untargeted sequencing, making it suitable for the detection of low viral loads (60 genome copies per ml (gc/ml)), but additional methods may be needed in a diagnostic setting to detect untargeted organisms. While untargeted ONT had good sensitivity at high viral loads (60,000 gc/ml), at lower viral loads (600–6000 gc/ml), longer and more costly sequencing runs would be required to achieve sensitivities comparable to the untargeted Illumina protocol. Untargeted ONT provided better specificity than untargeted Illumina sequencing. However, the application of robust thresholds standardized results between taxonomic classifiers. Host gene expression analysis is optimal with untargeted Illumina sequencing but possible with both the CVRP and ONT. Conclusions Metagenomics has the potential to become standard-of-care in diagnostics and is a powerful tool for the discovery of emerging pathogens. Untargeted Illumina and ONT metagenomics and capture with the Twist CVRP have different advantages with respect to sensitivity, specificity, turnaround time and cost, and the optimal method will depend on the clinical context.

Abstract Josephson junctions enable dissipation-less electrical current through metals and insulators below a critical current. Despite being central to quantum technology based on superconducting quantum bits and fundamental research into self-conjugate quasiparticles, the spatial distribution of super current flow at the junction and its predicted evolution with current bias and external magnetic field remain experimentally elusive. Revealing the hidden current flow, featureless in electrical resistance, helps understanding unconventional phenomena such as the nonreciprocal critical current, i.e., Josephson diode effect. Here we introduce a platform to visualize super current flow at the nanoscale. Utilizing a scanning magnetometer based on nitrogen vacancy centers in diamond, we uncover competing ground states electrically switchable within the zero-resistance regime. The competition results from the superconducting phase re-configuration induced by the Josephson current and kinetic inductance of thin-film superconductors. We further identify a new mechanism for the Josephson diode effect involving the Josephson current-induced phase. The nanoscale super current flow emerges as a new experimental observable for elucidating unconventional superconductivity, and optimizing quantum computation and energy-efficient devices.