bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial reversal of dominance maintains a resistance polymorphism under fluctuating insecticide selection
Authors: Karageorgi Marianthi , Lyulina Anastasia S. , Bitter Mark C. , Lappo Egor , Greenblum Sharon I. , Mouza Zach K. , Tran Caitlynn T. , Huynh Andy V. , Oken Hayes , Schmidt Paul , Petrov Dmitri A.
Published: October 2024

Large-effect functional genetic variation is commonly found in natural populations, even though natural selection should erode such variants. Theory suggests that under fluctuating selective pressures, beneficial reversal of dominance - where alleles are dominant when beneficial and recessive when deleterious - can protect these loci from selection, allowing them to persist. However, empirical evidence for this mechanism remains elusive because testing requires direct measurements of selection and dominance in natural conditions. Here, we show that insecticide-resistant alleles at theAcelocus inDrosophila melanogasterpersist worldwide at intermediate frequencies and exhibit beneficial reversal of dominance. By combining laboratory and large-scale field mesocosm experiments with insecticide manipulation, and mathematical modeling, we show that the benefits of the resistantAcealleles are dominant while their fitness costs recessive. We further show that fluctuating insecticide selection generates chromosome-scale genomic perturbations at sites linked to the resistantAcealleles, revealing broader genomic consequences of this mechanism. Overall, our results suggest that beneficial reversal of dominance contributes to the maintenance of functional genetic variation and impacts patterns of genomic diversity via linked fluctuating selection.
Evaluating Thrombectomy Devices and Combination Therapies in Acute ischemic Stroke: A systematic review & Network Meta-Analysis of 201 studies
Authors: Gulia Annu , Srivastava Manyata , Nath Manabesh , Misra Shubham , Kumar Patel Kamalesh , Datt Upadhyay Ashish , Vibha Deepti , Desai Shashvat , Kumar Pradeep
Published: October 2024

Background and Objective

Mechanical Thrombectomy (MT) has become the standard treatment for acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). However, the relative efficacy and safety of different MT devices remain uncertain. To evaluate and compare the safety and efficacy of different Thrombectomy devices and combination therapies in acute ischemic stroke, utilizing a network meta-analysis.

Methods

Patients receiving different MT devices (MERCI, TREVO, Solitaire, Penumbra, or a combination of MT devices) compared to Standard Care or Intravenous Thrombolysis (IVT), or Intra-arterial Thrombolysis (IAT) for AIS treatment. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days. Efficacy outcome were good functional recovery at 90 days (defined as a modified Rankin Scale score of 0–2) and successful recanalization (measured by a TICI score of 2b-3).

Results

We included 201 studies, comprising 43 RCTs and 159 cohort studies with 71,154 AIS patients. TREVO device demonstrated the highest efficacy for functional recovery (OR=3.63, 95% CrI: 2.45–5.43), followed by MT + IVT (OR=2.87, CrI: 2.30–3.59). TREVO also achieved the highest rate of successful recanalization (OR 3.35, CrI: 1.36–8.19). MERCI, Solitaire and Aspiration devices were linked to a higher risk of sICH. For all-cause mortality at 90 days, TREVO notably reduced the odds (OR=0.56, CrI: 0.37–0.86), whereas aspiration devices showed no significant difference from standard treatments.

Conclusion

Our findings demonstrate contemporary stent-retriever device technology as the most effective option for improving functional recovery, recanalization success, and reducing mortality in AIS patients. These results highlight the critical need for selecting the most effective and safest thrombectomy device to optimize outcomes in acute stroke care.
Transfer learning for mortality risk: A case study on the United Kingdom
Authors: Nalmpatian Asmik , Heumann Christian , Alkaya Levent , Jackson William
Published: October 2024

This study introduces a transfer learning framework to address data scarcity in mortality risk prediction for the UK, where local mortality data is unavailable. By leveraging a pretrained model built from data across eight countries (excluding the UK) and incorporating synthetic data from the country most similar to the UK, our approach extends beyond national boundaries. This framework reduces reliance on local datasets while maintaining strong predictive performance. We evaluate the model using the Continuous Mortality Investigation (CMI) dataset and a drift model to address discrepancies arising from local demographic differences. Our research bridges machine learning and actuarial science, enhancing mortality risk prediction and pricing strategies, particularly in data-poor settings.
Global, Regional, and National Burden of Pulmonary Arterial Hypertension, 1990-2021: a Systematic Analysis of the Global Burden of Disease Study 2021
Authors: Deng Yafang , Dong Xingbei , Qian Junyan , Zhao Jiuliang , Xu Dong , Wang Yanhong , Li Mengtao , Zeng Xiaofeng , Wang Qian
Published: October 2024

Aims

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease with high mortality rates. This research aimed to examine the disease burden of PAH including prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 across various age groups, sexes, and Socio-demographic Index (SDI) levels, at global, regional and national levels.

Methods

Data was collected from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2021, which established models to estimate the burden of PAH for 204 countries and territories from 1990 to 2021. Age-standardized rates for PAH prevalence, incidence, mortality, and DALYs were calculated. Joinpoint regression was used to assess temporal trends. The correlation between disease burden and socioeconomic development was analyzed.

Results

In 2021, the global age-standardized prevalence and incidence rates were 2.28 and 0.52 per 100,000 population, respectively. From 1990 to 2021, the age-standardized mortality rate decreased from 0.35 to 0.27 per 100,000, with an average annual trend of -0.82%. TheCorresponding AuthorDr. Qian Wang, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, No. 1, Shuaifuyuan, Wangfujing Ave, Dongcheng District, Beijing 100730, China E-Mail:wangqian_pumch@126.comage-standardized DALY rate decreased from 13.21 to 8.24 per 100,000 by -1.52%. Females exhibited a higher incidence rate but lower mortality and DALY rates. The burden of PAH distributed unequally, with regions possessing higher socioeconomic statuses exhibiting lower mortality and DALY rates. Such inequalities have been improved over past decades.

Conclusions

The decline in mortality and DALY rates of PAH indicates improvements in disease management and patient outcomes, while the health inequalities among different regions and countries persist. Improving survival and life quality, and global health equality are crucial for future progress.
Multiplex ACE2-RBD Binding Inhibition Assay: An Integrated Tool for Assessing Neutralizing Antibodies to SARS-CoV-2 Variants and Protection against Breakthrough Infections
Authors: Bloch Emma , Garcia Laura , Donnadieu Françoise , Rosado Jason , Planas Delphine , Bruel Timothée , Hocqueloux Laurent , Prazuck Thierry , Schwartz Olivier , Tondeur Laura , Pinaud Laurie , Fontanet Arnaud , Pelleau Stéphane , White Michael
Published: October 2024

SARS-CoV-2 remains a significant health threat due to its high infection and mutation rates. The emergence of new variants of concern poses challenges as they can lead to immune escape mutations, potentially reducing the efficacy of vaccines and antibody therapeutics. The receptor binding domain (RBD) of SARS-CoV-2 is particularly noteworthy as it is both the most rapidly evolving domain and the principal target of neutralizing antibodies. As an alternative to time-consuming and expensive neutralization assays, we have developed a bead-based multiplex surrogate virus neutralization test based on ACE2-RBD binding inhibition. We demonstrated how our high-throughput assay allows us to simultaneously assess anti-RBD neutralizing antibodies levels against multiple SARS-CoV-2 variants, providing data that is consistent with the gold-standard live virus neutralization assay. The utility of this assay was demonstrated by applying it to a large French population cohort to demonstrate that hybrid immunity (generated by a combination of vaccination and infection) is associated with protection against infection with the Omicron BA.1 and BA.2 lineages of SARS-COV-2.
Comparison of Oscillometry with Lung Function Parameters between Bronchial Asthma with Airflow Obstruction and COPD Patients
Authors: De Sajal , Sarda Aakansha Ashok
Published: October 2024

Background

Lung oscillometry is an emerging lung function test for assessing obstructive airway disease. Comparisons of oscillometry parameters and their bronchodilator responsiveness (BDR) between bronchial asthma and chronic obstructive pulmonary disease (COPD) patients are limited.

Research Question

Do oscillometry parameters and their BDR differ between stable asthma and COPD patients with similar severity of airflow obstruction?

Study Design and Methods

We included 467 consecutive adult patients with a clinical history of asthma (n=187) or COPD (n=280). Oscillometry, spirometry, and body plethysmography were performed before and after inhaling 400 μg of salbutamol. Patients were stratified based on the severity of airflow obstruction in spirometry. The z scores of the oscillometry parameters were used for the comparison. The BDR of oscillometry parameters with other lung function parameters was also compared.

Results

The average age of the study population was 54.9 years, and 76.4% were male. COPD patients were older, had a greater number of smokers, and had poorer lung function. The magnitude of oscillometry parameters worsened with increasing severity of airflow obstruction, regardless of the underlying disease. Asthma patients, particularly those with moderate and severe airway obstruction, had significantly higher R5 and R19 than COPD patients. The within- and whole-breath X5 of asthma were not different from those of COPD patients with similar severities of airflow obstruction. Expiratory flow limitation at tidal breaths (ΔX5 > 0.28 kPa/L/s) was observed in both asthma and COPD patients across all severities of airflow obstruction. The proportion of BDR in oscillometry was significantly lower than that in spirometry for both asthma (35.3% vs. 57.1%; p<0.01) and COPD patients (19.3% vs. 47.1%; p=0.02).

Interpretation

Oscillometry parameters except for R5 and R19 did not differ between asthma and COPD patients with similar severities of airflow obstruction. Similar to spirometry, COPD patients had lower BDR in oscillometry than asthma patients.

Take-home Points

Study Question

Are oscillometry parameters and their bronchodilator responsiveness different between bronchial asthma and COPD patients with similar severities of airflow obstruction?

Results

We compared the FOT between 187 bronchial asthma and 280 COPD patients. Except for R5 and R19, the severity and distribution of high oscillometry parameters did not differ between asthma and COPD patients.

Interpretation

The severity of oscillometry abnormalities is primarily determined by the severity of airflow obstruction, not the underlying disease.
Validation of a risk-prediction model for pediatric post-discharge mortality after hospital admission in Rwanda
Authors: Hooft Anneka , Umuhoza Christian , Mfuranziza Cynthia , Trawin Jessica , Uwiragiye Emmanuel , Zhang Cherri , Nguyen Vuong , Kornblith Aaron E , Kenya-Mugisha Nathan , Ansermino Mark , Wiens Matthew O
Published: October 2024

Mortality following hospital discharge remains a significant threat to child health, particularly in resource-limited settings. In Uganda, the Smart Discharges risk-prediction models have successfully predicted children at the highest risk of death after hospital admission for sepsis to guide a risk-based approach to post-discharge care. We externally validated five models derived from Smart Discharges Uganda in a new cohort of children ages 0 days to 60 months admitted for suspected sepsis at two hospitals in Rwanda. Of 1218 total children (n=413, Kigali; n=805, Ruhengeri), 1161 lived to discharge (95.3%) and 1123 of those completed 6-month follow-up (96.7%). The overall rate of post-discharge mortality was 4.8% (n=58). All five prediction models tested achieved an area under the receiver-operating curve (AUROC) greater than 0.7 (range 0.706 - 0.738). Low outcome rates resulted in moderately wide confidence intervals. Model degradation ranged from 1.1% to 7.7%, as determined by the percent reduction in AUROC between the internal validation of the original Ugandan cohort and the external Rwandan cohort. Calibration plots showed good calibration for all models at predicted probabilities below 10%. There were too few outcomes to assess calibration among those at the highest predicted risk levels. Discrimination was good with minimal degradation of the model despite low outcome rates. Future work to assess model calibration among the highest risk groups is required to ensure models are broadly generalizable to all children with suspected sepsis in Rwanda and in similar, resource-limited settings.
Treatment of obesity in US children and adolescents before and after the AAP guidelines
Authors: Rodriguez Patricia J , Do Duy , Gratzl Samuel , Cartwright Brianna M Goodwin , Stucky Nicholas L , Wright R. Davene
Published: October 2024

Importance

The American Academy of Pediatrics (AAP) published new comprehensive guidelines for childhood obesity treatment, including pharmacotherapy. However, changes in treatment patterns following these guidelines remain unknown.

Objective

To assess changes in childhood and adolescent obesity treatment following the new AAP guidelines.

Design

Using Truveta electronic health record (EHR) data, this cohort study analyzed outpatient visits between January 2021 and June 2024 for children (age 8-11) and adolescents (age 12-17) with obesity and no evidence of type 2 diabetes (T2D). For patients with multiple visits, one visit was randomly selected. Patients without a recent history of specific obesity treatments were followed for evidence of obesity treatment at or following their visit, including nutrition referral within 14 days or nutrition counseling within 90 days, and, separately, pharmacotherapy prescriptions for weight management (on- or off-label) within 14 days. Interrupted time series models were used to compare differences in nutrition counseling or referral and pharmacotherapy before versus after the AAP guidelines were released.

Setting

Clinical and prescribing data from EHRs from a collective of US health systems.

Participants

329,357 patients aged 8 to 17 with an outpatient office visit, a BMI percentile indicating obesity, and no T2D diagnosis.

Exposure

Release of the AAP guidelines in January 2023.

Main Outcomes and Measures

Evidence of obesity treatment at or following the eligible visit with (1) nutrition referral or counseling, and (2) pharmacotherapy.

Results

The study population of 329,581 patients included 120,734 (36.6%) children and 208,847 (63.4%) adolescents. The mean (SD) BMI percentile was 97.4 (1.6), with 119,864 (36.4%) having severe obesity (class 2 or 3). Overall, a minority of patients without a recent history of obesity treatment had evidence of nutrition referral or counseling (4.0%) or pharmacotherapy (0.4%) during or shortly after their visit. Following the AAP guidelines, indicators of both immediate (odds ratio [95% CI]: 1.38 [1.08-1.75]) and gradual monthly changes (1.06 [1.04-1.08]) were observed for pharmacotherapy use. An immediate change in nutrition counseling and referral was observed following guidelines (1.34 [1.24-1.45]), but no additional gradual monthly changes were observed (1.0 [0.99-1.01]).

Conclusions and Relevance

While nutrition counseling or referral and pharmacotherapy use increased, overall rates of obesity treatment remained low.
Patterns and predictors of COVID-19 vaccine uptake among United States active duty Service members, 2020-2022: Implications for future pandemics
Authors: Sercy Erica , Stewart Laveta , Craig-Kuhn Megan Clare , Stern Caryn , Graham Brock , Michel Amber , Parmelee Edward , Pollett Simon , Burgess Timothy , Tribble David R
Published: October 2024

Introduction

Vaccine mandates have been used to minimize the duty days lost and deaths attributable to infectious disease among active duty Service members (ADSMs). In response to the global COVID-19 pandemic, in August 2021, the United States Department of Defense issued a COVID-19 vaccine mandate for all ADSMs. This study aimed to investigate COVID-19 vaccine uptake among the ADSM population, as well as factors associated with timing of COVID-19 vaccine receipt.

Methods

This study included ADSMs on active duty between 1/1/2020-6/30/2022. Univariate analyses investigated associations between demographic factors (age, sex, race, ethnicity, branch of service, rank, state of residence) and COVID-19 diagnosis with the following outcomes: 1) time to primary series initiation in relation to the DoD vaccine mandate, 2) time between doses of the two-dose primary series, and 3) time between booster eligibility and receipt

Results

A total of 1,799,466 ADSMs were included, with 90% receiving ≥1 COVID-19 vaccine dose during the study period and 77% initiating the primary series prior to the mandate. Over 80% of ADSMs received a complete primary series, with 96% of those adhering to the recommended regimen. History of COVID-19 diagnosis was associated with later receipt of all doses.

Conclusions

COVID-19 vaccine uptake was high among all ADSMs, with the majority initiating the primary series before the mandate. The high vaccine uptake among ADSMs shown here may be used as a guide to both military and civilian pandemic policy and outreach efforts related to enhanced vaccine uptake.
Long-term hybridization in a karst window reveals the genetic basis of eye loss in cavefish
Authors: Kellermeyer Riley , Seidel Chris , Redwine William B. , Moran Rachel L. , Bertho Sylvain , Ornelas-García Claudia Patricia , Alegre Dana , Weaver Kyle , Unruh Jay , Troutwine Benjamin , Wang Yongfu , Collins Emily , Rutkowski Jennifer , McGaugh Suzanne E. , Espinasa Luis , Rohner Nicolas
Published: October 2024

Eye loss is a hallmark trait of animals inhabiting perpetual darkness, such as caves. The Mexican tetra (Astyanax mexicanus)provides an unparalleled model for studying the genetic basis of eye loss. There are two interfertile morphs of the Mexican tetra, sighted surface fish and multiple independently evolved eyeless, blind cavefish populations. Despite decades of research on eye loss in this species, our understanding of the precise genetic basis remains sparse. Here, we focused on the unique Caballo Moro cave, where there is a karst window collapse that introduced sunlight and coexistence of both eyed and eyeless cavefish of similar genetic background. This unique genetic mosaic allowed us to pinpoint coding mutations in Connexin 50 (Cx50), also known as gap junction protein alpha 8b (Gja8b), as critical in the genetic basis of eye loss. CRISPR based knockouts of Cx50 in surface fish result in small or absent eyes as young as 48 hours post-fertilization. Further, we identified similar mutations in Cx50 that alter predicted protein structure among other cave-dwelling fish and even subterranean mammals, indicating a conserved evolutionary mechanism of Cx50 mutations. We introduced a mutation (Cx50-S89K) in mice, which resulted in cataracts, smaller eyes, and smaller lenses. Mutations in Cx50 mimic those identified in human congenital cataracts. We additionally leveraged phenotypic variation in a hybrid cavefish population to demonstrate that eyes provide fish with a metabolic advantage, providing a mechanism by which loss of eyes could be favored by selection. This unique hybridization event allowed us to identify novel alleles that contribute to the convergent evolution of eye loss, providing profound insights into the genetic underpinnings of one of nature’s most fascinating adaptive traits.
A head-to-head comparison of plasma biomarkers to detect biologically defined Alzheimer in a memory clinic
Authors: Anastasi Federica , Fernández-Lebrero Aida , Ashton Nicholas J. , Ortiz-Romero Paula , Torres-Torronteras Javier , González-Escalante Armand , Milà-Alomà Marta , Contador José , García-Escobar Greta , Manero-Borràs Rosa María , Navalpotro-Gómez Irene , Sahajan Aparna , Hao Qinyu , Zhang Bingqing , Jeromin Andreas , Le Bastard Nathalie , Nadal Alicia , Mousavi Tahmine , Kollmorgen Gwendlyn , Carboni Margherita , Grau-Rivera Oriol , Zetterberg Henrik , del Campo Marta , Blennow Kaj , Puig-Pijoan Albert , Suárez-Calvet Marc
Published: October 2024

INTRODUCTION

Blood-based biomarkers for Alzheimer’s disease (AD) have been widely studied, but direct comparisons of several biomarkers in clinical settings remain limited.

METHODS

In this cross-sectional study, plasma biomarkers from 197 participants in the BIODEGMAR cohort at Hospital del Mar (Barcelona) were analysed. Participants were classified based on AD cerebrospinal fluid (CSF) core biomarkers. We assessed the ability of plasma p-tau181, p-tau217, p-tau231, t-tau, and Aβ42/40 to classify Aβ status.

RESULTS

Plasma p-tau biomarkers had a greater diagnostic performance and larger effect sizes compared to t-tau and Aβ42/40 assays in detecting biologically defined AD. Among them, plasma p-tau217 consistently outperformed the others, demonstrating superior AUC. Furthermore, p-tau217 showed the strongest correlation between plasma and CSF levels, underscoring its potential as a reliable surrogate for CSF biomarkers.

DISCUSSION

Several plasma biomarkers, targeting different epitopes and using different platforms, demonstrated high performance in distinguishing biologically defined AD in a memory clinic setting.
Altered resting state EEG microstate dynamics in acute-phase pediatric mild traumatic brain injury.
Authors: Sattari Sahar , Damji Samir , McLeod Julianne , Mirian Maryam M. , Wu Lyndia , Virji-Babul Naznin
Published: October 2024

Objective: Sport-related concussion presents significant diagnostic and monitoring challenges, especially in youth populations. This study investigates the potential of EEG microstate analysis as a tool for assessing acute-phase brain activity changes in adolescent male athletes following a concussion. We analyzed resting-state EEG data from 32 participants in a between-subjects design, comparing participants with acute concussion (within two weeks of injury) to an age- and sex- matched sample with no reported history of concussion. Methodology: We applied a modified k-means clustering algorithm to group resting-state EEG topographical maps into seven clusters, with each cluster represented by one of the canonical microstate classes (A-G). Average duration, occurrence rate, and time coverage for each microstate were extracted.  Results: Statistically significant differences in mean duration, occurrence rate, and time coverage of microstates B and E were observed. Specifically, the mean duration, occurrence and time coverage of microstate E showed a significant decrease in the concussed cohort in comparision to the controls (p < 0.001). In addition, the mean duration, occurrence rate and time coverage was higher in the concussed cohort in comparision with the healthy cohort (p = 0.003). A significant negative linear relationship was found between microstate E and symptom severity (p = 0.006, F = 15.72). Discussion: These results suggest that mild traumatic brain injury may disrupt the dynamic interaction of large-scale brain networks, hinting at potential biomarkers of injury. This study may help to inform future work on objective, brain-based tools for diagnosis and recovery assessment in concussed adolescents. Further research in larger, more diverse populations is necessary to validate these potential biomarkers.
Muscle-3D: scalable multiple protein structure alignment
Authors: Edgar Robert C. , Tolstoy Igor
Published: October 2024

Protein multiple alignment is an essential step in many bioinformatics analysis such as phylogenetic tree estimation, HMM construction and critical residue identification. Structure is conserved between distantly-related proteins where amino acid similarity is weak or undetectable, suggesting that structure-informed sequence alignments might offer advantages over alignments constructed from amino acid sequences alone. The advent of the AI folding era has unleashed millions of high-quality predicted structures, motivating the development and assessment of scalable multiple structure alignment (MStA) methods. Here, we describe Muscle-3D, a new MStA algorithm combining a rich sequence representation of structure context, the Reseek “mega-alphabet”, with state-of-the art alignment techniques from Muscle5 including a posterior decoding pair-HMM, consistency transformation, iterative refinement and ensemble construction. We show that Muscle-3D readily scales to thousands of structures. Comparative validation on several benchmark datasets using different quality metrics shows Muscle-3D to be among the higher-scoring methods, but we find that algorithm rankings from different metrics disagree despite low P-values according to the Wilcoxon rank-sum test. We suggest that these conflicts arise from the inherently fuzzy nature of structural alignment, and argue that a universal standard of MStA accuracy is not possible in principle. We describe contact map profiles for visualizing variation in inter-residue distances, and introduce a novel measure of local conformation similarity, LDDT-muw.

Muscle-3D software is available athttps://github.com/rcedgar/muscle.
Identification of Molecular Compounds Targeting Bacterial Propionate Metabolism with Topological Machine Learning
Authors: Tola Astrit , Aziz Shan , Zhabilov Dannie , Winkler Duane , Coskunuzer Baris , Candas Mehmet
Published: October 2024

This study demonstrates the effective integration of comparative protein sequence analysis with novel topological machine learning methods to tackle a key issue in computational biology: identifying potential inhibitor compounds for methylcitrate dehydratase—an enzyme essential to the methylcitrate pathway in bacteria and fungi. While many ML models have proven effective on benchmark datasets, we applied these techniques specifically to discover compounds for this target protein. This pathway, crucial for metabolizing propionic acid, is essential in pathogenic bacteria for utilizing host-derived lipids and amino acids, making it a promising antimicrobial target. Inefficient removal of propionate can lead to toxic accumulation, threatening microbial survival.

In our research, we utilize the latest methods in topological machine learning,multiparameter persistence, to transform the molecular structure of potential compounds into topological vectors for ligand-based drug discovery. By applying our tailored topological model, we prioritized 15 compounds with promising characteristics for inhibiting the active site of methylcitrate dehydratase. Computational molecular docking simulations reveal that these identified compounds interact with key amino acid residues critical to the enzyme’s function. Our findings underscore the power of integrating topology-based modeling with comparative sequencestructure-function analysis and ligand docking. Considering compounds’ geometric fit, energy, and interaction profiles enhances predictions and guides the design of optimized new compounds. This refined approach offers a solid foundation for lead optimization, representing the most promising molecular scaffolds for modification, advancing compound discovery, and providing valuable insights into binding interactions for further experimental validation and potential drug development. Our code is available athttps://github.com/AstritTola/Molecular-Compounds-Targeting
Functional characterization and optimization of protein expression inTreponema denticolashuttle plasmids
Authors: Paula Goetting-Minesky M. , Godovikova Valentina , Saraithong Prakaimuk , Rickard Alexander H. , Crawley Brigette R. , Agolli Sara M. , Fenno J. Christopher
Published: October 2024

Oral spirochetes are among a small group of keystone pathogens contributing to dysregulation of periodontal tissue homeostasis, leading to breakdown of the tissue and bone supporting the teeth in periodontal disease. Of the greater than sixty oralTreponemaspecies and phylotypes,T. denticolais one of the few that can be grown in culture and the only one in which genetic manipulation has been shown to be practicable.T. denticolais thus a model organism for studying spirochete metabolic processes, interactions with other microbes and host cell and tissue responses relevant to oral diseases as well as venereal and nonvenereal treponematoses. We recently demonstrated enhanced transformation efficiency using a SyngenicDNA-based shuttle plasmid resistant toT. denticolarestriction-modification systems. Here we expand on this work by further characterizing the shuttle plasmid and optimizing expression of cloned genes using several promoter-gene constructs for genetic complementation and exogenous gene expression, including the first inducible system for controlled expression of potentially toxic plasmid-encoded genes inTreponema. Our results highlight the importance of precise pairing of promoters and genes of interest to obtaining biologically optimal protein expression. This work expands the utility of the shuttle plasmid and will facilitate future studies employing shuttle plasmids in analysis ofTreponemaphysiology and behavior.

IMPORTANCE

Rigorous genetic analysis in oral spirochetes has been hampered by the limited utility of available versions of theE. coli-T. denticolashuttle plasmid system. We report expanded characterization of the shuttle plasmid, including relative activity of diverse promoters and the first inducible expression system described forT. denticola.We show that careful customization of the shuttle plasmid for specific applications is crucial for obtaining successful results.
Comparative meta transcriptomics uncovers the physiological responses of zooplankton to nutrient heterogeneity in their living environment
Authors: Nuruddin Muhammad Firman , Wu Longjun
Published: October 2024

Zooplankton plays a crucial role in coastal water ecosystems by linking energy transfer from primary producers to higher trophic level organisms and facilitating the biogeochemical cycle through their metabolism and vertical migration. However, our understanding of the zooplankton physiological response to nutrient variability in their living environment, particularly at the gene expression level, remains limited. This knowledge gap hinders our understanding of their physiological processes, which are essential for the biogeochemical cycle. To investigate the impact of coastal environmental nutrient heterogeneity on zooplankton community physiology, we conducted zooplankton samplings during the summer season in the western, southern, and eastern Coastal Hong Kong Waters. Meta transcriptomics analysis was employed to unravel the community composition and gene expression profiles of the sampled zooplankton. Our study revealed distinct patterns of differential gene expression associated with nitrogen and amino acid metabolism functions within the sampled zooplankton communities across the different sampling regions. Furthermore, we found several KEGG pathway members of gene modules which are classified as metabolism functions that highly correlated with nutrient concentrations. Importantly, these gene expression patterns corresponded to the observed heterogeneity in dissolved inorganic nitrogen and phosphorous concentration within coastal waters environment. To further validate our findings, we conducted reanalysis on the zooplankton model organism,Daphnia magna, transcriptome data under laboratory nitrogen and phosphorous imbalanced treatment which the result supported the gene ontology functions identified in the zooplankton community meta transcriptome. Our results contribute to a better understanding of zooplankton’s physiological processes, especially highlighting the importance of incorporating gene expression analysis in studying zooplankton’s role in the biogeochemical cycle.
Bacterial inoculation elicits changes to the coral epigenome
Authors: Barno Adam R. , Villela Helena D.M. , Cardoso Pedro M. , García Francisca C. , Cui Guoxin , Delgadillo-Ordoñez Nathalia , Rosado Alexandre S. , Thomas Torsten , Aranda Manuel , Voolstra Christian R. , Peixoto Raquel S.
Published: October 2024

Environmental shifts can cause epigenetic modifications in corals, which are associated with changes in gene expression and physiology, though it remains unclear if associated bacteria can also induce such changes. Here, we inoculated nubbins of the coralPocillopora verrucosawith an opportunistic pathogen,Vibrio coralliilyticus, and/or a coral probiotic,Cobetiasp., and subjected the nubbins to heat stress. We show that pathogen exposure led to distinct DNA methylation changes compared to the control, probiotic, and co-inoculation groups. We also demonstrate that DNA methylation correlates with coral gene expression and highlight genes altered by pathogen inoculation that showed similar responses in their expression and methylation. Notably, the coral probiotic was able to mitigate specific epigenetic changes, which correlated with increased stress resilience and higher coral survival rates. Thus, bacterial-induced changes to the coral epigenome may instigate long-term changes in host resilience.
Degradation of organic matter by ecologically distinct microbiomes uniformly promotes plant growth
Authors: Lee Bradie , Coleman-Derr Devin , Vogel John P.
Published: October 2024

In this study, we explore the relationship between ecologically distinct soil microbiomes and their role in plant growth promotion through organic matter (OM) decomposition. Using a controlled experimental system, we tested whether living microbiomes from geographically and ecologically distinct environments impact plant biomass when provided with OM in the form of dried, ground leaves. Results showed a consistent threefold increase in plant biomass when a living microbiome and organic matter were present, regardless of the microbiome’s origin, which included agricultural fields, desert soil, and pine-oak forest soil, municipal compost, and the microbiome on unautoclaved organic matter. Bacterial community profiling based on 16S amplicon sequencing revealed genera, e.g.Massilia, that were significantly associated with decomposition and subsequent plant growth promotion. This suggests a conserved functional capacity for organic matter decomposition across diverse microbiomes, likely due to evolutionary pressures to efficiently break down plant material for nutrient acquisition. The study provides a framework for further investigation into microbial consortia that enhance plant growth via decomposition, offering a robust experimental system to identify microbes and microbial processes that could be harnessed to improve nutrient uptake from organic inputs like cover crops.
Cooperative Nernst effect of multilayer systems: Parallel circuit model study
Authors: Matsuura Hiroyasu , Riss Alexander , Garmroudi Fabian , Parzer Michael , Bauer Ernst
Published: October 2024

Transverse thermoelectric power generation has emerged as a topic of immense interest in recent years owing to the orthogonal geometry which enables better scalability and fabrication of devices. Here, we investigate the thickness dependence of longitudinal and transverse responses in film-substrate systems, i.e., the Seebeck coefficient, the Hall coefficient, the Nernst coefficient, and the anomalous Nernst coefficient in a unified and general manner based on the circuit model, which describes the system as the parallel setup. By solving the parallel circuit model, we show that the transverse responses exhibit a significant peak, indicating the importance of a cooperative effect between the film and the substrate, arising from circulating currents that occur in these multilayer systems in the presence of a temperature gradient. Finally, on the basis of realistic material parameters, we predict that the Nernst effect in bismuth thin films on doped silicon substrates is boosted to unprecedented values if the thickness ratio is tuned accordingly, motivating experimental validation.

Published by the American Physical Society
2024
Time-resolved counterpropagating edge transport in the topological insulating phase
Authors: Kamata H. , Irie H. , Sasaki S. , Kumada N. , Muraki K.
Published: October 2024

We have investigated the time-resolved low-energy charge dynamics in counterpropagating edge channels formed in the quantum Hall regime of an electron-hole bilayer system in band-inverted InAs/InGaSb composite quantum wells. In the studied magnetic field range, the system remains in the topological phase where an equal number of counterpropagating electronlike and holelike edge channels exist in the bulk energy gap, analogous to the helical edge channels in a quantum spin Hall insulator. When the Fermi level was set in the conduction band, the injected charge pulses propagated unidirectionally as chiral edge magnetoplasmon (EMP) wave packets. In contrast, in the nonchiral regime with the Fermi level set in the band gap, the injected charge pulses propagated identically in both directions with significantly reduced velocity. In addition, as the channel length increased, we observed a sharp crossover from EMP transport to diffusive transport, manifested as pronounced waveform broadening and dissipation. Simulations using a distributed capacitance model including interchannel tunneling well reproduced the observed behavior in both chiral and nonchiral regimes, revealing that interchannel charge transfer between counterpropagating channels plays a crucial role. The slow EMP transport in the nonchiral regime and its crossover to diffusive transport are consequences of the strong interchannel interaction and interchannel tunneling, respectively. Our results will thus provide insights into charge dynamics and scattering mechanism in analogous one-dimensional systems, including a quantum spin Hall insulator with helical edge modes and its expected Tomonaga-Luttinger liquid behavior.

Published by the American Physical Society
2024
Structural comparison of [Ce(O
t
Bu)Cl(THF)5](BPh4) to smaller rare earth analogues
Authors: Thomas Jarrod R. , Sarma Kavisha A. , Giansiracusa Marcus J. , Sulway Scott A.
Published: October 2024

The introduction of the cerium(III) analogue (1-Ce, Ln = Ce) of (tert-butoxido)chloridopentakis(tetrahydrofuran)lanthanide(III) tetraphenylborate tetrahydrofuran disolvate, [Ln{OC(CH3)3}Cl(C4H8O)5][B(C6H5)4]·2C4H8O or [Ln(O
t
Bu)Cl(THF)5](BPh4)·2THF (1-Ln) has been achieved with a structural comparison between the existing solid-state structures of other rare earth analogues and the title compound at 100 and 180 K. The cation in 1-Ce is targeted as the cerium(III) ion possesses the criteria to exhibit slow magnetic relaxation in axial point-charge crystal fields, akin to the dysprosium(III) ion in 1-Dy. AC magnetic susceptibility experiments reveal no such behaviour for 1-Ce, putting the viability of cerium-based SMMs into question.
Synthesis, crystal structures and antiproliferative activities of a new indole-containing dipyridylmethanone hydrazone Schiff base and its cadmium(II) complex
Authors: Zhang Qing , Wang Zi-Quan , Xing Dian-Xiang , Wang Shou-Juan , Tan Xue-Jie
Published: October 2024

In this study, we introduce a novel indole-containing pyridine-based Schiff base, (E)-2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole, C20H15N5 (2-DPHI), and its cadmium(II) complex poly[[2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole]di-μ-chlorido-cadmium(II)], [CdCl2(C20H15N5)]
n
(pCd2), as potential anticancer agents. The Schiff base was synthesized by reacting dipyridylmethanone hydrazone with indole-2-formaldehyde, while the cadmium complex was prepared by combining CdCl2 and 2-DPHI in methanol at room temperature. Both compounds were evaluated for their cytotoxicity against three human cancer cell lines (A375, A549 and HeLa) and a normal cell line (HFF-1). The ligand 2-DPHI exhibited notable antitumour activity, with an IC50 value of 12.22 µM against A375 and 15.17 µM against A549 after 48 h, while the pCd2 complex showed an even stronger inhibition of A375 cells, with an IC50 value of 4.88 µM, outperforming both 2-DPHI and CdCl2. Both compounds demonstrated lower toxicity towards normal cells compared to cancer cells. The structures of 2-DPHI and pCd2 were fully characterized using single-crystal X-ray diffraction, elemental analysis, high-resolution mass spectrometry and FT–IR, 1H NMR, 13C NMR and UV–Vis spectroscopy.
Is blockchain cost-effective in construction project management? A systematic review from the perspective of transaction cost
Authors: Yu Haizhe , Deng Xiaopeng , Zhang Na , Zhang Xicheng
Published: October 2024

Purpose

Blockchain technology (BCT) is considered a promising tool to improve the productivity of construction project management. Existing research has studied its potential costs and benefits for the construction industry. However, the potential costs and benefits of BCT failed to be compared as actual costs and benefits of specific applications for stakeholders. To fill this gap, this study seeks to analyze the cost-effectiveness of BCT-based applications in construction project management.

Design/methodology/approach

This study is conducted with a customized systematic literature review based on transaction cost theory to enable qualitative comparison. With a deliberately designed structure confining extraneous variables, the costs and benefits of BCT-based applications are identified and compared. The inherent dependent relations of processes and the evolution relations of functions are identified. The cost-effectiveness of blockchain adoption is then analyzed.

Findings

Seven functions and six challenges are identified within five processes. The result suggests all identified functions are cost-effective except for manual instruction (coding smart contracts manually). The smart contracts require explicit definition and logic to be effective. However, the construction projects essentially require the institution to be flexible due to unpredictability. The adoption of smart contracts and corresponding additional requirements can increase the transaction cost of bounded rationality.

Research limitations/implications

As manual instruction is fundamental to realize other functions, and its advanced substitute relies on its broad adoption, its cost-effectiveness must be improved for applications to be acceptable to stakeholders. The establishment of a universal smart contract model and a universal, legitimate and efficient database structure are recommended to minimize the cost and maximize the effect of applications.

Originality/value

This study contributes to the knowledge by providing a comprehensive analysis of BCT adoption’s cost-effectiveness in construction project management. The adopted review structure can be extended to analyze the qualitative benefits and challenges of management automation in the early stages.
Auditor’s opinion, future abnormal cash holdings and internal control quality: evidence from an Asian market in pre-COVID-19 and post-COVID-19 pandemic
Authors: Arianpoor Arash , Khiyabani Mahla
Published: October 2024

Purpose

The present study aims to investigate the impact of the auditor’s opinion and internal control quality (ICQ) on future abnormal cash holdings for companies listed on the Tehran Stock Exchange (TSE).

Design/methodology/approach

Information about 216 companies in 2014–2021 was examined. This study used the absolute value of abnormal cash holdings to test the research hypotheses. However, future extra abnormal cash holdings and future deficit abnormal cash holdings were also tested. Modified multiple regression method and ordinary least squares (OLS) were used. The present study also applied the generalized method of moments (GMM) for endogeneity concerns.

Findings

The results showed that an unqualified audit opinion negatively and significantly affects a firm’s future abnormal cash holdings. Moreover, ICQ significantly strengthens the impact of an unqualified audit opinion on a firm’s future abnormal cash holdings. These results remained robust even after several robustness tests. This study tested the robustness of results through data division into the pre-COVID-19 and post-COVID-19 years. The test confirmed previous findings; however, the strength of these effects decreased in post-COVID-19 years.

Originality/value

Previous studies could not answer how an auditor’s opinion affects a company’s future abnormal cash holdings. Moreover, no empirical study has addressed the moderator role of ICQ in the relationship between unqualified audit opinion and future abnormal cash holdings. This study helps stakeholders evaluate the performance of firms more accurately, especially in any global health crisis such as the COVID-19 pandemic and similar crises. Combined with the research findings from developed countries, this study can potentially contribute to the global community’s efforts in advancing international objectives.
Multimodal flexible electronic skin with adjustable module size for robot collision detection
Authors: Xue Guangming , Chen Guodong , Sun Lining , Liu Huicong
Published: October 2024

Purpose

This paper aims to present a modular multimodal flexible electronic skin that can be used for robot collision detection in human–robot interactions. This type of electronic skin will meet the requirements of performance indicators such as sensing mode, sensing domain coverage and dynamic data update rate in human–robot interactions.

Design/methodology/approach

The electronic skin uses a modular architecture, and the sensing module is designed to be adjustable in size so that it can be easily deployed on complex robot surfaces, increasing area coverage, reducing power consumption, and improving data update rates.

Findings

The authors evaluated electronic skin through experiments using a UR5 robot. Electronic skin has high static scene perception differentiation and dynamic scene perception abilities. Moreover, the robot realizes a high-speed collision response based on the electronic skin proposed in this study.

Originality/value

The proposed electronic skin provides crucial technical support for advancing robotic technologies, and holds promising prospects for industrial applications.
What do Gen Z really want from a workplace?
Authors: Nichols Amy , Smith Simon M.
Published: October 2024

Purpose

This paper aims to offer a deeper understanding of Gen Z professional attitudes and expectations in the workplace through a large data set.

Design/methodology/approach

The authors provide reference to a unique survey of 1,234 adults who work full- or part-time across different age groups. Gen Z data were compared to three other generational cohorts, namely, Millennials, Gen X and Baby Boomers.

Findings

Broad findings reveal that Gen Z have lower satisfaction levels with their job compared to other generations. Furthermore, the findings show that Gen Z craves progress, challenge and better mental health and diversity commitments from employers. Related to that, mental health is reported as significantly lower amongst Gen Z participants.

Originality/value

The research reinforces that there is often a negative view of “other” generations. Indeed, the findings here indicate there are often negative assumptions made about Gen Z. Importantly, these are not aligned with how Gen Z perceive themselves. The authors offer some reflections and recommendations for strategic HR approaches.