bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-ABC: a robust demographic inference from low-coverage whole-genome data through ABC
Authors: Vizzari Maria Teresa , Ghirotto Silvia , Agostini Rajiv Boscolo , Delser Pierpaolo Maisano , Cassidy Lara , Manica Andrea , Benazzo Andrea
Published: August 2024

The reconstruction of past demographic histories relies on the pattern of genetic variation shown by the sampled populations; this means that an accurate estimation of genotypes is crucial for a reliable inference of past processes. A commonly adopted approach to reconstruct complex demographic dynamics is the Approximate Bayesian Computation (ABC) framework. It exploits coalescent simulations to generate the expected level of variation under different evolutionary scenarios. Demographic inference is then performed by comparing the simulated data with the genotypes called in the sampled individuals. Low sequencing coverage drastically affects the ability to reliably call genotypes, thus making low-coverage data unsuitable for such powerful inferential approaches.

Here, we present Low-ABC, a new ABC approach to infer past population processes using low-coverage whole-genome data. Under this framework, both observed and simulated genetic variation are not directly compared using called genotypes, but rather obtained using genotype likelihoods to consider the uncertainty caused by the low sequencing coverage. We first evaluated the inferential power of this procedure in distinguishing among different demographic models and in inferring model parameters under different experimental conditions, including a wide spectrum of sequencing coverage (1x to 30x), number of individuals, number, and size of genetic loci.

We showed that the use of genotype likelihoods integrated into an ABC framework provides a reliable inference of past population dynamics, thus making possible the application of model-based inference also for low-coverage data. We then applied Low-ABC to shed light on the relationship between Mesolithic and Early Neolithic European populations.
mosGraphFlow: a novel integrative graph AI model mining disease targets from multi-omic data
Authors: Zhang Heming , Cao Dekang , Xu Tim , Chen Emily , Li Guangfu , Chen Yixin , Payne Philip , Province Michael , Li Fuhai
Published: August 2024

Multi-omic data can better characterize complex cellular signaling pathways from multiple views compared to individual omic data. However, integrative multi-omic data analysis to rank key disease biomarkers and infer core signaling pathways remains an open problem. In this study, our novel contributions are that we developed a novel graph AI model,mosGraphFlow, for analyzing multi-omic signaling graphs (mosGraphs), 2) analyzed multi-omic mosGraph datasets of AD, and 3) identified, visualized and evaluated a set of AD associated signaling biomarkers and network. The comparison results show that the proposed model not only achieves the best classification accuracy but also identifies important AD disease biomarkers and signaling interactions. Moreover, the signaling sources are highlighted at specific omic levels to facilitate the understanding of the pathogenesis of AD. The proposed model can also be applied and expanded for other studies using multi-omic data. Model code is accessible via GitHub:https://github.com/FuhaiLiAiLab/mosGraphFlow
Lipidome visualisation, comparison, and analysis in a vector space
Authors: Olzhabaev Timur , Müller Lukas , Krause Daniel , Schwudke Dominik , Torda Andrew Ernest
Published: August 2024

A shallow neural network was used to embed lipid structures in a 2- or 3-dimensional space with the goal that structurally similar species have similar vectors. Tests on complete lipid databanks show that the method automatically produces distributions which follow conventional lipid classifications. The embedding is accompanied by the web-based software, Lipidome Projector. This displays user lipidomes as 2D or 3D scatterplots for quick exploratory analysis, quantitative comparison and interpretation at a structural level.

Author summary

Lipids are not just the basis of membranes. They carry signals and metabolic energy. This means that the presence, absence, and quantity of lipids reflects a cell’s biochemical state - starving, nourished, sick or healthy. Lipidomics (measuring all lipids in a biological specimen) provides lists of the chemical species and their quantities.

We have used a shallow neural network from natural language modelling to embed lipids in a continuous vector space. Firstly, this means that similar molecules have similar positions in this space. Conventional lipid categories cluster automatically. Secondly, the accompanying web-based software, Lipidome Projector imports a lipidome and displays it as a set of points. Reading several lipidomes at once allows quantitative and structural comparisons. Combined with the ability to show structure and abundance diagrams, the software allows exploratory analysis and interpretation of lipidomics datasets.
Temporal kinetics of brain state effects on visual perception
Authors: Schmid Paul , Klein Timon , Minakowski Piotr , Sager Sebastian , Reichert Christoph , Knight Robert T. , Dürschmid Stefan
Published: August 2024

We investigated the effects of brain states on human perception and early visual response comparing focused wakefulness (ON state) to external inattention (OFF state). In two experiments, we investigated the temporal kinetics of brain states changes during stimulus processing and assessed fluctuations across extended periods of time. We used a classifier to distinguish between these states on a single trial level using theta activity in MEG sensors. We found that participants shifted from an ON to an OFF state as rapidly as two seconds. Visual target discrimination was comparable in both states, but reaction times were slower and more variable during the OFF state. Broad band high-frequency activity (BHA) recorded in MEG sensors covering the occipital cortex tracked target grating orientation. BHA was reduced during the OFF state but participants were still able to distinguish sensory information highlighting the role of BHA in visual perception across cognitive brain states.
Newly developed structure-based methods do not outperform standard sequence-based methods for large-scale phylogenomics
Authors: Mutti Giacomo , Ocaña-Pallarès Eduard , Gabaldón Toni
Published: August 2024

Recent developments in protein structure prediction have allowed the use of this previously limited source of information at genome-wide scales. It has been proposed that the use of structural information may offer advantages over sequences in phylogenetic reconstruction, due to their slower rate of evolution and direct correlation to function. Here, we examined how recently developed methods for structure-based homology search and tree reconstruction compare to current state-of-the-art sequence-based methods in reconstructing genome-wide collections of gene phylogenies (i.e. phylomes). While structure-based methods can be useful in specific scenarios, we found that their current performance does not justify using the newly developed structured-based methods as a default choice in large-scale phylogenetic studies. On the one hand, the best performing sequence-based tree reconstruction methods still outperform structure-based methods for this task. On the other hand, structure-based homology detection methods provide larger lists of candidate homologs, as previously reported. However, this comes at the expense of missing hits identified by sequence-based methods, as well as providing homolog candidate sets with higher fractions of false positives. These insights help guide the use of structural data in comparative genomics and highlight the need to continue improving structure-based approaches. Our pipeline is fully reproducible and has been implemented in a snakemake workflow. This will facilitate a continuous assessment of future improvements of structure-based tools in the Alphafold era.
Tet2loss suppress α-synuclein pathology by stimulating ciliogenesis
Authors: Quansah Emmanuel , Vatsa Naman , Ensink Elizabeth , Brown Jaycie , Cave Tyce , Aguileta Miguel , Kuhn Emily , Lindquist Allison , Gilliland Carla , Steiner Jennifer A. , Escobar Galvis Martha L. , Milčiūtė Milda , Henderson Michael , Brundin Patrik , Brundin Lena , Marshall Lee L. , Gordevicius Juozas
Published: August 2024

There are no approved treatments that slow Parkinson’s disease (PD) progression and therefore it is important to identify novel pathogenic mechanisms that can be targeted. Loss of the epigenetic marker,Tet2appears to have some beneficial effects in PD models, but the underlying mechanism of action is not well understood. We performed an unbiased transcriptomic analysis of cortical neurons isolated from patients with PD to identify dysregulated pathways and determine their potential contributions to the disease process. We discovered that genes associated with primary cilia, non-synaptic sensory and signaling organelles, are upregulated in both early and late PD patients. Enhancing ciliogenesis in primary cortical neurons via sonic hedgehog signaling suppressed the accumulation of α-synuclein pathologyin vitro. Interestingly, deletion ofTet2in mice also enhanced the expression of primary cilia and sonic hedgehog signaling genes and rescued the accumulation of α-synuclein pathology and dopamine neuron degenerationin vivo. Our findings demonstrate the crucial role ofTet2loss in regulating ciliogenesis and potentially affecting the progression of PD pathology.
Impact of Blended NPSB Fertilizer Rates on Sugarcane (Saccharum officinarumL.) Varieties: Seed Cane Yield and Quality Insights from North Western Ethiopia
Authors: Ali Solomon , Belay Bahiru , Abate Mesfin
Published: August 2024

Sugarcane primarily cultivated for sugar production and other multiple uses. A field experiment was conducted at Tana Beles sugar project, North western Ethiopia during 2021 and 2022 cropping season to determine the optimum rate of NPSB fertilizer rate on three sugarcane varieties. The treatments were laid out in factorial randomized complete block design arranged with three replications. The experiment was arranged with five levels of NPSB blended fertilizer (0, 200, 260, 320 and 380 kg ha-1) combined with three sugarcane varieties (NCO-334, N-14 and C86/56). Among the parameters of seed cane crop; germination percent stalk weight, stalk diameter, node length, inter node number, plant height, stalk population, and sett yield for growth and yield parameters and sett moisture content, sett nitrogen content, reducing sugar content and total sugar content for seed cane quality parameters significantly affected by applied NPSB fertilizer, varieties and their interaction (p<0.05). Brix% and pol% were not significantly affected by different rates of NPSB fertilizer rates and varieties (p<0.05). The highest leaf area index, plant population, sett yield, average cane weight, seed cane moisture content and total nitrogen content was attained with 380 kg ha-1NPSB fertilizer applied on variety NCO-334 and N-14. Maximum population stand, average plant height, and sett yield of verity C86/56 were recorded at 320 kg ha-1NPSB fertilizer level. Sett yield, were positively correlated with germination percent, population stand count, inter node number, seed cane weight, seed cane diameter reducing sugar content, total sugar yield and sett moisture content. Therefore, it is advisable to recommend 380 kg NPSB ha1for variety NCO-334 and N-14, and 320 kg NPSB ha1for variety C86/56 with application of 160 kg ha-1urea at the age of two month and half for effective seed cane production. It was aimed to fill the seed cane fertilizer rate problems of different sugarcane varieties.
MiRNA-21-5p and MiRNA-125-5p Serve as Biomarkers for Diagnosis and Prognosis of Gastric Cancer
Authors: Zhang Xin , Xiang Yao , Wang Junpu
Published: August 2024

Background

Gastric cancer is one of the most common diseases worldwide. MicroRNAs (miRNAs) are small non-coding RNAs, typically 19-25 nucleotides in length, which represent potential targets for therapeutic intervention.

Methods and Results

In this study, we performed a data mining analysis for gastric cancer (GC) by integrating differentially expressed genes obtained from the Gene Expression Omnibus (GEO) database with data from The Cancer Genome Atlas (TCGA) database. We compared the expression levels of miRNA-125-5p and miRNA-21-5p in cancer cells and GES-1 cells. Our analysis revealed up-regulation of these two miRNAs in both GEO and TCGA datasets, which was further validated by quantitative polymerase chain reaction (qPCR). Additionally, survival analysis, risk score analysis, and downstream analyses, including functional enrichment analysis, target gene prediction, and protein-protein interaction analysis, were conducted.

Conclusion

The expression levels of miRNA-125-5p and miRNA-21-5p are upregulated in gastric cancer cells, which contribute to the diagnosis of gastric cancer and serve as novel biomarkers.
Silver Armor Against Bacteria: A Battle of Antimicrobial Effectiveness
Authors: Zaidi Alina
Published: August 2024

For many farmers, there is a need to improve crop resistance to pathogenic organisms. Florida’s climate and hurricane-prone location promotes the spread of many crop pathogens making management difficult and expensive. Therefore, this study evaluates using a Do-It-Yourself, DIY, method to produce colloidal silver solutions that may be used as effective inhibitors of bacteria growth. The efficacy was compared across gram-negative and gram-positive bacteria species. Production of colloidal silver used an electric current from eight 9-volt batteries wired in series. The starting silver was a jewelry chain, approx. 98% silver, suspended in a container of distilled water. Treatment effects were compared to a commercially available silver solution (10K, ppm) as the positive controlviathe Kirby-Baur method. Each petri dish was divided into four quadrants, into which each had a treated cellulose square impregnated with a treatment solution. Treatments were: T1-10K ppm AgNp; T-2-5ppm AgNp, T3-3ppm AgNp; and positive control T4-blank water control. The dimensions of Zones of Clearance (ZOC) and the bacterial growth surrounding treated squares were analyzed. The experiment was replicated four times. Data analysis conducted using one-way ANOVA withpost hocseparation of means using the T test and Tukey’s HSD. The positive control solution was the most effective bactericide across all species, followed by Treatment-2 (5-ppm treatment), which caused ZOC in gram-negative species. Treatment-3, the 3ppm, did not significantly affect bacterial suppression, while activity at 5ppm suggests that simple home-based, DIY systems can produce low cost, bactericidal nano-silver solutions. In this experiment the bacterium that tested that is also beneficial to plants,R. rubrum, showed an increased tolerance to all silver treatments. Improving homemade, DIY, systems may provide low-cost treatment solutions against some bacteria species important to backyard agriculturists.
Prevalence of Mild and Severe Cognitive Impairment in World Trade Center Exposed Fire Department of the City of New York (FDNY) and General Emergency Responders
Authors: Mann Frank D. , Mueller Alexandra K. , Zeig-Owens Rachel , Choi Jaeun , Prezant David J. , Carr Melissa M. , Fels Alicia M. , Hennington Christina M. , Armstrong Megan P. , Barber Alissa , Fontana Ashley E. , Kroll Cassandra H. , Chow Kevin , Melendez Onix A. , Smith Abigail J. , Luft Benjamin J. , Hall Charles B. , Clouston Sean A. P.
Published: August 2024

Background

The emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations.

Methods

A sample of WTC-exposed-FDNY responders (n = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests. The prevalences of domain-specific impairments were estimated based on the results of norm-referenced tests, and the Montreal Cognitive Assessment (MoCA), Jak/Bondi criteria, Petersen criteria, and the National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria were used to diagnose MCI. NIA-AA criteria were also used to diagnose severe cognitive impairment. Generalized linear models were used to compare prevalence estimates of cognitive impairment to a large sample of WTC-exposed-non-FDNY responders from the General Responder Cohort (GRC; n = 7102) who completed the MoCA during a similar time frame.

Result

Among FDNY responders under 65 years, the unadjusted prevalence of MCI varied from 52.57% to 71.37% depending on the operational definition of MCI, apart from using a conservative cut-off applied to MoCA total scores (18 < MoCA < 23), which yielded a markedly lower crude prevalence (24.31%) compared to alternative criteria. The prevalence of MCI was higher among WTC-exposed-FDNY-responders, compared to WTC-exposed-non-FDNY-GRC-responders (adjustedRR= 1.53,95% C.I. = [1.24, 1.88],p< .001) and meta-analytic estimates from different global, community, and clinical populations. Following NIA-AA diagnostic guidelines, 4.96% of WTC-exposed-FDNY-responders met the criteria for severe impairments (95% CI = [2.91% to 7.82%]), a prevalence that remained largely unchanged after excluding responders over the age of 65 years.

Discussion

There is a high prevalence of mild and severe cognitive impairment among WTC-responders highlighting the putative role of occupational/environmental and disaster-related exposures in the etiology of accelerated cognitive decline.
Causal relationship between gut microbiota and vulvar cancer: a two-sample bi-directional Mendelian randomization study
Authors: Chen Jiayan , Wang Peiyan , Xiao Changji , Kelaimu Kalibinuer , Zeng Youjie , Lyu Feng , Gao Xianshu , Li Xiaomei , Hu Jun
Published: August 2024

Objective: Recent investigations have proposed a link between gut microbiomes (GMs) and various cancers, yet the involvement of GMs in vulvar cancer (VC) remains unclear. The objective of this study was to discover the causal association between GMs and VC and identify the GM taxa with potential effect. Methods: Utilizing Mendelian randomization (MR) with genome-wide association study (GWAS) summary statistics, we analyzed 211 GM taxa and 190 VC cases with 167,189 healthy controls. The main analysis used the inverse-variance weighted (IVW) approach, complemented by weighted median test, MR-PRESSO global test, and leave-one-out analysis. Results: Four nominally significant causal relationships were identified between GM taxa and VC. Class Betaproteobacteria [odds ratio (OR)=0.064, 95% confidence interval (CI): 0.004-0.946, fp=0.045], order Burkholderiales [OR=0.074, 95% CI: 0.009-0.630, p=0.017], genus Intestinibacter [OR=0.073, 95% CI: 0.009-0.617, p=0.016], and genus RuminococcaceaeUCG003 [OR=0.162, 95% CI: 0.028-0.938, p=0.042] were linked to a lower chance of VC. The MR-Egger intercept test and MR-PRESSO global test confirmed the lack of horizontal pleiotropy (p>0.05), and leave-one-out analysis indicated result robustness. Conclusion: Our findings highlight four potential causal relationships and specific intestinal flora associated with decreased VC risk, offering insights for VC prevention and treatment.
Assessing the Role of Red Blood Cell Distribution Width in Hospital Mortality Among Elderly and Non-Elderly COVID-19 Patients: A Prospective Study in a Brazilian University Hospital
Authors: Duani Helena , Cabral Máderson Alvares de Souza , Machado Carla Jorge , Fonseca Thalyta Nogueira , Marcolino Milena Soriano , Nobre Vandack Alencar , Ravetti Cecilia Gómez , Vassallo Paula Frizera , Tupinambás Unaí
Published: August 2024

This study investigated the role of red blood cell distribution width (RDW) as a risk factor for hospital mortality in COVID-19 patients at a public hospital in Minas Gerais, Brazil. The study included 161 patients over 16 years old hospitalized between May and October 2020, with 39 (24.2%) deaths. Key mortality risk factors identified were age over 70 years (RR=2.78; p<0.001), male sex (RR=2.28; p=0.005), cardiovascular disease (RR=1.8; p=0.044), and abnormal chest X-ray upon admission (RR=3.07; p=0.022). Although high RDW at admission did not significantly predict mortality (31.1% vs 21.7%; RR=1.43; p=0.413), it was linked to higher mortality in patients aged 70 and over (66.7% vs 33.3%; RR=2; p=0.029). High RDW during hospitalization was a strong mortality factor for the entire cohort (41.1% vs 10.2%; RR=4.03; p<0.001) and at any time during the stay (39.7% vs 9.6%; RR=4.14; p<0.001). The Cox model analysis showed that age >70 years (HR=4.8; p<0.001), white race (HR=3.2; p=0.018), need for invasive ventilation (HR=3.8; p=0.001), and abnormal chest X-ray (HR=3.5; p=0.044) were significant risk factors, but RDW was not associated with mortality.
Standing Strong: A Systematic Review of Multifaceted Fall Prevention in Older Adults
Authors: Thomas Mony , Kirk Johnson , Patel Raul , Fred Mary
Published: August 2024

Background

Falls among older adults are a major public health concern, leading to significant morbidity, mortality, and healthcare costs. This systematic review and meta-analysis aimed to evaluate the effectiveness of falls prevention interventions for community-dwelling older adults aged 65 and above.

Methods

We searched PubMed, Cochrane Library, CINAHL, Embase, and Web of Science databases for randomized controlled trials published between January 1, 2000, and December 31, 2023. Studies evaluating interventions designed to reduce fall incidence or fall-related injuries in community-dwelling older adults were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the RoB 2 tool. Meta-analyses were conducted using random-effects models.

Results

Forty-seven studies met the inclusion criteria, involving 23,584 participants across 15 countries. The mean age of participants was 76.3 years (SD 4.7), and 68% were female. Overall, interventions significantly reduced fall rates (Rate Ratio 0.80, 95% CI 0.75-0.86, I2=67%). Multifaceted interventions showed the greatest reduction in fall rates (RR 0.75, 95% CI 0.68-0.82), followed by exercise interventions alone (RR 0.85, 95% CI 0.78-0.92). Interventions also reduced the risk of becoming a faller (Risk Ratio 0.85, 95% CI 0.80-0.90) and the risk of fall-related injuries (Risk Ratio 0.83, 95% CI 0.76-0.91). Subgroup analyses revealed greater effectiveness in high-risk populations (RR 0.72, 95% CI 0.65-0.80). Longer interventions (12 months or more) showed greater reductions in fall rates. The mean adherence rate was 76%, with no serious adverse events reported.

Conclusions

This review provides strong evidence supporting the implementation of multifaceted falls prevention programs for community-dwelling older adults, with a particular emphasis on exercise interventions. Future research should focus on long-term adherence, cost-effectiveness, and innovative approaches to fall prevention in diverse populations and settings.
Crossovers are regulated by a conserved and disordered synaptonemal complex domain
Authors: Rodrigues Neves Ana Rita , Cavka Ivana , Rausch Tobias , Koehler Simone
Published: August 2024

To ensure the accurate segregation of homologous chromosomes and enhance the genetic diversity in the progeny, meiosis depends on the formation of crossovers between homologous chromosomes. The number and distribution of these crossovers must be precisely regulated through crossover assurance and interference to prevent chromosome missegregation and genomic instability. Here we show that the regulation of crossovers depends on a disordered domain within the synaptonemal complex, which is highly conserved. This domain is located at the C-terminus of the central element protein SYP-4 in C. elegans. While not necessary for synapsis, the C-terminus of SYP-4 is crucial for both crossover assurance and interference. Although the SYP-4 C-terminus contains many potential phosphorylation sites, we found that phosphorylation is not the primary regulator of crossover events. Instead, we discovered that nine conserved phenylalanines recruit a pro-crossover factor predicted to be an E3 ligase and regulate the physical properties of the synaptonemal complex. We propose that this conserved and disordered domain plays a crucial role in maintaining the synaptonemal complex in an activated state to promote crossing-over. This activation allows the synaptonemal complex to regulate the number and distribution of crossovers along chromosomes, thereby protecting the genome for future generations.
Increased Nutrient Levels Enhance the Bacterial Contribution to an Algal-Bacterial Extracellular Matrix
Authors: Lipsman Valeria , Segev Einat
Published: August 2024

Microbial aggregation is central in environmental processes, such as marine snow and harmful marine mucilage events. Nutrient enrichment positively correlates with microbial aggregation. This correlation is largely attributed to the overgrowth of microalgae and the overproduction of agglomerating exopolysaccharides (EPS). However, recent studies highlight the significant contribution of bacterial EPS to algal-bacterial aggregation. Here, using controlled laboratory experiments and environmental metatranscriptomic analysis, we investigate the impact of nutrient enrichment on bacterial EPS production, while bacteria are in the context of their algal hosts. Our findings demonstrate a marked increase in bacterial EPS production in response to an increase of inorganic phosphorus and nitrogen levels, both in the lab and in the environment. These results highlight the interplay between nutrient regimes, bacterial physiology, and microbial aggregation in marine ecosystems and emphasize gaps in our understanding regarding the bacterial role in environmental processes that involve microbial aggregation.
Amyloid, Tau, and APOE in Alzheimer’s Disease: Impact on White Matter Tracts
Authors: Chandio Bramsh Qamar , Villalon-Reina Julio E. , Nir Talia M. , Thomopoulos Sophia I. , Feng Yixue , Benavidez Sebastian , Jahanshad Neda , Harezlak Jaroslaw , Garyfallidis Eleftherios , Thompson Paul M. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2024

Alzheimer’s disease (AD) is characterized by cognitive decline and memory loss due to the abnormal accumulation of amyloid-beta (Aβ) plaques and tau tangles in the brain; its onset and progression also depend on genetic factors such as the apolipoprotein E (APOE) genotype. Understanding how these factors affect the brain’s neural pathways is important for early diagnostics and interventions. Tractometry is an advanced technique for 3D quantitative assessment of white matter tracts, localizing microstructural abnormalities in diseased populationsin vivo. In this work, we applied BUAN (Bundle Analytics) tractometry to 3D diffusion MRI data from 730 participants in ADNI3 (phase 3 of the Alzheimer’s Disease Neuroimaging Initiative; age range: 55-95 years, 349M/381F, 214 with mild cognitive impairment, 69 with AD, and 447 cognitively healthy controls). Using along-tract statistical analysis, we assessed the localized impact of amyloid, tau, and APOE genetic variants on the brain’s neural pathways. BUAN quantifies microstructural properties of white matter tracts, supporting along-tract statistical analyses that identify factors associated with brain microstructure. We visualize the 3D profile of white matter tract associations with tau and amyloid burden in Alzheimer’s disease; strong associations near the cortex may support models of disease propagation along neural pathways. Relative to the neutral genotype, APOEɛ3/ɛ3, carriers of the AD-risk conferring APOEɛ4 genotype show microstructural abnormalities, while carriers of the protectiveɛ2 genotype also show subtle differences. Of all the microstructural metrics, mean diffusivity (MD) generally shows the strongest associations with AD pathology, followed by axial diffusivity (AxD) and radial diffusivity (RD), while fractional anisotropy (FA) is typically the least sensitive metric. Along-tract microstructural metrics are sensitive to tau and amyloid accumulation, showing the potential of diffusion MRI to track AD pathology and map its impact on neural pathways.
Inferring the composition of a mixed culture of natural microbial isolates by deep sequencing
Authors: Voorhies Mark , Joehnk Bastian , Uehling Jessie , Walcott Keith , Dubin Claire , Mead Heather L. , Homer Christina M. , Galgiani John N. , Barker Bridget M. , Brem Rachel B. , Sil Anita
Published: August 2024

Next generation sequencing has unlocked a wealth of genotype information for microbial populations, but phenotyping remains a bottleneck for exploiting this information, particularly for pathogens that are difficult to manipulate. Here, we establish a method for high-throughput phenotyping of mixed cultures, in which the pattern of naturally occurring single-nucleotide polymorphisms in each isolate is used as intrinsic barcodes which can be read out by sequencing. We demonstrate that our method can correctly deconvolute strain proportions in simulated mixed-strain pools. As an experimental test of our method, we perform whole genome sequencing of 66 natural isolates of the thermally dimorphic pathogenic fungusCoccidioides posadasiiand infer the strain compositions for large mixed pools of these strains after competition at 37°C and room temperature. We validate the results of these selection experiments by recapitulating the temperature-specific enrichment results in smaller pools. Additionally, we demonstrate that strain fitness estimated by our method can be used as a quantitative trait for genome-wide association studies. We anticipate that our method will be broadly applicable to natural populations of microbes and allow high-throughput phenotyping to match the rate of genomic data acquisition.

Author summary

The diversity of the gene pool in natural populations encodes a wealth of information about its molecular biology. This is an especially valuable resource for non-model organisms, from humans to many microbial pathogens, lacking traditional genetic approaches. An effective method for reading out this population genetic information is a genome wide association study (GWAS) which searches for genotypes correlated with a phenotype of interest. With the advent of cheap genotyping, high throughput phenotyping is the primary bottleneck for GWAS, particularly for microbes that are difficult to manipulate. Here, we take advantage of the fact that the naturally occurring genetic variation within each individual strain can be used as an intrinsic barcode, which can be used to read out relative abundance of each strain as a quantitative phenotype from a mixed culture.Coccidioides posadasii, the causative agent of Valley Fever, is a fungal pathogen that must be manipulated under biosafety level 3 conditions, precluding many high-throughput phenotyping approaches. We apply our method to pooled competitions ofC. posadasiistrains at environmental and host temperatures. We identify robustly growing and temperature-sensitive strains, confirm these inferences in validation pooled growth experiments, and successfully demonstrate their use in GWAS.
The Diffusion Exchange Ratio (DEXR): A minimal sampling of diffusion exchange spectroscopy to probe exchange, restriction, and time-dependence
Authors: Cai Teddy X. , Williamson Nathan H. , Ravin Rea , Basser Peter J.
Published: August 2024

Water exchange is increasingly recognized as an important biological process that can affect the study of biological tissue using diffusion MR. Methods to measure exchange, however, remain immature as opposed to those used to characterize restriction, with no consensus on the optimal pulse sequence(s) or signal model(s). In general, the trend has been towards data-intensive fitting of highly parameterized models. We take the opposite approach and show that a judicious sub-sample of diffusion exchange spectroscopy (DEXSY) data can be used to robustly quantify exchange, as well as restriction, in a data-efficient manner. This sampling produces a ratio of two points per mixing time: (i) one point with equal diffusion weighting in both encoding periods, which gives maximal exchange contrast, and (ii) one point with the sametotaldiffusion weighting in just the first encoding period, for normalization. We call this quotient the Diffusion EXchange Ratio (DEXR). Furthermore, we show that it can be used to probe time-dependent diffusion by estimating the velocity autocorrelation function (VACF) over intermediate to long times (∼ 2 − 500 ms). We provide a comprehensive theoretical framework for the design of DEXR experiments in the case of static or constant gradients. Data from Monte Carlo simulations and experiments acquired in fixed and viableex vivoneonatal mouse spinal cord using a permanent magnet system are presented to test and validate this approach. In viable spinal cord, we report the following apparent parameters from just 6 data points:τk= 17 ± 4 ms,fNG= 0.71 ± 0.01,Reff= 1.10 ± 0.01μm, andkeff= 0.21 ± 0.06μm/ms, which correspond to the exchange time, restricted or non-Gaussian signal fraction, an effective spherical radius, and permeability, respectively. For the VACF, we report a long-time, power-law scaling with ≈t− 2.4, which is approximately consistent with disordered domains in 3-D. Overall, the DEXR method is shown to be highly efficient, capable of providing valuable quantitative diffusion metrics using minimal MR data.
Metagenome-based diversity and functional analysis of culturable microbes in sugarcane
Authors: Lin Haidong , Wu Liang , zhang Lijun , Kiet Ta Quang , Liu Peng , Song Jinkang , Yang Xiping
Published: August 2024

Sugarcane, widely acknowledged as the foremost crop for sugar and energy production on a worldwide scale, is confronted with many diseases that pose serious threats to its production. Biological control has become more popular as an approach for preventing and controlling diseases because of its environment-friendly characteristics. However, there is a lack of thorough investigation and use of microbial resources in sugarcane. This study conducted a thorough analysis of culturable microbes and their functional features in different tissues and rhizosphere soil of four diverse sugarcane species using metagenomics techniques. The results revealed significant microbial diversity in sugarcane’s tissues and rhizosphere soil, including several important biomarker bacterial taxa identified, which are reported to engage in several processes that support plant growth. The LEfSe studies identified unique microbial communities in different parts of the same sugarcane species, particularlyBurkholderia, which exhibited significant variations across the sugarcane species. Microbial analysis of carbohydrate-active enzymes (CAZymes) indicated that genes related to sucrose metabolism were mostly present in specific bacterial taxa, includingBurkholderia, Pseudomonas, Paraburkholderia, andChryseobacterium. This study improves understanding of the diversities and functions of endophytes and rhizosphere soil microbes in sugarcane. Moreover, the approaches and findings of this study provide valuable insights for microbiome research and the use of comparable technologies in other agricultural fields.
Is there an anticholinergic effect of drugs beyond polypharmacy? A simulation study on death, dementia, and delirium in UK Biobank
Authors: Mur Jure , Stirland Lucy E. , Muniz-Terrera Graciela , Leist Anja K.
Published: August 2024

The use of anticholinergic drugs has been associated with adverse health outcomes. However, their effects cannot be completely separated from the effects of general polypharmacy using standard methods. The objective of this study was to explore the extent to which the detrimental health effects attributed to anticholinergic burden measured by anticholinergic burden scales (ABS) were distinct from those of polypharmacy. We compared observed effects of ABS against simulated effects of generated pseudoscales intended to measure polypharmacy using UK Biobank primary care data. We randomly sampled from 525 anticholinergic and non-anticholinergic drugs prescribed in the year 2015 to ~200,000 participants with an average age of 65 years. We then created 1,000 pseudoscales, the score of which was designed to represent the strength of the background effect of polypharmacy, differentiating pseudoscales constructed to capture either general polypharmacy or putative anticholinergic polypharmacy, and exhibiting similar distributional properties to 23 real-world ABS (statistical equivalence). We performed individual logistic regressions for each scale to estimate associations between ABS scales and pseudoscales, respectively, and risk of death, dementia, or delirium. Across outcomes, odds ratios for anticholinergic-polypharmacy pseudoscales were on average 0.03-0.05 greater than those of general-polypharmacy pseudoscales. The number of drugs composing the scales was correlated with the size of adverse effects for both pseudoscales (r=~0.5, p<0.001) and ABS (r=~0.7, p<0.001). In total, 50-90% of ABS showed stronger effects than the majority of pseudoscales. ABS exhibited stronger associations with the studied adverse health outcomes than would be expected from polypharmacy alone (range of differences in odds ratios: -0.05 to 0.20). Most existing ABS capture more variance in the association with death, dementia, and delirium than polypharmacy alone, but with varying degrees of strength.
Evaluation of alternative farm safety net program combination strategies
Authors: Gaku Sylvanus , Tsiboe Francis
Published: August 2024

Purpose

Several farm safety net strategies are available to farmers as a source of financial protection against losses due to price instability, government policies, weather fluctuations and global market changes. Producers can employ these strategies combining crop insurance policies with countercyclical policies for several crops and production areas; however, less is known about the efficiency of these strategies in enhancing profit and reducing its variability. In this study, we examine the efficiency of these strategies at minimizing inter crop year farm profit variability.

Design/methodology/approach

We utilized relative mean of profit and coefficient of variation, to compare counterfactually calculated farm safety net strategies for a sample of 28,615 observations across 2,486 farms and four dryland crops (corn, soybean, sorghum and wheat) in Kansas spanning nine crop years (2014–2022). A no farm safety net strategy is used as the benchmark for every alternative strategy to ascertain whether a policy customization is statistically different from a no farm safety case.

Findings

The general pattern of the results suggests that program combination strategies that have a high-profit enhancement potential necessarily have low profit risk for dryland wheat and sorghum production. On the contrary, such a connection is absent for dryland corn and soybeans production. Low-cost farm safety net strategies that enhance corn and soybeans profits do not necessarily lower profit risks.

Originality/value

This paper is one of the first to use a large sample of actual farm-level observations to evaluate how combinations of safety net programs offered under the Title I (PLC, ARCCO and ARCIC) and XI (FCIP) of the U.S. Farm Bill rank in terms of profit level enhancement and profit risk reduction.
Researching the Jordanian city: toward an urban planning research agenda in Jordan
Authors: Okour Yasmein , Dalgamoni Nermeen , Al-Rqaibat Sana'a
Published: August 2024

Purpose

Research and Development (R&D) plays a significant role in promoting social and economic development in cities. In urban planning practice, a lack of evidence-informed policies and misguided research efforts can undermine national and local development efforts. This research aims to outline the state of academic research in urban planning and propose a tentative urban planning research agenda in Jordan. Specifically, the study identifies emerging research areas within postgraduate urban planning research in Jordan, examines the extent to which current research activities align with national research priorities, and determines research areas of top priority for Jordanian cities.

Design/methodology/approach

The research employs a mixed-method approach using content analysis to analyze academic urban planning research in Jordan and the Delphi method targeting Jordanian urban planning experts to identify research areas that should be prioritized in Jordan within the next five years.

Findings

The findings indicate that while urban design and housing, neighborhoods, and community development were the dominant fields of study in postgraduate urban planning research, planning experts identified transportation and land use planning as research areas of top priority for the next five years. The results also suggest that national research priorities lack specificity and offer little guidance for researchers in complex and multifaceted scientific disciplines, such as urban planning.

Originality/value

This research lays the foundations for developing a comprehensive and feasible urban planning research agenda that is responsive to the diverse needs of communities and cities across Jordan. It offers three propositions to guide future knowledge production in urban planning: emphasizing research activity in priority areas, decentralizing research activities, and fostering inter/transdisciplinary research linkages. To the best of the author's knowledge, this study is the first to propose an urban planning research agenda in Jordan.
Awareness of net zero energy buildings among construction professionals in the Ghanaian construction industry
Authors: Oduro Samuel , Pittri Hayford , Simons Barbara , Baah Benjamin , Anteh Eunice Deedei , Oduro John Adjei
Published: August 2024

Purpose

Net zero energy buildings (NZEBs) play a crucial role in mitigating the environmental impact of the construction industry. However, this concept in Ghana is still in the infancy stage, and the level of embracement in the construction industry is uncertain which further poses challenges to its adoption. This can be attributed to the lack of awareness of NZEB among construction professionals. Hence, understanding the awareness among construction professionals is essential for promoting sustainable building practices and reducing the carbon footprint of buildings. Therefore, this study investigates the level of awareness of NZEBs among construction professionals in the Ghanaian construction industry (GCI).

Design/methodology/approach

The study adopted a quantitative research method where questionnaire survey was used to obtain data from sixty-six (66) construction professionals in the GCI through snowball sampling technique. The collected data were analysed using frequencies, mean scores, one-sample t-test and cross-tabulation.

Findings

The study revealed that thirty (30) construction professionals out of the sixty-six (66) had a moderate level of awareness of NZEBs, and 14 professionals had a low level of awareness. Thirteen had a high level of awareness. Three of the profesionals were extremely unaware, while six had a very high level of awareness. The study’s findings highlight the need to create awareness of NZEBs and their practices among construction professionals and employees in Ghana.

Originality/value

NZEB is an under-explored area in the Ghanaian context and therefore, this study uniquely highlights the nascent awareness of NZEBs among Ghanaian construction professionals, unlike previous studies in more developed contexts. It underscores the critical need for targeted awareness programs essential for reducing the carbon footprint and advancing the adoption of NZEBs in the GCI.
A study on substance abuse awareness and usage trends within the construction sector
Authors: Jamir Singh Paramjit Singh , Oke Ayodeji Emmanuel , Aliu John , Isaiah Kayode Tobi , Azura Ramli Rosfaraliza , Haizzan Yahaya Mohd , Idris Afifah
Published: August 2024

Purpose

To address safety risks, worker well-being concerns and productivity losses in construction due to substance misuse, this study aims to explore awareness and usage levels of various substances among Nigerian construction professionals. The findings aim to inform targeted interventions and policy development to tackle these industry-specific challenges.

Design/methodology/approach

A comprehensive literature review identified several substances and intoxicants commonly used in construction, which informed the development of a well-structured questionnaire. This questionnaire was distributed to both construction professionals and nonprofessionals. The Shapiro-Wilk test assessed the normality of awareness and utilization scores for each substance, while the Kruskal-Wallis H-test explored significant differences in awareness and usage scores among different respondent groups.

Findings

Despite reporting low awareness of substances commonly used in construction, a significant proportion (over 60%) of respondents admitted to using several of these substances in their construction activities. This highlights a concerning disconnect, with more than half (62.5%) exceeding a predefined threshold (3.5) for significant substance use. Ten out of the 16 substances surveyed fell into this category, indicating a widespread issue within the industry.

Practical implications

The findings of this study highlight the need for increased education and awareness programs about the dangers of substance misuse in the construction industry. Construction companies should implement regular training sessions and workshops to educate workers on the risks associated with substance use. Additionally, there should be stricter enforcement of substance use policies and routine substance testing to deter misuse. These measures can enhance safety, improve worker well-being and boost overall productivity in the construction industry.

Originality/value

The insights from this study can inform the development of international policies and best practices for substance use prevention and worker well-being in the construction industry. Sharing these findings with international organizations, policymakers and industry stakeholders can help create broader guidelines and frameworks adaptable for implementation in various countries.