bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leber Hereditary Optic Neuropathy in a Family of Carriers of MT-ND5 m.13042G>T (A236S) Novel Variant
Authors: Petrović Pajić Sanja , Suštar Habjan Maja , Brecelj Jelka , Fakin Ana , Volk Marija , Maver Aleš , Jezernik Gregor , Peterlin Borut , Glavač Damjan , Hawlina Marko , Jarc-Vidmar Martina 
Published: March 2023

Background:
A Slovenian three-generation family with 3 individuals with bilateral optic neuropathy and 2 unaffected relatives with a novel homoplasmic missense variant m.13042G > T (A236S) in the ND5 gene is described. A detailed phenotype at initial diagnosis and a follow-up of bilateral optic neuropathy progression is presented for 2 affected individuals.

Methods:
A detailed phenotype analysis with clinical examination in the early and chronic phase with electrophysiology and OCT segmentation is presented. Genotype analysis with full mitochondrial genome sequencing was performed.

Results:
Two affected male individuals (maternal cousins) had a profound visual loss at an early age (11 and 20 years) with no recovery. The maternal grandmother exhibited bilateral optic atrophy with a history of visual loss at the age 58 years. The visual loss of both affected male individuals was characterized by centrocecal scotoma, abnormal color vision, abnormal PERG N95, and VEP. Later with disease progression, retinal nerve fiber layer thinning was observed on OCT. We observed no other extraocular clinical features. Mitochondrial sequencing identified a homoplasmic novel variant m.13042G > T (A236S) in the MT-ND5 gene, belonging to a haplogroup K1a.

Conclusion:
Novel homoplasmic variant m.13042G > T (A236S) in the ND5 gene in our family was associated with Leber hereditary optic neuropathy-like phenotype. However, predicting the pathogenicity of a novel ultra-rare missense variant in the mitochondrial ND5 gene is challenging. Genetic counseling should consider genotypic and phenotypic heterogeneity, incomplete penetrance, haplogroup type, and tissue-specific thresholds.
Green Heart Louisville: intra-urban, hyperlocal land-use regression modeling of nitrogen oxides and ozone
Authors: Prathibha Pradeep , Yeager Raymond , Bhatnagar Aruni , Turner Jay 
Published: March 2023

AbstractExposure to urban air pollution is linked to increased mortality from cardiopulmonary causes. Urban areas juxtapose large numbers of residences and workplaces with near-road environments, exacerbating traffic-related air pollution (TRAP) exposure. TRAP is the primary source of variability in intraurban air quality, but continuous regulatory monitoring stations lack the spatial resolution to detect fine-scale pollutant patterns that recent studies using long-term, resource-intensive mobile measurements have established as persistent and associated with higher risk of cardiovascular events. This work evaluates a low-cost, fixed-site approach to characterizinglong-term, hyperlocal exposure to oxides of nitrogen (including NO2, a common surrogate for TRAP) as part of Green Heart Louisville, a prospective cohort study examining linkages between urban vegetation, local air quality, and cardiovascular health.We used a fixed 60-site network of Ogawa passive samplers in a 12 km2section of Louisville, KY, to measure two-week integrated NO2, NOx(NO + NO2), and O3mixing ratios nominally every two months between May 2018-March 2021. Seasonal NOxaverages were 2.5-fold higher during winter than in summer, and annual average NO (calculated by difference in NOxand NO2) and NO2ranged from 4-21 ppb and 5-12 ppb, respectively. NO increased 3-to-5-fold within 150 m of highways or major arterial roads and 2-to-3-fold near parking lots. While both NO and NO2were elevated in near-road environments, the corresponding O3was depressed, consistent with titration by NO.We developed land-use regression models for annual average NO, NO2, and NOxusing parameters of proximity (distance to nearest road type, restaurant, traffic signal), cumulative occurrence (length of roads, number of restaurants and traffic lights, all in buffers of up to 500 m in 50-m increments), and greenness (normalized difference vegetative index (NDVI)). Adjusted spatial variability explained by the models were 70% (p<0.05), 67% (p<0.05), and 75% (p<0.01) for NO, NO2, and NOx, respectively. Common predictors were distances to the nearest restaurant and road as well as total length of roads within 350 m. Only one greenness metric was significant: mean NDVI within 50 m was negatively associated (p=0.02) with NO2. We plan to use these hyperlocal models to estimate residential-level exposures of the clinical study participants.
Archetypal analysis of COVID-19 in Montana, USA, March 13, 2020 to April 26, 2022
Authors: Stone Emily , Coombs Sebastian , Landguth Erin 
Published: March 2023

AbstractGiven the potential consequences of infectious diseases, it is important to understand how broad scale incidence variability influences the probability of localized outbreaks. Often, these infectious disease data can involve complex spatial patterns intermixed with temporal trends. Archetypal Analysis is a method to mine complex spatiotemporal epidemiological data, and can be used to discover the dynamics of spatial patterns. The application of Archetypal Analysis to epistemological data is relatively new, and here we present one of the first applications using COVID-19 data from March 13, 2020 to April 26, 2022, in the counties of Montana, USA. We present three views of the data set with Archetypal Analysis. First, we evaluate the entire 56 county data set. Second, we compute mutual information of the 56 counties’ time series to remove counties whose dynamics are mainly independent from most of the other counties. We choose the top 17 counties ranked in terms of increasing total mutual information. Finally, to compare how population size might influence results, we conducted an analysis with 10 of the largest counties. Using the Archetypal Analysis results, we analyze the disease outbreaks across Montana, comparing and contrasting the three different cases and showing how certain counties can be found in distinct sets of archetypes. Using the reconstruction time series, we show how each outbreak had a unique trajectory across the state in terms of the archetypes.Author summaryArchetypal Analysis provides an additional tool for the study of spatio-temporal epidemiological data. We apply Archetypal Analysis to COVID-19 data and reveal how this approach can be used to analyse the dynamics of each COVID-19 outbreak across the state.
The impact of signal variability on epidemic growth rate estimation from wastewater surveillance data
Authors: Colman Ewan , Kao Rowland R. 
Published: March 2023

BackgroundTesting samples of waste water for markers of infectious disease became a widespread method of surveillance during the COVID-19 pandemic. While these data generally correlate well with other indicators of national prevalence, samples that cover localised regions tend to be highly variable over short time scales.MethodsWe introduce a procedure for estimating the realtime growth rate of pathogen prevalence using time series data from wastewater sampling. The number of copies of a target gene found in a sample is modelled as time-dependent random variable whose distribution is estimated using maximum likelihood. The output depends on a hyperparameter that controls the sensitivity to variability in the underlying data. We apply this procedure to data reporting the number of copies of the N1 gene of SARS-CoV-2 collected at water treatment works across Scotland between February 2021 and February 2023.ResultsThe real-time growth rate of the SARS-CoV-2 prevalence is estimated at 121 wastewater sampling sites covering a diverse range of locations and population sizes. We find that the sensitivity of the fitting procedure to natural variability determines its reliability in detecting the early stages of an epidemic wave. Applying the procedure to hospital admissions data, we find that changes in the growth rate are detected an average of 2 days earlier in wastewater than in hospital admissions data.ConclusionWe provide a robust method to generate reliable estimates of epidemic growth from highly variable data. Applying this method to samples collected at wastewater treatment works provides highly responsive situational awareness to inform public health.
Contraception ends the genetic maintenance of human same-sex sexual behavior
Authors: Song Siliang , Zhang Jianzhi 
Published: March 2023

ABSTRACTBecause human same-sex sexual behavior (SSB) is heritable and leads to fewer offspring, it is puzzling why SSB-associated alleles have not been selectively purged. Current evidence supports the antagonistic pleiotropy hypothesis that SSB-associated alleles benefit individuals exclusively performing opposite-sex sexual behavior by increasing their number of sexual partners and consequently their number of offspring. However, here we show that having more sexual partners no longer predicts more offspring since the availability of oral contraceptives in the 1960s and that SSB is now negatively genetically correlated with the number of offspring, indicating a loss of SSB’s genetic maintenance in modern societies.
Selection of antibody-binding covalent aptamers
Authors: Soxpollard Noah , Strauss Sebastian , Jungmann Ralf , MacPherson Iain 
Published: March 2023

AbstractAptamers are oligonucleotides with antibody-like binding function, selected from large combinatorial libraries. In this study, we modified a DNA aptamer library with N-hydroxysuccinimide esters, enabling covalent reactivity with cognate proteins. We selected for the ability to bind to mouse monoclonal antibodies, resulting in the isolation of two distinct covalent binding motifs. The covalent aptamers are specific for the Fc region of mouse monoclonal IgG1 and are cross-reactive with mouse IgG2a and other IgGs. Investigation into the covalent reactivity of the aptamers revealed a dependence on micromolar concentrations of Cu2+ions which can be explained by residual catalyst remaining after modification of the aptamer library. The aptamers were successfully used as adapters in the formation of antibody-oligonucleotide conjugates (AOCs) for use in detection of HIV protein p24 and super-resolution imaging of actin. This work introduces a new method for the site-specific modification of native monoclonal antibodies and may be useful in applications requiring AOCs or other antibody conjugates.
Serotonin in the orbitofrontal cortex enhances cognitive flexibility
Authors: Hyun Jung Ho , Hannan Patrick , Iwamoto Hideki , Blakely Randy D. , Kwon Hyung-Bae 
Published: March 2023

AbstractCognitive flexibility is a brain’s ability to switch between different rules or action plans depending on the context. However, cellular level understanding of cognitive flexibility have been largely unexplored. We probed a specific serotonergic pathway from dorsal raphe nuclei (DRN) to the orbitofrontal cortex (OFC) while animals are performing reversal learning task. We found that serotonin release from DRN to the OFC promotes reversal learning. A long-range connection between these two brain regions was confirmed anatomically and functionally. We further show that spatiotemporally precise serotonergic action directly enhances the excitability of OFC neurons and offers enhanced spike probability of OFC network. Serotonergic action facilitated the induction of synaptic plasticity by enhancing Ca2+influx at dendritic spines in the OFC. Thus, our findings suggest that a key signature of flexibility is the formation of choice specific ensembles via serotonin-dependent synaptic plasticity.
Genome-wide development of intra- and inter-specific transferable SSR markers and construction of a dynamic web resource for yam molecular breeding: Y2MD
Authors: Diouf Moussa , Zoclanclounon Yedomon Ange Bovys , Mboup Pape Adama , Diouf Diaga , Malédon Erick , Rivallan Ronan , Chair Hâna , Dossa Komivi 
Published: March 2023

AbstractBackgroundMicrosatellite markers represent a low-cost and efficient tool for rapid genotyping as compared to single nucleotide polymorphism markers in laboratories with limited resources. For the economically important yam species widely cultivated in developing countries, very few microsatellite markers are available and no marker database has been developed to date. Herein, we conducted a genome-wide microsatellite marker development among four yam species, identified cross-species transferable markers, and designed an easy-to-use web portal for the yam breeder community.ResultsThe screening of yam genomes resulted in 318,713; 322,501; 307,040 and 253,856 microsatellites inDioscorea alata,D. rotundata,D. dumetorum, andD. zingiberensis, respectively. Mono-, di- and tri-nucleotides were the most important types of repeats in the different species and a total of 864,128 primer pairs were designed. Furthermore, we identified 1170 cross-species transferable microsatellite markers. Among them, a subset of 17 markers were experimentally validated with good discriminatory power regarding the species and the ploidy levels. Ultimately, we created and deployed a dynamic Yam Microsatellite Markers Database (Y2MD) available athttp://yamdb.42web.io/. Y2MD is embedded with various useful tools such as JBrowse, Blast,insilicoPCR, and SSR Finder to facilitate the exploitation of microsatellite markers in yams.ConclusionsThe present work is the first comprehensive microsatellite marker mining across several yam species and will contribute to advance yam genetic research and marker-assisted breeding. The released user-friendly database constitutes a valuable platform for yam breeders, especially those in developing countries.
Integrated multi-omics data reveals the molecular subtypes and the contruction of novel signature to aid Immunotherapy
Authors: li zhenqing , Li Bin , Meng Yuqi , Zhai Kerong , Li Xuan 
Published: March 2023

AbstractMalignant cancer exhibits a severe imbalance between the active of immune response and tolerance. And the different and connection between the establishment and deficiency of the tumor immune response is still unknown entirely. Here, we used ten clustering algorithms based on five immune cells infiltration matrix to identified two specific molecular subtypes and determine its potential clinical outcomes and immune response effect. The cluster A subtype can be called the cold inflammatory subtype, which revealed the worst prognosis. And the cluster B can be identified as hot inflammatory subtype with high activated immune-related pathways. Then we used the WGCNA algorithms and limma to confirm the driven genes between the cluster A and B. 67 genes were identified the cluster A signature genes, and based on that we used the ssgsea algorithm to quantize the two subtypes. We confirmed the high score group had high activated level of immune activity pathways and better survival rate. The tumorigenesis-associated pathways were analysed in low score group, indicating active cell proliferation may be associated with poor prognosis. An in-silico drug screen predicted the erlotinib can be an effective compound in low score group based on the lung cancer cell line. Our research confirmed that the score can worked as an effective immunotherapy index, which provide a promising therapeutic strategies on immune therapeutics for lung adenocarcinoma.
Antecedents and boundary conditions of entrepreneurial intentions: perspective of theory of planned behaviour
Authors: Rehman Wali , Yosra Abdelwahed , Khattak Muhammad Sualeh , Fatima Goher 
Published: March 2023

PurposeThis paper aims to examine the effects of perceived desirability for entrepreneurship (PDE) and perceived self-efficacy (PSE) on the entrepreneurial intentions (EI) of business students, with the moderation effect of entrepreneurial knowledge (EK) in the context of the theory of planned behaviour.Design/methodology/approachWe used a self-administered survey of 200 students registered in the business schools of Pakistani universities. The causal association between the variables was estimated through SmartPLS by using hierarchal linear modelling.FindingsThe study findings indicate that PDE and PSE significantly influence EIs. Furthermore, EK significantly strengthens the nexus between PDE and EIs and between PSE and EIs. Those students who had already acquired self-efficacy and exhibited desirability for the business venture were more inclined towards entrepreneurship if they had acquired some EK and vice versa.Research limitations/implicationsThis study reveals that a model of EIs is needed to configure the students’ goals and motivations. Also, using new education programmes will help students acquire new knowledge for business startups. Further implications are also discussed.Originality/valueThis research fills a gap by using the moderating role of EK on the nexus between PDE, PSE and EIs, which has remained untouched in the educational sector.
Understanding Chinese Gen Z and their online shopping intentions through TAM
Authors: Copeland Lauren Reiter , Bhaduri Gargi , Huang Ouya 
Published: March 2023

PurposeThe purpose of this study is to examine the ease of use and usefulness of the application Taobao and whether involvement, self-confidence and self-expression of users are related and ultimately affect the purchase intention of Gen Z Chinese users on the site.Design/methodology/approachThe theoretical basis of Technology Acceptance Model (TAM) was utilized. An online survey of 46 questions and 190 responses of Chinese consumers between the ages of 18 and 23 was conducted. PROCESS and a linear regression were used to analyze the results.FindingsThrough the lens of the TAM (Davis, 1989), the findings of this study determined that for participants TAM was deemed more useful when TAM was viewed than as easier to use. However, in this case perceived ease of use and usefulness did not directly relate to attitude. Instead, attitude was directly related to self-expression, confidence and involvement as the determining factors of positive attitude leading to intention. The study found that self-expression was most significant regarding attitude. To influence perceived self-expression though, ease of use and usefulness were crucial to obtain this effective characteristic.Originality/valueIn this study how the ease of use and usefulness of the application and involvement, self-confidence and self-expression of users are related and affect the purchase intention is examined.
Can lean principles assist to reduce BIM implementation costs? A contemporary application of lean principles to the Sri Lankan construction industry
Authors: Weerasinghe Lichini Nikesha , Rathnasinghe Akila Pramodh , Jayasena Himal Suranga , Thurairajah Niraj , Thayaparan Menaha 
Published: March 2023

PurposeBuilding information modelling (BIM) claims to be spearheading the modern technological revolution in the global construction industry. While scholars have emphasised the cruciality of BIM, associated costs have been identified as one of the major barriers to successful BIM implementation, as is the case in Sri Lanka. Besides, lean principles (LPs) are known for increasing efficiency, quality and eliminating waste, thereby reducing overall costs. Hence, this research aims at addressing the BIM implementation barrier associated with costs by applying suitable LP, enhancing overall value by minimising value-insignificant activities.Design/methodology/approachThe study adopted a qualitative research approach. 10 experts with expertise in both BIM and LP were targeted for the primary data collection through semi-structured interviews. The collected data were analysed using manual content analysis.FindingsResearch findings discovered the cost centres that can be applied to the LPs and the effective LPs that can be applied with the cost centres of BIM implementation. The theoretical implication of the study is to provide insights into a potential application of LP for BIM cost centres, whereas practical consequences include the identification of LP's potential to minimise BIM cost centres, ergo, achieving a successful BIM implementation.Originality/valueThis study will be the first of its kind in the Sri Lankan construction industry, intending to apply LP with BIM implementation cost centres to achieve a successful implementation. This research also has paved the way forward for further research on the application of both the BIM and LP concepts for similar construction industries in developing countries across the world and in addressing other BIM implementation barriers.
A novel twin-support vector machine for binary classification to imbalanced data
Authors: Li Jingyi , Chao Shiwei 
Published: March 2023

PurposeBinary classification on imbalanced data is a challenge; due to the imbalance of the classes, the minority class is easily masked by the majority class. However, most existing classifiers are better at identifying the majority class, thereby ignoring the minority class, which leads to classifier degradation. To address this, this paper proposes a twin-support vector machines for binary classification on imbalanced data.Design/methodology/approachIn the proposed method, the authors construct two support vector machines to focus on majority classes and minority classes, respectively. In order to promote the learning ability of the two support vector machines, a new kernel is derived for them.Findings(1) A novel twin-support vector machine is proposed for binary classification on imbalanced data, and new kernels are derived. (2) For imbalanced data, the complexity of data distribution has negative effects on classification results; however, advanced classification results can be gained and desired boundaries are learned by using optimizing kernels. (3) Classifiers based on twin architectures have more advantages than those based on single architecture for binary classification on imbalanced data.Originality/valueFor imbalanced data, the complexity of data distribution has negative effects on classification results; however, advanced classification results can be gained and desired boundaries are learned through using optimizing kernels.
Activities as the critical link between motivation and destination choice in cultural tourism
Authors: Douglas Anneli , Hoogendoorn Gijsbert , Richards Greg 
Published: March 2023

PurposeThis study aimed to determine the motivations of a select group of South Africans in terms of their potential engagement with cultural tourism; more specifically, the study set out to show whether these motivations influence the cultural activities that the tourists want to participate in and whether their interest in specific cultural activities determines their destination choices. Furthermore, the mediating role of activities in the relationship between cultural motivations and destination choice was also assessed.Design/methodology/approachAn online panel survey collected responses from 1,530 potential cultural tourists across South Africa. Hypotheses were tested, using structural equation modelling.FindingsThe results show that tourists' motivations for cultural tourism influence their likelihood of participating in specific cultural activities. Cultural tourism is shown to be influenced by more than learning and includes entertainment, relaxation, novelty and escape dimensions. There also seems to be a difference in the activities engaged in by destination type. For example, tourists likely to take part in indigenous cultural tourism activities are more likely to do so at hedonic destinations.Practical implicationsThis paper contributes to the understanding of cultural tourism activities, aiding destinations in attracting cultural tourists. Destinations need to develop activities that match visitor motivations, increase satisfaction and encourage visitors to return.Originality/valueThe paper increases the understanding of cultural tourism in South Africa and underlines the importance of communities in providing distinctive tourism activities. The study also has an important social dimension, highlighting the role of social status in cultural tourism consumption and destination selection.