bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prewhitening and Normalization Help Detect a Strong Cross-Correlation Between Daily Wastewater SARS-CoV-2 RNA Abundance and COVID-19 Cases in a Community
Authors: Jeon Min Ki , Li Bo , Di Doris Yoong Wen , Yan Tao 
Published: December 2022

AbstractWastewater surveillance is a promising technology for real-time tracking and even early detection of COVID-19 infections in communities. Although correlation analysis between wastewater surveillance data and the daily clinical COVID-19 case numbers has been frequently conducted, the importance of stationarity of the time-series data has not been well addressed. In this study, we demonstrated that strong yet spurious correlation could arise from non-stationary time-series data in wastewater surveillance, and data prewhitening to remove trends helped to reveal distinct cross-correlation patterns between daily clinical case numbers and daily wastewater SARS-CoV-2 concentration during a lockdown period in 2020 in Honolulu, Hawaii. Normalization of wastewater SARS-CoV-2 concentration by the endogenous fecal viral markers in the same samples significantly improved the cross-correlation, and the best correlation was detected at a two-day lag of the daily clinical case numbers. The detection of a significant correlation between daily wastewater SARS-CoV-2 RNA abundance and clinical case numbers also suggests that disease burden fluctuation in the community should not be excluded as a contributor to the often observed weekly cyclic patterns of clinical cases.Water impactWastewater surveillance represents an emerging water technology with significant human health benefits. The study demonstrated that non-stationary time-series data could lead to spurious correlation, highlighting the need for prewhitening. Normalization strategies could alleviate variations in sample collection and analyses, which is useful for detecting actual underlying relationships between wastewater surveillance data and clinical data.
Perinuclear force regulates SUN2 dynamics and distribution on the nuclear envelope for proper nuclear mechanotransduction
Authors: Niu Jiahao , Wang Xiaotian , Zhao Wenxue , Wang Yao , Qin Yizhi , Huang Xiaoshuai , Xue Boxin , Li Cheng , Sun Yujie 
Published: December 2022

AbstractThe trans-luminal LINC (Linker of Nucleoskeleton and Cytoskeleton) complex plays a central role in nuclear mechanotransduction by coupling the nucleus with cytoskeleton. High spatial density and active dynamics of LINC complex have hindered its precise characterization for the understanding of underlying mechanisms how the linkages sense and respond to mechanical stimuli. In this study, we focus on SUN2, a core component of LINC complex interconnecting the nuclear lamina and actin cytoskeleton and apply single molecule super-resolution imaging to reveal how SUN2 responds to actomyosin contractility. Using stochastic optical reconstruction microscopy (STORM), we quantitated the distribution pattern and density of SUN2 on the basal nuclear membrane. We found that SUN2 undergoes bidirectional translocation between ER and nuclear membrane in response to actomyosin contractility, suggesting that dynamic constrained force on SUN2 is required for its proper distribution. Furthermore, single molecule imaging unveils interesting dynamics of SUN2 molecules that are regulated by both actomyosin contractility and laminA/C network, whereas SUN2 oligomeric states are not affected by actomyosin contractility. Lastly, the mechanical response of SUN2 to actomyosin contractility was found to regulate expression of mechano-sensitive genes located in lamina-associated domains (LADs) and perinuclear heterochromatin. Taken together, our results reveal how SUN2 responds to mechanical cues at the single-molecule level, providing new insights into the mechanism of nuclear mechanotransduction.
Selenium Silk Nanostructured Films for Antifungal and Antibacterial Treatments
Authors: Toprakcioglu Zenon , Wiita Elizabeth G. , Jayaram Akhila K. , Gregory Rebecca C. , Knowles Tuomas P. J. 
Published: December 2022

AbstractThe rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. An orthogonal approach, therefore, is to explore biomaterials with physical modes of action which have the potential to generate antimicrobial activity and in some cases even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and non-cytotoxic towards mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a two-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials.
The episodic resurgence of highly pathogenic avian influenza H5 virus
Authors: Xie Ruopeng , Edwards Kimberly M. , Wille Michelle , Wei Xiaoman , Wong Sook-San , Zanin Mark , El-Shesheny Rabeh , Ducatez Mariette , Poon Leo L. M. , Kayali Ghazi , Webby Richard J. , Dhanasekaran Vijaykrishna 
Published: December 2022

AbstractHighly pathogenic avian influenza (HPAI) H5N1 activity has intensified globally since 2021, replacing the dominant clade 2.3.4.4 H5N8 virus. H5N1 viruses have spread rapidly to four continents, causing increasing reports of mass mortality in wild birds and poultry. The ecological and virological properties required for future mitigation strategies are unclear. Using epidemiological, spatial and genomic approaches, we demonstrate changes in the source of resurgent H5 HPAI and reveal significant shifts in virus ecology and evolution. Outbreak data indicates key resurgent events in 2016/17 and 2020/21 that contributed to the panzootic spread of H5N1 in 2021/22, including an increase in virus diffusion velocity and persistence in wild birds. Genomic analysis reveals that the 2016/17 epizootics originated in Asia, where HPAI H5 reservoirs are documented as persistent. However, in 2020/21, 2.3.4.4b H5N8 viruses emerged in domestic poultry in Africa, featuring several novel mutations altering the HA structure, receptor binding, and antigenicity. The new H5N1 virus emerged from H5N8 through reassortment in wild birds along the Adriatic flyway around the Mediterranean Sea. It was characterized by extensive reassortment with low pathogenic avian influenza in domestic and wild birds as it spread globally. In contrast, earlier outbreaks of H5N8 were caused by a more stable genetic constellation, highlighting dynamic changes in HPAI H5 genomic evolution. These results suggest a shift in the epicenter of HPAI H5 beyond Asia to new regions in Africa, the Middle East, Europe, and North and South America. The persistence of HPAI H5 with resurgence potential in domestic birds indicates that elimination strategies remain a high priority.
Ongoing emergence of M1UKlineage among invasive group A streptococcus isolates in 2020 and use of allele-specific PCR
Authors: Zhi Xiangyun , Li Ho Kwong , Li Hanqi , Loboda Zuzanna , Charles Samson , Vieira Ana , Huse Kristin , Jauneikaite Elita , Coelho Juliana , Lamagni Theresa , Sriskandan Shiranee 
Published: December 2022

SummaryBackgroundAn increasing burden of invasive group A streptococcal infections is reported in multiple countries, notably England, where scarlet fever cases are also abundant. In England, increased scarlet fever and invasive infections have been associated with emergence of a sublineage ofemm1Streptococcus pyogenesthat expresses increased SpeA scarlet fever erythrogenic toxin. Wider surveillance for toxigenicStreptococcus pyogeneslineage M1UKis much needed however, to date, lineage assignment has required genome sequencing limiting surveillance to those centres with access to such facilities.MethodsTo circumvent the requirement for genome sequencing, an allele-specific PCR was developed to distinguish M1UKfrom otheremm1 strains. Additional PCR assays were developed to distinguish M1UKfrom two intermediate lineages that were detected previously. The assay was evaluated using DNA from genome-sequenced upper respiratory tractemm1S. pyogenesstrains and a further set of 16 genome-sequenced invasiveS. pyogenesisolates that included the two intermediate lineages. The assay was then applied to DNA from all 305 invasiveemm1 isolates that had been submitted to the reference laboratory in the one pear period Jan 1-Dec 31 2020, in order to assign lineage.ResultsThe allele specific PCR was 100% accurate when compared with genome sequencing, correctly identifying M1UK, two intermediate sublineages, and otheremm1 strains. The assay demonstrated the M1UKlineage to be dominant amongemm1 invasive isolates in England, representing 278/305 (91%) of invasiveemm1 isolates by end of 2020.ImplicationsEmm1S. pyogeneshave a prominent role in invasive infections; anyemm1 lineage that demonstrates enhanced fitness within the population is of public health concern. The allele specific PCR provides a readily available method to subtypeemm1 isolates and does not require access to complex sequencing facilities. The data confirm that the M1UKlineage has persisted and further expanded in England underlining the importance of wider global surveillance.
Extracellular vesicles improve GABAergic transmission in Huntington’s disease iPSC-derived neurons
Authors: Beatriz Margarida , Rodrigues Ricardo , Vilaça Rita , Egas Conceição , Pinheiro Paulo , Daley George Q. , Schlaeger Thorsten M. , Rego A. Cristina , Lopes Carla 
Published: December 2022

AbstractExtracellular vesicles (EVs) carry bioactive molecules associated with various biological processes, including miRNAs. In both Huntington’s disease (HD) models and human samples, altered expression of miRNAs involved in synapse regulation were reported. Recently, the use of EV cargo to reverse phenotypic alterations in disease models with synaptopathy as the end-result of the pathophysiological cascade has become an interesting possibility. Here, we assessed the contribution of EVs to GABAergic synaptic alterations using a human HD model and studied the miRNA content of isolated EVs. After differentiating HD human induced-pluripotent stem cells into electrophysiologically active striatal-like GABAergic neurons, we found that HD-derived neurons displayed reduced density of inhibitory synapse markers and of GABA receptor-mediated ionotropic signaling. Treatment with EVs secreted by control (CTR) fibroblasts reversed the deficits in GABAergic synaptic transmission and increased the density of inhibitory synapses on HD-neuron cultures, while EVs from HD-derived fibroblasts had the opposite effects on CTR-neurons. Moreover, analysis of miRNAs from purified EVs identified a set of differentially expressed miRNAs between manifest HD, premanifest and CTR lines with predicted synaptic targets. The EVs-mediated reversal of the abnormal GABAergic phenotype in HD-derived neurons reinforces the potential role of EVs-miRNAs on synapse regulation.
Novel uAUG creating variants in the 5’UTR of ENG causing Hereditary Hemorrhagic Telangiectasia
Authors: Soukarieh Omar , Tillet Emmanuelle , Proust Carole , Dupont Charlène , Jaspard-Vinassa Béatrice , Soubrier Florent , Goyenvalle Aurélie , Eyries Mélanie , Trégouët David-Alexandre 
Published: December 2022

AbstractHereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular disorder causing abnormal vessel formation and characterized by autosomal dominant transmission. The associated considerable variability in symptoms and clinical severity complicate the management of the disease. In clinical routine, 3 main genes,ACVRL1(also known asALK1),ENGandSMAD4are screened for pathogenic variants at the origin of HHT. About 80% of HHT cases are caused by pathogenic coding variants inACVRL1andENG. However, at least 15% remain with no molecular explanations in the 3 main genes. We here report the identification of 2 never reported variants, c.-79C>T and c.-68G>A, in the 5’UTR ofENGin 2 unrelated HHT patients. These 2 variants are predicted to create upstream AUGs (uAUGs) in the 5’UTR, which are in frame with a stop codon located within the CoDing Sequence (CDS), thus generating Overlapping upstream Open reading frames (uoORFs). In other cases, uAUGs can lead to fully upstream ORFs (uORFs) when associated with stop codons located within the 5’UTR or to elongated CDS (eCDS) when in frame with the CDS and associated with the main stop codon.In order to assess the pathogenicity of theseENGvariants, we performedin vitrofunctional assays based on the expression of wild-type and mutant constructs in human cells. We found that these 5’UTRENGvariants were associated with a decrease of protein levels in HeLa and HUVEC cells. They were also associated with a decreased ability to activate BMP9-stimulated ALK1 receptor in a BMP-response element (BRE) assay. This assay is a mandatory element before providing a definitive molecular diagnosis and has been so far applied only on codingENGvariants. We applied the same experimental workflow on 3 additional uoORF-creating variants (c.-142A>T, c.-127C>T and c.-10C>T) and one eCDS-creating variant (c.-9G>A) in the 5’UTR ofENGpreviously reported in HHT patients. We found that all the analysed uoORF-creating variants alter endoglin levels and function. A comparison of our experimental results with patients’ clinical characteristics suggests that uoORF-creating variants leading to ENG protein levels ≤ 40%in vitrowould be associated with HHT. Additional experiments relying on an artificial deletion in our mutated constructs show that created uAUGs predicted to create uoORFs are able to initiate the translation indicating that the associated effect is likely caused by an alteration of the translation mechanism.Overall, we here identified two never reported 5’UTRENGvariations in HHT patients and shed new lights on the role of upstream ORFs on ENG regulation. Our findings contribute to the amelioration of molecular diagnosis in HHT.
Association of the 609 C/T NAD(P)H: quinone oxidoreductase (NQO1) polymorphism with development of cutaneous malignant melanoma
Authors: Naghynajadfard Maryam , Hodges Nikolas J , Towler Adam , Lee Amanda J , Norman Joanna , Doran Ryan , David Rhiannon M , Pheasant Anne E , Marsden Jerry , Chipman James K 
Published: December 2022

AbstractCutaneous Malignant Melanoma (CMM) is a life threatening disease whose incidence and mortality rates have risen rapidly in the White Caucasian population in recent decades. The aim of the current study was to investigate the association between polymorphisms in genes involved in DNA-repair and detoxification of reactive metabolites and the development of CMM. The patient cohort consisted of 69 individuals while the control population consisted of 100 individuals. We found a statistically significant association between the presence of the wild type NQO1 C allele, MDHFR C667T, TS1494del6, TSER polymorphisms and development of CMM [P= 0.04; odds ratio = 2.35]. The NQO1 CC genotype was more strongly associated with CMM development [P= 0.016; odds ratio = 2.92]. The NQO1 gene codes for a protein that has been widely considered to be protective through its ability to detoxify quinones. However recent studies have also linked it to an important source of reactive oxygen and to NF-κB-dependent proliferation of cultured melanoma cells. In conclusion these results link molecular epidemiology and experimental evidence for the role of the NQO1 gene product in development of CMM. MDHFR and TS in Folic acid metabolism are responsible for methylation of methyl group. Two important roles of folate ‘related to this study’ are the conversion of homocysteine to methionine and the generation of thymidylate (dTMP) which is required for DNA synthesis (Hayward, 2003). According to many studies done at this area, folate deficiency has been associated with chromosome strand breaks (Blountet al, 1997), impaired DNA repair (Hayward, 2003), DNA hypomethylation and hypermethylation all of which have been associated with cancer cell formation (Simonettaet al2001) (Dong-Hyun K. 2007). The result of study shows, MTHFR C677T and TS 6bp deletion/insertion are not related to increased risk of CMM and therefore have no effect on an individual’s susceptibility.
When background music in audiovisual advertisements can boost the perceived competence of the advertised brands – an empirical study from South Korea
Authors: Hong You Jeong , Choi Beomjoon , Lee Kyogu 
Published: December 2022

PurposeThe authors aim to explore whether and how variations on pitch levels of background music in audiovisual commercials affect consumers' judgments of the competence of the advertised brands and for which group of consumers such changes in ad backgrounds are more influential.Design/methodology/approachConsumers are presented with an audiovisual advertisement in which the pitch of background music is lowered or raised. They are subsequently asked to evaluate the music and traits of the advertised brand and indicate their predisposed styles of thinking.FindingsConsumers tend to judge a brand in an audiovisual commercial as possessing a higher level of competence traits when the brand is accompanied by lower-pitched (vs higher-pitched) background music, which is mediated by levels of powerfulness they perceive from the background music. Consumers with holistic (vs analytic) thinking styles, who are known to devote more focused attention to background information, tend to be more (vs less) susceptible to the changes in pitch.Research limitations/implicationsThe current research approaches thinking styles as predisposed individual differences as in prior works in marketing. Provided that the predisposed thinking styles can be influenced by individuals' cultural backgrounds, the authors suggest cross-cultural studies as an approach to further validate the present findings.Practical implicationsGiven the recent trends that consumers are increasingly exposed to audiovisual ads with the rapid growth of various video-based platforms (e.g. YouTube) and mobile advertising, this empirical study may assist contemporary marketers in considering an acoustic strategy for brand communication using the audiovisual advertisement. This study suggests that the pitch of ad background music can serve as a manageable strategic tool that can assist in establishing an image of a competent brand.Originality/valueThis research highlights a seemingly-trivial element in audiovisual advertisements, the pitch of background music, as a crucial determinant of the perceived competence of an advertised brand upon which further brand evaluations (e.g. brand trust, purchase intention) are based. An important yet overlooked effect of ad recipients' predisposed thinking styles on how consumers respond to the changes of background cues in audiovisual commercials is also proposed.
Adoption of e-government services at different maturity levels: a qualitative study in India
Authors: Kumar Rajiv , Sachan Amit , Mukherjee Arindam 
Published: December 2022

Purpose
The purpose of this study is to determine the factors that enable citizens to adopt e-government services at different maturity levels: information, two-way communication, transaction and political participation.

Design/methodology/approach
The study uses a grounded approach by conducting semi-structured interviews.

Findings
The study reveals that the factors influencing the adoption of e-government services vary at different levels. It identifies 27 influencing factors. In total, 13 of these factors influence adoption at the information level; 13 at the two-way communication level; 25 at the transactional level; and 16 at the political participation level. Auxiliary facilities, connectedness, corruption avoidance, transparency and fairness, customer support and forced adoption, not commonly discussed as influencing factors for e-government adoption in the extant literature, have been revealed in this study.

Research limitations/implications
This study uses qualitative research and rather than generalization, the focus is explicitly on obtaining an in-depth understanding. Although the sampling used is sufficient for the purpose of this study and allows reasonable conclusions to be drawn; however, it cannot be considered representative of a vast country like India. Academicians and information systems researchers can use these findings for further research.

Practical implications
This study advances the understanding of e-government adoption. The findings have potential implications for public administrators and policymakers in successfully designing, developing and implementing e-government services at different maturity levels.

Originality/value
Existing e-government adoption theories are of limited scope and do not capture and specify the complete essence of citizens’ adoption characteristics at different levels of e-government services. Hence, a theoretical gap exists, which this study aims to fill.
Organization culture types and the replication of transferred human resource management practices in multinational subsidiaries in Nigeria
Authors: Oseghale Raphael Oriaghe , Pepple Dennis , Ifere Simeon Emezana , Amaugo Amarachi Ngozi 
Published: December 2022

PurposeGiven that institutional and cultural factors affect the transfer of HRM practices between multinational companies (MNCs) and their subsidiaries, the paper set out to investigate the explanatory mechanism for the replication of transferred HRM practices and the factors likely to influence the choice of transfer mechanisms.Design/methodology/approachUsing an exploratory qualitative approach, 40 interviews were conducted with senior managers and employees in two MNC subsidiaries located in the alcoholic beverage and oil industries in Nigeria.FindingsThe findings suggest that organizational culture (OC) was the mechanism for MNC HRM replication and inhibition. In addition to explaining the mechanisms for HRM practice replication, the authors developed a conceptual framework to explain how clan and hierarchical OC influence the extent to which human resource (HR) practices are replicated or inhibited and how institutional and cultural factors influence the choice of OC.Originality/valueThe study uncovered that MNCs deploy hierarchical OC to oversee the replication of transferred practices. Interestingly, the authors found that institutional and cultural environments were key factors that influenced the choice of mechanism for overseeing the replication of HR practices. The conceptual framework can help managers of MNCs to understand how to replicate transferred HRM practices in developing countries.