bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA-II-dependent neuroimmune changes in Group A Streptococcal Necrotizing Fasciitis
Authors: Ambigapathy Ganesh , Satpati Abhijit , Mukundan Santhosh , Nagamoto-Combs Kumi , Combs Colin K. , Nookala Suba 
Published: July 2022

AbstractIntroductionStreptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild uncomplicated skin infections (impetigo, erysipelas, cellulitis) to highly morbid and rapidly invasive life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA-Class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that while the host immune mediators regulate the immune responses against peripheral GAS infections, these interactions may simultaneously trigger neuropathology and, in some cases, induce persistent alterations in the glial phenotypes. Here we studied the consequences of peripheral GAS skin infection on the brain in an HLA-II transgenic mouse model of GAS NF with and without treatment with an antibiotic, clindamycin (CLN).MethodsMice expressing the human HLA-II DR3 (DR3) or the HLA-II DR4 (DR4) allele were divided into three groups: i) uninfected controls, ii) subcutaneously infected with a clinical GAS strain isolated from a patient with GAS NF, and iii) GAS infected with CLN treatment (10mg/kg/5 days, intraperitoneal). The groups were monitored for 15 days post-infection. Skin GAS burden and lesion area, splenic and hippocampal mRNA levels of inflammatory markers, and immunohistochemical changes in hippocampal GFAP and Iba-1 immunoreactivity were assessed.ResultsSkin GAS burden and hippocampal mRNA levels of inflammatory markers S100A8/A9, IL-1β, IL-33, inflammasome-related caspase-1 (Casp1), and NLRP6 were elevated in infected DR3 but not DR4 mice. The levels of these markers were significantly reduced following CLN treatment in DR3 mice. Although GAS was not detectable in the brain, astrocyte and microglia activation were evident from increased GFAP and Iba-1 mRNA levels respectively, in DR3 and DR4 mice. However, CLN treatment significantly reduced GFAP immunoreactivity in DR3 mice and not DR4 mice.ConclusionOur data suggest a skin-brain axis during GAS NF demonstrating that peripherally induced pathological conditions regulate neuroimmune and gliotic events, and CLN may attenuate peripheral infection and subsequent neuroimmune changes in an HLA-II-dependent manner.
Polymorphisms Predicting Phylogeny in Hepatitis B Virus (HBV)
Authors: Lourenço José , McNaughton Anna L , Pley Caitlin , Obolski Uri , Gupta Sunetra , Matthews Philippa C 
Published: July 2022

ABSTRACTHepatitis B viruses (HBV) are compact viruses with circular genomes of ∼3.2kb in length. Four genes (HBx, Core, Surface and Polymerase) generating seven products are encoded on overlapping reading frames. Ten HBV genotypes have been characterised (A-J), which may account for differences in transmission, outcomes of infection, and treatment response. However, HBV genotyping is rarely undertaken, and sequencing remains inaccessible in many settings. We used a machine learning approach based on random forest algorithms (RFA) to assess which amino acid (aa) sites in the genome are most informative for determining genotype. We downloaded 5496 genome-length HBV sequences from a public database, excluding recombinant sequences, regions with conserved indels, and genotypes I/J. Each gene was separately translated into aa, and the proteins concatenated into a single sequence (length 1614aa). Using RFA, we searched for aa sites predictive of genotype, and assessed co-variation among the sites with a Mutual Information (MI)-based method. We were able to discriminate confidently between genotypes A-H using 10 aa sites. 5/10 sites were identified in Polymerase (Pol), of which 4/5 were in the spacer domain, and a single site in reverse transcriptase. A further 4/10 sites were located in Surface protein, and a single site in HBx. There were no informative sites in Core. Properties of the aa were generally not conserved between genotypes at informative sites. Co-variation analysis identified 55 pairs of highly-linked sites. Three RFA-identified sites were represented across all pairs (two sites in spacer, and one in HBx). Residues that co-vary with these sites are concentrated in the small HBV surface gene. We also observe a cluster of sites adjacent to the Surface promoter region that co-vary with a spacer residue. Overall, we have shown that RFA analysis is a powerful tool for identifying aa sites that predict HBV lineage, with an unexpectedly high number of such sites in the spacer domain, which has conventionally been viewed as unimportant for structure or function. Our results improve ease of genotype prediction from limited regions of HBV sequence, and may have implications for understanding HBV evolution and the role of the spacer domain.
Understanding the dynamic relation between wastewater SARS-CoV-2 signal and clinical metrics throughout the pandemic
Authors: Hegazy Nada , Cowan Aaron , D’Aoust Patrick M. , Mercier Élisabeth , Towhid Syeda Tasneem , Jia Jian-Jun , Wan Shen , Zhang Zhihao , Kabir Md Pervez , Fang Wanting , Graber Tyson E. , MacKenzie Alex E. , Guilherme Stéphanie , Delatolla Robert 
Published: July 2022

AbstractWastewater surveillance (WWS) of SARS-CoV-2 was proven to be a reliable and complementary tool for population-wide monitoring of COVID-19 disease incidence but was not as rigorously explored as an indicator for disease burden throughout the pandemic. Prior to global mass immunization campaigns and during the spread of the wildtype COVID-19 and the Alpha variant of concern (VOC), viral measurement of SARS-CoV-2 in wastewater was a leading indicator for both COVID-19 incidence and disease burden in communities. As the two-dose vaccination rates escalated during the spread of the Delta VOC in Jul. 2021 through Dec. 2021, relations weakened between wastewater signal and community COVID-19 disease incidence and maintained a strong relationship with clinical metrics indicative of disease burden (new hospital admissions, ICU admissions, and deaths). Further, with the onset of the vaccine-resistant Omicron BA.1 VOC in Dec. 2021 through Mar. 2022, wastewater again became a strong indicator of both disease incidence and burden during a period of limited natural immunization (no recent infection), vaccine escape, and waned vaccine effectiveness. Lastly, with the populations regaining enhanced natural and vaccination immunization shortly prior to the onset of the Omicron BA.2 VOC in mid-Mar 2022, wastewater is shown to be a strong indicator for both disease incidence and burden. Hospitalization-to-wastewater ratio is further shown to be a good indicator of VOC virulence when widespread clinical testing is limited. In the future, WWS is expected to show moderate indication of incidence and strong indication of disease burden in the community during future potential seasonal vaccination campaigns.HighlightsNeed to elucidate interpretation of CoV-2 WWS for seasonal vaccination campaigns.WWS to incidence relation weakens with peak natural and vaccination immunization.WWS to hospitalization remains strong with natural and vaccination immunization.WWS as indicator of hospitalization during future seasonal vaccination campaigns.WWS/hospitalization as indicator of VOC virulence with limited clinical testing.
Dual targeting factors are required for LXG toxin export by the bacterial type VIIb secretion system
Authors: Klein Timothy A. , Grebenc Dirk W. , Shah Prakhar Y. , McArthur Owen D. , Dickson Brandon H. , Surette Michael G. , Kim Youngchang , Whitney John C. 
Published: July 2022

ABSTRACTBacterial type VIIb secretion systems (T7SSb) are multi-subunit integral membrane protein complexes found in Firmicutes that play a role in both bacterial competition and virulence by secreting toxic effector proteins. The majority of characterized T7SSb effectors adopt a polymorphic domain architecture consisting of a conserved N-terminal Leu-X-Gly (LXG) domain and a variable C-terminal toxin domain. Recent work has started to reveal the diversity of toxic activities exhibited by LXG effectors; however, little is known about how these proteins are recruited to the T7SSb apparatus. In this work, we sought to characterize genes encoding domains of unknown function (DUFs) 3130 and 3958, which frequently co-occur with LXG effector-encoding genes. Using coimmunoprecipitation-mass spectrometry analyses,in vitrocopurification experiments and T7SSb secretion assays, we find that representative members of these protein families form heteromeric complexes with their cognate LXG domain and in doing so, function as targeting factors that promote effector export. Additionally, an X-ray crystal structure of a representative DUF3958 protein, combined with predictive modelling of DUF3130 using AlphaFold2, reveals structural similarity between these protein families and the ubiquitous WXG100 family of T7SS effectors. Interestingly, we identify a conserved FxxxD motif within DUF3130 that is reminiscent of the YxxxD/E “export arm” found in Mycobacterial T7SSa substrates and mutation of this motif abrogates LXG effector secretion. Overall, our data experimentally link previously uncharacterized bacterial DUFs to type VIIb secretion and reveal a molecular signature required for LXG effector export.Significance statementType VIIb secretion systems (T7SSb) are protein secretion machines used by an array of Gram-positive bacterial genera includingStaphylococcus, Streptococcus, Bacillus, andEnterococcus. These bacteria use the T7SSb to facilitate interbacterial killing and pathogenesis through the secretion of toxins. Although the modes of toxicity for a number of these toxins have been investigated, the mechanisms by which they are recognized and secreted by T7SSb remains poorly understood. The significance of this work is the discovery of two new protein families, termed Lap1 and Lap2, that directly interact with these toxins and are required for their secretion. Overall, Lap1 and Lap2 represent two widespread families of proteins that function as targeting factors that participate in T7SSb-dependent toxin release from Gram-positive bacteria.
A Spectroscopic Approach to Unravel the Local Conformations of G-quadruplex Using CD-active Fluorescent Base Analogues
Authors: Jose Davis , Michael Miya Mary , Bentsen Christopher , Rosenblum Brandon , Zelaya Adriana 
Published: July 2022

ABSTRACTThe formation of a stable G-quadruplex (GQ) can inhibit the elevated telomerase activity that is common in most cancers. The global structure and the thermal stability of the GQs are usually evaluated by spectroscopic methods and thermal denaturation properties. However, most biochemical processes involving GQs might require local conformational changes at the guanine tetrad (G4) level. These local conformational changes of individual G4 layers during protein and drug interactions have not yet been explored in detail. In this study we monitored the local conformations of individual G4 layers in GQs using 6-methylisoxanthopterine (6MI) chromophores, which are circular dichroism (CD)-active fluorescent base analogues of guanine, as local conformational probes. A synthetic, tetra-molecular, parallel GQ with site-specifically positioned 6MI monomers or dimers was used as the experimental construct. Analytical ultracentrifugation studies and gel electrophoretic studies showed that properly positioned 6MI monomers and dimers could form stable GQs with CD-active fluorescent G4 layers. The local conformation of individual fluorescent G4 layers in the GQ structure was then tracked by monitoring the absorbance, fluorescence intensity, thermal melting, fluorescence quenching and CD changes of the incorporated probes. Overall, these studies showed that site-specifically incorporated fluorescent base analogues could be used as probes to monitor the local conformational changes of individual G4 layers of a GQ structure. This method can be applied to explore the details of small molecule-GQ interaction at the level of the individual G4 layers, which may prove useful in designing drugs to treat GQ-related genetic disorders, cancer and aging.
Patterns of inconsistency: a literature review of empirical studies on the multinationality–performance relationship
Authors: Schmuck Alice , Lagerström Katarina , Sallis James 
Published: July 2022

PurposeThis study aims to understand the performance implications of when a business internationalizes. Many managers take the performance implications of internationalization for granted. Whether seeking a broader customer base or cost reduction through cross-border outsourcing, the overwhelming belief is that internationalization leads to higher profits.Design/methodology/approachThis paper offers a systematic review, content analysis and cross-tabulation analysis of 115 empirical studies from over 40 major journals in management, strategy and international business between 1977 and 2021. Focusing on research settings, sample characteristics, underlying theoretical approaches, measurements of key variables and moderators influencing the multinationality and performance relationship, this study offers a detailed account of definitions and effects.FindingsThe findings of this study suggest a tenuous connection between internationalization and performance. No strain of research literature conclusively identifies a consistent direct path from internationalization to performance. The context specificity of the relationship makes general declarations impossible.Research limitations/implicationsFuture researchers should recognize that internationalization is a process taking different forms, with no specific dominant form. General declarations are misleading. The focus should be on the process of internationalization rather than on the outcome.Originality/valueThis study contributes to the international business literature by exploring reasons for the inconsistent results and lack of consensus. Through a detailed account of definitions and effects, this paper explores the lack of consensus as well as the identified shapes of the relationship.
Paving the way for industry 4.0 maturity of construction enterprises: a state of the art review
Authors: Das Priyadarshini , Perera Srinath , Senaratne Sepani , Osei-Kyei Robert 
Published: July 2022

PurposeIndustry 4.0 is characterised by the exponential pace of technological innovations compelling organisations to transform or be displaced. Industry 4.0 transformation of construction enterprises lacks systematic guidance and notable earlier studies have utilised maturity models to map transformation of enterprises. This paper proposes a conceptual maturity model for construction enterprises for business scenarios leading to Industry 4.0.Design/methodology/approachThe requirements for designing maturity models, including comparison with existing models and scientifically documenting the design process, make Systematic Literature Reviews (SLR) appropriate. Two systematic literature reviews (SLRs) are conducted to shortlist a total of 95 papers, which are subjected to subsequent content analysis.FindingsThe first SLR identifies the following process categories as critical levers of industry 4.0 maturity; data management, people and culture, leadership and strategy, collaboration and communication, automation, innovation and change management. The second SLR ascertains that the existing maturity models in construction literature do not adequately correspond to Industry 4.0 business scenarios with limited emphasis on data management, automation, change management and innovation. The findings are assimilated to propose a conceptual Smart Modern Construction Enterprise Maturity Model (SMCeMM).Originality/valueThe paper systematises the transformation of construction enterprises in Industry 4.0 and leads to state-of-the-art development of Industry 4.0 and maturity model research in construction. The proposed conceptual model addressed both the demands of the construction industry as well as what is required to navigate Industry 4.0 better.
Respect for patients’ rights in health facilities: experiences of patients during the early period of the COVID-19 pandemic in Ghana
Authors: Golo Harrison Kwame 
Published: July 2022

Purpose
This paper aims to identify human rights violations of patients during the early periods of the COVID-19 pandemic in Ghana by investigating the experiences of people on how health-care professionals discharged their responsibilities during the time in question.

Design/methodology/approach
Explanatory design of the mixed methods approach was adopted, with the intention of collecting both quantitative and qualitative data sequentially, and then integrating the results at the interpretation stage. The approach enriched the quality of data collected as it offered the advantage of shedding light on the primary motivations and reasons for attitudes and behaviours and helped to provide an in-depth understanding of how individuals interpret the happenings around them and their experiences. Thus, although some amount of quantitative method was used in the data collection, the core of this paper is based on the qualitative interpretations.

Findings
The study reveals that health-care professionals, especially those in the Tema Metropolis, undermined certain fundamental human rights of patients during the early period of the COVID-19 pandemic. This includes failure to provide information to patients about treatment options and potential risks of medications; failure to seek the informed consent of patients before performing medical procedures; denial of access to medical files of patients for transfer; and inability or failure to provide medical ambulances services to patients on time.

Originality/value
Although many publications on human rights dimensions and health protective issues on COVID-19 pandemic are available on a global scale, still little information pertaining to experiences of individuals with health-care professionals during the early days of the COVID-19 pandemic, especially in Ghana through the lens of patient’s rights exists. This paper, therefore, fills an important gap in health-care management information, critical for policy decision-making processes regarding patient’s rights in times of pandemic control.
Business process management effectiveness and maturity through lean management practices: the Brazilian federal police experience
Authors: Klein Leander Luiz , de Pádua Silvia Inês Dallavalle , Gera Rajat , Vieira Kelmara Mendes , Dorion Eric Charles Henri 
Published: July 2022

Purpose
This study aims to examine the influence of lean management practices on organizational process effectiveness and maturity. The underlying assumption of this paper is that lean management practices may have a positive relation with the initiation and the adoption of a process management approach and be a first step to process management success.

Design/methodology/approach
Through a quantitative perspective, a survey was carried out in the Brazilian Federal Police with a valid sample of 991 participants. Data analysis was executed with confirmatory factor analysis and structural equations modeling.

Findings
Lean management practices have a positive influence on the Brazilian Federal Police process maturity and on process effectiveness. Process maturity has a positive impact on process effectiveness. The results extend the applicability of lean management practices in the public service scenario. The results will decrease the high failure rates in process transformation projects.

Research limitations/implications
The main limitation of this study is that the researchers could not maintain full control of the research respondents because the data collection was carried out online.

Practical implications
Considering a scenario of increased pressure to upgrade organizational decisional process in the public sector and to offer better public services, the lean management practices can effectively contribute to the development of strategies and actions that will enhance a more effective public service management reality.

Social implications
This study may contribute as a source of empirical data for future research in other national public organizations and may assist others to redesigning its strategies and actions to achieve excellence in decision-making, by adopting a more agile quality public service with less costs and waste.

Originality/value
New measurement and structural models were defined to analyze lean management practices in the public service as the predictors of organizational process maturity and effectiveness. The discussion on lean management practices, as a first step in process approach applicability, enhances a new process-based management perspective.
Need for cognitive closure and mobile personalization: a cluster analysis
Authors: Quach Xuan , Lee Seung Hwan (Mark) 
Published: July 2022

PurposeThis study aims to profile mobile users based on their need for cognitive closure (NFC) (preference for order, preference for predictability, discomfort with ambiguity, close-mindedness and decisiveness) and identify differences among the groups regarding their perceptions of personalized preferences and privacy concerns.Design/methodology/approachBased on the data from 285 participants, the authors seek to identify and profile unique consumer segments (mobile users) generated based on their NFC. Second, once the segments are established, the authors analyze how the segments differ across their personalized preferences and privacy concerns.FindingsThe data generated three distinct consumer segments: equivocal users, structured users and eclectic users. Across the segments, there were differences in their mobile personalization (experience, value and actions) and preference for information privacy (perceived risks and fabrication of personal information).Research limitations/implicationsUnited States (US)-based sample may restrict the generalizability of this research. Thus, future research should include participants from other geographic regions to increase external validity.Practical implicationsRetail managers can apply this knowledge to implement appropriate personalization strategies for these distinct target groups.Originality/valueSegmenting clusters based on differences in consumption trait (NFC) provides key insights to retailers looking to deliver personalized customer experience, particularly in a mobile shopping context.