bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Chlorofluoroacetamide-Based Covalent Inhibitors for SARS-CoV-2 3CL Protease
Authors: Hirose Yuya , Shindo Naoya , Mori Makiko , Onitsuka Satsuki , Isogai Hikaru , Hamada Rui , Hiramoto Tadanari , Ochi Jinta , Takahashi Daisuke , Ueda Tadashi , Caaveiro Jose M.M. , Yoshida Yuya , Ohdo Shigehiro , Matsunaga Naoya , Toba Shinsuke , Sasaki Michihito , Orba Yasuko , Sawa Hirofumi , Sato Akihiko , Kawanishi Eiji , Ojida Akio 
Published: June 2022

AbstractThe pandemic of coronavirus disease 2019 (COVID-19) has urgently necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The 3C-like protease (3CLpro) is a promising target for COVID-19 treatment. Here, we report the new class of covalent inhibitors for 3CLpro possessing chlorofluoroacetamide (CFA) as a cysteine reactive warhead. Based on the aza-peptide scaffold, we synthesized the series of CFA derivatives in enantiopure form and evaluated their biochemical efficiencies. The data revealed that 8a (YH-6) with R configuration at the CFA unit strongly blocks the SARS-CoV-2 replication in the infected cells and this potency is comparable to that of nirmatrelvir. The X-ray structural analysis shows that 8a (YH-6) forms a covalent bond with Cys145 at the catalytic center of 3CLpro. The strong antiviral activity and sufficient pharmacokinetics property of 8a (YH-6) suggest its potential as a lead compound for treatment of COVID-19.
Global emergence of resistance to fluconazole and voriconazole in Candida parapsilosis in tertiary hospitals in Spain during the COVID-19 pandemic
Authors: Zaragoza Oscar , Alcázar-Fuoli Laura , Trevijano-Contador Nuria , Torres-Cano Alba , Carballo-González Cristina , Puig-Asensio Mireia , Martín-Gómez María Teresa , Jiménez-Martínez Emilio , Romero Daniel , Nuvials Francesc Xavier , Olmos-Arenas Roberto , Moretó-Castellsagué María Clara , Fernández-Delgado Lucía , Rodríguez-Sevilla Graciela , Aguilar-Sánchez María-Mercedes , Ayats-Ardite Josefina , Ardanuy-Tisaire Carmen , Sanchez-Romero Isabel , Muñoz-Algarra María , Merino-Amador Paloma , González-Romo Fernando , Megías-Lobón Gregoria , García-Campos Jose Angel , Ángeles Mantecón-Vallejo María , Durán-Valle Maria Teresa , Fraile-Torres Arturo Manuel , Roiz-Mesones María Pía , Lara-Plaza Isabel , de Ayala Ana Perez , Simón-Sacristán María , Collazos-Blanco Ana , Nebreda-Mayoral Teresa , March-Roselló Gabriel 
Published: June 2022

ABSTRACTBackgroundCandida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins and is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole non-susceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last two years at the Spanish Mycology Reference Laboratory.MethodsYeast were identified by molecular biology and antifungal susceptibility testing was performed using EUCAST protocol. ERG11 gene was sequenced to identify resistance mechanisms, and typification was carried out by microsatellite analysis.ResultsWe examined the susceptibility profile of the C. parapsilosis isolates available at our Reference Laboratory since 2000 (around 1,300 strains). During the last two years, the number of isolates with acquired resistance to fluconazole and voriconazole has increased in at least eight different Spanish hospitals. Typification of the isolates revealed that some prevalent clones had spread through several hospitals of the same geographical region. One of these clones was found in hospitals from the region of Catalonia, another in hospitals from Madrid and Burgos, and two other different genotypes from Santander.ConclusionsOur data suggests that the epidemiological situation caused by the COVID-19 pandemic might have induced a selection of fluconazole-resistant C. parapsilosis isolates that were already present at the hospitals. Further measures must be taken to avoid the establishment of clinical outbreaks that could threaten the life of infected patients.
Does place connectivity moderate the association between concentrated disadvantage and COVID-19 fatality in the United States?
Authors: Jing Fengrui , Li Zhenlong , Qiao Shan , Zhang Jiajia , Olatosi Bankole , Li Xiaoming 
Published: June 2022

AbstractConcentrated disadvantaged areas have been disproportionately affected by COVID-19 outbreak in the United States (US). Meanwhile, highly connected areas may contribute to higher human movement, leading to higher COVID-19 cases and deaths. This study examined whether place connectivity moderated the association between concentrated disadvantage and COVID-19 fatality. Using COVID-19 fatality over four time periods, we performed mixed-effect negative binomial regressions to examine the association between concentrated disadvantage, Twitter-based place connectivity, and county-level COVID-19 fatality, considering potential state-level variations. Results revealed that concentrated disadvantage was significantly associated with an increased COVID-19 fatality. More importantly, moderation analysis suggested that place connectivity significantly exacerbated the harmful effect of concentrated disadvantage on COVID-19 fatality, and this significant moderation effect increased over time. In response to COVID-19 and other future infectious disease outbreaks, policymakers are encouraged to focus on the disadvantaged areas that are highly connected to provide additional pharmacological and non-pharmacological intervention policies.
The T cell epitope landscape of SARS-CoV-2 variants of concern
Authors: Tennøe Simen , Gheorghe Marius , Stratford Richard , Clancy Trevor 
Published: June 2022

ABSTRACTDuring the COVID-19 pandemic, several SARS-CoV-2 variants of concern (VOC) emerged, bringing with them varying degrees of health and socioeconomic burdens. In particular, the Omicron VOC displayed distinct features of increased transmissibility accompanied by anti-genic drift in the spike protein that partially circumvented the ability of pre-existing anti-body responses in the global population to neutralize the virus. However, T cell immunity has remained robust throughout all the different VOC transmission waves and has emerged as a critically important correlate of protection against SARS-CoV-2 and it’s VOCs, in both vaccinated and infected individuals. Therefore, as SARS-CoV-2 VOCs continue to evolve, it is crucial that we characterize the correlates of protection and the potential for immune escape for both B cell and T cell human immunity in the population. Generating the insights necessary to understand T cell immunity, experimentally, for the global human population is at present critical but a time consuming, expensive, and laborious process. Further, it is not feasible to generate global or universal insights into T cell immunity in an actionable time frame for potential future emerging VOCs. However, using computational means we can expedite and provide early insights into the correlates of T cell protection. In this study, we generated and reveal insights on the T cell epitope landscape for the five main SARS-CoV-2 VOCs observed to date. We demonstrated here using a unique AI prediction platform, a strong concordance in global T cell protection across all mutated peptides for each VOC. This was modeled using the most frequent HLA alleles in the human population and covers the most common HLA haplotypes in the human population. The AI resource generated through this computational study and associated insights may guide the development of T cell vaccines and diagnostics that are even more robust against current and future VOCs, and their emerging subvariants.
SARS-CoV-2 S protein antagonizes type I interferon downstream signal pathway through interacting and attenuating phosphorylation of STAT1/STAT2
Authors: Ni Wenjia , Li Wenkang , Cai Zeng , Guo Wenhua , Zheng Yucheng , Zhao Yongliang , Wu Zhixuan , Liang Simeng , Ye Jiajie , Guo Xiao , Zhou Dan , Wu Xiaoying , Zhou Chanjuan , Tang Mingliang , Chen Yu , Lan Ke , Zhou Li , Xu Ke 
Published: June 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may keep patients in a clinically asymptomatic state by blocking cellular innate antiviral immunity, but the molecular mechanism remains unclear. Here, we screened the viral proteins of SARS-CoV-2 and found that the spike (S) protein inhibits the activation of interferon-stimulated genes (ISGs) and even reduces the expression of these genes to below background values. Mechanistically, the S protein interacted with STAT1, STAT2, and IRF9 and impedes the phosphorylation of STAT1/STAT2, thus preventing the formation of the interferon-stimulating gene factor 3 (ISGF3) complex and inhibiting the downstream production of Interferon-stimulated genes (ISGs). Remarkably, we also have found that the inhibitory mechanism of the S protein was conservative among SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Truncation studies indicated that the most conserved S2 domain played a major inhibitory role. Altogether, our findings unveil a new mechanism by which SARS-CoV-2 S protein attenuated the host’s antiviral immune response and provide new insights into the pathogenic mechanism of coronavirus.
Improving the efficacy and accessibility of intracranial viral vector delivery in non-human primates
Authors: Griggs Devon J , Garcia Aaron D. , Au Wing Yun , Ojemann William K. S. , Johnson Andrew Graham , Ting Jonathan T. , Buffalo Elizabeth A. , Yazdan-Shahmorad Azadeh 
Published: June 2022

AbstractNon-human primates (NHPs) are precious resources for cutting edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing surgical preparation practices of convection-enhanced delivery (CED), which is an efficient viral vector infusion technique for large brains such as NHPs’. Here we present both real-time and next-day MRI data of CED in the brains of ten NHPs, and we present a quantitative, inexpensive, and practical bench-side model of the in vivo CED data. Our bench-side model is composed of food coloring infused into a transparent agar phantom, and the spread of infusion is optically monitored over time. Our proposed method approximates CED infusions into the cortex, thalamus, medial temporal lobe and caudate nucleus of NHPs, confirmed by MRI data acquired with either gadolinium-based or manganese-based contrast agents co-infused with optogenetic viral vectors. These methods and data serve to guide researchers and surgical team members in key surgical preparations for intracranial viral delivery using CED in NHPs, and thus improve expression targeting and efficacy and, as a result, reduce surgical risks.
Prevalence of Neutralizing Antibodies against Adenoviruses types -C5, -D26 and -B35 used in vaccination platforms, in Healthy and HIV-Infected Adults and Children from Burkina Faso and Chad
Authors: Ouoba Aline Raissa , Paris Océane , Adawaye Chatté , Dzomo Guy Takoudjou , Fouda Abderrazzack Adoum , Kania Dramane , Diarra Amidou , Kallo Zenaba Abdramane , Traore Isidore Tiandiogo , Sirima Sodiomon Bienvenu , Tuaillon Edouard , Van de Perre Philippe , Kremer Eric J. , Daniel Mennechet Franck Jean 
Published: June 2022

AbstractVaccines derived from human adenoviruses (HAdV) are currently being used and trialed against numerous infectious agents. However, pre-existing humoral immunity can impair vaccines efficacy and safety. Strategies to circumvent this immunity often involve the use of vectors with lower seroprevalence. We evaluated HAdV-C5, HAdV-D26 and HAdV-B35 seroprevalence from healthy and HIV-infected populations from Burkina Faso and Chad. Seroprevalence for HAdV-C5 was high and comparable between countries (54%-66%), and the highest in the HIV-infected groups from sub-Saharan regions (∼90%). However, compared to France (4%), seroprevalence for HAdV-D26 was significantly higher in sub- Saharan groups (∼47%). By contrast, HAdV-B35 seroprevalence was low for all groups tested. We also found that HAdV-D26 complexed with immunoglobulins induced strong activation of dendritic cells in vitro. Our study fills gaps in the epidemiological data needed to optimize HAdV-derived vaccines in sub-Saharan regions, and highlights the necessity to better adjust vaccination strategies in Africa.Article summary lineHAdVs Seroprevalence in Burkina Faso and Chad
An examination of relationship between cognitive biases and customer satisfaction: empirical evidence from Thailand
Authors: Homsud Noppanon , Rompho Nopadol 
Published: June 2022

PurposeThis study aims to determine the effect of cognitive biases, that is, anchoring effect, illusion of control, and endowment effect, on customer satisfaction.Design/methodology/approachAn experimental design was applied using 524 undergraduate students as participants. A three-way ANOVA was employed for data analysis.FindingsPositive relationships were found between cognitive biases and customer satisfaction. However, no such relationships were found between the interactions of various types of cognitive bias and customer satisfaction, except the interaction between illusion of control and endowment effect.Research limitations/implicationsThis study focuses only on three types of cognitive biases; thus, it cannot be generalized to other such systematic patterns.Practical implicationsMarketers can introduce cognitive bias when implementing marketing campaigns to boost customer satisfaction.Originality/valueThis study expands the knowledge boundary by addressing the impact of the interaction between various aspects of cognitive bias that drive customer satisfaction.
Perceived barriers towards whole grain consumption among the Malaysian adult population: findings from a theory-based qualitative study
Authors: Ugunesh Danaselvam , Siau Ching Sin , Mohd Sanip Mohd Nor Ahmar Bin , Koo Hui Chin 
Published: June 2022

PurposeThe paper aimed to explore the factors leading to lower rates of whole grain consumption amongst the Malaysian adult population according to the Reasoned Action Approach (RAA) model.Design/methodology/approachThis paper employed a qualitative approach to explore the factors that influence whole grain consumption. Individual interviews were conducted online amongst Malaysian adults aged 18 years and above who purchase groceries and are responsible for food preparation at home. Interviews were transcribed verbatim and analysed thematically using the NVivo version 12 software.FindingsA majority of the respondents (N = 30; mean age = 39.2 years old) were females (n = 19, 63.3%) and lived in urban areas (n = 23, 76.7%). Even though over 86.7% of respondents (n = 26) had consumed whole grain products, a majority of them had inadequate knowledge surrounding whole grains (n = 25, 83.3%). Predominant barriers to whole grain consumption were perceived cost (n = 30, 100%), dislikes towards the sensory aspects of whole grain foods (n = 28, 93.3%), inadequate knowledge in identifying whole grains in foods (n = 25, 83.3%), poor awareness (n = 25, 83.3%), lack of knowledge in preparation of whole grain foods (n = 25, 83.3%), a wide variety of other tasty cuisine alternatives in Malaysia (n = 25, 83.3%), low availability and accessibility of whole grain products (n = 18, 60%), cultural eating behaviours (n = 17, 56.7%) and family influence (n = 16, 53.3%). Besides that, having a longer preparation time, restrictive diets and social influences were minor barriers.Research limitations/implicationsThis study addresses the barriers that should be highlighted in future health educational interventions, and presents a challenge to the food industry to develop whole grain foods which are easily accepted by consumers.Originality/valueThis is the first paper to outline the factors associated with poor consumption of whole grains amongst the Malaysian adult population.
Does public capital expenditure reduce energy poverty? Evidence from Nigeria
Authors: Dimnwobi Stephen Kelechi , Onuoha Favour Chidinma , Uzoechina Benedict Ikemefuna , Ekesiobi Chukwunonso Sylvester , Nwokoye Ebele Stella 
Published: June 2022

PurposeGiven the ever-growing fiscal commitments of Nigeria and her chequered history of electricity generation and distribution, the fortunes of the energy sector in the country have been affected by the prevalence of energy poverty. Government policies such as public capital expenditure (PCE) present a crucial option for reducing energy poverty in Nigeria, providing the purpose of this study.Design/methodology/approachTo investigate the relationship between government capital spending and five distinct energy poverty proxies, this research applies the Bayer–Hanck cointegration system and the auto-regressive distributed lag (ARDL) bound test.FindingsThe findings indicate that public capital spending in Nigeria worsens energy poverty by reducing access to electricity, urban electrification, renewable energy consumption and renewable electricity generation, with a positive but insignificant influence on rural electrification.Originality/valueThis inquiry presents a pioneering investigation of the nexus between PCE and energy poverty in Nigeria. Also, aside from the variables of energy poverty adopted by existing studies, this study incorporates renewable energy consumption and renewable electricity output with implications for energy poverty and sustainable development.
Localization in the United Arab Emirates: a study of stereotypes, organizational socialization, employability and work outcomes
Authors: Karam Abdulaziz , Ashill Nick , Jayashree Payyazhi , Lindsay Valerie 
Published: June 2022

PurposeThis paper aims to extend the traditional conceptualization of localization, which has largely focused on recruitment, by examining “employability” and “retention” as crucial determinants of localization success.Design/methodology/approachUsing survey data from local (Emirati) employees in private sector organizations in the United Arab Emirates (UAE), the authors develop a holistic model of localization and test the relationships between stereotypes, organizational socialization, employability and retention outcomes, using Smart-PLS.FindingsAmong the main findings are the significant influence of stereotypes on organizational socialization (OS) experiences of Emirati employees, with a negative relationship between “work ethics stereotypes” and perceptions of OS experiences. Strong evidence is also found for the indirect effects of OS experiences on retention of Emirati employees, mediated by employability.Research limitations/implicationsThis study contributes to the literature on localization by examining the relationships between key variables not examined together in previous research. In terms of limitations, the cross-sectional nature of the study prevents the identification of direction of causality among these relationships. Since employee integration, as part of localization efforts, is a gradual process, future research should include longitudinal studies.Practical implicationsEmployability has emerged as a significant challenge for organizations and governments working to implement successful localization initiatives. This study’s findings highlight several opportunities for organizational and governmental policy interventions to support successful localization.Originality/valueThe authors’ holistic model extends localization literature by providing evidence for the role of stereotypes and employability as key constructs to be examined along with OS experiences and retention.
Mixed methods evaluation on village neighborhood social cohesiveness and quality of life
Authors: Hou Su-I , Santis Esteban , Eskamani Anna V. , Holmes Khristen 
Published: June 2022

Purpose
The “Village” model has become an emerging, community-based, social initiative to help older adults age in place. This study aims to examine neighborhood social cohesion (NSC), or social connectedness and quality of life, from the perspective of village members.

Design/methodology/approach
A mixed-method evaluation was used to examine two Florida villages, a master-planned village (FV1) and a diverse neighborhood village (FV2). Both are full members of the National Village to Village Network.

Findings
The quantitative and qualitative data provided complementary and deeper understanding. Quantitative findings showed that FV1 members scored higher at NSC, and qualitative findings further confirmed that village program social activities were critical to building connections, especially for those who have lost loved ones and were single.

Research limitations/implications
Findings should be interpreted considering the predominantly white racial makeup and affluence of village participants.

Practical implications
Findings point to the importance of NSC as older adults age and suggest that programs should prioritize activities that strengthen social connectiveness.

Originality/value
This is one of the first mixed-methods evaluations examining NSC and quality of life among village participants.
A computational approach from design to degradation of additively manufactured scaffold for bone tissue engineering application
Authors: Kumar Mohit , Mohol Shubham Shankar , Sharma Varun 
Published: June 2022

Purpose
This paper aims to develop a computational approach to analyze the mechanical behavior, perfusion bioreactor test and degradation of the designed scaffolds. Five types of pore architecture scaffolds have been made using a computer-aided designed tool and fabricated through fused deposition modeling.

Design/methodology/approach
Compressive structural analysis has been performed using the finite element method to forecast the mechanical performance of the scaffolds. Also, the experimental study was done to validate the simulation outcomes. A computational fluid dynamic analysis was performed to ascertain the fluid pressure distribution, velocity profile, wall shear stress, strain rate and permeability of scaffolds. The interconnected pore architecture of the scaffolds plays a crucial role in enhancing the mechanical properties and fluid flow characteristics.

Findings
The scaffolds with continuous vertical support columns resulted in better strength because they provide better ways to transfer the load. The pore architecture of the scaffold plays a significant role in the path of fluid flow. Scaffolds with regular interconnected pore architecture showed better accessibility of the fluid. The degradation analysis showed that the degradation rate is dependent on the architecture of the scaffolds because of different surface area to volume ratios.

Originality/value
The simulation results provide a straightforward prediction of the scaffold suitability in terms of mechanical strength, perfusion and degradation behavior.

Graphical abstract
The importance of systemizing managerial support to reduce HR’s workload and maximize its corporate contributions
Authors: Yadegari Debi 
Published: June 2022

Purpose
The purpose of this paper is to explain the importance of systemizing managerial support to reduce the strain on human resource (HR) and maximize corporate contributions.

Design/methodology/approach
The author draws upon 20 years of experience in the fields of law and HR as well as data from 17 different publications.

Findings
Building a high-performing employer brand and workplace culture starts by better supporting managers as they navigate modern employee’s wants, needs and goals.

Originality/value
By systematizing how we train, engage and consistently aid managers as they navigate these new workplace expectations, companies reduce turnover, improve productivity and enhance happiness and well-being, and with these benefits, drive down HR time spent mitigating these daily hurdles. HR leaders can focus on broader and more meaningful corporate contributions with that time won back.