bluuebunny/crossref_metadata_2025 huggingface dataset:
The T cell epitope landscape of SARS-CoV-2 variants of concern
Authors: Tennøe Simen , Gheorghe Marius , Stratford Richard , Clancy Trevor
Published: June 2022

During 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

Severe 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

Non-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

Vaccines 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 line

HAdVs Seroprevalence in Burkina Faso and Chad
Determining the Class and Subclass of a Monoclonal Antibody by Ouchterlony Double-Diffusion Assays
Authors: Greenfield Edward A.
Published: June 2022

Originally, the Ouchterlony double-diffusion assays were the most common method for determining the class and subclass of a monoclonal antibody, and they still are useful, particularly when only a few assays will be performed. A sample of hybridoma tissue culture supernatant is placed in a well in a bed of agar, and class- and subclass-specific antisera are placed in other wells in a ring surrounding the test antibody. As the antibodies diffuse into the agar, they meet and multimeric immune complexes precipitate to form a visible “precipitin line.”
Synthesis, crystal structure and determination of the pK
a value of 2,6-dimethoxycyclohexa-2,5-diene-1,4-dione 1-[2-(quinolin-8-yl)hydrazone]
Authors: Kachi-Terajima Chihiro , Inaba Yuto , Tsuruga Kaito
Published: June 2022

The azo-coupling reaction between 8-aminoquinoline and 3,5-dimethoxyphenol produces 2,6-dimethoxycyclohexa-2,5-diene-1,4-dione 1-[2-(quinolin-8-yl)hydrazone], C17H15N3O3. Crystallization from methanol and strong alkaline solutions produced nonsolvated and solvated crystals, respectively. The crystal structure analysis and 1H NMR spectroscopy studies revealed that the compound exists only as the hydrazone form. A UV–Vis spectroscopic titration study revealed that the hydrazone compound has a relatively high pK
a value of 10.0.
Two-dimensional rare-earth-metal coordination polymers based on biphenyl-3,3′,5,5′-tetracarboxylic acid displaying luminescence
Authors: Zhou Juan , Zhang Xinlei , Zi Wenwen , Zhou Lian
Published: June 2022

Two coordination polymers were rationally designed and successfully constructed using the rigid multicarboxylic acid ligand biphenyl-3,3′,5,5′-tetracarboxylic acid (H4BPTC) and rare earth metal ions (Eu3+ and Ho3+) under solvothermal conditions. The compounds are poly[[tetra-μ2-acetato-bis(μ6-biphenyl-3,3′,5,5′-tetracarboxylato)tetrakis(dimethylacetamide)tetraeuropium(III)] dimethylacetamide disolvate dihydrate], {[Eu4(C16H6O8)2(C2H3O2)4(C4H9NO)4]·2C4H9NO·2H2O}
n
, and poly[[tetra-μ2-acetato-bis(μ6-biphenyl-3,3′,5,5′-tetracarboxylato)tetrakis(dimethylacetamide)tetraholmium(III)] pentahydrate], {[Ho4(C16H6O8)2(C2H3O2)4(C4H9NO)4]·5H2O}
n
, Single-crystal X-ray diffraction analysis reveals that both polymers possess a two-dimensional structure and they also display good thermal stability up to ca 280 °C and photoluminescence with an orange–red light emission.
Crystal structures of methyl 3,5-dimethylbenzoate, 3,5-bis(bromomethyl)phenyl acetate and 5-hydroxybenzene-1,3-dicarbaldehyde
Authors: Ebersbach Ben , Seichter Wilhelm , Mazik Monika
Published: June 2022

The crystal structures of the title compounds, methyl 3,5-dimethylbenzoate (C10H12O2; 1), 3,5-bis(bromomethyl)phenyl acetate (C10H10Br2O2; 2) and 5-hydroxybenzene-1,3-dicarbaldehyde (C8H6O3; 3) were determined by single-crystal X-ray analysis. The crystals of 1 are composed of strands of C—H...O=C bonded molecules, which are further arranged into layers. As a result of the presence of two bromomethyl substituents in compound 2, molecular dimers formed by crystallographically non-equivalent molecules are connected to structurally different two-dimensional aggregates in which the bromine atoms participate in Br...Br bonds of type I and type II. In the case of compound 3, which possesses three donor/acceptor substituents, the molecular association in the crystal creates a close three-dimensional network comprising Caryl—H...Ohydroxy, Cformyl—H...Oformyl and O—H...Oformyl bonds.
Sequence-assignment validation in cryo-EM models with checkMySequence
Authors: Chojnowski Grzegorz
Published: June 2022

The availability of new artificial intelligence-based protein-structure-prediction tools has radically changed the way that cryo-EM maps are interpreted, but it has not eliminated the challenges of map interpretation faced by a microscopist. Models will continue to be locally rebuilt and refined using interactive tools. This inevitably results in occasional errors, among which register shifts remain one of the most difficult to identify and correct. Here, checkMySequence, a fast, fully automated and parameter-free method for detecting register shifts in protein models built into cryo-EM maps, is introduced. It is shown that the method can assist model building in cases where poorer map resolution hinders visual interpretation. It is also shown that checkMySequence could have helped to avoid a widely discussed sequence-register error in a model of SARS-CoV-2 RNA-dependent RNA polymerase that was originally detected thanks to a visual residue-by-residue inspection by members of the structural biology community. The software is freely available at https://gitlab.com/gchojnowski/checkmysequence.
An examination of relationship between cognitive biases and customer satisfaction: empirical evidence from Thailand
Authors: Homsud Noppanon , Rompho Nopadol
Published: June 2022

Purpose

This study aims to determine the effect of cognitive biases, that is, anchoring effect, illusion of control, and endowment effect, on customer satisfaction.

Design/methodology/approach

An experimental design was applied using 524 undergraduate students as participants. A three-way ANOVA was employed for data analysis.

Findings

Positive 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/implications

This study focuses only on three types of cognitive biases; thus, it cannot be generalized to other such systematic patterns.

Practical implications

Marketers can introduce cognitive bias when implementing marketing campaigns to boost customer satisfaction.

Originality/value

This 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

Purpose

The 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/approach

This 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.

Findings

A 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/implications

This 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/value

This 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

Purpose

Given 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/approach

To 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.

Findings

The 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/value

This 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

Purpose

This 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/approach

Using 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.

Findings

Among 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/implications

This 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 implications

Employability 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/value

The 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.
Habitat availability alters the relative risk of a bovine tuberculosis breakdown in the aftermath of a commercial forest clearfell disturbance
Authors: Murphy Kilian J. , Morera‐Pujol Virginia , Ryan Eoin , Byrne Andrew W. , Breslin Philip , Ciuti Simone
Published: June 2022

Human modification of landscapes and associated disturbances may facilitate the emergence and spread of zoonotic diseases. Policy‐makers need better understanding of the link between anthropogenic disturbances and wildlife disease hosts at the interface of human society and the natural environment, for example agriculture, forestry and aquaculture. Empirical research is strongly needed for the control of novel zoonoses which might emerge, as well as the management of existing zoonoses with significant economic repercussions such as bovine tuberculosis (bTB).

We aimed to examine the link between ecological disturbance and relative bTB risk using Ireland as a case study. We analysed clearfell forestry operations and assessed bTB breakdowns within cattle farms across different spatio‐temporal scales over multiple years, examining how ecological conditions may modulate this relationship using conditional logistic regression models.

We found a significant effect of the interaction between the extent of clearfell forestry removed and the extent of natural grassland and mixed forestry present on relative bTB risk. This interaction was dynamic, leading to an increase or decrease of the relative bTB risk depending on where (between 2 and 6 km from the farm) and when (between 0 and 36 months prior to the bTB outbreak) the clearfell operations occurred.

Our study provides empirical evidence of the link between mechanised forestry operations and fluctuating relative bTB risk in cattle farms, although the mechanism behind it is yet to be elucidated. Given our data, we hypothesise that wildlife hosts may abandon the area subjected to clearfell when disturbance is highest (during active operations and shortly afterward) but are subsequently attracted back to the site as they regenerate, potentially affecting the contact rates with livestock and thus, relative bTB risk.

Synthesis and applications. Our analysis demonstrates that landscape modification is correlated with a change in relative bovine tuberculosis (bTB) risk that is dynamic in time and space. Understanding that the effect of landscape change is transient allows managers to understand the risk for neighbouring farms and inform policy accordingly. Landscape‐level studies are necessary to unveil subtle‐ecological processes, shifting research and management efforts away from cattle herd‐centric policy and toward macroecological surveillance of wildlife hosts and longitudinal assessment of bTB risk.
Does functional diversity in interfirm collaborations lead to innovation diversity? Firm‐level evidence from the Australian food industry*
Authors: Azeem Muhammad Masood , Fazal‐e‐Hasan Syed , Gutiérrez Leopoldo , Baker Derek
Published: June 2022

Research on the collaboration–innovation nexus emphasises that collaborations and innovation are multidimensional. Despite this emphasis, there is limited evidence on how firms' collaborative diversity affects their innovation diversity. This paper addresses this gap by examining the relationships between (i) a firm's functional diversity of collaboration (FDC) and innovation diversity, and (ii) innovation diversity and firm growth. We used longitudinal data from 738 Australian food firms, and our findings suggest that the positive relationship between FDC and innovation diversity reaches a point of saturation, beyond which additional collaboration negatively influences firms' innovation diversity. Moreover, innovation diversity depends on the motives behind alliance formation and the firm's focus on innovation. Finally, the association between innovation diversity and growth performance is heterogeneous across firms' conditional growth rate distribution.
The socio‐economic gradient of cognitive test scores: evidence from two cohorts of Irish children
Authors: Madden David
Published: June 2022

There is a well‐established socio‐economic gradient in child cognitive test scores. This gradient emerges at early ages, with some evidence that it can widen as children age. We investigate this phenomenon with two longitudinal cohorts of Irish children who take such tests at ages ranging from 9 months to 17 years, using maternal education and equivalised income as our measure of socio‐economic resources. The gradient is observed from the age of 3 with tentative evidence that it widens as children get older. We have evidence on a wide range of tests and there is some evidence that the gradient is slightly stronger for tests involving crystalised as opposed to fluid intelligence. Exploiting the longitudinal nature of the data, we also investigate mobility across the distribution of test scores, with some evidence that such mobility is less among poorer children, which raises the disturbing possibility that such children could become trapped in low achievement.
Lipid variability and risk of microvascular complications in Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: A post hoc analysis
Authors: Hukportie Daniel Nyarko , Li Fu‐Rong , Zhou Rui , Zheng Jia‐Zhen , Wu Xiao‐Xiang , Zou Meng‐Chen , Wu Xian‐Bo
Published: June 2022

Background

Greater lipid variability may cause adverse health events among diabetic patients. We aimed to examine the effect of lipid variability on the risk of diabetic microvascular outcomes among type 2 diabetes mellitus patients.

Methods

We assessed the association between visit‐to‐visit variability (measured by variability independent of mean) in high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein‐cholesterol (LDL), triglyceride, and remnant cholesterol (RC) measurements among participants involved in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and the risk of incident microvascular outcomes, including nephropathy, neuropathy, and retinopathy. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders.

Results

There were 2400, 2470, and 2468 cases of nephropathy, neuropathy, and retinopathy during a follow‐up period of 22 600, 21 542, and 26 701 person‐years, respectively. Higher levels of HDL, triglyceride, and RC variability were associated with an increased risk of incident nephropathy and neuropathy. Compared with the lowest quartile, the fully adjusted HRs (95% CI) for the highest quartile of HDL, triglyceride, and RC variability for nephropathy risk were 1.57 (1.22, 2.01), 1.50 (1.18, 1.92), and 1.40 (1.09, 1.80), respectively; and for neuropathy, the corresponding risks were 1.36 (1.05, 1.75), 1.47 (1.14, 1.91), and 1.35 (1.04, 1.74), respectively. Null association was observed between LDL variability and all microvascular complications. Additionally, all associations of variability in the other lipids with retinopathy risk were null.

Conclusion

Among individuals with type 2 diabetes mellitus, HDL, triglyceride, and RC variability were associated with increased risks of nephropathy and neuropathy but not retinopathy. Trial registration: ClinicalTrials.gov., no. NCT00000620.
Identification and quantification of chimeric sequencing reads in a highly multiplexed RAD‐seq protocol
Authors: Martin Cerezo Maria Luisa , Raval Rohan , de Haro Reyes Bernardo , Kucka Marek , Chan Frank Yingguang , Bryk Jarosław
Published: June 2022

Highly multiplexed approaches have become common in genomic studies. They have improved the cost‐effectiveness of genotyping hundreds of individuals using combinatorially barcoded adapters. These strategies, however, can potentially misassigned reads to incorrect samples. Here, we used a modified quaddRAD protocol to analyse the occurrence of index hopping and PCR chimeras in a series of experiments with up to 100 multiplexed samples per sequencing lane (639 samples in total). We created two types of sequencing libraries: four libraries of type A, where PCRs were run on individual samples before multiplexing, and three libraries of type B, where PCRs were run on pooled samples. We used fixed pairs of inner barcodes to identify chimeric reads. Type B libraries show a higher percentage of misassigned reads (1.15%) than type A libraries (0.65%). We also quantify the commonly undetectable chimeric sequences that occur whenever multiplexed groups of samples with different outer barcodes are sequenced together on a single flow cell. Our results suggest that these types of chimeric sequences represent up to 1.56% and 1.29% of reads in type A and B libraries, respectively. We also show that increasing the number of mismatches allowed for barcode rescue to above 2 dramatically increases the number of recovered chimeric reads. We provide recommendations for developing highly multiplexed RAD‐seq protocols and analysing the resulting data to minimize the generation of chimeric sequences, allowing their quantification and a finer control on the number of PCR cycles necessary to generate enough input DNA for library preparation.
Two‐year efficacy of SNK01 plus pembrolizumab for non‐small cell lung cancer: Expanded observations from a phase I/IIa randomized controlled trial
Authors: Park Hyung Jun , Kim Yong Man , Jung Jae Seob , Ji Wonjun , Lee Jae Cheol , Choi Chang‐Min
Published: June 2022

Background

A previous trial showed that autologous ex‐vivo expanded NK cell (SNK01) treatment combined with pembrolizumab showed better efficacy than pembrolizumab monotherapy in advanced non‐small cell lung cancer (NSCLC). This study was a 2‐year follow‐up of that previous study to determine the long‐term efficacy of the combination treatment.

Methods

This trial included 20 patients with advanced NSCLC with a PD‐L1 tumor proportion score of 1% or greater who failed prior to front‐line platinum‐based therapy. The patients received pembrolizumab with low‐dose SNK01 (2 × 109 cells/dose) or high‐dose SNK01 (4 × 109 cells/dose), or pembrolizumab monotherapy. The primary study endpoint was overall survival (OS), and the secondary endpoint was progression‐free survival (PFS).

Results

Two patients were excluded following serious adverse events. Among the 11 patients who died, five were from the NK groups (41.6%, n = 5/12), and six received pembrolizumab monotherapy (100%, n = 6/6). The estimated 2‐year survival rate was 58.3% versus 16.7% (pembrolizumab plus SNK01 vs. pembrolizumab monotherapy). The hazard ratio of pembrolizumab plus SNK01 compared with pembrolizumab monotherapy was 0.32 (95% CI: 0.1, 1.08, p‐value: 0.066). Although the median PFS was significantly higher in the pembrolizumab plus SNK01 group than in the pembrolizumab alone group, OS and PFS did not differ statistically between patients who received low doses of NK cells and those who received high doses of NK cells.

Conclusions

Autologous NK cells can enhance the long‐term OS and PFS for NSCLC. A larger study is needed to confirm this result.

Clinical Research Information Service number: KCT0003463.
Young transgenic hMTH1 mice are protected against dietary fat‐induced metabolic stress—implications for enhanced longevity
Authors: Marcon Francesca , Meschini Roberta , Iorio Egidio , Palleschi Simonetta , De Luca Gabriele , Siniscalchi Ester , Conti Luigi , Chirico Mattea , Pisanu Maria Elena , De Battistis Francesca , Rossi Barbara , Minoprio Anna , Giuliani Alessandro , Karran Peter , Bignami Margherita
Published: June 2022

hMTH1 protects against mutation during oxidative stress. It degrades 8‐oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS‐induced senescence, and its overexpression in hMTH1‐Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high‐fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild‐type (WT) and hMTH1‐Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD‐induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD‐induced effects were less severe and hMTH1‐Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non‐growing, differentiated tissues of adult mice. In hMTH1‐Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity.
The prevalence for the risk of serious infection in hypothermic infants ≤ 60 days: A systematic review
Authors: Delaney Kristen M. , Bober Jacqueline G. , Koos Jessica A. , Hom Jeffrey
Published: June 2022

Background

Temperature abnormalities in infants may be a sign of a serious infection (SI) and there is literature regarding the workup of the febrile infant to help guide management. The prevalence of SIs in hypothermic infants and the development of established guidelines for this population has not been established. Our primary objective was to determine the prevalence of SI in hypothermic infants who are 60 days old or younger presenting to the emergency department (ED). In addition, we calculated the prevalence of SI by organ system and identified its microorganism.

Methods

We performed a systematic review by searching the literature in Medline, Embase, Web of Science, and CINAHL. We limited our search to infants ≤ 60 days with a rectal temperature <36.5°C who presented to the ED. We defined SI as bacteremia, urinary tract infection (UTI), meningitis, herpes simplex virus infections, or pneumonia. We calculated the prevalence of SI. Quality of studies and bias was assessed using QUADAS‐2. Our study was registered with PROSPERO, 2020 CRD42020153477.

Results

We identified 1242 articles from our initial search in December 2019 followed by a second search in February 2021 to capture any recent publications. We identified four studies meeting our inclusion criteria. We estimated the prevalence of SI as 4.86% (95% confidence Interval [CI] 1.97–8.82) for infants ≤ 60 days old. In a subgroup analysis of infants ≤ 28 days (n = 16/374), we estimated the prevalence of SI as 5.15 (95% CI 0.95–12.0). The most common source for SI was UTI, with a prevalence of 2.16% (95% CI 1.18–3.60).

Conclusion

The overall prevalence of SI was 4.86% in hypothermic young infants ≤ 60 days old presenting to the ED. Infants ≤ 28 days had a slightly higher prevalence of 5.15%. The most common source for serious bacterial infection was UTI.
Permanent pacing in a very long‐term follow‐up after orthotopic heart transplantation: A matter of when or why?
Authors: Alyaydin Emyal , Pogoda Christian , Dell'Aquila Angelo , Frommeyer Gerrit , Sindermann Juergen R. , Reinecke Holger , Tuleta Izabela
Published: June 2022

Background

Orthotopic heart transplantation (OHT) is associated with a high incidence of conduction disturbances (CD) leading to permanent pacemaker (PPM) implantation. However, the improved posttransplant survival raises the question about the pacemaker dependence (PD) in a prolonged follow‐up.

Hypothesis

The prevalence of PPM in OHT is high but not all patients are PD in a very long‐term follow‐up. Device implantation has no prognostic relevance.

Methods

We performed a retrospective analysis of patient medical records focusing on device interrogation data at the most recent follow‐up.

Results

The study population consisted of 183 patients with a mean follow‐up of 15.0 ± 6.8 years. One‐fourth of the patients had undergone PPM implantation (n = 49, 26.8%). Among these, two‐thirds were PD at last follow‐up (n = 32, 65.3%). PPM was more often in biatrial OHT and cardiac allograft vasculopathy (OR 3.0, 95% CI 1.26–7.29, p = .013 and OR 2.0, 95% CI 1.03–3.87, p = .041, respectively). Early sinus node dysfunction (SND) was the most persistent CD. PPM was associated with a poorer outcome in OHT (HR 1.9, 95% CI 1.06–3.46, p = .031) and a higher rate of fatal septicemia (HR 5.1, 95% CI 1.41–18.14, p = .013).

Conclusions

One‐fourth of the OHT recipients develop CD requiring PPM implantation, although one‐third among these are not PD in follow‐up. Early SND is associated with a higher rate of PD. PPM is associated with an inferior prognosis.
“What is Our City Doing for Us?”: Placing Collective Care into Atlanta’s Post‐Public Housing Movements
Authors: Rodriguez Akira Drake
Published: June 2022

Throughout the 20th century, housing movements in Atlanta were anchored by public housing tenant associations and a politics that materially and spatially addressed intersectional issues of discrimination in employment, welfare, education, and housing. I argue the strategies and outcomes of these movements collectivised, embedded, and placed Anneli Anttonen and Jorma Sipilä’s “care capital”—or an expansion of resources for care—in bell hooks’ “homeplaces”, for those marginalised both in social welfare policies and urban politics. Following the loss of over 7,000 public housing units in Atlanta, tenant associations’ care politics and the residents served were displaced and disembedded from the revitalised city. Using archival data, semi‐structured individual and group interviews, and observation of tenant organising meetings, this work examines how care politics are materially and spatially situated across housing movement geographies through Black resistance strategies to collectivise and embed care capital for a broader public.
A comparative review of the epidemiology of mental disorders in Australia and India
Authors: Pai Nagesh , Vella Shae‐Leigh , Castle David
Published: June 2022

Mental illness and substance use disorders have been increasing worldwide. Mental illness has a significant impact upon the lives of the individual as well as their loved ones. Mental disorders are known to result in a high level of disability. This article provides a comparative review of the epidemiology of mental disorders in Australia and India, summarizing and comparing prevalence rates in both countries based upon available data. Overall, it is evident that Australia has higher prevalence rates of mental disorders than India, across most diagnostic groups. Australia has the highest prevalence of anxiety disorders whereas India has the highest prevalence of substance use disorders; including tobacco use disorders. The next most prevalent mental disorders in India are depressive disorders. However, there are demographic parameters such as gender and age as well as service‐provision differences across the countries that need to be factored into any interpretation of the data. There are also problems associated with different diagnostic instruments with language and cultural nuances that may impact comparisons. We suggest that a joint epidemiological survey between the two countries would help better understand and delineate the key similarities pertaining to the epidemiology of mental disorders in Australia and India. This will in turn assist with the development of policy and treatment of mental disorders.
The archaeological and scientific analysis of blue‐decorated ceramics in the Tang and Song dynasties
Authors: Zhang Yun , Pollard A. Mark
Published: June 2022

This paper reviews studies of Tang and Song blue‐and‐white porcelains, both archaeologically and scientifically, based on published data, and compares blue‐and‐white withsancai, which represents the earliest use of cobalt pigment in Chinese ceramics. Thirty‐nine Tang blue‐and‐white wares and seven Song wares have been excavated from city sites, kilns, a tomb, a shipwreck, and pagodas. These findings identify Tang blue‐and‐white as export ware related to the Maritime Silk Road or suggest it was produced for international merchants and visitors in China for daily use or personal collection. Also, the results reflected the connection with Buddhist culture. All Tang and Song blue‐and‐white are vessels and the motifs on them are plants, insects, a child, geometric and combination patterns. Palmette and lozenge motifs show the influence of Middle Eastern taste. Additionally, we reanalyse and discuss the previous scientific evidence of Tang and Song blue‐and‐white, including body, glaze, and cobalt pigment to reveal the origin of materials and technology of Tang blue‐and‐white porcelain. The raw pigment of Tang blue‐and‐white was possibly inherited fromsancai, probably from the Middle East, and the biscuit body and high‐fired clear lime glaze were provided by white porcelain. Song blue‐and‐white may utilise native cobalt ore, which possibly was from Zhejiang.
Clostridial panophthalmitis – An unusual case of localised malignant oedema in Merino lambs associated withClostridium chauvoei
Authors: Moloney BJ , Evers JV
Published: June 2022

The authors report an unusual case ofClostridium chauvoeicausing severe panophthalmitis in Merino lambs. More than half of the lambs affected survived, which is unusual for clostridial disease; however, there have been reports in humans that the mortality risk for ocular gas gangrene is lower than when other body parts are affected. A combination of factors in this case included environmental contamination (specific to a particular paddock), genetics predisposing to entropion (lambs born of maiden 2‐year‐old ewes with some inbreeding), the practice of manually everting eyelids for the entropion and vaccination strategies.C. chauvoeiwas cultured in pure growth from the eye of a lamb affected by severe panophthalmitis. Histopathology was consistent with severe acute infection, and microscopic sections showed Gram‐positive organisms associated with the inflammatory response in the eye. In the acutely affected animal examined there were no signs that the lesions were long‐standing. Animals that recovered had one or both eyes destroyed. This report describes that malignant oedema in sheep due toC. chauvoeican manifest as acute and severe panophthalmitis. The case fatality rate of lambs with panophthalmitis was less than 50%, lower than normally occurs for clostridial diseases. Clostridial vaccination of the ewes may have provided a low level of protection in reducing the case fatality rate in the affected lambs as well localisation of the infection from the blood–ocular barrier.
Spatio‐temporal patterns in the abundance of active terrestrial leeches in a Malaysian rainforest
Authors: Jambari Asrulsani , Nakabayashi Miyabi , Numata Shinya , Hosaka Tetsuro
Published: June 2022

Terrestrial leeches can be useful tools for wildlife assessment. However, limited information is available on their fundamental ecology, such as temporal activity patterns and habitat preferences in tropical rainforests. Therefore, this study aimed to reveal the temporal (diel and seasonal) and spatial patterns of active leech abundance and identify abiotic and biotic factors (abundance of potential hosts) involved in shaping the abundance patterns at Endau Rompin National Park (ERNP) in southern peninsular Malaysia. We conducted surveys on the relative abundance of active brown leeches (Haemadipsa sp.) at 99 sampling points repeatedly over 18 months, and installed camera traps to quantify the relative abundance of wildlife and humans at 24 of the sampling points. Although no consistent diel and seasonal patterns were observed in leech relative abundance, the abundance showed a strong positive correlation with air humidity at the sampling time. Similarly, the spatial pattern of leech relative abundance was positively correlated with air humidity and proximity to the nearest river at the sampling sites. The mean relative abundance of active leeches was 2–3 times higher on trails than off trails. However, there was no significant correlation between relative abundance of leeches and that of wildlife and humans on trails. Therefore, leech abundance was largely determined by air humidity rather than host abundance, suggesting the difficulty of its use as an indicator of wildlife abundance at fine spatial scales. Instead, utilizing the sensitivity of leeches to drier environments, terrestrial leeches could be useful as an indicator of intact tropical rainforests.

Abstract in Malay is available with online material.