bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood flow restriction added to usual care exercise in patients with early weight bearing restrictions after cartilage or meniscus repair in the knee joint: A feasibility study
Authors: Jakobsen Thomas Linding , Thorborg Kristian , Fisker Jakob , Kallemose Thomas , Bandholm Thomas
Published: April 2022

Purpose

In musculoskeletal rehabilitation, blood flow restriction – low load strength training (BFR-LLST) is theoretically indicated – as opposed to traditional heavy strength training – in patients who can or may not heavily load tissues healing from recent surgery. The main purpose was to examine the feasibility of BFR-LLST added to usual care exercise early after cartilage or meniscus repair in the knee joint.

Methods

We included 42 patients with cartilage (n=21) or meniscus repair (n=21) in the knee joint. They attended 9 weeks of BFR-LLST added to a usual care exercise at an outpatient rehabilitation center. Outcome measures were assessed at different time points from 4 (baseline) to 26 weeks postoperatively. They included: Adherence, harms, knee joint and thigh pain, perceived exertion, thigh circumference (muscle size proxy), isometric knee-extension strength, self-reported disability and quality of life.

Results

On average, patients with cartilage and meniscus repair performed >84 % of the total BFR-LLST supervised sessions. Thirty-eight patients reported 146 adverse events (e.g., dizziness) - none considered serious. A decrease in thigh circumference of the operated leg was not found in both groups from baseline to the end of the intervention period with no exacerbation of knee joint or quadriceps muscle pain.

Conclusions

BFR-LLST added to usual care exercise initiated early after cartilage or meniscus repair seems feasible and may prevent disuse thigh muscle atrophy during a period of weight bearing restrictions. Harms were reported, but no serious adverse events were found. Our findings are promising but need replication using RCT-design.
Predictors of all-cause mortality among patients hospitalized with influenza, respiratory syncytial virus, or SARS-CoV-2
Authors: Hamilton Mackenzie A. , Liu Ying , Calzavara Andrew , Sundaram Maria E. , Djebli Mohamed , Darvin Dariya , Baral Stefan , Kustra Rafal , Kwong Jeffrey C. , Mishra Sharmistha
Published: April 2022

Background

Shared and divergent predictors of clinical severity across respiratory viruses may support clinical and community responses in the context of a novel respiratory pathogen.

Methods

We conducted a retrospective cohort study to identify predictors of 30-day all-cause mortality following hospitalization with influenza (N=45,749; 2011-09 to 2019-05), respiratory syncytial virus (RSV; N=24,345; 2011-09 to 2019-04), or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; N=8,988; 2020-03 to 2020-12; pre-vaccine) using population-based health administrative data from Ontario, Canada. Multivariable modified Poisson regression was used to assess associations between potential predictors and mortality. We compared the direction, magnitude, and confidence intervals of risk ratios to identify shared and divergent predictors of mortality.

Results

3,186 (7.0%), 697 (2.9%) and 1,880 (20.9%) patients died within 30 days of hospital admission with influenza, RSV, and SARS-CoV-2, respectively. Shared predictors of increased mortality included: older age, male sex, residence in a long-term care home, and chronic kidney disease. Positive associations between age and mortality were largest for patients with SARS-CoV-2. Few comorbidities were associated with mortality among patients with SARS-CoV-2 as compared to those with influenza or RSV.

Conclusions

Our findings may help identify patients at greatest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local prevention and therapeutic strategies to communities with higher prevalence of risk factors.
Scanning Single Molecule Localization Microscopy (scanSMLM) for super-resolution optical volume imaging
Authors: Basumatary Jigmi , Baro Neptune , Joshi Prakash , Mondal Partha Pratim
Published: April 2022

Over the last decade, single molecule localization microscopy (SMLM) has developed into a set of powerful techniques that has improved spatial resolution over diffraction-limited microscopy and demonstrated the ability to resolve biological features at the very molecular scale. We introduce a single molecule based scanning SMLM (scanSMLM) system that enables rapid volume imaging. Using a standard widefield illumination, the system employs a scanning based detection 4f-sub-system suited for volume interrogation. The 4f system comprises of a combination of electrically-tunable lens and high NA detection objective lens. By rapidly changing the aperture (or equivalently the focus) of electrically-tunable lens (ETL) in a 4f detection system, the selectivity of axial (Z) plane can be achieved in the object plane, for which the corresponding image forms in the image/detector plane. So, in-principle one can scan the object volume by just changing the aperture of ETL. To carry out volume imaging, a cyclic scanning scheme is developed and compared with conventional scanning routinely used in SMLM. The scanning scheme serves the purpose of distributing photobleaching evenly by ensuring uniform dwell time on each frame for collecting data (single molecule events) throughout the specimen volume. With minimal change in the system hardware (requiring an addition of ETL lens and related hardware for step-voltage generation) in the existing SMLM system, volume scanning (along z-axis) can be achieved. To demonstrate, we imaged fluorescent beads embedded in a gel-matrix 3D block as a test sample. Subsequently, scanSMLM is employed to understand clustering of HA single molecules in a transfected cell (Influenza A disease model). The system for the first time enables visualization of HA distribution in a 3D cells that reveal its clustering across the cell volume. Critical biophysical parameters related to HA clusters (density, #HA/cluster and clustered fraction) are also determined.
VMHdm/cSF-1Neuronal Circuits Regulate Skeletal Muscle PGC1-α via the Sympathoadrenal Drive
Authors: Yoshida Takuya , Fujitani Mina , Farmer Scotlynn , Harada Ami , Shi Zhen , Lee Jenny J. , Tinajero Arely , Singha Ashish K. , Fujikawa Teppei
Published: April 2022

Objective

To adapt to metabolically challenging environments, the central nervous system (CNS) orchestrates metabolism of peripheral organs including skeletal muscle. The organ-communication between the CNS and skeletal muscle has been investigated, yet our understanding of the neuronal pathway from the CNS to skeletal muscle is still limited. Neurons in the dorsomedial and central parts of the ventromedial hypothalamic nucleus (VMHdm/c) expressing steroidogenic factor-1 (VMHdm/cSF-1neurons) are key for metabolic adaptations to exercise, including increased basal metabolic rate and skeletal muscle mass in mice. However, the mechanisms by which VMHdm/cSF-1neurons regulate skeletal muscle function remain unclear. Here, we show that VMHdm/cSF-1neurons increase the sympathoadrenal activity and regulate skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) in mice via multiple downstream nodes.

Methods

Optogenetics was used to specifically manipulate VMHdm/cSF-1neurons combined with genetically-engineered mice and surgical manipulation of the sympathoadrenal activity.

Results

Optogenetic activation of VMHdm/cSF-1neurons dramatically elevates mRNA levels of skeletal musclePgc-1α, which regulates a spectrum of skeletal muscle function including protein synthesis and metabolism. Mechanistically, the sympathoadrenal drive coupled with β2 adrenergic receptor (β2AdR) is essential for VMHdm/cSF-1neurons-mediated increases in skeletal muscle PGC1-α. Specifically, both adrenalectomy and β2AdR knockout block augmented skeletal muscle PGC1-α by VMHdm/cSF-1neuronal activation. Optogenetic functional mapping reveals that downstream nodes of VMHdm/cSF-1neurons are functionally redundant to increase circulating epinephrine and skeletal muscle PGC1-α.

Conclusions

Collectively, we propose that VMHdm/cSF-1neurons-skeletal muscle pathway, VMHdm/cSF-1neurons→multiple downstream nodes→the adrenal gland→skeletal muscle β2AdR, underlies augmented skeletal muscle function for metabolic adaptations.
Asexual male production by ZW recombination in Artemia parthenogenetica
Authors: Boyer Loreleï , Jabbour-Zahab Roula , Joncour Pauline , Glémin Sylvain , Haag Christoph R. , Lenormand Thomas
Published: April 2022

In some asexual species, parthenogenetic females occasionally produce males, which may strongly affect the evolution and maintenance of asexuality if they cross with related sexuals and transmit genes causing asexuality to their offspring (“contagious parthenogenesis”). How these males arise in the first place has remained enigmatic, especially in species with sex chromosomes. Here, we test the hypothesis that rare, asexually produced males of the crustacean Artemia parthenogenetica are produced by recombination between the Z and W sex chromosomes during non-clonal parthenogenesis, resulting in ZZ males through loss of heterozygosity at the sex determination locus. We used RAD-sequencing to compare asexual mothers with their male and female offspring. Markers on several sex-chromosome scaffolds indeed lost heterozygosity in all male but no female offspring, suggesting that they correspond to the sex-determining region. Other sex-chromosome scaffolds lost heterozygosity in only a part of the male offspring, consistent with recombination occurring at a variable location. Alternative hypotheses for the production of these males (such as partial or total hemizygosity of the Z) could be excluded. Rare males are thus produced because recombination is not entirely suppressed during parthenogenesis in A. parthenogenetica. This finding may contribute to explaining the maintenance of recombination in these asexuals.
A comparison of feature selection methodologies and learning algorithms in the development of a DNA methylation-based telomere length estimator
Authors: Doherty Trevor , Dempster Emma , Hannon Eilis , Mill Jonathan , Poulton Richie , Corcoran David , Sugden Karen , Williams Ben , Caspi Avshalom , Moffitt Terrie E , Delany Sarah Jane , Murphy Therese M.
Published: April 2022

The field of epigenomics holds great promise in understanding and treating disease with advances in machine learning (ML) and artificial intelligence being vitally important in this pursuit. Increasingly, research now utilises DNA methylation measures at cytosine-guanine dinucleotides (CpG) to detect disease and estimate biological traits such as aging. Given the high dimensionality of DNA methylation data, feature-selection techniques are commonly employed to reduce dimensionality and identify the most important subset of features. In this study, we test and compare a range of feature-selection methods and ML algorithms in the development of a novel DNA methylation-based telomere length (TL) estimator. We found that principal component analysis in advance of elastic net regression led to the overall best performing estimator when evaluated using a nested cross-validation analysis and two independent test cohorts. In contrast, the baseline model of elastic net regression with no prior feature reduction stage performed worst - suggesting a prior feature-selection stage may have important utility. The variance in performance across tested approaches shows that estimators are sensitive to data set heterogeneity and the development of an optimal DNA methylation-based estimator should benefit from the robust methodological approach used in this study. Additionally, we observed that different DNA methylation-based TL estimators, which have few common CpGs, are associated with many of the same biological entities. Moreover, our methodology which utilises a range of feature-selection approaches and ML algorithms could be applied to other biological markers and disease phenotypes, to examine their relationship with DNA methylation and predictive value.
SEACells: Inference of transcriptional and epigenomic cellular states from single-cell genomics data
Authors: Persad Sitara , Choo Zi-Ning , Dien Christine , Masilionis Ignas , Chaligné Ronan , Nawy Tal , Brown Chrysothemis C , Pe’er Itsik , Setty Manu , Pe’er Dana
Published: April 2022

Metacells are cell groupings derived from single-cell sequencing data that represent highly granular, distinct cell states. Here, we present single-cell aggregation of cell-states (SEACells), an algorithm for identifying metacells; overcoming the sparsity of single-cell data, while retaining heterogeneity obscured by traditional cell clustering. SEACells outperforms existing algorithms in identifying accurate, compact, and well-separated metacells in both RNA and ATAC modalities across datasets with discrete cell types and continuous trajectories. We demonstrate the use of SEACells to improve gene-peak associations, compute ATAC gene scores and measure gene accessibility in each metacell. Metacell-level analysis scales to large datasets and are particularly well suited for patient cohorts, including facilitation of data integration. We use our metacells to reveal expression dynamics and gradual reconfiguration of the chromatin landscape during hematopoietic differentiation, and to uniquely identify CD4 T cell differentiation and activation states associated with disease onset and severity in a COVID-19 patient cohort.
Integrative analysis of metabolite GWAS illuminates the molecular basis of pleiotropy and genetic correlation
Authors: Smith Courtney J. , Sinnott-Armstrong Nasa , Cichońska Anna , Julkunen Heli , Fauman Eric , Würtz Peter , Pritchard Jonathan K.
Published: April 2022

Pleiotropy and genetic correlation are widespread features in GWAS, but they are often difficult to interpret at the molecular level. Here, we perform GWAS of 16 metabolites clustered at the intersection of amino acid catabolism, glycolysis, and ketone body metabolism in a subset of UK Biobank. We utilize the well-documented biochemistry jointly impacting these metabolites to analyze pleiotropic effects in the context of their pathways. Among the 213 lead GWAS hits, we find a strong enrichment for genes encoding pathway-relevant enzymes and transporters. We demonstrate that the effect directions of variants acting on biology between metabolite pairs often contrast with those of upstream or downstream variants as well as the polygenic background. Thus, we find that these outlier variants often reflect biology local to the traits. Finally, we explore the implications for interpreting disease GWAS, underscoring the potential of unifying biochemistry with dense metabolomics data to understand the molecular basis of pleiotropy in complex traits and diseases.
Cardiac impairment in Long Covid 1-year post-SARS-CoV-2 infection
Authors: Roca-Fernández Adriana , Wamil Malgorzata , Telford Alison , Carapella Valentina , Borlotti Alessandra , Monteiro David , Thomaides-Brears Helena , Kelly Matthew D , Dennis Andrea , Banerjee Rajarshi , Robson Matthew D. , Brady Michael , Lip Gregory Y. H. , Bull Sacha , Heightman Melissa , Ntusi Ntobeko , Banerjee Amitava
Published: April 2022

Background

Long Covid is associated with multiple symptoms and impairment in multiple organs. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiac magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid.

Methods

534 individuals with Long Covid underwent baseline CMR (T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms and 330 were rescanned at 12.6 (IQR 11.4, 14.2) months if abnormal findings were reported at baseline. Symptoms, standardised questionnaires, and blood samples were collected at both timepoints. Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. A significant change over time was reported by comparison with 92 healthy controls.

Results

The technical success of this multiorgan assessment in non-acute settings was 99.1% at baseline, and 98.3% at follow up, with 99.6% and 98.8% for CMR respectively. Of individuals with Long Covid, 102/534 [19%] had cardiac impairment at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and low GLS were associated with cardiac impairment. Low LVEF at baseline was associated with persistent cardiac impairment at 12 months.

Conclusion

Cardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options.
Clinical Variables Correlate with Serum Neutralizing Antibody Titers after COVID-19 mRNA Vaccination in an Adult, US-based Population
Authors: Zhao Min , Slotkin Rebecca , Sheth Amar H. , Pischel Lauren , Kyriakides Tassos C. , Emu Brinda , McNamara Cynthia , Shi Qiaosu , Delgobbo Jaden , Xu Jin , Marhoffer Elizabeth , Mercer-Falkoff Aleagia , Holleck Jürgen , Ardito David , Sutton Richard E. , Gupta Shaili
Published: April 2022

Background

We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population.

Methods

Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively.

Results

After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19+ individuals (132-fold increase). Age >65 years (β=-0.94, p=0.001) and malignancy (β=-0.88, p=0.002) reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p=0.004); (β=-0.66, p=0.014)], diabetes mellitus [(β=-0.57, p=0.032); (β=-0.44, p=0.028)], and systemic steroid use [(β=-0.066, p=0.032); (β=-0.55, p=0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2, but the immune response decreased with malignancy (β =-0.68, p=0.03) and increased with prior COVID-19 (p-value < 0.0001).

Conclusion

Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Prior COVID-19 infection enhances the booster-dose response except in individuals with malignancy, suggesting a need for clinically guiding vaccine dosing regimens.

Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination. All subjects, irrespective of prior COVID infection, benefited from a third dose. Malignancy decreased response following third dose, suggesting the importance of clinically guided vaccine regimens.
A Miniaturized 3D-Printed Pressure Regulator (μPR) for Microfluidic Cell Culture Applications
Authors: Hsu Meng-Chun , Mansouri Mehran , Ahamed Nuzhet N.N. , Joshi Indranil M. , Ahmed Adeel , Borkholder David A. , Abhyankar Vinay V.
Published: April 2022

Controlled fluid flows are the hallmark feature of microfluidic culture systems and provide precise definition over the biophysical and biochemical microenvironment. Flow control is commonly achieved using displacement-based (e.g., syringe or peristaltic pumps) or pressure-based techniques. These methods offer complex flow capabilities but can be challenging to integrate into incubators or other confined environments due to their large form factors and accompanying peripheral equipment. Since many microfluidic cell culture studies use a single controlled flow rate to maintain or stimulate cells, a portable flow control platform that fits easily into an incubator will benefit the microfluidic community. Here, we demonstrate that a tunable, 3D printed micro pressure regulator (μPR), combined with a battery-powered miniature air pump, can operate as a stand-alone pneumatic flow control platform for microfluidic applications. We detail the design and fabrication of the μPR and demonstrate: i) a tunable outlet pressure range relevant for microfluidic applications (1-10 kPa), ii) highlight dynamic control in a microfluidic network, and iii) maintain human umbilical vein endothelial cells (HUVECs) in a multi-compartment membrane-based culture device under continuous flow conditions. We anticipate that our 3D-printed fabrication approach and open access designs will allow other laboratories to rapidly customize μPRs to support a broad range of applications.
Kinetic and Redox Characterization of KRAS G12C Inhibition
Authors: Huynh Minh V. , Parsonage Derek , Forshaw Tom E. , Chirasani Venkata R. , Hobbs G. Aaron , Wu Hanzhi , Lee Jingyun , Furdui Cristina M. , Poole Leslie B. , Campbell Sharon L.
Published: April 2022

The development of mutant-selective inhibitors for the KRASG12C allele has generated considerable excitement. These KRASG12C inhibitors covalently engage the mutant C12 thiol located within the phosphoryl binding loop of RAS, locking the KRASG12C protein in an inactive state. While clinical trials of these inhibitors have been promising, mechanistic questions regarding the reactivity of this thiol remain, motivating the present studies. Measurement of the C12 thiol pKa by NMR and an independent biochemical assay found a depressed pKa (relative to free cysteine) of 7.6 consistent with its susceptibility to chemical ligation. Using a novel and validated fluorescent KRASY137W variant amenable to stopped-flow spectroscopy, we characterized the kinetics of KRASG12C fluorescence changes upon addition of ARS-853 or AMG 510, noting that ARS-853 addition at 5°C elicited both a rapid first phase (attributed to binding, yielding a Kd of 36.0 ± 0.7 μM), and a second, slower pH-dependent phase taken to represent covalent ligation. Consistent with the lower pKa of the C12 thiol, we found that reversible and irreversible oxidation of KRASG12C occurred readily both in vitro and in the cellular environment, preventing the covalent binding of ARS-853. Moreover, we found that oxidation of the KRASG12C thiol to sulfinic acid alters RAS conformation and dynamics to be more similar to KRASG12D in comparison to the unmodified protein, as assessed by molecular dynamics simulations. Taken together, these findings provide insight for future KRASG12C drug discovery efforts as well as identifying the occurrence of G12C oxidation with currently unknown biological ramifications.
Growth rate controls the sensitivity of gene regulatory circuits
Authors: Julou Thomas , Gervais Théo , de Groot Daan , van Nimwegen Erik
Published: April 2022

Unicellular organisms adapt to their changing environments by gene regulatory switches that sense chemical cues and induce specific target genes when the inducing signal is over a critical threshold. Using mathematical modeling we here show that, because growth rate sets the dilution rate of intracellular molecules, the sensitivity of gene regulatory switches automatically couples to growth rate, in a way that can be exploited by natural selection. We confirm the modeling predictions by experimentally demonstrating that, as nutrient quality is varied, the concentration of inducer required for activating thelacoperon inE. coliincreases quadratically with the population’s growth rate. Our theory further predicts that, when growth rate is instead modulated by translation inhibition, critical inducer levels are invariant, and we experimentally validate this prediction as well. Moreover, we establish that this growth-coupled sensitivity allows bacteria to implement concentration-dependent sugar preferences, in which a new carbon source is used only if its concentration is high enough to improve upon the current growth rate of the cells. Using microfluidics in combination with time-lapse microscopy, we validate experimentally that this strategy governs how mixtures of glucose and lactose are used inE. coliat single-cell level. Overall, growth-coupled sensitivity provides a general mechanism through which cells can ‘mute’ external signals in beneficial conditions when growth is fast, and become highly sensitive to alternative nutrients or stresses when growth is slow or arrested.
Linking cohort data and Welsh routine health records to investigate children at risk of delayed primary vaccination
Authors: Walton Suzanne , Cortina-Borja Mario , Dezateux Carol , Griffiths Lucy J , Tingay Karen , Akbari Ashley , Bandyopadhyay Amrita , Lyons Ronan A , Roberts Richard , Bedford Helen
Published: April 2022

Background

Delayed primary vaccination is one of the strongest predictors of subsequent incomplete immunisation. Identifying children at risk of such delay may enable targeting of interventions, thus decreasing vaccine preventable illness.

Objectives

To explore socio-demographic factors associated with delayed receipt of the Diphtheria, Tetanus and Pertussis (DTP) vaccine.

Methods

We included 1,782 children, born between 2000 and 2001, participating in the Millennium Cohort Study (MCS) and resident in Wales, whose parents gave consent for linkage to National Community Child Health Database records at the age seven years contact. We examined child, maternal, family and area characteristics associated with delayed receipt of the first dose of the DTP vaccine.

Results

98.6% received the first dose of DTP. The majority, 79.6% (n=1,429) received it on time (between 8 and 12 weeks of age), 14.2% (n=251) received it early (prior to 8 weeks of age) and 4.8% (n=79) were delayed (after 12 weeks of age); 1.4% (n=23) never received it. Delayed primary vaccination was more likely among children with older natural siblings (risk ratio 3.82, 95% confidence interval (1.97, 7.38)), children admitted to special/intensive care (3.15, (1.65, 5.99)), those whose birth weight was >4Kg (2.02, (1.09, 3.73)) and boys (1.53, (1.01, 2.31)). There was a reduced risk of delayed vaccination with increasing maternal age (0.73, (0.53, 1.00) per 5 year increase) and for babies born to graduate mothers (0.27, (0.08, 0.90)).

Conclusions

Although the majority of infants were vaccinated in a timely manner, identification of infants at increased risk of early or delayed vaccination will enable targeting of interventions to facilitate timely immunisation. This is to our knowledge the first study exploring individual level socio-demographic factors associated with delayed primary vaccination in the UK and demonstrates the benefits of linking cohort data to routinely-collected child health data.
Anatomy and Symbiosis of the digestive system of the vent shrimps Rimicaris exoculata and Rimicaris chacei revealed through imaging approaches
Authors: Guéganton Marion , Rouxel Ouafae , Durand Lucile , Cueff-Gauchard Valérie , Gayet Nicolas , Pradillon Florence , Cambon-Bonavita Marie-Anne
Published: April 2022

The shrimps Rimicaris exoculata and Rimicaris chacei are visually dominant fauna co-occurring at deep-sea hydrothermal sites of the Mid-Atlantic Ridge (MAR). Their co-existence was related to contrasted life-history traits, among which differences in their diet and reliance on chemoautotrophic symbionts at adult stage. Both shrimps are colonized by diversified chemosynthetic symbiotic microbial communities in their cephalothoracic cavity. Symbiotic association with bacteria was also evidenced in their digestive system, and the major lineages were identified through sequencing (Mycoplasmatales lineages mainly in the foregut and Deferribacteres lineages mainly in the midgut) but their clear distribution within each host species was not assessed. For the first time, we used Fluorescence in situ Hybridization (FISH) to visualize these lineages. Then, we described their association with digestive structures of both Rimicaris species. The aim was to identify possible differences between host species that could be related to their different life-history traits. For this purpose, we first developed specific FISH probes targeting Deferribacteres and Mycoplasmatales lineages identified in the digestive system of these shrimps. After signal specificity validation for each the new probe, we showed a partitioning of the bacterial lineages according to the digestive organ. Despite morphological differences between the foregut of R. exoculata and R. chacei that could be related to the adult diet, our FISH results showed overall similar distribution of digestive symbionts for the two host species. However, a more comprehensive study is needed with specimens at different life or molt stages to bring potentially host specific patterns out. Such comparative approach using FISH is now warranted thanks to our newly designed probes. These will be valuable tools to track symbiont lineages in the environment, allowing a better understanding of their relationship with their host along its life cycle, including acquisition mechanisms.
Serial macromolecular crystallography at ALBA Synchrotron Light Source
Authors: Martin-Garcia Jose M. , Botha Sabine , Hu Hao , Jernigan Rebecca , Castellví Albert , Lisova Stella , Gil Fernando , Calisto Barbara , Crespo Isidro , Roy-Chowdhury Shatabdi , Grieco Alice , Ketawala Gihan , Weierstall Uwe , Spence John , Fromme Petra , Zatsepin Nadia , Boer Dirk Roeland , Carpena Xavi
Published: April 2022

The increase in successful adaptations of serial crystallography at synchrotron radiation sources continues. To date, the number of serial synchrotron crystallography (SSX) experiments has grown exponentially, with over 40 experiments reported so far. In this work, we report the first SSX experiments with viscous jets conducted at ALBA beamline BL13-XALOC. Small crystals (15–30 µm) of five soluble proteins (lysozyme, proteinase K, phycocyanin, insulin and α-spectrin-SH3 domain) were suspended in lipidic cubic phase (LCP) and delivered to the X-ray beam with a high-viscosity injector developed at Arizona State University. Complete data sets were collected from all proteins and their high-resolution structures determined. The high quality of the diffraction data collected from all five samples, and the lack of specific radiation damage in the structures obtained in this study, confirm that the current capabilities at the beamline enables atomic resolution determination of protein structures from microcrystals as small as 15 µm using viscous jets at room temperature. Thus, BL13-XALOC can provide a feasible alternative to X-ray free-electron lasers when determining snapshots of macromolecular structures.
The structure of Synechococcus elongatus enolase reveals key aspects of phosphoenolpyruvate binding
Authors: González Javier M. , Martí-Arbona Ricardo , Chen Julian C.-H. , Unkefer Clifford J.
Published: April 2022

A structure–function characterization of Synechococcus elongatus enolase (SeEN) is presented, representing the first structural report on a cyanobacterial enolase. X-ray crystal structures of SeEN in its apoenzyme form and in complex with phosphoenolpyruvate are reported at 2.05 and 2.30 Å resolution, respectively. SeEN displays the typical fold of enolases, with a conformationally flexible loop that closes the active site upon substrate binding, assisted by two metal ions that stabilize the negatively charged groups. The enzyme exhibits a catalytic efficiency of 1.2 × 105 M
−1 s−1 for the dehydration of 2-phospho-D-glycerate, which is comparable to the kinetic parameters of related enzymes. These results expand the understanding of the biophysical features of these enzymes, broadening the toolbox for metabolic engineering applications.
Consumer segmentation and motives for choice of cultured meat in two Chinese cities: Shanghai and Chengdu
Authors: Wang Ou , Scrimgeour Frank
Published: April 2022

Purpose

The widespread dietary adoption of cultured meat could provide important benefits to animal welfare, the environment, food safety and security. This study examines consumer segmentation and consumer motives for choice of cultured meat in China.

Design/methodology/approach

The data were collected by means of a web-based questionnaire (n = 608) distributed in the two cites of Shanghai and Chengdu. Factor analysis, cluster analysis and path analysis were employed for data analysis.

Findings

Three consumer segments were identified with regard to the acceptance of cultured meat in China: Conservatives (25.7%), Acceptors (41.9%) and Pioneers (32.4%). Significant differences were recognised in age, household income, education and household size between the three consumer segments. The following meat choice motives (MCMs) have significant influences on Chinese participants’ attitudes and/or purchase intentions towards cultured meat: usually eat, environmental concern, societal concern, mood, purchase convenience and price.

Originality/value

This is the first study to develop a factorial construct of MCMs based on a previous theoretical model of food choice motives (FCMs) in China. The study contributes understanding of choice motives for cultured meat in a non-Western setting, particularly in China - the country consuming the largest quantity of pork. Further, this is the first study to recognise segments that are directly based on consumer attitudes and purchase intentions towards cultured meat. The findings of this study will help global producers and policymakers to create effective promotion strategies and policies for this innovative product in developing countries, particularly in China.
The effect of logistical immediacy on logistics service providers' (LSPs') business
Authors: Vivaldini Mauro
Published: April 2022

Purpose

This study discusses the influence of logistical immediacy on logistics service providers' (LSPs’) business. Specifically, its role in the face of the emerging business scenario (e-commerce, disruptive technologies, and new models of logistical services) is examined.

Design/methodology/approach

As logistical immediacy is a nascent topic, this study utilizes a systematic literature review focusing on academic articles from the last five years related to logistical outsourcing to understand the changes imposed by logistical immediacy on LSPs.

Findings

The impact of transformations arising from an increasingly digital virtual world (DVW) on LSPs is contextualized. A theoretical view of the factors affecting LSPs' shift towards more immediate operations is presented, and how logistical immediacy impacts LSPs is discussed. Finally, a research agenda is presented as the study's main contribution.

Research limitations/implications

Due to the timeframe chosen, the restriction to a single database (Scopus), the specific search terms used related to LSPs, and limiting the search parameters to operations management, some relevant work may have been overlooked.

Practical implications

The article help LSPs' and contracting companies' managers to understand the influence of the immediacy expected in logistics operations. Possible logistics services trends and how they may impact companies are discussed.

Originality/value

This is one of the first articles in the area of operations and supply chains that addresses the issue of logistical immediacy and its impact on LSPs.
Wax and wane: a case study of Flying Colours
Authors: Faridi Mohammad Rishad , Patni Arun , Ebad Ryhan , Patni Neelima
Published: April 2022

Learning outcomes

At the end of the case study discussion, students will able to state the importance of outsourcing with comparing pros and cons in business decision-making; review the value bestowed to the community in using sustainable raw material while at the same time conserving the ancient style of artwork particular to the area; discuss the utility of the products manufactured by “Flying Colours,” especially for the lockdown period which was because of the pandemic; and demonstrate and interpret the use of shark and mosquito bite matrix.

Case overview/synopsis

Arun Kumar Patni, 47, and his wife Neelima Patni, 43, are co-founders of Flying Colours, a start-up company based in Jaipur, in the state of Rajasthan, India. Their enterprise was engaged in the manufacturing and marketing of bird products and accessories, including bird feeders, bird houses, earthen water bowls, etc. In July 2020, post-lockdown, they were desperate to hire carpenters to restart their factory. However, COVID-19 posed a serious challenge, making it very difficult to replace their skilled carpenters, who had returned to their native places and had not come back. This disrupted production and order fulfilment. Keeping this situation in perspective in anticipation of the continuing pandemic crisis, Neelima was in favour of outsourcing basic production and designing the birdfeed decoration and artwork in-house. Meanwhile, Arun instead favoured continuing full in-house production as before, by hiring replacement carpenters. Yet for an in-house full-scale production, procuring raw material was a difficult task because of the lockdown. The situation had earlier taken a turn for the worse when Arun had advertised an exchange marketing policy to let customers return their old bird feeders for a 20% discount on a new one. This campaign was a huge success and resulted in a sales spike but unfortunately it caused a huge stock of returned products in their warehouse. Arun initially planned to repair and resell them as refurbished products. It now seemed impossible, because local carpenters demanded higher labour charges than the regular carpenters did. Flying Colours had provided skills workshops and hired external trainers to train unskilled carpenters prior to lockdown, so now all the training investment was in vain. Cash liquidity, sales, marketing, etc. were almost at a standstill.

Complexity academic level

This case particularly focuses on undergraduate-level students pursuing business or commerce programs, especially those studying core course: Entrepreneurial Strategic Management.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 3: Entrepreneurship.
Feeling the love? How consumer's political ideology shapes responses to AI financial service delivery
Authors: Riedel Aimee , Mulcahy Rory , Northey Gavin
Published: April 2022

Purpose

This paper aims, first, to examine artificial intelligence (AI) vs human delivery of financial advice; second, to examine the serial mediating roles of emotion and trust between AI use in the financial service industry and their impact upon marketing outcomes including word of mouth (WOM) and brand attitude; and third, to examine how political ideology moderates' consumers' reactions to AI financial service delivery.

Design/methodology/approach

A review of the extant literature is conducted, yielding seven hypotheses underpinned by affect-as-information theory. The hypotheses are tested via three online scenario-based experiments (n = 801) using Process Macro.

Findings

The results of the three experiments reveal consumers experience lower levels of positive emotions, specifically, affection, when financial advice is provided by AI in comparison to human employees. Secondly, across the three experiments, conservative consumers are shown to perceive somewhat similar levels of affection in financial advice provided by AI and human employees. Whereas liberal consumers perceive significantly lower levels of affection when serviced by AI in comparison to conservatives and human employee financial advice. Thirdly, results reveal affection and trust to be serial mediators which explain consumers' WOM and brand attitudes when financial services are provided by AI. Fourthly, the investment type plays an important role in consumers’ reactions to the use of AI.

Originality/value

To the best of the authors’ knowledge, this research is one of the first to study political ideology as a potential moderator of consumers’ responses to AI in financial services, providing novel contributions to the literature. It further contributes unique insights by examining emotional responses to AI and human financial advice for different amounts and types of investments using a comprehensive approach of examining both valence and discrete emotions to identify affection as a key explanatory emotion. The study further sheds insights relating to how emotions (affection) and trust mediate the relationship between AI and WOM, and brand attitudes, demonstrating an affect-attitude psychological sequence that explains consumers’ reactions to AI in financial services.
Key investor information disclosure regulation and retail mutual fund flows in the Finnish market
Authors: Turtiainen Matti , Saastamoinen Jani , Suhonen Niko , Kainulainen Tuomo
Published: April 2022

Purpose

In the European Union, the Undertakings for Collective Investment in Transferable Securities Directive (UCITS IV) requires fund management companies to provide a Key Investor Information Document (UCITS KIID) for investors. This papers uses archival data from the Finnish mutual fund market to test how the regulation's information disclosure requirements concerning past performance, risk and fund fees are associated with mutual fund flows.

Design/methodology/approach

The study uses archival data on the mutual funds market in Finland to test how the regulation relating to retail investors' information requirements is associated with mutual fund flows.

Findings

Our findings suggest that the UCITS KIID predicts retail investors' fund flows. While past performance is associated with fund flows throughout the observation period, retail investors appear to have become more sensitive to fund fees and invest in less risky funds following the adoption of the UCITS IV period.

Practical implications

Information relating to fund fees and risk appears to be relevant to retail investors, which should be acknowledged in future iterations of short-form disclosure and in mutual fund marketing.

Originality/value

This paper is the first to assess the significance of KIID in actual market environment.
Exploring teaching effectiveness and research on teaching and learning at AACSB accredited business schools in Canada and the US
Authors: Siddiqui Sanobar , Lento Camillo
Published: April 2022

Purpose

This study explores the implementation of two Association to Advance Collegiate Schools of Business (AACSB) standards by business schools across Canada and the US. First, this study examines how teaching effectiveness is defined and measured in light of Standard 7 (Teaching Effectiveness and Impact). Second, this study explores the value of research on teaching and learning in relation to Standard 8 (Impact of Scholarship).

Design/methodology/approach

This study adopts a thematic analysis framework based on data obtained from an online survey, semi-structured interviews, and policy documents.

Findings

The results reveal that business schools rarely define teaching effectiveness; instead, they adopt various measures to evaluate teaching effectiveness. The results reveal that research on teaching and learning alone usually does not lead to tenure; however, it is valued if part of a portfolio that includes discipline-specific research. Lastly, this research highlights a stigma associated with research on teaching and learning relative to discipline-specific research.

Practical implications

This study introduces a comprehensive and integrated teaching evaluation framework that can be adopted to define teaching effectiveness and elevate the teaching function. In addition, the authors argue that business schools should nurture a niche set of academics that holds PhDs in their respective disciplines and are education experts to increase the production of research-informed instructional strategies curated for business schools.

Originality/value

This is the first study to explore how AACSB standards related to teaching effectiveness and research on teaching and learning are interpreted and implemented at AACSB accredited business schools.
The role of education in filling the gender gap in financial inclusion in low-income economies
Authors: Pahlevan Sharif Saeed , Naghavi Navaz , Waheed Hassam , Ehigiamusoe Kizito Uyi
Published: April 2022

Purpose

This study aims to investigate whether gender predicts financial inclusion and whether education can fill the gender gap in financial inclusion when controlling for the effects of supply side factors of financial inclusion in low-income economies.

Design/methodology/approach

This study aims to investigate whether gender predicts financial inclusion and whether education can fill the gender gap in financial inclusion when controlling for the effects of supply side factors of financial inclusion in low-income economies.

Findings

The findings provided support for the gender gap in financial inclusion using the most basic measure of financial inclusion. However, using formal savings and access to credit, the gender gap hypothesis is not supported. Moreover, the results revealed that education reduces the gender gap in the basic form of financial inclusion. However, this study could not find any significant difference between men and women's financial inclusion in terms of saving at a bank or borrowing from a bank though men tend to save more than women informally.

Originality/value

The current study contributes to the literature by examining the role of education in the relationship between gender gap and financial inclusion when controlling for the effects of heterogeneous infrastructure and the supply side factors of financial inclusion among the selected countries.
The role of electronic word of mouth (eWOM) and the marketing mix on women’s purchasing intention of children's dietary supplements
Authors: Al-Dmour Hani , Al-Qawasmi Sheeraz , Al-Dmour Rand , Basheer Amin Eatedal
Published: April 2022

Purpose

This study aims to examine and validate the role of electronic word of mouth (eWOM), a mediating factor between the marketing mix elements (product, price, place and promotion) and women's purchasing intention of children's dietary supplements in the Jordanian environment culture context.

Design/methodology/approach

The data of the research was collected through online and offline questionnaires using a connivance sample of 370 women who have children and live in Amman, the largest city in Jordan.

Findings

The findings showed a partial effect of the eWOM as mediating factor on the relationship between marketing mix elements and women's purchasing intention of children's dietary supplements. The findings also revealed significant positive effects of price and place as marketing mix elements on women's purchasing intention of children's dietary supplements, while the product and promotion elements were found insignificant.

Originality/value

This paper contributed to consumer buying behaviour theories by filling a gap in the literature regarding the role of eWOM as a mediating factor on the relationship between marketing mix elements and women's purchasing intention of children's dietary supplements in a developing country like Jordan for the first time.