bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective Analysis of Clinical Utilization between Patients who used Telemedicine and Office Visits in Outpatient Physical Medicine & Rehabilitation Clinics during the COVID-19 Pandemic
Authors: Gilmer Gabrielle , Jackson Natalie , Koscumb Stephen , Marroquin Oscar , Sowa Gwendolyn
Published: March 2022

Objective

To describe the demographic characteristics of patients who used telemedicine and office visits in Physical Medicine and Rehabilitation (PM&R) during the COVID-19 pandemic and to quantify differences in clinical utilization between groups. Clinical utilization was defined as emergency department, urgent care, and hospital visits.

Design

Retrospective cohort study of 1,096 patients who used telemedicine and 1,171 patients who used office visits from April to June 2020 in outpatient PM&R at UPMC for musculoskeletal-related complaints

Results

The telemedicine groups contained proportionally more people of color and higher comorbidities than the office visit groups. Patients who were seen in the telemedicine groups were more likely to be prescribed opioids than the office visit group. There were no differences in clinical utilizations between the telemedicine and office visit groups.

Conclusions

The higher use of telemedicine in patients of color suggests a need for studying long-term outcomes to evaluate differences in care standards. We also identified that there is an urgent need to understand how telemedicine affects opioid prescribing practices. Lastly, future studies are needed to understand why there were no differences in clinical utilization between the telemedicine and office visit groups.
Glocal dendritic spikes: variation in branch activity during dendritic spiking indicates multiple functional units in the pyramidal neuron apical tuft
Authors: Geron Erez
Published: March 2022

There is a lively debate on how many functional units exist within the dendritic tree of pyramidal neurons (PNs). The classical view that the PN’s dendritic tree comprises several computational units 1-4 was challenged by recent in-vivo studies that identified mainly widespread dendritic spikes 5-10, suggesting a low degree of dendritic compartmentalization. We reasoned that global spikes do not rule out dendritic compartmentalization if these spikes contain a high variation in branch activity. Therefore, we turned to image Ca2+ activity in many apical dendrites from individual layer (L) 5 PNs of the primary motor cortex (M1). For proper dendritic morphology and Ca2+ activity analysis, we used mice with sparse double labeling of PNs with a structural marker (tdTomato) and a GCaMP6s probe. We first collected data for complete registration of the apical tuft dendritic structure. We then used 3D two-photon microscopy to image Ca2+ activity within these tufts during treadmill running. Using these, we imaged up to 30 apical branches from individual L5 PNs, including branches separated by as many as 11 bifurcations and more than 1000 µm of intracellular distance. We found that local spikes were rare, but global spikes often displayed heterogeneous Ca2+ elevation across branches, giving rise to an activity pattern across the tuft. This spiking pattern was dynamic and according to unsupervised hierarchical cluster analysis, fitted to 2-6 distinct patterns, even over short imaging periods. Taken together, we find a considerable variation in branch activity within and between global dendritic spikes, supporting multiple dendritic functional units.

Graphical abstract

We detected three main spike types. Local spikes were evident in a minority of the branches and had low amplitude. Contrastingly, global spikes often displayed homogeneous levels of branch activity and were the strongest and most prolonged spikes. An intermediate pattern was the “glocal spike,” where a global spike exhibited heterogeneous branch activity. Spikes with heterogeneous Ca2+ elevation across branches constituted at least a quarter of all spikes. In the social sciences, the term “glocalization” refers to global phenomena that are adjusted locally, such as food items sold worldwide but attuned to local tastes 11. Influenced by that, we refer to global spikes with heterogeneous branch activity as “glocal spikes.”
The use of pigs vocalisation structure to assess the quality of human-pig relationship
Authors: Villain Avelyne S , Guérin Carole , Tallet Céline
Published: March 2022

Studying human-animal interactions in domestic species and how they affect the establishment of a positive Human-Animal Relationship (HAR) may help us improve animal welfare and better understand the evolution of interspecific interactions associated with the domestication process. Understanding and describing the quality of an HAR requires information on several aspects of the animal biology and emotional states (social, spatial and postural behaviours, physiological and cognitive states). Growing evidence shows that acoustic features of animal vocalisations may be indicators of emotional states. Here, we tested the hypothesis that vocal structure may indicate the quality of HAR. At weaning, 30 piglets were positively handled by an experimenter who talked to and physically interacted with them three times a day, while 30 other piglets only received the contact necessary for proper husbandry. After two weeks, we recorded the behaviours and vocalisations produced in the presence of the static experimenter for 5 min. We repeated this test two weeks later, after a conditioning period during which human presence with additional positive contacts was used as a reward for all piglets. We hypothesized this conditioning period would lead to a positive human-piglet relationship for all piglets. As expected, piglets that were positively handled at weaning expressed a higher attraction toward the experimenter, and, after the conditioning, piglets that were not positively handled at weaning expressed a similar level of attraction than the positively handled ones. Piglets positively handled at weaning produced shorter grunts than the other ones, regardless of the context of recording, which may indicate a more positive affect. During reunions with the static experimenter, a more positive HAR was associated with a decrease in vocal reactivity to human proximity. However, during reunions with the experimenter providing additional positive contacts and over the conditioning, proximity to the human systematically triggered shorter and higher pitched grunts, indicator of positive a emotional state. Results first show that changes in vocal structure are consistent with indicators of positive states in the presence of a human. Second, these changes are stronger when the human positively interact with the piglets, supposedly emphasizing a higher positive arousal state during these interactions. We show that vocalisation structure may be a promising indicator of the quality of human-pig relationship.
Case-control analysis of single-cell RNA-seq studies
Authors: Petukhov Viktor , Igolkina Anna , Rydbirk Rasmus , Mei Shenglin , Christoffersen Lars , Khodosevich Konstantin , Kharchenko Peter V.
Published: March 2022

Single-cell RNA-seq (scRNA-seq) assays are being increasingly utilized to investigate specific hypotheses in both basic biology and clinically-applied studies. The design of most such studies can be often reduced to a comparison between two or more groups of samples, such as disease cases and healthy controls, or treatment and placebo. Comparative analysis between groups of scRNA-seq samples brings additional statistical considerations, and currently there is a lack of tools to address this common scenario. Based on our experience with comparative designs, here we present a computational suite (Cacoa – case-control analysis) to carry out statistical tests, exploration, and visualization of scRNA-seq sample cohorts. Using multiple example datasets, we demonstrate how application of these techniques can provide additional insights, and avoid issues stemming from inter-individual variability, limited sample size, and high dimensionality of the data.
Genomics epidemiology analysis reveals hidden signatures of drug resistance in Mycobacterium tuberculosis
Authors: Mejía-Ponce P.M. , Ramos-González E.J. , Ramos-García A.A. , Lara-Ramírez E.E. , Soriano-Herrera A.R. , Medellín-Luna M.F. , Valdez-Salazar F. , Castro-Garay C.Y. , Núñez-Contreras J. , De Donato-Capote M. , Sharma A. , Castañeda-Delgado J.E. , Zenteno-Cuevas R. , Enciso-Moreno J.A. , Licona-Cassani C.
Published: March 2022

Mycobacterium tuberculosis (Mtb) causes the majority of reported cases of human tuberculosis (TB), one of the deadliest infectious diseases worldwide. New diagnostic tools and approaches to detect drug-resistance must be introduced by 2025 to achieve the End-TB Strategy goals set for 2030 by the WHO. Genomic epidemiology of TB has allowed the expansion of catalogs listing genetic signatures of Mtb drug-resistance. However, very few Mtb strains from Latin America have participate in previous genomic epidemiologic efforts. Here we present the first functional genomic epidemiology study of drug-resistant Mtb strains in Mexico, incorporating the genomic characterization of 133 genomes, including 53 newly sequenced isolates, to provide a comprehensive phylogeographic analysis of drug resistant Mtb in Mexico. The study evidences the prevalence of Euro-American Lineage L4 (96.2%), featuring a uniform distribution of the sublineages X-type (33.08%), LAM (22.56%), and Haarlem (21.05%). Our results demonstrate low levels of agreement with traditional drug sensitivity tests (DST), raising concerns for drug-resistant isolates lacking any previously reported genetic signatures of resistance. Finally, we propose a novel functional networking tool (FuN-TB) to explore metabolic and cellular signatures of drug resistance. Applying functional genomics approaches to Latin American Mtb genomes will provide new drug-resistance screening targets that can contribute to bed side decision-making and advise local public policy.

Abstract importance

We presented the first phylogeographic analysis of Mycobacterium tuberculosis (Mtb) of Mexico. Our analysis integrates 133 genome sequences and is focused on the identification of genetic signatures associated to drug-resistance. The results show the geographic distribution of sublineages and drug-resistance phenotypic classes. Additionally, we propose a novel functional networking tool (FuN-TB) to explore metabolic and cellular signatures of drug resistance associated. We show for the first time that Mtb isolates from Mexico encode for region-specific genetic signarures of antimicrobial resistance. Applying functional genomics approaches to Latin American Mtb genomes will provide new drug-resistance screening targets that can contribute to bed side decision-making and advise local public policy.
The transcriptional profile of keloidal Schwann cells
Authors: Direder Martin , Wielscher Matthias , Weiss Tamara , Laggner Maria , Copic Dragan , Klas Katharina , Bormann Daniel , Vorstandlechner Vera , Tschachler Erwin , Ankersmit Hendrik Jan , Mildner Michael
Published: March 2022

Recently, a specific Schwann cell type with pro-fibrotic and tissue regenerative properties has been identified that contributes to keloid formation. In the present study, we have reanalysed published single cell RNA sequencing (scRNAseq) studies of keloids, healthy skin and normal scars to reliably determine the specific gene expression profile of the keloid-specific Schwann cell type in more detail.

We were able to confirm the presence of the repair-like, pro-fibrotic Schwann cell type in the datasets of all three studies and identified a specific gene set for these Schwann cells. In contrast to keloids, in normal scars the number of Schwann cells was neither increased nor was their gene expression profile distinctly different from Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the kruppel-like factor family and members of the immediate early response genes, in the de-differentiation process of keloidal Schwann cells.

Together, our analysis strengthens the role of the pro-fibrotic Schwann cell type in the formation of keloids. Knowledge on the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.
Variant-specific burden of SARS-CoV-2 in Michigan: March 2020 through November 2021
Authors: Petrie Joshua G. , Eisenberg Marisa C. , Lauring Adam S. , Gilbert Julie , Harrison Samantha M. , DeJonge Peter M. , Martin Emily T.
Published: March 2022

Accurate estimates of total burden of SARS-CoV-2 are needed to inform policy, planning and response. We sought to quantify SARS-CoV-2 cases, hospitalizations, and deaths by age in Michigan. COVID-19 cases reported to the Michigan Disease Surveillance System were multiplied by age and time-specific adjustment factors to correct for under-detection. Adjustment factors were estimated in a model fit to incidence data and seroprevalence estimates. Age-specific incidence of SARS-CoV-2 hospitalization, death, and vaccination, and variant proportions were estimated from publicly available data. We estimated substantial under-detection of infection that varied by age and time. Accounting for under-detection, we estimate cumulative incidence of infection in Michigan reached 75% by mid-November 2021, and over 87% of Michigan residents were estimated to have had ≥1 vaccination dose and/or previous infection. Comparing pandemic waves, the relative burden among children increased over time. Adults ≥80 years were more likely to be hospitalized or die if infected in fall 2020 than if infected during later waves. Our results highlight the ongoing risk of periods of high SARS-CoV-2 incidence despite widespread prior infection and vaccination. This underscores the need for long-term planning for surveillance, vaccination, and other mitigation measures amidst continued response to the acute pandemic.
Rethinking the nature of intraspecific variability and its consequences on species coexistence
Authors: Girard-Tercieux Camille , Maréchaux Isabelle , Clark Adam T. , Clark James S. , Courbaud Benoît , Fortunel Claire , Guillemot Joannès , Künstler Georges , Maire Guerric le , Pélissier Raphaël , Rüger Nadja , Vieilledent Ghislain
Published: March 2022

Context

Intraspecific variability (IV) has been proposed to explain species coexistence in diverse communities. Assuming, sometimes implicitly, that conspecific individuals can perform differently in the same environment and that IV blurs species differences, previous studies have found contrasting results regarding the effect of IV on species coexistence.

Objective

We aim at showing that the large IV observed in data does not mean that conspecific individuals are necessarily different in their response to the environment and that the role of high-dimensional environmental variation in determining IV has been largely underestimated in forest plant communities.

Methods and Results

We first used a simulation experiment where an individual attribute is derived from a high-dimensional model, representing “perfect knowledge” of individual response to the environment, to illustrate how a large observed IV can result from “imperfect knowledge” of the environment. Second, using growth data from clonal Eucalyptus plantations in Brazil, we estimated a major contribution of the environment in determining individual growth. Third, using tree growth data from long-term tropical forest inventories in French Guiana, Panama and India, we showed that tree growth in tropical forests is structured spatially and that despite a large observed IV at the population level, conspecific individuals perform more similarly locally than compared with heterospecific individuals.

Synthesis

As the number of environmental dimensions that are typically quantified is generally much lower than the actual number of environmental dimensions influencing individual attributes, a great part of observed IV might be misinterpreted as random variation across individuals when in fact it is environmentally-driven. This mis-representation has important consequences for inference about community dynamics. We emphasize that observed IV does not necessarily impact species coexistence per se but can reveal species response to high-dimensional environment, which is consistent with niche theory and the observation of the many differences between species in nature.
Subjectivity of time perception alters choice preference for future rewards through fronto-striatal value signal dynamics
Authors: Shintaki Reiko , Tanaka Daiki , Okayasu Moe , Suzuki Shinsuke , Yoshimoto Takaaki , Sadato Norihiro , Chikazoe Junichi , Jimura Koji
Published: March 2022

Our preference for a reward depends on the time of delay for its delivery. Here we show that changes in the external environment can manipulate the perceived duration of time, which alters the formation of the choice preference through value signals in the cortical and subcortical brain regions. Humans anticipated a real liquid reward delayed by tens of seconds, during which colors of visually presented panels gradually changed. The color-change delay was perceived as shorter than a control color-constant delay. Interestingly, participants with greater perceptual bias of the delay showed stronger preference for rewards with the color-change delay. The ventrolateral prefrontal cortex (vlPFC) and ventral striatum (VS) showed dynamic neural signatures of value components that were modulated by subjectively perceived duration. Crucially, these effects were specifically observed while a future reward was anticipated, and moreover, the vlPFC activity was weaker in participants with greater bias in the duration perception. These results demonstrate that subjective time experience leads to biased choice preference of delayed rewards, which is regulated by dynamic value signals of future rewards and accurate perception of the external world in the vlPFC-VS systems.
T cell migration requires ion and water influx to regulate actin polymerization
Authors: de Boer Leonard L. , Vanes Lesley , Melgrati Serena , O’May Joshua Biggs , Hayward Darryl , Driscoll Paul C. , Day Jason , Griffiths Alexander , Magueta Renata , Morrell Alexander , MacRae James I. , Köchl Robert , Tybulewicz Victor L. J.
Published: March 2022

Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into the cell. However, it is not known why ion entry is necessary for T cell movement. Here we show that signaling from the chemokine receptor CCR7 leads to activation of WNK1 and its downstream pathway at the leading edge of migrating CD4+T cells, resulting in ion influx and water entry by osmosis. We propose that WNK1-induced water entry is required to swell the membrane at the leading edge, generating space into which actin filaments can polymerize, thereby facilitating forward movement of the cell. Given the broad expression of WNK1 pathway proteins, our study suggests that ion and water influx are likely to be essential for migration in many cell types, including leukocytes and metastatic tumor cells.

One Sentence Summary

Chemokine-induced migration of T cells requires water entry at the leading edge to facilitate actin polymerization.
Electroencephalography-derived functional connectivity in sensorimotor networks in Stroke and Multiple Sclerosis Fatigue
Authors: Wu Chi-Hsu , De Doncker William , Croce Pierpaolo , Bertoli Massimo , Tecchio Franca , Kuppuswamy Annapoorna
Published: March 2022

A common mechanism of altered sensory processing is the basis of chronic fatigue in neurological disorders. Here we test the hypothesis ‘Altered connectivity in sensory networks underlies chronic fatigue in stroke and multiple sclerosis’.

In 46 non-depressed, minimally impaired stroke survivors (n=29) and multiple sclerosis patients (n=17), median disease duration of 5 years, resting state neuronal activity was measured using 64-channel electroencephalography. Graph theory-based network analysis measure of functional connectivity (small-world index) was calculated in right and left motor (Brodmann areas 4, 6, 8, 9, 24 and 32) and somatosensory (Brodmann areas 1, 2, 3, 5, 7, 40 and 43) networks, in 5 frequency bands: delta, theta, alpha, beta and gamma. Fatigue was measured using Fatigue Severity Scale (Stroke) and modified Fatigue Impact Scale (MS), with scores of >4 (FSS) and >38 (mFIS), defined as high fatigue.

Both stroke survivors and multiple sclerosis patients with high fatigue showed significantly more small-worldness in the right sensory networks in the beta band frequency. Additionally, only in stroke survivors with high fatigue, there was decreased small-worldness in the left motor network in the delta and theta bands.

Altered sensory network connectivity is common to both stroke and MS fatigue, indicating impaired sensory processing as a disease-independent mechanism of chronic fatigue in neurological conditions. Furthermore, such difference in functional connectivity emerges in beta band activity, further strengthening the idea of altered sensorimotor processing as the basis of chronic neurological fatigue.
Engineering ecologically complementary rhizosphere probiotics using consortia of specialized bacterial mutants
Authors: Yang Chunlan , Li Jingxuan , Jousset Alexandre , Wang Xiaofang , Xu Zhihui , Yang Tianjie , Mei Xinlan , Zhong Zengtao , Xu Yangchun , Shen Qirong , Wei Zhong , Friman Ville-Petri
Published: March 2022

While bacterial diversity is beneficial for the functioning of rhizosphere microbiomes, multi-species bioinoculants often fail to promote plant growth. One potential reason for this is that competition between inoculated consortia members create conflicts for their survival and functioning. To circumvent this, we used transposon mutagenesis to increase the functional diversity within Bacillus amyloliquefaciens bacterial species and tested if we could improve plant growth-promotion by assembling consortia of closely related but functionally specialized mutants. While most insertion mutations were harmful, some improved strains’ plant growth-promotion traits without increasing antagonism between them. Crucially, plant growth-promotion could be improved by applying these specialist mutants as consortia, leading to clear positive relationships between consortia richness, plant root colonization and protection from bacterial wilt disease. Together, our results suggest that increasing intra-species diversity could be an effective way to increase probiotic consortia multifunctionality, leading to more stable plant growth-promotion throughout growth cycle via insurance effects.
Case-only exome variation analysis of severe alcohol dependence using a multivariate hierarchical gene clustering approach
Authors: Gentry Amanda E. , Alexander Jeffry C. , Ahangari Mohammad , Peterson Roseann E. ,   VCU Alcohol Research Center working group, Miles Michael F. , Bettinger Jill C. , Davies Andrew G. , Groteweil Mike , Bacanu Silviu A. , Kendler Kenneth S. , Riley Brien P. , Webb Bradley T.
Published: March 2022

Background

Variation in genes involved in ethanol metabolism has been shown to influence risk for alcohol dependence (AD) including protective loss of function alleles in ethanol metabolizing genes. We therefore hypothesized that people with severe AD would exhibit different patterns of rare functional variation in genes with strong prior evidence for influencing ethanol metabolism and response when compared to genes not meeting these criteria.

Objective

Leverage a novel case only design and Whole Exome Sequencing (WES) of severe AD cases from the island of Ireland to quantify differences in functional variation between genes associated with ethanol metabolism and/or response and their matched control genes.

Methods

First, three sets of ethanol related genes were identified including those a) involved in alcohol metabolism in humans b) showing altered expression in mouse brain after alcohol exposure, and altering ethanol behavioral responses in invertebrate models. These genes of interest (GOI) sets were matched to control gene sets using multivariate hierarchical clustering of gene-level summary features from gnomAD. Using WES data from 190 individuals with severe AD, GOI were compared to matched control genes using logistic regression to detect aggregate differences in abundance of loss of function, missense, and synonymous variants, respectively.

Results

Three non-independent sets of 10, 117, and 359 genes were queried against control gene sets of 139, 1522, and 3360 matched genes, respectively. Significant differences were not detected in the number of functional variants in the primary set of ethanol-metabolizing genes. In both the mouse expression and invertebrate sets, we observed an increased number of synonymous variants in GOI over matched control genes. Post-hoc simulations showed the estimated effects sizes observed are unlikely to be under-estimated.

Conclusion

The proposed method demonstrates a computationally viable and statistically appropriate approach for genetic analysis of case-only data for hypothesized gene sets supported by empirical evidence.
Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer
Authors: Brown Benjamin P. , Zhang Yun-Kai , Kim Soyeon , Finneran Patrick , Yan Yingjun , Du Zhenfang , Kim Jiyoon , Hartzler Abigail Leigh , LeNoue-Newton Michele L. , Smith Adam W. , Meiler Jens , Lovly Christine M.
Published: March 2022

Oncogenic mutations within the epidermal growth factor receptor (EGFR) are found in 15-30% of all non-small cell lung carcinomas. The term exon 19 deletion (ex19del) is collectively used to refer to more than 20 distinct genomic alterations within exon 19 that comprise the most common EGFR mutation subtype in lung cancer. Despite this heterogeneity, clinical treatment decisions are made irrespective of which EGFR ex19del variant is present within the tumor, and there is a paucity of information regarding how individual ex19del variants influence protein structure and function. Herein, we identify allele-specific functional differences among ex19del variants attributable to recurring sequence and structure motifs. We build all-atom structural models of 60 ex19del variants identified in patients and combine ~400 μs of molecular dynamics simulations with biochemical and biophysical experiments to analyze three ex19del mutations (E746_A750, E746_S752>V, and L747_A750>P). We demonstrate that sequence variation in ex19del alters oncogenic cell growth, dimerization propensity, and tyrosine kinase inhibitor (TKI) sensitivity. We show that in contrast to E746_A750 and E746_S752>V, the L747_A750>P variant forms highly active ligand-independent dimers. E746_S752>V displays the least TKI sensitivity among the variants tested, which enzyme kinetic analysis and TKI inhibition experiments suggest is due to increased ATP Km relative to the common E746_A750 variant. Through these analyses, we propose an expanded framework for interpreting ex19del variants and new considerations for therapeutic intervention.

Significance

EGFR mutations are detected in approximately 30% of all lung adenocarcinomas, and the most common EGFR mutation occurring in ~50% of patients is termed “exon 19 deletion” (ex19del). Despite the existence of dozens of different genomic variants comprising what is generically referred to clinically as ex19del, clinicians currently do not distinguish between ex19del variants in considering treatment options, and the differences between ex19del variants are largely unstudied in the broader scientific community. Herein, we describe functional differences between distinct EGFR ex19del variants attributable to the structural features of each variant. These findings suggest a possible explanation for observed differences in patient outcomes stratified by ex19del subtype and reinforce the need for allele-specific considerations in clinical treatment decision making.
Structure of dynein-dynactin on microtubules shows tandem recruitment of cargo adaptors
Authors: Chaaban Sami , Carter Andrew P.
Published: March 2022

Cytoplasmic dynein is a microtubule motor that is activated by its cofactor dynactin and a coiled-coil cargo adaptor. There is currently limited structural information on how the resulting complex interacts with microtubules and how adaptors are recruited. Here, we develop a cryo-EM processing pipeline to solve the high-resolution structure of dynein-dynactin and the adaptor BICDR1 bound to microtubules. This reveals the asymmetric interactions between neighbouring dynein motor domains and how it relates to their motile behaviour. We find unexpectedly that two adaptors occupy the complex. Both adaptors make similar interactions with the dyneins but diverge in their contacts with each other and dynactin. Our structure has implications for the stability and stoichiometry of motor recruitment by cargos.
Dietary inclusion of nitrite-containing frankfurter exacerbates colorectal cancer pathology, alters metabolism and causes gut dybiosis in APCminmice
Authors: Crowe William , Pan Xiaobei , Mackle James , Harris Adam , Hardiman Gary , Elliott Chris T , Green Brian D
Published: March 2022

Colorectal cancer (CRC) is the second most prevelant malignancy in Europe and diet is an important modifiable risk factor. Processed meat consumption, including meats with preservative salts such as sodium nitrite, have been implicated in CRC pathogenesis. This study investigated how the CRC pathology and metabolic status of adenomatous polyposis coli (APC) multiple intestinal neoplasia(min) mice was perturbed following 8 weeks of pork meat consumption. Dietary inclusions (15%) of either nitrite-free pork, nitrite-free sausage or nitrite-containing sausage (frankfurter) were compared against a parallel control group (100% chow). Comprehensive studies investigated: gastrointestinal tract histology (tumours, aberrant crypt foci (ACF) and mucin deplin foci (MDF), lipid peroxidation (urine and serum), faecal microbiota and serum metabolomics (599 metabolites). After 8 weeks mice consuming the frankfurter diet had 53% more (P=0.014) gastrointestinal tumours than control, although ACF and MDF did not differ. Urine and serum lipid peroxidation markers were 59% (P=0.001) and 108% (P=0.001) higher, respectively in the frankfurter group. Gut dysbiosis was evident in these mice with comparably fewerBacteriodesand moreFirmicutes. Fasting serum levels of trimethylamine N-oxide (TMAO) and numerous triglycerides were elevated. Various serum phosphotidylcholine species were decreased. These results demonstrate that nitrite-containing sausages may exaccerbate the development of CRC pathology in APCMinmice to a greater extent than nitrite-free sausages, and this is associated with greater lipid peroxidation, wide-ranging metabolic alternation and gut dysbiosis.
Prime-boost vaccinations with two serologically distinct chimpanzee adenovirus vectors expressing SARS-CoV-2 spike or nucleocapsid tested in a hamster COVID-19 model
Authors: Hasanpourghadi Mohadeseh , Novikov Mikhail , Ambrose Robert , Chekaoui Arezki , Newman Dakota , Ding Jianyi , Giles-Davis Wynetta , Xiang Zhiquan , Zhou Xiang Yang , Liu Qin , Swagata Kar , Ertl Hildegund CJ
Published: March 2022

Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing the spike (S) or nucleocapsid (N) proteins of an early SARS-CoV-2 isolate were tested individually or as a mixture in a hamster COVID-19 challenge model. The N protein, which was expressed as a fusion protein within herpes simplex virus glycoprotein D (gD) stimulated antibodies and CD8+ T cells. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gDN fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable that the S protein may potentiate and prolong protection achieved by the currently used genetic COVID-19 vaccines.
Crystal structure of a constitutive active mutant of adenosine A2Areceptor
Authors: Cui Min , Zhou Qingtong , Xu Yueming , Weng Yuan , Yao Deqiang , Zhao Suwen , Song Gaojie
Published: March 2022

The adenosine A2Areceptor (A2AAR) is a prototypical member of the class A subfamily of G-protein-coupled receptors (GPCRs) that is widely distributed in various tissues and organs of the human body, and participates in many important signal-regulation processes. We have previously summarized a common activation pathway of class A GPCRs in which a series of conserved residues/motifs undergo conformational change during extracellular agonist binding and finally induce the coupling of intracellular G protein. Through this mechanism we have successfully predicted several novel constitutive active or inactive mutations for A2AAR. To reveal the molecular mechanism of mutation-induced constitutive activity, we determined the structure of a typical mutant I92N complexed with the agonist UK-432097. The mutated I92N forms a hydrophilic interaction network with nearby residues including Trp6.48of the CWxP motif, which is absent in wild-type A2AAR. Although the mutant structure is similar overall to the previously determined intermediate-state A2AAR structure (PDB ID 3qak) [Xu, Wu, Katritch, Han, Jacobson, Gao, Cherezov & Stevens (2011).Science,332, 322–327], molecular dynamics simulations suggest that the I92N mutant stabilizes the metastable intermediate state through the hydrophilic interaction network and favors the conformational transition of the receptor towards the active state. This research provides a structural template towards the special pharmacological outcome triggered by conformational mutation and sheds light on future structural or pharmacological studies among class A GPCRs.
Entrepreneurial intentions among business students: the mediating role of attitude and the moderating role of university support
Authors: Anjum Temoor , Amoozegar Azadeh , Farrukh Muhammad , Heidler Petra
Published: March 2022

Purpose

This study aims to examine the potential determinants of entrepreneurial intentions (EIs) among business students. To that end, the study investigates the role of entrepreneurship education (EE) and entrepreneurial passion (EP) (inventing and founding), as well as the mediating role of attitude towards entrepreneurship (ATE) and the moderating role of university support.

Design/methodology/approach

A close-ended questionnaire measured on a seven-point Likert scale was used to collect data from business students at nine universities in Punjab, Pakistan. The sample size comprises 377 participants who were selected using a stratified random sampling technique. Partial least square structural equation modeling (PLS-SEM) was then applied to assess the study’s model and the postulated hypothesis.

Findings

The findings indicated that (a) every independent variable (IV) directly impacts EI [dependent variable (DV)] except EP for founding (EPF), (b) ATE significantly mediates the relationship between IV and DV (c) perceived university support positively moderates the relationship between ATE and EI.

Originality/value

As an implication to policy, the Government must ensure that students are exposed to business environments and find university support through different paths. Specifically, Pakistan’s Minister of Education and the Higher Education Commission (HEC) may consider designing university programs that lead to more influential EE. The empirical findings may help policymakers develop effective policies for promoting entrepreneurship.
Mitigating risk perception in imbalanced supply chain relationships: roles of contract framing and IT integration
Authors: Wang Yuting , Liu Hefu , Fang Jie
Published: March 2022

Purpose

This paper aims to investigate that how to mitigate the weaker party's risk perception in imbalanced supply chain relationships by framing contracts according to complexity and recurrence. The level of information technology (IT) integration is considered as the moderator influencing the effectuation of contract framing.

Design/methodology/approach

The authors conducted a questionnaire survey with 229 firms involved in imbalanced supply chains. Hierarchical regression analysis was used to test the hypotheses.

Findings

The authors found contractual complexity positively influenced performance and relational risk, while contractual recurrence negatively impacted performance and relational risk. This study further reveals the positive moderating effect of IT integration in influencing contractual complexity on relational risk and performance risk and the negative impact of IT integration in influencing contractual recurrence on relational risk and performance risk.

Research limitations/implications

Overall, this study posits the coordinating role of contracts in reducing the weaker party's risk perception in imbalanced supply chain relationships.

Practical implications

The authors concluded by illustrating how to customize contracts based on the level of IT integration to maximize their role in reducing risk perception.

Originality/value

This study is embedded in imbalanced supply chain relationship, aiming to solve the problem of high-risk perception held by the weaker party, which is a salient threat to the sustainability of collaboration. Contract framing is proposed as an effective approach for mitigating risk perception, which should be carefully designed based on the level of IT integration of the relationship. The authors found that contractual complexity has a positive influence on performance and relational risk, but contractual recurrence has a negative impact on performance and relational risk. This study further reveals the moderating effect of IT integration on the effectuation of contractual framing.
Impacts of platform design on consumer commitment and online review intention: does use context matter in dual-platform e-commerce?
Authors: Xiao Quan , Siponen Mikko , Zhang Xing , Lu Fucai , Chen Si-hua , Mao Mingsong
Published: March 2022

Purpose

The purpose of this study is to explore the antecedents of consumers’ online review intention in e-commerce platforms from a unique perspective of consumer commitment and platform design. Meanwhile, for the dual-platform strategy, i.e. providing both the web and mobile platforms simultaneously, which is widely adopted in the industry but lacks theoretical concerns, this study aims to examine the differences that platform design influences consumer commitment, consequently contributing to online review intention, between the web and mobile contexts.

Design/methodology/approach

A cross-sectional online survey is employed, and a structural equation model-based approach is utilized to analyze the data collected from both the website-preferred consumers (N = 167) and the mobile app-preferred consumers (N = 247).

Findings

The results indicate that instrumental support design factors and socio-emotional support factors positively influence consumer commitment, which further affect online review intention positively. Furthermore, design factors in different use contexts generate different impacts, and consumer commitment generates a greater effect on online review intention in the mobile than in the web context. Empathy is found to be an important motivator of consumer commitment in both contexts.

Originality/value

To the best of the authors’ knowledge, as one of the first attempts to capture the differences in the relationship between platform design on consumer commitment and online review intention in different use contexts within the dual-platform e-commerce, this study provides insights for e-commerce platform managers and designers to promote consumer commitment and online review engagement by prioritizing the platform design.
The relevance of XBRL extensions for stock markets: evidence from cross-listed firms in the US
Authors: Cormier Denis , Teller Pierre , Dufour Dominique
Published: March 2022

Purpose

The study investigates the relevance for stock markets of voluntary disclosure of eXtensible Business Reporting Language (XBRL) extensions [based on International Financial Reporting Standards (IFRS) or US-GAAP] for an international sample of US cross-listed firms.

Design/methodology/approach

The study examines if the disclosure of XBRL extensions by a firm provides relevant information to market participants. Towards that end, this paper investigates whether this type of disclosure affects the level of information asymmetry between insiders and investors and if it is value relevant. This study measures information asymmetry by bid-ask spread and value relevance by stock price or Tobin's Q.

Findings

After a certain level of disclosure of XBRL extensions, the impact on stock pricing is negative (creates noise on stock markets). Controlling for that phenomenon, both IFRS and US-GAAP XBRL extensions are value relevant. Second, results indicate that XBRL extensions are positively (negatively) related to stock market value for firms that exhibit positive (negative) earnings. This suggests a complementary effect between earnings and XBRL extensions on their relation with stock price or Tobin's Q. Finally, the results also indicate that both IFRS extensions and US-GAAP extensions are associated with lower information asymmetry (i.e. bid-ask spread).

Originality/value

To the best of the authors’ knowledge, this study is the first to investigate the relevance of XBRL extensions under IFRS for US cross-listed firms since the availability of the IFRS taxonomy for foreign private issuers that prepare financial statements under IFRS standards.
Oriented extrapolation of common‐midpoint gathers in the absence of near‐offset data using predictive painting
Authors: Khoshnavaz M. Javad
Published: March 2022

Seismic reconstruction of missing traces is an extremely important subject in seismic data processing. It includes both interpolation and extrapolation of sparsely recorded data. Extrapolation is often performed in the absence of near‐offset seismic data recorded through marine acquisition. Several reconstruction methods have been designed to circumvent this sparsity in time–offset, frequency–offset and time–frequency domains. In this research, I propose an oriented extrapolation workflow to reconstruct near‐offset missing traces. The term oriented or velocity‐independent refers to those techniques that are based on the use of local slopes. In the proposed workflow, I use an oriented time‐warping algorithm called predictive painting. This algorithm is suitable to predict two‐way traveltimes between two distinctive points of an event. Seismic events recorded by an off‐end array very rarely contain dips of both signs with respect to their zero‐offset location in common‐midpoint domain. This makes the domain an ideal choice to run the algorithm. The proposed algorithm is demonstrated on synthetic and field data examples. I decimate near‐offset seismic traces and reconstruct them through the algorithm. The reconstruction results are compared with the original data before decimation. Furthermore, insensitivity of the proposed workflow to the presence of class II amplitude‐versus‐offset anomalies is demonstrated on a synthetic example. I also perform a velocity‐dependent (a normal‐moveout‐based) technique on the field data and compare the corresponding outcomes with the results achieved by the application of the proposed velocity‐independent approach. All the results suggest that the proposed technique has the potential to be used in the exploration industry.
Peritumoral histopathologic findings in patients with chronic viral hepatitis‐associated hepatocellular carcinoma
Authors: Pehlivanoglu Burcin , Aysal Anil , Agalar Cihan , Egeli Tufan , Ozbilgin Mucahit , Unek Tarkan , Unek Tugba , Oztop Ilhan , Sagol Ozgul
Published: March 2022

Data on peritumoral histopathologic findings in patients with hepatocellular carcinoma (HCC) is limited. In this retrospective study, we evaluated the peritumoral histopathologic changes in patients with chronic viral hepatitis (CVH)‐associated HCC (CVH‐HCC) and their prognostic value. 61 consecutive cirrhotic patients who underwent liver transplantation due to CVH‐HCC were included. Histopathologic features within 1 cm distance of the tumor, and their association with clinicopathological characteristics and prognosis were evaluated. A random representative slide of cirrhotic parenchyma unrelated to invasive and/or dysplastic foci was also evaluated for the same histopathologic criteria. The majority (85%, n = 52) were male with a median age of 55 ± 6.38 (range, 39–67). The etiologic agent was only HBV in 90% (n = 55). The most common peritumoral findings were portal inflammation (100%; n = 61), ductular reaction (100%; n = 61) and sinusoidal dilatation (95%; n = 58). Macrovascular invasion was observed only in four cases (7%) with mild peritumoral portal inflammation. Neutrophilic infiltration of the peritumoral portal tracts (n = 18; 30%) was significantly associated with pT4 tumor stage, tumor grade, macrovascular invasion, and pretransplant therapy. Patients with moderate or severe peritumoral sinusoidal dilatation tended to have worse prognosis, albeit not significantly. Peritumoral ballooning degeneration was associated with multifocality, recurrence and recurrence‐free survival in both uni‐ and multivariate analysis. Peritumoral histopathologic changes in CVH‐HCC can be classified as: changes related to pathogenesis, changes indirectly affecting prognosis, and changes directly affecting prognosis. Peritumoral prominent ballooning degeneration may be a predictor of recurrence while portal neutrophilic infiltration and sinusoidal dilatation seem to indicate poor prognosis.
Patterns of emergency admission for IBD patients over the last 10 years in Lothian, Scotland: a retrospective prevalent cohort analysis
Authors: Lyons Mathew , Derikx Lauranne A. A. P. , Fulforth James , McCall Sophie , Plevris Nikolas , Jenkinson Philip W. , Kirkwood Kathryn , Siakavellas Spyros , Lucaciu Laura , Constantine‐Cooke Nathan , Arnott Ian D. , Henderson Paul , Russell Richard K. , Wilson David C. , Lees Charlie W. , Jones Gareth‐Rhys
Published: March 2022

Objective

It is unclear how the compounding prevalence of inflammatory bowel disease (IBD) has translated into the causes and rates of hospitalisation, particularly in an era of increased biologic prescribing. We aimed to analyse these trends in a population‐based IBD cohort over the last 10 years.

Design

The Lothian IBD registry is a complete, validated, prevalent database of IBD patients in NHS Lothian, Scotland. ICD‐10 coding of hospital discharge letters from all IBD patient admissions to secondary care between 1 January 2010 and 31 December 2019 was interrogated for admission cause, with linkage to local/national data sets on death and prescribed drugs.

Results

Fifty‐seven per cent (4673/8211) of all IBD patients were admitted to secondary care for >24 h between 1 January 2010 and 31 December 2019. In patients <40 years, IBD was the commonest reason for admission (38% of admissions), whereas infection was the most common cause in those >60 years (19% of admissions). Three per cent (243/8211) of IBD patients accounted for 50% of the total IBD bed‐days over the study period.

Age‐standardised IBD admission rates fell from 39.4 to 25.5 admissions per 100,000 population between 2010 and 2019, an average annual percentage reduction of 3% (95% CI −4.5% to −2.1%, p < 0.0001). Non‐IBD admission rates were unchanged overall (145–137 per 100,000 population) and specifically for serious (hospitalisation) and severe (ITU admission or death) infection over the same period.

Conclusion

Despite compounding prevalence and increased biologic use, IBD admission rates are falling. The cause of admission varies with age, with infection the predominant cause in older patients.