bluuebunny/crossref_metadata_2025 huggingface dataset:
An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome
Authors: Liu Shixuan , Ezran Camille , Wang Michael F. Z. , Li Zhengda , Awayan Kyle ,   The Tabula Microcebus Consortium, Long Jonathon Z. , De Vlaminck Iwijn , Wang Sheng , Epelbaum Jacques , Kuo Christin , Terrien Jeremy , Krasnow Mark A. , Ferrell James E.
Published: December 2021

Hormones mediate long-range cell communication in multicellular organisms and play vital roles in normal physiology, metabolism, and health. Using the newly-completed organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), we have systematically identified hormone-producing and -target cells for 84 classes of hormones, and have created a browsable atlas for hormone signaling that reveals previously unreported sites of hormone regulation and species-specific rewiring. Hormone ligands and receptors exhibited cell-type-dependent, stereotypical expression patterns, and their transcriptional profiles faithfully classified the molecular cell type identities, despite their comprising less than 1% of the transcriptome. Cells of similar cell types further display stage, subtype or organ-dependent specification of hormonal signaling, reflecting the precise control of global hormonal regulation. By linking ligand-expressing cells to the cells expressing the corresponding receptor, we constructed an organism-wide map of the hormonal cell communication network. This network was remarkably densely and robustly connected and included a myriad of feedback circuits. Although it includes classical hierarchical circuits (e.g. pituitary → peripheral endocrine gland → diverse cell types), the hormonal network is overall highly distributed without obvious network hubs or axes. Cross-species comparisons among humans, lemurs, and mice suggest that the mouse lemur better models human hormonal signaling, than does the mouse. Hormonal genes show a higher evolutionary conservation between human and lemur vs. human and mouse at both the genomic level (orthology-mapping and sequence identity) and the transcriptional level (cell type expression patterns). This primate hormone atlas provides a powerful resource to facilitate discovery of regulation on an organism-wide scale and at single-cell resolution, complementing the single-site-focused strategy of classical endocrine studies. The network nature of hormone regulation and the principles discovered here further emphasize the importance of a systems approach to understanding hormone regulation.
Morphological variation and phylogeny ofKarenia selliformis(Gymnodiniales, Dinophyceae) in an intensive cold-water algal bloom in eastern Hokkaido, Japan in September–November 2021
Authors: Iwataki Mitsunori , Lum Wai Mun , Kuwata Koyo , Takahashi Kazuya , Arima Daichi , Kuribayashi Takanori , Kosaka Yuki , Hasegawa Natsuki , Watanabe Tsuyoshi , Shikata Tomoyuki , Isada Tomonori , Orlova Tatiana Yu. , Sakamoto Setsuko
Published: December 2021

Harmful algal blooms responsible for mass mortalities of marine organisms have so far been rare in Hokkaido, northern Japan, although fish killing blooms have been frequently reported from western Japanese coasts. In September–November 2021, a huge and prolonged cold-water bloom occurred along the Pacific coast of eastern Hokkaido, Japan, and was associated with intensive mortalities of sea urchin, fish, octopus, shellfish, etc. In this study, morphology and phylogeny of the dominant and co-occurred unarmored dinoflagellates of the Kareniaceae in the bloom were examined by using light microscopy, scanning electron microscopy and molecular phylogeny inferred from ITS and LSU rDNA (D1–D3) sequences. Morphological observation and molecular phylogeny showed that the dominant species wasKarenia selliformis, with co-occurrences of other kareniacean dinoflagellates,Kr. longicanalis,Kr. mikimotoi,Karlodiniumsp.,Takayamacf.acrotrocha,Takayama tuberculataandTakayamasp. The typical cell forms ofK. selliformisin the bloom were discoid, dorsoventrally flattened, and larger than the cell sizes in previous reports, 35.3–43.6 (39.4±2.1) μm in length. Transparent cells ofKr. selliformislacking or having several shrunken chloroplasts and oil droplets were also found. Cells ofKr. selliformishad morphological variation, but the species could be distinguished from other co-occurredKareniaspecies by its numerous (46–105) and small granular (2.9–4.6 μm in diameter) chloroplasts and the nucleus positioned in the hypocone. Cell density ofKr. selliformisexceeding 100 cells/mL was recorded in the range of temperature 9.8–17.6°C. The rDNA sequences determined fromKr. selliformisin the blooms of Hokkaido, Japan in 2021 were identical to those from another bloom in Kamchatka, Russia in 2020.

Highlights

A marine fauna-destructive harmful algal bloom in the Pacific coast of eastern Hokkaido, Japan in September–November 2021 was dominated byKarenia selliformis.

Cells ofKarenia selliformistypical in the bloom were discoid and possessing numerous small chloroplasts, approximately 70 in number.

Cells ofKarenia selliformisshowed morphological variation in size and shape, and transparent motile cells lacking or having degraded chloroplasts were also present.

Co-occurred kareniaceans in the bloom wereKarenia longicanalis,Karenia mikimotoi,Karlodiniumsp. andTakayamaspp.

rDNA sequences ofKarenia selliformisin the blooms of Hokkaido in 2021 and Kamchatka in 2020 were identical, which belong to the group I ofKr. selliformis.
Myricetin allosterically inhibits Dengue NS2B-NS3 protease as studied by NMR and MD simulations
Authors: Dang Mei , Lim Liangzhong , Roy Amrita , Song Jianxing
Published: December 2021

Dengue NS2B-NS3 protease existing in equilibrium between the active and inactive forms is essential for virus replication, thus representing a key drug target. Here Myricetin, a plant flavonoid, was characterized to non-competitively inhibit Dengue protease. Further NMR study identified the protease residues perturbed by binding to Myricetin, which were utilized to construct the Myricetin-protease complexes. Strikingly, in the active form Myricetin binds a new allosteric site (AS2) far away from the active site pocket and allosteric site (AS1) for binding Curcumin, while in the inactive form it binds both AS1 and AS2. To decipher the mechanism for the allosteric inhibition by Myricetin, we conducted molecular dynamics (MD) simulations on different forms of Dengue NS2B-NS3 protease. Unexpectedly, the binding of Myricetin to AS2 is sufficient to disrupt the active conformation by displacing the characteristic NS2B C-terminal β- hairpin from the active site pocket. By contrast, the binding of Myricetin to AS1 and AS2 results in locking the inactive conformation. Therefore Myricetin represents the first small molecule which allosterically inhibits Dengue protease by both disrupting the active conformation and locking the inactive conformation. The results enforce the notion that a global allosteric network exists in Dengue NS2B-NS3 protease, which is susceptible to allosteric inhibition by small molecules such as Myricetin and Curcumin. As Myricetin has been extensively used as a food additive, it might be directly utilized to fight the Dengue infections and as a promising starting for further design of potent allosteric inhibitors.

Graphic Abstract
A model for reconstructing trends and distribution in age at first sex from multiple household surveys with reporting biases
Authors: Nguyen Van Kính , Eaton Jeffrey W
Published: December 2021

Age at first sex (AFS) is a key indicator for monitoring sexual behaviour risk for HIV and sexually transmitted diseases. Reporting of AFS data, however, suffer social-desirability and recall biases which obscure AFS trends and inferences constructed from it. We illustrated examples of the biases using data from multiple nationally-representative Demographic and Health Surveys household surveys conducted between 1992 and 2019 in Ethiopia (4 surveys), Guinea (4 surveys), Senegal (8 surveys), and Zambia (8 surveys). Based on this, we proposed a time-to-event, interval censored model for the AFS that uses overlapping reports by the same birth cohort in successive surveys to adjust reporting biases. The three-parameter log-skew-logistic distribution described the asymmetric and nonmonotonic hazard exhibited by empirical AFS data. In cross-validation analysis, incorporating a term for AFS reporting bias as a function of age improved model predictions for the trend of AFS over birth cohorts. The interquartile range for the AFS was 16 years to 23 years for Ethiopian and Senegalese women and 15 years to 20 years for Guinean and Zambian men. Median AFS increased by around one to 1.5 years between the 1960 and 1989 birth cohorts for all four datasets. Younger male respondents tended to report a younger AFS while female respondents tended to report an older AFS than when asked in later surveys. Above age 30, both male and female respondents tended to report older AFS compared to when surveyed in their late twenties. Simulations validated that the model recovers the trend in AFS over birth cohorts in the presence of reporting biases. At least three surveys are needed to obtain reliable trend estimate for a 20-years trend. Mis-specified reference age at which reporting is assumed unbiased did not affect the trend estimate but resulted in biased estimates for the median AFS in the most recent birth cohorts.
Elevation drives activity of soil bacteria, but not of bacterial viruses
Authors: Merges D. , Schmidt Alexandra , Schmitt Imke , Neuschulz Eike Lena , Dal Grande Francesco , Bálint Miklós
Published: December 2021

Soil microbial diversity affects ecosystem functioning and global biogeochemical cycles. Soil bacterial communities catalyze a diversity of biogeochemical reactions and have thus sparked considerable scientific interest. One driver of bacterial community dynamics in natural ecosystems has so far been largely neglected: the predator-prey interactions between bacterial viruses (bacteriophages) and bacteria. To generate ground level knowledge on environmental drivers of these particular predator-prey dynamics we propose an activity-based ecological framework to simultaneous capture community dynamics of bacteria and bacteriophages in soils. An ecological framework and specifically the analyses of community dynamics across latitudinal and altitudinal gradients have been widely used in ecology to understand community-wide responses of innumerable taxa to environmental change, in particular to climate. Here, we tested the hypothesis that the activity of bacteria and bacteriophages co-decline across an elevational gradient. We used metatranscriptomics to investigate bacterial and bacteriophage activity patterns at 5 sites across 400 elevational meters in the Swiss Alps in 2015 and 2017. We found that metabolic activity (transcription levels) of bacteria declined significantly with increasing elevation, but activity of bacteriophages did not. We showed that bacteriophages are consistently active in soil along the entire gradient. Bacteriophage activity pattern, however, is divergent from that of their putative bacterial prey. Future efforts will be necessary to link the environment-activity relationship to predator-prey dynamics, to understand the magnitude of viral contributions to mobilize bacterial cell carbon when infection causes bacterial cell death, a process that may represent an overlooked component of soil biogeochemical cycles.
Viral infection engenders bona fide and bystander lung memory B cell subsets through permissive selection
Authors: Gregoire Claude , Spinelli Lionel , Villazala-Merino Sergio , Gil Laurine , Moussa Myriam , Dong Chuang , Zarubica Ana , Fallet Mathieu , Navarro Jean-Marc , Malissen Bernard , Milpied Pierre , Gaya Mauro
Published: December 2021

Lung-resident memory B cells (MBCs) provide localized protection against reinfection in the respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity. scRNA-seq analysis and confocal imaging revealed that two main transcriptionally distinct subsets of MBCs colonize the lung peribronchial niche after infection. These subsets arise from different progenitors and are both class-switched, somatically mutated and intrinsically biased in their differentiation fate towards plasma cells. Combined analysis of antigen-specificity and B cell receptor repertoire unveiled a highly permissive selection process that segregates these subsets into “bona fide” virus-specific MBCs and “bystander” MBCs with no apparent specificity for eliciting viruses. Thus, diverse transcriptional programs in MBCs are not linked to specific effector fates but rather to divergent strategies of the immune system to simultaneously provide rapid protection from reinfection while diversifying the initial B cell repertoire.
Transection of the ventral hippocampal commissure impairs spatial reference but not contextual or spatial working memory
Authors: Jordan Jake T. , Tong Yi , Pytte Carolyn L.
Published: December 2021

Plasticity is a neural phenomenon in which experience induces long-lasting changes to neuronal circuits and is at the center of most neurobiological theories of learning and memory. However, too much plasticity is maladaptive and must be balanced with substrate stability. Area CA3 of the hippocampus provides such a balance via hemispheric lateralization, with the left hemisphere dominant in providing plasticity and the right specialized for stability. Left and right CA3 project bilaterally to CA1; however, it is not known whether this downstream merging of lateralized plasticity and stability is functional. We hypothesized that interhemispheric convergence of input from these pathways is essential for integrating spatial memory stored in the left CA3 with navigational working memory facilitated by the right CA3. To test this, we severed interhemispheric connections between the left and right hippocampi in mice and assessed learning and memory. Despite damage to this major hippocampal fiber tract, hippocampus-dependent navigational working memory and short- and long-term memory were both spared. However, tasks that required the integration of information retrieved from memory with ongoing navigational working memory and navigation were impaired. We propose that one function of interhemispheric communication in the mouse hippocampus is to integrate lateralized processing of plastic and stable circuits to facilitate memory-guided spatial navigation.
Cavitation erosion behavior of hydraulic concrete under high-speed flow
Authors: Wang Xin , Xie Ting-Qiang
Published: December 2021

Purpose

Cavitation erosion has always been a common technical problem in a hydraulic discharging structure. This paper aims to investigate the cavitation erosion behavior of hydraulic concrete under high-speed flow.

Design/methodology/approach

A high-speed and high-pressure venturi cavitation erosion generator was used to simulate the strong cavitation. The characteristics of hydrodynamic loads of cavitation bubble collapse zone, the failure characteristics and the erosion development process of concrete were investigated. The main influencing factors of cavitation erosion were discussed.

Findings

The collapse of the cavitation bubble group produced a high frequency, continuous and unsteady pulse load on the wall of concrete, which was more likely to cause fatigue failure of concrete materials. The cavitation action position and the main frequency of impact load were greatly affected by the downstream pressure. A power exponential relationship between cavitation load, cavitation erosion and flow speed was observed. With the increase of concrete strength, the degree of damage of cavitation erosion was approximately linearly reduced.

Originality/value

After cavitation erosion, a skeleton structure was formed by the accumulation of granular particles, and the relatively independent bulk structure of the surface differed from the flake structure formed after abrasion.
Family-supportive supervisor behaviors and employee turnover intention in the foodservice industry: does gender matter?
Authors: Jolly Phillip M. , Gordon Susan E. , Self Timothy T.
Published: December 2021

Purpose

The restaurant industry is characterized by long hours, intense job demands and a lack of work-life balance. While a growing body of research has investigated methods for decreasing role conflict-related stress and strain in foodservice and hospitality employees, there is still little understanding of what supervisors can do to decrease work-life-related employee strain. This study aims to investigate how family-supportive supervisor behaviors (FSSB) influence employee emotional exhaustion (EE) and subsequent turnover intentions, as well as the role of gender in moderating these effects.

Design/methodology/approach

A survey-based design using a national panel of 226 foodservice employees was used to investigate the hypotheses developed in this paper.

Findings

Results indicated that FSSB decreased employee EE and subsequent turnover intentions. The authors also found that this relationship was stronger for female employees.

Research limitations/implications

The study provides insight into the role that employee gender may play in response to the perception of and reactions to FSSB. Women still shoulder a majority of home and non-work caring duties, and therefore, they may be more positively affected when supervisors engage in behaviors that allow for balancing work and non-work demands.

Originality/value

There is little hospitality or foodservice-focused research into the effects of FSSB, and little overall research that investigates the role that gender may play in shaping the beneficial effects of FSSB. Given that women make up a majority of foodservice employees in the USA, yet there is a lack of female representation at higher levels of organizations, the study provides insights into ways in which organizations and supervisors can improve female employees’ working experiences and potentially increase their retention.
Exploring key factors influencing customer behavioral intention in robot restaurants
Authors: Guan Xinhua , Gong Jinhong , Li Mingjie , Huan Tzung-Cheng
Published: December 2021

Purpose

The purpose of this study is to explore the impact of the robot restaurant servicescape and robot service competence (RSC) on customers’ behavioral intentions and to analyze the mediating role of hedonic value (HV) and utilitarian value (UV) in these relationships and the moderating role of individual characteristics.

Design/methodology/approach

This research involves seven constructs to be measured, namely, servicescape, RSC, negative attitude toward robots (NAR), openness to change (OC), HV, UV and behavioral intention. This research selects Foodom robot restaurants, located in Shunde and Guangzhou of China, as the research site, and the research objects are customers having dinner in the restaurant. A total of 485 valid data was collected. Structural equation modeling was used to analyze the data, verify the proposed research model, and test the research hypotheses.

Findings

The study finds that servicescape and RSC improve customer behavioral intention. Additionally, HV and UV mediate the influence of servicescape and RSC on customer behavioral intention. Moreover, OC negatively moderates the influence of servicescape on UV and that a NAR negatively moderates the influence of RSC on HV.

Originality/value

Through carefully design of servicescape and the improvement in service capabilities of robots, the original service delivery dominated by frontline service personnel can be transformed into service delivery dominated by service robots, which is conductive to providing a pleasant and unforgettable experience for customers.
Can ambulance dispatch categories discriminate traffic incidents that do/do not require a lights and sirens response?
Authors: Ceklic Ellen , Tohira Hideo , Finn Judith , Brink Deon , Bailey Paul , Whiteside Austin , Brown Elizabeth , Brits Rudolph , Ball Stephen
Published: December 2021

Purpose

Traffic incidents vary considerably in their severity, and the dispatch categories assigned during emergency ambulance calls aim to identify those incidents in greatest need of a lights and sirens (L&S) response. The purpose of this study was to determine whether dispatch categories could discriminate between those traffic incidents that do/do not require an L&S response.

Design/methodology/approach

A retrospective cohort study of ambulance records was conducted. The predictor variable was the Traffic/Transportation dispatch categories assigned by call-takers. The outcome variable was whether each incident required an L&S response. Possible thresholds for identifying dispatch categories that require an L&S response were developed. Sensitivity and specificity were calculated for each threshold.

Findings

There were 17,099 patients in 13,325 traffic incidents dispatched as Traffic/Transportation over the study period. “Possible death at scene” ‘had the highest odds (OR 22.07, 95% CI 1.06–461.46) and “no injuries” the lowest odds (OR 0.28 95% CI 0.14–0.58) of requiring an L&S response compared to the referent group. The area under the ROC curve was 0.65, 95% CI [0.64, 0.67]. It was found that Traffic/Transportation dispatch categories allocated during emergency ambulance calls had limited ability to discriminate those incidents that do/do not require an L&S response to the scene of a crash.

Originality/value

This research makes a unique contribution, as it considers traffic incidents not as a single entity but rather as a number of dispatch categories which has practical implications for those emergency medical services dispatching ambulances to the scene.
Experimental and analytical investigation of using externally bonded, hybrid, fiber-reinforced polymers to repair and strengthen heated, damaged RC beams in flexure
Authors: Al Rjoub Yousef , Obaidat Ala , Ashteyat Ahmed , Alshboul Khalid
Published: December 2021

Purpose

This study aims to conduct an experimental study and finite element model (FEM) to investigate the flexural behavior of heat-damaged beams strengthened/repaired by hybrid fiber-reinforced polymers (HFRP).

Design/methodology/approach

Two groups of beams of (150 × 250 × 1,200) mm were cast, strengthened and repaired using different configurations of HFRP and tested under four-point loadings. The first group was kept at room temperature, while the second group was exposed to a temperature of 400°C.

Findings

It was found that using multiple layers of carbon fiber-reinforced polymer (CFRP) and glass fiber-reinforced polymer (GFRP) enhanced the strength more than a single layer. Also, the order of two layers of FRP showed no effect on flexural behavior of beams. Using a three-layer scheme (attaching the GFRP first and followed by two layers of CFRP) exhibited increase in ultimate load more than the scheme attached by CFRP first. Furthermore, the scheme HGC (heated beam repaired with glass and carbon, in sequence) allowed to achieve residual flexural capacity of specimen exposed to 400°C. Typical flexural failure was observed in control and heat-damaged beams, whereas the strengthened/repaired beams failed by cover separation and FRP debonding, however, specimen repaired with two layers of GFRP failed by FRP rupture. The FEM results showed good agreement with experimental results.

Originality/value

Few researchers have studied the effects of HFRP on strengthening and repair of heated, damaged reinforced concrete (RC) beams. This paper investigates, both experimentally and analytically, the performance of externally strengthened and repaired RC beams, in flexure, with different FRP configurations of CFRP and GFRP.
COVID‐19 and housing market effects: Evidence from U.S. shutdown orders
Authors: D'Lima Walter , Lopez Luis Arturo , Pradhan Archana
Published: December 2021

This paper provides novel evidence on pricing effects in housing markets following government shutdown responses to COVID‐19 using microlevel data on U.S. residential property transactions. We find that post‐shutdown pricing effects not only depend on population density but also the size and structural density of properties. The average price of a three‐bedroom property fell by approximately 1.4% in densely populated locations (e.g., downtown) but increased by about 1.5% in low‐density locations (e.g., suburbs) where shutdowns were enacted. The effects are more drastic for properties with fewer bedrooms. We also document a significant decrease in sales for markets under a shutdown.
The impacts of antimicrobial and antifungal activity of cell‐free supernatants from lactic acid bacteria in vitro and foods
Authors: Mani‐López Emma , Arrioja‐Bretón Daniela , López‐Malo Aurelio
Published: December 2021

Lactic acid bacteria (LAB) are distinguished by their ability to produce lactic acid, among other interesting metabolites with antimicrobial activity. A cell‐free supernatant (CFS) is a liquid containing the metabolites resulting from microbial growth and the residual nutrients of the medium used. CFS from LAB can have antimicrobial activity due to organic acids, fatty acids, and proteinaceous compounds, among other compounds. This review aims to summarize the information about CFS production, CFS composition, and the antimicrobial (antibacterial and antifungal) activity of CFS from LAB in vitro, on foods, and in active packaging. In addition, the mechanisms of action of CFS on cells, the stability of CFS during storage, CFS cytotoxicity, and the safety of CFS are reviewed. The main findings are that CFS's antibacterial and antifungal activity in vitro has been widely studied, particularly in members of the genus Lactobacillus. CFS has produced strong inhibition of bacteria and molds on foods when applied directly or in active packaging. In most studies, the compounds responsible for antimicrobial activity are identified. A few studies indicate that CFSs are stable for 1 to 5 months at temperatures ranging from 4 to 35°C. The cytotoxicity of CFS on human cells has not been well studied. However, the studies that have been performed reported no toxicity of CFS. Therefore, it is necessary to investigate novel growth mediums for CFS preparation that are compatible with food sensory properties. More studies into CFS stability and cytotoxic effects are also needed.
Evaluation of genetic divergence of coffee genotypes using the volatile compounds and sensory attributes profile
Authors: Machado Jéssica Louzada , Tomaz Marcelo Antonio , da Luz José Maria Rodrigues , Osório Vanessa Moreira , Costa Adilson Vidal , Colodetti Tafarel Victor , Debona Danieli Grancieri , Pereira Lucas Louzada
Published: December 2021

The quality of the coffee beverage is related to the chemical, physical, and sensory attributes of the coffee beans that vary with the geographic location of the crop, genetic factors, and post‐harvest processing. So, the objective of this study was to evaluate the genetic divergence of 27 genotypes of Coffea canephora using the volatile compounds and sensory attributes profile to select genotypes that produce a coffee beverage with high sensory quality. This genetic diversity was estimated from the Euclidean distance matrix using non‐standard data and the Unweighted Pair‐Group Method Using Arithmetic Averages (UPGMA). The 2‐furyl‐methanol, 4‐ethenyl‐2‐methoxyphenol, furfural, 5‐methylfurfural, methylpyrazine, and 2,6‐dimethylpyrazine were predominating volatile compounds in the genotypes. The sensory attributes had a positive Pearson's correlation with the total score. The volatile compounds had a different relative contribution to the genetic divergence between the genotypes of C. canephora. The 4‐ethenyl‐2‐methoxyphenol, 2‐furyl‐methanol, and furfural were volatile compounds that most contributed to the formation of the groups in the UPGMA dendrogram. The relative contribution of sensory attributes to dissimilarity among genotypes was 6.42% to 20.20%. Therefore, this study verified the relative contribution of volatile compounds, in specially 4‐ethenyl‐2‐methoxyphenol, 2‐furyl‐methanol, and furfural, and sensory attributes (flavor, mouthfeel, and bitterness/sweetness) to the genetic divergence between the genotypes of the three clonal varieties. Thus, this work points out compounds that positively contribute to the sensory quality of the Conilon coffee beverage.
Increased gene expression of B cell‐activating factor of tumor necrosis factor family, in remitting antineutrophil cytoplasmic antibody‐associated vasculitis patients
Authors: Jha Saket , Singh Jagdeep , Minz Ranjana W. , Dhooria Aadhar , Naidu GSRSNK , Ranjan Kumar Rajiv , Rathi Manish , Jain Sanjay , Anand Shashi , Sharma Aman
Published: December 2021

Aim

To study the expression of B cell‐activating factor of tumor necrosis factor family (BAFF) and A proliferation‐inducing ligand (APRIL) genes in active and remitting patients with anti‐neutrophil cytoplasmic antibody‐associated vasculitis (AAV) and healthy controls and their correlation with disease activity.

Methods

This was a prospective case‐control study. Gene expressions of BAFF and APRIL were studied in 32 patients with AAV (16 each with active disease and in remission) and 30 healthy age and sex matched controls by real‐time polymerase chain reaction.

Results

Out of 32 AAV patients, 26 had granulomatosis with polyangiitis (GPA) and 6 had microscopic polyangiitis (MPA). Mean ages of patients in active (12 GPA and 4 MPA) and remission (14 GPA and 2 MPA) groups were 39.4 ± 17.2 and 44.6 ± 16.1 years, respectively. BAFF gene expression was significantly higher in both the active AAV group and remission AAV group compared to controls (P < .01). The BAFF expression was significantly higher in AAV patients in remission compared to active AAV patients (P = .003). In contrast, APRIL expression did not differ between AAV patients and controls (P = .829). However, APRIL had significantly higher expression in remission as compared to active patients (P = .048). There was no significant correlation of both BAFF and APRIL expression with disease activity markers (erythrocyte sedimentation rate, C‐reactive protein, platelets and Birmingham Vasculitis Activity Score version 3).

Conclusion

BAFF gene is significantly expressed in patients with AAV. Among AAV patients, there is a significantly higher expression of BAFF and APRIL in remitting state of the disease as compared to active state. There is no significant change in APRIL gene expression in patients with AAV as compared to controls. This makes a case for anti‐BAFF therapy in future for AAV patients in northern India.
The ROAD to continuous business model innovation: A longitudinal study unveiling patterns of cognitive sensing dynamic capabilities
Authors: Bitetti Leandro , Gibbert Michael
Published: December 2021

The dynamic capabilities of sensing, seizing and transforming enable business model innovation. The emerging literature on the cognitive antecedents of business model innovation identifies several sensing capabilities that could facilitate the design of a new business model. However, little attention has been paid to the configuration of different patterns of sensing capabilities as enablers of business model innovations over time. This longitudinal case study uses a cognitive perspective to explore such sensing dynamic capabilities across three generations of business owners of a butcher's shop that has engaged in four business model innovations over 80 years. The innovations allowed the firm to grow, whereas most of its competitors faced severe crises or even failed because they decided to retain the same business model. Our cognitive perspective allows us to unveil different patterns of four sensing capabilities (i.e. Responding, Overturning, Anticipating and Dribbling) that allowed us to describe the ‘ROAD’ the business owners travelled to initiate their business model innovation processes. This ROAD to business model innovation and the detailed patterns underlying the four capabilities may help other small business owners develop viable business models and overcome the challenges of business model innovations.
Cost‐effectiveness of second‐line empagliflozin versus liraglutide for type 2 diabetes in the United States
Authors: Reifsnider Odette S. , Pimple Pratik , Brand Sarah , Bergrath Washington Evelien , Shetty Sharash , Desai Nihar R.
Published: December 2021

Aim

To estimate the cost‐effectiveness of sequential use of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin and glucagon‐like peptide‐1 receptor agonist liraglutide after metformin in patients with type 2 diabetes (T2D) from the US payer perspective.

Materials and Methods

An economic simulation model with a lifetime horizon was developed to estimate T2D‐related complications (including cardiovascular [CV] death, myocardial infarction, stroke, and renal outcomes) using EMPA‐REG OUTCOME data or UK Prospective Diabetes Study risk equations, in patients with or without a history of cardiovascular disease (CVD), respectively. Evidence synthesis methods were used to provide effectiveness inputs for empagliflozin and liraglutide. Population characteristics, adverse event rates, treatment escalation, costs ($2019), and utilities (both discounted 3%/year) were taken from US sources.

Results

Compared with second‐line liraglutide in the overall T2D population, second‐line empagliflozin was dominant as it was associated with lower total lifetime cost ($11 244/patient less) and resulted in a quality‐adjusted life‐year (QALY) gain (0.32/patient). Second‐line empagliflozin was associated with reductions in CV death (by 5%) and lower cumulative complication rates in patients with CVD (by 2%), relative to second‐line liraglutide. These findings were consistent among patients with co‐morbid CVD, with gains in incremental QALYs (0.43/patient) and lower lifetime cost (by $10 175/patient) relative to second‐line liraglutide. Scenario analyses consistently showed dominance for second‐line empagliflozin.

Conclusion

For patients with T2D, use of second‐line empagliflozin combined with metformin was a dominant strategy for US payers, associated with extended survival, improved QALYs, and lower costs compared with second‐line liraglutide.
The effect of empagliflozin on the total burden of cardiovascular and hospitalization events in the Asian and non‐Asian populations of the EMPA‐REG OUTCOME trial of patients with type 2 diabetes and cardiovascular disease
Authors: Kaku Kohei , Wanner Christoph , Anker Stefan D. , Pocock Stuart , Yasui Atsutaka , Mattheus Michaela , Lund Søren S.
Published: December 2021

Aims

The sodium‐glucose co‐transporter 2 inhibitor empagliflozin reduced the total burden of cardiovascular, mortality, and all‐cause hospitalization events, including first and recurrent events, in EMPA‐REG OUTCOME participants with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD). We investigated the effect of empagliflozin on the total burden of cardiovascular and hospitalization events in Asian participants.

Materials and methods

Participants were randomized to empagliflozin 10 mg, 25 mg or placebo plus standard of care. The primary and key secondary outcomes were the composite of cardiovascular death, non‐fatal myocardial infarction, and non‐fatal stroke and the primary outcome plus hospitalization for unstable angina, respectively. The effect of pooled empagliflozin versus placebo on total (first plus recurrent) cardiovascular and hospitalization events was analysed using a negative binomial model that preserves randomization and accounts for within‐patient correlation of multiple events. We analysed Asian versus non‐Asian EMPA‐REG OUTCOME population subgroups post hoc.

Results

Among 1517 Asian participants, empagliflozin reduced the relative risk of total events of the primary outcome by 39% versus placebo [rate ratio (95% confidence interval): 0.61 (0.43, 0.89)], the key secondary outcome by 33% [0.67 (0.48, 0.93)], the composite of cardiovascular death (excluding fatal stroke) and hospitalization for heart failure by 43% [0.57 (0.33, 0.996)], and all‐cause hospitalization by 21% [0.79 (0.65, 0.97)]. The effects of empagliflozin were consistent between Asian and non‐Asian populations (treatment‐by‐subgroup interaction p > .05).

Conclusions

Empagliflozin reduced the total burden of cardiovascular and hospitalization events in Asian and non‐Asian EMPA‐REG OUTCOME participants with T2D and established ASCVD, consistent with the overall trial population.
Syntax‐based metamorphic relation prediction via the bagging framework
Authors: Yin Yuyu , Ruan Jiajie , Li Youhuizi , Li Yu , Pan Zhijin
Published: December 2021

Software testing is an indispensable part of the software engineering industry, which guarantees product reliability and safety. Traditional testing approaches face the testing Oracle problem, they are difficult to construct the expected outputs with the increasing of program complexity. As a result, metamorphic testing, which tests the program by examining the relationship between the execution results, is proposed. However, existing manual metamorphic relation construction requires huge effects of domain experts, and automatic methods are unstable and inefficient due to the insufficient software feature mining. Hence, we proposed a multi‐dimensional program structure‐based metamorphic relation prediction approach, which is composed of feature extraction and prediction model building. In the feature extraction stage, the testing program is converted to multiple intermediate structures (such as control flow graphs and abstract syntax trees) to explore its features. In the prediction model building stage, the extracted feature set is used as the training set, and a novel semi‐supervised support vector machine‐bagging‐K‐nearest neighbors algorithm is designed to train the prediction model. Besides, a two‐phase hybrid granularity search algorithm is proposed to improve the prediction performance by selecting the optimal number of weak classifiers. Compared with existing approaches, our proposed model can improve the accuracy by around 14%.
Parental burnout during the COVID‐19 pandemic
Authors: Skjerdingstad Nora , Johnson Miriam S. , Johnson Sverre U. , Hoffart Asle , Ebrahimi Omid V.
Published: December 2021

Increased and long‐term parental stress related to one's parental role can lead to parental burnout. In the early phase of the COVID‐19 pandemic, families experienced intensified pressure due to the government‐initiated contact restrictions applied to prevent the spread of the virus in the population. This study investigates the risk factors and predictors of parental burnout in a large sample of parents (N = 1488) during the COVID‐19 pandemic in Norway. Demographic and psychosocial factors were assessed at two timepoints: at the beginning of the pandemic outbreak in March 2020 (T1) and at 3 months follow‐up (T2). A hierarchical regression analysis was applied to identify the factors that contribute to parental burnout at T2. Parental burnout was additionally explored across subgroups. Findings revealed that younger age was associated with more parental burnout. Concurrent (T2) use of unhelpful coping strategies, insomnia symptoms, parental stress, and less parental satisfaction was significantly associated with the presence of greater parental burnout (T2). Additionally, parental stress and satisfaction measured in the earliest phase of the pandemic (T1) were associated with parental burnout 3 months later (T2) over and above concurrent parental stress/satisfaction. Unemployed parents and individuals with a mental health condition were identified as subgroups with substantially heightened levels of parental burnout.
High dietary protein and fat contents exacerbate hepatic senescence and SASP in mice
Authors: Nehme Jamil , Yang Dengbao , Altulea Abdullah , Varela‐Eirin Marta , Wang Lu , Hu Sumei , Wu Yingga , Togo Jacques , Niu Chaoqun , Speakman John R. , Demaria Marco
Published: December 2021

Dietary choices have a profound impact on the aging process. In addition to the total amount of energy intake, macronutrient composition influences both health and lifespan. However, the exact mechanisms by which dietary macronutrients influence onset and progression of age‐associated features remain poorly understood. Cellular senescence is a state of stable growth arrest characterized by the secretion of numerous bioactive molecules with pro‐inflammatory properties. Accumulation of senescent cells is considered one of the basic mechanisms of aging and an important contributor to chronic inflammation and tissue degeneration. Whether dietary macronutrients affect the accumulation and the phenotype of senescent cells with age is still unknown. Here, we show that feeding on diets with varying ratios of dietary macronutrients for 3 months has a significant effect on different senescence‐associated markers in the mouse liver. High protein intake is associated with higher expression levels of the two classical senescence‐associated growth arrest genes, p21 and p16. Furthermore, the expression of many pro‐inflammatory secretory markers was increased in diets enriched in protein and further enhanced by increases in fat content. These results provide preliminary evidence that dietary macronutrients have a significant influence on senescence markers and merit further investigation.
PREFIGURATIVE HUMANITIES
Authors: DOMAŃSKA EWA
Published: December 2021

In this article, I propose that a future‐oriented project of prefigurative humanities will provide a much‐needed framework for fostering alternative ways of approaching the past beyond history. I consider whether such future‐oriented humanities, which are guided by the idea of critical hope and epistemic justice (understood as the inclusion of knowledges created in “epistemic peripheries”), might provide critical tools for imagining different scenarios of the future, as manifested in realistic and responsible utopias. The prototypes of such utopias might be found in art, film, literature, and history as well as in real, everyday life. Following Ruth Levitas's approach to utopia and Ariella Azoulay's project of potential history, I also consider how utopia might function not only as a goal but as a method to revive more positive thinking about the future.
Biochemical properties, nutritional quality, colour profile and techno‐functional properties of whole grain sourdough and malted cowpea and quinoa flours
Authors: Kewuyemi Yusuf Olamide , Kesa Hema , Adebo Oluwafemi Ayodeji
Published: December 2021

The particular interest in biomodifications of underutilised but nutritionally distinct whole grains is vital to promote diet diversity, nutrition transition and food security. This study investigated the use of short‐term solid‐state fermentation and germination to ease processability and improve the quality characteristics of whole grain (WG) cowpea and quinoa flours. The fermented and germinated WG flours were prepared at 28 °C for 48 h. The biochemical, nutritional quality and techno‐functional properties of the obtained flours were determined. The macromolecules’ biomodification by microbial metabolism and endogenous enzymes activation influenced quality variations in the biomodified flours. The cowpea sourdough flour (CSF) presented lower acidity (pH 4.72), higher total flavonoid (29.63 mg QE/g), total phenolic (8.21 mg GAE/g) and antioxidant activity. The flour also showed high contents of fibre (5.30%), ash (4.42%), calcium (864.49 mg/kg), potassium (12848.64 mg/kg), zinc (33.83 mg/kg), good protein (21.43%) and a moderate fat level (2.65%). Higher oil absorption and water solubility indices were also noted for CSF. In contrast, malted quinoa flour (MQF) exhibited higher swelling power, increased dispersibility and improved final, peak and trough viscosities. The CSF displayed higher redness and browning index, whereas MQF had greater lightness. The results suggest that CSF and MQF had the best complementary quality attributes. Their formulation as gluten‐free, whole and multigrain ingredients may promote healthy choices for individualised growing dietary needs.
An integrative review: Chronic kidney disease awareness and the social determinants of health inequities
Authors: Iroegbu Christin , Lewis Lisa , Matura Lea Ann
Published: December 2021

Background

Chronic kidney disease is a common and prevalent condition in the United States. However, 90% of individuals with chronic kidney disease are unaware of their diagnosis.

Aims

To summarize the empirical and theoretical literature to provide a comprehensive understanding of the social determinants of health inequities associated with CKD awareness. Social determinants of health inequities are underlying pathways that shape the health opportunities of individuals based on their social position.

Design

Integrative review.

Data Sources

(May 2020 through July 2020) Data sources included PubMed, sociological abstracts, ScienceDirect, CINAHL and Google Scholar.

Review Methods

Quantitative, qualitative and theoretical articles describing the association of social determinants of health inequities and chronic kidney disease awareness were included.

Results

A total of 19 articles were reviewed: two qualitative, one theoretical and 16 quantitative.

Conclusion

Findings from this review revealed that socioeconomic status, education, race and gender are consistently associated with patient chronic kidney disease awareness. These findings should serve as a basis for further research on interventions to improve chronic kidney disease awareness as well as guide nurses and health care professionals in caring for this population.
microRNA‐19b‐3p‐containing extracellular vesicles derived from macrophages promote the development of atherosclerosis by targeting JAZF1
Authors: Wang Qingshan , Dong Yuandi , Wang Haiyang
Published: December 2021

Atherosclerosis has been regarded as a major contributor to cardiovascular disease. The role of extracellular vesicles (EVs) in the treatment of atherosclerosis has been increasingly reported. In this study, we set out to investigate the effect of macrophages‐derived EVs (M‐EVs) containing miR‐19b‐3p in the progression of atherosclerosis, with the involvement of JAZF1. Following isolation of EVs from macrophages, the M‐EVs were induced with ox‐low density lipoprotein (LDL) (ox‐LDL‐M‐EVs), and co‐cultured with vascular smooth muscle cells (VSMCs). RT‐qPCR and western blot assay were performed to determine the expression of miR‐19b‐3p and JAZF1 in M‐EVs and in VSMCs. Lentiviral infection was used to overexpress or knock down miR‐19b‐3p. EdU staining and scratch test were conducted to examine VSMC proliferation and migration. Dual‐luciferase gene reporter assay was performed to examine the relationship between miR‐19b‐3p and JAZF1. In order to explore the role of ox‐LDL‐M‐EVs carrying miR‐19b‐3p in atherosclerotic lesions in vivo, a mouse model of atherosclerosis was established through high‐fat diet induction. M‐EVs were internalized by VSMCs. VSMC migration and proliferation were promoted by ox‐LDL‐M‐EVs. miR‐19b‐3p displayed upregulation in ox‐LDL‐M‐EVs. miR‐19b‐3p was transferred by M‐EVs into VSMCs, thereby promoting VSMC migration and proliferation. mir‐19b‐3p targeted JAZF1 to decrease its expression in VSMCs. Atherosclerosis lesions were aggravated by ox‐LDL‐M‐EVs carrying miR‐19b‐3p in ApoE−/− mice. Collectively, this study demonstrates that M‐EVs containing miR‐19b‐3p accelerate migration and promotion of VSMCs through targeting JAZF1, which promotes the development of atherosclerosis.