bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating protection afforded by prior infection in preventing reinfection: Applying the test-negative study design
Authors: Ayoub Houssein H. , Tomy Milan , Chemaitelly Hiam , Altarawneh Heba N. , Coyle Peter , Tang Patrick , Hasan Mohammad R. , Kanaani Zaina Al , Kuwari Einas Al , Butt Adeel A. , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Nasrallah Gheyath K. , Benslimane Fatiha M. , Khatib Hebah A. Al , Yassine Hadi M. , Kuwari Mohamed G. Al , Al Romaihi Hamad Eid , Abdul-Rahim Hanan F. , Al-Thani Mohamed H. , Khal Abdullatif Al , Bertollini Roberto , Abu-Raddad Laith J.
Published: January 2022

Background

The Coronavirus Disease 2019 (COVID-19) pandemic has highlighted an urgent need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection (PES) by novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods

Mathematical modeling was used to demonstrate the applicability of the test-negative, case-control study design to derive PES. Modeling was also used to investigate effects of bias in PES estimation. The test-negative design was applied to national-level testing data in Qatar to estimate PES for SARS-CoV-2 infection and to validate this design.

Results

Apart from the very early phase of an epidemic, the difference between the test-negative estimate for PES and the true value of PES was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of PES even when PES began to wane after prior infection. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated PES, but the underestimate was considerable only when >50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated PES. PES against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI: 93.6-98.6) and 85.5% (95% CI: 82.4-88.1), respectively. These estimates were validated using a cohort study design.

Conclusions

The test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection.
Integrin/TGF-β1 inhibitor GLPG-0187 blocks SARS-CoV-2 Delta and Omicron pseudovirus infection of airway epithelial cells which could attenuate disease severity
Authors: Huntington Kelsey E. , Carlsen Lindsey , So Eui-Young , Piesche Matthias , Liang Olin , El-Deiry Wafik S.
Published: January 2022

As COVID-19 continues to pose major risk for vulnerable populations including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate blockade of SARS-CoV-2 pseudovirus infection of target cells. Omicron pseudovirus infected normal human small airway epithelial (HSAE) cells significantly less than D614G or Delta variant pseudovirus, and GLPG-0187 effectively blocked SARS-CoV-2 pseudovirus infection in a dose-dependent manner across multiple viral variants. GLPG-0187 inhibited Omicron and Delta pseudovirus infection of HSAE cells more significantly than other variants. Pre-treatment of HSAE cells with MEK inhibitor (MEKi) VS-6766 enhanced inhibition of pseudovirus infection by GLPG-0187. Because integrins activate TGF-β signaling, we compared plasma levels of active and total TGF-β in COVID-19+ patients. Plasma TGF-β1 levels correlated with age, race, and number of medications upon presentation with COVID-19, but not with sex. Total plasma TGF-β1 levels correlated with activated TGF-β1 levels. In our preclinical studies, Omicron infects lower airway lung cells less efficiently than other COVID-19 variants. Moreover, inhibition of integrin signaling prevents SARS-CoV-2 Delta and Omicron pseudovirus infectivity, and may mitigate COVID-19 severity through decreased TGF-β1 activation. This therapeutic strategy may be further explored through clinical testing in vulnerable and unvaccinated populations.
Target attainment of extended-interval dosing of tobramycin in patients less than five years of age with cystic fibrosis: A pharmacokinetic analysis
Authors: Downes Kevin J , Grim Austyn , Shanley Laura , Rubenstein Ronald C , Zuppa Athena F , Gastonguay Marc R.
Published: January 2022

Background

Extended interval dosing (EID) of tobramycin is recommended for treatment of pulmonary exacerbations in adults and older children with cystic fibrosis (CF), but data are limited in patients less than 5 years of age.

Methods

We performed a retrospective population pharmacokinetic (PK) analysis of hospitalized children with CF <5 years of age prescribed intravenous tobramycin for a pulmonary exacerbation from March 2011 to September 2018 at our hospital. Children with normal renal function who had ≥1 tobramycin concentration available were included. Nonlinear mixed effects population PK modeling was performed using NONMEM® using data from the first 48 hours of tobramycin treatment. Monte Carlo simulations were implemented to determine the fraction of simulated patients that met published therapeutic targets with regimens of 10-15 mg/kg/day once daily dosing.

Results

Fifty-eight patients received 111 tobramycin courses (range 1-9/patient). A 2-compartment model best described the data. Age, glomerular filtration rate, and vancomycin coadministration were significant covariates on tobramycin clearance. The typical values of clearance and central volume of distribution were 0.252 L/hr/kg^0.75 and 0.308 L/kg, respectively. No once daily regimens achieved all pre-specified targets simultaneously in >75% of simulated subjects. A dosage of 13 mg/kg/dose best met the predefined targets of Cmax >25 mg/L and AUC24 of 80-120 mg*h/L.

Conclusions

Based on our population PK analysis and simulations, once daily dosing of tobramycin would not achieve all therapeutic goals in young patients with CF. However, extended-interval dosing regimens may attain therapeutic targets in the majority of young patients.
One year landscape of the inactivated virus vaccine triggered RBD-specific IgG, IgM and IgA responses against the Omicron variant
Authors: Xue Jun-biao , Lai Dan-yun , Jiang He-wei , Zhou Jie , Tao Sheng-ce
Published: January 2022

We reported the first map of vaccine stimulated RBD-specific antibody responses (IgG, IgM and IgA) against the Omicron variant. We generated the map using a protein microarray, by analyzing longitudinal sera collected spanning one year from individuals immunized with 3 doses of an inactivated virus vaccine. The IgG response to RBD-Omicron is: 1/3-1/5 that of RBD-wild type; ∼6x higher for the booster dose vs. the 2nd dose; and reaches the plateau in about two weeks after the booster dose, then drops ∼5x in another two weeks. Similar results were also obtained for IgM and IgA. Because of the high correlation between RBD-specific antibody response and the neutralization activity to authentic virus, we at least indirectly revealed the landscape of antibody protection against the Omicron variant throughout the vaccination stages. Our results strongly support the necessity of booster vaccination. However, post-booster vaccination may need to be considered.
ClusTrast: a short readde novotranscript isoform assembler guided by clustered contigs
Authors: Westrin Karl Johan , Kretzschmar Warren W. , Emanuelsson Olof
Published: January 2022

Background

Transcriptome assembly from RNA-sequencing data in species without a reliable reference genome has to be performedde novo, but studies have shown thatde novomethods often have inadequate ability to reconstruct transcript isoforms. We address this issue by constructing an assembly pipeline whose main purpose is to produce a comprehensive set of transcript isoforms.

Results

We present thede novotranscript isoform assembler ClusTrast, which takes short read RNA-seq data as input, constructs a primary assembly, clusters a set of guiding contigs, aligns the short reads to the guiding contigs, assembles each clustered set of short reads individually, and merges the primary and clusterwise assemblies into the final assembly. We tested ClusTrast on real datasets from six eukaryotic species, and showed that Clus-Trast reconstructed more expressed known isoforms than any of the other testedde novoassemblers, at a moderate reduction in precision. For recall, ClusTrast was on top in the lower end of expression levels (<15% percentile) for all tested datasets, and over the entire range for almost all datasets. Reference transcripts were often (35–69% for the six datasets) reconstructed to at least 95% of their length by ClusTrast, and more than half of reference transcripts (58–81%) were reconstructed with contigs that exhibited polymorphism, measuring on a subset of reliably predicted contigs. ClusTrast recall increased when using a union of assembled transcripts from more than one assembly tool as primary assembly.

Conclusion

We suggest that ClusTrast can be a useful tool for studying isoforms in species without a reliable reference genome, in particular when the goal is to produce a comprehensive transcriptome set with polymorphic variants.
How can suppliers increase their buyers’ CSR engagement: the role of internal and relational factors
Authors: Peng Ye , Zhang Xuan , van Donk Dirk Pieter , Wang Can
Published: January 2022

Purpose

Buyer engagement proves important supports for suppliers' corporate social responsibility (CSR); however, little is known about whether and how buyer CSR engagement can be actively searched for by a supplier and what activities and policies of suppliers could enhance buyer CSR engagement. From the perspective of resource dependence theory, this study aims to explore how suppliers seek to achieve buyers' CSR engagement.

Design/methodology/approach

The proposed model and hypotheses were tested by structural equation modeling methodology using survey data collected from 243 manufacturing and service firms in China.

Findings

The results show that instrumental CSR motives and internalization of CSR policies jointly improve buyers' dependence, which in turn increases buyers' CSR engagement. In addition, this study investigates the influence of suppliers' trust on the effect of buyers' dependence on buyers' CSR engagement and finds a negative moderating effect on the dependence–engagement relation.

Practical implications

The findings show that suppliers can actively engage in CSR to strengthen their position and improve the buyer CSR engagement. In fact, proactive CSR policies and implementation do pay off in the long run for them.

Originality/value

This study offers a fresh perspective on the role of suppliers in improving CSR. In contrast to much of the literature that has considered buyer-initiated practices and policies, this is the first theoretical and empirical investigation into how suppliers can increase the buyer CSR engagement.
An open systems model of successful school leadership
Authors: Gurr David , Drysdale Lawrie , Goode Helen
Published: January 2022

Purpose

Through description and consideration of 12 models developed as part of the International Successful School Principalship Project (ISSPP), a new model of successful school leadership is developed.

Design/methodology/approach

The paper is necessarily descriptive in nature. For the first time, 12 ISSPP models are described together, and these descriptions are then used inductively to create a new successful school leadership model.

Findings

The open systems approach adopted depicts schools as a continuous cycle of input-transformation-output with feedback loops that inform each stage of the cycle. The inputs are the variables that lead to transformation. The transformation stage is the actions or processes that individuals, groups and organisations engage in because of the inputs, and these lead to a range of student and school outcomes. Feedback loops connect the stages, and the whole model is open to the influence of five contextual forces: economic, political, socio-cultural, technological and system, institutional and educational.

Originality/value

Models are an important way to make sense of complex phenomena. A new model of successful school leadership, with an open systems approach, provides a different frame to consider the findings of the ISSPP and potentially allows the ISSPP research to inform practice and connect with other school leadership views in new ways.
How do barriers to the activities of social enterprises affect their financial situation? Evidence based on data from Poland and resource mobilization theory
Authors: Mikołajczak Paweł
Published: January 2022

Purpose

The purpose of the research is to identify the degree of intensity of barriers to the activities of social enterprises (SEs) and to examine the significance of such barriers regarding the financial situation of SE’s in emerging economies.

Design/methodology/approach

The data relates to 200 SEs selected from a national survey of 1,300 Polish non-governmental organizations (NGOs). An analysis of barriers to SEs according to the frequency of their occurrence was conducted. An indicator of the intensity of barriers to the activities of social enterprises and an indicator on these enterprises’ overall financial condition were determined. Spearman rank correlation analysis was used to assess the relationship between the indices.

Findings

The results of the study indicate that in addition to excessive bureaucracy in public administration and the complex formalities related to the use of private and public funds, SEs have difficulties in maintaining good staff and volunteers, whereas people in key positions reference burnout, not only among their own employees but also in themselves. These have a significant impact on the financial situation of SEs.

Originality/value

This study contributes to the field of social entrepreneurship in two ways. One is at the macro level in that it provides suggestions for public authorities in emerging economies interested in maintaining SEs in good financial condition so that they can effectively fulfil their social functions. The second contribution – the micro approach – is recognizing the extent of the impact of barriers on the financial condition of SEs and also determining the intensity of such barriers with regard to the mobilization of resources by managers, especially in the field of human resources.
A review of research in activity-based working over the last ten years: lessons for the post-COVID workplace
Authors: Marzban Samin , Candido Christhina , Mackey Martin , Engelen Lina , Zhang Fan , Tjondronegoro Dian
Published: January 2022

Purpose

The purpose of this paper is to map and describe findings from research conducted in workspaces designed to support activity-based working (ABW) over the past 10 years (2010–2020) with a view of informing post-COVID workplaces of the positive and negative attributes of ABW.

Design/methodology/approach

Scopus was used as the search engine for this review. Papers which reported findings related to ABW and performed field study in ABW workspaces with adult occupants were included. Out of the 442 initial papers, 40 papers were included following iterative title and abstract and full text review process and consideration of inclusion and exclusion criteria. These papers were divided into three groupings (organizational, human and physical environment) based on their major focus. Positive and negative effects of ABW environments on occupants are discussed within these three topics in consideration of the implications for the post-COVID workplace.

Findings

Although the included studies were inclined to be either more positive (i.e. interior design) or negative (i.e. indoor environmental quality, productivity, distraction and privacy) in relation to various attributes of ABW, no single effect of ABW environments on occupants was in full agreement between the studies. The shortcomings of ABW environments are more related to how this way of working is implemented and how occupants use it, rather than the concept itself. A partial uptake of ABW leads to occupants’ dissatisfaction, lower productivity and lower well-being, while a holistic approach increases the chance of success. It is hypothesised that many currently reported negative aspects of the ABW concept might diminish overtime as ABW evolves and as new challenges arise. A continuous post-occupancy evaluation after relocation to an ABW-supportive environment can inform the organization about the changing needs and preference of the occupants; hence, the organization can tailor the ABW solution to the arising needs. The inter-connection between the three key ABW pillars (organizational, human and physical environment) is crucial to the success of this concept specifically in the context of the post-COVID-19 workplace.

Originality/value

This paper highlights the key shortcomings and limitations of studies produced over the past decade and identifies keys gaps in the current body of literature. It provides a new insight on how findings related to open-plan offices designed to support ABW can be categorized on the three big heading of organizational, physical and human-related aspects, and further investigates the positive and negatives outcomes reported on ABW under these headings. It also discusses how the findings arising from this literature review can inform the post-COVID workplace.
From ivory tower to a storyteller of value creation: integrated reporting at Japanese and South African universities
Authors: Sun Yanqi , Ip Pui San , Arunachalam Murugesh , Davey Howard
Published: January 2022

Purpose

The paper examines integrated reporting (IR) practices of two Japanese universities and three South African universities by evaluating and comparing their 2019 integrated reports.

Design/methodology/approach

A multiple case study research method is used in this study.

Findings

The paper reveals that IR is in its infancy at the sample universities. Some universities have initiated disclosing information to their stakeholders on how they create value. However, the universities lack a comprehensive approach to integrating financial and non-financial information, thereby affecting the IR disclosure quality. The findings indicate that informal coercive pressure of South African universities is a primary driving factor that enables the universities to achieve a higher IR disclosure quality than their Japanese counterparts.

Research limitations/implications

This paper argues that institutional theory is relevant for explaining the differences in IR practices of the universities in the two different jurisdictional settings.

Practical implications

The research will be of interest to university administrators, policymakers, regulators and other stakeholder groups of universities. The assessment of integrated reports serves as a first step to help the universities improve IR practices as well as to facilitate the diffusion of IR in higher education institutions (HEIs) globally. There is also a need for universities to pay more attention to the storytelling of their value creation in future IR disclosures.

Originality/value

It is the first to assess the IR quality of the Japanese sample universities as well as the first to conduct a comparative analysis for IR practices of universities in two different jurisdictional settings that have adopted IR. The findings of this study add to the current scholarly debate on universities' ability to tell their stories on their value creation to stakeholders via integrated reports.
Rapid response pathway united to reduce self-harm (RUSH): a case study of a pilot pathway for children and young people
Authors: Cross Molly , Clarke Tim
Published: January 2022

Purpose

In response to elevated local self-harm and suicide rates, and the lack of a dedicated pathway for children and young people (CYP) who self-harm, a rapid response pathway united to reduce self-harm (RUSH) was developed and implemented within Norwich (Norfolk, England). This public health case study aims to describe the pathway model and share its outcomes, learnings, and reflections over the pilot year.

Design/methodology/approach

RUSH was a community-based pilot pathway aiming to support CYP, 11–18 years old, engaging in or at risk of engaging in repeated self-harm and subsequently at risk of repeated attendance at local emergency departments. From May 2020 to April 2021, RUSH supported 61 CYP using funding from NHS England and Improvement.

Findings

This case study shares the pathway’s outcomes, through a mixed-method evaluation. Results indicate statistically significant reductions in self-harm frequency (p = 0.01) and anxiety and depression symptomatology (p < 0.001); a statistically significant increase in progress towards goals (p < 0.001); and a general downward trend in re-attendance at local emergency departments following RUSH. Findings also illustrate high service user satisfaction. Framework analysis of focus group data highlights positive experiences with hope for recommissioning from a staff perspective.

Originality/value

This study will be valuable for services looking to develop and implement a similar service provision, in response to the need to tackle self-harm rates as a broader approach to suicide prevention. In light of the NHS long-term plan (2019), it also serves as an example of how to develop and use a strategic co-production group, and work collaboratively with the voluntary, community and social enterprise sectors.
Ferguson as a distal crisis: Chief assessments of changes in the police institutional environment
Authors: Jurek Alicia L. , Matusiak Matthew C. , King William R.
Published: January 2022

Research Summary

We explore how a widely publicized crisis in another jurisdiction, a distal crisis, affects police agencies that were far removed from the crisis. Using data from a two‐wave, panel‐design survey of 411 police chiefs in Texas, we investigate how the events occurring in Ferguson, Missouri during 2014 changed chiefs’ perceptions of their institutional environmental sectors. Although distant from Ferguson, in the immediate aftermath chiefs rated two (local and national media) of eight (federal, state, and local law enforcement organizations as well as elected officials, police employee associations, local emergency medical organizations, and local advocacy groups) institutional sectors (including local and national media) as less impactful or legitimate.

Policy Implications

Police leaders react to crises involving other, distant agencies. Events in Ferguson led chiefs in Texas to rate the media as less potentially impactful for their agency, a change that signals decreasing legitimacy of the media in the eyes of the police. Increased animus between the media and police may threaten the media's effectiveness as watchdogs of policing and impede cooperation between the police and media.
News media and public attitudes toward the protests of 2020: An examination of the mediating role of perceived protester violence
Authors: Baranauskas Andrew J.
Published: January 2022

Research Summary

This study investigates the role of the news media in shaping attitudes toward the protests of 2020. Using data from a nationally representative election survey, it examines the association between news consumption and support for law‐and‐order policies to address protest violence, with perceptions that the protesters were violent as a potential mediator. Findings indicate that viewers of online news are less likely to support law‐and‐order policies. This relationship is mediated by perceived protester violence, with perceived violence enhancing support for law‐and‐order policies. Further examination shows that political bias plays a role: viewers of left‐leaning sites are less likely to support law‐and‐order policies to address protest violence, while viewers of right‐leaning sites are more likely. These relationships are also mediated by perceived violence.

Policy Implications

A slight majority of respondents indicate that they lean toward solving problems of racism and police violence, indicating that much of the American public is open to criminal justice reform. Perceived violence helps to shape the association of online news media with support for law‐and‐order policies. Activists should avoid violence in their protests and use Internet‐based media sources to publicize their peaceful activities and demands. Law enforcement agencies should use the Internet and social media to keep the public informed of the reality of protests, especially of any violence that occurs, in an effort to justify forceful tactics.
Hyperproduction of PHA copolymers containing high fractions of 4‐hydroxybutyrate (4HB) by outer membrane‐defected Halomonas bluephagenesis grown in bioreactors
Authors: Wang Ziyu , Zheng Yifei , Ji Mengke , Zhang Xu , Wang Huan , Chen Yuemeng , Wu Qiong , Chen Guo‐Qiang
Published: January 2022

Bacterial outer membrane (OM) is a self‐protective and permeable barrier, while having many non‐negligible negative effects in industrial biotechnology. Our previous studies revealed enhanced properties of Halomonas bluephagenesis based on positive cellular properties by OM defects. This study further expands the OM defect on membrane compactness by completely deleting two secondary acyltransferases for lipid A modification in H. bluephagenesis, LpxL and LpxM, and found more significant advantages than that of the previous lpxL mutant. Deletions on LpxL and LpxM accelerated poly(3‐hydroxybutyrate) (PHB) production by H. bluephagenesis WZY229, leading to a 37% increase in PHB accumulation and 84‐folds reduced endotoxin production. Enhanced membrane permeability accelerates the diffusion of γ‐butyrolactone, allowing H. bluephagenesis WZY254 derived from H. bluephagenesis WZY229 to produce 82wt% poly(3‐hydroxybutyrate‐co‐23mol%4‐hydroxybutyrate) (P(3HB‐co‐23mol%4HB)) in shake flasks, showing increases of 102% and 307% in P(3HB‐co‐4HB) production and 4HB accumulation, respectively. The 4HB molar fraction in copolymer can be elevated to 32 mol% in the presence of more γ‐butyrolactone. In a 7‐l bioreactor fed‐batch fermentation, H. bluephagenesis WZY254 supported a 84 g l−1 dry cell mass with 81wt% P(3HB‐co‐26mol%4HB), increasing 136% in 4HB molar fraction. This study further demonstrated that OM defects generate a hyperproduction strain for high 4HB containing copolymers.
Signalling long‐term focus through textual emphasis on innovation: are firms putting their money where their mouth is?
Authors: Enache Luminita , Fogel‐Yaari Hila , Li Heather
Published: January 2022

Most Form 10‐K filings include non‐informative innovation‐related words. This study shows that textual emphasis on innovation (TEI) reflects the firm’s intention to focus on the long term and finds TEI to be trustworthy. TEI is positively associated with a firm’s long‐term investment and negatively associated with a firm’s under‐investment. Trustworthiness increases when the firm is subject to increased scrutiny. However, this signal is costly, because it is associated with over‐investment in innovation. The study contributes to the impression management and soft disclosure literatures and presents an efficient firm‐level measure in fighting short‐termism pressure.
A mathematical estimation for quantified calcium supplementation during intermittent hemodialysis using regional citrate anticoagulation
Authors: Bi Xiao , Zhang Qi , Zhuang Feng , Ding Feng
Published: January 2022

Background

Regional citrate anticoagulation has been recommended as an alternative of anticoagulation for patients at high risk of bleeding undergoing intermittent hemodialysis. Precise calcium supplementation is important for the safety of regional citrate anticoagulation. In this study, we aimed to develop a possible method to optimize calcium supplementation for regional citrate anticoagulation in intermittent hemodialysis.

Methods

The investigation consisted of a pilot study and a validation study. 18 patients undergoing intermittent hemodialysis anticoagulated by citrate, and six types of filters were included in the pilot study. The ionized calcium levels were monitored and maintained in the targeted range. Calcium‐free dialysate was used in the study. After linear regression analysis of the clearance of non‐protein bound calcium and calculating the ratio of the non‐protein bound calcium concentration to total calcium concentration, we developed a mathematical model for estimation of extracorporeal circuit calcium removal. Another 8 maintenance hemodialysis patients (12 sessions) were enrolled in the validation study to validate the new version of the calcium supplementation approach.

Results

In the pilot study, positive correlations were found between the clearance of non‐protein bound calcium and the hematocrit‐adjusted clearance of creatinine and phosphate given in the dialyzer leaflet (R2 = 0.31, p = 0.0165). The ratio of the non‐protein bound calcium concentration to total calcium concentration at the pre‐filter point after infusion of citrate were constant about 0.75. In the validation study, we found that the systemic ionized calcium levels were stably maintained in the safe range and no filter clotting occurred during the hemodialysis when we used the new model of calcium supplementation.

Conclusions

We developed a possible method to quantify calcium supplementation for intermittent hemodialysis anticoagulated by citrate which may help to avoid negative calcium balance and reduce the incidence of complications.
Enhanced phosphate absorption in intestinal epithelial cell‐specific NHE3 knockout mice
Authors: Xue Jianxiang , Thomas Linto , Murali Sathish Kumar , Levi Moshe , Fenton Robert A. , Dominguez Rieg Jessica A. , Rieg Timo
Published: January 2022

Aims

The kidneys play a major role in maintaining Pi homeostasis. Patients in later stages of CKD develop hyperphosphatemia. One novel treatment option is tenapanor, an intestinal‐specific NHE3 inhibitor. To gain mechanistic insight into the role of intestinal NHE3 in Pi homeostasis, we studied tamoxifen‐inducible intestinal epithelial cell‐specific NHE3 knockout (NHE3IEC‐KO) mice.

Methods

Mice underwent dietary Pi challenges, and hormones as well as urinary/plasma Pi were determined. Intestinal 33P uptake studies were conducted in vivo to compare the effects of tenapanor and NHE3IEC‐KO. Ex vivo Pi transport was measured in everted gut sacs and brush border membrane vesicles. Intestinal and renal protein expression of Pi transporters were determined.

Results

On the control diet, NHE3IEC‐KO mice had similar Pi homeostasis, but a ~25% reduction in FGF23 compared with control mice. Everted gut sacs and brush border membrane vesicles showed enhanced Pi uptake associated with increased Npt2b expression in NHE3IEC‐KO mice. Acute oral Pi loading resulted in higher plasma Pi in NHE3IEC‐KO mice. Tenapanor inhibited intestinal 33P uptake acutely but then led to hyper‐absorption at later time points compared to vehicle. In response to high dietary Pi, plasma Pi and FGF23 increased to higher levels in NHE3IEC‐KO mice which was associated with greater Npt2b expression. Reduced renal Npt2c and a trend for reduced Npt2a expression were unable to correct for higher plasma Pi.

Conclusion

Intestinal NHE3 has a significant contribution to Pi homeostasis. In contrast to effects described for tenapanor on Pi homeostasis, NHE3IEC‐KO mice show enhanced, rather than reduced, intestinal Pi uptake.
MAFA and MAFB regulate exocytosis‐related genes in human β‐cells
Authors: Cataldo Luis Rodrigo , Singh Tania , Achanta Kavya , Bsharat Sara , Prasad Rashmi B. , Luan Cheng , Renström Erik , Eliasson Lena , Artner Isabella
Published: January 2022

Aims

Reduced expression of exocytotic genes is associated with functional defects in insulin exocytosis contributing to impaired insulin secretion and type 2 diabetes (T2D) development. MAFA and MAFB transcription factors regulate β‐cell physiology, and their gene expression is reduced in T2D β cells. We investigate if loss of MAFA and MAFB in human β cells contributes to T2D progression by regulating genes required for insulin exocytosis.

Methods

Three approaches were performed: (1) RNAseq analysis with the focus on exocytosis‐related genes in MafA−/− mouse islets, (2) correlational analysis between MAFA, MAFB and exocytosis‐related genes in human islets and (3) MAFA and MAFB silencing in human islets and EndoC‐βH1 cells followed by functional in vitro studies.

Results

The expression of 30 exocytosis‐related genes was significantly downregulated in MafA−/− mouse islets. In human islets, the expression of 29 exocytosis‐related genes correlated positively with MAFA and MAFB. Eight exocytosis‐related genes were downregulated in MafA−/− mouse islets and positively correlated with MAFA and MAFB in human islets. From this analysis, the expression of RAB3A, STXBP1, UNC13A, VAMP2, NAPA, NSF, STX1A and SYT7 was quantified after acute MAFA or MAFB silencing in EndoC‐βH1 cells and human islets. MAFA and MAFB silencing resulted in impaired insulin secretion and reduced STX1A, SYT7 and STXBP1 (EndoC‐βH1) and STX1A (human islets) mRNA expression. STX1A and STXBP1 protein expression was also impaired in islets from T2D donors which lack MAFA expression.

Conclusion

Our data indicate that STXBP1 and STX1A are important MAFA/B‐regulated exocytosis genes which may contribute to insulin exocytosis defects observed in MAFA‐deficient human T2D β cells.
Peptide fragments of bradykinin show unexpected biological activity not mediated by B1 or B2 receptors
Authors: Souza‐Silva Igor Maciel , de Paula Cristiane Amorim , Bolais‐Ramos Lucas , Santos Anderson Kenedy , da Silva Filipe Alex , de Oliveira Vívian Louise Soares , da Rocha Isabella Domingos , Antunes Maísa Mota , Cordeiro Lídia Pereira Barbosa , Teixeira Vanessa Pereira , Scalzo Júnior Sérgio Ricardo Aluotto , Raabe Adriana Campezatto , Guimaraes Pedro Pires Goulart , Amaral Flávio Almeida , Resende Jarbas Magalhães , Fontes Marco Antônio Peliky , Menezes Gustavo Batista , Guatimosim Silvia , Santos Robson Augusto Souza , Verano‐Braga Thiago
Published: January 2022

Background and Purpose

Bradykinin (BK‐(1–9)) is an endogenous nonapeptide involved in multiple physiological and pathological processes. Peptide fragments of bradykinin are believed to be biologically inactive. We have now tested the two major peptide fragments of bradykinin in human and animals.

Experimental Approach

BK peptides were quantified by MS in male rats. NO release was quantified from human, mouse and rat cells loaded with DAF‐FM. Rat aortic rings were used to measure vascular reactivity. Changes in BP and HR were measured in conscious male rats. To evaluate pro‐inflammatory effects both vascular permeability and nociception were measured in adult mice.

Key Results

BK‐(1–7) and BK‐(1–5) are produced in vivo from BK‐(1–9). Both peptides induced NO production in all cell types tested. However, unlike BK‐(1–9), NO production elicited by BK‐(1–7) or BK‐(1–5) was not inhibited by B1 or B2 receptor antagonists. BK‐(1–7) and BK‐(1–5) induced concentration‐dependent vasorelaxation of aortic rings, without involvement of B1 or B2 receptors. Intravenous or intra‐arterial administration of BK‐(1–7) or BK‐(1–5) induced similar hypotensive response in vivo. Nociceptive responses of BK‐(1–7) and BK‐(1–5) were reduced compared to BK‐(1–9), and no increase in vascular permeability was observed for BK‐(1–9) fragments.

Conclusions and Implications

BK‐(1–7) and BK‐(1–5) are endogenous peptides present in plasma. BK‐related peptide fragments show biological activity, not mediated by B1 or B2 receptors. These BK fragments could constitute new, active components of the kallikrein–kinin system.
Normative coherence for development and regionalism: Gender equality in ASEAN's migration policies
Authors: Häbel Sandra , Koff Harlan , Adam Marie
Published: January 2022

Motivation

The United Nations 2030 Agenda recognizes regions as important actors in implementing the sustainable development agenda. At the same time, regions are often criticized for lacking effective implementation, especially in relation to gender equality.

Purpose

This study examines whether the Association of Southeast Asian Nations (ASEAN) implements its global commitment to gender equality at a regional level.

Methods and approach

We apply qualitative analysis of key ASEAN documents in order to determine how gender equality is implemented regionally. We particularly focus on frameworks related to female migrant workers in ASEAN.

Findings

The analysis shows that ASEAN is formally committed to improving gender equality at a regional level, however, female migrants often end up in unfavourable conditions and precarious work relationships without any institutionalized protection because ASEAN's gender equality initiatives are largely concentrated in the Cultural Community and absent from the Economic Community, indicating an absence of normative coherence for development with regard to gender equality.

Policy implications

This limited impact of emerging regional commitments to gender equality arises from incoherences in ASEAN's normative governance framework which undermine normative coherence for development at the regional level.
Pupillometry and the vigilance decrement: Task‐evoked but not baseline pupil measures reflect declining performance in visual vigilance tasks
Authors: Martin Joel T. , Whittaker Annalise H. , Johnston Stephen J.
Published: January 2022

Baseline and task‐evoked pupil measures are known to reflect the activity of the nervous system's central arousal mechanisms. With the increasing availability, affordability and flexibility of video‐based eye tracking hardware, these measures may one day find practical application in real‐time biobehavioural monitoring systems to assess performance or fitness for duty in tasks requiring vigilant attention. But real‐world vigilance tasks are predominantly visual in their nature and most research in this area has taken place in the auditory domain. Here, we explore the relationship between pupil size—both baseline and task‐evoked—and behavioural performance measures in two novel vigilance tasks requiring visual target detection: (1) a traditional vigilance task involving prolonged, continuous and uninterrupted performance (n = 28) and (2) a psychomotor vigilance task (n = 25). In both tasks, behavioural performance and task‐evoked pupil responses declined as time spent on task increased, corroborating previous reports in the literature of a vigilance decrement with a corresponding reduction in task‐evoked pupil measures. Also in line with previous findings, baseline pupil size did not show a consistent relationship with performance measures. Our data offer novel insights into the complex interplay of brain systems involved in vigilant attention and question the validity of the assumption that baseline (prestimulus) pupil size and task‐evoked (poststimulus) pupil measures reflect the tonic and phasic firing modes of the locus coeruleus.
Self‐referential processes and resting‐state connectivity in breast cancer patients before and 1 year after chemotherapy
Authors: Perrier Joy , Joue Gina , Desgranges Béatrice , Allouache Djelila , Levy Christelle , Noal Sabine , Dayan Jacques , Eustache Francis , Joly Florence , Viard Armelle , Giffard Bénédicte
Published: January 2022

Modifications in the processing of information relevant to oneself have been reported in breast cancer (BC) patients. Here, we characterize the longitudinal changes to self‐representations in BC patients and how they are related to intrinsic functional brain connectivity. We tested 16 BC patients before (T1) and 1 year after the end of chemotherapy (T2) along with 24 healthy control participants (HC) at similar time points. Participants underwent resting‐state fMRI and completed the Questionnaire of Self‐Representation (QSR), which evaluates self‐assertion and self‐esteem. Resting‐state functional connectivity (RSFC) was calculated for regions implicated in self‐referential processes (dorsomedial prefrontal cortex [dmPFC], posterior cingulate cortex [PCC], and dorsal anterior cingulate cortex [dACC]) and correlated with QSR scores. QSR scores were on average larger in patients compared with HC and did not vary over time. RSFC between the dACC and regions supporting body awareness (precentral/postcentral and supramarginal gyri, superior parietal lobule) decreased more between T1 and T2 in BC patients than in HC. BC patients had lower RSFC than HC between the dmPFC and the PCC, and regions supporting mental imagery (precuneus, lingual gyrus), at each time point, and a greater decrease from T1 and T2. QSR scores negatively correlated with RSFC. Patients described themselves as having greater self‐awareness and positive self‐image, reflecting a fighting spirit. In parallel, patients presented a decrease in cortical activity related to body awareness and mental imagery of self‐representations over time that may be related to the positive self‐image patients have and could reflect a temporary adaptive strategy.
3D‐printed design of a stereotaxic adaptor for the precision targeting of brain structures in infant mice
Authors: Steffens Simon , Bakker Joanne , Glat Micaela , Keimpema Erik , Pollak Daniela D. , Hökfelt Tomas , Harkany Tibor
Published: January 2022

Experimental investigation of early postnatal brain development in infant mice (<postnatal day 10) is challenging because of the rapid expansion of their brain volume and the fragility of cranial bones. Stereotaxic adaptors that are commercially available usually evoke significant compression forces, thus limiting the accuracy of micromanipulations. Here, we took advantage of recent progress in 3D printing for the cost‐effective production of stereotaxic adaptors for infant mice. Our designs offer gentle head positioning, tailored incisor placement and high precision, while also integrating evaporator and tubing components for gaseous anaesthesia. Thus, post‐procedural lethality is minimized even upon time‐consuming surgeries. Viral microinjections through glass capillaries are shown as proof of principle to experimentally validate targeting accuracy in mice aged 6–10 days. The exact engineering workflow and printing protocol are disseminated for open‐label use. Overall, we present technical details and experimental data on a stereotaxic device that can help neurobiologists working at a particularly complex developmental stage in mice.
Loop replacement design: a new way to improve potency of plant cystatins
Authors: Kunert Karl J. , Pillay Priyen
Published: January 2022

Plant cystatins function as competitive inhibitors of cysteine proteases. Similar to other defence proteins, cystatins include hypervariable, positively selected amino acid sites presumably impacting their biological activity. Protein engineering approaches, such as point mutations, at these functionally relevant amino acid sites have already been found to be a powerful tool in improving the inhibitory properties of cystatins. Such engineered cystatins not only better protect against digestive proteases of herbivorous arthropods but also against cysteine proteases of several other plant pests as well as against cysteine proteases produced in plant during stress‐induced senescence. Despite previous engineering successes, an urgent need still exists to further improve both plant cystatin potency and specificity. Tremblay and colleagues propose in this issue a new cystatin engineering strategy to substitute the function‐related structural elements (SEs) of a cystatin by the corresponding elements of an alternative cystatin. This strategy, possibly combined with direct cystatin gene editing in a target plant, might provide an innovative way to control cysteine protease activity.

Comment on https://doi.org/10.1111/febs.16288
Social media and the demotic turn in Africa's media ecology
Authors: Kperogi Farooq A.
Published: January 2022

Social media platforms have exploded in the last decade and have emerged as the arenas for discursive democracy, sociality, and digital dissidence across Africa. This article historicizes and genealogizes the exponential, if slightly imperceptible but nonetheless phenomenal, growth, maturation, and spread of social media on a continent that had been described in the scholarly literature as the blackhole of informational capitalism. It argues that the progressive centrality of social media in the quotidian lives of Africans, which has invited consternation and censorship from many African governments and inspired precarity in the traditional media sphere, instantiates the materialization of the demotic turn in communication, which situates the ordinary person as the fulcrum of the communicative process.
The satisfaction of healthcare consumers: analysis and comparison of different methodologies
Authors: Vieira Inês , Ferreira Diogo , Pedro Maria Isabel
Published: January 2022

Patient satisfaction and the factors influencing it are becoming a significant concern for health organizations and patients around the world. This study evaluates patients' satisfaction regarding the inpatient service while tackling the existent literature gap on which method best suits the patient satisfaction analysis. We perform a methodological comparison (using factor analysis, structural equation modeling, ordinal logistic regression (OLR), and multicriteria satisfaction analysis (MUSA)) to contrast the different results from different methodologies. After implementing the methods, we concluded that, out of the eleven analyzed factors, seven influence satisfaction: accommodations, auxiliary staff, exams and treatments, medical staff, food quality, volunteering staff, and obtained information. Three were consistent for structural equation modeling and OLR: accommodations, exams and treatments, and health services. The outputs of MUSA were not compatible with the other methods. However, we concluded that the MUSA method is a good option when dealing with patient satisfaction studies since it provides insightful outputs that facilitate managers' decision making and improve the provider's performance efficiency.
A stochastic approach for planning airport ground support resources
Authors: Guimarans Daniel , Padrón Silvia
Published: January 2022

Airport ground operations are one of the main causes of late departures. Hence, reliable work plans for ground support resources can help mitigate these delays while limiting the under‐/over‐utilization of equipment. In this paper, we propose a stochastic approach for modeling the routing problems encountered during scheduling of each activity. We embed Monte Carlo simulation within an optimization approach to assess solutions during the search and guide the algorithm toward more robust schedules that account for resource cost. Actual flight arrival data, random service, and travel times are used in the simulation process. Results prove that our method clearly increases the robustness of the obtained schedules and the number of aircraft being handled within the planned time. To further identify potential causes of delay, we propose a reliability analysis based on the study of survival functions for each turnaround activity, combined with the dispersion of the resources' arrival to the parking stand.