bluuebunny/crossref_metadata_2025 huggingface dataset:
The gender wage gap and the presence of foreign firms in Vietnam: evidence from unconditional quantile regression decomposition
Authors: Nguyen Dao Dinh , Zhang Xinran , Nguyen Trang Huyen
Published: March 2021

Purpose

The objective of this study is to estimate the gender wage gap in Vietnam and its rural and urban areas, especially with the presence of foreign firms.

Design/methodology/approach

The authors use cross-sectional data from three rounds of the Vietnam Household Living Standards Survey (VHLSS 2008, 2012, and 2016) to investigate this issue. The unconditional quantile regression and Oaxaca–Blinder (OB) decomposition are used in this article.

Findings

The article finds the gender wage gap favouring men, especially in higher quantiles of the wage distribution. The gap in urban Vietnam was higher than in rural areas. The OB decomposition indicates that gender wage gap is mainly driven by gender discrimination. The differences in return to participation in foreign companies only contributed significantly and positively to such a gap in some models. It suggests that the gap in those models is affected by gender discrimination in employment opportunities in foreign companies. Regarding the endowment effect, some models provide the significantly negative impacts of foreign firms on gender wage inequality.

Originality/value

The study suggests that policies to reduce the gender wage gap should pay more attention to foreign firms, especially at higher wage classes.
Lessons from mandated implementation of a performance management system
Authors: Marchand Jean-Sebastien , Breton Mylaine , Saulpic Olivier , Côté-Boileau Élizabeth
Published: March 2021

Purpose

Lean-inspired approaches and performance management systems are being implemented in public healthcare organisations internationally. However, the literature is inconclusive regarding the benefits of these management tools and there is a lack of knowledge regarding processes for large-scale implementation of these tools. This article aims to describe the implementation process and to better understand how this process influences the mandated performance management system.

Design/methodology/approach

This research is based on a comparative case study of three healthcare organisations in Canada. Data consist documents, non-participant observation and semi-structured interviews with key actors (n = 30). Analysis is based on a sociotechnical approach to management tools that considers organisational context, and the tool's technical substrate, theory of action and managerial philosophy.

Findings

Results show that despite a standardised national mandate, the tool as implemented varied between organisations in terms of technical substrate and managerial philosophy. These variations are explained by the flexibility of the technical substrate, the lack of clarity of the managerial philosophy, and some contextual elements. Successful implementation may rest upon high hybridization of the tool on these different dimensions. A precise and prescribed technical substrate is not sufficient to guarantee implementation of a managerial philosophy.

Practical implications

Mandated implementation of management tools may be more successful if it is explicit on the managerial philosophy, the technical substrate and the link between the two, and if it provides some leeway to adapt both to the organisational context.

Originality/value

This is one of the few studies to describe and analyse the process involved in mandated large-scale implementation of performance management systems in public healthcare organisations.
The role of plant secondary metabolites in shaping regional and local plant community assembly
Authors: Endara María‐José , Soule Abrianna J. , Forrister Dale L. , Dexter Kyle G. , Pennington R. Toby , Nicholls James A. , Loiseau Oriane , Kursar Thomas A. , Coley Phyllis D.
Published: March 2021

The outstanding diversity of Amazonian forests is predicted to be the result of several processes. While tree lineages have dispersed repeatedly across the Amazon, interactions between plants and insects may be the principal mechanism structuring the communities at local scales.

Using metabolomic and phylogenetic approaches, we investigated the patterns of historical assembly of plant communities across the Amazon based on the Neotropical genus of trees Inga (Leguminosae) at four, widely separated sites.

Our results show a low degree of phylogenetic structure and a mixing of chemotypes across the whole Amazon basin, suggesting that although biogeography may play a role, the metacommunity for any local community in the Amazon is the entire basin. Yet, local communities are assembled by ecological processes, with the suite of Inga at a given site more divergent in chemical defences than expected by chance

Synthesis. To our knowledge, this is the first study to present metabolomic data for nearly 100 species in a diverse Neotropical plant clade across the whole Amazonia. Our results demonstrate a role for plant–herbivore interactions in shaping the clade's community assembly at a local scale, and suggest that the high alpha diversity in Amazonian tree communities must be due in part to the interactions of diverse tree lineages with their natural enemies providing a high number of niche dimensions.
Unifying the concepts of stability and resilience in ecology
Authors: Van Meerbeek Koenraad , Jucker Tommaso , Svenning Jens‐Christian
Published: March 2021

Characterizing how ecosystems are responding to rapid environmental change has become a major focus of ecological research. The empirical study of ecological stability, which aims to quantify these ecosystem responses, is therefore more relevant than ever.

Based on a historical review and bibliometric mapping of the field of ecological stability, we show that the two main schools relating to the study of stability—one focusing on systems close to their equilibrium and the other on non‐equilibrium behaviour—have developed in parallel leading to divergence in both concepts and definitions.

We synthesize and expand previous frameworks and capitalize on the latest developments in the field to build towards an integrated framework by elaborating the overarching concept of ecological stability and its properties. Finally, the broad applicability of our work is demonstrated in two empirical cases.

Synthesis. With rapidly changing environmental conditions, the stability of ecosystems has become a major focus of ecological research. Still, the concept of stability remains a major source of confusion and disagreement among ecologists. The conceptual framework presented here provides a basis to integrate currently diverging views on the study of ecological stability.
Does air pollution affect investor cognition and land valuation? Evidence from the Chinese land market
Authors: Huang Zhonghua , Du Xuejun
Published: March 2021

This study investigates whether and how air pollution affects investor cognition and valuation in the land market. We find that air pollution significantly affects investor behavior and decreases the bidding prices for land, based on the daily transaction data from the Chinese primary land market. The effect of air pollution on land prices is much stronger for high unit price land parcels and private real estate developers. We exploit the quasi‐natural experiment of Huai River policy as instrument variable and find a causal effect of air pollution on cognitive bias and under valuation in the land market. We further explore the underlying mechanism and find that pollution‐induced change of cognition, mood and behavioral bias play a role. Air pollution‐induced projection bias decreases the demand and bidding price for land. Moreover, air pollution influences investors’ mood and decreases land price premiums.
Real‐time use of a computer‐aided system for polyp detection during colonoscopy, an ambispective study
Authors: Shen Ping , Li Wei Zhi , Li Jia Xin , Pei Zheng Cun , Luo Yu Xuan , Mu Jin Bao , Li Wen , Wang Xi Mo
Published: March 2021

Objective

This study aimed to evaluate ambispectively the effectiveness of a real‐time computer‐aided detection (CADe) system on the number of polyp (PPC) or adenoma per colonoscopy (APC), and polyp (PDR) or adenoma detection rate (ADR).

Methods

Eight‐five videos marked using the CADe system, together with the unmarked videos, were reviewed by two senior endoscopists. Polyps detected in the marked and unmarked videos were recounted in parallel. Additionally, 128 consecutive patients were enrolled for a prospective evaluation using a standard colonoscopy or the CADe monitor alternately every 2 weeks. The PC, APC, PDR and ADR were compared between the two groups.

Results

The total number of polyps reported in the unmarked and marked videos were 73 and 88, respectively (mean PPC 0.86 vs 1.04, P = 0.001). The proportion of polyps detected per colonoscopy increased by 20.5%. Of the 128 prospectively enrolled patients, 186 polyps were detected. The mean PPC was higher in the CADe colonoscopy than in the standard colonoscopy (1.66 vs 1.13, P = 0.039). The PDR using the CADe colonoscopy was significantly higher than that of the standard colonoscopy (78.1% vs 56.3%, P = 0.008).

Conclusion

Real‐time CADe system significantly increases the PDR and PPC under the situation of a high rate of polyp detection.
Remarkable response of non‐small cell lung cancer to nintedanib treatment in a patient with idiopathic pulmonary fibrosis
Authors: Kai Yoshiro , Matsuda Masayuki , Fukuoka Atsuhiko , Hontsu Shigeto , Yamauchi Motoo , Yoshikawa Masanori , Muro Shigeo
Published: March 2021

Nintedanib is a multi‐target receptor tyrosine kinase inhibitor that reduces the decline in forced vital capacity (FVC) and prevents acute exacerbations in idiopathic pulmonary fibrosis (IPF), which is a risk factor for lung cancer. However, it remains unclear whether nintedanib is an effective treatment for lung cancer in patients with IPF. Here, we describe an 82‐year‐old man with non‐small cell lung carcinoma complicated by IPF who was treated with nintedanib. High‐resolution computed tomography (HRCT) showed a subpleural basal‐predominant reticular shadow and traction bronchiectasis with a honeycomb pattern. His FVC decreased over time, and his 6‐min walk test showed oxygen desaturation. Furthermore, an enlarged nodular lesion was detected after 6 months of referral. Biopsy confirmed non‐small cell carcinoma. Because of the risk of acute exacerbation of IPF by chemotherapy, supportive care was selected. Nintedanib was started as treatment for the IPF. Nine months later, HRCT revealed partial remission without exacerbation of IPF. This case indicates the possibility of nintedanib monotherapy in suppressing lung cancer complicated by IPF. Patients with lung cancer complicated by IPF in whom treatment is effective remain unknown. Additional research is needed to identify effective therapy for lung cancer with IPF.
Cap‐independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α‐estradiol
Authors: Shen Ziqian , Hinson Abby , Miller Richard A. , Garcia Gonzalo G.
Published: March 2021

We hypothesized that rapamycin (Rapa), acarbose (ACA), which both increase mouse lifespan, and 17α‐estradiol, which increases lifespan in males (17aE2) all share common intracellular signaling pathways with long‐lived Snell dwarf, PAPPA‐KO, and Ghr−/− mice. The long‐lived mutant mice exhibit reduction in mTORC1 activity, declines in cap‐dependent mRNA translation, and increases in cap‐independent translation (CIT). Here, we report that Rapa and ACA prevent age‐related declines in CIT target proteins in both sexes, while 17aE2 has the same effect only in males, suggesting increases in CIT. mTORC1 activity showed the reciprocal pattern, with age‐related increases blocked by Rapa, ACA, and 17aE2 (in males only). METTL3, required for addition of 6‐methyl‐adenosine to mRNA and thus a trigger for CIT, also showed an age‐dependent increase blunted by Rapa, ACA, and 17aE2 (in males). Diminution of mTORC1 activity and increases in CIT‐dependent proteins may represent a shared pathway for both long‐lived‐mutant mice and drug‐induced lifespan extension in mice.
The phenotype of recovery V: Does delay discounting predict the perceived risk of relapse among individuals in recovery from alcohol and drug use disorders
Authors: Turner Jamie K. , Athamneh Liqa N. , Basso Julia C. , Bickel Warren K.
Published: March 2021

Background

Substance use recovery is a dynamic process. Relapse, often part of the recovery process, is a persistent problem for individuals seeking freedom from their harmful substance use and has become a focus of research on the improvement of recovery outcomes. Delay discounting is associated with substance use disorder severity, both its negative outcomes and the propensity to relapse. However, the association between delay discounting and perceived risk of relapse as measured by the Alcohol Warning of Relapse Questionnaire has not previously been examined in a population of individuals in long‐term recovery from substance misuse.

Methods

In this study, using data collected from the International Quit and Recovery Registry, we investigated the association between delay discounting, self‐reported time in recovery, and perceived risk of relapse. Data from 193 individuals self‐reporting to be in recovery from harmful substance use were included in the study.

Results

Delay discounting rates were significantly negatively associated with length of recovery (p = 0.036) and positively with perceived risk of relapse (p = 0.027) even after controlling for age, gender, education, marital status, ethnicity, race, primary substance, and length in the registry. Moreover, a mediation analysis using Hayes’ methods revealed that the association between the length of recovery and perceived relapse risk was partially mediated by delay discounting, accounting for 21.2% of the effect.

Conclusions

Our finding supports previous characterizations of delay discounting as a candidate behavioral marker of substance misuse and may help to identify individuals at higher perceived risk of relapse in an extended recovery population.
Estimating temperature effects on Drosophila suzukii life cycle parameters
Authors: Winkler Alicia , Jung Jeanette , Kleinhenz Benno , Racca Paolo
Published: March 2021

Drosophila suzukii is an invasive, polyphagous pest of soft‐skinned fruits, having huge impact on fruit production in Asia, North and South America and Europe including Germany.

To investigate the effect of temperature on oviposition, egg‐to‐adult development success and duration, as well as immature heat survival and adult cold survival for a German D. suzukii population several experiments were conducted under different constant temperatures in the laboratory. The resulting life cycle data were described mathematically as functions of temperature and compared with experimental results of other researchers in a summary table.

Curve fittings used herein revealed that minimum, optimum and maximum temperatures are: 13.2, 26.7 and 33.6 °C for oviposition, 14.1, 22.6 and 30.0 °C for egg‐to‐adult development success, and 9.6, 27.3 and 35.7 °C for egg‐to‐adult development duration. Eggs and larvae of D. suzukii showed a reduced heat survival within the tested temperature range of 29 to 41 °C and exposure durations from 1 to 8 h. A cold survival rate of 50% was measured at e.g. −6 °C for 4 h in summer morph adults and at e.g. −6 °C for 45 h in winter morph adults confirming that the latter are more cold tolerant.

Results obtained in this study for a German population of D. suzukii are similar to those obtained for populations of other origins such as Canada, Japan, Spain and USA. Thus, presumably, present data based on a German D. suzukii population can be used for a new or fine‐tune of already existing population dynamics models of D. suzukii in order to support an effective pest management strategy.
“Mask up to keep it up”: Preliminary evidence of the association between erectile dysfunction and COVID‐19
Authors: Sansone Andrea , Mollaioli Daniele , Ciocca Giacomo , Colonnello Elena , Limoncin Erika , Balercia Giancarlo , Jannini Emmanuele A.
Published: March 2021

Background

Erectile dysfunction (ED), as the hallmark of endothelial dysfunction, could be a short‐ or long‐term complication of COVID‐19. Additionally, being ED a clinical marker and predictor of non‐communicable chronic diseases, particularly cardiovascular, subjects with ED could potentially have a higher risk of contracting COVID‐19.

Objectives

To investigate the prevalence of ED among subjects with a reported diagnosis of COVID‐19 and to measure the association of COVID‐19 and ED.

Materials and methods

We reviewed data from the Sex@COVID online survey (performed between April 7 and May 4, 2020, in Italy) to retrieve a sample of Italian male sexually active subjects with reported SARS‐CoV‐2 infection. A matching sample of COVID‐19‐negative male sexually active subjects was also retrieved using propensity score matching in a 3:1 ratio. The survey used different standardized psychometric tools to measure effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of Italian subjects.

Results

One hundred subjects were included in the analysis (25 COVID‐positive; 75 COVID‐negative). The prevalence of ED, measured with the Sexual Health Inventory for Men, was significantly higher in the COVID+ group (28% vs. 9.33%; p = 0.027). Logistic regression models confirmed a significant effect of COVID‐19 on the development of ED, independently of other variables affecting erectile function, such as psychological status, age, and BMI [OR 5.66, 95% CI: 1.50–24.01]. Likewise, subjects with ED were more likely to have COVID‐19, once corrected for age and BMI [OR 5.27, 95% CI: 1.49–20.09].

Discussion and conclusion

On top of well‐described pathophysiological mechanisms, there is preliminary evidence in a real‐life population of ED as a risk factor of developing COVID‐19 and possibly occurring as a consequence of COVID‐19. Universal vaccination against the COVID‐19 and the personal protective equipment could possibly have the added benefit of preventing sexual dysfunctions.
Circumferential (360°) trabeculotomy in primary congenital glaucoma: 19–245 months of follow‐up
Authors: Tønset Turid Skei , Jakobsen Jan Erik , Tveit Jon Henrik , Jørstad Anna‐Katharina L. , Brevik Tone Beate , Sten Lotte‐Guri Bogfjellmo , Drolsum Liv
Published: March 2021

Purpose

To evaluate the long‐term efficacy and safety of circumferential trabeculotomy (CT) in the treatment of primary congenital glaucoma (PCG).

Methods

Retrospective, single‐institutional case series of CT performed for PCG in years 1997–2016. The surgery could be completed in 42 out of 65 eyes (65%) intended for CT, and 39 of them were included in the study. A follow‐up examination was performed in 2017. Success was defined as intraocular pressure ≤ 16 mmHg without (complete) or with (qualified) glaucoma medication.

Results

Complete success was obtained in 33/39 eyes (85%), qualified success in 34/39 eyes (87%). Of the 39 eyes with CT, 4 eyes (10%) needed additional surgery. Median follow‐up time was 120 months (range, 19–245 months). Median pre‐ and postoperative IOP were 26.0 mmHg (range, 10–41 mmHg) and 11.0 mmHg (range, 8–19 mmHg), respectively (p < 0.001). Cup‐disc ratio was ≥0.5 in 82% at baseline, at follow‐up in 9%. The median distance corrected visual acuity at follow‐up was logMAR 0.06 (range, −0.2 to 1.1). Median number of glaucoma medication at follow‐up was 0 (range, 0–2), at baseline 1.0 (range, 0–2). No serious complications were noted.

Conclusion

Circumferential trabeculotomy is an efficacious, safe and medication saving surgical treatment for PCG in the long term. After a median follow‐up of 10 years (120 months), the morphological status of the optic nerve was either normalized or stabilized, and the visual acuity overall well preserved.
High rates of antibiotic prescriptions in children with COVID‐19 or multisystem inflammatory syndrome: A multinational experience in 990 cases from Latin America
Authors: Yock‐Corrales Adriana , Lenzi Jacopo , Ulloa‐Gutiérrez Rolando , Gómez‐Vargas Jessica , Antúnez‐Montes Omar Yassef , Rios Aida Jorge Alberto , del Aguila Olguita , Arteaga‐Menchaca Erick , Campos Francisco , Uribe Fadia , Parra Buitrago Andrea , Maria Betancur Londoño Lina , Brizuela Martin , Buonsenso Danilo
Published: March 2021

Aim

This study aims to assess rates of antibiotic prescriptions and its determinants in in children with COVID‐19 or Multisystem Inflammatory Syndrome (MIS‐C).

Methods

Children <18 years‐old assessed in five Latin Americas countries with a diagnosis of COVID‐19 or MIS‐C were enrolled. Antibiotic prescriptions and factors associated with their use were assessed.

Results

A total of 990 children were included: 921 (93%) with COVID‐19, 69 (7.0%) with MIS‐C. The prevalence of antibiotic use was 24.5% (n = 243). MIS‐C with (OR = 45.48) or without (OR = 10.35) cardiac involvement, provision of intensive care (OR = 9.60), need for hospital care (OR = 6.87), pneumonia and/or ARDS detected through chest X‐rays (OR = 4.40), administration of systemic corticosteroids (OR = 4.39), oxygen support, mechanical ventilation or CPAP (OR = 2.21), pyrexia (OR = 1.84), and female sex (OR = 1.50) were independently associated with increased use of antibiotics. There was significant variation in antibiotic use across the hospitals.

Conclusion

Our study showed a high rate of antibiotic prescriptions in children with COVID‐19, in particular in those with severe disease or MIS‐C. Prospective studies are needed to provide better evidence on the recognition and management of bacterial infections in COVID‐19 children.
Quality of life, mental health, and family functioning of schizophrenia caregivers: A community‐based cross‐sectional study
Authors: Khatimah Cut Husnul , Adami Aulina , Abdullah Asnawi , Marthoenis
Published: March 2021

The caregivers of people with schizophrenia might suffer from various problems. We investigated the prevalence of depression, anxiety, and stress among them, and factors associated with their quality of life. A cross‐sectional study in communities of rural areas was conducted. We found that the prevalence of depression, anxiety, and stress were 14.2%, 25.5%, and 6.6%, respectively. Their quality of life was independently associated with family functioning (affective responsiveness, problem solving, communication) and the presence of depressive symptoms (p < .05). Schizophrenia caregivers need more supports from health care professionals to improve their skills in problem solving.
Acute toxicity and micronucleus test of conotoxin lt14a in mice
Authors: Wu Yun , Qiang Yuanyuan , Zhang Guangxian , Zhou Maojun
Published: March 2021

Conotoxins, which target ion channels or neurotransmitter receptors with high specificity, are valuable in drug development for pain, epilepsy and other neurological diseases. However, the toxicology of conotoxins is rarely reported. In this study, we primarily researched parts of the pharmacological and toxicological properties of an analgesic conotoxin lt14a. Three doses of lt14a (1, 5 and 10 mg/kg) could prolong the pentobarbital‐induced sleep time of mice and showed no significant effect on the spontaneous locomotor activity of mice. Three doses of lt14a (50, 100 and 200 mg/kg) did not increase micronucleus rate in the micronucleus test. In addition, three doses of lt14a (200, 500 and 1000 mg/kg) showed no pathological change on the heart or brain of mice in the acute toxicity test. The high dose of lt14a (1000 times the effective analgesic dose) had a certain damaging effect on the liver and lung according to serological detection and histopathology. As part of the preclinical studies, our results provide acute toxicity and mutagenicity evaluation of the promising analgesic conotoxin lt14a.
The dissociable influence of social context on judgements of facial attractiveness and trustworthiness
Authors: Carragher Daniel J. , Thomas Nicole A. , Nicholls Michael E. R.
Published: March 2021

The cheerleader effect occurs when the same face is rated to be more attractive when it is seen in a group compared to when seen alone. We investigated whether this phenomenon also occurs for trustworthiness judgements, and examined how these effects are influenced by the characteristics of the individual being evaluated and those of the group they are seen in. Across three experiments, we reliably replicated the cheerleader effect. Most faces became more attractive in a group. Yet, the size of the cheerleader effect that each face experienced was not related to its own attractiveness, nor to the attractiveness of the group or the group’s digitally averaged face. We discuss the implications of our findings for the hierarchical encoding and contrast mechanisms that have previously been used to explain the cheerleader effect. Surprisingly, judgements of facial trustworthiness did not experience a ‘cheerleader effect’. Instead, we found that untrustworthy faces became significantly more trustworthy in all groups, while there was no change for faces that were already trustworthy alone. Taken together, our results demonstrate that social context can have a dissociable influence on our first impressions, depending on the trait being evaluated.
Fluorescent‐ and tagged‐protoxin II peptides: potent markers of the Nav1.7 channel pain target
Authors: Montnach Jérôme , De Waard Stephan , Nicolas Sébastien , Burel Sophie , Osorio Nancy , Zoukimian Claude , Mantegazza Massimo , Boukaiba Rachid , Béroud Rémy , Partiseti Michel , Delmas Patrick , Marionneau Céline , De Waard Michel
Published: March 2021

Background and Purpose

Protoxin II (ProTx II) is a high affinity gating modifier that is thought to selectively block the Nav1.7 voltage‐dependent Na+ channel, a major therapeutic target for the control of pain. We aimed at producing ProTx II analogues entitled with novel functionalities for cell distribution studies and biochemical characterization of its Nav channel targets.

Experimental Approach

We took advantage of the high affinity properties of the peptide, combined to its slow off rate, to design a number of new tagged analogues useful for imaging and biochemistry purposes. We used high‐throughput automated patch‐clamp to identify the analogues best matching the native properties of ProTx II and validated them on various Nav‐expressing cells in pull‐down and cell distribution studies.

Key Results

Two of the produced ProTx II analogues, Biot‐ProTx II and ATTO488‐ProTx II, best emulate the pharmacological properties of unlabelled ProTx II, whereas other analogues remain high affinity blockers of Nav1.7. The biotinylated version of ProTx II efficiently works for the pull‐down of several Nav isoforms tested in a concentration‐dependent manner, whereas the fluorescent ATTO488‐ProTx II specifically labels the Nav1.7 channel over other Nav isoforms tested in various experimental conditions.

Conclusions and Implications

The properties of these ProTx II analogues as tools for Nav channel purification and cell distribution studies pave the way for a better understanding of ProTx II channel receptors in pain and their pathophysiological implications in sensory neuronal processing. The new fluorescent ProTx II should also be useful in the design of new drug screening strategies.
A retrospective analysis of actionable pharmacogenetic/genomic biomarker language in FDA labels
Authors: Yamazaki Shinji
Published: March 2021

The primary goal of precision medicine is to maximize the benefit‐risk relationships for individual patients by delivering the right drug to the right patients at the right dose. To achieve this goal, it has become increasingly important to assess gene‐drug interactions (GDIs) in clinical settings. The US Food and Drug Administration (FDA) periodically updates the table of pharmacogenetic/genomic (PGx) biomarkers in drug labeling on their website. As described herein, an effort was made to categorize various PGx biomarkers covered by the FDA‐PGx table into certain groups. There were 2 major groups, oncology molecular targets (OMT) and drug‐metabolizing enzymes and transporters (DMETs), which constitute ~70% of all biomarkers (~33% and ~35%, respectively). These biomarkers were further classified whether their labeling languages could be actionable in clinical practice. For OMT biomarkers, ~70% of biomarkers are considered actionable in clinical practice as they are critical for the selection of appropriate drugs to individual patients. In contrast, ~30% of DMET biomarkers are considered actionable for the dose adjustments or alternative therapies in specific populations, such as CYP2C19 and CYP2D6 poor metabolizers. In addition, the GDI results related to some of the other OMT and DMET biomarkers are considered to provide valuable information to clinicians. However, clinical GDI results on the other DMET biomarkers can possibly be used more effectively for dose recommendation. As the labels of some drugs already recommend the precise doses in specific populations, it will be desirable to have clear language for dose recommendation of other (or new) drugs if appropriate.
Identification of small molecules that mitigate vincristine‐induced neurotoxicity while sensitizing leukemia cells to vincristine
Authors: Diouf Barthelemy , Wing Claudia , Panetta John C. , Eddins Donnie , Lin Wenwei , Yang Wenjian , Fan Yiping , Pei Deqing , Cheng Cheng , Delaney Shannon M. , Zhang Wei , Bonten Erik J. , Crews Kristine R. , Paugh Steven W. , Li Lie , Freeman Burgess B. , Autry Robert J. , Beard Jordan A. , Ferguson Daniel C. , Janke Laura J. , Ness Kirsten K. , Chen Taosheng , Zakharenko Stanislav S. , Jeha Sima , Pui Ching‐Hon , Relling Mary V. , Eileen Dolan M. , Evans William E.
Published: March 2021

Vincristine (VCR) is one of the most widely prescribed medications for treating solid tumors and acute lymphoblastic leukemia (ALL) in children and adults. However, its major dose‐limiting toxicity is peripheral neuropathy that can disrupt curative therapy. Peripheral neuropathy can also persist into adulthood, compromising quality of life of childhood cancer survivors. Reducing VCR‐induced neurotoxicity without compromising its anticancer effects would be ideal. Here, we show that low expression of NHP2L1 is associated with increased sensitivity of primary leukemia cells to VCR, and that concomitant administration of VCR with inhibitors of NHP2L1 increases VCR cytotoxicity in leukemia cells, prolongs survival of ALL xenograft mice, but decreases VCR effects on human‐induced pluripotent stem cell‐derived neurons and mitigates neurotoxicity in mice. These findings offer a strategy for increasing VCR’s antileukemic effects while reducing peripheral neuropathy in patients treated with this widely prescribed medication.
Angiotensin 1‐7 protects against ventilator‐induced diaphragm dysfunction
Authors: Yoshihara Toshinori , Deminice Rafael , Hyatt Hayden W. , Ozdemir Mustafa , Nguyen Branden L. , Powers Scott K.
Published: March 2021

Mechanical ventilation (MV) is a life‐saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator‐induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and, therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin‐angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the nonclassical RAS signaling pathway via angiotensin 1‐7 (Ang1‐7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1‐7 protects the diaphragm against MV‐induced contractile dysfunction and fiber atrophy in both fast and slow muscle fibers. Further, Ang1‐7 shielded diaphragm fibers against MV‐induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1‐7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang1‐7 has the therapeutic potential to protect against VIDD by preventing MV‐induced contractile dysfunction and atrophy of both slow and fast muscle fibers.
Bribery, hold‐up, and bureaucratic structure
Authors: Bennett John , Rablen Matthew D.
Published: March 2021

We consider infrastructure provision by a foreign investor when the domestic bureaucracy is corrupt, but also cares for domestic welfare. Bureaucrats bargain with the investor over price and (potentially) bribes, both before the investment is sunk and afterwards, using the threat of expropriation. We show that domestic welfare may be greater in equilibria with bribery than in equilibria without. We specify conditions under which changes in the degree of bureaucratic centralization or of bureaucratic care have a positive, negative, or nonmonotonic effect on domestic welfare. The impact of centralization on domestic welfare is mediated through the level of bureaucratic care.
The real effects of liquidity: Puerto Rico as a natural experiment
Authors: Ramirez Carlos D.
Published: March 2021

This paper investigates the consequences of a large and sustained liquidity infusion on the real economy using Section 936 tax incentives in Puerto Rico as a natural experiment. I find that the tax incentives increased liquidity and lowered the cost of funds for PR banks. Furthermore, 936 funds stimulated C&I and real estate loans. However, the incidence of troubled loans increases with the amount of 936 funds received, pointing to excessive and inefficient financing in those sectors. The implementation and subsequent removal of these incentives induced a structural shift in Puerto Rico's economy, generating an unintended and long‐lasting boom‐bust cycle.
Effects of affective content and motivational context on neural gain functions during naturalistic scene perception
Authors: Tebbe Anna‐Lena , Friedl Wendel M. , Alpers Georg W. , Keil Andreas
Published: March 2021

Visual scene processing is modulated by semantic, motivational, and emotional factors, in addition to physical scene statistics. An open question is to what extent those factors affect low‐level visual processing. One index of low‐level visual processing is the contrast response function (CRF), representing the change in neural or psychophysical gain with increasing stimulus contrast. Here we aimed to (a) establish the use of an electrophysiological technique for assessing CRFs with complex emotional scenes and (b) examine the effects of motivational context and emotional content on CRFs elicited by naturalistic stimuli, including faces and complex scenes (humans, animals). Motivational context varied by expectancy of threat (a noxious noise) versus safety. CRFs were measured in 18 participants by means of sweep steady‐state visual evoked potentials. Results showed a facilitation in visuocortical sensitivity (contrast gain) under threat, compared with safe conditions, across all stimulus categories. Facial stimuli prompted heightened neural response gain, compared with scenes. Within the scenes, response gain was smaller for scenes high in emotional arousal, compared with low‐arousing scenes, consistent with interference effects of emotional content. These findings support the notion that motivational context alters the contrast sensitivity of cortical tissue, differing from changes in response gain (activation) when visual cues themselves carry motivational/affective relevance.
Quantifying uncertainty and dynamical changes in multi‐species fishing mortality rates, catches and biomass by combining state‐space and size‐based multi‐species models
Authors: Spence Michael A. , Thorpe Robert B. , Blackwell Paul G. , Scott Finlay , Southwell Richard , Blanchard Julia L.
Published: March 2021

In marine management, fish stocks are often managed on a stock‐by‐stock basis using single‐species models. Many of these models are based upon statistical techniques and are good at assessing the current state and making short‐term predictions; however, as they do not model interactions between stocks, they lack predictive power on longer timescales. Additionally, there are size‐based multi‐species models that represent key biological processes and consider interactions between stocks such as predation and competition for resources. Due to the complexity of these models, they are difficult to fit to data, and so many size‐based multi‐species models depend upon single‐species models where they exist, or ad hoc assumptions when they do not, for parameters such as annual fishing mortality. In this paper, we demonstrate that by taking a state‐space approach, many of the uncertain parameters can be treated dynamically, allowing us to fit, with quantifiable uncertainty, size‐based multi‐species models directly to data. We demonstrate this by fitting uncertain parameters, including annual fishing mortality, of a size‐based multi‐species model of the Celtic Sea, for species with and without single‐species stock assessments. Consequently, errors in the single‐species models no longer propagate through the multi‐species model and underlying assumptions are more transparent. Building size‐based multi‐species models that are internally consistent, with quantifiable uncertainty, will improve their credibility and utility for management. This may lead to their uptake by being either used to corroborate single‐species models; directly in the advice process to make predictions into the future; or used to provide a new way of managing data‐limited stocks.
Four decades of reef observations illuminate deep‐water grouper hotspots
Authors: Paxton Avery B. , Harter Stacey L. , Ross Steve W. , Schobernd Christina M. , Runde Brendan J. , Rudershausen Paul J. , Johnson Katrina H. , Shertzer Kyle W. , Bacheler Nathan M. , Buckel Jeffrey A. , Kellison G. Todd , Taylor J. Christopher
Published: March 2021

Fish often aggregate to spawn, feed, rest, or avoid predation. Direct observations of very high counts of large‐bodied grouper on deep shipwrecks, however, do not fit into typical descriptions of spawning‐, resource‐, or predation‐driven aggregations. To investigate whether these observations are rare or part of an underlying pattern, we synthesized four decades (1979–2019) of direct observations of groupers on deep‐water (50–300 m) habitats along the southeastern United States (Cape Hatteras, NC to Cape Canaveral, FL). The direct observations, which included 439 remotely operated vehicle transects, 235 human‐occupied vehicle transects, and 881 hook‐and‐line drops, revealed six hotspots of deep‐water groupers on three shipwrecks, two artificial reefs, and one boulder field. Grouper counts at these hotspots (0.10–5.40 grouper per linear m surveyed) exceeded counts of grouper outside of hotspots (<0.01–0.02 grouper per linear m surveyed) by multiple orders of magnitude. Commonalities among the sites with grouper hotspots included that all are relatively isolated structures surrounded by unconsolidated sediments and located in shelf‐edge to upper‐slope depths. Thus, it appears that these isolated habitats, despite their small spatial footprint, represent a disproportionate abundance of deep‐water groupers. Future research efforts should determine how groupers derive sufficient resources from, and thus co‐occur on, these small habitats and how these aggregations relate to the large‐scale dynamics of these populations.
Unexpected greening in a boreal permafrost peatland undergoing forest loss is partially attributable to tree species turnover
Authors: Dearborn Katherine D. , Baltzer Jennifer L.
Published: March 2021

Time series of vegetation indices derived from satellite imagery are useful in measuring vegetation response to climate warming in remote northern regions. These indices show that productivity is generally declining in the boreal forest, but it is unclear which components of boreal vegetation are driving these trends. We aimed to compare trends in the normalized difference vegetation index (NDVI) to forest growth and demographic data taken from a 10 ha mapped plot located in a spruce‐dominated boreal peatland. We used microcores to quantify recent growth trends and tree census data to characterize mortality and recruitment rates of the three dominant tree species. We then compared spatial patterns in growth and demography to patterns in Landsat‐derived maximum NDVI trends (1984–2019) in 78 pixels that fell within the plot. We found that NDVI trends were predominantly positive (i.e., “greening”) in spite of the ongoing loss of black spruce (the dominant species; 80% of stems) from the plot. The magnitude of these trends correlated positively with black spruce growth trends, but was also governed to a large extent by tree mortality and recruitment. Greening trends were weaker (lower slope) in areas with high larch mortality, and high turnover of spruce and birch, but stronger (higher slope) in areas with high larch recruitment. Larch dominance is currently low (~11% of stems), but it is increasing in abundance as permafrost thaw progresses and will likely have a substantial influence on future NDVI trends. Our results emphasize that NDVI trends in boreal peatlands can be positive even when the forest as a whole is in decline, and that the magnitude of trends can be strongly influenced by the demographics of uncommon species.
Assessing the relevant time frame for temperature acclimation of leaf dark respiration: A test with 10 boreal and temperate species
Authors: Reich Peter B. , Stefanski Artur , Rich Roy L. , Sendall Kerrie M. , Wei Xiaorong , Zhao Changming , Hou Jihua , Montgomery Rebecca A. , Bermudez Raimundo
Published: March 2021

Plants often adjust their leaf mitochondrial (“dark”) respiration (Rd) measured at a standardized temperature such as 20°C (R20) downward after experiencing warmer temperatures and upward after experiencing cooler temperatures. These responses may help leaves maintain advantageous photosynthetic capacity and/or be a response to recent photosynthate accumulation, and can occur within days after a change in thermal regime. It is not clear, however, how the sensitivity and magnitude of this response change over time, or which time period prior to a given measurement best predicts R20. Nor is it known whether nighttime, daytime, or 24‐hour temperatures should be most influential. To address these issues, we used data from 1620 Rd temperature response curves of 10 temperate and boreal tree species in a long–term field experiment in Minnesota, USA to assess how the observed nearly complete acclimation of R20 was related to past temperatures during periods of differing lengths. We hypothesized that R20 would be best related to prior midday temperatures associated with both photosynthetic biochemistry and peak carbon uptake rates that drive carbohydrate accumulation. Inconsistent with this hypothesis, prior night temperatures were the best predictors of R20 for all species. We had also hypothesized that recent (prior 3–10 days) temperatures should best predict R20 because they likely have stronger residual impacts on leaf‐level physiology than periods extending further back in time, whereas a prior 1‐ to 2‐day period might be a span shorter than one to which photosynthetic capacity and Rd adjust. There was little to no support for this idea, as for angiosperms, long time windows (prior 30–60 nights) were the best predictors, while for gymnosperms both near‐term (prior 3–8 nights for pines, prior 10–14 nights for spruce/fir) and longer‐term periods (prior 45 nights) were the best predictors. The importance of nighttime temperatures, the relatively long “time‐averaging” that best explained acclimation, and dual peaks of temporal acclimation responsiveness in some species were all results that were unanticipated.
NGOs working for gender justice with boys and men: Exploring challenges of accountability
Authors: Keddie Amanda
Published: March 2021

The gender politics of the present moment are challenging for NGOs working for gender justice with boys and men especially in terms of navigating the different forms of accountability their work is subject to. This paper explores these challenges through concerns expressed by a small group of NGO leaders about issues of accountability. These concerns are theorized within a three‐part model where accountability is conceptualized as (1) imposed, (2) felt, and (3) adaptive. The insights from the leaders highlight particular tensions within and between these different forms of accountability for NGOs working in the space of gender justice and, in particular, how these tensions can support and compromise feminist goals. Amid renewed public commitment to gender justice and greater attention and funding in this space for NGOs working with boys and men, ongoing critical examination of these tensions of accountability is imperative.
Effects of cricket powder on selected physical properties and US consumer perceptions of whole‐wheat snack crackers
Authors: Ardoin Ryan , Marx Brian D. , Boeneke Charles , Prinyawiwatkul Witoon
Published: March 2021

Successful introduction of insect consumption to a reluctant US population requires novel insect‐based foods that are responsive to consumers’ expectations of sensory quality. Based on our ‘product appropriateness’ data, snack crackers were formulated with increasing levels of cricket powder (0%, 5%, 10%, 15%, and 20%) in substitution of whole‐wheat flour. Colour, texture, flavour and overall perceptions of snack crackers were evaluated by 150 US consumers in terms of preference (2‐alternative choice), degree of liking (9‐point scale) and acceptability (yes/no). Flavour liking was most highly correlated with overall liking (r = 0.93). Instrumental analyses indicated that increasing cricket powder resulted in darker and harder crackers, negatively impacting colour and texture preference at 5% and 15% cricket powder addition, respectively. Snack crackers remained acceptable at 15% wheat flour substitution (80% acceptability; mean overall liking = 5.5). However, to promote future consumption, an upper limit of 7.9% cricket powder addition is recommended until sensory quality can be improved.
Evaluation of mannitol and xylitol on the quality of wheat flour and extruded flour products
Authors: Yang Heng , Fu Yang , Zhang Yudong , Zhou Jian , Wang Danfeng , Gao Zhen , Ke Yuan , Lv Qingyun , Ding Beibei , Wang Xuedong
Published: March 2021

Effects of polyols (mannitol and xylitol) on physical properties, pasting properties and dynamic rheological properties of wheat flour and the microstructure, water activity (Aw), radial expansion ratio (ER), oil absorption rate (OAR) and texture of extruded flour products were evaluated in this work. The results show that both mannitol and xylitol can promote gluten network formation, enhance tensile resistance and increase the storage modulus (G') and loss modulus (G'') of the dough. More dense and uniform particles were also found on the surface of extruded flour products in the presence of polyols by scanning electron microscopy (SEM). Furthermore, the Aw, hardness and chewiness were reduced while the ER and ORA were increased for extruded flour products by incorporation of polyols. Thus, the extruded flour products with improved quality by polyols exhibit great application prospect in food industry.