bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast Nurse Intervention to Improve Adherence to Endocrine Therapy Among Breast Cancer Patients in South Ethiopia
Authors: Getachew Sefonias , Addissie Adamu , Seife Edom , Wakuma Tariku , Unverzagt Susanne , Jemal Ahmedin , Taylor Lesley , Wienke Andreas , Kantelhardt Eva J
Published: April 2022

Introduction

Many women in rural Ethiopia do not receive adjuvant therapy following breast cancer surgery despite the majority being diagnosed with estrogen-receptor-positive breast cancer and tamoxifen being available in the country. We aimed to compare a breast nurse intervention to improve adherence to tamoxifen therapy for breast cancer patients.

Methods and Materials

The 8 hospitals were randomized to intervention and control sites. Between February 2018 and December 2019, patients with breast cancer were recruited after their initial surgery. The primary outcome of the study was adherence to tamoxifen therapy by evaluating 12-month medication-refill data with medication possession ratio (MPR) and using a simplified medication adherence scale (SMAQ) in a subjective assessment.

Results

A total of 162 patients were recruited (87 intervention and 75 control). Trained nurses delivered education and provided literacy material, gave additional empathetic counselling, phone call reminders, and monitoring of medication refill at the intervention hospitals. Adherence according to MPR at 12 months was high in both the intervention (90%) and control sites (79.3%) (P = .302). The SMAQ revealed that adherence at intervention sites was 70% compared with 44.8% in the control sites (P = .036) at 12 months. Persistence to therapy was found to be 91.2% in the intervention and 77.8% in the control sites during the one-year period (P = .010).

Conclusion

Breast nurses can improve cost-effective endocrine therapy adherence at peripheral hospitals in low-resource settings. We recommend such task sharing to overcome the shortage of oncologists and distances to central cancer centers.
Utilization of Immunotherapy in Patients with Cancer Treated in Routine Care Settings: A Population-Based Study Using Health Administrative Data
Authors: Raphael Jacques , Richard Lucie , Lam Melody , Blanchette Phillip S , Leighl Natasha B , Rodrigues George , Trudeau Maureen E , Krzyzanowska Monika K
Published: April 2022

Introduction

The introduction of immunotherapy (IO) in the treatment of patients with cancer has significantly improved clinical outcomes. Population level information on actual IO utilization is limited.

Methods

We conducted a retrospective cohort study using provincial health administrative data from Ontario, Canada to: (1) assess the extent of IO use from 2011 (pre-IO funding) to 2019; and (2) identify factors associated with IO use in patients with advanced cancers for which IO is reimbursed including melanoma, bladder, lung, head and neck, and kidney tumors. The datasets were linked using a unique encoded identifier. A Fine and Gray regression model with death as a competing risk was used to identify factors associated with IO use.

Results

Among 59 510 patients assessed, 8771 (14.7%) received IO between 2011 and 2019. Use of IO increased annually from 2011 (3.3%) to 2019 (39.2%) and was highest in melanoma (52%) and lowest in head and neck cancer (6.6%). In adjusted analysis, factors associated with lower IO use included older age (hazard ratio (HR) 0.91 (95% CI, 0.89-0.93)), female sex (HR 0.85 (95% CI, 0.81-0.89)), lower-income quintile, hospital admission (HR 0.78 (95% CI, 0.75-0.82)), high Charlson score and de novo stage 4 cancer. IO use was heterogeneous across cancer centers and regions.

Conclusion

IO utilization for advanced cancers rose substantially since initial approval albeit use is associated with patient characteristics and system-level factors even in a universal healthcare setting. To optimize IO utilization in routine practice, survival estimates and potential inequity in access should be further investigated and addressed.
Age-structured model reveals prolonged immigration is key for colony establishment in Gentoo Penguins
Authors: Herman Rachael W , Lynch Heather J
Published: April 2022

Understanding the mechanisms of site colonization and range expansion is crucial to understanding population dynamics, particularly for colonial seabirds that may struggle to shift their breeding ranges under climate change. We provide an alternative and simple approach to estimating the number of migrating individuals among colonies when original mark–recapture datasets are not available for use in more integrated and established methods. Here we fit an age-structured population model with published vital rates and breeding success rates to simple point counts of abundance using rejection-based approximate Bayesian computation (ABC) to estimate the contribution of immigration to four recently colonized Gentoo Penguin (Pygoscelis papua) breeding sites on the Western Antarctic Peninsula. We found that sustained immigration over several years was required to generate the rapid population growth observed, with some sites even showing evidence of an accelerating immigration rate following initial colonization. We demonstrate that our method is capable of estimating the contribution of immigration to population growth in a species where mark–recapture datasets are unavailable. By leveraging census data that are relatively easy to obtain, our approach provides a new method for understanding how range expansions occur in species such as Antarctic penguins whose habitat is undergoing changing climate conditions.
Strong migratory connectivity indicates Willets need subspecies-specific conservation strategies
Authors: Huysman Allison E , Cooper Nathan W , Smith Joseph A , Haig Susan M , Heath Susan A , Johnson Luanne , Olson Elizabeth , Regan Kevin , Wilson Jennifer K , Marra Peter P
Published: April 2022

By combining all available banding and tracking data, we found that Willets (Tringa semipalmata) have a strong migratory connectivity between breeding and nonbreeding locations at the range-wide and subspecies levels, exposing two subspecies to varying threats such as hunting for the eastern subspecies (Tringa semipalmata semipalmata) and climatically-altered coastal habitats for both subspecies. We found that western Willets (Tringa semipalmata inornata) primarily used nonbreeding habitats along the Pacific Coast of the United States, although their reported nonbreeding range extends to the US Atlantic and Gulf Coasts and the Pacific Coast of Central and South America. Eastern Willets wintered in Central and South America, which covers much of the subspecies’ known nonbreeding range. By quantifying migratory connectivity within and between two subspecies, we could suggest subspecies-specific threats and potential limiting factors in the breeding and nonbreeding periods of the annual cycle of a declining migratory shorebird. Effective management of the species will likely require a range of conservation strategies across the diverse nonbreeding regions the two subspecies occupy within the United States, Central America, and South America. However, more data are needed from Willets breeding in mid-continental North America to understand the complete extent of overlap of the two subspecies throughout the annual cycle. The strong migratory connectivity documented here highlights the need to manage Willets by subspecies and protect a diversity of breeding and nonbreeding habitats, which will benefit the conservation of other shorebird species that overlap with Willets throughout the annual cycle.
Old challenges, new solutions: getting major projects right in the twenty-first century
Authors: Ansar Atif
Published: April 2022

Major projects are high-value (£100 million+) investments across sectors such as transport, energy, health, defence, or IT systems. Globally, a significant proportion of government policy initiatives are delivered through major projects. There is, however, a paradox at the heart of the major project phenomenon. Although major projects are indispensable tools for turning policy ideals into reality, their track record is strikingly poor. Cost and time overruns, financial engineering, under-supply, poor service, environmental detriment, and social dissatisfaction blight major projects. Poor outcomes have been a feature of the wide array of delivery mechanisms deployed over the past 150 years, including direct public provision, regulated private provision, public–private partnerships, and concessions, agreements, and franchises. The papers in this issue of the Oxford Review of Economic Policy explore the nature of this paradox and offer strategies designed to get major projects right, including repeatable platform strategies; mission-orientated investments; and deliberative and collaborative incentive schemes.
Splicing-mediated activation of SHAGGY-like kinases underpinning carbon partitioning in Arabidopsis seeds
Authors: Li Chengxiang , Chen Bin , Yu Hao
Published: April 2022

Glycogen synthase kinase 3 (GSK3) family members serve as signaling hubs for plant development and stress responses, yet the underlying mechanism of their transcriptional regulation remains a long-standing mystery. Here we show that the transcription of SHAGGY-like kinase 11/12 (SK11/12), two members of the GSK3 gene family, is promoted by the splicing factor SmD1b, which is essential for distributing carbon sources into storage and protective components in Arabidopsis seeds. The chromatin recruitment of SmD1b at the SK11/12 loci promotes their transcription associated with co-transcriptional splicing of the first introns in the 5′-untranslated region of SK11/12. The loss of SmD1b function generates transcripts with unspliced introns that create disruptive R-loops to hamper the transcriptional elongation of SK11/12, in addition to compromising the recruitment of RNA polymerase II to the SK11/12 genomic regions. These effects imposed by SmD1b determine the transcription of SK11/12 to confer a key switch of carbon flow among metabolic pathways in zygotic and maternal tissues in seeds.
Integrated omics reveal novel functions and underlying mechanisms of the receptor kinase FERONIA inArabidopsis thaliana
Authors: Wang Ping , Clark Natalie M , Nolan Trevor M , Song Gaoyuan , Bartz Parker M , Liao Ching-Yi , Montes-Serey Christian , Katz Ella , Polko Joanna K , Kieber Joseph J , Kliebenstein Daniel J , Bassham Diane C , Walley Justin W , Yin Yanhai , Guo Hongqing
Published: April 2022

The receptor kinase FERONIA (FER) is a versatile regulator of plant growth and development, biotic and abiotic stress responses, and reproduction. To gain new insights into the molecular interplay of these processes and to identify new FER functions, we carried out quantitative transcriptome, proteome, and phosphoproteome profiling of Arabidopsis (Arabidopsis thaliana) wild-type and fer-4 loss-of-function mutant plants. Gene ontology terms for phytohormone signaling, abiotic stress, and biotic stress were significantly enriched among differentially expressed transcripts, differentially abundant proteins, and/or misphosphorylated proteins, in agreement with the known roles for FER in these processes. Analysis of multiomics data and subsequent experimental evidence revealed previously unknown functions for FER in endoplasmic reticulum (ER) body formation and glucosinolate biosynthesis. FER functions through the transcription factor NAI1 to mediate ER body formation. FER also negatively regulates indole glucosinolate biosynthesis, partially through NAI1. Furthermore, we found that a group of abscisic acid (ABA)-induced transcription factors is hypophosphorylated in the fer-4 mutant and demonstrated that FER acts through the transcription factor ABA INSENSITIVE5 (ABI5) to negatively regulate the ABA response during cotyledon greening. Our integrated omics study, therefore, reveals novel functions for FER and provides new insights into the underlying mechanisms of FER function.
transcranial Direct Current Stimulation (tDCS) for the treatment and investigation of Phantom Limb Pain (PLP)
Authors: Damercheli Shahrzad , Ramne Malin , Ortiz-Catalan Max
Published: April 2022

Phantom limb pain (PLP) is a complex medical condition that is often difficult to treat, and thus can become detrimental to patients’ quality of life. No standardized clinical treatments exist and there is no conclusive understanding of the underlying mechanisms causing it. Noninvasive brain stimulation (NIBS) has been used to find correlations between changes in brain activity and various brain conditions, including neurological disease, mental illnesses, and brain disorders. Studies have also shown that NIBS can be effective in alleviating pain. Here, we examined the literature on a particular type of NIBS, known as transcranial direct current stimulation (tDCS), and its application to the treatment of PLP. We first discuss the current hypotheses on the working mechanism of tDCS and then we examine published evidence of its efficacy to treat PLP. We conclude this article by discussing how tDCS alone, and in combination with brain imaging techniques such as electroencephalography (EEG) and magnetic resonance imagining, could be applied to further investigate the mechanisms underlying PLP.
Association between accuracy of weight perception and life satisfaction among adults with and without anxiety and mood disorders: a cross-sectional study of the 2015–2018 Canadian Community Health Survey
Authors: Hadwen Brook , He Jennifer , Funk Celine , McKinney Kelly , Wilk Piotr
Published: April 2022

Background

Weight status and weight perception have a significant impact on life satisfaction. As overweight prevalence increases in Canada, it is important to understand how accuracy of weight perception (AWP) is associated with life satisfaction. This study explored the association between AWP and life satisfaction among Canadian adults with and without anxiety and/or mood disorders.

Methods

Using data from the 2015–2018 cycles of the Canadian Community Health Survey, an indicator of AWP was created to capture concordance between perceived weight and actual weight status. Univariate and multivariate Gaussian generalized linear models were assessed while stratifying by sex and presence of anxiety and/or mood disorders.

Results

Our sample included 88 814 males and 106 717 females. For both sexes, perceiving oneself as overweight or underweight, regardless of actual weight status, was associated with lower life satisfaction (β = −0.93 to −0.30), compared to those who accurately perceived their weight as ‘just about right’. Perceiving oneself as overweight or underweight was associated with more pronounced differences in life satisfaction scores in those with anxiety and/or mood disorders (β = −1.49 to −0.26) than in those without these disorders (β = −0.76 to −0.25).

Conclusion

Weight perception is more indicative of life satisfaction than actual weight status, especially in those with anxiety and/or mood disorders.
Does Welfare Prevent Crime? the Criminal Justice Outcomes of Youth Removed from Ssi
Authors: Deshpande Manasi , Mueller-Smith Michael
Published: April 2022

We estimate the effect of losing Supplemental Security Income (SSI) benefits at age 18 on criminal justice and employment outcomes over the next two decades. To estimate this effect, we use a regression discontinuity design in the likelihood of being reviewed for SSI eligibility at age 18 created by the 1996 welfare reform law. We evaluate this natural experiment with Social Security Administration data linked to records from the Criminal Justice Administrative Records System. We find that SSI removal increases the number of criminal charges by a statistically significant 20% over the next two decades. The increase in charges is concentrated in offenses for which income generation is a primary motivation (60% increase), especially theft, burglary, fraud/forgery, and prostitution. The effect of SSI removal on criminal justice involvement persists more than two decades later, even as the effect of removal on contemporaneous SSI receipt diminishes. In response to SSI removal, youth are twice as likely to be charged with an illicit income-generating offense than they are to maintain steady employment at ${\$}$15,000/year in the labor market. As a result of these charges, the annual likelihood of incarceration increases by a statistically significant 60% in the two decades following SSI removal. The costs to taxpayers of enforcement and incarceration from SSI removal are so high that they nearly eliminate the savings to taxpayers from reduced SSI benefits.
Non-hyperbolicity of the inviscid Cattaneo–Christov system for compressible fluid flow in several space dimensions
Authors: Angeles Felipe
Published: April 2022

We consider the coupling between the equations of motion of a compressible fluid in two and three space dimensions with Christov’s equation for the heat flux. Christov’s equation is a frame indifferent formulation of the classical model of Cattaneo that allows for the heat flux to be eliminated to obtain a single hyperbolic equation for the temperature. The obtained system is written in quasilinear form for the state variables density, velocity, temperature and heat flux. It is then shown that this system is not of hyperbolic type as a consequence of the presence of the Lie–Oldroyd upper-convected material derivative involved in Christov’s formulation.
Low-lying zeros in families of holomorphic cusp forms: the weight aspect
Authors: Devin Lucile , Fiorilli Daniel , Södergren Anders
Published: April 2022

We study low-lying zeros of L-functions attached to holomorphic cusp forms of level 1 and large even weight. In this family, the Katz–Sarnak heuristic with orthogonal symmetry type was established in the work of Iwaniec, Luo and Sarnak for test functions ϕ satisfying the condition supp$(\widehat \phi) \subset(-2,2)$. We refine their density result by uncovering lower-order terms that exhibit a sharp transition when the support of $\widehat \phi$ reaches the point 1. In particular, the first of these terms involves the quantity $\widehat \phi(1)$ which appeared in the previous work of Fouvry–Iwaniec and Rudnick in symplectic families. Our approach involves a careful analysis of the Petersson formula and circumvents the assumption of the Generalized Riemann Hypothesis (GRH) for higher-degree automorphic L-functions. Finally, when supp$(\widehat \phi)\subset (-1,1)$ we obtain an unconditional estimate which is significantly more precise than the prediction of the L-functions ratios conjecture.
Creating evaluative homogeneity: Experience of constructing a national journal ranking
Authors: Krzeski Jakub , Szadkowski Krystian , Kulczycki Emanuel
Published: April 2022

The study investigates the process of creating evaluative homogeneity within a performance-based research funding system. It does so in reference to the experience of creating a national journal ranking in Poland in 2019. It refers to the cases of two disciplines: biology and history. The use of this case is justified by its unique character, that is creating the ranking through means of both bibliometric indicators and expert panels. We therefore asked: What guided the actors who participated in the process of creating the ranking through the use of bibliometric indicators when introducing changes to its initial form? To answer this question, a mixed-methods approach was used. First, we conducted a quantitative analysis of changes made to the ranking during the consecutive steps of its creation. Second, we conducted a qualitative analysis of semi-structured interviews regarding actors’ motivations. By reflecting on the qualitative analysis along with the results of the quantitative part, this study reveals the extent to which actors impacted the form evaluative homogeneity took within the system. It further argues that this is dictated by how actors position themselves in relation to two opposing forces: those favouring the homogenization of research and those maintaining its heterogeneity. As these forces remain imbalanced, the study concludes with a call for further exploration of the interplay between the forces of homogenization and heterogenization and how the tensions between them are mediated within a performance-based research funding system.
A World Equilibrium Model of the Oil Market
Authors: Bornstein Gideon , Krusell Per , Rebelo Sergio
Published: April 2022

We use new, comprehensive micro data on oil fields to build and estimate a structural model of the oil industry embedded in a general equilibrium model of the world economy. In the model, firms that belong to Organization of the Petroleum Exporting Countries (OPEC) act as a cartel. The remaining firms are a competitive fringe. We use the model to study the macroeconomic impact of the advent of fracking. Fracking weakens the OPEC cartel, leading to a large long-run decline in oil prices. Fracking also reduces the volatility of oil prices in the long run because fracking firms can respond more quickly to changes in oil demand.
Slicing the Pie: Quantifying the Aggregate and Distributional Effects of Trade
Authors: Galle Simon , Rodríguez-Clare Andrés , Yi Moises
Published: April 2022

We develop a multi-sector gravity model with heterogeneous workers to quantify the aggregate and group-level welfare effects of trade. The model generalizes the specific-factors intuition to a setting with labour reallocation, leads to a parsimonious formula for the group-level welfare effects from trade, and nests the aggregate results in Arkolakis, Costinot and Rodríguez-Clare (2012, “New Trade Models, Same Old Gains?”, American Economic Review, 102, 94–130). We estimate the model using the structural relationship between China-shock driven changes in manufacturing employment and average earnings across US groups defined as commuting zones. We find that the China shock increases average welfare but some groups experience losses as high as four times the average gain. However, adjusting for plausible measures of inequality aversion barely affects the welfare gains. We also develop and estimate an extension of the model that endogenizes labour force participation and unemployment, finding similar welfare effects from the China shock.
CESIUM-RICH MICROPARTICLES RUNOFF DURING RAINFALL: A CASE STUDY IN THE TAKASE RIVER
Authors: Tatsuno Takahiro , Waki Hiromichi , Kakuma Minato , Nihei Naoto , Wada Toshihiro , Yoshimura Kazuya , Nakanishi Takahiro , Ohte Nobuhito
Published: April 2022

Cesium-rich microparticles (CsMPs) with high cesium-137 (137Cs) concentrations were released and deposited in surface soil after the Fukushima Daiichi Nuclear Power Plant accident. Radioactive materials on the soil surface layer enter rivers owing to soil erosion during rainfall. In this study, we investigated CsMPs runoff through the river via soil erosion during rainfall in the Takase River watershed in Namie Town, Fukushima Prefecture, Japan. CsMPs were rarely detected in suspended solids (SS) in water samples collected during four rainfalls between February and July 2021. Furthermore, the proportion of 137Cs concentration derived from CsMPs to 137Cs concentration in the form of SS (particulate 137Cs) in the water was ~6% on average, which suggests that 137Cs runoff in the form of CsMPs from the forest to the Takase River was not large.
DISTRIBUTIONS OF 210PB, 137CS AND PHYSICAL PROPERTIES IN BOTTOM SEDIMENTS OF WEST NANAO BAY, JAPAN
Authors: Ochiai Shinya , Fujita Atsushi , Tokunari Takeo , Sakai Hideo , Nagao Seiya
Published: April 2022

This study revealed sedimentation processes based on 137Cs and 210Pb distribution, grain size and magnetic susceptibility of bottom sediments in West Nanao Bay, Japan. Surface sediment concentrations and inventories of these radionuclides were relatively low in the middle and eastern areas of the bay and high in the western area, which has several major river mouths, suggesting that the contribution of riverine input affected only the western area. In the middle and eastern areas, the level of 137Cs inventory was much lower than that of the soils, and the excess 210Pb inventory was at the same level or lower. These results indicate that removal effects are stronger than accumulation effects (riverine input) in these areas. The patterns of radionuclides were consistent with the results, that grain size was relatively large in the middle and eastern areas, implying strong current conditions, and that fine sediment accumulated less in these areas.
LEVELS OF ATMOSPHERIC TRITIUM IN THE SITE OF FUSION TEST FACILITY
Authors: Tanaka Masahiro , Iwata Chie , Nakada Miki , Kato Akemi , Akata Naofumi
Published: April 2022

In the deuterium plasma experiment using Large Helical Device at the National Institute for Fusion Science (NIFS), a small amount of tritium is produced by the D–D fusion reaction. Then, a part of produced tritium is discharged into the environment via a stack. Thus, the atmospheric tritium in the site of NIFS has been monitored before starting the deuterium plasma experiment. The atmospheric tritium concentrations at NIFS were indicated to be background levels in Japan. To investigate the impact of tritium discharged from the stack, the correlation between the atmospheric tritium concentration and the tritium concentration observed in the stack was evaluated, and no significant correlation was found. In addition, the atmospheric tritium concentration at NIFS ranged within the background levels in Japan. Therefore, the impact of discharged tritium from the stack would be negligible in the environment at NIFS.
THE APPLICATION OF NEURAL NETWORK TECHNOLOGY BASED ON MEA-BP ALGORITHM IN THE PREDICTION OF MICRODOSIMETRIC QUALITIES
Authors: Gao Yunan , Li Haiyang , Gao Han , Chen Zhen , Wang Yidi , Tang Wei , Li Zhanpeng , Li Xiang , Chen Long , Yan Congchong , Sun Liang
Published: April 2022

The most abundant products of the interaction between radiation and matter are low-energy electrons, and the collisions between these electrons and biomolecules are the main initial source of radiation-based biological damage. To facilitate the rapid and accurate quantification of low-energy electrons (0.1–10 keV) in liquid water at different site diameters (1–2000 nm), this study obtained ${\overline{y}}_{\mathrm{F}}$ and ${\overline{y}}_{\mathrm{D}}$data for low-energy electrons under these conditions. This paper proposes a back-propagation (BP) neural network optimized by the mind evolutionary algorithm (MEA) to construct a prediction model and evaluate the corresponding prediction effect. The results show that the ${\overline{y}}_{\mathrm{F}}$ and ${\overline{y}}_{\mathrm{D}}$ values predicted by the MEA-BP neural network algorithm reach a training precision on the order of ${10}^{-8}$. The relative error range between the prediction results of the validated model and the Monte Carlo calculation results is 0.03–5.98% (the error range for single-energy electrons is 0.1–5.98%, and that for spectral distribution electrons is 0.03–4.4%).
The Organisational Pattern of Rohingya Refugee Community in Malaysia: Structural Opportunities, Constraints, and Intra-Community Dynamics
Authors: Putri Ratu Ayu Asih Kusuma , Gabiella Dennyza
Published: April 2022

This article draws attention to the proliferation of Rohingya community organisations in Malaysia. Based on interviews with Rohingya activists in Kuala Lumpur greater area, evidence shows that the refugee community organisations continue to be the focal points for welfare service and protection. It is argued that the ambivalent asylum policy and increasingly unfavourable socio-political environment of the host state were mediated by the organisations through support from the accumulated social capital and established social networks in their localities. We also found that despite a call for a united, collaborative Rohingya voice in Malaysia from humanitarian observers, the community continues to mobilise in separate, locally oriented organisations. Contributing factors are shown to derive partly from the structural opportunities and constraints encountered in the local contexts of Malaysia and partly from the persistent intergroup tensions. This article contributes to debates on refugee self-reliance and their prospective role in enhancing host countries’ social and economic life, as indicated by the Global Compact on Refugees. It is also relevant to general debates about refugee mobilisation in transit countries in Southeast Asia.
Deletion of Schizophrenia Susceptibility Gene Ulk4 Leads to Abnormal Cognitive Behaviors via Akt-GSK-3 Signaling Pathway in Mice
Authors: Hu Ling , Zhou Bing-Yao , Yang Cui-Ping , Lu Da-Yun , Tao Yun-Chao , Chen Lin , Zhang Lei , Su Jun-Hui , Huang Ying , Song Ning-Ning , Chen Jia-Yin , Zhao Li , Chen Yi , He Chun-Hui , Wang Yu-Bing , Lang Bing , Ding Yu-Qiang
Published: April 2022

Objectives

Despite of strenuous research in the past decades, the etiology of schizophrenia (SCZ) still remains incredibly controversial. Previous genetic analysis has uncovered a close association of Unc-51 like kinase 4 (ULK4), a family member of Unc-51-like serine/threonine kinase, with SCZ. However, animal behavior data which may connect Ulk4 deficiency with psychiatric disorders, particularly SCZ are still missing.

Methods

We generated Emx1-Cre:Ulk4flox/flox conditional knockout (CKO) mice, in which Ulk4 was deleted in the excitatory neurons of cerebral cortex and hippocampus.

Results

The cerebral cellular architecture was maintained but the spine density of pyramidal neurons was reduced in Ulk4 CKO mice. CKO mice showed deficits in the spatial and working memories and sensorimotor gating. Levels of p-Akt and p-GSK-3α/β were markedly reduced in the CKO mice indicating an elevation of GSK-3 signaling. Mechanistically, Ulk4 may regulate the GSK-3 signaling via putative protein complex comprising of two phosphatases, protein phosphatase 2A (PP2A) and 1α (PP1α). Indeed, the reduction of p-Akt and p-GSK-3α/β was rescued by administration of inhibitor acting on PP2A and PP1α in CKO mice.

Conclusions

Our data identified potential downstream signaling pathway of Ulk4, which plays important roles in the cognitive functions and when defective, may promote SCZ-like pathogenesis and behavioral phenotypes in mice.
Achieving societal and academic impacts of research: A comparison of networks, values, and strategies
Authors: Brenninkmeijer Jonna
Published: April 2022

Science policymakers and funding agencies are increasingly interested in the societal impact of research. In practice, this means that, when applying for funding, researchers have to justify the academic impact (e.g. publications and conferences) and the societal impact (e.g. influence on policy and practice) of their proposed research. This paper aims to find out how these requirements relate by comparing two ethnographic case studies of research in health care and health assessment that aim to combine both forms of impact. I analyze the networks, values, and strategies in both research groups, and show that achieving societal and academic impacts are different research practices. Hence, I argue that academic and societal impacts should not simply be added up as requirements for research funding or academic career development but should be understood and appreciated on their own terms.
A ‘Silent’ Pandemic? 1918–1919 Influenza Pandemic in Greece: Evidence from Hermoupolis, Syros
Authors: Raftakis Michail
Published: April 2022

The 1918–19 influenza pandemic was the most lethal pandemic in contemporary history. Exceptionally high mortality levels were also found in Hermoupolis during the 1918 pandemic, for which very limited work is available in Greece due to the lack of population statistics. Mortality increased within every age group while the W-shaped curve was confirmed when age-specific mortality is plotted. In particular, young adults and adults experienced the largest excess mortality, while short increases occurred among the very young and elderly due to their pre-existing high mortality risk most likely due to the aftermaths of the 1916–17 naval blockade in parts of the country. Finally, the limited references to the pandemic in the Athenian press—no qualitative sources are available in Hermoupolis—suggest that the Greek government may have attempted to conceal the extent of the pandemic because of the turbulent situation in the country at that time.
FGF10 Triggers De Novo Alveologenesis in a Bronchopulmonary Dysplasia Model: Impact on Resident Mesenchymal Niche Cells
Authors: Taghizadeh Sara , Chao Cho-Ming , Guenther Stefan , Glaser Lea , Gersmann Luisa , Michel Gabriela , Kraut Simone , Goth Kerstin , Koepke Janine , Heiner Monika , Vazquez-Armendariz Ana Ivonne , Herold Susanne , Samakovlis Christos , Weissmann Norbert , Ricci Francesca , Aquila Giorgio , Boyer Laurent , Ehrhardt Harald , Minoo Parviz , Bellusci Saverio , Rivetti Stefano
Published: April 2022

Bronchopulmonary dysplasia (BPD) is a neonatal lung disease developing in premature babies characterized by arrested alveologenesis and associated with decreased Fibroblast growth factor 10 (FGF10) expression. One-week hyperoxia (HYX) exposure of newborn mice leads to a permanent arrest in alveologenesis. To test the role of Fgf10 signaling to promote de novo alveologenesis following hyperoxia, we used transgenic mice allowing inducible expression of Fgf10 and recombinant FGF10 (rFGF10) protein delivered intraperitoneally. We carried out morphometry analysis, and IF on day 45. Alveolospheres assays were performed co-culturing AT2s from normoxia (NOX) with FACS-isolated Sca1Pos resident mesenchymal cells (rMC) from animals exposed to NOX, HYX-PBS, or HYX-FGF10. scRNAseq between rMC-Sca1Pos isolated from NOX and HYX-PBS was also carried out. Transgenic overexpression of Fgf10 and rFGF10 administration rescued the alveologenesis defects following HYX. Alveolosphere assays indicate that the activity of rMC-Sca1Pos is negatively impacted by HYX and partially rescued by rFGF10 treatment. Analysis by IF demonstrates a significant impact of rFGF10 on the activity of resident mesenchymal cells. scRNAseq results identified clusters expressing Fgf10, Fgf7, Pdgfra, and Axin2, which could represent the rMC niche cells for the AT2 stem cells. In conclusion, we demonstrate that rFGF10 administration is able to induce de novo alveologenesis in a BPD mouse model and identified subpopulations of rMC-Sca1Pos niche cells potentially representing its cellular target.
Historians’ Uses of Archived Material from Sociological Research: Some Observations with Reference to the Affluent Worker Study
Authors: Goldthorpe John
Published: April 2022

Of late, historians of twentieth-century Britain have made increasing use of archived material from sociological research. Such use is examined in the case of the Affluent Worker study. It is argued that established historiographical practice needs to be maintained, and careful consideration given to the provenance and purposes of the documentary material that is drawn upon—with close reference to the context, objectives, and design of the original research. So far as the Affluent Worker study is concerned, such a consideration has not always been adequate, and with untoward consequences. Further, where, as with the Affluent Worker study, the original research was of a survey-based, quantitative kind, serious methodological differences regarding data analysis can arise. These become most apparent where the re-use of the relics of such research is aimed at qualifying the conclusions of its authors or at critically ‘deconstructing’ the research processes in which they were involved.
History and Sociology: A Twenty-First Century Rapprochement?
Authors: Savage Mike
Published: April 2022

This article reflects on the significance of re-analysing material from social-science archives in the context of John Goldthorpe's critique of the use of data from the Affluent Worker project. Drawing on my own role in elaborating this approach, most comprehensively in my book Identities and Social Change, I defend the value of re-analysis both as a means of bringing out previously unknown popular testimonies, and also in reflecting on the way that social scientific research has itself been a significant force for social change in recent decades. I consider how the practice of re-analysis can be defended even when social-science protocols regarding replication cannot be used, and reflect more broadly the significance of the Affluent Worker study in shaping understandings of social change in Britain.
Benchmark Dose Modeling Approaches for Volatile Organic Chemicals Using a Novel Air-Liquid Interface In Vitro Exposure System
Authors: Speen Adam M , Murray Jessica R , Krantz Quentin Todd , Davies David , Evansky Paul , Harrill Joshua A , Everett Logan J , Bundy Joseph L , Dailey Lisa A , Hill Jazzlyn , Zander Wyatt , Carlsten Elise , Monsees Michael , Zavala Jose , Higuchi Mark A
Published: April 2022

Inhalation is the most relevant route of volatile organic chemical (VOC) exposure; however, due to unique challenges posed by their chemical properties and poor solubility in aqueous solutions, in vitro chemical safety testing is predominantly performed using direct application dosing/submerged exposures. To address the difficulties in screening toxic effects of VOCs, our cell culture exposure system permits cells to be exposed to multiple concentrations at air-liquid interface (ALI) in a 24-well format. ALI exposure methods permit direct chemical-to-cell interaction with the test article at physiological conditions. In the present study, BEAS-2B and primary normal human bronchial epithelial cells (pHBEC) are used to assess gene expression, cytotoxicity, and cell viability responses to a variety of volatile chemicals including acrolein, formaldehyde, 1,3-butadiene, acetaldehyde, 1-bromopropane, carbon tetrachloride, dichloromethane, and trichloroethylene. BEAS-2B cells were exposed to all the test agents, whereas pHBECs were only exposed to the latter 4 listed above. The VOC concentrations tested elicited only slight cell viability changes in both cell types. Gene expression changes were analyzed using benchmark dose (BMD) modeling. The BMD for the most sensitive gene set was within one order of magnitude of the threshold-limit value reported by the American Conference of Governmental Industrial Hygienists, and the most sensitive gene sets impacted by exposure correlate to known adverse health effects recorded in epidemiologic and in vivo exposure studies. Overall, our study outlines a novel in vitro approach for evaluating molecular-based points-of-departure in human airway epithelial cell exposure to volatile chemicals.
Evaluation of Variability Across Rat Acute Oral Systemic Toxicity Studies
Authors: Karmaus Agnes L , Mansouri Kamel , To Kimberly T , Blake Bevin , Fitzpatrick Jeremy , Strickland Judy , Patlewicz Grace , Allen David , Casey Warren , Kleinstreuer Nicole
Published: April 2022

Regulatory agencies rely upon rodent in vivo acute oral toxicity data to determine hazard categorization, require appropriate precautionary labeling, and perform quantitative risk assessments. As the field of toxicology moves toward animal-free new approach methodologies (NAMs), there is a pressing need to develop a reliable, robust reference data set to characterize the reproducibility and inherent variability in the in vivo acute oral toxicity test method, which would serve to contextualize results and set expectations regarding NAM performance. Such a data set is also needed for training and evaluating computational models. To meet these needs, rat acute oral LD50 data from multiple databases were compiled, curated, and analyzed to characterize variability and reproducibility of results across a set of up to 2441 chemicals with multiple independent study records. Conditional probability analyses reveal that replicate studies only result in the same hazard categorization on average at 60% likelihood. Although we did not have sufficient study metadata to evaluate the impact of specific protocol components (eg, strain, age, or sex of rat, feed used, treatment vehicle, etc.), studies were assumed to follow standard test guidelines. We investigated, but could not attribute, various chemical properties as the sources of variability (ie, chemical structure, physiochemical properties, functional use). Thus, we conclude that inherent biological or protocol variability likely underlies the variance in the results. Based on the observed variability, we were able to quantify a margin of uncertainty of ±0.24 log10 (mg/kg) associated with discrete in vivo rat acute oral LD50 values.
Is There an Association between Vitamin D Concentrations and Overweight in Children and Adolescents?
Authors: Coelho Stephanie Ramos , Faria João Carlos Pina , Fonseca Fernando Luiz Affonso , de Souza Fabiola Isabel Suano , Sarni Roseli Oselka Saccardo
Published: April 2022

Objective

To describe the 25-hydroxyvitamin D [25(OH)D] concentrations in children and adolescents and to verify the association with the body mass index z-score (ZBMI), lipid profile and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR).

Method

Cross-sectional study with 170 children and adolescents aged between 4 and 15 years (106 normal weight and 64 overweight) from a public institution in Santo André—Brazil. Weight, height and waist circumference were verified and ZBMI and waist-to-height ratio (WHtR) were calculated. Biochemical analysis: 25(OH)D levels [deficiency: 25(OH)D < 20 ng/ml]; glycemia and insulin (HOMA-IR), lipid profile and ultra-sensitive C-reactive protein.

Results

Mean age was 8.37 ± 3.17 years; 89 (52.4%) were male; 77 (45.3%) Caucasians and 121 (71.2%) pre-pubescent. Overweight was observed in 64 (37.6%), dyslipidemia in 108 (63.5%) and 25(OH)D deficiency in 117 (68.8%) of the individuals. ZBMI (r = −0.209; p = 0.006), WHtR (r = −0.154; p = 0.045), triglycerides (TGs) (r = −0.161; p = 0.037) and TGs/high-density lipoprotein (HDL) ratio (r = −0.168; p = 0.028) were inversely correlated with 25(OH)D concentrations. Overweight children and adolescents were four times more likely to have vitamin D deficiency (odds ratio = 4.28; 95% confidence interval 1.152 to 4.907; p = 0.019), after adjustment for pubertal development (prepubertal), sex (male), HDL-c (<45 mg/dl), non-HDL (>120 mg/dl), TG/HDL ratio (>2.0) and HOMA-IR.

Conclusions

A high prevalence of vitamin D deficiency (68.8%) was observed. There was an independent association between vitamin D deficiency and overweight, not observed for dyslipidemia and insulin resistance. The data point to the need for periodic monitoring of serum concentrations of 25(OH)D and reinforcement of guidelines for combating and preventing overweight in the pediatric age group.
The Bayelsa Health Summit: strategizing for health at a subnational level in Nigeria
Authors: Ogoina Dimie , Kaduru Chijioke , Stow Jones , Okoyen Ebikapaye , Igwele Pabara N
Published: April 2022

Nigeria is falling short of global targets for universal health coverage (UHC) and the country's journey toward the accelerated achievement of UHC is dependent on progress made by all its subnational governments. The Bayelsa State Health Summit (BSHS) was organized by a subnational government in the Niger Delta region of Nigeria to deepen the understanding of the state's health system and to strategize for improved health outcomes. In this article we share our experience with the planning, organization and outcomes of the BSHS. The BSHS titled ‘Achieving Improved Health Systems Performance through Strategic Planning and Stakeholder Engagement’ was held for 3 d in April 2021. More than 1800 participants across diverse national and international organizations deliberated and made recommendations across the summit theme and subthemes. At the end of the summit, the state government and summit participants resolved to enact a state health law, to develop and adopt a state 10-y health system improvement plan and to establish a Bayelsa Centre for Disease Control. The BSHS exposed the context-specific needs, challenges and expectations of the Bayelsa health system. It served as a platform for extensive stakeholder engagement and buy-in and fostered high-level political commitment for the transformation of the Bayelsa health system.
Is noma a neglected/overlooked tropical disease?
Authors: Feller Liviu , Lemmer Johan , Khammissa Razia Abdool Gafaar
Published: April 2022

Noma is a debilitating orofacial necrotizing bacterial disease that disproportionately affects impoverished malnourished persons, particularly young children, the vast majority of whom live in tropical and subtropical areas in sub-Saharan Africa. It has a very high mortality rate; causes significant physical and psychological morbidity, stigmatization and social discrimination; could be prevented, controlled and indeed eliminated by common public health interventions; and is overlooked with regard to public health awareness, in-depth scientific research activities and allocation of funding for prevention, treatment and research.

According to the WHO, noma comprises five sequential ‘stages’: (1) necrotizing gingivitis, (2) edema, (3) gangrene, (4) scarring and (5) sequelae. This WHO staging of noma is contentious, leading to diagnostic confusion with misestimation of the number of noma cases reported in epidemiological studies. We therefore suggest a simpler, more practical and scientifically valid two-stage classification comprising only (1) acute noma and (2) arrested noma.

Noma meets all the WHO criteria for classification as a neglected tropical disease (NTD). Most survivors of noma live with gross physical disfigurement and disability, and with impaired psychosocial functioning, so they are very often stigmatized and unjustifiably discriminated against. Owing to the paucity of evidence-based epidemiological data on noma, the relatively low number of people affected worldwide, and its apparently limited geographic distribution, noma does not yet feature on the WHO's list of NTDs, or on any global health agenda, and thus has not become a health priority for global action. We strongly support the inclusion of noma within the WHO list of NTDs. Without doubt this will increase the awareness of noma among healthcare providers and promote the systematic international accumulation and recording of data about noma.
Phylogeny of the order Phoenicopteriformes and population genetics of the Caribbean flamingo (Phoenicopterus ruber: Aves)
Authors: Frias-Soler Roberto Carlos , Bauer Andreas , Grohme Markus A , Espinosa López Georgina , Gutiérrez Costa María , Llanes-Quevedo Alexander , Van Slobbe Frank , Frohme Marcus , Wink Michael
Published: April 2022

Flamingos are highly mobile waterbirds that can be found in tropical and subtropical regions worldwide. The large distribution range of flamingos, the inaccessibility of most of their breeding sites and the lack of species-specific molecular markers, such as microsatellites, have hampered population genetics studies of these majestic birds. Here, we developed a library of microsatellite loci primers using high-throughput sequencing technology that could be used for further genetic studies on Phoenicopteriformes. Microsatellite and mitochondrial markers were employed for the genetic characterization of individuals of all flamingo species and their hybrids, and to conduct a population genetics study of the Caribbean flamingo. The phylogeny of Phoenicopteriformes was confirmed with six species grouped in two major clades that diverged approximately 13 Mya. This suggests the existence of two genera of flamingos, not three, as is currently accepted. The analysis of the genetic structure of the Caribbean flamingo shows that all Cuban demes constitute a single population isolated from the Bonairean colony. This supports suggestions of the existence of limited connectivity between northern and southern Caribbean colonies. The small Galápagos colony was confirmed as an isolated population with low genetic diversity; thus, it should be considered as threatened.