bluuebunny/crossref_metadata_2025 huggingface dataset:
Niche and neutral processes leave distinct structural imprints on indirect interactions in mutualistic networks
Authors: Simmons Benno I. , Beckerman Andrew P. , Hansen Katrine , Maruyama Pietro K. , Televantos Constantinos , Vizentin‐Bugoni Jeferson , Dalsgaard Bo
Published: December 2020

Indirect interactions are central to ecological and evolutionary dynamics in pollination communities, yet we have little understanding about the processes determining patterns of indirect interactions, such as those between pollinators through shared flowering plants. Instead, research has concentrated on the processes responsible for direct interactions and whole‐network structures. This is partly due to a lack of appropriate tools for characterising indirect interaction structures, because traditional network metrics discard much of this information.

The recent development of tools for counting motifs (subnetworks depicting interactions between a small number of species) in bipartite networks enables detailed analysis of indirect interaction patterns. Here we generate plant–hummingbird pollination networks based on three major assembly processes—neutral effects (species interacting in proportion to abundance), morphological matching and phenological overlap—and evaluate the motifs associated with each one.

We find that different processes produce networks with significantly different patterns of indirect interactions. Neutral effects tend to produce densely connected motifs, with short indirect interaction chains, and motifs where many specialists interact indirectly through a single generalist. Conversely, niche‐based processes (morphology and phenology) produced motifs with a core of interacting generalists, supported by peripheral specialists. These results have important implications for understanding the processes determining indirect interaction structures.

A free Plain Language Summary can be found within the Supporting Information of this article.
A molecular screening assay to identify Chlamydia trachomatis and distinguish new variants of C. trachomatis from wild‐type
Authors: Xiu Leshan , Li Yamei , Zhang Chi , Li Yizhun , Zeng Yaling , Wang Feng , Peng Junping
Published: December 2020

Chlamydia trachomatis is the most common sexually transmitted pathogen globally, causing serious health problems and representing a burden on public health. A new variant of C. trachomatis (nvCT) that carries mutations (C1514T, C1515T and G1523A) in the 23S rRNA gene has eluded detection in Aptima Combo 2 assays. This has led to false negatives in diagnostics tests and poses a challenge for C. trachomatis diagnostics on a global level. In this study, we developed a simple and cost‐effective assay to identify C. trachomatis, with a potential application to screen for nvCT. We developed a screening assay based on high‐resolution melting (HRM), targeting the 23S rRNA gene and cryptic plasmid. To evaluate the performance of the assay, 404 archived C. trachomatis DNA specimens and 570 extracted clinical specimens were analysed. Our HRM assay not only identified C. trachomatis in clinical specimens, but also correctly differentiated nvCT carrying C1514T, C1515T and G1523A mutations from the wild‐type. We observed no cross‐reactions with other clinically related agents, and the limit of detection was 11.26 (95% CI; 7.61–31.82) copies per reaction. Implementation of this screening assay could reduce detection times and costs for C. trachomatis diagnoses, and facilitate increased research on the presence and monitoring of nvCT.
Dilmun boats on seals, horned figureheads, and the serpent/dragon slaying myth, c. 2050–1500 BC
Authors: Terp Laursen Steffen
Published: December 2020

Seals of Dilmun type from Bahrain and Failaka island (Kuwait) in 18 cases have depictions of boats. Contrary to previous studies, it is argued here that these vessels represent a distinct class of single‐masted sail boats and further that this boat type probably is synonymous with the “Dilmun boats” mentioned in Babylonian textual sources as a specific long‐distance vessel type native to Dilmun. The prow of the Dilmun boats typically exhibit a characteristic “figurehead” with two horns, large jaws and two forward‐projecting “prongs”. Based on comparatively similar looking serpent/dragon representations in Dilmun’s glyptic art and the mythological information that can be understood from the scene in which they appear, the horned figureheads of the Dilmun boats are identified as a possible Dilmunite goddess of the primordial sea, somehow comparable to the Babylonian Tiamat. Following analysis of this serpent/dragon on the seals, it is argued that there existed a Dilmunite version of the near omnipresent conflict myth. This myth and its distinct topos are discussed, and it is concluded that in Dilmun it played a role in royal ideology and the legitimisation of kingship.
Does compliance with Green Bond Principles bring any benefit to make G20’s ‘Green economy plan’ a reality?
Authors: Nanayakkara Kariyawasam Galoluwage Madurika , Colombage Sisira
Published: December 2020

We examine the impact and degree of compliance with Green Bond Principles (GBPs) on investor demand for Green Bonds (GBs) in G20 countries by employing cross‐sectional regression to analyse data over the period 2007–2016. After controlling for common bond‐specific and macroeconomic variables, we find a significant positive impact of higher compliance with principles on investor demand, as measured by bid‐ask spread and yield spread. We show that GBs issued by government institutions are able to minimise the adverse effects of low compliance with GBPs and the investor demand for fixed‐coupon GBs is higher than float‐coupon GBs.
Stock performance under alternative Shariah screening methods: Evidence from Australia
Authors: El Saleh Ali I. , Jurdi Doureige J.
Published: December 2020

This paper examines the effect of Shariah screening on performance. We use the constituents of the ASX200 to identify Shariah‐compliant investments (SCI) using eight different Shariah screening methods (SSMs) and investigate the effect of quantitative screening ratios and purification ratios on performance. We find significant differences in the constituents of the SCI universe and performance across SSMs. Our results demonstrate consistent evidence that the debt and purification ratios are negatively associated with SCI performance. However, we find mixed results for the impact of liquidity ratios on performance.
Habitat use across multiple scales suggests resilience to rising seas for endangered island endemic compared to sympatric invasive species
Authors: Taillie P. J. , Jolly S. R. , Bobay L. R. , Sneckenberger S. , McCleery R. A.
Published: December 2020

Wildlife is increasingly threatened by a suite of anthropogenic factors including climate change, habitat loss from human development, and invasive species. These threats are particularly pronounced on islands where species are more likely to go extinct. To better understand how native and invasive species on islands might respond to these threats, we compared habitat use between the endangered silver rice rat (SRR) Oryzomys palustris natator and invasive black rat Rattus rattus across multiple scales. We used a specialized camera trap design to survey rodents across the Lower Florida Keys, USA, a region vulnerable to emerging threats, such as rising sea level, and persistent threats, such as human development. Additionally, we used a novel modeling approach to investigate temporal variation in rodent activity as a function of lunar tides. Silver rice rat occurrence was greatest in regularly inundated mangroves that could potentially increase in extent as sea level rises. Black rats were widespread and often co‐occurred with SRR, but we observed temporal resource partitioning between these species, which suggests competition may be limited. Of the stressors we investigated, we conclude that contjaceinued urban development is the most substantial threat to SRR, and potentially other island species. Our results highlight island species’ disparate responses to different aspects of global change and the potential conservation opportunities that may result.
Cementation of the highly cross‐linked polyethylene liner into a well‐fixed acetabular shell to treat patients with recurrent dislocation after total hip arthroplasty
Authors: Wang Pai‐Han , Tsai Shang‐Wen , Chen Cheng‐Fong , Wu Po‐Kuei , Chen Chao‐Ming , Chang Ming‐Chau , Chen Wei‐Ming
Published: December 2020

Cementation of a highly cross‐linked polyethylene liner into a well‐fixed acetabular shell provided a good durability for liner wear. However, its efficacy in treating recurrent instability due to malposition cup is less reported. The aim of this study is to evaluate the outcome of this surgical technique to treat hip instability. From 2009 to 2019, we have identified 38 patients who had been surgically treated for recurrent instability, including cementation liner (N = 20) and revision cup (N = 18) procedures. Patients were followed for a mean of 45.66 months. We have recorded and analyzed all causes of implant failure including recurrent instability. Clinical outcomes were assessed including complication and Harris Hip Score (HHS) preoperatively and at the latest follow‐up. Revision‐free survivorship for any cause was 95.0% at 1 year, and 84.4% at 5 years in cementation liner group and 88.9% at 1 year and 5 years in revision cup group. Mean Harris hip score improved from 48.3 points preoperatively to 79.5 points at the last follow‐up in cementation liner group and mean HHS improved from 43.3 points preoperatively to 77.2 points in revision cup group. There were two implant failures in each group, including one is due to persistent hip instability and the other is due to periprosthetic joint infection in the cementation liner group and two implant failure are due to persistent hip instability in the revision cup group. Functional scores and implant survival were similar in both groups. We demonstrated that orientation correction via the cementation of the polyethylene liner into well‐fixed acetabular shell is a promising option to treat and prevent instability.

Level of Evidence: Therapeutic Level IV.
An exploratory study of basic income fidelity index
Authors: Kim Sang Kyun , Lee Bong Joo
Published: December 2020

There is growing interest in adopting basic income as a new social protection policy in many countries. South Korea is no exception. There have been heated discussions on the benefits and costs of adopting basic income as a universal income support program among policy makers and academics in South Korea. However, one of the problems in the discourse of basic income discussion in South Korea has been a lack of clear definition of basic income. In this study, we develop a basic income fidelity index (BIFI) that can be applied to basic income programs to show how fully a program fits to the basic income concept. Such an index can be useful in making the terminologies and concepts of basic income clearer. We test feasibility of BIFI by applying it to four different case examples of basic income; Alaska Permanent Fund, UK Child Trust Fund, Switzerland’s Basic Income Plan, and Finland’s Basic Income Experiment. We show BIFI can be a useful tool to differentiate various types of basic income. It can be also used to identify strengths and weaknesses of a basic income scheme.
Review: Exercise for depression in children and adolescents – a systematic review and meta‐analysis
Authors: Axelsdóttir Brynhildur , Biedilæ Sølvi , Sagatun Åse , Nordheim Lena V. , Larun Lillebeth
Published: December 2020

Background

The objective of this systematic review was to examine the treatment effects of exercise on children and adolescents with depression compared to either other nonexercise treatments or no treatment. A study protocol was registered in PROSPERO (CRD42018101982).

Method

Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid), Embase (Ovid), PsycINFO (Ovid), AMED (Ovid), SPORTDiscus, PEDro, CINAHL (EBSCO), ERIC (EBSCO), Web of Science, and databases for grey literature and dissertations were searched from their inception through 30 August 2020 for randomized controlled trials. Varieties of search terms for depression, children and adolescents, exercise, and study design were applied. No limits were placed on publication year, language or publication type. Registers for ongoing trials were also searched. Two authors independently screened references, extracted data and assessed risk of bias in the included trials. The effect sizes for depression postintervention were pooled in a meta‐analysis, and the certainty of the evidence was assessed using GRADE (Grading of Recommendations Assessments, Development, and Evaluation).

Results

13,307 references were screened. Four trials were included (n = 159). Participants were between 12 and 18 years old, and predominantly female. A meta‐analysis with a random‐effects model was performed, and a moderate effect in favour of exercise on postintervention depression severity was identified (SMD = −0.59, 95% CI = −1.08 to −0.10,p = .02). However, the overall certainty of the evidence for this outcome was low. One trial found a nonsignificant decrease in depression severity at six‐month follow‐up (n = 42, SMD = −0.59, 95% CI = −1.22 to 0.04,p = 0.07), and the overall certainty of the evidence for this outcome was very low. One trial found no statistically significant differences between the exercise and control groups on quality of life. Other outcomes, including adverse events, psychological well‐being and social functioning, were not evaluated.

Conclusion

Low certainty evidence suggests that exercise interventions may be associated with a decrease in adolescent depression severity. However, our confidence in the effect estimate is limited, and the true effect may be substantially different. Thus, large, high‐quality trials including follow‐up periods are needed.
α‐Emitting cancer therapy using 211At‐AAMT targeting LAT1
Authors: Kaneda‐Nakashima Kazuko , Zhang ZiJian , Manabe Yoshiyuki , Shimoyama Atsushi , Kabayama Kazuya , Watabe Tadashi , Kanai Yoshikatsu , Ooe Kazuhiro , Toyoshima Atsushi , Shirakami Yoshifumi , Yoshimura Takashi , Fukuda Mitsuhiro , Hatazawa Jun , Nakano Takashi , Fukase Koichi , Shinohara Atsushi
Published: December 2020

α‐Methyl‐l‐tyrosine (AMT) has a high affinity for the cancer‐specific l‐type amino acid transporter 1 (LAT1). Therefore, we established an anti‐cancer therapy, with 211At‐labeled α‐methyl‐l‐tyrosine (211At‐AAMT) as a carrier of 211At into tumors. 211At‐AAMT had high affinity for LAT1, inhibited tumor cell growth, and induced DNA double‐stranded breaks in vitro. We evaluated the accumulation of 211At‐AAMT in vivo and the role of LAT1. Treatment with 0.4 MBq/mouse 211At‐AAMT inhibited tumor growth in the PANC‐1 tumor model and 1 MBq/mouse 211At‐AAMT inhibited metastasis in the lung of the B16F10 metastasis model. Our results suggested that 211At would be useful for anti‐cancer therapy and that LAT1 is suitable as a target for radionuclide therapy.
Neuropsychological study in 19 French patients with White‐Sutton syndrome and POGZ mutations
Authors: Garde Aurore , Cornaton Jenny , Sorlin Arthur , Moutton Sébastien , Nicolas Claire , Juif Christine , Geneviève David , Perrin Laurence , Khau‐Van‐Kien Philippe , Smol Thomas , Vincent‐Delorme Catherine , Isidor Bertrand , Cogné Benjamin , Afenjar Alexandra , Keren Boris , Coubes Christine , Prieur Fabienne , Toutain Annick , Trousselet Yann , Bourgouin Solène , Gonin‐Olympiade Coralie , Giraudat Kim , Piton Amélie , Gérard Bénédicte , Odent Sylvie , Tessier Fanny , Lemasson Lola , Heide Solveig , Gelineau Anne‐Claire , Sarret Catherine , Miret Anne , Schaefer Elise , Piard Juliette , Mathevet Rémi , Boucon Marion , Bruel Ange‐Line , Mau‐Them Frederic Tran , Chevarin Martin , Vitobello Antonio , Philippe Christophe , Thauvin‐Robinet Christel , Faivre Laurence
Published: December 2020

White‐Sutton syndrome is a rare developmental disorder characterized by global developmental delay, intellectual disabilities (ID), and neurobehavioral abnormalities secondary to pathogenic pogo transposable element‐derived protein with zinc finger domain (POGZ) variants. The purpose of our study was to describe the neurocognitive phenotype of an unbiased national cohort of patients with identified POGZ pathogenic variants. This study is based on a French collaboration through the AnDDI‐Rares network, and includes 19 patients from 18 families with POGZ pathogenic variants. All clinical data and neuropsychological tests were collected from medical files. Among the 19 patients, 14 patients exhibited ID (six mild, five moderate and three severe). The five remaining patients had learning disabilities and shared a similar neurocognitive profile, including language difficulties, dysexecutive syndrome, attention disorders, slowness, and social difficulties. One patient evaluated for autism was found to have moderate autism spectrum disorder. This study reveals that the cognitive phenotype of patients with POGZ pathogenic variants can range from learning disabilities to severe ID. It highlights that pathogenic variations in the same genes can be reported in a large spectrum of neurocognitive profiles, and that children with learning disabilities could benefit from next generation sequencing techniques.
Influence of implant‐specific radiation doses on peri‐implant hard and soft tissue: An observational pilot study
Authors: Neckel Norbert , Wagendorf Pia , Sachse Claudia , Stromberger Carmen , Vach Kirstin , Heiland Max , Nahles Susanne
Published: December 2020

Objectives

The aim of this study was to investigate the influence of real implant‐bed‐specific radiation doses on peri‐implant tissue health in head and neck cancer (HNC) patients after radiotherapy.

Material and methods

Specific radiation doses in the area of 81 implants, in 15 irradiated HNC patients, were analyzed by matching data from the radiotherapy planning system with those of three‐dimensional follow‐up scans after implantation. Peri‐implant bone resorption was measured radiographically after 1 and 3 years, and peri‐implant tissue health was evaluated clinically. Individual parameters, such as age, gender, and localization, regarding the implant‐specific radiation dose distribution were analyzed statistically.

Results

The mean implant‐bed‐specific radiation dose was high, with 45.95 Gy to the mandible and 29.02 Gy to the maxilla, but significantly lower than the mean total dose to the tumor bed. Peri‐implant bone resorption correlated with local inflammation and plaque. After 1 year, women temporarily showed significantly more bone loss than men and implant‐specific radiation dose had a significant impact on peri‐implant bone loss after 3 years.

Conclusions

The presented method is a feasible option to define precise implant‐bed‐specific radiation doses for research or treatment planning purposes. Implant‐based dental restoration after radiotherapy is a relatively safe procedure, but a negative radiation dose‐dependent long‐term effect on peri‐implant bone resorption calls for interdisciplinary cooperation between surgeons and radio‐oncologists to define high‐risk areas.
A guide to using the internet to monitor and quantify the wildlife trade
Authors: Stringham Oliver C. , Toomes Adam , Kanishka Aurelie M. , Mitchell Lewis , Heinrich Sarah , Ross Joshua V. , Cassey Phillip
Published: December 2020

The unrivaled growth in e‐commerce of animals and plants presents an unprecedented opportunity to monitor wildlife trade to inform conservation, biosecurity, and law enforcement. Using the internet to quantify the scale of the wildlife trade (volume and frequency) is a relatively recent and rapidly developing approach that lacks an accessible framework for locating relevant websites and collecting data. We produced an accessible guide for internet‐based wildlife trade surveillance. We detailed a repeatable method involving a systematic internet search, with search engines, to locate relevant websites and content. For data collection, we highlight web‐scraping technology as an efficient way to collect data in an automated fashion at regularly timed intervals. Our guide is applicable to the multitude of trade‐based contexts because researchers can tailor search keywords for specific taxa or derived products and locations of interest. We provide information for working with the diversity of websites used in wildlife trade. For example, to locate relevant content on social media (e.g., posts or groups), each social media platform should be examined individually via the site's internal search engine. A key advantage of using the internet to study wildlife trade is the relative ease of access to an increasing amount of trade‐related data. However, not all wildlife trade occurs online and it may occur on unobservable sections of the internet.
High‐flow nasal cannula oxygen versus conventional oxygen for hypercapnic chronic obstructive pulmonary disease: A meta‐analysis of randomized controlled trials
Authors: Huang Xuan , Du Yanping , Ma Zhiyi , Zhang Huaping , Jun Liu , Wang Zhiyong , Lin Meixia , Ni Fayu , Li Xi , Tan Hui , Tan Shifan
Published: December 2020

Introduction

Low‐concentration oxygen is an established way for the treatment of chronic obstructive pulmonary disease (COPD) with Type II respiratory failure. Hypercapnia can complicate both COPD exacerbations and stable COPD. Treating with noninvasive ventilation (NIV) can reduce carbon dioxide tension in arterial (PaCO2) in hypercapnic COPD. As an open system, high‐flow nasal cannula oxygen (HFNC) is easy to tolerate and use. More researches are needed to focus on how HFNC is used to treat COPD patients with hypercapnic respiratory failure.

Methods

The Cochrane Library, Medline, EMBASE, and CINAHL database were retrieved from inception to October 2019. Eligible trials were clinical randomized controlled trials comparing the effects of HFNC and conventional oxygen on hypercapnic COPD patients. Two researchers assessed the quality of each study and extracted the data into RevMan 5.3 independently. The primary outcome was PaCO2 and the secondary outcome was PaO2.

Results

Four RCTs with 329 patients were included. The research results indicated that PaCO2 in the HFNC group was similar to the conventional oxygen group. No significant difference were observed in PaCO2 (MD −0.98, CI: −2.67 to 0.71, Z = 1.14, p = 0.25) and PaO2 (MD −0.72, CI: −6.99 to 5.55, Z = 0.23, p = 0.82) between the HFNC group and conventional oxygen group.

Conclusions

Our meta‐analysis showed no difference in PO2 and PCO2 between the HFNC and conventional oxygen. But we should treat this conclusion with caution because the number of studies and participants is small and, there is heterogeneity in the PaO2 and PCO2 measurements between stable and AECOPD.
G970R‐CFTR Mutation (c.2908G>C) Results Predominantly in a Splicing Defect
Authors: Fidler Meredith C. , Buckley Alexandra , Sullivan James C. , Statia Marvin , Boj Sylvia F. , Vries Robert G. J. , Munck Anne , Higgins Mark , Moretto Zita Matteo , Negulescu Paul , van Goor Fredrick , De Boeck Kris
Published: December 2020

In previous work, participants with a G970R mutation in cystic fibrosis transmembrane conductance regulator (CFTR) (c.2908G>C) had numerically lower sweat chloride responses during ivacaftor treatment than participants with other CFTR gating mutations. The objective of this substudy was to characterize the molecular defect of the G970R mutation in vitro and assess the benefit of ivacaftor in participants with this mutation. This substudy assessed sweat chloride, spirometry findings, and nasal potential difference on and off ivacaftor treatment in three participants with a G970R/F508del genotype. Intestinal organoids derived from rectal biopsy specimens were used to assess ivacaftor response ex vivo and conduct messenger RNA splice and protein analyses. No consistent or meaningful trends were observed between on‐treatment and off‐treatment clinical assessments. Organoids did not respond to ivacaftor in forskolin‐induced swelling assays; no mature CFTR protein was detected in Western blots. Organoid RNA analysis demonstrated that 3 novel splice variants were created by G970R‐CFTR: exon 17 truncation, exons 13–15 and 17 skipping, and intron 17 retention. Functional and molecular analyses indicated that the c.2908G>C mutation caused a cryptic splicing defect. Organoids lacked an ex vivo response with ivacaftor and supported identification of the mechanism underlying the CFTR defect caused by c.2908G>C. Analysis of CFTR mutations indicated that cryptic splicing was a rare cause of mutation misclassification in engineered cell lines. This substudy used organoids as an alternative in vitro model for mutations, such as cryptic splice mutations that cannot be fully assessed using cDNA expressed in recombinant cell systems.
Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of Vixotrigine in Healthy Volunteers
Authors: Naik Himanshu , Steiner Deb J. , Versavel Mark , Palmer Joanne , Fong Regan
Published: December 2020

Neuropathic pain affects ~ 6.9–10% of the general population and leads to loss of function, anxiety, depression, sleep disturbance, and impaired cognition. Here, we report the safety, tolerability, and pharmacokinetics of a voltage‐dependent and use‐dependent sodium channel blocker, vixotrigine, currently under investigation for the treatment of neuropathic pain conditions. The randomized, placebo‐controlled, phase I clinical trials were split into single ascending dose (SAD) and multiple ascending dose (MAD) studies. Healthy volunteers received oral vixotrigine as either single doses followed by a ≥ 7‐day washout period for up to 5 dosing sessions (SAD, n = 30), or repeat doses (once or twice daily) for 14 and 28 days (MAD, n = 51). Adverse events (AEs), maximum observed vixotrigine plasma concentration (Cmax), area under the concentration‐time curve from predose to 24 hours postdose (AUC0–24), time to Cmax (Tmax), and terminal half‐life (t1/2), among others, were assessed. Drug‐related AEs were reported in 47% and 53% of volunteers in the SAD and MAD studies, respectively, with dizziness as the most commonly reported drug‐related AE. SAD results showed that Cmax and AUC increased with dose, Tmax was 1–2 hours, and t1/2 was ~ 11 hours. A twofold increase in accumulation was observed when vixotrigine was taken twice vs. once daily (MAD). Steady‐state was achieved from day 5 onward. These data indicate that oral vixotrigine is well‐tolerated when administered as single doses up to 825 mg and multiple doses up to 450 mg twice daily.
Implications of Polymorphisms in the BCKDK and GATA‐4 Gene Regions on Stable Warfarin Dose in African Americans
Authors: Bargal Salma A. , Kight Jennifer N. , Augusto de Oliveira Felipe , Shahin Mohamed H. , Langaee Taimour , Gong Yan , Hamadeh Issam S. , Cooper-DeHoff Rhonda M. , Cavallari Larisa H.
Published: December 2020

VKORC1 and CYP2C9 genotypes explain less variability in warfarin dose requirements in African Americans compared with Europeans. Variants in BCKDK and GATA‐4 gene regions, purported to regulate VKORC1 and CYP2C9 expression, have been shown to play an important role in warfarin dose requirements in Europeans and Asians, respectively. We sought to determine whether rs56314408 near BCKDK or GATA‐4 rs2645400 influence warfarin dose requirements in 200 African Americans. Unlike the strong linkage disequilibrium (LD) between rs56314408 and VKORC1 rs9923231 in Europeans, they were not in LD in African Americans. No associations were found on univariate analysis. On multivariable analysis, rs56314408 was associated (P = 0.027) with dose in a regression model excluding VKORC1 rs9923231, and GATA‐4 rs2645400 was associated (P = 0.032) with dose in a model excluding CYP2C (CYP2C9*2, *3, *5, *6, *8, and *11, CYP2C rs12777823) variants. Neither variant contributed to dose in the model that included both VKORC1 rs9923231 and CYP2C variants. Our results do not support contributions of the studied variants to warfarin dose requirements in African Americans. However, they illustrate the value of studies in African descent populations, who have low LD in their genome, in teasing out genetic variation underlying drug response associations. They also emphasize the importance of confirming associations in persons of African ancestry.
Performance Index for Types of Clinical Research Support Service Providers for Academic Research Organizations in Japan: A Cross‐Sectional Survey
Authors: Ueda Keiko , Uemura Naoto , Matsuyama Kotone , Nishizaki Yuji , Tanemura Nanae , Asano Kento , Otsuka Yuki , Yanagisawa Naotake , Otsuka Toshiaki , Yasuno Shinji , Ueda Rieko , Seo Yumiko , Nakagami Hironori , Sanada Shoji
Published: December 2020

The purpose of this study was to conduct a factual survey to evaluate the type of clinical research support offered by service providers (supporters) in Japanese academic research organizations (AROs). From September to October 2018, we conducted an online questionnaire targeting researchers and supporters of AROs, including individuals supporting research and development (R&D) planning, as well as those involved in study management, biostatistics, coordination, data management, monitoring, and auditing. The number of responses was tabulated for each survey item. For items with written descriptions, we compiled summaries using the inductive regression method of qualitative research. Responses were obtained from 124 researchers, 258 supporters, and 40 AROs. None of the institutions responded that they had a performance index for all types of service providers, whereas 47% of institutions had an index for 1–3 types of service providers, and 40% of institutions had no index. Many institutions responded that they had a performance index for coordinators and data management, but few responded that there was a performance index for individuals engaged in R&D and study management. Furthermore, for all evaluations of AROs and researchers, the level of supporter satisfaction was low at only 20%. There was a discrepancy between the levels of researcher expectations and the actual contribution of R&D in the process of research planning. Our survey revealed that there is currently no performance index for services supporting clinical research. In future studies, we need to examine a performance index that accurately reflects the researcher attitudes revealed in this study.
Neighborhood racial demographics predict infants’ neural responses to people of different races
Authors: Hwang Hyesung G. , Debnath Ranjan , Meyer Marlene , Salo Virginia C. , Fox Nathan A. , Woodward Amanda
Published: December 2020

Early in life, greater exposure to diverse people can change the tendency to prefer one's own social group. For instance, infants from racially diverse environments show less preference for their own‐race (ingroup) over other‐race (outgroup) faces than infants from racially homogeneous environments. Yet how social environment changes ingroup versus outgroup demarcation in infancy remains unclear. A commonly held assumption is that early emerging ingroup preference is based on an affective process: feeling more comfortable with familiar ingroup than unfamiliar outgroup members. However, other processes may also underlie ingroup preference: Infants may attend more to ingroup than outgroup members and/or mirror the actions of ingroup over outgroup individuals. By aggregating 7‐ to 12‐month‐old infants’ electroencephalography (EEG) activity across three studies, we disambiguate these different processes in the EEG oscillations of preverbal infants according to social environment. White infants from more racially diverse neighborhoods exhibited greater frontal theta oscillation (an index of top‐down attention) and more mu rhythm desynchronization (an index of motor system activation and potentially neural mirroring) to racial outgroup individuals than White infants from less racially diverse neighborhoods. Neighborhood racial demographics did not relate to White infants’ frontal alpha asymmetry (a measure of approach‐withdrawal motivation) toward racial outgroup individuals. Racial minority infants showed no effects of neighborhood racial demographics in their neural responses to racial outgroup individuals. These results indicate that neural mechanisms that may underlie social bias and prejudices are related to neighborhood racial demographics in the first year of life.
Payment‐by‐results for health interventions in low‐ and middle‐income countries: A critical review
Authors: Duvendack Maren
Published: December 2020

Motivation

Payment‐by‐results (PbR) is now an important form of conditionality, whereby donors disburse development aid on achieving a pre‐agreed measure.

Purpose

The article presents a critical review of PbR for health interventions, aiming to draw out lessons about the implementation and impact of PbR in international development programmes.

Approach and Methods

An extensive search identified 81 studies that varied widely in terms of health sub‐themes, geographical regions and methodological quality.

Findings

Employing the Measure‐Agent‐Principal (MAP) framework we find that governments are the dominant principal in most of these studies, and health facilities and individuals the dominant agent; 60% of the evidence reports a wide range of heterogeneous output‐level measures.

Policy implications

We assess PbR in the context of health to better understand whether it is an effective aid‐delivery mechanism more broadly, and find that positive and significant effects dominate. We include evidence maps to highlight research gaps in the PbR literature.
Does household laborer migration promote farmland abandonment in China?
Authors: Lu Chong
Published: December 2020

This paper investigates the effects of household labor migration on rural household decision making over on the abandonment of farmland using 11,413 rural households' data from 2012 to 2016 in China. The results demonstrate that with every 1% increase in the number of 1, 2, 3, or more household migrant laborers, the average probability of rural households' farmland abandonment increases by 2.9%, 5.0%, and 7.8%, respectively. There is an inverted U‐shaped relationship between the average age of household migrant laborers and farmland abandonment. Both off‐farm employment and part‐time employment have positive impacts on farmland abandonment. If the age of the household head is younger, the number of household members is smaller, the village has suffered natural disasters, and village elevation is higher, rural households with laborers migrating are most likely to abandon farmland. As the rural household laborer migrates, the wage earning of rural household increases, which leads to the households gradually giving up management of farmland, which may be an important mechanism for Chinese households abandoning farmland. The establishment of a paid transfer system may be an effective way to solve the issue of farmland abandonment.
A Dye Tracer Approach for Quantifying Fluid and Solute Flux Across the Sediment–Water Interface
Authors: Cascarano Ryan N. , Reeves Donald M. , Henry Mark A.
Published: December 2020

We propose a dye tracer method to characterize fluid and solute fluxes across the sediment‐water interface. Zones of groundwater discharge within the streambed are first identified, and small volume slugs of 0.5 to 1 mL fluorescein dye are released at known subsurface depths. Fluorescein dye allows for visual identification of interface breakthrough locations and times, and dye concentrations at the point of discharge are recorded over time by a fluorometer to generate high resolution breakthrough curves. Groundwater velocities and dispersivities at the demonstration site are estimated by numerically fitting dye breakthroughs to the classical advection‐dispersion equation, although the methodology is not limited to a specific transport model. Breakthroughs across the stream‐sediment interface at the demonstration site are nonlinear with tracer release depth, and velocity estimates from breakthrough analysis are significantly more reliable than visual dye (time to first dye expression) and Darcy methods which tend to overestimate and underestimate groundwater velocity, respectively. The use of permanent injection points within the streambed and demonstrated reproducibility of dye breakthroughs allow for study of fluid and solute fluxes under seasonally varying hydrologic conditions. The proposed approach also provides a framework for field study of nonconservative, reactive solutes and allows for the determination of characteristic residence times at various depths in the streambed to better understand chemical and nutrient transformations.
Assessing the current knowledge, attitude and behaviour of adolescents and young adults living with haemophilia
Authors: Mohan Richa , Radhakrishnan Nita , Varadarajan Meera , Anand Sandip
Published: December 2020

Introduction

There is significant incidence of Haemophilia in India, with second largest number of persons with Haemophilia A. 20,778 patients registered with Haemophilia Foundation of India in 2018. Research in India includes diagnostic studies, complications and co‐morbidities, prenatal diagnosis, inhibitor development and gene therapy. Limited is known about quality of life of these patients. Since Haemophilia leads to the loss of ‘normal lifestyle’ in young people resulting in emotional distress and depression, it is important to analyse Knowledge, Attitude and Behaviour of persons with Haemophilia.

Aim

The aim of the study is to focus on exploring the status of Haemophilia and knowledge, attitude, behaviour of adolescents and youths with haemophilia with the objectives to study 1) the current medical status of haemophilia amongst target population; 2) the knowledge, attitude and behaviour of patients with haemophilia towards their condition.

Methods

Respondents in the age group of 15–30 years, who were registered with the Hemophilia Treatment Centers of Government Hospitals/Hemophilia Societies, were interviewed. Data were collected using a structured questionnaire. The study was conducted in two different states and with respondents of two different age groups.

Findings

Most respondents suffered from severe haemophilia and co‐morbidities such as anxiety, stress, chronic pain and head‐ache. All of them felt that haemophilia interferes in leading a normal life and perceive a grim future.

Conclusion

Young people in India need technical, financial and psychological support to prevent complications related to haemophilia. While most of them take responsibility for their health, more behavioural changes need to be inducted to improve quality of life.
Mineral trioxide aggregate‐induced AMPK activation stimulates odontoblastic differentiation of human dental pulp cells
Authors: Kim Yoon‐Jung , Kim Won‐Jae , Bae Sun‐Woong , Yang Sun‐Mi , Park Sam‐Young , Kim Seon‐Mi , Jung Ji‐Yeon
Published: December 2020

Aim

To investigate the role of autophagy in MTA‐induced odontoblastic differentiation of human dental pulp cells (HDPCs).

Methodology

In MTA‐treated HDPCs, odontoblastic differentiation was assessed based on expression levels of dentine sialophosphoprotein (DSPP) and dentine matrix protein 1 (DMP1), alkaline phosphatase activity (ALP) activity by ALP staining and the formation of mineralized nodule by Alizarin red S staining. Expression of microtubule‐associated protein 1A/1B‐light chain3 (LC3), adenosine monophosphate‐activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signalling molecules and autophagy‐related genes was analysed by Western blot analysis and Acridine orange staining was used to detect autophagic lysosome. For in vivo experiments, tooth cavity preparation models on rat molars were established and the expression of proteins‐related odontogenesis and autophagy markers was observed by Immunohistochemistry and Western blot analysis. Kruskal–Wallis with Dunn’s multiple comparison was used for statistical analysis.

Results

Mineral trioxide aggregate (MTA) promoted odontoblastic differentiation of HDPCs, accompanied by autophagy induction, including formation of autophagic lysosome and cleavage of LC3 to LC3II (P < 0.05). Conversely, inhibition of autophagy through 3MA significantly attenuated the expression level of DSPP (P < 0.05) and DMP1 (P < 0.05) as well as formation of mineralized nodules (P < 0.05), indicating the functional significance of autophagy in MTA‐induced odontoblastic differentiation. Also, MTA increased the activity of AMPK (P < 0.01), whereas inhibition of AMPK by compound C downregulated DSPP (P < 0.01) and DMP1 (P < 0.05), but increased the phosphorylation of mTOR (P < 0.05), p70S6 (P < 0.01) and Unc‐51‐like kinases 1 (ULK1) (ser757) (P < 0.01), explaining the involvement of AMPK pathway in MTA‐induced odontoblast differentiation. In vivo study, MTA treatment after tooth cavity preparation on rat molars upregulated DMP‐1 and DSPP as well as autophagy‐related proteins LC3II and p62, and enhanced the phosphorylation of AMPK.

Conclusion

MTA induced odontoblastic differentiation and mineralization by modulating autophagy with AMPK activation in HDPCs. Autophagy regulation is a new insight on regenerative endodontic therapy using MTA treatment.
Effective removal of cationic methylene blue dye using nano‐hydroxyapatite synthesized from fish scale bio‐waste
Authors: Swamiappan Sathiskumar , Ganesan Sivarasan , Sekar Vanaraj , Devaraj Sabarinathan , Subramanian Arulmani , Ponnusamy Vinoth Kumar , Kathirvel Preethi
Published: December 2020

Nano‐hydroxyapatite (NHAp) with a novel rod shape was synthesized from an economical and easily accessible Labeo rohita fish scale bio‐waste by facile and straightforward alkaline heat treatment method. The purity, functionality, morphology, and surface area of the green synthesized NHAp powder were well‐characterized via X‐ray diffraction (XRD), Fourier‐transform infrared (FT‐IR) spectroscopy, transmission electron microscopy (TEM), and Brunauer‐Emmett‐Teller (BET). The TEM and BET results indicate that the apatite is prepared as a rod‐like particle and highly porous with high surface area (112.36 m2 g−1). The NHAp powder was used for the adsorptive removal of cationic dye‐methylene blue (MB) from the aqueous samples. Batch experiments were performed to evaluate the mechanism of adsorption and kinetic models. The NHAp achieved an enhanced adsorption efficiency (666.67 mg g−1) for the adsorption process. The obtained results perfectly obeyed the pseudo‐second‐order model, and the Langmuir isotherm exhibited an excellent relationship with the experimental data. Furthermore, thermodynamic studies reveal that the adsorption process was exothermic and spontaneous. Thus, the results proved that Labeo rohita fish scale bio‐waste derived NHAp can be inventively utilized as a cost‐effective and eco‐friendly adsorbent for wastewater treatment.
Effects of different aberrations in the CRLF2 gene on the biological characteristics and drug sensitivities of Nalm6 cells
Authors: Gu Min , Jia Yannan , Xu Meizhen , Feng Juan , Tian Zheng , Ma Xiaotong , Wang Min , Wang Jianxiang , Xu Yingxi , Rao Qing , Hao Liangchun , Mi Yingchang , Yang Wei
Published: December 2020

Introduction

To investigate the effects and mechanism of action of upregulated CRLF2 expression resulting from different aberrations in the CRLF2 gene (CRLF2, CRLF2 + IK6, P2RY8‐CRLF2 and CRLF2 F232C) in the B cell ALL cell line Nalm6.

Methods

Cell proliferation was measured using cell counting kit‐8. Transcriptome sequencing technology (RNA‐seq) was used to compare changes in gene expression resulting from different aberrations in CRLF2. High‐throughput drug sensitivity testing was used to determine the drug sensitivity of cells.

Results

All four aberrations in CRLF2 upregulated CRLF2 expression and promoted the proliferation of Nalm6 cells. The RNA‐seq results showed the upregulation of genes in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and the downregulation of genes in the cell cycle pathway in the CRLF2 F232C‐overexpressing cells. Western blotting showed that the expression of p‐STAT5 protein was significantly higher in the CRLF2 F232C‐overexpressing cells. Cells with aberrations in CRLF2 were more resistant to cyclophosphamide and drugs commonly used during treatment than cells in the vector group. The half‐maximal inhibitory concentration (IC50 or GI50) of dexamethasone was significantly higher in the CRLF2 F232C‐overexpressing cell line.

Conclusions

The overexpression of CRLF2, CRLF2 + IK6, P2RY8‐CRLF2 and CRLF2 F232C promotes the proliferation of Nalm6 cells, activates the JAK/STAT signalling pathway and leads to a reduction in sensitivity towards various chemotherapeutic drugs.
Roadmap to a plasma cell: Epigenetic and transcriptional cues that guide B cell differentiation
Authors: Wiggins Keenan J. , Scharer Christopher D.
Published: December 2020

Antibody‐secreting cells (ASCs) or plasma cells secrete antibodies and form a cornerstone of humoral immunity. B cells that receive activation signals in the presence or absence of T cells initiate a differentiation program that requires epigenetic and transcriptional reprogramming in order to ultimately form ASC. Reprogramming is accomplished through the interplay of transcription factors that initiate gene expression programs and epigenetic mechanisms that maintain these programs and cell fates. An important consideration is that all of these factors are operating in the context of cell division. Recent technical advances now allow mechanistic studies to move beyond genetic studies to identify the promoters and enhancer repertoires that are regulated by epigenetic mechanisms and transcription factors in rare cell types and differentiation stages in vivo. This review will detail efforts to integrate transcriptional and epigenetic changes during B cell differentiation with cell division in vivo. What has emerged is a multiphased differentiation model that requires distinct transcription factors and epigenetic programs at each step. The identification of markers that define each phase will help facilitate the manipulation of B cell differentiation for vaccine development or to treat diseases where antibodies are a component.
Care dependency and management of urinary incontinence in nursing homes: A descriptive study
Authors: Huion Anja , De Witte Nico , Everaert Karel , Halfens Ruud J.G. , Schols Jos M.G.A.
Published: December 2020

Aim

To explore the differences in managing urinary incontinence in residents in nursing homes aged 65 years or older in relation to their care dependency.

Design

The 2015 data of the Dutch annual independent (Inter)national Prevalence Measurement of Quality of Care of Maastricht University were used. The design involved a cross‐sectional, multi‐centre point prevalence measurement in hospitals, care homes, and home care.

Methods

Secondary data analysis on the data provided by care home organizations.

Results

In the care independent group, the solely use of absorbing material was the mostly applied intervention. In the group of care dependent persons, the combination of absorbing material with toilet on set times and on individual basis was the most common approach.

Conclusion

The outcome of this study indicated that the management of urinary incontinence in residents in nursing homes differs depending on their care dependency.

Impact

Caregivers in nursing homes should be aware of preferences of residents regarding the management of their urinary incontinence.

Researchers should investigate criteria used by caregivers and care receivers into the decision of the application of interventions for urinary incontinence.