bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical evaluation of rapid 3D print‐formed implants for surgical reconstruction of large cranial defects
Authors: Kwarcinski Jeremy , Boughton Philip , van Gelder James , Damodaran Omprakash , Doolan Alessandra , Ruys Andrew
Published: October 2020

Background

To clinically evaluate 3D print‐formed implant process, using cranioplasty as a proof of concept, to examine its effectiveness and utility as a method of intraoperative implant fabrication.

Methods

Twelve patients had a 3D print‐formed template created for patient‐specific implant manufacture. Of these patients, 10 received intraoperatively formed polymethylmethacrylate cranioplasty implants between 2013 and 2019. The 3D print‐formed implant templates produced to manufacture these patient‐specific implants were generated using patient computed tomography scans and 3D printed using fused deposition modelling technology. Cosmetic and functional results were determined by participating surgeons, in conjunction with a patient questionnaire.

Results

The functional results and stability of the implants were deemed to be favourable by participating surgeons. Three of the 10 patients completed a post‐cranioplasty survey, all of whom judged their cosmetic results as good or excellent. At time of writing, the rate of surgical revision was zero and without clinically adverse outcomes.

Conclusions

3D print‐formed implants are an effective method of patient‐specific implant formation.
Borderline ovarian tumors in Denmark 1997‐2018: Time trends in incidence by histology, age and educational level
Authors: Baandrup Louise , Faber Mette T. , Aalborg Gitte L. , Kjaer Susanne K.
Published: October 2020

Introduction

After some decades with an increasing incidence of borderline ovarian tumors, more recent studies have observed that the incidence rate seems to be leveling off or declining. In this study, we describe the incidence of borderline ovarian tumors in Denmark 1997‐2018 by histology, age at diagnosis and educational level.

Material and methods

All borderline ovarian tumors registered in the Danish Pathology Registry during 1997‐2018 were identified and individual‐level educational information was retrieved from nationwide registers. Age‐standardized incidence rates were estimated according to histology, age at diagnosis and educational level. To investigate incidence trends over time, the average annual percentage change and corresponding 95% confidence intervals (CIs) were estimated using Poisson regression.

Results

We identified 3927 women with borderline ovarian tumors during the study period, of which 1997 (50.9%) were serous and 1743 (44.4%) were mucinous. The age‐standardized incidence rate of serous borderline ovarian tumors did not change significantly over calendar time (average annual percentage change = −0.13, 95% confidence interval [CI] −1.13 to 0.88). For mucinous tumors, the age‐standardized incidence rate was also relatively stable during the first half of the study period, followed by a decrease from 2.56 to 1.25 per 100 000 person‐years between 2007‐2011 and 2017‐2018. Over the entire study period, the incidence rate of mucinous borderline tumors declined on average by 2.91% (95% CI −4.24 to −1.51) per year. The incidence of both types of borderline ovarian tumors seemed to be highest among women with a low educational level. Over calendar time, the incidence of mucinous tumors decreased in all educational groups, whereas the incidence of serous tumors decreased exclusively in women with a high educational level. Time trends did not differ markedly by age at diagnosis.

Conclusions

In Denmark, the incidence of serous borderline ovarian tumors was stable during 1997‐2018, whereas the incidence of mucinous borderline ovarian tumors decreased. The incidence rates of both types of borderline ovarian tumors tended to be highest among women with a low educational level throughout the study period.
The bio‐surfactant mannosylerythritol lipid acts as a selective antibacterial agent to modulate rumen fermentation
Authors: Okuhira Kana , Koike Satoshi , Ito Shinji , Kobayashi Yasuo
Published: October 2020

Methyl‐mannosylerythritol lipid (MEL), a new sugar esterified lipid synthesized by Pseudozyma aphidis, was assessed for its functionality in modulating rumen fermentation and microbiota toward more propionate and less methane production. A pure culture study using rumen representatives showed that MEL selectively inhibited the growth of most Gram‐positive bacteria including Streptococcus bovis, ruminococci, and Fibrobacter succinogenes, but not Gram‐negative bacteria such as Megasphaera elsdenii, Succinivibrio dextrinosolvens, and Selenomonas ruminantium. A batch culture study revealed that MEL significantly decreased methane production in a dose‐dependent manner with accumulation of hydrogen, while propionate production was enhanced. A continuous culture (Rusitec) study confirmed all of these changes. A feeding study revealed that sheep fed a MEL diet showed an increased proportion of propionate, while proportions of acetate and butyrate were decreased without affecting total VFA level. These changes disappeared after cessation of MEL feeding. Based on these results, dietary application of MEL can favorably modify rumen fermentation in terms of the efficiency of dietary energy utilization.
Pharmacokinetically guided dosing has the potential to improve real‐world outcomes of pazopanib
Authors: Fukudo Masahide , Tamaki Gaku , Azumi Makoto , Shibata Hiroaki , Tandai Susumu
Published: October 2020

It remains unclear whether therapeutic drug monitoring (TDM) of pazopanib improves treatment outcomes in routine clinical practice. We did a prospective cohort study to evaluate the benefits of TDM for pazopanib therapy in real‐world practice. Among 25 patients with pharmacokinetically guided dosing, only 5 (20%, 95% confidence interval 6.8–40.7%) discontinued treatment because of adverse events. However, 5 (41.7%, 95% confidence interval 15.2–72.3%) of historical controls including 12 patients not receiving such a strategy experienced adverse events leading to early termination. PK‐guided dosing significantly increased median time‐to‐treatment discontinuation (252 vs 74 days, P = .012) with reduced toxicity and improved overall survival (not reached vs 313 days, P = .002) relative to conventional dosing in the control group. In conclusion, PK‐guided dose adaptation through the use of TDM has the potential to improve treatment outcomes of pazopanib in routine clinical practice, warranting larger, randomized studies.
QRICH1 variants in Ververi‐Brady syndrome—delineation of the genotypic and phenotypic spectrum
Authors: Föhrenbach Melanie , Jamra Rami Abou , Borkhardt Arndt , Brozou Triantafyllia , Muschke Petra , Popp Bernt , Rey Linda K. , Schaper Jörg , Surowy Harald , Zenker Martin , Zweier Christiane , Wieczorek Dagmar , Redler Silke
Published: October 2020

Ververi‐Brady syndrome (VBS, # 617982) is a rare developmental disorder, and loss‐of‐function variants in QRICH1 were implicated in its etiology. Furthermore, a recognizable phenotype was proposed comprising delayed speech, learning difficulties and dysmorphic signs. Here, we present four unrelated individuals with one known nonsense variant (c.1954C > T; p.[Arg652*]) and three novel de novo QRICH1 variants, respectively. These included two frameshift mutations (c.832_833del; p.(Ser278Leufs*25), c.1812_1813delTG; p.(Glu605Glyfs*25)) and interestingly one missense mutation (c.2207G > A; p.[Ser736Asn]), expanding the mutational spectrum. Enlargement of the cohort by these four individuals contributes to the delineation of the VBS phenotype and suggests expressive speech delay, moderate motor delay, learning difficulties/mild ID, mild microcephaly, short stature and notable social behavior deficits as clinical hallmarks. In addition, one patient presented with nephroblastoma. The possible involvement of QRICH1 in pediatric cancer assumes careful surveillance a key priority for outcome of these patients. Further research and enlargement of cohorts are warranted to learn about the genetic architecture and the phenotypic spectrum in more detail.
Expanding the genetic and phenotypic spectrum of the subcortical maternal complex genes in recurrent preimplantation embryonic arrest
Authors: Zheng Wei , Hu Huiling , Dai Jing , Zhang Shuoping , Gu Yifan , Dai Can , Guo Jing , Xu Xinxin , Li Yuan , Zhang Shunji , Hu Liang , Gong Fei , Lu Guangxiu , Lin Ge
Published: October 2020

The subcortical maternal complex (SCMC) is an oocyte‐to‐embryo‐specific maternal functional module. Some variants of SCMC genes that contribute to preimplantation embryonic arrest have been identified. However, more novel variants should be identified to broaden the genetic and phenotypic spectrum of SCMC genes and establish their roles in embryonic development. We identified 13 novel variants in the SCMC genes, TLE6, NLRP5, NLRP2, and PADI6, from 10 of a total of 50 infertile females with recurrent preimplantation embryonic arrest. Six variants in TLE6 were found in five patients with embryonic arrest, accompanied by direct cleavage and severe fragmentation at the cleavage stage. Three patients carried NLRP5 variants, and one patient each who carried NLRP2 and PADI6 variants had subsequent poor or failed fertilization and cleavage arrest with a relatively lower ratio of severely fragmented embryos. Our findings expand the genetic and phenotypic spectrum of SCMC genes associated with human embryogenesis and might help lay the foundation for the genetic diagnosis of female infertility.
Hypothalamic plasticity in response to changes in photoperiod and food quality: An adaptation to support pre‐migratory fattening in songbirds?
Authors: Majumdar Gaurav , Yadav Garima , Malik Shalie , Rani Sangeeta , Balthazart Jacques , Kumar Vinod
Published: October 2020

In latitudinal avian migrants, increasing photoperiods induce fat deposition and body mass increase, and subsequent night‐time migratory restlessness in captive birds, but the underlying mechanisms remain poorly understood. We hypothesized that an enhanced hypothalamic neuronal plasticity was associated with the photostimulated spring migration phenotype. We tested this idea in adult migratory red‐headed buntings (Emberiza bruniceps), as compared with resident Indian weaverbirds (Ploceus philippinus). Birds were exposed to a stimulatory long photoperiod (14L:10D, LP), while controls were kept on a short photoperiod (10L:14D, SP). Under both photoperiods, one half of birds also received a high calorie, protein‐ and fat‐rich diet (SP‐R, LP‐R) while the other half stayed on the normal diet (SP‐N, LP‐N). Thirty days later, as expected, the LP had induced multiple changes in the behaviour and physiology in migratory buntings. Photostimulated buntings also developed a preference for the rich food diet. Most interestingly, the LP and the rich diet, both separately and in association, increased neurogenesis in the mediobasal hypothalamus (MBH), as measured by an increased number of cells immunoreactive for doublecortin (DCX), a marker of recently born neurons, in buntings, but not weaverbirds. This neurogenesis was associated with an increased density of fibres immunoreactive for the orexigenic neuropeptide Y (NPY). This hypothalamic plasticity observed in a migratory, but not in a non‐migratory, species in response to photoperiod and food quality might represent an adaptation to the pre‐migratory fattening, as required to support the extensive energy expenses that incur during the migratory flight.
Can aspects of the discharge regime associated with juvenile Atlantic salmon (Salmo salar L.) and trout (S. trutta L.) densities be identified using historical monitoring data from five UK rivers?
Authors: Gillson Jonathan P. , Maxwell David L. , Gregory Stephen D. , Posen Paulette E. , Riley William D. , Picken Jessica L. , Assunção Marta G.L.
Published: October 2020

Understanding salmonid discharge requirements can help inform management to conserve wild populations in a changing climate. This study developed Bayesian hierarchical mixed‐effects models relating 0+ Atlantic salmon (Salmo salar L.) and trout (Salmo trutta L.) densities to different aspects of river discharge. Associations between these densities and nine hydrological variables representing the magnitude, frequency and duration of discharge events were evaluated using historical monitoring data from 36 sites on five rivers in England and Wales. All hydrological variables had weak associations with 0+ salmonid densities. More frequent high discharges between spawning and emergence were positively and negatively associated with 0+ salmon and trout densities, respectively. High discharges might increase spawning site availability for salmon and decrease egg‐to‐fry survival for trout. However, overall, only equivocal evidence was found regarding which discharge aspects affect juvenile salmonid densities. Therefore, a strategic review of juvenile salmonid monitoring programmes integrating environmental data collection is recommended.
(Pro)renin receptor/ATP6AP2 is required for autophagy and regulates proliferation in lung adenocarcinoma cells
Authors: Ohba Koji , Endo Moe , Sato Shigemitsu , Kashio‐Yokota Yurina , Hirose Takuo , Takahashi Kazuhiro
Published: October 2020

(Pro)renin receptor ((P)RR)/ ATP6AP2 (ATPase, H+ transporting, lysosomal accessory protein 2) functions as an essential accessory subunit of vacuolar H+‐ATPase (V‐ATPase). V‐ATPase is necessary for lysosome function and autophagy. Autophagy is related to cell proliferation, migration and invasion of various cancer cells. In this study, we aim to clarify the relationship between (P)RR and autophagy in lung adenocarcinoma. Expression of (P)RR and Ki‐67 (a proliferation marker) was studied in sixty‐four adenocarcinoma cases by immunohistochemistry. Lung adenocarcinoma cell line, A549, was transfected with (P)RR‐specific siRNA. Autophagy inhibitors, bafilomycin A1 and chloroquine, were used as positive controls. Cell proliferation and migration were measured by WST‐8 assay and wound healing assay. Autophagosome markers, p62 and LC3, were analyzed by RT‐qPCR, Western blot and immunocytochemistry. Immunohistochemistry showed that (P)RR was expressed in all adenocarcinoma tissues. The intensity of (P)RR immunoreactivity was significantly associated with Ki‐67. Treatment of (P)RR‐specific siRNA suppressed (P)RR expression and significantly reduced cell proliferation and migration as did the autophagy inhibitors. Western blot and immunocytochemistry showed that (P)RR‐specific siRNA, as well as the autophagy inhibitors, induced p62 and LC3 accumulation in cytoplasmic granules. These results suggest that (P)RR is involved in cell proliferation and progression of lung adenocarcinoma via regulating autophagy.
The novel form of amyloidosis derived from EGF‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1) preferentially affects the lower gastrointestinal tract of elderly femalesa
Authors: Dao Linda N , Kurtin Paul J , Smyrk Thomas C , Theis Jason D , Dasari Surendra , Vrana Julie A , Dispenzieri Angela , Nasr Samih H , McPhail Ellen D
Published: October 2020

Aims

To characterise the clinicopathological features of amyloidosis due to EGF‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1), a newly described amyloid type.

Methods and results

We identified cases by searching the Mayo Clinic amyloid liquid chromatography and tandem mass spectrometry typing database for specimens with the universal amyloid signature proteins, abundant EFEMP1 spectra and absence of other specific amyloid precursor proteins. We also developed an immunohistochemical stain for EFEMP1 applicable to formalin‐fixed tissue sections and performed electron microscopy in one case. We identified 33 specimens from 32 patients with EFEMP1 amyloid. Most patients were female (91%) with a mean age of 75 years, and most specimens (94%) were from the bowel. EFEMP1 amyloid was incidentally identified in specimens biopsied/resected for a variety of clinical indications. In bowel specimens, EFEMP1 amyloid involved blood vessels and interstitium of the lamina propria, submucosa and/or muscularis propria. Although the EFEMP1 deposits were weakly to moderately Congo red‐positive with absent to weak birefringence, they were strongly positive for EFEMP1 by immunohistochemistry, had the characteristic fibrillar ultrastructure of amyloid and were readily identified by mass spectrometry.

Conclusions

EFEMP1 amyloid is a recently described novel amyloid type that predominantly affects the bowel of elderly females. Because EFEMP1 amyloid is only weakly Congo red‐positive, it may be overlooked without a high index of suspicion. However, its characteristic microanatomical distribution is highlighted by immunohistochemistry and its identity is readily confirmed by mass spectrometry. Based on its distinctive features, we propose that EFEMP1 amyloidosis be considered a new amyloid type.
Self‐correction through corpus‐based tasks: Improving writing skills of Arabic learners
Authors: Zaki Mai
Published: October 2020

Most research in corpus‐based teaching has focused on using corpora in vocabulary building and the teaching of grammar. The present study discusses how corpus‐based tasks can help to improve the writing skills of the learners of Arabic as a foreign language through inducing self‐correction. The paper argues that a corpus‐based approach allows learners the opportunity for self‐correction and exploration of new ways to improve their sense of natural structures in Arabic. It presents a case study of intermediate level Arabic learners who complete corpus‐based tasks designed based on their errors in written assignments. A combination of online and offline tasks were used, with the aim to actively engage learners in “thinking” about their errors and how to correct them.
Consumers’ willingness to pay for organic versus all‐natural milk – Does certification make a difference?
Authors: Yormirzoev Mirzobobo , Li Tongzhe , Teuber Ramona
Published: October 2020

While there is ample evidence on consumers’ perceptions and willingness to pay (WTP) for organic food in developed markets, empirical evidence for transition economies is scarce. This paper is based on a survey of 608 Russian consumers that combined a questionnaire with a contingent valuation approach to investigate the impact of perceptions and trust on consumers’ WTP for certified organic, uncertified all‐natural and conventional milk, respectively. A between‐subject treatment design was used to analyse how consumers’ WTP responds to different information treatments. Our results suggest that most participants connect health benefits with the consumption of organic food, followed by slightly fewer respondents connecting organic production with environmental benefits. In the case of animal welfare benefits, the picture is less clear, as only 46% of respondents indicated that they agree that organic livestock production is associated with animal welfare benefits. Concerning the trust in farmer’s adherence to organic standards, a substantially higher share of respondents expressed trust in producers from the European Union versus their Russian counterparts. About 51% of respondents exhibited a positive WTP for organic milk in comparison to conventional milk. At the same time, there is no statistically significant difference in respondents’ WTP between all‐natural and organic milk. This similarity suggests that respondents do not seem to differentiate between uncertified all‐natural milk and certified organic milk.
Targeting immunometabolism in host defence against Mycobacterium tuberculosis
Authors: Sheedy Frederick J. , Divangahi Maziar
Published: October 2020

In the face of ineffective vaccines, increasing antibiotic resistance and the decline in new antibacterial drugs in the pipeline, tuberculosis (TB) still remains pandemic. Exposure to Mycobacterium tuberculosis (Mtb), which causes TB, results in either direct elimination of the pathogen, most likely by the innate immune system, or infection and containment that requires both innate and adaptive immunity to form the granuloma. Host defence strategies against infectious diseases are comprised of both host resistance, which is the ability of the host to prevent invasion or to eliminate the pathogen, and disease tolerance, which is defined by limiting the collateral tissue damage. In this review, we aim to examine the metabolic demands of the immune cells involved in both host resistance and disease tolerance, chiefly the macrophage and T‐lymphocyte. We will further discuss how baseline metabolic heterogeneity and inflammation‐driven metabolic reprogramming during infection are linked to their key immune functions containing mycobacterial growth and instructing protective immunity. Targeting key players in immune cellular metabolism may provide a novel opportunity for treatments at different stages of TB disease.
An analysis of inventory policies for substitute pharmaceuticals with purchasing or selling constraints
Authors: Chen Jingxian , Liang Liang , Yao Dong‐Qing
Published: October 2020

To improve patients' welfare, governments can regulate the availability of the low‐price drugs (LPDs) through lower wholesale purchasing or retail selling of the LPD. This paper characterizes two common constrained policies from the practices of pharmaceutical markets. The first (policy P) controls the ratios of the LPD's purchasing quantity and fee. The second (policy S) controls the ratios of the LPD's selling quantity and revenue. Considering a pharmaceutical supply chain consisting of two independent manufacturers and a hospital, we investigate the impacts of two policies on the LPD's availability and the whole industry gains. Our results show that policy P dominates policy S in two aspects: (a) policy P provides a higher product availability of the LPD and (b) policy P reduces less profits for the pharmaceutical supply chain. Specifically, policy P could incur a win‐win outcome for the patient and the supply chain. We further show that the demand allocation of the LPD, the substitution degree, and the profit margins' difference can significantly affect the performances of the policies.
Educational needs and disaster response readiness: A cross‐sectional study of clinical nurses
Authors: Jang Insil , Kim Ji‐Su , Lee Jungsun , Seo Yeji
Published: October 2020

Aim

To analyse clinical nurses’ educational needs and disaster response readiness and the factors influencing their disaster response readiness.

Design

This was a cross‐sectional study.

Methods

A convenience sample comprising 260 nurses with more than a year of working experience at a hospital in Korea was selected from 1‐31 August 2019. Data on nurses’ educational needs and disaster response readiness were collected from participants. A multiple regression model was used to examine the factors influencing disaster response readiness among nurses.

Results

Factors influencing personal readiness were number of years of clinical experience, being female, working in a medical ward, and educational needs for disaster response. Factors influencing self‐protection were working in a medical ward and working in the emergency room. Factors influencing the emergency response were working in a medical ward and working in the emergency room. Factors influencing clinical management were a graduate‐level education or higher, working in a medical ward, working in the emergency room, working in the paediatric ward, experience receiving disaster‐related education, and educational needs for disaster response.

Conclusion

It is essential to be aware of the educational needs and disaster readiness of hospital clinical nurses, to develop their capacity to respond such situations. In addition, to improve the disaster competency of nurses, it is necessary to develop an education programme that considers the factors influencing disaster response readiness in this study.

Impact

Nurses must have the knowledge and skills to respond to a disaster. Nurse educators should help nurses strengthen their disaster‐related knowledge, skills, and judgment. Hospital administrators should encourage nurse educators to provide disaster‐related training and simulation‐based education to increase nurses’ disaster competency to act during disasters.
The relationships among self‐efficacy, social support, resilience, and subjective well‐being in persons with spinal cord injuries
Authors: Bhattarai Muna , Jin Yuanyuan , Smedema Susan Miller , Cadel Kabita Raj , Baniya Mandira
Published: October 2020

Aims

To examine the contribution of self‐efficacy, social support, and resilience to subjective well‐being (SWB), to examine the mediating effect of resilience in the relationship between social support and SWB, and to investigate if marital status moderates the relationship between social support and SWB among people with spinal cord injuries (SCI).

Design

A descriptive cross‐sectional study, conducted from November 2017–January 2018.

Methods

One hundred and two individuals with SCI were recruited from a rehabilitation center and a community setting in Nepal. SWB, self‐efficacy, social support, resilience, demographics and injury‐related information was collected using self‐reported questionnaires. Hierarchical regression analysis, mediation analysis, and moderation analysis were performed in SPSS and R to test the hypotheses.

Results

Self‐efficacy, social support, and resilience uniquely explained 19% of the variance on SWB after controlling for demographic covariates. In the mediation analysis, resilience partially mediated the relationship between social support and SWB. In the moderation analysis, marital status moderated the relationship between resilience and SWB.

Conclusion

Subjective well‐being of persons with SCI is associated with many factors. Interventions to strengthen self‐efficacy, resilience, and social networks can be effective to enhance SWB. A stronger association between resilience and SWB among single participants reflects the need to provide specific considerations for persons with SCI who are single. Longitudinal and/or experimental studies are needed to further validate these findings.

Impact

This study identified external and internal factors contributing to SWB in persons with SCI. Self‐efficacy, social support, and resilience were found to be significantly associated with SWB. Resilience acted as a mediator between social support and SWB. The relationship between resilience and SWB was stronger in single participants than married participants. The findings have potential implications in the field of nursing since nurses are one of the integral members of the SCI rehabilitation team.
Divided groups need leadership: A study of the effectiveness of collective identity, dual identity, and intergroup relational identity rhetoric
Authors: Kershaw Christine , Rast David E. , Hogg Michael A. , van Knippenberg Daan
Published: October 2020

Reducing intergroup conflict is a significant leadership challenge. Leaders can alleviate conflict by promoting a collective, dual, or intergroup relational identity, but they should avoid provoking subgroup identity distinctiveness threat. Drawing on intergroup leadership theory, we conducted an experiment (N = 184) examining evaluations of a leader who promoted a dual, collective, or intergroup relational identity under low or high subgroup identity distinctiveness threat. We hypothesized that identity distinctiveness threat would improve evaluations of a leader promoting an intergroup relational identity, and worsen evaluations of a leader promoting a collective identity. Although a leader promoting a dual identity is typically preferred to one promoting a collective identity, we expected a leader promoting dual identity to receive worse evaluations than a leader promoting an intergroup relational identity. These hypotheses were supported, providing additional support for intergroup leadership theory and demonstrating the utility of employing intergroup relational identity rhetoric.
An interpolated biogeographical framework for tropical Africa using plant species distributions and the physical environment
Authors: Marshall Cicely A.M. , Wieringa Jan J. , Hawthorne William D.
Published: October 2020

Aim

Existing phytogeographical frameworks for tropical Africa lack either spatial completeness, unit definitions smaller than the regional scale or a quantitative approach. We investigate whether physical environmental variables can be used to interpolate floristically defined vegetation units, presenting an interpolated, hierarchical, quantitative phytogeographical framework for tropical Africa, which is compared to previously defined regions.

Location

Tropical mainland Africa 24°N to 24°S.

Taxon

31,046 vascular plant species and infraspecific taxa.

Methods

We calculate a betasim dissimilarity matrix from a comprehensive whole‐flora database of plant species distributions. We investigate environmental correlates of floristic turnover with local non‐metric multidimensional scaling. We derive a hierarchical biogeographical framework by clustering the dissimilarity matrix. The framework is modelled using a classification decision tree method and 12 physical environmental variables to interpolate and increase the resolution of the framework across the study region.

Results

Floristic turnover is related strongly to water availability and temperature, with smaller contributions from land cover, topographic ruggedness and lithology. Region can be predicted with 90% accuracy by the model. We define 19 regions and 99 districts. We find a novel arrangement of the arid regions. Regional subdivision within the savanna biome is supported with minor variation to borders. Within the forests of west and central Africa, our whole‐flora gridded regionalization supports the divisions identified by a previous analysis of trees only.

Main conclusions

Physical environmental variables can be used to predict floristically defined vegetation units with very high accuracy, and the approach could be pursued for other incompletely sampled taxa and areas outside of tropical Africa. Geographical coherence is higher than in previous quantitative phytoregional definitions. For most tropical African vascular plant species, we provide predictions of which species will occur within each mapped district and region of tropical Africa. The framework should be useful for future studies in ecology, evolution and conservation.
The ghost of connections past: A role for mainland vicariance in the isolation of an insular population of the red‐billed chough (Aves: Corvidae)
Authors: Morinha Francisco , Milá Borja , Dávila José A. , Fargallo Juan A. , Potti Jaime , Blanco Guillermo
Published: October 2020

Aim

Oceanic islands have often been colonized by small groups of individuals dispersing from the nearest mainland, giving rise to insular populations characterized by locally adapted phenotypes and low genetic diversity. Alternatively, due to past geo‐climatic changes, the present‐day distribution of the species may not correspond to that found at the time of the original colonization so that the current mainland distribution may not include the original source area, leading to erroneous assumptions regarding colonization history. Here, we use patterns of genetic variation to evaluate alternative colonization scenarios of an insular passerine in the Canary Islands.

Location

La Palma (Canary Islands), Northern Africa and the Iberian Peninsula.

Taxon

Red‐billed chough (Pyrrhocorax pyrrhocorax).

Methods

We use phylogeographical and coalescent analyses of mitochondrial DNA sequences and 10 microsatellite loci, together with Bayesian demographic modelling, to determine whether choughs on the island of La Palma originate from (a) present‐day populations in Iberia, (b) present‐day populations in the mountains of inland Morocco or (c) former populations in coastal Morocco, where suitable habitat existed in the past.

Results

Both the mitochondrial and nuclear datasets indicate that the chough population on La Palma is genetically well differentiated from those in Iberia and Morocco, and that La Palma choughs are more closely related to choughs in Iberia than to those in Morocco. Genetic diversity in La Palma is lower than that of mainland populations, but shows no evidence of past bottlenecks. The best supported demographic model to explain the origin of La Palma choughs that is congruent with both genetic datasets includes a ‘ghost’ population closely related to Iberia, from which the insular population diverged within the last 30,000 years.

Main conclusions

Our results are most consistent with the existence of a former connection between La Palma and Iberia along the North African coast, when suitable habitat was found there. Subsequent desertification of these coastal areas led to local extinctions that restricted gene flow between Iberia and the islands, promoting genetic differentiation. Our results provide a counterintuitive solution to a biogeographical enigma, and could help resolve the colonization history of other systems with similarly complex climatic pasts.
Exosomes derived from smooth muscle cells ameliorate diabetes‐induced erectile dysfunction by inhibiting fibrosis and modulating the NO/cGMP pathway
Authors: Song Jingyu , Sun Taotao , Tang Zhe , Ruan Yajun , Liu Kang , Rao Ke , Lan Ruzhu , Wang Shaogang , Wang Tao , Liu Jihong
Published: October 2020

Erectile dysfunction (ED) is a major health issue among men with diabetes, and ED induced by diabetes mellitus (DMED) is particularly difficult to treat. Therefore, novel therapeutic approaches for the treatment of DMED are urgently needed. Exosomes, nanosized particles involved in many physiological and pathological processes, may become a promising tool for DMED treatment. In this study, we investigated the therapeutic effect of exosomes derived from corpus cavernosum smooth muscle cells (CCSMC‐EXOs) on erectile function in a rat model of diabetes and compared their effect with that of exosomes derived from mesenchymal stem cells (MSC‐EXOs). We incubated labelled CCSMC‐EXOs and MSC‐EXOs with CCSMCs and then observed uptake of the exosomes at different time points using laser confocal microscopy. CCSMC‐EXOs were more easily taken up by CCSMCs. The peak concentration and retention time of labelled CCSMC‐EXOs and MSC‐EXOs in the corpus cavernosum of DMED rats after intracavernous injection were compared by in vivo imaging techniques. Intracavernous injection of CCSMC‐EXOs was associated with a relatively high peak concentration and long retention time. Our data showed that CCSMC‐EXOs could improve erectile function in DMED rats. Meanwhile, CCSMC‐EXOs could exert antifibrotic effects by increasing the smooth muscle content and reducing collagen deposition. CCSMC‐EXOs also increased the expression of eNOS and nNOS, followed by increased levels of NO and cGMP. These findings initially identify the possible role of CCSMC‐EXOs in ameliorating DMED through inhibiting corporal fibrosis and modulating the NO/cGMP signalling pathway, providing a theoretical basis for a breakthrough in the treatment of DMED.
DEPDC1 up‐regulates RAS expression to inhibit autophagy in lung adenocarcinoma cells
Authors: Wang Wei , Li Aili , Han Xiaodan , Wang Qingqing , Guo Jinyong , Wu Youru , Wang Chen , Huang Guojin
Published: October 2020

DEP domain containing 1(DEPDC1) is involved in the tumorigenesis of a variety of cancers. But its role in tumorigenesis of lung adenocarcinoma (LUAD) is not fully understood. Here, we investigated the role and the underlying mechanisms of DEPDC1 in the development of LUAD. The expression and prognostic values of DEPDC1 in LUAD were analysed by using the data from public databases. Gene enrichment in TCGA LUAD was analysed using GSEA software with the pre‐defined gene sets. Cell proliferation, migration and invasion of A549 cells were examined with colony formation, Transwell and wound healing assays. The function of DEPDC1 in autophagy and RAS‐ERK1/2 signalling was determined with Western blot assay upon DEPDC1 knockdown and/or overexpression in A549, HCC827 and H1993 cells. The results demonstrated that DEPDC1 expression was up‐regulated in LUAD tissues, and its high expression was correlated with unfavourable prognosis. The data also showed that DEPDC1 knockdown impaired proliferation, migration and invasion of A549 cells. Most notably, the results showed that DEPDC1 up‐regulated RAS expression and thus enhanced ERK1/2 activity, through which DEPDC1 could inhibit autophagy. In conclusion, our study revealed that DEPDC1 is up‐regulated in LUAD tissues and plays an oncogenic role in LUAD, and that DEPDC1 inhibits autophagy through the RAS‐ERK1/2 signalling in A549, HCC827 and H1993 cells.
Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression
Authors: Ji Ting‐Ting , Qi Ying‐Hui , Li Xiao‐Ying , Tang Bo , Wang Ya‐Kun , Zheng Peng‐Xi , Li Weiliang , Qu Xiaolei , Feng Linhong , Bai Shou‐Jun
Published: October 2020

Diabetic nephropathy (DN) is a serious kidney disease resulted from diabetes. Dys‐regulated proliferation and extracellular matrix (ECM) accumulation in mesangial cells contribute to DN progression. In this study, we tested expression level of MIAT in DN patients and mesangial cells treated by high glucose (HG). Up‐regulation of MIAT was observed in DN. Then, functional assays displayed that silence of MIAT by siRNA significantly repressed the proliferation and cycle progression in mesangial cells induced by HG. Meanwhile, we found that collagen IV, fibronectin and TGF‐β1 protein expression was obviously triggered by HG, which could be rescued by loss of MIAT. Then, further assessment indicated that MIAT served as sponge harbouring miR‐147a. Moreover, miR‐147a was decreased in DN, which exhibited an antagonistic effect of MIAT on modulating mesangial cell proliferation and fibrosis. Moreover, bioinformatics analysis displayed that E2F transcription factor 3 (E2F3) could act as direct target of miR‐147a. We demonstrated that E2F3 was greatly increased in DN and the direct binding association between miR‐147a and E2F3 was evidenced using luciferase reporter assay. In summary, our data explored the underlying mechanism of DN pathogenesis validated that MIAT induced mesangial cell proliferation and fibrosis via sponging miR‐147a and regulating E2F3.
Impaired insulin secretion predicting unstable glycemic variability and time below range in type 2 diabetes patients regardless of glycated hemoglobin or diabetes treatment
Authors: Miya Aika , Nakamura Akinobu , Handa Takahisa , Nomoto Hiroshi , Kameda Hiraku , Cho Kyu Yong , Nagai So , Miyoshi Hideaki , Atsumi Tatsuya
Published: October 2020

Aims/Introduction

To identify the coefficient of variation (CV) threshold for unstable glucose variability (GV) and hypoglycemia, and to characterize a patient population with unstable GV and hypoglycemia.

Materials and Methods

This was an observational study that enrolled 284 Japanese outpatients with type 2 diabetes who underwent continuous glucose monitoring. The C‐peptide index (CPI = [(fasting serum C‐peptide) / (plasma glucose)] × 100) was used as a marker of endogenous insulin secretion. The CV threshold between stable and unstable GV was defined as the upper limit of the CV distribution in the subgroup of patients who did not receive insulin nor insulin secretagogues (relatively stable GV subgroup, n = 104). The optimal CV range corresponding to time below target range ≥4% was determined for all patients using receiver operating characteristic curve analysis. Various characteristics of patients with unstable GV and hypoglycemia were extracted using multivariate logistic regression analysis.

Results

The upper limit of the CV in the relatively stable GV subgroup was 40. The optimal CV range corresponding to time below target range ≥4% was also defined as CV ≥40 (area under the curve 0.85) for all patients. The CPI was an independent risk for CV ≥40 (odds ratio 0.17, 95% confidence interval 0.04–0.50, P < 0.01). The optimal cut‐off point for CPI to predict a CV cut‐off value of 40 was equivalent to 0.81 (area under the curve 0.80).

Conclusions

A CV of 40 discriminates unstable GV and hypoglycemia from stable GV in Japanese outpatients with type 2 diabetes. Impaired insulin secretion might affect the stability of GV.
Building a Global Evidence Base to Guide Policy and Implementation for Group Antenatal Care in Low‐ and Middle‐Income Countries: Key Principles and Research Framework Recommendations from the Global Group Antenatal Care Collaborative
Authors: Grenier Lindsay , Lori Jody R. , Darney Blair G. , Noguchi Lisa Miyako , Maru Sheela , Klima Carrie , Lundeen Tiffany , Walker Dilys , Patil Crystal L. , Suhowatsky Stephanie , Musange Sabine
Published: October 2020

Evidence from high‐income countries suggests that group antenatal care, an alternative service delivery model, may be an effective strategy for improving both the provision and experience of care. Until recently, published research about group antenatal care did not represent findings from low‐ and middle‐income countries, which have health priorities, system challenges, and opportunities that are different than those in high‐income countries. Because high‐quality evidence is limited, the World Health Organization recommends group antenatal care be implemented only in the context of rigorous research. In 2016 the Global Group Antenatal Care Collaborative was formed as a platform for group antenatal care researchers working in low‐ and middle‐income countries to share experiences and shape future research to accelerate development of a robust global evidence base reflecting implementation and outcomes specific to low‐ and middle‐income countries. This article presents a brief history of the Collaborative's work to date, proposes a common definition and key principles for group antenatal care, and recommends an evaluation and reporting framework for group antenatal care research.
Effect of a low‐fat diet on serum triglyceride and cholesterol concentrations and lipoprotein profiles in Miniature Schnauzers with hypertriglyceridemia
Authors: Xenoulis Panagiotis G. , Cammarata Paul J. , Walzem Rosemary L. , Suchodolski Jan S. , Steiner Jörg M.
Published: October 2020

Background

Hypertriglyceridemia is common in Miniature Schnauzer (MS). Dietary management of hypertriglyceridemia is important, but no studies are available.

Hypothesis/Objectives

To evaluate the effect of a commercially available low‐fat diet on serum triglyceride and cholesterol concentrations and lipoprotein profiles in MS with hypertriglyceridemia.

Animals

Sixteen MS with hypertriglyceridemia and 28 MS without hypertriglyceridemia.

Methods

Prospective clinical trial. Four blood samples (1‐2 months before and 1 day before diet change and 2 and 3 months after the dogs were fed the low‐fat diet) were collected from the MS with hypertriglyceridemia.

Results

Serum triglyceride concentrations for the 2 samples after the diet change (median of sample 3 = 177 mg/dL; range, 48‐498; median of sample 4 = 168 mg/dL; range, 77‐745) were significantly lower than the 2 samples before the diet change (median of sample 1 = 480 mg/dL; range, 181‐1320; median of sample 2 = 493 mg/dL; range, 114‐1395; P < .001). Serum cholesterol concentrations for the 2 samples after the diet change (mean for sample 3 = 257 mg/dL, SD = 82.2; mean for sample 4 = 178 mg/dL, SD = 87.4) were also significantly lower than the 2 samples before the diet change (mean for sample 1 = 381 mg/dL, SD = 146.1; mean for sample 2 = 380 mg/dL, SD = 134.7; P < .001). Before the diet change, 15/16 (94%) of hyperlipidemic MS were classified as hyperlipidemic based on their lipoprotein profiles alone. After the diet change, significantly fewer MS (7/16; 44%; odds ratio = 19.3; 95% CI = 2.0‐184.0; P = .006) were classified as hyperlipidemic based on lipoprotein profile analysis.

Conclusions and Clinical Importance

The study diet was effective in reducing serum triglyceride and cholesterol concentrations and correcting lipoprotein profiles in MS with hypertriglyceridemia.
Age estimation and growth layer patterns in teeth of crabeater seals: A comparison of techniques
Authors: Cebuhar Julieta , Negrete Javier , Botta Silvina
Published: October 2020

Age estimation of marine mammals provides important information about ecological and life history parameters. Counting growth layer groups (GLGs) in the dentine and cementum of teeth is the most common technique for age estimation in pinnipeds. In this study, we used acid‐etched canines (n = 38) and decalcified stained postcanine sections (n = 40) to calibrate readings in mummified crabeater seals (Lobodon carcinophaga). A subsample of this group received a prior cleaning treatment of boiling the teeth with hydrogen peroxide (H2O2). Ages ranged from 0 to 31 years. Dentine from canines and cementum from postcanines showed higher estimated ages (maximum 31 years) than dentine from postcanines (maximum 24 years), mainly in those teeth that did not receive prior treatment. Boiling with H2O2 has shown to affect cementum structure and, thus, results in underestimated ages, but dentine did not seem to be affected. The results presented here showed that ages can be estimated for the crabeater seal regardless of which tooth/tissue or method is used, at least for seals <13 years old. However, nontreated, stained thin sections of postcanine teeth are recommended because more reliable age estimations in older crabeater seals are obtained.
Individual differences in risk‐taking affect foraging across different landscapes of fear
Authors: Steinhoff Philip O. M. , Warfen Bennet , Voigt Sissy , Uhl Gabriele , Dammhahn Melanie
Published: October 2020

One of the strongest determinants of behavioural variation is the tradeoff between resource gain and safety. Although classical theory predicts optimal foraging under risk, empirical studies report large unexplained variation in behaviour. Intrinsic individual differences in risk‐taking behaviour might contribute to this variation. By repeatedly exposing individuals of a small mesopredator to different experimental landscapes of risks and resources, we tested 1) whether individuals adjust their foraging behaviour according to predictions of the general tradeoff between energy gain and predation avoidance and 2) whether individuals differ consistently and predictably from each other in how they solve this tradeoff. Wild‐caught individuals (n = 42) of the jumping spider Marpissa muscosa, were subjected to repeated release and open‐field tests to quantify among‐individual variation in boldness and activity. Subsequently, individuals were tested in four foraging tests that differed in risk level (white/dark background colour) and risk variation (constant risk/variable risk simulated by bird dummy overflights) and contained inaccessible but visually perceivable food patches. When exposed to a white background, individuals reduced some aspects of movement and foraging intensity, suggesting that the degree of camouflage serves as a proxy of perceived risk in these predators. Short pulses of acute predation risk, simulated by bird overflights, had only small effects on aspects of foraging behaviour. Notably, a significant part of variation in foraging was due to among‐individual differences across risk landscapes that are linked to consistent individual variation in activity, forming a behavioural syndrome. Our results demonstrate the importance of among‐individual differences in behaviour of animals that forage under different levels of perceived risk. Since these differences likely affect food‐web dynamics and have fitness consequences, future studies should explore the mechanisms that maintain the observed variation in natural populations.