bluuebunny/crossref_metadata_2025 huggingface dataset:
A reassessment of the diversity of green toads (Bufotes) in the circum‐Aegean region
Authors: DUFRESNES Christophe , PROBONAS Nikolas M. , STRACHINIS Ilias
Published: September 2020

The dynamic biogeography of glacial refugia may cause complex patterns of genetic admixture between parapatric taxa, which in turn can mislead their systematics, diversity, and distributions. We investigated this issue for green toads (Bufotes) inhabiting the circum‐Aegean region, a biodiversity hotspot of the Eastern Mediterranean. A previous phylogeographic study based on mitochondrial and microsatellite loci identified the hybrid zone between the European (viridis) and Anatolian (sitibundus) lineages of B. viridis all over the Balkan Peninsula, but subsequent range‐wide genomic analyses (>1000 SNPs) located this transition in Turkey, a thousand kilometers eastwards. In order to clarify the diversity and taxonomy of the circum‐Aegean populations, we reconciled these conflicting findings by integrating previous data with pure sitibundus individuals. Our results confirmed that the viridis/sitibundus hybrid zone extends in Western Anatolia, but that southeastern European populations feature cytonuclear discordances and a high and structured microsatellite diversity. This remarkable situation may stem from a massive geographic displacement of the hybrid zone during the last glacial fluctuations, an underappreciated yet seemingly common feature among the herpetofauna of the region. Our study thus contributes to the rising view that mitochondrial DNA can be a poor predictor of current phylogeographic structure, hence the need for genomic data, especially for narrowly distributed taxa. Finally, the analyses unambiguously support the distinction of a micro‐endemic clade of green toads unique to some Cyclades islands, for which we provide a formal taxonomic description.
Ontogenetic resource use and trophic dynamics of endangered juvenile Tachypleus tridentatus among diversified nursery habitats in the northern Beibu Gulf, China
Authors: KWAN Kit Yue , BOPP Justin , HUANG Shuyan , CHEN Qiao , WANG Chun‐Chieh , WANG Xueping , ZHEN Wenquan , ZHU Junhua , HUANG Xing
Published: September 2020

Horseshoe crabs, the most well‐known example of “living fossils”, are iconic and ecologically important macroinvertebrates in coastal and estuarine ecosystems. Their blood is a crucial resource for manufacturing Limulus or Tachypleus amebocyte lysate to detect bacterial endotoxins or fungal contamination in drug and medical devices. An enhanced understanding of their ecological roles and trophic interactions in the food webs is fundamental to facilitate resource management for the declining populations in Asia. Foraging information of the Asian species, however, is mainly derived from preliminary, scattered reports from a limited number of study locations. In this study, resource utilization, trophic niche dynamics, and trophic interaction of the juvenile tri‐spine horseshoe crab, Tachypleus tridentatus (instars 1–12, approximately 0.5–8 years old) across ontogeny was assessed in diversified nursery habitats along the northern Beibu Gulf, China, using carbon and nitrogen stable isotopes. Our results suggest that: (i) T. tridentatus are ecological generalists given the vast range of carbon isotopic values and trophic niche width estimates exhibited between multiple instar groups; (ii) juvenile T. tridentatus across most habitat types predominantly assimilated energy from a variety of basal production sources in the food web, but primarily depended on sedimentary organic matter and seagrass resource pools; (iii) ontogenetic shifts in juvenile dietary proportions were evident, with decreased reliance on sedimentary organic matter, coupled with increased reliance on benthic macroinvertebrate grazers, detritivores, and omnivores with age; and (iv) nearly all juvenile instars occupied similar trophic positions in the food web with slight shifts in trophic position present with increasing size. Our findings indicate that resource availability and ontogenetic diet shifts strongly influence horseshoe crab trophic dynamics, and age should be accounted when formulating habitat conservation measures based on resource use for Asian horseshoe crabs.
Integrating univariate and multivariate statistical models to investigate genotype × environment interaction in durum wheat
Authors: Mohammadi Reza , Sadeghzadeh Behzad , Poursiahbidi Mohammad Mehdi , Ahmadi Malak Masoud
Published: September 2020

There has been a significant trend in the use of different statistical tools to analyse genotype × environment (GE) interaction for grain yield in multi‐environment trials. Several statistical models including 16 univariate stability methods and four multivariate models such as the additive main effects and multiplicative interaction (AMMI), GGE biplot (G+GE biplot), and factorial regression and partial least squares regression were applied to investigate the GE interaction for grain‐yield data of 18 durum wheat genotypes grown in 14 environments (location‐year combinations). The main objectives were to use the different statistical models to evaluate GE interaction for grain yield in durum wheat and to investigate the effect of some climatic variables on the interactions. The main effect of environment, genotype and GE interactions were significant (p < .01), and accounted for 85.1, 0.8 and 6.8% of total variation, respectively. Using the cluster and discriminant analyses, a pattern map developed simultaneously for clustering of stability methods and genotypes, which allowed identifying seven genotypic groups for genotypes and four groups for stability methods. The different stability groups explained genotypic performance differently, with or without respect to yield. The AMMI stability value, Wricke's ecovalence (Wi), Shukla's stability variance (σ2), Perkins and Jinks's (β and Dj) indices, joint regression parameters (bi and S2di, R2) and Tai's stability (σ and λ) methods did not correlate with genotypic mean yields, while the dynamic stability GGE distance and superiority measure (Pi) showed significant positive correlations with genotypic mean yields, showing selection based on these two methods would improve yield stability and performance. Using the applied methods, the breeding lines G12, G13 and G7 showed high mean yield and stability performance. The results also showed that the GE interactions were mostly influenced by the climatic data of rainfall, freezing days, minimum temperature and relative humidity. Although the multivariate methods provided valuable information on GE interaction, the univariate methods seem to be useful alternatives to complement improving screening efficiency.
The Rationality of USDA Forecasts under Multivariate Asymmetric Loss
Authors: Bora Siddhartha S. , Katchova Ani L. , Kuethe Todd H.
Published: September 2020

A large number of previous studies suggest that many USDA forecasts are biased and/or inefficient. These findings, however, may be the result of the assumed loss function of USDA forecasters. We test the rationality of the USDA net cash income forecasts and the WASDE production and price forecasts between 1988 and 2018 using a flexible multivariate loss function that allows for asymmetric loss and non‐separable forecast errors. Our results provide robust evidence that USDA forecasters are rational expected loss minimizers yet demonstrate a tendency to place a greater weight on under‐ or overprediction. As a result, this study provides an alternate interpretation of previous findings of forecast irrationality.
High‐dose methotrexate monotherapy for newly diagnosed primary central nervous system lymphoma: 15‐year multicenter experience
Authors: Yoon Wan‐Soo , Park Jae‐Sung , Kim Young‐il , Chung Dong‐Sup , Jeun Sin‐Soo , Hong Yong‐Kil , Yang Seung Ho
Published: September 2020

Aim

Primary central nervous system lymphoma (PCNSL) is rare disease and shows poor prognosis although methotrexate‐based chemotherapy is used. Here, we present our experiences with high‐dose methotrexate (HD‐MTX) monotherapy for immunocompetent patients with PCNSL at three institutions and investigate factors related to survival.

Methods

PCNSL patients, who were histologically confirmed with diffuse large B cells and treated with HD‐MTX monotherapy from 2001 to 2016, were retrospectively reviewed. Patients underwent induction chemotherapy with 8 g/m2 of MTX every 10 days (maximum three cycles). Maintenance chemotherapy of 3.5 g/m2 of MTX (maximum six cycles) was selectively performed depending on the response to induction chemotherapy.

Results

A total of 67 patients were included. Although seven patients discontinued induction chemotherapy because of MTX toxicity, 40 (59.7%) patients showed a complete response (CR) to induction chemotherapy. Twenty‐six (38.8%) and three (4.5%) patients showed a CR and partial response, respectively, after maintenance chemotherapy. Forty‐one patients with recurrence or progression following HD‐MTX underwent second‐line treatment. Progression‐free survival rates were 43% and 24% at 1 and 2 years, respectively. The median overall survival was 40.3 months. In a multivariate analysis, a radiological CR to induction chemotherapy was a significant factor related to prolonged progression‐free survival and overall survival (P < 0.05).

Conclusion

MTX‐monotherapy is tolerable in terms of adverse effects and still considered as a treatment option in patients with PCNSL. However, an additional therapeutic option should be prepared for non‐CR responders to induction chemotherapy.
Radiotherapy service need in the Pacific Island countries
Authors: Shafiq Jesmin , Gabriel Gabriel Sam , Barton Michael B.
Published: September 2020

Background

Pacific Island Countries and Territories (PICTs) have experienced an increase in cancer burden in the recent years. There is need for major investments in the cancer treatment facilities including radiotherapy (RT).

Aims

This study aimed to provide a quantitative estimation of the effect of establishing new RT facilities on patient access through Geographic Information System (GIS) modelling of population density and service availability to assess the best location for a new RT centre when there are multiple competing locations.

Methods

Methods involved cancer epidemiological data collection and assessing RT demand (proportion needing RT) in 2040, assessment of current RT facilities meeting the demand, GIS‐based assessment of minimal travel distance in relation to RT demand and scenario‐based location planning with adoption of the principles of efficiency, availability and equity for establishment of suitability of new RT facilities.

Results

In 2040, three highest new cancer case projections are for Papua New Guinea (PNG) (22662), Fiji (2058) and New Caledonia (2037). Twenty‐nine megavoltage machines (MVMs) are needed to meet adequate RT demand with three existing in New Caledonia, Guam and French Polynesia meeting 2–6% demand. PNG with highest RT demand of 68% and Fiji with second highest (6%) demand are found as the choice venues for maximum accessibility of cancer population within the PICTs.

Conclusion

The travel distance‐based GIS modelling estimation of establishment of new RT facilities will provide useful information for planning of RT services in the PICTS with improved patient outcome.
Baicalein inhibits FURIN‐MT1‐MMP‐mediated invasion of ectopic endometrial stromal cells in endometriosis possibly by reducing the secretion of TGFB1
Authors: Ke Jun‐Ya , Yang Jing , Li Jing , Xu Zhen , Li Ming‐Qing , Zhu Zhi‐Ling
Published: September 2020

Problem

Endometriosis (EMs) is characterized by the presence of endometrial stroma and glands outside the uterus. Our previous study showed that baicalein inhibited proliferation and induced apoptosis in EMs. However, the effects of baicalein on the invasiveness of ectopic endometrial stromal cells (EcESCs) remain unclear. The aim of this study was to assess the potential anti‐invasive effect of baicalein and determine the underlying mechanism.

Methods

The invasive and migratory properties of EcESCs were assessed in vitro using Transwell and wound healing assays. The expression of functional markers of EcESCs, including matrix metalloproteases (MMPs), FURIN, and TGFB1, was analyzed using WB and ELISA. Additionally, a mouse model of EMs was treated with baicalein (10 mg/kg/d and 35 mg/kg/d) for 4 weeks. The weight and number of ectopic lesions were determined, and the expression of markers was assessed using immunohistochemistry.

Results

Baicalein inhibited the invasion of EcESCs and the expression of certain invasion‐related proteins, including MMP9, MMP2, and MT1‐MMP. Exposure to baicalein reduced the extracellular levels of TGFB1 in EcESCs and the reduced expression of TGFB1, resulting in decreased expression of FURIN in EcESCs, which serves a pivotal role in the transformation of pro‐MT1‐MMP to activated MT1‐MMP. In the mouse model of EMs, intraperitoneal injection of baicalein inhibited the growth of ectopic lesions and reduced MT1‐MMP, FURIN, and TGFB1 expression.

Conclusions

Baicalein reduced the invasion of EMs, potentially by restricting the FURIN‐MT1‐MMP‐mediated cell invasion of EcESCs maybe through reduction of the autocrine of TGFB1.
Assessment of the right ventricle in donation after circulatory death hearts
Authors: Kadowaki Sachiko , Kotani Yasuhiro , Kobayashi Yasuyuki , Goto Takuya , Kasahara Shingo
Published: September 2020

In donation after circulatory death heart transplantation, the donor heart is exposed to circulatory load. The right ventricle, due to its structure, has high compliance for volume load but is particularly vulnerable to increased pressure load. This study used a porcine model to conduct a functional assessment of the hemodynamics of the heart, with a focus on the right ventricle. Six pigs weighing 24.6 ± 1.4 kg were used. Circulatory death was induced by asphyxiation after median sternotomy. After 30 minutes in the state of global warm ischemia, the ascending aorta was clamped, followed by a 20‐minute reperfusion of the heart with a 20°C blood cardioplegia solution. Systemic circulation was established by cardiopulmonary bypass after aortic cross‐clamping. After initial reperfusion, the blood cardioplegia solution was replaced with blood. The blood was then rewarmed while the heart was still in a non‐working state. Cardiac function was assessed twice in situ, first by the thermodilution method, and then, by the pressure–volume measurement both at preischemia and at three hours after initiation of reperfusion. The recovery rate of cardiac output was 75%. End‐systolic elastance (P = .02) and pulmonary arterial elastance significantly increased (P = .03), but the ratio of arterial elastance to end‐systolic elastance was preserved (P = .91) in the right ventricle. Despite a decrease in cardiac output after reperfusion from warm ischemia, the right ventricle had a potential to respond the elevated afterload. It is important that donations after circulatory death heart transplantation should be performed with attention to avoiding right ventricular distension.
Risk factor for lung infection in recipients after liver transplantation: A meta‐analysis
Authors: Zhang Jiaxue , He Qiang , Du Ling , Ji Renyue , Yuan Lingyue , Zhang Hongyang , Yuan Xinyu , Shen LiFei , Li Yingli
Published: September 2020

Lung infection (LI) often occurs in patients with liver transplantation (LT). This meta‐analysis was conducted to determine the risk factors associated with LI after LT. We retrieved relevant research published as of February 2020 from eight electronic databases. The studies were reviewed against the inclusion and exclusion criteria. The Z test was used to determine the combined odds ratio (OR) or the standardized mean difference (SMD) of the risk factors. We used the OR and its corresponding 95% confidence interval (CI) or the SMD and its corresponding 95% CI to identify significant differences in risk factors. A total of nine studies were included, comprising a total of 1624 recipients. Six risk factors associated with LI were identified after LT: Model for end‐stage liver disease score (MELD score) (SMD = 0.40), Child‐Pugh class C (OR = 3.00), intensive care unit (ICU) hospital stay (SMD = 1.35), mechanical ventilation (SMD = 1.03), bilirubin (SMD = 0.39), and atelectasis (OR = 7.28). Although certain risk factors have been identified as important factors for LI after LT, which may provide a basis for clinical prevention, a well‐designed prospective study should be conducted to validate the findings of this study.
The importance of low HbA1c during childhood on glycaemic control in adulthood and the risk of late complications
Authors: Samuelsson Ulf , Anderzen Johan , Åkesson Karin , Hanberger Lena
Published: September 2020

Aim

To evaluate whether a very low glycated haemoglobin A (HbA1c) (<48 mmol/mol, 6.5%) during childhood compared to higher HbA1c values further decreases the risk for microvascular complications.

Methods

Data were included from the 5116 patients with type 1 diabetes transferred from the Swedish paediatric diabetes quality registry to the Swedish National Diabetes Register (NDR), until 2014. All HbA1c values ever registered in the paediatric registry were used to divide patients into six groups based on the mean HbA1c. Values were compared with HbA1c registered in 2013 and 2014 in NDR, together with data on retinopathy, micro‐ and macroalbuminuria, age at onset and duration of diabetes.

Results

The group with lowest mean‐HbA1c during childhood had also the lowest mean as young adults during 2013 and 2014. The most common complication as young adults was retinopathy. The proportion with macroalbuminuria was 3% in the lowest HbA1c group during childhood and 3.9% in the highest group, and lower in the groups in between. Microalbuminuria had the same pattern. Retinopathy increased with each HbA1c group.

Conclusion

Children with the lowest HbA1c values had the lowest HbA1c values as adults. HbA1c was associated with retinopathy but the relationship with albuminuria was not obvious.
A shorter breastfeeding duration in late preterm infants than term infants during the first year
Authors: Jonsdottir Rakel B. , Jonsdottir Helga , Orlygsdottir Brynja , Flacking Renée
Published: September 2020

Aim

Little attention has been paid to breastfeeding late preterm (LPT) infants. This study compared breastfeeding, worries, depression and stress in mothers of LPT and term‐born infants throughout the first year. We also described factors associated with shorter breastfeeding duration of LPT infants.

Methods

This longitudinal cohort study of the mothers of singleton infants—129 born LPT and 277 born at term—was conducted at Landspitali—The National University Hospital of Iceland, which has the country's only neonatal intensive care unit. The mothers answered questionnaires when their infants were 1, 4, 8 and 12 months of age.

Results

Mothers breastfed LPT infants for a significantly shorter time than term infants: a median of 7 months (95% confidence interval 5.53‐8.48) vs 9 months (95% confidence interval 8.39‐9.61) (P < .05). Starting solids at up to 4 months was the strongest risk factor for LPT breastfeeding cessation during the first year, after adjusting for confounders (P < .001). Their mothers reported more worries about their infants’ health and behaviour during the first year and were more likely to experience depression at 4 months.

Conclusion

Mothers with LPT infants are vulnerable and need greater practical breastfeeding and emotional support in hospital and at home.
PIXE, ED‐XRF and optical analysis to authenticate the Garvăn gold monetary treasury
Authors: Mirea D. A. , Ciulavu F. , Ilie M. V. , Iancu D. A.
Published: September 2020

Nowadays the forgery of cultural heritage is on the rise, damaging the patrimony and its cultural value. Objects of value may still be unveiled at various construction sites or by other digging actions. Such objects will always raise questions about their authenticity because they were not unveiled by experts. Such findings will need to be analysed in order to establish their authenticity. The present study is aimed at establishing the authenticity of a small monetary treasury unveiled by archaeological looting in Garvăn, Tulcea, Romania. The treasury was later confiscated from the looters by the Romanian authorities, and in order to eliminate questions about the pieces’ authenticity, studies involving characteristic X‐ray emissions and optical microscopy were applied in order to obtain data concerning the treasury's authenticity.
Analytical Study of the Suspected Wushi Powder Excavated from the Southern Dynasty Tombs in Xiangyang, Hubei, China
Authors: Qin Y. , Zhang Y. , Yuan M. Y. , Liu J. S. , Li H. M.
Published: September 2020

Wushi Powder initially was used as medicine for typhoid fever in ancient China. In the Wei, Jin and Northern and Southern dynasties, Wushi Powder became fashionable among the upper classes. However, because of the limitation of documentary evidence, it is difficult to find the true identity of Wushi Powder. Little archaeological evidence has been discovered to date, and no scientific analysis have been performed for Wushi Powder. This paper focuses on the suspected items of Wushi Powder from the Xiangyang Institute of Cultural Relics and Archaeology. X‐ray diffraction (XRD), X‐ray fluorescence (XRF), polarized optical microscopy, Raman spectroscopy and atomic fluorescence spectrophotometry (AFS) were employed to characterize the compositions. The results show that the granular suspected items consist of quartz (SiO2), magnesium calcite [(Mg0.03Ca0.97)CO3], muscovite [KAl (Si3AlO10)(OH,F)2], alum [KAl (SO4)2(OH)6], sulfur (S8), chlorite or clinochlore [(MgAl)6(Si,Al)4O10(OH)8], kaolinite [Al2Si2O5(OH)4] and albite (NaAlSi3O8). According to the mineral paragenetic relationship and modern knowledge of mineral medicine, the granules contain quartz, alum, kaolinite, sulfur, stalactite and lapis chloriti. They are probably the famous Wushi Powder from history. These findings provide further new clues for the study of Chinese medical history.
A pilot study of4CYTE™ Epiitalis® Forte, a novel nutraceutical, in the management of naturally occurring osteoarthritis in dogs
Authors: Beths T , Munn R , Bauquier SH , Mitchell P , Whittem T
Published: September 2020

The primary goal of this pilot study was to assess, the efficacy of a new nutraceutical, 4CYTE™ Epiitalis® Forte, containing, as a standalone, a proprietary plant oil extract, Epiitalis, in dogs presenting with signs of osteoarthritis (OA). Fifty dogs aged 9.2 (±3.2) years with signs of naturally occurring OA were included in this report. They were free of other comorbidities and were not on any medications except for those utilised for managing their OA. In these dogs, the current treatments were continued to avoid any sudden changes in their disease management. The effects of the 4CYTE Epiitalis Forte were assessed both at the beginning and at the end of a 1 month‐long treatment period. The evaluation consisted of an objective lameness assessment (TPI%[total pressure index]) using a gait analysis (GAITRite® Portable Walkway System) and a subjective quality‐of‐life questionnaire, the Helsinki Chronic Pain Index (HCPI). Additional exploratory objective measurements included the Symmetry Index (SI) and the fore/hind limb ratio (T/P TPI%). Of dogs, 74% (34/46) registered a numerical improvement in TPI% in their worse limb. In addition, of the 93.5% of the dogs that demonstrated improvement in their HCPI scores by at least 5% on the quality‐of‐life questionnaire, 79% demonstrated improvements in gait based on TPI%. Finally, there were improvements measured in both exploratory objective endpoints SI and T/P TPI%. These encouraging results will be used to develop a protocol for a follow‐up placebo‐controlled randomised study to confirm the efficacy of this new nutraceutical for dogs suffering from OA.
Buffel grass (Cenchrus ciliaris) eradication in arid central Australia enhances native plant diversity and increases seed resources for granivores
Authors: Wright Boyd R. , Latz Peter K. , Albrecht David E. , Fensham Roderick J.
Published: September 2020

Questions

Buffel grass (Cenchrus ciliaris L.) is a drought‐adapted invasive plant that has become a serious environmental weed in many arid and semi‐arid systems. This paper examined whether eradication of buffel grass infestations: (i) increases frequency, richness and diversity of native vegetation and seed bank pools; and (ii) improves availability of seed resources for granivores.

Location

Alluvial ironwood/corkwood woodlands in arid central Australia.

Methods

We assessed differences in floristic and seed bank composition between buffel‐infested sites and sites where buffel grass had been eradicated ca. 12 years previously. Plant species frequency data from nested‐quadrat sampling were amalgamated into plant functional groups to examine their relationship to buffel treatment. A seed flotation method was employed to: (i) assess seed bank composition of functional groups at eradicated vs. infested sites; and (ii) test whether the mass of seeds available for granivores was higher at buffel‐free sites.

Results

Buffel‐eradicated sites supported richer and more diverse vegetation and seed banks across all functional groups except perennial grasses. The effect was strongest for perennial forbs, annual/short‐lived forbs, and annual/short‐lived grasses. The overall mass of seeds of non‐buffel grass species was ca. 10‐fold higher at buffel‐removed sites. Numbers of seeds of species in the 0.001–0.009 9 g and 0.000 1–0.000 99 g size classes, both of which contain species with seeds consumed by granivores, were ca. 20‐ and 14‐fold higher respectively at buffel‐removed sites.

Conclusions

Buffel grass removal at localised scales provides islands of habitat with improved opportunities for native plant re‐establishment and abundant foraging resources for granivores. Future research must disentangle the relative importance of dispersal vs. residual seed banks for community restoration after buffel grass invasion. Extended delays in eradication could allow seed bank reserves to deteriorate to a state that no longer permits regeneration.
Risk of congenital malformations in offspring of women using β‐blockers during early pregnancy: An updated meta‐analysis of observational studies
Authors: Wu Yin , Yao Jiang‐wei , Xu Li‐jie , Chen Miao , Wan Long
Published: September 2020

Aims

Beta‐blockers are commonly used to treat hypertension that arises during pregnancy. However, reproductive safety concerns have been expressed. Here, we investigated whether the use of β‐blockers during early pregnancy increased the risk of congenital malformations.

Methods

A systematic literature search was performed in PubMed, Embase and Cochrane Library to identify relevant studies published from database inception until February 2020. Observational studies evaluating associations between maternal β‐blocker use and congenital malformations were included in this meta‐analysis. Two reviewers independently extracted data and assessed study quality. Meta‐analysis of outcomes was performed and a summary odds ratio (OR) was calculated with consideration of heterogeneity.

Results

Twenty observational studies were identified. Beta‐blocker use during early pregnancy was not associated with an increased risk of congenital malformations (OR = 1.01, 95% confidence interval [CI] = 0.93–1.09). Subgroup analysis of organ‐specific malformations revealed that β‐blocker use was associated with an increased risk of heart malformations (OR = 1.29, 95% CI = 1.02–1.63) and an increased risk of cleft lip or palate (OR = 1.5, 95% CI = 1.18–1.91); however, these associations (OR = 1.11, 95% CI = 0.94–1.32 for heart malformations; OR = 1.34, 95% CI = 0.98–1.85 for cleft lip or palate) disappeared when the adjusted data were pooled. Beta‐blocker use was not associated with increased risks of central nervous system malformations, neural tube defects or hypospadias.

Conclusion

Exposure to β‐blockers during early pregnancy does not appear to be associated with congenital malformations or heart malformations in offspring. Other organ‐specific congenital malformations should be evaluated in further studies.
New horizons of DNA adductome for exploring environmental causes of cancer
Authors: Totsuka Yukari , Watanabe Masatoshi , Lin Yingsong
Published: September 2020

Chemical carcinogenesis is focused on the formation of DNA adducts, a form of DNA damage caused by covalent binding of a chemical moiety to DNA. The detection of carcinogen‐DNA adducts in human tissues, along with demonstration of mutagenicity/carcinogenicity in experimental systems, and validation of adducts as biomarkers of environmental exposure and indicators of cancer risk in molecular epidemiological studies suggests a pivotal role of DNA adducts in cancer development. However, accurate measurement of DNA adducts in varied biological samples is challenging. Advances in mass spectrometry have prompted the development of DNA adductome analysis, an emerging method that simultaneously screens for multiple DNA adducts and provides relevant structural information. In this review, we summarize the basic principle and applications of DNA adductome analysis that would contribute to the elucidation of the environmental causes of cancer. Based on parallel developments in several fields, including next‐generation sequencing, we describe a new approach used to explore cancer etiology, which integrates analyses of DNA adductome data and mutational signatures derived from whole‐genome/exome sequencing.
Predictive value of the Ages and Stages Questionnaire® for school performance and school intervention in late preterm‐ and term‐born children
Authors: Martínez‐Nadal Sílvia , Schonhaut Luisa , Armijo Iván , Demestre Xavier
Published: September 2020

Background

The new health supervision guidelines emphasize the importance of surveillance or a formal developmental screening test at 4 years, one of the most used tests is Ages & Stages Questionnaire. Nevertheless, there is still not enough evidence whether these tools will be useful to predict future school performance (SP).

Objectives

The objectives of this study were to evaluate the Ages & Stages Questionnaire 3rd edition 48‐month interval (ASQ3‐48) translated to Spanish for predicting the need for school intervention (SI) and poor SP at 8–9 years of age, in late preterm infants (LPIs) and term‐born infants (Terms) and to compare the prevalence of SI and poor SP in the two groups.

Methods

Data were collected from a cohort of 75 LPIs and 58 Terms assessed with ASQ3‐48 and with a further assessment of academic results at 8–9 years, through a standardized school test of the Education Department of Catalonia. SI data were obtained through a parent report. Area under the curve (AUC), sensitivity, specificity and predictive values were calculated, and logistic regression analysis was used.

Results

The prevalence of poor SP was 12.8%, without statistically significant differences between LPIs and Terms. LPIs had higher SI than Terms (29.3% vs. 10.3%, P = 0.001). AUC for poor SP was 0.73 and for receiving SI was 0.56 without differences between the two groups. The sensitivity of the ASQ3‐48 for poor SP was 41%, for specificity 92%, and for receiving SI 14% and 89%, respectively. Poor SP was related to having positive screening in the ASQ3‐48 (OR 6.5 [95% CI, 1.9–22.2]) while having received SI was related to late prematurity (OR 3.6 [95% CI, 1.3–9.6]).

Conclusions

The ASQ3‐48 shows acceptable predictive properties for poor SP but not for receiving SI. No differences were found in SP between LPI and Term cohorts, but LPIs are likelier to require SI.
Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage
Authors: Amor S , Fernández Blanco L , Baker D
Published: September 2020

Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses, SARS-CoV-2 has evolved strategies to circumvent innate immune detection, including low cytosine–phosphate–guanosine (CpG) levels in the genome, glycosylation to shield essential elements including the receptor-binding domain, RNA shielding and generation of viral proteins that actively impede anti-viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion, SARS-CoV-2 infection activates innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or, alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin–angiotensin system due to down-regulation of angiotensin-converting enzyme 2, the receptor for SARS-CoV-2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system, but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS-CoV-2 infection, much of which is based on the knowledge from SARS-CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID-19 may help to explain factors that contribute to the variety of clinical manifestations and outcome of SARS-CoV-2 infection.
Islet autoantibody profiles associated with higher diabetes risk in Lithuanian compared with English schoolchildren
Authors: Long A E , Caygill C H , Gillespie K M , Marčiulionytė D , Williams A J K
Published: September 2020

During a 15-year period, the incidence of type 1 diabetes has doubled in Lithuania, while increasing by a third in England; however, England still has a higher incidence. Analysis of sera collected from non-diabetic schoolchildren from Lithuania and England more than 20 years ago showed a similar number of multiple autoantibody-positive schoolchildren between the populations, but a higher prevalence of islet antigen-2 autoantibodies (IA-2A) in English schoolchildren. We aimed to use recently developed, more specific islet autoantibody tests to characterize differences in humoral autoimmunity between these two general population cohorts in greater detail. Samples from 88 Lithuanian and 133 English schoolchildren previously found islet autoantibody-positive were selected for measurement of additional islet autoantibodies by radioimmunoassay. Samples were tested for autoantibodies to zinc transporter 8 (ZnT8A), GAD (96–585), the protein tyrosine phosphatase region of islet antigen-2 (PTPA) and the related IA-2βA, while autoantibodies to IA-2A were reassayed using the current harmonized method. IA-2-related autoantibodies PTPA (0·13 versus 0·45%, P = 0·027) and IA-2βA (0 versus 0·35%, P < 0·001), but not IA-2A measured using the harmonized method, were less common in Lithuanian compared to English schoolchildren. Lithuanian schoolchildren who were islet autoantibody-positive were positive for fewer biochemical autoantibodies compared with English schoolchildren (P = 0·043). Background rates of islet autoimmunity in childhood differ subtly between countries, which have different incidences of type 1 diabetes. The optimal screening strategy (age and combination of markers) for detection of islet autoimmunity may vary between countries, dependent upon the pattern of autoantibodies found in the general population.
Risk stratification of adrenal masses by [18F]FDG PET/CT: Changing tactics
Authors: Salgues Betty , Guerin Carole , Amodru Vincent , Pattou François , Brunaud Laurent , Lifante Jean‐Christophe , Mirallié Eric , Sahakian Nicolas , Castinetti Frédéric , Loundou Anderson , Baumstarck Karine , Sebag Fréderic , Taïeb David
Published: September 2020

Context

[18F]FDG PET/CT improves adrenal tumour characterization. However, there is still no consensus regarding the optimal imaging biomarkers of malignancy.

Objectives

To assess the performance of Tumour standardized uptake value (SUV)max:Liver SUVmax for malignancy‐risk and to build and evaluate a prediction model.

Design/Methods

The cohort consisted of consecutive patients with adrenal masses evaluated by [18F]FDG PET/CT. The gold standard for malignancy was based on histology or a multidisciplinary consensus in nonoperated cases. The performance of the previously reported cut‐off for Tumour SUVmax:Liver SUVmax (>1.5) was evaluated in this independent cohort. Additionally, a predictive model of malignancy was built from the training cohort (previous study) and evaluated in the validation cohort (current study).

Results

Sixty‐four patients were evaluated; 28% of them had a Cushing's syndrome. Fifty‐four adrenal masses were classified as benign and 10 as malignant (including 7 adrenocortical carcinomas). Compared to benign masses, malignant lesions were larger in size, had higher unenhanced densities and higher [18F]FDG uptake. CT‐derived anthropometric parameters did not differ between benign and malignant masses. A tumour SUVmax:Liver SUVmax > 1.5 showed a good diagnostic performance: Se = 90.0%/Sp = 92.6%/PPV = 69.2%/NPV = 98.0% and accuracy = 92.2%. A predictive model based on tumour size and tumour‐to‐liver uptake SUVmax ratio for malignancy‐risk was validated and provides a complementary approach to the ratio.

Conclusions

Tumour SUVmax:Liver SUVmax uptake ratio is a useful biomarker for diagnosis of adrenal masses. Another tactic would be to calculate with the model an individual risk of malignancy and integrate this information into a shared decision‐making process.
Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH‐producing adenomas
Authors: Gil Joan , Marques‐Pamies Montserrat , Jordà Mireia , Fajardo‐Montañana Carmen , García‐Martínez Araceli , Sampedro Miguel , Serra Guillermo , Salinas Isabel , Blanco Alberto , Valassi Elena , Sesmilo Gemma , Carrato Cristina , Cámara Rosa , Lamas Cristina , Casano‐Sancho Paula , Alvarez Clara V. , Bernabéu Ignacio , Webb Susan M. , Picó Antonio , Marazuela Mónica , Puig‐Domingo Manel ,   on behalf REMAH investigators
Published: September 2020

Objective

Large somatotrophic adenomas depict poor response to somatostatin receptor ligands (SRLs). Debulking has shown to enhance SRLs effect in some but not all cases and tumour volume reduction has been proposed as the main predictor of response. No biological studies have been performed so far in this matter. We aimed to identify molecular markers of response to SRLs after surgical debulking in GH‐secreting adenomas.

Design

We performed a multicenter retrospective study.

Patients

24 patients bearing large GH‐producing tumours.

Measurements

Clinical data and SRLs response both before and after surgical debulking were collected, and 21 molecular biomarkers of SRLs response were studied in tumour samples by gene expression.

Results

From the 21 molecular markers studied, only two of them predicted enhanced SRLs response after surgery. Tumours with improved response to SRLs after surgical debulking showed lower levels of Ki‐67 (MKI67, FC = 0.17 and P = .008) and higher levels of RAR‐related orphan receptor C (RORC) (FC = 3.1 and P ˂ .001). When a cut‐off of no detectable expression was used for Ki‐67, the model provided a sensitivity of 100% and a specificity of 52.6% with an area under the curve of 65.8%. Using a cut‐off of 2 units of relative expression of RORC, the prediction model showed 100% of sensitivity and specificity.

Conclusions

High levels of RORC and low levels of Ki‐67 identify improved SRLs response after surgical debulking in large somatotropic adenomas. To determine their expression would facilitate medical treatment decision‐making after surgery.
Patient satisfaction and quality of life in hypothyroidism: An online survey by the british thyroid foundation
Authors: Mitchell Anna L. , Hegedüs Laszlo , Žarković Miloš , Hickey Janis L. , Perros Petros
Published: September 2020

Objective

Dissatisfaction with treatment and impaired quality of life (QOL) are reported among people with treated hypothyroidism. We aimed to gain insight into this.

Design and patients

We conducted an online survey of individuals with self‐reported hypothyroidism.

Results

Nine hundred sixty‐nine responses were analysed. Dissatisfaction with treatment was common (77.6%), and overall QOL scores were low. Patient satisfaction did not correlate with type of thyroid hormone treatment, but treatment with combination levothyroxine (L‐T4) and liothyronine (L‐T3) or with desiccated thyroid extract (DTE) was associated with significantly better reported QOL than L‐T4 or L‐T3 monotherapies (P < .001); however, multivariate analysis inclusive of other clinical parameters failed to confirm an association between type of thyroid hormone treatment and QOL or satisfaction. Multivariate analysis showed positive correlations between satisfaction and age (P = .026), male gender (P = .011), being under the care of a thyroid specialist (P < .001), family doctor (GP) prescribing DTE or L‐T4 + L‐T3 or L‐T3 (P < .001) and being well informed about hypothyroidism (P < .001); negative correlations were observed between satisfaction and negative experiences with L‐T4 (P < .001) and expectations for more support from the GP (P < .001), for L‐T4 to resolve all symptoms (P = .004), and to be referred to a thyroid specialist (P < .001). For QOL, positive correlations were with male gender (P = .011) and duration of hypothyroidism (P = .002); negative correlations were with age (P = .027), visiting the GP more than 3 times before diagnosis (P < .001), sourcing DTE or L‐T3 independently (P = .014), negative experiences with L‐T4 (P = .013), having expectations for L‐T4 to resolve all symptoms (P < .001) and of more support from the GP (P = .006).

Conclusions

Multiple parameters including prior healthcare experiences and expectations influence satisfaction with hypothyroidism treatment and QOL. Focusing on enhancing the patient experience and clarifying expectations at diagnosis may improve satisfaction and QOL.
Sociodemographic, lifestyle and medical influences on serum testosterone and sex hormone–binding globulin in men from UK Biobank
Authors: Yeap Bu B. , Marriott Ross J. , Antonio Leen , Bhasin Shalender , Dobs Adrian S. , Dwivedi Girish , Flicker Leon , Matsumoto Alvin M. , Ohlsson Claes , Orwoll Eric S. , Raj Suchitra , Reid Christopher M. , Vanderschueren Dirk , Wittert Gary A. , Wu Frederick C. W. , Murray Kevin
Published: September 2020

Objective

Serum testosterone concentrations are affected by factors unrelated to hypothalamo‐pituitary‐testicular axis pathology. We evaluated the impact of sociodemographic, lifestyle and medical factors, on serum testosterone and sex hormone–binding globulin (SHBG) in men aged 40‐69 years.

Design

Cross‐sectional analysis of 208,677 community‐dwelling men from the UK Biobank.

Measurements

We analysed associations of different factors with serum testosterone and SHBG (immunoassays) and calculated free testosterone (cFT), using smoothed centile plots, linear mixed models and effect size estimates.

Results

Median (interquartile range) for serum testosterone was 11.6 (9.4‐14.1) nmol/L, SHBG 36.9 (27.9‐48.1) nmol/L and cFT 213 (178‐255) pmol/L. Age and BMI were inversely associated with testosterone and cFT, while SHBG was associated with age and inversely with BMI (all P < .001). Living with a partner, (South) Asian ethnicity, never or previous smoker and some medical conditions were associated with lower testosterone. Poultry or fish eater, and higher physical activity were associated with higher testosterone (all P < .001). Testosterone was lowered by ~0.5 nmol/L across ages, ~1.5 nmol/L for BMI 30 vs 25 kg/m2, ~2 nmol/L for (South) Asian ethnicity, living with partner, college/university qualifications, low red meat eater, insufficient physical activity and 0.3‐1.0 nmol/L with cardiovascular disease or diabetes. Different combinations of these factors varied serum testosterone by ~4 nmol/L, SHBG by ~30 nmol/L and cFT by ~60 pmol/L.

Conclusions

The identified modifiable risk factors support lifestyle‐based interventions in men with low testosterone concentrations. Considering sociodemographic, lifestyle and medical factors facilitates more personalized interpretation of testosterone testing results with respect to existing reference ranges.
Iatrogenic hypoglycaemia following glucose‐insulin infusions for the treatment of hyperkalaemia
Authors: Tee Su Ann , Devine Kerri , Potts Adam , Javaid Usman , Razvi Salman , Quinton Richard , Roberts Graham , Leech Nicola J.
Published: September 2020

Objectives

To study the incidence of, and risk factors for, iatrogenic hypoglycaemia following GwI infusion in our institution.

Context

Hyperkalaemia is a life‐threatening biochemical abnormality. Glucose‐with‐insulin (GwI) infusions form standard management, but risk iatrogenic hypoglycaemia (glucose ≤ 3.9 mmol/L). Recently updated UK guidelines include an additional glucose infusion in patients with pretreatment capillary blood glucose (CBG) < 7.0 mmol/L.

Design

Retrospective analysis of outcomes for GwI infusions prescribed for hyperkalaemia from 1 January to 28 February 2019, extracted from the Newcastle upon Tyne Hospitals NHS Foundation Trust electronic platform (eRecord).

Participants

132 patients received 228 GwI infusions for hyperkalaemia.

Main outcome measures

Incidence, severity and time to onset of hypoglycaemia.

Results

Hypoglycaemia incidence was 11.8%. At least 1 hypoglycaemic episode occurred in 18.2% of patients with 6.8% having at least 1 episode of severe hypoglycaemia (< 3.0 mmol/L). Most episodes (77.8%) occurred within 3 h of treatment. Lower pretreatment CBG (5.9 mmol/L [4.1 mmol/L‐11.2 mmol/L], versus 7.6 mmol/L [3.7 mmol/L‐31.3 mmol/L], P = .000) was associated with hypoglycaemia risk. A diagnosis of type 2 diabetes and treatment for hyperkalaemia within the previous 24 h were negatively associated.

Conclusions

Within our inpatient population, around 1 in 8 GwI infusions delivered as treatment for hyperkalaemia resulted in iatrogenic hypoglycaemia. Higher pretreatment CBG and a diagnosis of type 2 diabetes were protective, irrespective of renal function. Our findings support the immediate change to current management, either with additional glucose infusions or by using glucose‐only infusions in patients without diabetes. These approaches should be compared via a prospective randomized study.