bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of major bleeding among users of direct oral anticoagulants combined with interacting drugs: A population‐based nested case–control study
Authors: Zhang Yumao , Souverein Patrick C. , Gardarsdottir Helga , van den Ham Hendrika A. , Maitland‐van der Zee Anke‐Hilse , de Boer Anthonius
Published: February 2020

Aims

To assess the association between concurrent use of potential pharmacokinetic or pharmacodynamic interacting drugs and major bleeding among direct oral anticoagulant (DOAC) users.

Methods

We performed a case–control study nested in a cohort of new users of DOACs (dabigatran etexilate, apixaban or rivaroxaban). Data were obtained from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics (2008–2015). Cases were patients hospitalized having a primary diagnosis of major bleeding. Up to 4 controls were matched on age, sex, index date and region. Odds ratios (ORs) for the risk of major bleeding were assessed by conditional logistic regression analysis and adjusted for well‐known covariates for the risk of bleeding.

Results

We identified 393 patients with a major bleeding from a total of 23 492 new users of DOACs and 1494 matched controls. Most subjects were users of rivaroxaban (58.8%) on the index date. The concurrent use of pharmacodynamic interacting drugs was associated with an increased risk of major bleeding (21.6% of cases vs 13.5% of controls, adjusted odds ratio [aOR] 1.92; 95% confidence interval [CI], 1.40–2.66). For the antiplatelet drugs the aOR was 2.01 (95% CI, 1.29–3.11) and for the selective serotonin reuptake inhibitors the aOR was 1.68 (95% CI, 1.10–2.59). We found no increased risk of major bleeding for concurrent use of pharmacokinetic interacting drugs vs DOACs alone (45.0 vs 51.2%; aOR: 0.77; 95% CI: 0.53–1.10).

Conclusion

Among patients taking DOACs the concurrent use of antiplatelet drugs or selective serotonin reuptake inhibitors was associated with increased risk of major bleeding, while pharmacokinetic interacting drugs do not increase this risk.
Allogeneic stem cell transplantation in AML with t(6;9)(p23;q34);DEK‐NUP214 shows a favourable outcome when performed in first complete remission
Authors: Díaz‐Beyá Marina , Labopin Myriam , Maertens Johan , Alijurf Mahmoud , Passweg Jakob , Dietrich Beelen , Schouten Harry , Socié Gerard , Schaap Nicolaas , Schwerdtfeger Rainer , Volin Liisa , Michallet Mauricette , Polge Emmanuelle , Sierra Jorge , Mohty Mohamad , Esteve Jordi , Nagler Arnon ,   the Acute Leukaemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Published: February 2020

Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a poor‐risk entity, commonly associated with FLT3‐ITD (internal tandem duplication). Allogeneic stem‐cell tranplantation (allo‐SCT) is recommended, although studies analysing the outcome of allo‐SCT in this setting are lacking. We selected 195 patients with t(6;9) AML, who received a first allo‐SCT between 2000 and 2016 from the EBMT (European Society for Blood and Marrow Transplantation) registry. Disease status at time of allo‐SCT was the strongest independent prognostic factor, with a two‐year leukaemia‐free survival and relapse incidence of 57% and 19% in patients in CR1 (first complete remission), 34% and 33% in CR2 (second complete remission), and 24% and 49% in patients not in remission, respectively (P < 0·001). This study, which represents the largest one available in t(6;9) AML, supports the recommendation to submit these patients to allo‐SCT in CR1.
Critical analysis of a multicentric experience with holmium laser enucleation of the prostate for benign prostatic hyperplasia: outcomes and complications of 10 years of routine clinical practice
Authors: Romero‐Otero Javier , García‐Gómez Borja , García‐González Lucía , García‐Rojo Esther , Abad‐López Pablo , Justo‐Quintas Juan , Duarte‐Ojeda José , Rodríguez‐Antolín Alfredo
Published: February 2020

Objective

To assess the perioperative outcomes of holmium laser enucleation of the prostate (HoLEP) in real‐life practice and investigate the factors influencing the safety and effectiveness of the technique.

Patients and Methods

Critical analysis of patients with benign prostate hyperplasia (BPH) treated with HoLEP over 10 years of routine practice in three hospitals. Analysed variables included: preoperative characteristics (prostate size, active antiplatelet/anticoagulant therapy, blood parameters. prostate‐specific antigen (PSA) level, maximum urinary flow rate [Qmax], and International Prostate Symptom Score [IPSS]), intraoperative variables (operation time, concomitant removal of bladder calculi, and complications), early postoperative outcomes (change in blood parameters, catheterisation time, and hospital stay), and 12‐month follow‐up outcomes (change in IPSS, PSA level, and Qmax).

Results

The analysis included 963 patients, aged 48–91 years, with a mean (range) prostate size of 91 (35–247) mL. The mean (sd) operation time was 77 (29) min, and the hospital stay and catheterisation time were 4 (2) and 1.3 (2) days, respectively. In all, 56 patients (5.6%) required concomitant removal of bladder calculi and 36 (3.7%) were converted to open prostatectomy or transurethral resection of the prostate due to intraoperative complications. Patients had a significant decrease in haemoglobin and haematocrit, but no differences were seen between patients with and without anticoagulant/antiplatelet therapy and those with prostates ≥ and <100 mL. The concomitant removal of bladder calculi and having a prostate ≥100 mL resulted in a longer operation time, but did not influence the safety and effectiveness outcomes.

Conclusions

HoLEP is suitable for real‐life patients with BPH, irrespective of the presence of active treatment with anticoagulant/antiplatelet, bladder lithiasis or a prostate ≥100 mL.
Proteolysis‐targeting chimeras in drug development: A safety perspective
Authors: Moreau Kevin , Coen Muireann , Zhang Andrew X. , Pachl Fiona , Castaldi M. Paola , Dahl Goran , Boyd Helen , Scott Clay , Newham Pete
Published: February 2020

Proteolysis‐targeting chimeras are a new drug modality that exploits the endogenous ubiquitin proteasome system to degrade a protein of interest for therapeutic benefit. As the first‐generation of proteolysis‐targeting chimeras have now entered clinical trials for oncology indications, it is timely to consider the theoretical safety risks inherent with this modality which include off‐target degradation, intracellular accumulation of natural substrates for the E3 ligases used in the ubiquitin proteasome system, proteasome saturation by ubiquitinated proteins, and liabilities associated with the “hook effect” of proteolysis‐targeting chimeras This review describes in vitro and non‐clinical in vivo data that provide mechanistic insight of these safety risks and approaches being used to mitigate these risks in the next generation of proteolysis‐targeting chimera molecules to extend therapeutic applications beyond life‐threatening diseases.
Comparing the Social Attitudes of Young Adult Evangelicals in Canada and the United States: Differences in Subcultural Boundaries among Evangelical School Graduates
Authors: Reimer Sam , Sikkink David
Published: February 2020

In this study, we examine social trust and the social attitudes of young adult evangelicals in the United States and Canada to better understand how national context shapes these attitudes. While some differences are predictable in light of national cultural differences, other differences between Canadian evangelical school graduates and American evangelical school graduates do not mirror national differences in the larger population of public school graduates. Here we suggest that differences are better understood by the ways evangelicals draw selectively from their cultural (and religious subcultural) repertoires to create unique boundaries. In general, we find lower levels of social trust and more restrictive subcultural boundaries in the United States.
SANTAMARINE: Mechanistic studies on multiple diseases
Authors: Jalal Sajid , Ahmad Bashir , Zhang Ting , Guo Lianying , Huang Lin
Published: February 2020

Medicinal plants are vital sources of modern and traditional Chinese medicines. Sesquiterpene lactones (SLs) consist of a large group of plant secondary metabolites and belong to C15 terpenoid group. SLs have shown various biological activities including antitumor and anti‐inflammatory activities. Santamarine (STM), C15H20O3, is a kind of sesquiterpene lactone, whose molecular weight is 248.322 g/mol. Santamarine has been isolated from several plants species and has shown eminent biological activities, such as anticancer activity and anti‐inflammatory activity. In this mini‐review, we summarize the studies on the effects and the mechanisms of STM, and explore the avenues of application.
Comparative QSAR model generation using pyrazole derivatives for screening Janus kinase‐1 inhibitors
Authors: Sarithamol Suvarna , Pushpa Vadakkethil Lalithabhai , Divya Vasanthakumari , Manoj Kanthimathi Bahuleyan
Published: February 2020

Asthma is a multitargeted disease. IL‐4‐JAK‐STAT signaling pathway is a promising route for the effective control of the disease. JAK inhibition by small molecules could effectively block the IL‐4 signaling pathway. It was established that JAK1 is responsive toward IL‐4‐mediated signaling process. In the present study, three‐dimensional QSAR analyses on a set of pyrazole derivatives against JAK1 and JAK2 enzyme inhibition had been executed. Molecular docking studies were conducted with the target JAK1 using the pyrazole derivative compounds and found out potential intermolecular interactions operating among them. The binding energy of all the derivative compounds with the target JAK1 has calculated and found out their affinity toward the target system. These models have predicted the JAK1 inhibitory activity of some five JAK1 active drugs and 50 structurally similar compounds. These models can, thus, suggestively be recommended for virtual screening of JAK1‐selective candidates as a lead for immunomodulatory diseases like asthma.
Clinical and pathological characterization of FLNC‐related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese
Authors: Lee Han‐Chih Hencher , Wong Shun , Sheng Bun , Pan Nin‐Yuan Keith , Leung Ying‐Kit Frank , Lau Kwok‐Kwong Dominic , Cheng Yue Sandy , Ho Luen‐Cheung , Li Richard , Lee Chi‐Nam , Tsoi Tak‐Hong , Cheung Yuk‐Fai Nelson , Fu Yat‐Pang Michael , Kan Nim‐Chi Amanda , Chu Yim‐Pui , Au Wing‐Chi Lisa , Yeung Hon‐Ming Jonas , Li Siu‐Hung , Cheung Chi‐Fung Mark , Tong Hok‐Fung , Hung Ling‐Yin Esther , Chan Tina Yee‐Ching , Li Chi Terence , Tong Tsz‐Yan Tammy , Tong Tin‐Wing Candy , Leung Ho‐Ying Cory , Lee Ka‐Ho , Yeung Sung‐Yan Sue , Lee Sau‐Yin Blanka , Lau Tze‐Chin Gene , Lam Ching‐Wan , Mak Chloe Miu , Chan Albert Yan‐Wo
Published: February 2020

FLNC‐related myofibrillar myopathy could manifest as autosomal dominant late‐onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC‐related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Twenty‐six patients were symptomatic when diagnosed; four patients died of pneumonia and/or respiratory failure. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two‐thirds. We also show by haplotype analysis the founder effect associated with this Hong Kong variant, which might have occurred 42 to 71 generations ago or around Tang and Song dynasties, and underlain a higher incidence of myofibrillar myopathy among Hong Kong Chinese. The late‐onset nature and slowly progressive course of the highly penetrant condition could have significant impact on the family members, and an early diagnosis could benefit the whole family. Considering another neighboring founder variant in FLNC in German patients, we advocate development of specific therapies such as chaperone‐based or antisense oligonucleotide strategies for this particular type of myopathy.
Comparison of in‐situ bone ring technique and tent‐pole technique for horizontally deficient alveolar ridge in the anterior maxilla
Authors: Yuan Shuai , Mu Zhixiang , Huang Yuanding , Bai Shi , Xu Peng , Chen Tao
Published: February 2020

Background

Limited studies focused on the bone profile maintenance at the alveolar ridge crest applying horizontal bone augmentation.

Purpose

A novel approach named as “in‐situ bone ring technique” was introduced to be compared with tent‐pole technique to evaluate their horizontal bone gain, resorption, and postoperative perception.

Materials and methods

A total of 30 patients were included in this retrospective cohort study. All patients required horizontal bone augmentation at anterior site. Accordingly, quantitative and qualitative analyses were conduct radiographically and histologically between in‐situ bone ring (ring group) and tent‐pole technique (tent group). Moreover, the visual analog scale (VAS) was introduced to assess the patients' perception toward both treatments.

Results

Cone‐beam computed tomography results showed great significant difference regarding horizontal bone width at 0 mm and 3 mm from alveolar ridge crest between two groups (P < .05). On the basis of histological outcomes, delightful bony fusion was shown 6‐month postoperatively in ring group. The VAS ratings for pain and swelling reflected similar results between two groups.

Conclusions

In‐situ bone ring technique evidently increased and maintained horizontal bone mass at the alveolar ridge crest compared to tent‐pole technique, which might be favorable for implant rehabilitation in anterior area. Meanwhile, no further discomfort was caused according to VAS scoring between two groups.
Complex and nonlinear climate‐driven changes in freshwater insect communities over 42 years
Authors: Baranov Viktor , Jourdan Jonas , Pilotto Francesca , Wagner Rüdiger , Haase Peter
Published: February 2020

The ongoing biodiversity crisis becomes evident in the widely observed decline in abundance and diversity of species, profound changes in community structure, and shifts in species’ phenology. Insects are among the most affected groups, with documented decreases in abundance up to 76% in the last 25–30 years in some terrestrial ecosystems. Identifying the underlying drivers is a major obstacle as most ecosystems are affected by multiple stressors simultaneously and in situ measurements of environmental variables are often missing. In our study, we investigated a headwater stream belonging to the most common stream type in Germany located in a nature reserve with no major anthropogenic impacts except climate change. We used the most comprehensive quantitative long‐term data set on aquatic insects available, which includes weekly measurements of species‐level insect abundance, daily water temperature and stream discharge as well as measurements of additional physicochemical variables for a 42‐year period (1969–2010). Overall, water temperature increased by 1.88 °C and discharge patterns changed significantly. These changes were accompanied by an 81.6% decline in insect abundance, but an increase in richness (+8.5%), Shannon diversity (+22.7%), evenness (+22.4%), and interannual turnover (+34%). Moreover, the community's trophic structure and phenology changed: the duration of emergence increased by 15.2 days, whereas the peak of emergence moved 13.4 days earlier. Additionally, we observed short‐term fluctuations (<5 years) in almost all metrics as well as complex and nonlinear responses of the community toward climate change that would have been missed by simply using snapshot data or shorter time series. Our results indicate that climate change has already altered biotic communities severely even in protected areas, where no other interacting stressors (pollution, habitat fragmentation, etc.) are present. This is a striking example of the scientific value of comprehensive long‐term data in capturing the complex responses of communities toward climate change.
Evaluating and expanding the European Union's protected‐area network toward potential post‐2020 coverage targets
Authors: Müller Anke , Schneider Uwe A. , Jantke Kerstin
Published: February 2020

The Convention on Biological Diversity's (CBD) strategic plan will expire in 2020, but biodiversity loss is ongoing. Scientists call for more ambitious targets in the next agreement. The nature‐needs‐half movement, for example, has advocated conserving half of Earth to solve the biodiversity crisis, which has been translated to protecting 50% of each ecoregion. We evaluated current protection levels of ecoregions in the territory of one of the CBD's signatories, the European Union (EU). We also explored the possible enlargement of the Natura 2000 network to implement 30% or 50% ecoregion coverage in the EU member states’ protected area (PA) network. Based on the most recent land‐use data, we examined whether ecoregions have enough natural area left to reach such high coverage targets. We used a spatially explicit mixed integer programing model to estimate the least‐cost expansion of the PA network based on 3 scenarios that put different emphasis on total conservation cost, ecological representation of ecosystems, or emphasize an equal share of the burden among member states. To realize 30% and 50% ecoregion coverage, the EU would need to add 6.6% and 24.2%, respectively, of its terrestrial area to its PA network. For all 3 scenarios, the EU would need to designate most recommended new PAs in seminatural forests and other semi‐ or natural ecosystems. Because 15 ecoregions did not have enough natural area left to implement the ecoregion‐coverage targets, some member states would also need to establish new PAs on productive land, allocating the largest share to arable land. Thirty percent ecoregion coverage was met by protecting remaining natural areas in all ecoregions except 3, where productive land would also need to be included. Our results support discussions of higher ecoregions protection targets for post‐2020 biodiversity frameworks.
A computational algorithm based on biogeography‐based optimization method for computing power system security constrains with multi FACTS devices
Authors: Kumar M. Manoj , Alli Rani A. , Sundaravazhuthi V.
Published: February 2020

A major role is played by the analysis of power system security in heightening system security and in system collapse condition avoidance. This article presents a cutting edge mechanism which is devised applying transmission line loadings as well as variance in bus voltage magnitude. The use of flexible alternating current transmission systems devices improves the objectives of generation fuel charges in addition to the severity index proposed which were investigated considering the contingency circumstances of generator(s) or/and transmission channel(s). To boost system security in spite of contingency circumstances in the existence of unified power flow controller or UPFC, it would be most appropriate to pinpoint a most advantageous position to install aforementioned device. We propose a model of UPFC where power insertion is done by using voltage source. Also a procedure to incorporate the same and a strategy to find optimum position has been proposed which uses line overload sensitivity indices. This work mainly focused on establishment of available transfer capability on the heavily congested line. The proposed congestion management scheme alleviates the heavy stress in transmission line and provides an ample corridor for the power to flow. Biogeography‐based optimization or BBO in short, is a technique which is a growing recognized optimization method which has been lucratively engaged in solving intricate optimization problem in dissimilar fields. The BBO provides better results than the metaheuristic counter parts such as Genetic Algorithm and Particle Swarm Optimization. The effectiveness of proposed BBO has been tested on standard IEEE 30 bus system and the results are compared with classic methods and other metaheuristic methods. This is established through the MATLAB package. Improved bus voltage profile was also attained and it can be inferred from the outcome that the prospective approach can drastically enhance security of power system when comparing with other optimization methods.
Current state of whole slide imaging use in cytopathology: Pros and pitfalls
Authors: Eccher Albino , Girolami Ilaria
Published: February 2020

Whole slide imaging (WSI) allows generation of large whole slide images and their navigation with zoom in and out like a true virtual microscope. It has become widely used in surgical pathology for many purposes, such as education and training, research activity, teleconsultation, and primary diagnosis. However, in cytopathology, the use of WSI has been lagging behind histology, mainly due to the cytological specimen's characteristics, as groups of cells of different thickness are distributed throughout the slide. To allow the same focusing capability of light microscope, slides have to be scanned at multiple focal planes, at the cost of longer scan times and larger file size. These are the main technical pitfalls of WSI for cytopathology, partly overcome by solutions like liquid‐based preparations. Validation studies for the use in primary diagnosis are less numerous and more heterogeneous than in surgical pathology. WSI has been proved effective for training students and successfully used in proficiency testing, allowing the creation of digital cytology atlases. Longer scan times are also a barrier for use in rapid on‐site evaluation, but WSI retains its advantages of easy sharing of images for consultation, multiple simultaneous viewing in different locations, the possibility of unlimited annotations and easy integration with medical records. Moreover, digital slides set the laboratory free from reliance on a physical glass slide, with no more concern of fading of stain or slide breakage. Costs are still a problem for small institutions, but WSI can also represent the beginning of a more efficient way of working.
Global changes threaten functional and taxonomic diversity of insular species worldwide
Authors: Leclerc Camille , Villéger Sébastien , Marino Clara , Bellard Céline
Published: February 2020

Aim

The assessment of biodiversity patterns under global changes is currently biased towards taxonomic diversity, thus overlooking the ecological and functional aspects of species. Here, we characterized both taxonomic and functional diversity of insular biodiversity threatened by multiple threats.

Location

Worldwide islands (n = 4,348).

Methods

We analysed the relative importance of eleven major threats, including biological invasions or climate change, on 2,756 insular endemic mammals and birds. Species were functionally described using five ecological traits related to diet, habitat and body mass. We computed complementary taxonomic and functional diversity indices (richness, specialization, originality and vulnerability) of species pools affected by each threatening process to investigate relationships between diversity dimensions and threats. We also determined whether species‐specific traits are associated with specific threats.

Results

On average, 8% of insular endemic species at risk of extinction are impacted by threats, while 20% of their functional richness is affected. However, a marked disparity in functional richness values associated with each threat can be highlighted. In particular, cultivation and wildlife exploitation are the greatest threats to insular endemic species. Moreover, each threat may contribute to the loss of at least 10% of functional diversity, because it affects threatened species that support unique and extreme functions. Finally, we found complex patterns of species‐specific traits associated with particular threats that is not explain by the threatening processes (directly affecting survival or modifying habitat). For instance, cultivation threatens very large mammals, while urbanization threatens very small mammals.

Main conclusions

These findings reinforce the importance of exploring the vulnerability of biodiversity facets in the face of multiple threats. Anthropogenic pressures may result in a loss of unique functions within insular ecosystems, which provides important insights into the understanding of threatening processes at a global scale.
Systematic review and meta‐analysis of randomized controlled trials of psychological interventions to improve glycaemic control in children and adults with type 1 diabetes
Authors: Winkley K. , Upsher R. , Stahl D. , Pollard D. , Brennan A. , Heller S. , Ismail K.
Published: February 2020

Aim

We conducted a systematic review aggregate and network meta‐analysis of psychological interventions for people with type 1 diabetes to assess their effectiveness in improving glycaemic levels.

Methods

We searched the following databases from 1 January 2003 to 1 July 2018: MEDLINE, CINAHL, PsycINFO, Embase, Cochrane Controlled Trials, Web of Science, clinicaltrials.gov, Dissertation Abstract International. We included randomized controlled trials (RCT) of psychological interventions for children and adults with type 1 diabetes reported in any language. We extracted data on publications, participant characteristics at baseline, intervention and control group, and data for the primary outcome, change in glycaemic control [HbA1c (mmol/mol/%)]. Study authors were contacted for missing data. The review was registered with international prospective register of systematic reviews registration (PROSPERO) CRD42016033619.

Results

Twenty‐four adult RCTs and 23 of children with type 1 diabetes were included in the systematic review. In aggregate meta‐analysis there was no overall effect of psychological intervention compared with control on HbA1c [adults, nine RCTs, n = 1102, pooled mean difference −0.12, 95% confidence intervals (CI) −0.27 to 0.03, I2 = 29.0%, P = 0.19; children, 20 RCTs, n = 2567, −0.09, 95% CI −0.22 to 0.04, I2=54.0% P=0.002]. Network meta‐analysis suggested that probability and rank‐ordering of effectiveness is highest for attention control groups (b = −0.47, 95% CI −0.80 to −0.12) followed by cognitive behavioural therapy (CBT) (−0.26, 95% CI −0.45 to −0.06) compared with usual care for adults.

Conclusions

Overall psychological interventions for children and adults with type 1 diabetes do not improve glycaemic control. For adults, CBT‐based interventions have the potential to be effective.
Adverse drug reactions of statins in children and adolescents: a descriptive analysis from VigiBase, the WHO global database of individual case safety reports
Authors: Conte Cécile , Rousseau Vanessa , Vert Charlotte , Montastruc François , Montastruc Jean‐Louis , Durrieu Geneviève , Olivier Pascale
Published: February 2020

In adults, statins safety profile is well known. However, literature data on their adverse drug reactions (ADRs) remain scarce in children in real‐life setting. In order to better characterize ADRs related to ‘real‐life’ use of statins in children, we reviewed statin‐related ADRs recorded in the World Health Organization (WHO) global database of individual case safety reports (ICSRs), VigiBase. Methods. Individual case safety reports (ICSRs) in children (2–11 years) and adolescents (12–17 years) associated with statins from January 1, 1987, to July 18, 2017, were extracted from VigiBase. Characteristics of ICSRs, type of ADRs according to MedDRA classification (SOC and PT), and ICSR seriousness were described using SAS 9.4. A total of 311 ICSRs were identified for 8 statins with 712 ADRs. Musculoskeletal disorders (n = 85, 27.3%) were the first registered ADRs followed by general disorders (n = 67, 21.5%; mainly asthenia and pain). More than 1 out of 5 ADRs were ‘injury, poisoning and procedural complications’ (n = 67), mainly accidental or intentional exposures (n = 44, 14.1%), overdoses (n = 14, 4.5%), or off‐label use (n = 11, 3.5%). Overall, 133 (42.8%) reports were ‘serious’, including 11 deaths. Deaths mainly involved adolescents with intentional overdose and completed suicide with other associated drugs in 75% of reports. Our study identified rare but serious safety issues (rhabdomyolysis, myalgia, and hepatocellular injury). These ADRs can impact quality of life or lead to life‐threatening complications in children. Our results should be supplemented with other data sources. Spontaneous statin ADR reports in children to pharmacovigilance networks must be promoted.
Cumulative fatigue damage of stress below the fatigue limit in weldment steel under block loading
Authors: He Lei , Akebono Hiroyuki , Sugeta Atsushi , Hayashi Yoshiichirou
Published: February 2020

To investigate the cumulative fatigue damage below the fatigue limit of multipass weldment martensitic stainless steel, and to clarify the effect of cycle ratios and high‐stress level in the statement, fatigue tests were conducted under constant and combined high‐ and low‐stress amplitude relative to stress above and below the fatigue limit. The outcomes indicate that neither modified Miner's nor Haibach's approach provided accurate evaluation under repeated two‐step amplitude loading. Moreover, effect of cycle ratios has been determined. Additionally, the cumulative fatigue damage saturated model is established and validated. Cumulative fatigue damage contributed by low‐stress below the fatigue limit in high stress of 700 MPa is higher than that with 650 MPa at identical conditions (fatigue limit 575 MPa). Thus, high stress affects fatigue damage behaviour below the fatigue limit. A new predicted approach has been proposed based on Corten‐Dolan law, whose accuracy and applicability have been proven.
Intra‐annual variation of phytoplankton community responses to factorial N, P, and CO2 enrichment in a temperate mesotrophic lake
Authors: Katkov Egor , Low‐Décarie Étienne , Fussmann Gregor F.
Published: February 2020

Across primary producer communities in different lakes, nitrogen (N) and phosphorus (P) can exhibit many different patterns of limitation. Here, we look at the intra‐annual variability of these patterns in a single lake. Furthermore, we investigate whether a third resource, carbon dioxide (CO2) can have significant effects on phytoplankton biomass and community composition.

We performed five in situ lacustrine mesocosm experiments at different times of the year. In each experiment, we had a factorial design with two levels of N, P and CO2 enrichment (no enrichment or double lake concentrations for N and P and atmospheric (400 ppm) and c. 1,000 ppm for CO2) resulting in a total of eight treatments. Mesocosms of c. 1,600 L were suspended in a temperate, mesotrophic lake (Lac Hertel, Canada). Each experiment lasted 2 weeks and chlorophyll a biomass, coarse chemotaxonomic community composition (measured using fluorometry), and several environmental variables were recorded at a minimum of four time points.

We found that the limiting, synergistic, and community composition effects of N and P varied between experiments. TN:TP ratios explained, in part, some of this variability, along with insolation and water temperature.

Despite relatively high levels of CO2 in the control mesocosms, we found a constant synergistic effect of CO2 with N. In combination with the synergistic effect of P with N found in some experiments, this provides support for CO2 as one of the multiple limiting resources in nutrient‐enriched systems. This finding could have implications for eutrophic lakes exposed to increasing concentrations of CO2.

We also found that the effects of CO2 on community composition varied intra‐annually. Thus, we conclude that generalised predictions about the effect of CO2 on community composition at a coarse chemotaxonomic scale are unlikely to hold, but predictions specific to season and system are likely to be reliable.
Mapping tree species vulnerability to multiple threats as a guide to restoration and conservation of tropical dry forests
Authors: Fremout Tobias , Thomas Evert , Gaisberger Hannes , Van Meerbeek Koenraad , Muenchow Jannes , Briers Siebe , Gutierrez‐Miranda Claudia E. , Marcelo‐Peña José L. , Kindt Roeland , Atkinson Rachel , Cabrera Omar , Espinosa Carlos I. , Aguirre‐Mendoza Zhofre , Muys Bart
Published: February 2020

Understanding the vulnerability of tree species to anthropogenic threats is important for the efficient planning of restoration and conservation efforts. We quantified and compared the effects of future climate change and four current threats (fire, habitat conversion, overgrazing and overexploitation) on the 50 most common tree species of the tropical dry forests of northwestern Peru and southern Ecuador. We used an ensemble modelling approach to predict species distribution ranges, employed freely accessible spatial datasets to map threat exposures, and developed a trait‐based scoring approach to estimate species‐specific sensitivities, using differentiated trait weights in accordance with their expected importance in determining species sensitivities to specific threats. Species‐specific vulnerability maps were constructed from the product of the exposure maps and the sensitivity estimates. We found that all 50 species face considerable threats, with an average of 46% of species’ distribution ranges displaying high or very high vulnerability to at least one of the five threats. Our results suggest that current levels of habitat conversion, overexploitation and overgrazing pose larger threats to most of the studied species than climate change. We present a spatially explicit planning strategy for species‐specific restoration and conservation actions, proposing management interventions to focus on (a) in situ conservation of tree populations and seed collection for tree planting activities in areas with low vulnerability to climate change and current threats; (b) ex situ conservation or translocation of populations in areas with high climate change vulnerability; and (c) active planting or assisted regeneration in areas under high current threat vulnerability but low climate change vulnerability, provided that interventions are in place to lower threat pressure. We provide an online, user‐friendly tool to visualize both the vulnerability maps and the maps indicating priority restoration and conservation actions.
Satellite‐based estimates reveal widespread forest degradation in the Amazon
Authors: Bullock Eric L. , Woodcock Curtis E. , Souza Carlos , Olofsson Pontus
Published: February 2020

Anthropogenic and natural forest disturbance cause ecological damage and carbon emissions. Forest disturbance in the Amazon occurs in the form of deforestation (conversion of forest to non‐forest land covers), degradation from the extraction of forest resources, and destruction from natural events. The crucial role of the Amazon rainforest in the hydrologic cycle has even led to the speculation of a disturbance “tipping point” leading to a collapse of the tropical ecosystem. Here we use time series analysis of Landsat data to map deforestation, degradation, and natural disturbance in the Amazon Ecoregion from 1995 to 2017. The map was used to stratify the study area for selection of sample units that were assigned reference labels based on their land cover and disturbance history. An unbiased statistical estimator was applied to the sample of reference observations to obtain estimates of area and uncertainty at biennial time intervals. We show that degradation and natural disturbance, largely during periods of severe drought, have affected as much of the forest area in the Amazon Ecoregion as deforestation from 1995 to 2017. Consequently, an estimated 17% (1,036,800 ± 24,800 km2, 95% confidence interval) of the original forest area has been disturbed as of 2017. Our results suggest that the area of disturbed forest in the Amazon is 44%–60% more than previously realized, indicating an unaccounted for source of carbon emissions and pervasive damage to forest ecosystems.
Art, climate change and (other) eco materials: rethinking the cosmopolitanization of aesthetics and the aesthetics of cosmopolitanization with Ulrich Beck
Authors: THORSEN LINE MARIE
Published: February 2020

Based on fieldwork in Japan and Hong Kong, I ask how methodological cosmopolitanism, as formulated by Ulrich Beck, may afford new and highly needed modes for grappling with climatically concerned art and aesthetic practices across geographical regions. I will argue that methodological cosmopolitanism serves as an important framework for approaching such art practices, and suggest that two overall intertwined strands concerning aesthetic practices engaged in global issues of climate change, emerge from this – the cosmopolitanization of aesthetics and, reversely, the aesthetics of cosmopolitanization. Departing from my fieldwork among farming artists in the Hong Kong countryside and in the Japanese satoyama – rural mountain – areas, I will, on the one hand, argue that art practices are ‘cosmopolitanized’ by the awareness of global risks, manifested in anticipation of the comprehensive climatic changes (in)discriminately affecting across nations and regions. At the same time, and importantly, art practices are actively attending to this ‘risky’ cosmopolitanization, giving aesthetic voice, form and ‘visuality’ to unfolding climatic issues and concerns and hereby practising what I will call an ‘aesthetics of cosmopolitanization’.
Excavating eurypterids, giant arthropods of the Palaeozoic
Authors: Briggs Derek E.G. , Roach Brian T.
Published: February 2020

The eurypterids of the Silurian Bertie Group of North America are some of the most striking fossils known, with their dark organic cuticle outlined against a background of light coloured dolomite. Eurypterus is the most abundant genus but the pterygotids with their long grasping claws have fired our imagination as giant extinct predators. Large complete specimens are rarely found—the specimens are dominated by moulted exoskeletons that often disarticulate—but a giant that emerged from the rock more than 50 years ago is being prepared to go on display.
Headache at the Chronic Stage of Ischemic Stroke
Authors: Carvalho Dias Mariana , Martins Teresa , Basílio Gonçalo , Lucas Neto Lia , Caeiro Lara , Ferro José M. , Verdelho Ana
Published: February 2020

Background

Headache in ischemic stroke survivors after the acute stage is incompletely described.

Objective

We aimed to prospectively describe the characteristics of headache and the predictors of headache at the chronic stage after ischemic stroke.

Methods

We conducted a prospective observational cohort study including 102 acute ischemic stroke patients admitted to a Stroke Unit. Patients were interviewed at the acute and the chronic stage (12 months after stroke). Characteristics of those headaches were collected using a previously validated headache questionnaire enabling headache classification following the International Headache Society criteria. Pre‐stroke headache history was registered using the same instrument.

Results

Forty‐five patients out of 89 with completed follow‐up (51%) reported headache at the chronic stage. In most of the patients, headache was sporadic, mild, pressure‐like, with a duration of minutes to hours, with characteristics of tension‐type headache in 51% (n = 23/45). Headache was a reactivation of pre‐stroke headache in 33% (n = 15/45), different from pre‐stroke headache in 44% (n = 20/45), and of new‐onset in 22% (n = 10/45). Only 1 patient had a new‐onset headache at the acute stage that persisted with the same characteristics at the chronic stage.

Pre‐stroke headache (OR = 5.3; 95% CI [2.01‐13.98] P = .001) and female sex (OR = 3.5; 95% CI [1.3‐9.4] P = .013) predicted headache at the chronic stage after stroke, controlling for age, severity, and location of stroke.

Conclusions

Headache in ischemic stroke survivors at the chronic stage is more frequent in women and in patients with pre‐stroke headache. It is most frequently a headache with different characteristics of the pre‐stroke headache and only rarely a new‐onset headache starting at the acute stage and persisting at the chronic stage.
The earliest stage of Izu rear‐arc volcanism revealed by drilling at Site U1437, International Ocean Discovery Program Expedition 350
Authors: Sato Tomoki , Miyazaki Takashi , Tamura Yoshihiko , Gill James B. , Jutzeler Martin , Senda Ryoko , Kimura Jun‐Ichi
Published: February 2020

The International Ocean Discovery Program Expedition 350 drilled between two Izu rear‐arc seamount chains at Site U1437 and recovered the first complete succession of rear‐arc rocks. The drilling reached 1806.5 m below seafloor. In situ hyaloclastites, which had erupted before the rear‐arc seamounts came into existence at this site, were recovered in the deepest part of the hole (∼15–16 Ma). Here it is found that the composition of the oldest rocks recovered does not have rear‐arc seamount chain geochemical signatures, but instead shows affinities with volcanic front or some of the extensional zone basalts between the present volcanic front and the rear‐arc seamount chains. It is suggested that following the opening of the Shikoku back‐arc Basin, Site U1437 was a volcanic front or a rifting zone just behind the volcanic front, and was followed at ~ 9 Ma by the start of rear‐arc seamount chains volcanism. This geochemical change records variations in the subduction components with time, which might have followed eastward moving of hot fingers in the mantle wedge and deepening of the subducting slab below Site U1437 after the cessation of Shikoku back‐arc Basin opening.
A review of applicant faking in selection interviews
Authors: Melchers Klaus G. , Roulin Nicolas , Buehl Anne‐Kathrin
Published: February 2020

Interviews are commonly used for selection but research on interview faking only gained momentum relatively recently. We review both theoretical and empirical work on prevalence, antecedents, processes, and effects of interview faking. Most applicants fake at least to some degree. Personality (e.g., Conscientiousness, Honesty‐humility, the Dark Triad) and attitudes toward faking substantially correlate with faking behaviors. Research concerning applicants' ability, interview structure components, or contextual factors is limited. Furthermore, the impact of faking on interview ratings is mixed and effects on criterion‐related validity are not consistently negative. Finally, the detection of faking seems hardly possible and there are limited options available to reduce interview faking. Throughout our review, we describe important gaps and derive suggestions and propositions for future research.
Robotics for catheter ablation of cardiac arrhythmias: Current technologies and practical approaches
Authors: Bassil Guillaume , Markowitz Steven M. , Liu Christopher F. , Thomas George , Ip James E. , Lerman Bruce B. , Cheung Jim W.
Published: February 2020

Robotic technology has emerged as an important tool to facilitate catheter ablation of arrhythmias. Robotic cardiac electrophysiology technology includes remote magnetic navigation and manual robotic navigation. Robotics can confer advantages with respect to ease of catheter manipulation in anatomically challenging spaces, minimization of fluoroscopic exposure to both patients and operators, and reduction in operator fatigue. This review provides a comprehensive summary of robotic electrophysiology technology, its practical applications and its safety and efficacy for targeting cardiac arrhythmias.
IL‐22 produced by Th22 cells aggravates atherosclerosis development in ApoE−/− mice by enhancing DC‐induced Th17 cell proliferation
Authors: Shi Lei , Ji Qingwei , Liu Ling , Shi Ying , Lu Zhengde , Ye Jing , Zeng Tao , Xue Yan , Yang Zicong , Liu Yu , Lu Jianyong , Huang Xinshun , Qin Qiuwen , Li Tianzhu , Lin Ying‐zhong
Published: February 2020

Th22 cells are a novel subset of CD4+ T cells that primarily mediate biological effects through IL‐22, with both Th22 cells and IL‐22 being closely associated with multiple autoimmune and chronic inflammatory diseases. In this study, we investigated whether and how Th22 cells affect atherosclerosis. ApoE−/− mice and age‐matched C57BL/6J mice were fed a Western diet for 0, 4, 8 or 12 weeks. The results of dynamic analyses showed that Th22 cells, which secrete the majority of IL‐22 among the known CD4+ cells, play a major role in atherosclerosis. ApoE−/− mice fed a Western diet for 12 weeks and administered recombinant mouse IL‐22 (rIL‐22) developed substantially larger plaques in both the aorta and aortic root and higher levels of CD3+ T cells, CD68+ macrophages, collagen, IL‐6, Th17 cells, dendritic cells (DCs) and pSTAT3 but lower smooth muscle cell (SMC) α‐actin expression than the control mice. Treatment with a neutralizing anti–IL‐22 monoclonal antibody (IL‐22 mAb) reversed the above effects. Bone marrow‐derived DCs exhibited increased differentiation into mature DCs following rIL‐22 and ox‐LDL stimulation. IL‐17 and pSTAT3 were up‐regulated after stimulation with IL‐22 and ox‐LDL in cells cocultured with CD4+ T cells and mature DC supernatant, but this up‐regulation was significantly inhibited by IL‐6mAb or the cell‐permeable STAT3 inhibitor S31‐201. Thus, Th22 cell‐derived IL‐22 aggravates atherosclerosis development through a mechanism that is associated with IL‐6/STAT3 activation, DC‐induced Th17 cell proliferation and IL‐22–stimulated SMC dedifferentiation into a synthetic phenotype.
KRT8 phosphorylation regulates the epithelial‐mesenchymal transition in retinal pigment epithelial cells through autophagy modulation
Authors: Miao Qi , Xu Yufeng , Yin Houfa , Zhang Huina , Ye Juan
Published: February 2020

Proliferative vitreoretinopathy (PVR) is a severe ocular disease which results in complex retinal detachment and irreversible vision loss. The epithelial‐mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is considered to be critical in the pathogenesis of PVR. In this study, we focused on the potential impact of keratin 8 (KRT8) phosphorylation and autophagy on TGF‐β2–induced EMT of RPE cells and explored the relationship between them. Using immunofluorescence and Western blot analysis, the co‐localization of KRT8 and autophagy marker, as well as the abundance of phosphorylated KRT8 (p‐KRT8) expression, was observed within subretinal and epiretinal membranes from PVR patients. Moreover, during TGF‐β2–induced EMT process, we found that p‐KRT8 was enhanced in RPE cells, which accompanied by an increase in autophagic flux. Inhibition of autophagy with pharmacological inhibitors or specific siRNAs was associated with a reduction in cell migration and the synthesis of several EMT markers. In the meantime, we demonstrated that p‐KRT8 was correlated with the autophagy progression during the EMT of RPE cells. Knockdown the expression or mutagenesis of the critical phosphorylated site of KRT8 would induce autophagy impairment, through affecting the fusion of autophagosomes and lysosomes. Therefore, this study may provide a new insight into the pathogenesis of PVR and suggests the potential therapeutic value of p‐KRT8 in the prevention and treatment of PVR.