bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical utility of target capture‐based panel sequencing in hematological malignancies: A multicenter feasibility study
Authors: Yasuda Takahiko , Sanada Masashi , Nishijima Dai , Kanamori Takashi , Iijima Yuka , Hattori Hiroyoshi , Saito Akiko , Miyoshi Hiroaki , Ishikawa Yuichi , Asou Norio , Usuki Kensuke , Hirabayashi Shinsuke , Kato Motohiro , Ri Masaki , Handa Hiroshi , Ishida Tadao , Shibayama Hirohiko , Abe Masahiro , Iriyama Chisako , Karube Kennosuke , Nishikori Momoko , Ohshima Koichi , Kataoka Keisuke , Yoshida Kenichi , Shiraishi Yuichi , Goto Hiroaki , Adachi Souichi , Kobayashi Ryoji , Kiyoi Hitoshi , Miyazaki Yasushi , Ogawa Seishi , Kurahashi Hiroki , Yokoyama Hisayuki , Manabe Atsushi , Iida Shinsuke , Tomita Akihiro , Horibe Keizo
Published: July 2020

Although next‐generation sequencing‐based panel testing is well practiced in the field of cancer medicine for the identification of target molecules in solid tumors, the clinical utility and clinical issues surrounding panel testing in hematological malignancies have yet to be fully evaluated. We conducted a multicenter prospective clinical sequencing study to verify the feasibility of a panel test for hematological tumors, including acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, and diffuse large B‐cell lymphoma. Out of 96 eligible patients, 79 patients (82%) showed potentially actionable findings, based on the clinical sequencing assays. We identified that genetic alterations with a strong clinical significance were found at a higher frequency in terms of diagnosis (n = 60; 63%) and prognosis (n = 61; 64%) than in terms of therapy (n = 8; 8%). Three patients who harbored a germline mutation in either DDX41 (n = 2) or BRCA2 (n = 1) were provided with genetic counseling. At 6 mo after sequencing, clinical actions based on the diagnostic (n = 5) or prognostic (n = 3) findings were reported, but no patients were enrolled in a clinical trial or received targeted therapies based on the sequencing results. These results suggest that panel testing for hematological malignancies would be feasible given the availability of useful diagnostic and prognostic information. This study is registered with the UMIN Clinical Trial Registry (UMIN000029879, multiple myeloma; UMIN000031343, adult acute myeloid leukemia; UMIN000033144, diffuse large B‐cell lymphoma; and UMIN000034243, childhood leukemia).
Ribociclib, a CDK 4/6 inhibitor, plus endocrine therapy in Asian women with advanced breast cancer
Authors: Yap Yoon‐Sim , Chiu Joanne , Ito Yoshinori , Ishikawa Takashi , Aruga Tomoyuki , Kim Seung Jin , Toyama Tatsuya , Saeki Toshiaki , Saito Mitsue , Gounaris Ioannis , Su Fei , Ji Yan , Han Yu , Gazdoiu Mihaela , Masuda Norikazu
Published: July 2020

The ongoing, Phase Ib MONALEESASIA study is evaluating the efficacy and safety of ribociclib plus endocrine therapy in Asian patients with hormone receptor‐positive, human epidermal growth factor receptor 2‐negative advanced breast cancer. Eligible patients from Japan, Hong Kong, and Singapore were enrolled in this 2‐phase study consisting of a dose‐escalation phase to determine the maximum‐tolerated dose and the recommended Phase II dose of ribociclib plus letrozole, and a dose‐expansion phase to evaluate safety and tolerability of ribociclib plus letrozole, fulvestrant, or tamoxifen. An exploratory biomarker analysis evaluating expression of target genes was also conducted. In the dose‐escalation phase, the maximum‐tolerated/recommended Phase II doses of ribociclib were lower in Japanese patients (300 mg) than in Asian non‐Japanese patients (600 mg). Ribociclib plus endocrine therapy at the recommended Phase II dose had a manageable safety profile, with neutropenia and elevated liver transaminases being the most common adverse events leading to dose modifications or discontinuations, and it demonstrated evidence of clinical activity in both Japanese and Asian non‐Japanese patients. Preliminary efficacy in Asian populations is similar to that observed in White populations studied in previous ribociclib (MONALEESA) trials. Biomarker analysis demonstrated suppression of pharmacodynamic biomarker gene expression, indicating inhibition of target genes by ribociclib combined with endocrine therapy. Results from the ongoing study support the use of ribociclib in combination with letrozole in Asian non‐Japanese patients at the same dose (600 mg) as White patients. In Japanese patients, a lower dose of ribociclib (300 mg) should be considered. Clinicaltrials.gov: NCT02333370.
De novo missense variants in the RAP1B gene identified in two patients with syndromic thrombocytopenia
Authors: Niemann Jan Hendrik , Du Chen , Morlot Susanne , Schmidt Gunnar , Auber Bernd , Kaune Beate , Göhring Gudrun , Ripperger Tim , Schlegelberger Brigitte , Hofmann Winfried , Smol Thomas , Ait‐Yahya Emilie , Raimbault Anna , Lambilliotte Anne , Petit Florence , Steinemann Doris
Published: July 2020

We present two independent cases of syndromic thrombocytopenia with multiple malformations, microcephaly, learning difficulties, dysmorphism and other features. Exome sequencing identified two novel de novo heterozygous variants in these patients, c.35G>T p.(Gly12Val) and c.178G>C p.(Gly60Arg), in the RAP1B gene (NM_001010942.2). These variants have not been described previously as germline variants, however functional studies in literature strongly suggest a clinical implication of these two activating hot spot positions. We hypothesize that pathogenic missense variants in the RAP1B gene cause congenital syndromic thrombocytopenia with a spectrum of associated malformations and dysmorphism, possibly through a gain of function mechanism.
Globalizing the Sociology of Gentrification
Authors: Valle Melissa M.
Published: July 2020

How can the gentrification scholarship of US urban sociologists be enhanced by expanding beyond the confines of the Global North to include empirical and theoretical analyses of Southern gentrifications? This article engages the debate around the utility of the gentrification concept outside of postindustrial Northern cities. It argues that, in contrast to geographers and other interdisciplinary urbanists, many US-based sociologists have unduly overlooked or minimized two aspects of gentrification that may be more clearly observed in the Global South: the roles of local political-economic forces and the state. This article also notes what the discipline of sociology can add to apt explorations of gentrification in the Global South. It marries the oft-disparate discourses of sociologists of gentrification primarily in North America and Western Europe with geographers and other urbanists conducting gentrification research in the Global South in order to globalize the sociology of gentrification.
Predicting outcomes of pelvic exenteration using machine learning
Authors:   PelvEx Collaborative
Published: July 2020

Aim

We aim to compare machine learning with neural network performance in predicting R0 resection (R0), length of stay > 14 days (LOS), major complication rates at 30 days postoperatively (COMP) and survival greater than 1 year (SURV) for patients having pelvic exenteration for locally advanced and recurrent rectal cancer.

Method

A deep learning computer was built and the programming environment was established. The PelvEx Collaborative database was used which contains anonymized data on patients who underwent pelvic exenteration for locally advanced or locally recurrent colorectal cancer between 2004 and 2014. Logistic regression, a support vector machine and an artificial neural network (ANN) were trained. Twenty per cent of the data were used as a test set for calculating prediction accuracy for R0, LOS, COMP and SURV. Model performance was measured by plotting receiver operating characteristic (ROC) curves and calculating the area under the ROC curve (AUROC).

Results

Machine learning models and ANNs were trained on 1147 cases. The AUROC for all outcome predictions ranged from 0.608 to 0.793 indicating modest to moderate predictive ability. The models performed best at predicting LOS > 14 days with an AUROC of 0.793 using preoperative and operative data. Visualized logistic regression model weights indicate a varying impact of variables on the outcome in question.

Conclusion

This paper highlights the potential for predictive modelling of large international databases. Current data allow moderate predictive ability of both complex ANNs and more classic methods.
Native distribution characteristics rather than functional traits explain preadaptation of invasive species to high‐UV‐B environments
Authors: Hock Maria , Hofmann Rainer , Essl Franz , Pyšek Petr , Bruelheide Helge , Erfmeier Alexandra
Published: July 2020

Aim

Alien species successfully colonize new ranges if they encounter favourable environmental conditions there and possess traits that match new challenges. Climate‐matching approaches comparing native and exotic ranges mostly consider temperature and precipitation niches of alien species, but have largely ignored UV‐B radiation. UV‐B fundamentally differs between hemispheres, with much higher levels at southern than at northern latitudes. Consequently, UV‐B might act at the global scale and present a so far neglected filter that species need to overcome when invading high‐UV‐B environments.

Location

We performed two multi‐species common garden experiments, conducted in the native European range (Germany) and the high‐UV‐B exotic range (New Zealand) to test for preadaptation to UV‐B.

Methods

We used 25 herbaceous species from open habitats, which we exposed in each range to three UV radiation treatments: (a) natural sunlight, (b) exclusion of UV‐B while allowing natural UV‐A, and (c) exclusion of UV‐B and UV‐A. We additionally used plant traits (TRY), global distribution data (GBIF, GloNAF) and global UV‐B satellite data (glUV) to determine species‐specific characteristics as fostering agents of UV‐B tolerance. The joint analysis of experimental and macroecological data allowed quantification of species plasticity and identification of beneficial species traits in high‐UV‐B environments.

Results

Our results showed an overall limiting effect of UV‐B in both common gardens but the UV‐stress response tended to be more pronounced in the invaded range. Across all species, we found little evidence for preadaptation by functional plant traits. In contrast, preadaptation to climatic conditions related to the species’ native UV‐B niche was of greater importance for plant performance in the presence of UV‐B radiation.

Main conclusions

For predicting alien species’ ability to expand into high‐UV‐B environments, macroclimatic niche characteristics of the species’ native range might be better predictors than functional traits and should be more considered in future projection models.
Zebrafish models of impulsivity and impulse control disorders
Authors: de Abreu Murilo S. , C. V. V. Giacomini Ana , Genario Rafael , Fontana Barbara D. , Parker Matthew O. , Marcon Leticia , Scolari Naiara , Bueno Barbara , Demin Konstantin A. , Galstyan David , Kolesnikova Tatyana O. , Amstislavskaya Tamara G. , Zabegalov Konstantin N. , Strekalova Tatyana , Kalueff Allan V.
Published: July 2020

Impulse control disorders (ICDs) are characterized by generalized difficulty controlling emotions and behaviors. ICDs are a broad group of the central nervous system (CNS) disorders including conduct disorder, intermittent explosive, oppositional‐defiant disorder, antisocial personality disorder, kleptomania, pyromania and other illnesses. Although they all share a common feature (aberrant impulsivity), their pathobiology is complex and poorly understood. There are also currently no ICD‐specific therapies to treat these illnesses. Animal models are a valuable tool for studying ICD pathobiology and potential therapies. The zebrafish (Danio rerio) has become a useful model organism to study CNS disorders due to high genetic and physiological homology to mammals, and sensitivity to various pharmacological and genetic manipulations. Here, we summarize experimental models of impulsivity and ICD in zebrafish and highlight their growing translational significance. We also emphasize the need for further development of zebrafish ICD models to improve our understanding of their pathogenesis and to search for novel therapeutic treatments.
Assessing multifunctionality of agricultural soils: Reducing the biodiversity trade‐off
Authors: Vazquez Carmen , de Goede Ron G. M. , Rutgers Michiel , de Koeijer Tanja J. , Creamer Rachel E.
Published: July 2020

Soils are indispensable for the provision of several functions. Agricultural intensification and its focus on increasing primary productivity (PP) poses a threat to soil quality, due to increases in nutrient loads, greenhouse gas emissions and declining biodiversity. The EU Horizon 2020 Landmark project has developed multi‐criteria decision models to assess five soil functions: PP, nutrient cycling (NC), soil biodiversity and habitat provision (B‐HP), climate mitigation and water regulation, simultaneously in agricultural fields. Using these algorithms, we evaluated the supply of PP, NC and B‐HP of 31 grasslands and 21 croplands as low, medium or high. The multi‐criteria decision models showed that 38% of the farms had a medium to high supply of all three soil functions, whereas only one cropland had a high supply for all three. Forty‐eight per cent of the farms were characterized by a high supply of PP and NC. We observed a clear trade‐off between these two functions and B‐HP. Multivariate statistical analyses indicated that higher organic inputs combined with a lower mineral fertilization concur with higher biodiversity scores while maintaining a medium delivery of PP and NC. Additionally, we compared the outputs of the model predictions to independent variables that served as proxies for the soil functions and found: (a) croplands (but not grasslands) with high PP had a higher standardized yield than those with medium PP; (b) grasslands (but not croplands) with high NC had a significantly lower fungal to bacterial biomass ratio, suggesting faster decomposition channels; and (c) a positive though non‐significant trend between B‐HP score and rank according to soil invertebrate biodiversity. These comparisons suggest a successful upscaling of the models from field to farm level. Our study highlights the need for systematic collection of management‐related data for the assessment of soil functions. Multifunctionality can be achieved in agricultural soils; however, without specifically managing for it, biodiversity might come at a loss.

Highlights

We study how well soils can provide primary productivity, nutrient cycling and biodiversity.

We study trade‐offs and synergies among soil functions, as well as the drivers of these relationships.

Soil biodiversity is largely sacrificed for primary productivity and nutrient cycling

Changes in pesticide and fertilizer management can increase soil multifunctionality.
Energetic analysis of fatigue hysteresis by thermographic and digital image correlation methodologies
Authors: La Rosa Guido , Lo Savio Fabio , Giudice Fabio , Clienti Carmelo , Marino Cugno Garrano Adriana
Published: July 2020

A hysteresis cycle can define the variation in mechanical characteristics of fatigue life and failure response. Traditional analysis is performed using force‐displacement signals derived from the testing equipment, but this approach is prone to large errors due to clearances and slips in the measuring chain. For this reason, the authors here propose a novel setup able to assess accurately the strain status of specimens by digital image correlation (DIC) and a procedure to calculate the hysteresis energy by thermographic analysis in order to measure the damping energy with precision. The results obtained by an experimental investigation on a common austenitic steel (AISI 304) highlight that the hysteresis areas defined by the DIC displacements, and those found by the testing machine outputs have substantial differences in value. The thermal variations and the areas of the hysteresis loops, both linked to the plastic energy, were also compared, showing a reliable correlation.
Watershed‐scale climate influences productivity of Chinook salmon populations across southcentral Alaska
Authors: Jones Leslie A. , Schoen Erik R. , Shaftel Rebecca , Cunningham Curry J. , Mauger Sue , Rinella Daniel J. , St. Saviour Adam
Published: July 2020

The ecosystems supporting Pacific salmon (Oncorhynchusspp.) are changing rapidly as a result of climate change and habitat alteration. Understanding how—and how consistently—salmon populations respond to changes at regional and watershed scales has major implications for fisheries management and habitat conservation. Chinook salmon (O. tshawytscha) populations across Alaska have declined over the past decade, resulting in fisheries closures and prolonged impacts to local communities. These declines are associated with large‐scale climate drivers, but uncertainty remains about the role of local conditions (e.g., precipitation, streamflow, and stream temperature) that vary among the watersheds where salmon spawn and rear. We estimated the effects of these and other environmental indicators on the productivity of 15 Chinook salmon populations in the Cook Inlet basin, southcentral Alaska, using a hierarchical Bayesian stock‐recruitment model. Salmon spawning during 2003–2007 produced 57% fewer recruits than the previous long‐term average, leading to declines in adult returns beginning in 2008. These declines were explained in part by density dependence, with reduced population productivity following years of high spawning abundance. Across all populations, productivity declined with increased precipitation during the fall spawning and early incubation period and increased with above‐average precipitation during juvenile rearing. Above‐average stream temperatures during spawning and rearing had variable effects, with negative relationships in many warmer streams and positive relationships in some colder streams. Productivity was also associated with regional indices of streamflow and ocean conditions, with high variability among populations. The cumulative effects of adverse conditions in freshwater, including high spawning abundance, heavy fall rains, and hot, dry summers may have contributed to the recent population declines across the region. Identifying both coherent and differential responses to environmental change underscores the importance of targeted, watershed‐specific monitoring and conservation efforts for maintaining resilient salmon runs in a warming world.
The space‐time evolution and driving forces of county economic growth in China from 1998 to 2015
Authors: Li Zaijun , Hu Meijuan , Wang Zhenyu
Published: July 2020

Coordinated growth in regional economies is fundamental for sustainable economic development. In this study, the space‐time dynamics of GDP per capita for 2,303 counties in China from 1998 to 2015 were analyzed based on an exploratory space‐time data analysis (ESTDA) framework. The results showed that: (a) there was significant and increasing positive spatiotemporal correlation among county‐level economic growth; (b) local spatiotemporal correlation pattern demonstrated a high–high cluster at the eastern coast, and low–low dispersion in the vast central and western regions; (c) changes in LISA time trajectory revealed that economic growth in the coastal urban agglomeration and Inner Mongolia was more dynamic, indicating the emergence of a local spatial structure locking feature and trajectory dependence; and (d) industrialization and informatization were the two primary contributors to county economic growth. Our study suggests that Chinese government should construct network channels linking the central region with eastern China, cultivate economic growth poles and growth axis, and focus on technological innovation to unlock path dependence in county economic growth.
Effect of intercropping and nitrogen fertilization on production characteristics of Stylosanthes cv. Campo Grande and Xaraés grass
Authors: Jardim Renata Rodrigues , Fries Daniela Deitos , Dias Daniel Lucas Santos , de Figueiredo Abdias José , Pires Aureliano José Vieira , Teixeira Fábio Andrade , Amaral Júnior Francisco Paulo , Paiva Leliane Santos
Published: July 2020

The aim of this study was to evaluate the effect of cultivation systems and nitrogen fertilization on the dry mass yield and botanical composition of Brachiaria brizantha cv. Xaraés and Stylosanthes cv. Campo Grande in the four seasons of the year. The experiment took place in an area previously established with Xaraés grass, where Stylosanthes cv. Campo Grande was introduced. Yield traits were evaluated in a 3 × 2 factorial arrangement corresponding three cultivation systems (Xaraés monocrop, Stylosanthes monocrop and an intercrop between the two species), with or without nitrogen fertilization (75 kg N/ha), with four replicates. Nitrogen fertilization did not affect the yield traits of the evaluated cultivation systems. In the winter, the Xaraés monocrop and the intercrop showed the highest total dry mass yields. The highest yield in the spring was obtained with the intercrop; in the summer, with the Stylosanthes monocrop. In the fall and in the entire year, the cultivation systems did not differ for total dry mass yield. The intercrop between Xaraés grass and Stylosanthes is recommended, as it exhibits satisfactory dry mass yield besides reducing dependence on the use of chemical fertilizers and contributing to the conservation of natural resources.
Physiological responses and forage accumulation of Marandu palisadegrass and Mombaça guineagrass to nitrogen fertilizer in the Brazilian forage‐based systems
Authors: Domiciano Leandro F. , dos Santos Mariely L. , Boote Kenneth J. , dos Santos Patrícia M. , Pereira Dalton H. , Pedreira Bruno C.
Published: July 2020

In Brazil, the livestock systems are mainly forage‐based, and nitrogen inputs are an uncommon practice, despite its great benefits. The objective was to evaluate the effect of nitrogen input on the physiological responses of Marandu palisadegrass (Urochloa brizantha [Hochst. ex A. Rich.] R. D. Webster) and Mombaça guineagrass (Megathyrsus maximus [Jacq.] B. K. Simon & S. W. L. Jacobs), and its impacts on the forage accumulation rate (FAR). The experiment was carried out in Sinop, MT, Brazil, in a randomized block design with a 2 × 2 × 5 factorial arrangement (two cultivars: Mombaça and Marandu; unfertilized and fertilized [50 kg N ha−1 cycle−1]; and five seasons: autumn 2015, winter 2015, spring 2015, summer 2015 and autumn 2016) with three replicates. The experimental period was from March 2015 to June 2016, when plots were harvested to mimic intermittent stocking. Fertilized Mombaça presented greater FAR pastures (74.0 kg DM ha−1 day−1) than unfertilized (26.6 kg DM ha−1 day−1) and Marandu fertilized (52.5 kg DM ha−1 day−1), with the greatest values during the summer (147.6 kg DM ha−1 day−1). The greatest leaf (A) and canopy photosynthesis (CP) rates occurred on fertilized pastures during the summer 2015 and autumn 2015. Marandu presented 19% greater A than Mombaça. During the winter, under water stress, Marandu had greater water use efficiency (WUE). However, during the summer 2015 and autumn 16, Mombaça had the greatest WUE (12.76 μmol CO2/mol H2O). In all seasons, Marandu presented the greatest chlorophyll index, which may support the greatest photosynthetic rates. It was concluded that Mombaça was highly responsive to nitrogen input during the rainy season with accumulation over 140 kg DM ha−1 day−1 and is recommended to intensified systems. Marandu had the greatest WUE in the lower precipitation seasons and is an alternative to a year‐round strategy in forage‐based systems.
Physical, thermal and structural properties of rice starch as affected by the addition of bamboo shoot shell fibres
Authors: Huang Shan , Wang Nan , Zhang Yue , Zhang Fusheng , Zheng Jiong
Published: July 2020

The effects of different bamboo shoot shell fibre (BSSF) content (1, 2, 5 and 10%, w/w) on the physical, thermal and structural properties of rice starch were investigated. BSSFs significantly affected the properties of rice starch by competitive water absorption and hydrogen bonding. With increased BSSF content, the breakdown value and pasting temperature of rice starch were increased, whereas the peak viscosity, final viscosity and setback value were decreased. Thermodynamic results showed that the gelatinisation temperature and gelatinisation enthalpy of rice starch were significantly increased by the 5% and 10% BSSFs. Furthermore, BSSFs interconnected with amylose through hydrogen bonds to restrain gel‐structure formation, thereby resulting in low storage modulus and loss modulus of rice starch paste. A loose structure of rice starch supplemented with 10% BSSFs was clearly visible, exhibiting the minimum values of hardness (32.12 ± 4.47 g) and adhesiveness (64.70 ± 17.32 g). Moreover, BSSFs increased the amount of short‐range ordered structures but had no effect on the crystal type of rice starch. These results may contribute to the manufacture and development of fibre‐enriched starchy products.
Comparative evaluation of instant 'poundo' cocoyam (Colocasia esculenta) and yam (Dioscorea rotundata) flours produced by flash and cabinet drying
Authors: Adeboyejo Folasade Olabimpe , Aderibigbe Olaide Ruth , Obarayi Monsurat Titilope , Sturm Barbara
Published: July 2020

Cocoyam, an important staple crop especially among the low‐income earners in tropical regions of the world, is highly underutilised for industrial applications. This study investigates the nutritional, colour and rheological properties of instant flours (‘poundo’) from two cultivars of Colocasia esculenta (white‐NCe010 and purple‐NCe003) and Dioscorea rotundata (var. Oginni), and sensory attributes of doughs prepared from reconstituted flours. Tubers were processed into instant flours using cabinet and flash drying methods. Significant differences (P < 0.05) in the proximate and mineral composition and pasting properties of flours were found. Sensory panellists rated reconstituted poundo yam (8.17–8.20) and white cocoyam (7.50–7.95) higher than purple cocoyam (6.60–7.10) meals. Influence of drying method on sensory characteristics of flours was not significant. Instant poundo cocoyam and yam flours could serve as novel convenience and ready‐to‐eat food products which could contribute to increasing the commercial and industrial application options for these underutilised tubers beyond their present basic use.
The paediatric weight management office visit via telemedicine: pre‐ to post‐COVID‐19 pandemic
Authors: O'Hara Valerie M. , Johnston Starr V. , Browne Nancy T.
Published: July 2020

Telemedicine is a powerful tool that erases many logistical barriers to care and may increase access. Due to the need for social distancing, the COVID‐19 pandemic has temporarily reduced in‐person visits for clinical care. Providers, clinical staff and patients are pressed to acutely learn new skills and adapt clinical care through the use of telemedicine whilst administrators, policy makers and regulatory organizations make changes to existing policies to meet this national emergency. Our tertiary care, interdisciplinary paediatric weight management clinic began the use of telemedicine 5 years ago to bring access to an underserved, rural population at their primary care office, which has allowed our clinic to pivot seamlessly to in‐home telemedicine visits during the pandemic. Telemedicine rules and regulations are rapidly changing to meet the COVID‐19 national emergency, but many supports for new telemedicine providers are already in place. In this article, we provide an overview of telemedicine components, policies and regulations. We review the operationalization of our clinic's telemedicine visit prior to the pandemic. We discuss how telemedicine services are impacted by COVID‐19 and key resources are provided. Finally, we reimagine telemedicine services post‐pandemic to expand effective, coordinated health care, particularly for patients with chronic needs such as obesity.
Tricuspid annular plane systolic excursion is a predictor of mortality for septic shock
Authors: Dong Jun , White Seth , Nielsen Kirsten , Banchs Jose , Wang Jian , Botz Gregory H. , Nates Joseph L.
Published: July 2020

Background

Cardiac dysfunction is a common sequela in patients with sepsis and multi‐organ dysfunction. Echocardiography is commonly used in the investigation of circulatory failure.

Aims

We aimed to evaluate the prognostic value of echocardiographic parameters in patients with septic shock.

Methods

This study was a retrospective trial. We included patients who were admitted to intensive care unit (ICU) with septic shock. The patients' echocardiograms, clinical data and outcomes were obtained from their medical records. Associations between echocardiogram variables and mortality were assessed using logistic regression, controlled for age, sex, body mass index and the interval between the ICU admission and echocardiogram. The utility of statistically significant echocardiogram variables to predict mortality were assessed using receiver operating characteristic (ROC) curves.

Results

The outcomes presented that tricuspid annular plane systolic excursion (TAPSE) was statistically significantly associated with both ICU (P = 0.02) and 90‐day (P = 0.001) mortality. From the ROC curves, TAPSE emerged a significant and moderate predictor for 90‐day (area under curve (AUC) = 0.69, 95% CI = 0.565–0.814) and in‐ICU mortality (AUC = 0.762, 95% CI = 0.652–0.871). The optimal cut‐off for TAPSE was 2.1 cm for both 90‐day mortality (sensitivity of 80% and specificity and 58%) and in‐ICU mortality (sensitivity of 69% and specificity of 77%).

Conclusions

TAPSE was associated with increased mortality in those with sepsis and suspicion of cardiac dysfunction. This is a hypothesis generating article that an association may be present and requires significant more work with expansion to the entire population base.
Retailers' endogenous sequencing game and information acquisition game in the presence of information leakage
Authors: Kim Yongjae
Published: July 2020

Timely and accurate order placement is critical to the success of all partners in a supply chain. This study explores the equilibrium states of the endogenous timing of order placement that could lead to information leakage in the supply chain. Competition and information asymmetry in the business environment adversely affect firms across industries, often leading to suboptimal outcomes. We examine the dynamics of two competing retailers and the impact of information leakage due to asymmetric information on their decision‐making strategies. Specifically, we analyze a supply chain with one supplier and two competing retailers under demand uncertainty in which the retailers' decisions on the timing of order placement and acquisition of demand information are endogenous. We characterize the retailers' choices in equilibrium and analyze the impact of these choices on their order quantities and profits. In reality, owing to outsourcing to overseas suppliers and long lead times, suppliers prefer early orders from their downstream partners. We find that a retailer that decides to invest to obtain demand information would end up ordering earlier than its competing firm even if information asymmetry and leakage exist. We also show that information is more valuable and beneficial to the retailer that has the first‐mover advantage.
Reconstructing historical shifts in suitable habitat of Sceloporus lineages using phylogenetic niche modelling
Authors: Rivera Julio A. , Lawing A. Michelle , Martins Emília P.
Published: July 2020

Aim

We tested whether we could detect geographical shifts in modelled‐suitable habitat. We aim to enhance phylogenetic niche models of past suitable habitats for Sceloporus lineages by integrating modern and fossil occurrences with ecological and phylogenetic comparative modelling methods. Specifically, we hypothesized that our integrated approach is sensitive enough to detect geographical shifts in suitable habitat between lineages and through evolutionary time.

Location

North America.

Taxon

Sceloporus lizards.

Methods

We used extant and fossil occurrence data, general circulation models of palaeoclimate, climate envelope modelling and phylogenetic comparative methods to reconstruct past suitable climates for Sceloporus lizards over the last 20 million years, and then visualized the geographical locations of individual lineages using multivariate environmental similarity surfaces (MESS) maps.

Results

We were able to reconstruct ancestral suitable climate for Sceloporus lineages with sufficient resolution to identify shifts in geographical location between lineages. We found that large shifts in climate regimes drove the expansion and contraction of suitable habitat through time. We found a positive association between tectonic events, like mountain uplift, and lineage diversification in the Sceloporus clade. Mountain uplift also facilitated the emergence of open grassland habitat, which excluded many Sceloporus species.

Main conclusions

Our approach was sensitive enough to detect differences in geographical location of suitable habitat across lineages and through evolutionary time. Doing so is a critical first step to tracking the evolutionary ecology of individual taxa over long periods of evolutionary time, and to inferring which species co‐existed in which locations. Such inferences would allow for more precise predictions of current and future ecological needs for conservation efforts, and to inform efforts to mitigate climate change.
The research‐teaching nexus in a graduate CALL course: An action research study
Authors: Abdel Latif Muhammad M. M.
Published: July 2020

The ‘research‐teaching nexus’ means integrating disciplined‐based research into course content to develop students’ research ability. Though such integration has been investigated in various higher education content areas, no previous CALL teacher education research seems to have addressed it. This study explored how research should be integrated into a graduate CALL course and how such integration influences students’ research awareness and skills. The content‐focused and process‐focused forms of the research‐teaching nexus were integrated into a graduate CALL course taught in a language teacher education programme at an Arab university. The course was taught to a group of female MA student teachers for a 15‐week academic term. Qualitative data was collected using observation and an open‐end questionnaire within an action research framework. The students reported positive evaluation of research integration into the CALL course. Meanwhile, the observational data indicates that research integration has fostered their CALL research awareness and enabled them to learn how to craft some key research elements, namely developing research titles and questions, and selecting the research method. The results generally imply that developing students’ CALL research skills through the process‐focused teaching forms is a more complicated task than enhancing their research awareness via the content‐focused ones.
Diagnosis of chronic stage of hypertensive retinopathy based on spectral domain optical coherence tomography
Authors: Feng Xue , Wang Haiwei , Kong Yuanyuan , Zhang Junyan , He Jingfang , Zhang Bozheng , Zhang Jianqiang , Qi Hong , Wang Yanling
Published: July 2020

Hypertensive retinopathy refers to the retinal vascular changes associated with systemic arterial hypertension. Hypertensive retinopathy can be divided into chronic and acute phases. A cross‐sectional study was performed to explore a method of measurement in the diameters of retinal vessels for diagnosis of chronic hypertensive retinopathy based on spectral domain optical coherence tomography (SD‐OCT). The central retinal artery diameter (CRAD), the central retinal vein diameter (CRVD), and the artery‐to‐vein ratio (AVR) were measured. A total of 119 subjects with 119 eyes were included in this study, in which 56 subjects with 56 eyes were included in hypertensive group and 63 subjects with 63 eyes were included in normotensive group. There were significant differences between the two groups in the CRAD (t = −2.14, P = .04) and the AVR (t = −2.59, P = .01). The cutoff point of 0.75 was determined by receiver operating characteristic (ROC) curve (area under the curve, AUC 0.786; 95% confidence interval, 95% CI 0.70‐0.87). Multivariate logistic regression analysis showed the probability of AVR below to 0.75 was more in patients with high systolic blood pressure (odds ratio OR 4.39; P = .048), more in male (OR 4.15; P = .004) and more in smokers (OR 5.80; P = .01). Bland‐Altman plots showed small mean bias between the measurements of the two technicians in the CRAD, the CRVD, and the AVR. In summary, application of SD‐OCT is an accurate, reproducible, convenient method for measuring the diameters of retinal vessels. It is valuable for the diagnosis of chronic stage of hypertensive retinopathy.
WWP2 regulates SIRT1‐STAT3 acetylation and phosphorylation involved in hypertensive angiopathy
Authors: Zhang Ying , You Shilong , Tian Yichen , Lu Saien , Cao Liu , Sun Yingxian , Zhang Naijin
Published: July 2020

WWP2 is a HECT‐type E3 ubiquitin ligase that regulates various physiological and pathological activities by binding to different substrates, but its function and regulatory mechanism in vascular smooth muscle cells (VSMCs) are still unknown. Here, we clarified the role of WWP2 in the regulation of SIRT1‐STAT3 and the impact of this regulatory process in VSMCs. We demonstrated that WWP2 expression was significantly increased in angiotensin II‐induced VSMCs model. Knockdown of WWP2 significantly inhibited angiotensin II‐induced VSMCs proliferation, migration and phenotypic transformation, whereas overexpression of WWP2 had opposite effects. In vivo experiments showed that vascular smooth muscle‐specific WWP2 knockout mice significantly relieved angiotensin II‐induced hypertensive angiopathy. Mechanistically, mass spectrometry and co‐immunoprecipitation assays identified that WWP2 is a novel interacting protein of SIRT1 and STAT3. Moreover, WWP2 formed a complex with SIRT1‐STAT3, inhibiting the interaction between SIRT1 and STAT3, then reducing the inhibitory effect of SIRT1 on STAT3, ensuing promoting STAT3‐K685 acetylation and STAT3‐Y705 phosphorylation in angiotensin II‐induced VSMCs and mice. In conclusion, WWP2 modulates hypertensive angiopathy by regulating SIRT1‐STAT3 and WWP2 suppression in VSMCs can alleviate hypertensive angiopathy vitro and vivo. These findings provide new insights into the treatment of hypertensive vascular diseases.
CRISPR/Cas9‐mediated whole genomic wide knockout screening identifies mitochondrial ribosomal proteins involving in oxygen‐glucose deprivation/reperfusion resistance
Authors: Guan Xinjie , Zhang Hainan , Qin Haiyun , Chen Chunli , Hu Zhiping , Tan Jieqiong , Zeng Liuwang
Published: July 2020

Recanalization therapy by intravenous thrombolysis or endovascular therapy is critical for the treatment of cerebral infarction. However, the recanalization treatment will also exacerbate acute brain injury and even severely threatens human life due to the reperfusion injury. So far, the underlying mechanisms for cerebral ischaemia‐reperfusion injury are poorly understood and effective therapeutic interventions are yet to be discovered. Therefore, in the research, we subjected SK‐N‐BE(2) cells to oxygen‐glucose deprivation/reperfusion (OGDR) insult and performed a pooled genome‐wide CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR‐associated protein 9) knockout screen to discover new potential therapeutic targets for cerebral ischaemia‐reperfusion injury. We used Metascape to identify candidate genes which might involve in OGDR resistance. We found that the genes contributed to OGDR resistance were primarily involved in neutrophil degranulation, mitochondrial translation, and regulation of cysteine‐type endopeptidase activity involved in apoptotic process and response to oxidative stress. We then knocked down some of the identified candidate genes individually. We demonstrated that MRPL19, MRPL32, MRPL52 and MRPL51 inhibition increased cell viability and attenuated OGDR‐induced apoptosis. We also demonstrated that OGDR down‐regulated the expression of MRPL19 and MRPL51 protein. Taken together, our data suggest that genome‐scale screening with Cas9 is a reliable tool to analyse the cellular systems that respond to OGDR injury. MRPL19 and MRPL51 contribute to OGDR resistance and are supposed to be promising targets for the treatment of cerebral ischaemia‐reperfusion damage.
Diagnostic and therapeutic potential of exosomes in Alzheimer’s disease
Authors: Soares Martins Tânia , Trindade Dário , Vaz Margarida , Campelo Inês , Almeida Martim , Trigo Guilherme , da Cruz e Silva Odete A. B. , Henriques Ana Gabriela
Published: July 2020

Exosomes are small extracellular vesicles released by almost all cell types in physiological and pathological conditions. The exosomal potential to unravel disease mechanisms, or to be used as a source of biomarkers, is being explored, in particularly in the field of neurodegenerative diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world and exosomes appear to have a relevant role in disease pathogenesis. This review summarizes the current knowledge on exosome contributions to AD as well as their use as disease biomarker resources or therapeutic targets. The most recent findings with respect to both protein and miRNA biomarker candidates for AD, herein described, highlight the state of the art in this field and encourage the use of exosomes derived from biofluids in clinical practice in the near future.

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Only some attempts at meaning making are successful: The role of change‐relatedness and positive implications for the self
Authors: Huang Manxia , Schmiedek Florian , Habermas Tilmann
Published: July 2020

Objective

Although meaning making and specifically autobiographical reasoning are expected to relate to well‐being, findings tend to be mixed. Attempts at meaning making do not always lead to meaning made. We aimed to disentangle these complex relationships and also explore the role of level of education.

Method

Ninety participants (mean age 36.73 years,SD = 7.27; 74.4% women, 25.6% men) who had experienced the loss of a parent through death, going missing, or Alzheimer's disease narrated this loss, a sad, a turning point, and a self‐defining memory, and completed questionnaires assessing depression, trauma symptoms, and protracted grief. Three aspects of autobiographical reasoning (quantity, valence, and change‐relatedness of self‐event connections) were related to meaning made (sophistication of meaning making) and symptom level.

Results

Years of education correlated both with positive implications of autobiographical reasoning and with meaning made. The quantity, positivity, and change‐relatedness of attempts at meaning making (self‐event connections) predicted accomplished meaning made, and positivity alone predicted less prolonged grief.

Conclusions

Adapting the life story after a loss such that change of the self is acknowledged and positive change can be constructed helps finding meaning and lowering protracted grief. These changes in narrative identity are supported by more years of education.
Sleep disturbances and disability following work‐related injury and illness: Examining longitudinal relationships across three follow‐up waves
Authors: Fan Jonathan K. , Sim Malcolm , Lilley Rebbecca , Wong Imelda S. , Smith Peter M.
Published: July 2020

Despite the high burden of sleep disturbances among the general population, there is limited information on prevalence and impact of poor sleep among injured workers. This study: (a) estimated the prevalence of sleep disturbance following work‐related injury; and (b) examined the longitudinal association between sleep disturbances and disability/functioning, accounting for reciprocal relationships and mental illness. Longitudinal survey data were collected from workers' compensation claimants with a time‐loss claim in Victoria, Australia (N = 700). Surveys were conducted at baseline, 6 months and 12 months. Sleep disturbance was measured using the Patient‐Reported Outcomes Measurement Information System (PROMIS) questionnaire. Disability/functioning was based on self‐reported activity limitations, participation restrictions and emotional functioning. Path models examined the association between disability/functioning and sleep. Mean sleep disturbance T‐scores were 55.2 (SD 11.4) at 6 months, with 36.4% of the sample having a T‐score of 60+. Longitudinal relationships were observed between disability (specifically, emotional functioning) and sleep disturbances across successive follow‐up waves. For example, each unit increase in T2 emotional functioning (five‐point scale) was associated with a 1.1 unit increase in T3 sleep disturbance (approximately 29–76 scale). Cross‐lagged path models found evidence of a reciprocal relationship between disability and sleep, although adjustment for mental illness attenuated the estimates to the null. In conclusion, sleep disturbances are common among workers' compensation claimants with work injuries/illnesses. Given the links between some dimensions of disability, mental health and sleep disturbances, the findings have implications for the development of interventions that target the high prevalence of sleep problems among working populations.
Normal utilization rate in the Sraffa framework
Authors: Huang Biao
Published: July 2020

This paper deals with the normal utilization rate in the Sraffa framework. It further presents two arguments about the utilization controversy surrounding the neo‐Kaleckian theory of growth and distribution: First, it shows that the normal utilization rate is generally not independent of demand and the growth rate, and this result does not rely on the neo‐classical production function and other restrictive assumptions. Second, it argues that endogenizing the normal utilization rate is not a general solution for the utilization controversy.
Visualising virulence factors: Trichophyton benhamiaes subtilisins demonstrated in a guinea pig skin ex vivo model
Authors: Baumbach Christina‐Marie , Michler Jule Kristin , Nenoff Pietro , Uhrlaß Silke , Schrödl Wieland
Published: July 2020

Background

Dermatophytoses rank among the most frequent communicable diseases in humans, and the zoonotic transmission is increasing. The zoophilic dermatophyte Trichophyton (T.) benhamiae is nowadays one of the main causes of tinea faciei et corporis in children. However, scientific data on molecular pathomechanisms and specific virulence factors enabling this ubiquitous occurrence are scarce.

Objectives

To study tissue invasion and the expression of important virulence factors of T. benhamiae, isolates that were recovered from two groups of hosts (humans vs. guinea pigs (GP)) using an ex vivo skin model.

Methods

After confirmation of species identity by ITS sequencing, CFU suspensions of dermatophyte isolates (n = 20) were applied to the skin infection model and cultured. Employing specific immunofluorescence staining techniques, the expression of subtilisin 3 and 6 and metallocarboxypeptidase A was analysed. The general mode of invasion was explored. Results were compared with biopsies of naturally infected GP.

Results

All isolates were successfully recovered and proliferated well after application to the infection model. Progressive invasion of hyphae through all skin structures and destruction of explants were observed with early events being comparable to natural infection. An increasing expression of the examined virulence factors towards the end of culture was noticed but no difference between the two groups of isolates.

Conclusions

For the first time, important in vivo markers of dermatophytosis were visualised immunohistochemically in an ex vivo skin infection model and in skin biopsies of GP naturally infected with T. benhamiae. More research on the underlying pathomechanisms of dermatophyte infection is urgently needed.