bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated investment management: Comparing the design and performance of international robo‐managers
Authors: Helms Nils , Hölscher Reinhold , Nelde Matthias
Published: August 2021

Robo‐managers offer automated asset management; however, their overall performance is highly debated. We analyze 15 robo‐managers from Germany, the United States and the United Kingdom by conducting a comprehensive qualitative and quantitative study. The qualitative comparison shows considerable differences between the various robo‐managers, not only across but also within countries. The quantitative evaluation utilizes different measures to evaluate the performance of the robo‐manager sample. Our results indicate that each country has one particularly favourable robo‐manager. Furthermore, we find that the costs and characteristics of rebalancing measures have only a small effect on performance.
Diagnosis of infectious factors in patients with chronic glomerular disease using deep learning‐based health information data
Authors: Zhou Canxin , Chen Siqi , Li Xinhan , Ying Xuxia
Published: August 2021

The study was aimed to explore the effect of information health data based on deep learning of neural network to diagnose the infectious factors of patients with chronic glomerular disease (CGD) and evaluate its diagnostic effect. Ninety patients with CGD were selected and randomly rolled into control group A, control group B, and observation group, with 30 cases in each group. Big data scientific research analysis platform was used for data integration, convolutional neural network (CNN) was employed for feature analysis, correlation analysis, and screening of disease‐related biomarkers. The patients were diagnosed by observation of symptoms and signs, combined diagnosis of blood test and urine test, and information health data diagnosis based on deep learning CNN. As a result, the specificity, sensitivity, and accuracy of information health data diagnosis based on deep learning CNN were 78.9%, 87.6%, and 92.1%, respectively. The main sources of infections in patients were lung infections, bloodstream infections, urinary system infections, skin and soft tissue infections, and upper respiratory tract infections. Amongst them, lung infection accounted for the highest proportion, reaching 65.4%, followed by blood infection (11.2%) and skin tissue infection (9.6%). The pathogens of infection were mainly bacteria, viruses, fungi, tuberculosis, and pneumocystis pneumonia (PCP), amongst which bacterial infections accounted for the highest proportion (31.5%), followed by PCP (25.6%). In short, the information health data based on deep learning CNN had high specificity, sensitivity, and accuracy for the diagnosis of CGD. The main infectious factors of CGD were pulmonary infection and blood infection, and the pathogens were mainly bacteria and viruses.
The ups and downs of elevator‐type di‐/tricarboxylate membrane transporters
Authors: Sauer David B. , Wang Bing , Sudar Joseph C. , Song Jinmei , Marden Jennifer , Rice William J. , Wang Da‐Neng
Published: August 2021

The divalent anion sodium symporter (DASS) family contains both sodium‐driven anion cotransporters and anion/anion exchangers. The family belongs to a broader ion transporter superfamily (ITS), which comprises 24 families of transporters, including those of AbgT antibiotic efflux transporters. The human proteins in the DASS family play major physiological roles and are drug targets. We recently determined multiple structures of the human sodium‐dependent citrate transporter (NaCT) and the succinate/dicarboxylate transporter from Lactobacillus acidophilus (LaINDY). Structures of both proteins show high degrees of structural similarity to the previously determined VcINDY fold. Conservation between these DASS protein structures and those from the AbgT family indicates that the VcINDY fold represents the overall protein structure for the entire ITS. The new structures of NaCT and LaINDY are captured in the inward‐ or outward‐facing conformations, respectively. The domain arrangements in these structures agree with a rigid body elevator‐type transport mechanism for substrate translocation across the membrane. Two separate NaCT structures in complex with a substrate or an inhibitor allowed us to explain the inhibition mechanism and propose a detailed classification scheme for grouping disease‐causing mutations in the human protein. Structural understanding of multiple kinetic states of DASS proteins is a first step toward the detailed characterization of their entire transport cycle.
Capturing the RNA castle: Exploiting MicroRNA inhibition for wound healing
Authors: Bibby George , Krasniqi Blerta , Reddy Izaak , Sekar Durairaj , Ross Kehinde
Published: August 2021

The growing pipelines of RNA‐based therapies herald new opportunities to deliver better patient outcomes for complex disorders such as chronic nonhealing wounds associated with diabetes. Members of the microRNA (miRNA) family of small noncoding RNAs have emerged as targets for diverse elements of cutaneous wound repair, and both miRNA enhancement with mimics or inhibition with antisense oligonucleotides represent tractable approaches for miRNA‐directed wound healing. In this review, we focus on miRNA inhibition strategies to stimulate skin repair given advances in chemical modifications to enhance the performance of antisense miRNA (anti‐miRs). We first explore miRNAs whose inhibition in keratinocytes promotes keratinocyte migration, an essential part of re‐epithelialisation during wound repair. We then focus on miRNAs that can be targeted for inhibition in endothelial cells to promote neovascularisation for wound healing in the context of diabetic mouse models. The picture that emerges is that direct comparisons of different anti‐miRNAs modifications are required to establish the most translationally viable options in the chronic wound environment, that direct comparisons of the impact of inhibition of different miRNAs are needed to quantify and rank their relative efficacies in promoting wound repair, and that a standardised human ex vivo model of the diabetic wound is needed to reduce reliance on mouse models that do not necessarily enhance mechanistic understanding of miRNA‐targeted wound healing.
Effects of land‐use change in the Amazon on precipitation are likely underestimated
Authors: Baudena Mara , Tuinenburg Obbe A. , Ferdinand Pendula A. , Staal Arie
Published: August 2021

The Amazon forest enhances precipitation levels regionally as trees take up water from the soil and release it back into the atmosphere through transpiration. Therefore, land‐use changes in the Amazon affect precipitation patterns but to what extent remains unclear. Recent studies used hydrological and atmospheric models to estimate the contribution of tree transpiration to precipitation but assumed that precipitation decreases proportionally to the transpired portion of atmospheric moisture. Here, we relaxed this assumption by, first, relating observed hourly precipitation levels to atmospheric column water vapor in a relatively flat study area encompassing a large part of the Amazon. We found that the effect of column water vapor on hourly precipitation was strongly nonlinear, showing a steep increase in precipitation above a column water vapor content of around 60 mm. Next, we used published atmospheric trajectories of moisture from tree transpiration across the whole Amazon to estimate the transpiration component in column water vapor in our study area. Finally, we estimated precipitation reductions for column water vapor levels without this transpired moisture, given the nonlinear relationship we found. Although loss of tree transpiration from the Amazon causes a 13% drop in column water vapor, we found that it could result in a 55%–70% decrease in precipitation annually. Consequences of this nonlinearity might be twofold: although the effects of deforestation may be underestimated, it also implies that forest restoration may be more effective for precipitation enhancement than previously assumed.
Welcome to the Pyrocene: Animal survival in the age of megafire
Authors: Nimmo Dale G. , Carthey Alexandra J. R. , Jolly Chris J. , Blumstein Daniel T.
Published: August 2021

Planet Earth is entering the age of megafire, pushing ecosystems to their limits and beyond. While fire causes mortality of animals across vast portions of the globe, scientists are only beginning to consider fire as an evolutionary force in animal ecology. Here, we generate a series of hypotheses regarding animal responses to fire by adopting insights from the predator–prey literature. Fire is a lethal threat; thus, there is likely strong selection for animals to recognize the olfactory, auditory, and visual cues of fire, and deploy fire avoidance behaviours that maximize survival probability. If fire defences are costly, it follows that intraspecific variation in fire avoidance behaviours should correspond with variation in fire behaviour and regimes. Species and populations inhabiting ecosystems that rarely experience fire may lack these traits, placing ‘fire naive’ populations and species at enhanced extinction risk as the distribution of fire extends into new ecosystem types. We outline a research agenda to understand behavioural responses to fire and to identify conservation interventions that could be used to overcome fire naivety.
Sentinel lymph node tumour burden using digital cell count estimation predicts outcomes in melanoma
Authors: Hartsough Emily M , Miller Daniel , Shanley Ryan , Domingo‐Musibay Evidio , Giubellino Alessio
Published: August 2021

Background and aims

Cutaneous melanoma often metastasises in primis to sentinel lymph nodes (SLNs). Currently, there is no standardized method of characterizing the micrometastatic tumour burden in SLN biopsies for melanoma. Different criteria have been developed to evaluate SLN biopsies, yet none consider the number of cells identified. Here, we used software analysis to digitally quantify metastatic tumour burden within SLNs and correlated these data with clinicopathological and prognostic information.

Methods and results

We identified 246 cases of SLN biopsies, including 63 positive (26%) and183 (74%) negative for metastatic melanoma. Digital cell counting was performed within the greatest metastatic focus and the entire metastatic tumour burden within the same SLN. Increasing cell count in the largest metastatic deposit correlated with the previously described Rotterdam [Spearman's r = 0.91; 95% confidence interval (CI) = 0.84, 0.94], Starz (Spearman's r = 0.78; 95% CI = 0.68, 0.87) and Dewar criteria (P < 0.01), validating our method of using cell count to define SLN tumour burden. Additionally, increasing cell count was associated with decreased metastasis‐free survival (hazard ratio = 2.29; 95% CI = 1.22, 4.31).

Conclusion

These data support the use of computerized cell count analysis for prognostication of outcomes in patients undergoing SLN biopsy.
Effect of regioisomers of hydroxystearic acids as peroxisomal proliferator‐activated receptor agonists to boost the anti‐ageing potential of retinoids
Authors: Rawlings Anthony V. , Wandeler Eliane , Bendik Igor , Fuchs Pascale , Monneuse Jean‐Marc , Imfeld Dominik , Schütz Rolf
Published: August 2021

Introduction

We report on the in vitro and ex vivo effects of chiral (R)‐10‐hydroxystearic acid (10‐HSA) compared with other mono‐hydroxystearic acid regioisomers and stearic acid (SA) together with its benefit when combined with retinol.

Methods

Following treatment with hydroxystearic acids peroxisomal proliferator‐activated receptor alpha (PPARα) activity was determined in a luciferase reporter gene assay, collagen type I was assessed in primary human dermal fibroblasts by immunohistochemistry, modification of the intracellular fibroblast collagen proteome was studied by mass‐spectrometry‐based proteomics and collagen type III was assessed by immunohistochemistry on human ex vivo skin.

Results

10‐HSA was the most effective PPARα agonist (15.7× induction; p < 0.001), followed by 9‐HSA (10.1× induction) and then 12‐HSA (4.9× induction) with 17‐HSA (1.7× induction) being similar to the effects of stearic acid (1.8× induction). Collagen type I levels were increased in primary human fibroblasts by 2.12× and 1.56× for 10‐HSA and 9‐HSA, respectively, in vitro with the10‐HSA being significant (p < 0.05), whereas 12‐HSA and SA had no statistical effect over the untreated control. 10‐HSA and 12‐HSA modified the intracellular fibroblast collagen proteome slightly with significant increases in collagen alpha‐1 (VI) and alpha‐3 (VI) proteins but only 10‐HSA increased levels of collagen alpha‐2 (V), alpha‐1 (III), alpha‐1 (I) and alpha‐2 (I) (all p < 0.05) with the increases being significantly different between 10‐HSA and 12‐HSA for collagen alpha‐1 (I), collagen‐3 (VI) and collagen alpha‐2 (I) (p < 0.01). Collagen type III in ex vivo skin was increased +47% (p < 0.05) by 0.05% (1.7 mM) retinol, +70% (p < 0.01) by 0.01% (0.33 mM) 10‐HSA and the combination increased levels by +240% (p < 0.01 for either ingredient).

Conclusion

Chiral (R)‐10‐HSA has been shown to be superior to 9, 12 and 17‐HSA as a PPARα agonist. Moreover, 10‐HSA stimulated collagen synthesis in monolayer fibroblast culture as assessed by proteomics and immunohistochemically. Furthermore, we also show the synergistic effects of 10‐HSA with retinol on collagen III synthesis in skin explants. These results further highlight the efficacy of 10‐HSA as a cosmetically acceptable PPARα agonist and anti‐ageing ingredient.
The alkaloid centcyamine increases expression of klotho and lamin B1, slowing the onset of skin ageing in vitro and in vivo
Authors: Abadie Sophie , Leduc Claire , Lintner Karl , Bedos Philippe
Published: August 2021

Background

Klotho is a protein known for its beneficial effects on longevity. Centcyamine is an alkaloid present in certain plants whose extracts have an anti‐inflammatory effect. Skin fibroblasts are essential to the formation and structure of the dermis.

Objective

Centcyamine is an indole‐based alkaloid composed of coumaric acid, a resveratrol precursor and methoxytryptamine, which can be both a precursor, or a derivative, of melatonin. Given these building blocks and their well‐known bioactivities, it was of interest to explore the potential benefits of using this aryl‐alkaloid, in cosmetic skincare applications.

Methods

We tested cultured normal human dermal fibroblasts (NHDF) in vitro to observe how supplementation with centcyamine improves properties of the cells to counteract the effect of ageing. The expression of genes and proteins of interest was quantified. The effect on doubling time and cell function was evaluated following treatment of the cells over several replication cycles. Skin firmness, red spot index and skin isotropy were measured with Dynaskin®, Visia® and Primos® equipment, respectively, and compared over two months in a vehicle‐controlled clinical trial on 60 persons.

Results

Centcyamine activates the expression of the gene KL and the related protein Klotho in dermal fibroblasts. Moreover, centcyamine slows the replicative ageing process of fibroblasts in culture. These cells retain cellular functions identical to those of young cells: the synthesis of lamin B1, a crucial regulatory protein of proliferation, as well as of collagen I and elastin is retained in aged cells. The clinical data are shown to improve skin isotropy in a majority of subjects, to reduce the red spot intensity and to maintain skin firmness in the treated group vs. the vehicle.

Conclusion

The alkaloid centcyamine induces changes in the metabolism of the ageing process of human dermal fibroblasts. The up‐to‐now unobserved implication of both Klotho and lamin B1 to maintain homeostasis of the skin opens new venues for the prevention of age‐related changes in skin structure. The in vitro and clinical data, while not demonstrated to be causally related, converge towards a common goal of skin repair and slower ageing processes.
Cemental tear: Literature review, proposed classification and recommendations for treatment
Authors: Lee Angeline H. C. , Neelakantan Prasanna , Dummer Paul M. H. , Zhang Chengfei
Published: August 2021

Cemental tears are an important condition of relevance to Endodontics but are often overlooked. A cemental tear is the partial or complete detachment of the cementum from the cemento‐dentinal junction or along the incremental line within the body of cementum. The limited attention received is most likely due to the limited awareness amongst dental professionals and challenges in accurately diagnosing them, resulting in misdiagnosis and erroneous treatment. The aim of this review is to describe the: (i) epidemiology and predisposing factors; (ii) clinical, radiographic and histological features and (iii) the clinical management and treatment outcomes of cemental tear. The review included 37 articles published in English that comprised eight observational studies and 29 case reports. The prevalence of cemental tears was reported to be lower than 2%; whilst the incidence remains unknown.Internal factorsdue to the inherent structural weakness of cementum and its interface with the dentine, andexternal factorsthat are associated withstresshave been proposed as the two mechanisms responsible for the development and propagation of cemental tears. Predisposing factors that have been implicated weretooth type,gender,age,previous root canal treatment,history of dental trauma,occlusal trauma and excessive occlusal force; however, evidence is limited. Common clinical and radiographic manifestations of cemental tears resemble the presentations of primary endodontic diseases, primary periodontal diseases and combined endodontic–periodontal lesions. Clinical management tended to focus on complete removal of the torn fragments and periodontal treatment, often combined with regenerative treatment. In this article, a new classification for cemental tears is developed that consists ofclasses 0to6andstages A,B,CandDbased on the: (i) location and accessibility of the torn cemental fragment; (ii) the pattern and extension of the associated bony defect in relation to the root length and (iii) the number of root surface/s affected by the cemental tear/s and the associated bony defect. Recommendations for treatment strategies are also provided and linked to the classification to aid in streamlining the process of treatment decision making.
Acquired epidermodysplasia verruciformis: clinical presentation and treatment update
Authors: Moore Stephen , Rady Peter , Tyring Stephen
Published: August 2021

Acquired epidermodysplasia verruciformis (AEV) is a form of epidermodysplasia verruciformis (EV) that is most commonly found in immunocompromised or immunosuppressed patients. EV is commonly associated with human papillomavirus (HPV), which is often found in EV and AEV lesions. Clinical presentation of AEV in patients with organ transplantation, HIV+, congenital HIV+, hematological diseases, and other iatrogenic immunosuppression are reviewed. Treatment options include topical cidofovir, topical retinoids, topical imiquimod, topical glycolic acid, HPV 9‐valent vaccine, acitretin, improving cellular immunity, and changing transplant medication to mycophenolate mofetil.
Advanced practice nurses: Analysis of their role from a multicentre cross‐sectional study
Authors: Sevilla Guerra Sonia , Zabalegui Adelaida , Comellas Oliva Montserrat , Estrem Cuesta Mercè , Martín‐Baranera Montse , Ferrús Estopà Lena
Published: August 2021

Background

Stronger healthcare models are increasingly sought to address new population needs, health workforce inefficiencies and nursing shortages. One strategy is to focus on employees’ strengths to capitalize on their competencies and maximize their scope of practice.

Introduction

Globally, there is an exponential demand for advanced practice nursing services. This study aimed to identify the roles and positions of nurses who align with APN defining criteria at all levels of care in Catalonia, Spain.

Methods

The first step of the study included the translation and validation to Catalan of the Advanced Practice Nurse Role Delineation Tool (IDREPA) and step 2 comprised a multicentre cross‐sectional study, in which 126 healthcare centres participated: 1209 nurses were included in the study. The STROBE checklist was used to report this study.

Results

Transcultural equivalence and validation of the instrument showed a content validity index of 0.958 and the reliability of the questionnaire. The instrument identified 269 nurses who align with international APN defined criteria. They worked in specialized care, mental healthcare and primary and community care, especially in chronic conditions, ageing and end‐of‐life care.

Discussion

Most areas of Catalonia have access to nurses practicing at APN defining criteria. These nurses were developed as an optimal resource to respond to patient needs in the context of study. Both recognition and strategic implementation are necessary to apply their full competencies to solve healthcare problems.

Conclusion

Understanding the supply of services delivered by nurses practicing at an advanced level and their scope of practice may lay the foundations for effective workforce planning in a dynamic context. Nurses who align with APN defining criteria are working mainly in large acute services without regulation and recognition.

Implications for nursing

Advanced practice nurses show the value of their role and activities in healthcare services.

Implications for health policy

Promoting the establishment of APN defining criteria that includes credentialing and a regulatory framework within international guidelines should be a priority to make an impact on healthcare policy.
Hospital nurses' moral distress and mental health during COVID‐19
Authors: Lake Eileen T. , Narva Aliza M. , Holland Sara , Smith Jessica G. , Cramer Emily , Rosenbaum Kathleen E. Fitzpatrick , French Rachel , Clark Rebecca R. S. , Rogowski Jeannette A.
Published: August 2021

Aims

To explore factors associated with nurses' moral distress during the first COVID‐19 surge and their longer‐term mental health.

Design

Cross‐sectional, correlational survey study.

Methods

Registered nurses were surveyed in September 2020 about their experiences during the first peak month of COVID‐19 using the new, validated, COVID‐19 Moral Distress Scale for Nurses. Nurses' mental health was measured by recently experienced symptoms. Analyses included descriptive statistics and regression analysis. Outcome variables were moral distress and mental health. Explanatory variables were frequency of COVID‐19 patients, leadership communication and personal protective equipment/cleaning supplies access. The sample comprised 307 nurses (43% response rate) from two academic medical centres.

Results

Many respondents had difficulty accessing personal protective equipment. Most nurses reported that hospital leadership communication was transparent, effective and timely. The most distressing situations were the transmission risk to nurses' family members, caring for patients without family members present, and caring for patients dying without family or clergy present. These occurred occasionally with moderate distress. Nurses reported 2.5 days each in the past week of feeling anxiety, withdrawn and having difficulty sleeping. Moral distress decreased with effective communication and access to personal protective equipment. Moral distress was associated with longer‐term mental health.

Conclusion

Pandemic patient care situations are the greatest sources of nurses' moral distress. Effective leadership communication, fewer COVID‐19 patients, and access to protective equipment decrease moral distress, which influences longer‐term mental health.

Impact

Little was known about the impact of COVID‐19 on nurses' moral distress. We found that nurses' moral distress was associated with the volume of care for infected patients, access to personal protective equipment, and communication from leaders. We found that moral distress was associated with longer‐term mental health. Leaders should communicate transparently to decrease nurses' moral distress and the negative effects of global crises on nurses' longer‐term mental health.
Colonizing the Caribbean: New geological data and an updated land‐vertebrate colonization record challenge the GAARlandia land‐bridge hypothesis
Authors: Ali Jason R. , Hedges S. Blair
Published: August 2021

Over the past three decades, the hypothesized mid‐Cenozoic GAARlandia walkway (34 ± 1 Ma) has featured prominently in discussions on Caribbean biogeography. However, a fundamental issue has been a lack of geological and geophysical data from the Aves Ridge with which to evaluate the proposal. Consequently, opinions have been based purely on biological data, mainly from molecular‐clock studies but also from fossils and taxonomic composition. For whatever reasons, a polarization of views has occurred; some champion the land‐bridge to explain the colonizations of the island group, whereas others prefer over‐water dispersal. We examine the hypothesis drawing upon an updated compilation of land‐vertebrate colonizations (35 clades: 6 amphibian, 6 mammal and 23 reptile) plus a newly published geological study of the Aves Ridge and the adjacent Grenada Basin (to the east). The former indicates that the colonizations were heavily filtered and assembled in a piecemeal fashion consistent with over‐water dispersal; a mid‐Cenozoic ecological corridor would likely have led to a richer assemblage with a wider variety of components. The latter, which draws upon drill‐core and seismic data, indicates that the southern and central Aves Ridge was submerged at the aforesaid time. With the GAARlandia hypothesis geologically falsified, many biogeographical scenarios that have been proposed for the Greater Antillean biota now require re‐evaluation.
Astragaloside IV ameliorates fat metabolism in the liver of ageing mice through targeting mitochondrial activity
Authors: Luo Zhixiao , Wang Yaqi , Xue Mengzhen , Xia Fangqi , Zhu Leiqi , Li Yuanyang , Jia Dengke , Chen Silong , Xu Guangfu , Lei Yan
Published: August 2021

Astragaloside IV (AST) is a major bioactive compound of Radix Astragali with medical and health benefits. Previous studies have found that AST can reduce the body weights of high‐fat diet fed mice. However, the effect of AST on fat metabolism of ageing mice is unclear. In this study, naturally ageing mice were administered intragastrically with AST at 30 mg/kg/day (ageing + AST‐L group) and 90 mg/kg/day (ageing + AST‐H group) for 16–20 months. Adult (4 months old) and ageing mice were given 1% sodium carboxyl methylcellulose as vehicle. Energy metabolism‐related biological parameters of living mice were examined. Moreover, mRNA and protein levels of key enzymes/proteins involved in triglyceride (TG) lipolysis, fatty acid β‐oxidation (FAO), ketone body (KB) production and mitochondrial respiratory chain were also examined after sacrifice. Results demonstrated that treatment with AST significantly reduced body weight, white fat and liver/body weight ratio of ageing mice, significantly reduced serum/hepatic TG levels, respiratory quotient, promoted fatty acid mobilization in white adipose tissue, mitochondrial FAO and KB production and mitochondrial biosynthesis/functions in the liver of ageing mice. AST also up‐regulated the expression of phosphorylated AMP‐activated protein kinase, acetyl‐CoA carboxylase, acetyl‐coenzyme A synthetase, carnitine palmitoyltransferase 1a/1b, enoyl coenzyme A hydratase‐short chain, acyl‐CoA dehydrogenase medium chain and mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA synthase‐2 involved in fat metabolism. These results indicated that mitochondrial activity could be the target of AST to treat abnormal fat metabolism during ageing.
Plant Metabolic Network 15: A resource of genome‐wide metabolism databases for 126 plants and algae
Authors: Hawkins Charles , Ginzburg Daniel , Zhao Kangmei , Dwyer William , Xue Bo , Xu Angela , Rice Selena , Cole Benjamin , Paley Suzanne , Karp Peter , Rhee Seung Y.
Published: August 2021

To understand and engineer plant metabolism, we need a comprehensive and accurate annotation of all metabolic information across plant species. As a step towards this goal, we generated genome‐scale metabolic pathway databases of 126 algal and plant genomes, ranging from model organisms to crops to medicinal plants (https://plantcyc.org). Of these, 104 have not been reported before. We systematically evaluated the quality of the databases, which revealed that our semi‐automated validation pipeline dramatically improves the quality. We then compared the metabolic content across the 126 organisms using multiple correspondence analysis and found that Brassicaceae, Poaceae, and Chlorophyta appeared as metabolically distinct groups. To demonstrate the utility of this resource, we used recently published sorghum transcriptomics data to discover previously unreported trends of metabolism underlying drought tolerance. We also used single‐cell transcriptomics data from the Arabidopsis root to infer cell type‐specific metabolic pathways. This work shows the quality and quantity of our resource and demonstrates its wide‐ranging utility in integrating metabolism with other areas of plant biology.
Sesamoid bones also show functional adaptation in their microanatomy—The example of the patella in Perissodactyla
Authors: Houssaye Alexandra , de Perthuis Adrien , Houée Guillaume
Published: August 2021

The patella is the largest sesamoid bone of the skeleton. It is strongly involved in the knee, improving output force and velocity of the knee extensors, and thus plays a major role in locomotion and limb stability. However, the relationships between its structure and functional constraints, that would enable a better understanding of limb bone functional adaptations, are poorly known. This contribution proposes a comparative analysis, both qualitative and quantitative, of the microanatomy of the whole patella in perissodactyls, which show a wide range of morphologies, masses, and locomotor abilities, in order to investigate how the microanatomy of the patella adapts to evolutionary constraints. The inner structure of the patella consists of a spongiosa surrounded by a compact cortex. Contrary to our expectations, there is no increase in compactness with bone size, and thus body size and weight, but only an increase in the tightness of the spongiosa. No particular thickening of the cortex associated with muscle insertions is noticed but a strong thickening is observed anteriorly at about mid‐length, where the strong intermediate patellar ligament inserts. The trabeculae are mainly oriented perpendicularly to the posterior articular surface, which highlights that the main stress is anteroposteriorly directed, maintaining the patella against the femoral trochlea. Conversely, anteriorly, trabeculae are rather circumferentially oriented, following the insertion of the patellar ligament and, possibly also, of the quadriceps tendon. A strong variation is observed among perissodactyl families but also intraspecifically, which is in accordance with previous studies suggesting a higher variability in sesamoid bones. Clear trends are nevertheless observed between the three families. Equids have a much thinner cortex than ceratomorphs. Rhinos and equids, both characterized by a development of the medial border, show an increase in trabecular density laterally suggesting stronger stresses laterally. The inner structure in tapirs is more homogeneous despite the absence of medial development of the medial border with no “compensation” of the inner structure, which suggests different stresses on their knees associated with a different morphology of their patellofemoral joint.
Fatty acid synthase mediates high glucose‐induced EGFR activation in oral dysplastic keratinocytes
Authors: Wisniewski David J. , Ma Tao , Schneider Abraham
Published: August 2021

Background

Recent studies point to the epidermal growth factor receptor (EGFR) as a critical mediator of type 2 diabetes mellitus (T2DM)‐induced renal, cardiac, and ocular complications. T2DM is considered a systemic contributing factor in oral carcinogenesis. Similarly, increased EGFR gene copy number and protein expression strongly predict tumor progression. Yet, the impact of hyperglycemia on EGFR activity in oral potentially malignant disorders remains unclear. We recently reported that fatty acid synthase (FASN), a key de novo lipogenic enzyme, mediates EGFR activation in nicotine‐treated oral dysplastic keratinocytes. While in non‐malignant tissues FASN expression is extremely low, it is frequently upregulated in several cancers, including oral squamous cell carcinoma. The present study was carried out to investigate whether high glucose conditions trigger pro‐oncogenic responses in oral dysplastic keratinocytes via FASN‐mediated EGFR activation.

Methods

Cell viability and migration of oral dysplastic keratinocytes were evaluated when exposed to normal (5 mM) or high (20 mM) glucose conditions in the presence of FASN and EGFR inhibitors. Western blotting was also performed to assess changes in FASN protein expression and EGFR activation.

Results

Oral dysplastic keratinocytes exposed to high glucose led to EGFR activation in a FASN‐dependent manner. Likewise, high glucose significantly enhanced cell viability and migration in a FASN/EGFR‐mediated fashion. Notably, EGFR inhibition by the anti‐EGFR monoclonal antibody cetuximab significantly reduced the proliferation of FASN‐overexpressing oral dysplastic keratinocytes.

Conclusion

These novel findings suggest that FASN may act as a key targetable metabolic regulator of glucose‐induced EGFR oncogenic signaling in oral potentially malignant disorders.
A production economic analysis of different stocking density and fry size combinations of milkfish, Chanos chanos, farming in Taiwan
Authors: Lee Yi‐Chung , Lu Yung‐Hsiang , Lee Jie‐Min , Schafferer Christian , Yeh Chun‐Yuan , Chu Tah‐Wei , Huang Yi‐Wei
Published: August 2021

Milkfish, Chanos chanos, is often cultured with white shrimp, Penaeus indicus, to maintain ecological stability and increase profits. This study uses the outputs and cost data of 169 milkfish farmers in Taiwan for the years 2018 and 2019 and applies translog cost function modeling to analyze the production scale economy and input–input demand combinations of two stocking densities (<10,000, ≥10,000 fry/ha) and two fry stocking sizes (2–3 in. and ≥4 in.). The study found that high‐density stocking (≥10,000 fry/ha) of small or large milkfish fry has economies of scale overall. Thus, the average culture cost may be reduced by expanding the scale of milkfish production. High‐density stocking of small fry exhibits a comparatively higher own‐price elasticity of fry. As such, farmers are sensitive to fry price variations. The study also found that labor and capital exhibit the highest substitutability. Capital inputs may thus be increased to mitigate the effects of wage increments. In terms of production, the four observed clusters do not exhibit cost complementarity. Moreover, the survival rate of white shrimp in high‐density stocking milkfish polycultures is relatively low. It is thus recommended to strictly control the stocking density of white shrimp and to minimize the risk of excessively high stocking densities by stocking white shrimp in batches.
Changing epidemiology of liver disease in Asia: Dual infection of HBV and HCV
Authors: Liu Chun‐Jen , Chen Pei‐Jer
Published: August 2021

Transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) is similar regarding the mode of transmission and related risk factors. Therefore, it is not rare to encounter dual HBV/HCV infection in populations at risk of parenteral exposure to hepatitis viruses. Besides, in HBV endemic countries before the era of global HBV vaccination, dual HBV/HCV infection was clinically significant likely because of HCV superinfection over pre‐existing HBsAg carriage. Universal childhood HBV vaccination was implemented worldwide since 1992. Public education programs for prevention of new hepatitis viral infections have been actively promoted recently by World Health Organization. Apart from preventive measures, potent anti‐HBV agents effective in the control of viral replication have been introduced gradually in the past three decades. Direct acting antiviral agents capable of curing HCV infection in more than 97% of patients with chronic hepatitis C have also been widely implemented in the past decade. These interventions will change the epidemiology of new HBV or HCV mono‐infection and dual HBV/HCV infection. Understanding the evolution in the epidemiology of dual HBV/HCV infection is important for evaluation of current public health policy towards infectious disease control in different countries. The changing prevalence of dual HBV/HCV infection in certain Asia‐Pacific countries will be re‐visited based on endemicity of HBV or HCV, as well as in populations at risk of parenteral viral infection.
Diel pCO2 fluctuations alter the molecular response of coral reef fishes to ocean acidification conditions
Authors: Schunter Celia , Jarrold Michael D. , Munday Philip L. , Ravasi Timothy
Published: August 2021

Environmental partial pressure of CO2 (pCO2) variation can modify the responses of marine organisms to ocean acidification, yet the underlying mechanisms for this effect remain unclear. On coral reefs, environmental pCO2 fluctuates on a regular day–night cycle. Effects of future ocean acidification on coral reef fishes might therefore depend on their response to this diel cycle of pCO2. To evaluate the effects on the brain molecular response, we exposed two common reef fishes (Acanthochromis polyacanthus and Amphiprion percula) to two projected future pCO2 levels (750 and 1,000 µatm) under both stable and diel fluctuating conditions. We found a common signature to stable elevated pCO2 for both species, which included the downregulation of immediate early genes, indicating lower brain activity. The transcriptional programme was more strongly affected by higher average pCO2 in a stable treatment than for fluctuating treatments, but the largest difference in molecular response was between stable and fluctuating pCO2 treatments. This indicates that a response to a change in environmental pCO2 conditions is different for organisms living in a fluctuating than in stable environments. This differential regulation was related to steroid hormones and circadian rhythm (CR). Both species exhibited a marked difference in the expression of CR genes among pCO2 treatments, possibly accommodating a more flexible adaptive approach in the response to environmental changes. Our results suggest that environmental pCO2 fluctuations might enable reef fishes to phase‐shift their clocks and anticipate pCO2 changes, thereby avoiding impairments and more successfully adjust to ocean acidification conditions.
Deep learning‐based model for diagnosing Alzheimer's disease and tauopathies
Authors: Koga Shunsuke , Ikeda Akihiro , Dickson Dennis W.
Published: August 2021

Aims

This study aimed to develop a deep learning‐based model for differentiating tauopathies, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick's disease (PiD), based on tau‐immunostained digital slide images.

Methods

We trained the YOLOv3 object detection algorithm to detect five tau lesion types: neuronal inclusions, neuritic plaques, tufted astrocytes, astrocytic plaques and coiled bodies. We used 2522 digital slide images of CP13‐immunostained slides of the motor cortex from 10 cases each of AD, PSP and CBD for training. Data augmentation was performed to increase the size of the training dataset. We next constructed random forest classifiers using the quantitative burdens of each tau lesion from motor cortex, caudate nucleus and superior frontal gyrus, ascertained from the object detection model. We split 120 cases (32 AD, 36 PSP, 31 CBD and 21 PiD) into training (90 cases) and test (30 cases) sets to train random forest classifiers.

Results

The resultant random forest classifier achieved an average test score of 0.97, indicating that 29 out of 30 cases were correctly diagnosed. A validation study using hold‐out datasets of CP13‐ and AT8‐stained slides from 50 cases (10 AD, 17 PSP, 13 CBD and 10 PiD) showed >92% (without data augmentation) and >95% (with data augmentation) diagnostic accuracy in both CP13‐ and AT8‐stained slides.

Conclusion

Our diagnostic model trained with CP13 also works for AT8; therefore, our diagnostic tool can be potentially used by other investigators and may assist medical decision‐making in neuropathological diagnoses of tauopathies.
A case of rheumatoid meningoencephalitis induced by pembrolizumab
Authors: Matsuoka Chika , Omote Yoshio , Kawahara Yuko , Sasaki Ryo , Matsumoto Namiko , Tadokoro Ko , Taira Yuki , Takemoto Mami , Morihara Ryuta , Yamashita Toru , Abe Koji
Published: August 2021

Immune checkpoint inhibitors occasionally cause various side effects, but the occurrence of a severe immune‐related adverse event (irAE) is rare in neurology. We report on a 56‐year‐old woman who suffered from rheumatoid arthritis and recurrent uterine cancer. After treatment with pembrolizumab, she showed visual disturbance followed by acute fever and consciousness disturbance with high‐intensity lesions around the midbrain aqueduct and bilateral caudate heads on FLAIR images of a brain MRI. Her symptoms improved after steroid therapy. However, symptoms relapsed leading to an elevation of the anti‐CCP antibody index. Pembrolizumab‐induced rheumatoid meningoencephalitis was suspected, so additional steroid therapy was provided. This improved her symptoms, turning the anti‐CCP antibody index negative. The present case is the first case of rheumatoid meningoencephalitis induced by pembrolizumab. The combination of MRI findings and elevated anti‐CCP index seems useful for diagnosing rheumatoid meningoencephalitis.
Successful treatment of anti‐GAD antibody‐associated autoimmune cerebellar ataxia with combined immunotherapies
Authors: Omote Yoshio , Matsuoka Chika , Sasaki Ryo , Hishikawa Nozomi , Kawahara Yuko , Nomura Emi , Matsumoto Namiko , Taira Yuki , Takemoto Mami , Morihara Ryuta , Yamashita Toru , Abe Koji
Published: August 2021

Anti‐glutamic acid decarboxylase (GAD) antibody (Ab)‐associated autoimmune cerebellar ataxia (CA) is a rare neurological disorder, and a standardized therapy has not been established. Here, we report on a 58 year‐old man with type 1 diabetes mellitus, who developed progressive CA with high levels of serum and cerebrospinal fluid (CSF) anti‐GAD‐Ab. He was initially treated with intravenous high‐dose methylprednisolone and intravenous immunoglobulin (IVIg), but his CA was gradually worsened. Additional combined immunotherapies with plasma exchange, intravenous cyclophosphamide, and rituximab finally stabilized the progressive CA and suppressed the CSF anti‐GAD‐Ab index. Our case suggests the effectiveness of combined immunotherapies against progressive CA and the usefulness of the CSF anti‐GAD‐Ab index as a therapeutic indicator.
Functions of the SNAI family in chondrocyte‐to‐osteocyte development
Authors: Razmara Ehsan , Bitaraf Amirreza , Karimi Behnaz , Babashah Sadegh
Published: August 2021

Different cellular mechanisms contribute to osteocyte development. And while critical roles for members of the zinc finger protein SNAI family (SNAIs) have been discussed in cancer‐related models, there are few reviews summarizing their importance for chondrocyte‐to‐osteocyte development. To help fill this gap, we review the roles of SNAIs in the development of mature osteocytes from chondrocytes, including the regulation of chondro‐ and osteogenesis through different signaling pathways and in programmed cell death. We also discuss how epigenetic factors—including DNA methylation, histone methylation and acetylation, and noncoding RNAs—contribute differently to both chondrocyte and osteocyte development. To better grasp the important roles of SNAIs in bone development, we also review genotype–phenotype correlations in different animal models. We end with comments about the possible importance of the SNAI family in cartilage/bone development and the potential applications for therapeutic goals.
FOXD1‐AS1 upregulates FOXD1 to promote oral squamous cell carcinoma progression
Authors: Ma Yuxin , Han Jingchao , Luo Xi
Published: August 2021

Objectives

Recently, increasing attention has been concentrated on decrypting the potential of long non‐coding RNAs (lncRNAs) in influencing the progression of human tumors, oral squamous cell carcinoma (OSCC) included. The role of a novel lncRNA, forkhead box D1 antisense RNA 1 (FOXD1‐AS1), has been discussed in multiple cancers. Nevertheless, its function and relevant mechanism in OSCC have been not probed yet.

Materials and methods

FOXD1‐AS1 expression was detected via RT‐qPCR. Colony formation, EdU, transwell and Western blot analyses tested the functional role of FOXD1‐AS1 in OSCC cells. The relationship between RNAs was assessed by a series of mechanical assays.

Results

FOXD1‐AS1 was expressed at a high level in head and neck squamous cell carcinoma (HNSC). Knockdown of FOXD1‐AS1 exerted repressive impacts on OSCC cell proliferation, migration, invasion, and EMT. Moreover, FOXD1‐AS1 positively regulated its nearby gene FOXD1 via interacting with miR‐369‐3p. In addition, adenosine deaminase RNA specific (ADAR), known as a RNA‐binding protein (RBP), was capable to bind with FOXD1‐AS1 and FOXD1 simultaneously, and could regulate the stability of FOXD1 mRNA. Aside from that, rescue assays delineated that FOXD1‐AS1 promoted OSCC progression via upregulating FOXD1.

Conclusions

FOXD1‐AS1 elevates FOXD1 expression to promote OSCC malignant phenotypes through miR‐369‐3p and ADAR.
Temporal changes of local and regional processes in the assembly of herbivorous insect communities
Authors: Shinohara Naoto , Yoshida Takehito
Published: August 2021

Herbivorous insect communities are structured by multiple processes operating locally (e.g. bottom–up effects of plants) and regionally (e.g. dispersal limitation). Although the relative strength of these processes has been well documented, how it varies in time is less understood, especially in relation with the temporal dynamics of plant communities. If temporal turnover of local plant species composition is too rapid for insect community assembly to keep up with, bottom–up effects are expected to be weak. Here, in plant and herbivorous insect communities in Japanese grasslands, we studied how the relative importance of local (bottom–up effects of plants, structures of plant communities and top–down effects of predators) and regional (dispersal limitation) processes varies over the growing season. In addition, we tested the hypothesis that larger temporal turnover of plant species composition is related to the weaker bottom–up effects, that is, the lower explanation power of plant communities for insect communities. We found that, throughout the growing season, the insect species composition was mainly explained by local variables (plant species composition, vegetation height and predator abundance), and their explanation power was higher during later phases of the season (late summer). Furthermore, the variation not explained by plant species composition was correlated with the degree of temporal turnover of plants, suggesting that insect communities failed to track the temporal turnover of plant species. These results were pronounced when we focused on leaf sucker insects, whose host plant range is presumably more limited. We conclude that herbivorous insect communities are mainly regulated by local processes, especially bottom–up effects from plants, while stochasticity may have played a role in early phases of the season. Furthermore, we underscore the importance of considering relative time scale of community assembly and environmental shifts, especially in systems characterized by dynamic changes.