bluuebunny/crossref_metadata_2025 huggingface dataset:
Appy Pie integrated mobile learning: Design and feasibility to help the 3D geometry learning process in the time of Covid 19 pandemic
Authors: Taufan Mochammad , Nurafifah Luthfiyati
Published: September 2021

Banyak penelitian yang mengungkapkan bahwa penggunaan ICT memberikan warna baru dalam interaksi proses pembelajaran. Namun, masih banyak kendala yang dihadapi ketika mengintegrasikan teknologi dalam proses pembelajaran khususnya pembelajaran matematika. Oleh sebab itu, tujuan penelitian ini menyoroti kelayakan dari mobile learning berbantuan Appy Pie pada pembelajaran matematika di masa pandemi Covid 19. Untuk mencapai tujuan tersebut penelitian ini menggunakan desain pengembangan ADDIE yang terdiri dari tahapan-tahapan analisis, pendesainan, pengembangan, implementasi, evaluasi. Pada penelitian ini tahap evaluasi tidak dilakukan karena keterbatasan waktu pelaksanaan. Tahap analisis yang dilakukan yakni analisis masalah dan kebutuhan, analisis ruang lingkup materi, analisis proses integrasi dan pengumpulan bahan pendukung. Selanjutnya untuk tahap pendesainan melakukan proses penyusun desain instruksional, menyusun alur kerja dan alur cerita dan menyiapkan aset-aset elemen pembuatan produk. Tahap pengembangan yakni menghasilkan aplikasi berbantuan Appy Pie materi geometri bangun ruang. Tahap implementasi melakukan proses pengujian internal, penilaian ke ahli media dan ahli materi, uji lapangan. Berdasarkan hasil temuan diperoleh bahwa aplikasi mobile learning terintegrasi Appy Pie layak digunakan untuk pembelajaran geometri di kelas VIII SMP. Oleh karena itu, aplikasi mobile learning terintegrasi Appy Pie memiliki potensi meningkatkan pemahaman geometri siswa sekolah.
Vocal Imitation and Linguistic Processing of Super Mario Theme Music by Yorùbá Gamers
Authors: Akinbo Samuel
Published: September 2021

An aspect of gaming culture among Yorùbá millennials is the linguistic interpretations of the background music that accompanies the popular video game called Super Mario. The themes of the interpretations are comparable to those of music texts at traditional Yorùbá events. Drawing on the Yorùbá tradition, the account is that the gamers assumed that the background music of the game has a similar function as the music at traditional Yorùbá events. The choice of words in the interpretation is conditioned by the situational contexts where the music is heard in the video game. The results of acoustic analyses show that the interpretations are also determined by mapping the pitch trajectories of the music melodies to the tones of the gamers’ language. Notably, the results of this study suggest that the linguistic processing of music may not only involve phonetic iconicity (Steinbeis and Koelsch, 2011) but situational context and social expectation.
Arbeidsinnkludering som en vei til varig arbeidslivstilknytning og et verdig voksenliv: Hvordan metoder for arbeidsinnkludering kan brukes i opplæringen av lærekandidater
Authors: Dyrnes Eva Martinsen , Sträng Dan Roger
Published: September 2021

The labour market in many European countries is changing and for many young people it leads to challenges in gaining a lasting connection to working life.

School dropout and deficiencies in their education lead to challenges for many young people on the road to adulthood. Students who find it difficult to complete a vocational education in upper secondary school, now have the opportunity to be training candidates in a practically oriented education with a limited number of competence goals.

Work inclusion means that the individual's ability to work will be examined in various ways to increase the possibility of permanent work. However, work inclusion is a complex phenomenon, where several actors may be involved and where the goals and progress plan will vary. This is costly and stressful for both the individual and the society. Working life is a central learning arena within upper secondary education, and there will be a need to facilitate participation in this arena also for students with a need for adapted education.
Physics-Aware Deep-Learning-Based Proxy Reservoir Simulation Model Equipped With State and Well Output Prediction
Authors: Coutinho Emilio Jose Rocha , Dall’Aqua Marcelo , Gildin Eduardo
Published: September 2021

Data-driven methods have been revolutionizing the way physicists and engineers handle complex and challenging problems even when the physics is not fully understood. However, these models very often lack interpretability. Physics-aware machine learning (ML) techniques have been used to endow proxy models with features closely related to the ones encountered in nature; examples span from material balance to conservation laws. In this study, we proposed a hybrid-based approach that incorporates physical constraints (physics-based) and yet is driven by input/output data (data-driven), leading to fast, reliable, and interpretable reservoir simulation models. To this end, we built on a recently developed deep learning–based reduced-order modeling framework by adding a new step related to information on the input–output behavior (e.g., well rates) of the reservoir and not only the states (e.g., pressure and saturation) matching. A deep-neural network (DNN) architecture is used to predict the state variables evolution after training an autoencoder coupled with a control system approach (Embed to Control—E2C) along with the addition of some physical components (loss functions) to the neural network training procedure. Here, we extend this idea by adding the simulation model output, for example, well bottom-hole pressure and well flow rates, as data to be used in the training procedure. Additionally, we introduce a new architecture to the E2C transition model by adding a new neural network component to handle the connections between state variables and model outputs. By doing this, it is possible to estimate the evolution in time of both the state and output variables simultaneously. Such a non-intrusive data-driven method does not need to have access to the reservoir simulation internal structure, so it can be easily applied to commercial reservoir simulators. The proposed method is applied to an oil–water model with heterogeneous permeability, including four injectors and five producer wells. We used 300 sampled well control sets to train the autoencoder and another set to validate the obtained autoencoder parameters. We show our proxy’s accuracy and robustness by running two different neural network architectures (propositions 2 and 3), and we compare our results with the original E2C framework developed for reservoir simulation.
Biallelic Mutations in ACACA Cause a Disruption in Lipid Homeostasis That Is Associated With Global Developmental Delay, Microcephaly, and Dysmorphic Facial Features
Authors: Lou Xiaoting , Zhou Xiyue , Li Haiyan , Lu Xiangpeng , Bao Xinzhu , Yang Kaiqiang , Liao Xin , Chen Hanxiao , Fang Hezhi , Yang Yanling , Lyu Jianxin , Zheng Hong
Published: September 2021

Objective

We proposed that the deficit of ACC1 is the cause of patient symptoms including global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. We evaluated the possible disease-causing role of the ACACA gene in developmental delay and investigated the pathogenesis of ACC1 deficiency.

Methods

A patient who presented with global developmental delay with unknown cause was recruited. Detailed medical records were collected and reviewed. Whole exome sequencing found two variants of ACACA with unknown significance. ACC1 mRNA expression level, protein expression level, and enzyme activity level were detected in patient-derived cells. Lipidomic analysis, and in vitro functional studies including cell proliferation, apoptosis, and the migratory ability of patient-derived cells were evaluated to investigate the possible pathogenic mechanism of ACC1 deficiency. RNAi-induced ACC1 deficiency fibroblasts were established to assess the causative role of ACC1 deficit in cell migratory disability in patient-derived cells. Palmitate supplementation assays were performed to assess the effect of palmitic acid on ACC1 deficiency-induced cell motility deficit.

Results

The patient presented with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. A decreased level of ACC1 and ACC1 enzyme activity were detected in patient-derived lymphocytes. Lipidomic profiles revealed a disruption in the lipid homeostasis of the patient-derived cell lines. In vitro functional studies revealed a deficit of cell motility in patient-derived cells and the phenotype was further recapitulated in ACC1-knockdown (KD) fibroblasts. The cell motility deficit in both patient-derived cells and ACC1-KD were attenuated by palmitate.

Conclusion

We report an individual with biallelic mutations in ACACA, presenting global development delay. In vitro studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate.
Effect of Melatonin for Regulating Mesenchymal Stromal Cells and Derived Extracellular Vesicles
Authors: Feng Zi-Yi , Yang Shu-De , Wang Ting , Guo Shu
Published: September 2021

Melatonin is a hormone, synthesized in the pineal gland, which primarily controls the circadian rhythm of the body. In recent years, melatonin has also been shown to regulate metabolism, provide neuroprotection, and act as an anti-inflammatory, free radical scavenger. There has also been a recent research interest in the role of melatonin in regulating mesenchymal stromal cells (MSCs). MSCs are pivotal for their ability to differentiate into a variety of different tissues. There is also increasing evidence for the therapeutic prospects of MSCsviaparacrine signaling. In addition to secreting cytokines and chemokines, MSCs can secrete extracellular vesicles (EVs), allowing them to respond to injury and promote tissue regeneration. While there has been a major research interest in the use of MSCs for regenerative medicine, the clinical application is limited by many risks, including tumorigenicity, senescence, and sensitivity to toxic environments. The use of MSC-derived EVs for cell-free therapy can potentially avoid the disadvantages of MSCs, which makes this an exciting prospect for regenerative medicine. Prior research has shown that MSCs,viaparacrine mechanisms, can identify receptor-independent responses to melatonin and then activate a series of downstream pathways, which exert a variety of effects, including anti-tumor and anti-inflammatory effects. Here we review the synthesis of melatonin, its mechanisms of action, and the effect of melatonin on MSCsviaparacrine signaling. Furthermore, we summarize the current clinical applications of melatonin and discuss future prospects.
Identification of a Novel Prognostic Gene Signature From the Immune Cell Infiltration Landscape of Osteosarcoma
Authors: Fan Lei , Ru Jingtao , Liu Tao , Ma Chao
Published: September 2021

Background: The tumor microenvironment (TME) mainly comprises tumor cells and tumor-infiltrating immune cells mixed with stromal components. Latestresearch hasdisplayed that tumor immune cell infiltration (ICI) is associated with the clinical outcome of patients with osteosarcoma (OS). This work aimed to build a gene signature according to ICI in OS for predicting patient outcomes.

Methods: The TARGET-OS dataset was used for model training, while the GSE21257 dataset was taken forvalidation. Unsupervised clustering was performed on the training cohort based on the ICI profiles. The Kaplan–Meier estimator and univariate Cox proportional hazards models were used to identify the differentially expressed genes between clusters to preliminarily screen for potential prognostic genes. We incorporated these potential prognostic genes into a LASSO regression analysis and produced a gene signature, which was next assessed with the Kaplan–Meier estimator, Cox proportional hazards models, ROC curves, IAUC, and IBS in the training and validation cohorts. In addition, we compared our signature to previous models. GSEAswere deployed to further study the functional mechanism of the signature. We conducted an analysis of 22 TICsfor identifying the role of TICs in the gene signature’s prognosis ability.

Results: Data from the training cohort were used to generate a nine-gene signature. The Kaplan–Meier estimator, Cox proportional hazards models, ROC curves, IAUC, and IBS validated the signature’s capacity and independence in predicting the outcomes of OS patients in the validation cohort. A comparison with previous studies confirmed the superiority of our signature regarding its prognostic ability. Annotation analysis revealed the mechanism related to the gene signature specifically. The immune-infiltration analysis uncoveredkey roles for activated mast cells in the prognosis of OS.

Conclusion: We identified a robust nine-gene signature (ZFP90, UHRF2, SELPLG, PLD3, PLCB4, IFNGR1, DLEU2, ATP6V1E1, and ANXA5) that can predict OS outcome precisely and is strongly linked to activated mast cells.
A Novel Sequential Approach for the Design of Heat Exchanger Networks
Authors: Caballero Jose A. , Pavão Leandro V. , Costa Caliane B. B. , Ravagnani Mauro A. S. S.
Published: September 2021

This paper presents a new algorithm for the design of heat exchanger networks (HEN) that tries to take advantage of the strengths of the sequential and simultaneous approaches. It is divided into two sequential parts. The first one is an adaptation of the transportation model (TransHEN). It maintains the concept of temperature intervals and considers the possibility of heat transfer between all the hot and cold streams inside those intervals, and at the same time it allows the a priori calculation of the logarithmic mean temperature difference between all possible heat exchanges, and therefore it maintains the area estimation linear in the model. The second step (HENDesign model), uses a superstructure that contains all the possible alternatives in which the matches predicted by the first stage model can exchange heat to design the final heat exchanger network. Unlike the sequential approach, in this model, all heat flows, temperatures, areas, etc. are reoptimized maintaining the set of matches predicted in the first stage. The model is highly nonlinear and nonconvex, however, it is relatively easy to get good results, because the model starts with the values predicted by the TransHEN model. The algorithm has been tested using fifteen benchmark problems commonly used in literature to compare the performance of heat exchanger network algorithms. In eleven out of the fifteen cases present better or equal results than the best ones reported in the open literature. In three the results presented only marginal differences in total annualized cost (lower than 0.5%) and only a difference of 2.4% in the largest one.
Plasmonic Imaging of Electrochemical Reactions at Individual Prussian Blue Nanoparticles
Authors: Garcia Adaly , Wang Kinsley , Bedier Fatima , Benavides Miriam , Wan Zijian , Wang Shaopeng , Wang Yixian
Published: September 2021

Prussian blue is an iron-cyanide-based pigment steadily becoming a widely used electrochemical sensor in detecting hydrogen peroxide at low concentration levels. Prussian blue nanoparticles (PBNPs) have been extensively studied using traditional ensemble methods, which only provide averaged information. Investigating PBNPs at a single entity level is paramount for correlating the electrochemical activities to particle structures and will shed light on the major factors governing the catalyst activity of these nanoparticles. Here we report on using plasmonic electrochemical microscopy (PEM) to study the electrochemistry of PBNPs at the individual nanoparticle level. First, two types of PBNPs were synthesized; type I synthesized with double precursors method and type II synthesized with polyvinylpyrrolidone (PVP) assisted single precursor method. Second, both PBNPs types were compared on their electrochemical reduction to form Prussian white, and the effect from the different particle structures was investigated. Type I PBNPs provided better PEM sensitivity and were used to study the catalytic reduction of hydrogen peroxide. Progressively decreasing plasmonic signals with respect to increasing hydrogen peroxide concentration were observed, demonstrating the capability of sensing hydrogen peroxide at a single nanoparticle level utilizing this optical imaging technique.
Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects
Authors: Gómez Inmaculada , Thomas M. Carmen , Palacios Génesis , Egui Adriana , Carrilero Bartolomé , Simón Marina , Valladares Basilio , Segovia Manuel , Carmelo Emma , López Manuel Carlos
Published: September 2021

Infection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multiple immune mechanisms in the host to combat the pathogen. Chagas disease has a variable clinical presentation and progression, producing in the chronic phase a fragile balance between the host immune response and parasite replication that keeps patients in a clinically silent asymptomatic stage for years. Since the parasite is intracellular and replicates within cells, the cell-mediated response of the host adaptive immunity plays a critical role. This function is mainly orchestrated by T lymphocytes, which recognize parasite antigens and promote specific functions to control the infection. However, little is known about the immunological markers associated with this asymptomatic stage of the disease. In this large-scale analysis, the differential expression of 106 immune system-related genes has been analyzed using high-throughput qPCR in T. cruzi antigen-stimulated PBMC from chronic Chagas disease patients with indeterminate form (IND) and healthy donors (HD) from endemic and non-endemic areas of Chagas disease. This analysis revealed that there were no differences in the expression level of most genes under study between healthy donors from endemic and non-endemic areas determined by PCA and differential gene expression analysis. Instead, PCA revealed the existence of different expression profiles between IND patients and HD (p < 0.0001), dependent on the 32 genes included in PC1. Differential gene expression analysis also revealed 23 upregulated genes (expression fold change > 2) and 11 downregulated genes (expression fold change < 0.5) in IND patients versus HD. Enrichment analysis showed that several upregulated genes in IND patients participate in relevant immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, and cytokine-inflammatory response. The antigen-specific differential gene expression profile detected in these patients and the relevant immunological pathways that seem to be activated could represent potential biomarkers of the asymptomatic form of Chagas disease, helpful to diagnosis and infection control.
An Innovative Protocol for Metaproteomic Analyses of Microbial Pathogens in Cystic Fibrosis Sputum
Authors: Graf Alexander C. , Striesow Johanna , Pané-Farré Jan , Sura Thomas , Wurster Martina , Lalk Michael , Pieper Dietmar H. , Becher Dörte , Kahl Barbara C. , Riedel Katharina
Published: September 2021

Hallmarks of cystic fibrosis (CF) are increased viscosity of mucus and impaired mucociliary clearance within the airways due to mutations of the cystic fibrosis conductance regulator gene. This facilitates the colonization of the lung by microbial pathogens and the concomitant establishment of chronic infections leading to tissue damage, reduced lung function, and decreased life expectancy. Although the interplay between key CF pathogens plays a major role during disease progression, the pathophysiology of the microbial community in CF lungs remains poorly understood. Particular challenges in the analysis of the microbial population present in CF sputum is (I) the inhomogeneous, viscous, and slimy consistence of CF sputum, and (II) the high number of human proteins masking comparably low abundant microbial proteins. To address these challenges, we used 21 CF sputum samples to develop a reliable, reproducible and widely applicable protocol for sputum processing, microbial enrichment, cell disruption, protein extraction and subsequent metaproteomic analyses. As a proof of concept, we selected three sputum samples for detailed metaproteome analyses and complemented and validated metaproteome data by 16S sequencing, metabolomic as well as microscopic analyses. Applying our protocol, the number of bacterial proteins/protein groups increased from 199-425 to 392-868 in enriched samples compared to nonenriched controls. These early microbial metaproteome data suggest that the arginine deiminase pathway and multiple proteases and peptidases identified from various bacterial genera could so far be underappreciated in their contribution to the CF pathophysiology. By providing a standardized and effective protocol for sputum processing and microbial enrichment, our study represents an important basis for future studies investigating the physiology of microbial pathogens in CF in vivo – an important prerequisite for the development of novel antimicrobial therapies to combat chronic recurrent airway infection in CF.
Ratemaking as Climate Adaptation Governance
Authors: Monast Jonas J.
Published: September 2021

Electric utilities are directly affected by, and in some cases are a source of, many pressing climate adaptation challenges: wildfires, vulnerable infrastructure, extreme storms, and drought. The state Public Utilities Commission (PUC) is one of the most consequential government agencies guiding the electricity sector's response to climate change. Rate-regulated utilities may not charge ratepayers for new capital investments without PUC approval. When PUCs decide which costs are eligible for rate recovery, they also define which risks utilities seek to manage and which hedging strategies they use to do so. This Article argues that the foundational principles of ratemaking allow the state PUC to manage many aspects of electricity sector adaptation planning, coordination, and implementation. The Article begins with an overview of ratemaking for electric utilities and identifies how the process is an exercise in risk management. The Article then explains how a risk governance perspective can position the PUC to explicitly incorporate climate adaptation into ratemaking procedures as well as help coordinate adaptation policy across multiple agencies.
Neuroscientific Research on the Processing of Easy Language
Authors: Borghardt Liv , Deilen Silvana , Fuchs Julia , Gros Anne-Kathrin , Hansen-Schirra Silvia , Nagels Arne , Schiffl Laura , Sommer Johanna
Published: September 2021

In an increasingly networked world, people who cannot participate in written communication are particularly at risk of social exclusion. Like other concepts of barrier-free communication, Easy Language (“Leichte Sprache”) attempts to enhance perceptibility and comprehensibility of texts for people with reading impairments by means of a rule-based reduction of complexity on the text side. The underlying assumption of simplified languages is that the reduction of linguistic complexity correspondingly reduces cognitive processing costs. However, this interplay between linguistic complexity and cognitive processing costs still needs to be investigated by empirical research as up to date there are only a few studies investigating the perception and reception of Easy Language, mostly using offline methods (e.g., questionnaires or retrospective interviews). In contrast to offline methods, which are only capable of assessing comprehension products, online methods allow researchers to track what a participant is focusing their attention on at any given time and to thereby develop a detailed representation of the time-course of cognitive language processing. In our paper, we aim to point out how different online methods (eye-tracking, EEG and fMRI) can be used for investigating the empirical validity of the postulated rules for Easy Language by evaluating cognitive processing efficiency. Besides discussing the applicability of those neuroscientific online methods in Easy Language research, we discuss the importance of collecting personal and neuropsychological data to gain detailed profiles of the participants and therefore not only contribute to the explanation of variance but furthermore to determine the role of neuropsychological skills on reading proficiency. For each online method we elaborate basic principles, discuss some of the main findings in cognitive sciences and demonstrate the greatest advantages but also restrictions of the method and challenges related to the data collection process with impaired participants. Furthermore, we outline current challenges in Easy Language research and summarize remaining research gaps. On a final note, we emphasize that it is both the establishment of online methods and the data triangulation in Easy Language research that enable researchers to gain a profound insight into the cognitive processing of simplified languages.
Digital Therapeutics: Exploring the Possibilities of Digital Intervention for Myopia
Authors: Lee Yong Sun , Choi Seung Eun , Hahm Jarang , Kim Myoung Joon , Bae Hyo Sook , Yi Kayoung , Lim Hyun Taek , Hyon Joon Young
Published: September 2021

Pediatric myopia is increasing globally and has become a major public health issue. However, the mechanism of pediatric myopia is still poorly understood, and there is no effective treatment to prevent its progression. Based on results from animal and clinical studies, certain neuronal–humoral factors (NHFs), such as IGF-1, dopamine, and cortisol may be involved in the progression of pediatric myopia. Digital therapeutics uses evidence-based software as therapeutic interventions and it has the potential to offer innovative treatment strategies for pediatric myopia beyond conventional treatment methods. In this perspective article, we introduce digital therapeutics SAT-001, a software algorithm that modulates the level of NHFs to reduce the progression of pediatric myopia. The proposed mechanism is based on a theoretical hypothesis derived from scientific research and clinical studies and will be further confirmed by evidence generated from clinical studies involving pediatric myopia.
Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship
Authors: Henry Michelle , Thomas Kevin Garth Flusk , Ross Ian Louis
Published: September 2021

Sleep is a critical biological process, essential for cognitive well-being. Neuroscientific literature suggests there are mechanistic relations between sleep disruption and memory deficits, and that varying concentrations of cortisol may play an important role in mediating those relations. Patients with Addison’s disease (AD) experience consistent and predictable periods of sub- and supra-physiological cortisol concentrations due to lifelong glucocorticoid replacement therapy, and they frequently report disrupted sleep and impaired memory. These disruptions and impairments may be related to the failure of replacement regimens to restore a normal circadian rhythm of cortisol secretion. Available data provides support for existing theoretical frameworks which postulate that in AD and other neuroendocrine, neurological, or psychiatric disorders, disrupted sleep is an important biological mechanism that underlies, at least partially, the memory impairments that patients frequently report experiencing. Given the literature linking sleep disruption and cognitive impairment in AD, future initiatives should aim to improve patients’ cognitive performance (and, indeed, their overall quality of life) by prioritizing and optimizing sleep. This review summarizes the literature on sleep and cognition in AD, and the role that cortisol concentrations play in the relationship between the two.
Latent Adrenal Insufficiency: From Concept to Diagnosis
Authors: Younes Nada , Bourdeau Isabelle , Lacroix Andre
Published: September 2021

Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of autoimmune origin, resulting in glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies. Initial signs and symptoms can be nonspecific, contributing to late diagnosis. Loss of zona glomerulosa function may precede zona fasciculata and reticularis deficiencies. Patients present with hallmark manifestations including fatigue, weight loss, abdominal pain, melanoderma, hypotension, salt craving, hyponatremia, hyperkalemia, or acute adrenal crisis. Diagnosis is established by unequivocally low morning serum cortisol/aldosterone and elevated ACTH and renin concentrations. A standard dose (250 µg) Cosyntropin stimulation test may be needed to confirm adrenal insufficiency (AI) in partial deficiencies. Glucocorticoid and mineralocorticoid substitution is the hallmark of treatment, alongside patient education regarding dose adjustments in periods of stress and prevention of acute adrenal crisis. Recent studies identified partial residual adrenocortical function in patients with AI and rare cases have recuperated normal hormonal function. Modulating therapies using rituximab or ACTH injections are in early stages of investigation hoping it could maintain glucocorticoid residual function and delay complete destruction of adrenal cortex.
Endogenous Glucocorticoid Metabolism in Bone: Friend or Foe
Authors: Martin Claire S. , Cooper Mark S. , Hardy Rowan S.
Published: September 2021

The role of tissue specific metabolism of endogenous glucocorticoids (GCs) in the pathogenesis of human disease has been a field of intense interest over the last 20 years, fuelling clinical trials of metabolism inhibitors in the treatment of an array of metabolic diseases. Localised pre-receptor metabolism of endogenous and therapeutic GCs by the 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes (which interconvert endogenous GCs between their inactive and active forms) are increasingly recognised as being critical in mediating both their positive and negative actions on bone homeostasis. In this review we explore the roles of endogenous and therapeutic GC metabolism by the 11β-HSD enzymes in the context of bone metabolism and bone cell function, and consider future strategies aimed at modulating this system in order to manage and treat various bone diseases.
Insulin Resistance Adversely Affect IVF Outcomes in Lean Women Without PCOS
Authors: Wang Haoyu , Zhang Yu , Fang Xuhui , Kwak-Kim Joanne , Wu Li
Published: September 2021

Objective

To investigate the effects of insulin resistance (IR) on IVF outcomes and a potential underlying mechanism in lean women without PCOS.

Design

A prospective cohort study at the University Clinic.

Setting

IVF center at the University setting.

Patients

A total of 155 lean women (body mass index <25) without PCOS undergoing IVF cycle.

Intervention

Patients were allocated to IR and non-IR groups based on HOMA-M120.

Main Outcome Measure(s)

IVF outcomes, including egg quality, the percentage of mature oocytes, fertilization rate, blastocyst formation rate, advanced embryo rate, and cumulative live birth rate were investigated. Auto-immune parameters, peripheral blood immunophenotypes, thyroid hormone, homocysteine, and 25-OH-vitamin D3 (25-OH-VD3) levels were analyzed.

Results

The percentage of mature oocytes and blastocyst formation rate were significantly lower in the IR group as compared with those of the non-IR group (p<0.05, respectively). The proportion of peripheral blood CD19+ B cells was significantly higher in the IR group than those of the non-IR group (p<0.05). Homocysteine, 25-OH-VD3, and auto-immune parameters were the same between the two groups.

Conclusion

In lean infertile women without PCOS, IR is associated with the decreased percentage of mature eggs and poor embryo quality in which B cell immunity may play a role.
A New Non-invasive Method for Collecting DNA From Small Mammals in the Field, and Its Application in Simultaneous Vector and Disease Monitoring in Brushtail Possums
Authors: Emami-Khoyi Arsalan , Agnew Thomas W. , Adair Matthew G. , Murphy Elaine C. , Benmazouz Isma , Monsanto Daniela M. , Parbhu Shilpa P. , Main Devon C. , Le Roux Rynhardt , Golla Tirupathi Rao , Schnelle Claudia , Alizadeh Hossein , Csányi Sándor , Heltai Miklòs , Jansen van Vuuren Bettine , Paterson Adrian M. , Teske Peter R. , Ross James G.
Published: September 2021

Large-scale monitoring of wild populations in remote areas using traditional live-capturing methods is logistically and financially challenging. Devices that can be used to obtain biological material remotely and store it for an extended period have considerable potential to monitor population densities and health status, but their applicability remains largely unexplored. The present study describes a device that collects trace amounts of DNA from the saliva of small mammals that is deposited on the surface of a collection medium (WaxTags®). The device’s performance was evaluated on Australian brushtail possums (Trichosurus vulpecula), an invasive pest species and the most significant vector of bovine tuberculosis infective agent (Mycobacterium bovis), under field conditions in Canterbury, New Zealand. The retrieved DNA was used to amplify eight possum-specific microsatellite markers and bacterial 16S rRNA. The design is mechanically robust, and the quality of the recovered DNA was adequate for microsatellite-based identification of individual possums, estimation of population density, and partial reconstruction of their oral microbiomes as a potential indicator of health. Several medically important bacteria, including strains of environmental Mycobacterium sp., were detected. The design can be refined to monitor other animals’ populations proactively and provide different levels of information necessary to manage wild populations.
Relationships Among Trophic Niche Width, Morphological Variation, and Genetic Diversity of Hemiculter leucisculus in China
Authors: Li Wenjing , Zhai Dongdong , Wang Chunling , Gao Xin , Liu Huanzhang , Cao Wenxuan
Published: September 2021

According to the niche variation hypothesis (NVH), the populations with wider niches are phenotypically more variable than those with narrow niches. Giller expanded the NVH, suggesting that the niche width, morphological variation, and genetic diversity are all positively correlated. However, the hypothesis has been a subject of debate and discussion. In the present study, the NVH was tested by analyzing the relationships among trophic niche width, morphological variation, and genetic diversity of Hemiculter leucisculus, a widespread cyprinid fish. The fish samples were collected from six sites across Haihe, the Yellow, and the Yangtze River basins in China. The relationships among trophic niche width, morphological variation, and genetic diversity were analyzed using Pearson correlation at the inter-population level. Our analysis indicated that trophic niche width is significantly positively correlated with morphological variation, which corroborates the NVH. Morphological variation was significantly correlated to genetic diversity. However, no relationship was observed between trophic niche width and genetic diversity. We inferred that the dietary niche of H. leucisculus might change due to the plastic response toward environmental changes rather than due to the genetic variation. We also suggest that the effects of environment and heredity on the niche of the freshwater fish should be quantified separately in further studies.
The Emerging Role of Non-coding RNAs in Drug Resistance of Ovarian Cancer
Authors: Lan Hua , Yuan Jing , Zeng Da , Liu Chu , Guo Xiaohui , Yong Jiahui , Zeng Xiangyang , Xiao Songshu
Published: September 2021

Ovarian cancer is one of the most common gynecological malignancies with highest mortality rate among all gynecological malignant tumors. Advanced ovarian cancer patients can obtain a survival benefit from chemotherapy, including platinum drugs and paclitaxel. In more recent years, the administration of poly-ADP ribose polymerase inhibitor to patients with BRCA mutations has significantly improved the progression-free survival of ovarian cancer patients. Nevertheless, primary drug resistance or the acquisition of drug resistance eventually leads to treatment failure and poor outcomes for ovarian cancer patients. The mechanism underlying drug resistance in ovarian cancer is complex and has not been fully elucidated. Interestingly, different non-coding RNAs (ncRNAs), such as circular RNAs, long non-coding RNAs and microRNAs, play a critical role in the development of ovarian cancer. Accumulating evidence has indicated that ncRNAs have important regulatory roles in ovarian cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically highlight the emerging roles and the regulatory mechanisms by which ncRNAs affect ovarian cancer chemoresistance. Additionally, we suggest that ncRNAs can be considered as potential diagnostic and prognostic biomarkers as well as novel therapeutic targets for ovarian cancer.
Validation of a 6-Dye Short Tandem Repeat System: A Dry Kit With Lyophilized Amplification Reagent
Authors: Li Shuanglin , Lin Jinfeng , Hao Honglei , Jin Haiying , Song Danlu , Zhu Bofeng
Published: September 2021

The SureID®S6 system used a lyophilized pellet as the amplification reagent to enable multiplexing of sex-determining marker Amelogenin, 21 autosomal short tandem repeats (STRs), and one Y-STR. To assess the performance, reliability, and limitation of the dry amplification system, the validation studies including PCR condition, reproducibility, sizing and precision, analytical threshold calculation, sensitivity and stochastic threshold calculation, species specificity, stability, mixture, case sample, and population and concordance were conducted according to the Scientific Working Group on DNA Analysis Methods (SWGDAM) Validation Guidelines. Experimental data suggested that the optimal range of total input DNA was from 125 to 500 pg; the appropriate analytical threshold was 80 relative fluorescence units (RFUs) while the stochastic threshold was 260 RFUs; for the stability studies, SureID®S6 system could resist against less than 500 μmol/L of hematin, 100 ng/μl of humic acid, 4 mM of indigotin, 800 mM of tannic acid, and 800 mM of calcium ion. Population and concordance studies using 500 unrelated individuals showed that the combined probability of discrimination (CPD) and cumulative probability of exclusion (CPE) values were 0.999999999999 and 0.999999998416, respectively. The genotypes for the same sample were concordant with the previously validated HUAXIA™ Platinum kit. The validation results demonstrated that the SureID®S6 system could be used for forensic applifications.
Crosstalk Between Intestinal Microbiota Derived Metabolites and Tissues in Allogeneic Hematopoietic Cell Transplantation
Authors: Fujiwara Hideaki
Published: September 2021

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an evidence based- cellular immunotherapy for hematological malignancies. Immune reactions not only promote graft-versus-tumor effects that kill hematological malignant cells but also graft-versus-host disease (GVHD) that is the primary complication characterized by systemic organ damages consisting of T-cells and antigen presenting cells (APCs) activation. GVHD has long been recognized as an immunological reaction that requires an immunosuppressive treatment targeting immune cells. However immune suppression cannot always prevent GVHD or effectively treat it once it has developed. Recent studies using high-throughput sequencing technology investigated the impact of microbial flora on GVHD and provided profound insights of the mechanism of GVHD other than immune cells. Allo-HSCT affects the intestinal microbiota and microbiome-metabolome axis that can alter intestinal homeostasis and the severity of experimental GVHD. This axis can potentially be manipulatedviadietary intervention or metabolites produced by intestinal bacteria affected post-allo-HSCT. In this review, we discuss the mechanism of experimental GVHD regulation by the complex microbial community-metabolites-host tissue axis. Furthermore, we summarize the major findings of microbiome-based immunotherapeutic approaches that protect tissues from experimental GVHD. Understanding the complex relationships between gut microbiota-metabolites-host tissues axis provides crucial insight into the pathogenesis of GVHD and advances the development of new therapeutic approaches.
Impact of Toll-Like Receptor-Specific Agonists on the Host Immune Response to the Yersinia pestis Plague rF1V Vaccine
Authors: Biryukov Sergei , Dankmeyer Jennifer L. , Shamsuddin Zain , Velez Ivan , Rill Nathaniel O. , Rosario-Acevedo Raysa , Klimko Christopher P. , Shoe Jennifer L. , Hunter Melissa , Ward Michael D. , Cazares Lisa H. , Fetterer David P. , Bozue Joel A. , Worsham Patricia L. , Cote Christopher K. , Amemiya Kei
Published: September 2021

Relatively recent advances in plague vaccinology have produced the recombinant fusion protein F1-V plague vaccine. This vaccine has been shown to readily protect mice from both bubonic and pneumonic plague. The protection afforded by this vaccine is solely based upon the immune response elicited by the F1 or V epitopes expressed on the F1-V fusion protein. Accordingly, questions remain surrounding its efficacy against infection with non-encapsulated (F1-negative) strains. In an attempt to further optimize the F1-V elicited immune response and address efficacy concerns, we examined the inclusion of multiple toll-like receptor agonists into vaccine regimens. We examined the resulting immune responses and also any protection afforded to mice that were exposed to aerosolizedYersinia pestis. Our data demonstrate that it is possible to further augment the F1-V vaccine strategy in order to optimize and augment vaccine efficacy.
Seasonal Variations in the Biodiversity, Ecological Strategy, and Specialization of Diatoms and Copepods in a Coastal System With Phaeocystis Blooms: The Key Role of Trait Trade-Offs
Authors: Breton Elsa , Christaki Urania , Sautour Benoit , Demonio Oscar , Skouroliakou Dimitra-Ioli , Beaugrand Gregory , Seuront Laurent , Kléparski Loïck , Poquet Adrien , Nowaczyk Antoine , Crouvoisier Muriel , Ferreira Sophie , Pecqueur David , Salmeron Christophe , Brylinski Jean-Michel , Lheureux Arnaud , Goberville Eric
Published: September 2021

Although eutrophication induced by anthropogenic nutrient enrichment is a driver of shifts in community composition and eventually a threat to marine biodiversity, the causes and consequences on ecosystem functioning remain greatly unknown. In this study, by applying a trait-based approach and measuring niche breadth of diatoms and copepods, the drivers and underlying mechanisms of the seasonal species succession of these ecological communities in a coastal system dominated in spring by Phaeocystis blooms were explored. It is suggested that the seasonal succession of diatoms and copepods is the result of several trade-offs among functional traits that are controlled by the seasonal abiotic and biotic pressure encountered by the plankton communities. The results of this study highlight that a trade-off between competition and predator, i.e., weak competitors are better protected against predation, plays an important role in promoting plankton species richness and triggers the Phaeocystis bloom. As often observed in eutrophicated ecosystems, only the biotic homogenization of the copepod community and the shift in the diet of copepods toward Phaeocystis detrital materials have been detected during the Phaeocystis bloom. The diatom and copepod communities respond synchronously to fluctuating resources and biotic conditions by successively selecting species with specific traits. This study confirms the key role of competition and predation in controlling annual plankton succession.
Prevalence of Stony Coral Tissue Loss Disease at El Seco, a Mesophotic Reef System off Vieques Island, Puerto Rico
Authors: Williams Stacey M. , García-Sais Jorge , Sabater-Clavell Jorge
Published: September 2021

Mesophotic coral ecosystems (MCEs) are ecologically and functionally vital, as they are Essential Fish Habitats that function as refugia for corals and sponges of shallow-water reefs. Stony Coral Tissue Loss Disease (SCTLD) is a relatively new lethal coral disease, first affecting coral reefs in Florida and has now spread through most of the Caribbean. SCTLD was observed in Puerto Rico in December 2019 in Culebra Island. Since then, SCTLD has appeared along the east coast of Puerto Rico, affecting primarily shallow reefs in San Juan, Culebra and Vieques Island, and Fajardo. During late June and July 2020, four mesophotic reef habitats were surveyed at El Seco (off Vieques Island), on the southeast coast of Puerto Rico. SCTLD was observed at colonized pavement (CPRT – 23–30 m), bank coral reef (BCR – 35–40 m), patch coral reef (PCR – 36–42 m), and rhodolith (Rhodo – 40–50 m) habitats. The mean percent substrate cover by sessile-benthic categories varied significantly between habitats (PERMANOVA, p < 0.001), with a higher mean (± SE) coral cover at BCR (26.95 ± 5.60%), followed by PCR (12.88 ± 3.88%). SCTLD was detected in all habitats, but the disease prevalence was significantly higher at BCR, ranging from 9.70 to 21.13% of colonies infected (Kruskal-Wallis ANOVA, p < 0.007). Even though PCR habitats exhibited less coral cover, SCTLD prevalence was still elevated ranging from 6.66 to 15.07%. The deepest record of SCTLD at El Seco was 40.9 m. The majority (∼98%) of the corals infected with the disease were from the Orbicella complex spp. (faveolata/franksi). However, there were other infected species, such as Agaricia grahamae, A. lamarcki, Montastraea cavernosa, and Porites astreoides. As seen in the surveys conducted in 2011 and 2020, the loss of coral cover allows for the emergence of other benthic “detractors,” such as peyssonnelids, specifically Ramicrusta spp. Ramicrusta spp., an aggressive encrusting red alga known to take over available space and overgrow corals, significantly increased its substrate cover at the impacted reefs. Therefore, the severity and virulence of SCTLD will most likely have severe and long-lasting negative impacts on the coral communities at El Seco mesophotic reef system.