bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive report of the National Coordinated Varietal Trial (NCVT) of Cotton conducted during 2019-20 in National Cotton Varietal Testing Program
Authors: Ahsan Muhammad Zahir
Published: March 2021

One hundred and two cotton cultivars, developed by the different scientists were grouped in four sets and tested at six locations in Punjab, four locations in Sindh, three locations in Balochistan and one location in KPK to test the adaptability of seed cotton yield. The quantitative and qualitative analysis of Bt toxin of these cultivars were conducted at four designated labs. The results revealed highly significant differences among the cultivars for seed cotton yield per hectare. In Set-A top performance cultivar is Saim-102 (2519kgha-1) followed by the Tahafuz 12 (2350kgha-1), in set-B Rustram-11 (2655kgha-1) and BF-1 (2288kgha-1) perform best as compared to the other cultivars. In Set–C cultivar, NIAB-1011 (2604kgha-1) and GH-Uhad (2531kgha-1) out yield the all other cultivars and in Set-D cultivar, Bt-CIM-775 (2588kgha-1) and Sahara-Klean-5 (2508kgha-1) surpass the yield from other candidate cultivars. Overall top varieties in Punjab, Sindh, Balochistan and National level were Rustam-11 (2484kgha-1), Sahara-Klean-5 (2714kgha-1), Diamon-2 (3742kgha-1), GH-Hamaliya (2594kgha-1), Rustam-11 (2655kgha-1),The average trait purity for BG-I (Cry1Ac) was 25 to 100%, for BG-II (Cry1Ac and Cry2Ab) none of the variety observed positive and for BG-III (Cry1Ac, Cry2Ab and RR) trait purity was 57 to 100%.
Yield and some agronomic parameters of upland cotton as affected by planting dates
Authors: Lashari Waqas Ahmed , Naimatullah Salma , Afzal Hamza
Published: March 2021

A field experiment was conducted at ICI Research Farm, Multan to evaluate the effect of different sowing dates on plant height, number of monopodia, number of sympodia, number of bolls per plant, boll weight, seed cotton yield kg/ha of two upland cotton varieties (ICI-2121 and ICI-2424) developed by ICI Pakistan Limited, Multan against a standard check variety IUB-2013 during 2019, and 2020 years.  These varieties were planted on 1st April, 15th April, 1st May, 15th May, 1st June, and 15th June, at ICI Cotton Research Station, 19-Kasi Vehari Road, Multan.  Results revealed that statistically highly significant differences in planting dates were observed for all the parameters studied except number of monopodial branches and boll weight which depicted non-significant differences. Regarding varieties and interaction between varieties and planting times, similar trend of statistical differences was observed. As regards to planting dates, generally, all the parameters under study showed their maximum performance when crop was planted on 1st May followed by 1st April planting date, whereas, minimum performance of the parameters was recorded when the crop was planted on 15th June followed by 1st June. Regarding varietal performance, on an average, maximum plant height (146cm) was observed in ICI-2121 followed by IUB-2013. Same trend of performance of varieties regarding number of monopodia and sympodia per plant was observed.  Regarding average number of bolls per plant in different varieties, it was observed that ICI-2121 produced maximum (32 bolls) followed by ICI-2424 (31 bolls) and IUB-2013 (28 bolls) irrespective of planting dates. The same trend of varietal performance regarding boll weight was recorded. When seed cotton yield (kg/ha) was evaluated, on an average of varieties, ICI-2121 produced maximum seed cotton yield (1228 kg/ha) followed by ICI-2424 and IUB-2013 which produced 1147 and 1046 kg/ha seed cotton yield respectively irrespective of planting dates. It was concluded that under agro-climatic conditions of Multan, 1st May planting date was evaluated as optimum cotton sowing time. Before or after 1st May, this study does not recommend growing cotton in this particular zone.  Among cotton varieties, ICI-2121 is recommended for sowing under this planting time being producing higher yields.
Extracellular Matrix Proteins Confer Cell Adhesion-Mediated Drug Resistance Through Integrin αv in Glioblastoma Cells
Authors: Yu Qi , Xiao Weikun , Sun Songping , Sohrabi Alireza , Liang Jesse , Seidlits Stephanie K.
Published: March 2021

Chemotherapy resistance to glioblastoma (GBM) remains an obstacle that is difficult to overcome, leading to poor prognosis of GBM patients. Many previous studies have focused on resistance mechanisms intrinsic to cancer cells; the microenvironment surrounding tumor cells has been found more recently to have significant impacts on the response to chemotherapeutic agents. Extracellular matrix (ECM) proteins may confer cell adhesion-mediated drug resistance (CAMDR). Here, expression of the ECM proteins laminin, vitronectin, and fibronectin was assessed in clinical GBM tumors using immunohistochemistry. Then, patient-derived GBM cells grown in monolayers on precoated laminin, vitronectin, or fibronectin substrates were treated with cilengitide, an integrin inhibitor, and/or carmustine, an alkylating chemotherapy. Cell adhesion and viability were quantified. Transcription factor (TF) activities were assessed over time using a bioluminescent assay in which GBM cells were transduced with lentiviruses containing consensus binding sites for specific TFs linked to expression a firefly luciferase reporter. Apoptosis, mediated by p53, was analyzed by Western blotting and immunocytofluorescence. Integrin αv activation of the FAK/paxillin/AKT signaling pathway and effects on expression of the proliferative marker Ki67 were investigated. To assess effects of integrin αv activation of AKT and ERK pathways, which are typically deregulated in GBM, and expression of epidermal growth factor receptor (EGFR), which is amplified and/or mutated in many GBM tumors, shRNA knockdown was used. Laminin, vitronectin, and fibronectin were abundant in clinical GBM tumors and promoted CAMDR in GBM cells cultured on precoated substrates. Cilengitide treatment induced cell detachment, which was most pronounced for cells cultured on vitronectin. Cilengitide treatment increased cytotoxicity of carmustine, reversing CAMDR. ECM adhesion increased activity of NFκB and decreased that of p53, leading to suppression of p53-mediated apoptosis and upregulation of multidrug resistance gene 1 (MDR1; also known as ABCB1 or P-glycoprotein). Expression of Ki67 was correlative with activation of the integrin αv-mediated FAK/paxillin/AKT signaling pathway. EGFR expression increased with integrin αv knockdown GBM cells and may represent a compensatory survival mechanism. These results indicate that ECM proteins confer CAMDR through integrin αv in GBM cells.
ActiveDriverDB: Interpreting Genetic Variation in Human and Cancer Genomes Using Post-translational Modification Sites and Signaling Networks (2021 Update)
Authors: Krassowski Michal , Pellegrina Diogo , Mee Miles W. , Fradet-Turcotte Amelie , Bhat Mamatha , Reimand Jüri
Published: March 2021

Deciphering the functional impact of genetic variation is required to understand phenotypic diversity and the molecular mechanisms of inherited disease and cancer. While millions of genetic variants are now mapped in genome sequencing projects, distinguishing functional variants remains a major challenge. Protein-coding variation can be interpreted using post-translational modification (PTM) sites that are core components of cellular signaling networks controlling molecular processes and pathways. ActiveDriverDB is an interactive proteo-genomics database that uses more than 260,000 experimentally detected PTM sites to predict the functional impact of genetic variation in disease, cancer and the human population. Using machine learning tools, we prioritize proteins and pathways with enriched PTM-specific amino acid substitutions that potentially rewire signaling networks via induced or disrupted short linear motifs of kinase binding. We then map these effects to site-specific protein interaction networks and drug targets. In the 2021 update, we increased the PTM datasets by nearly 50%, included glycosylation, sumoylation and succinylation as new types of PTMs, and updated the workflows to interpret inherited disease mutations. We added a recent phosphoproteomics dataset reflecting the cellular response to SARS-CoV-2 to predict the impact of human genetic variation on COVID-19 infection and disease course. Overall, we estimate that 16-21% of known amino acid substitutions affect PTM sites among pathogenic disease mutations, somatic mutations in cancer genomes and germline variants in the human population. These data underline the potential of interpreting genetic variation through the lens of PTMs and signaling networks. The open-source database is freely available at www.ActiveDriverDB.org.
The Effects of Hemodialysis and Peritoneal Dialysis on the Gut Microbiota of End-Stage Renal Disease Patients, and the Relationship Between Gut Microbiota and Patient Prognoses
Authors: Luo Dan , Zhao Wenbo , Lin Zhiming , Wu Jianhao , Lin Hongchun , Li Yongjie , Song Jun , Zhang Jun , Peng Hui
Published: March 2021

Gut microbiota alterations occur in end-stage renal disease (ESRD) patients with or without dialysis. However, it remains unclear whether changes in gut microbiota of dialysis ESRD patients result from dialysis or ESRD, or both. Similarly, there is a dearth of information on the relationship between gut microbiota and ESRD prognoses. We collected fecal samples and tracked clinical outcomes from 73 ESRD patients, including 33 pre-dialysis ESRD patients, 19 peritoneal dialysis (PD) patients, and 21 hemodialysis (HD) patients. 16S rRNA sequencing and bioinformatics tools were used to analyze the gut microbiota of ESRD patients and healthy controls. Gut microbiota diversity was different before and after dialysis. Bacteroidetes were significantly deceased in HD patients. Twelve bacterial genera exhibited statistically significant differences, due to dialysis (all P < 0.05, FDR corrected). HD reversed abnormal changes in Oscillospira and SMB53 in pre-dialysis patients. Functional predictions of microbial communities showed that PD and HD altered signal transduction and metabolic pathways in ESRD patients. Furthermore, Bacteroides and Phascolarctobacterium were associated with cardiovascular mortality. Dorea, Clostridium, and SMB53 were related to peritonitis in PD patients. This study not only demonstrated differences in gut microbiota between pre-dialysis and dialysis ESRD patients, but also firstly proposed gut bacteria may exert an impact on patient prognosis.
Multimodal Assessment of Vascular and Ventricular Function in Children and Adults With Bicuspid Aortic Valve Disease
Authors: Weismann Constance G. , Ljungberg Sara , Åkesson Anna , Hlebowicz J
Published: March 2021

Background: Bicuspid aortic valve (BAV), the most common congenital cardiac anomaly, has been associated with an aortopathy, increased aortic stiffness and diastolic dysfunction. The involved mechanisms and impact of age remain unclear. It was the aim of this study to characterize arterial and cardiac function, their correlation, and the effect of age in children and adults with a history of BAV.

Methods: Multimodal cardiovascular assessment included echocardiography, ascending aortic distensibility, common carotid intima media thickness [cIMT], parameters of wave reflection [central (cAIx75) and peripheral (pAIx75) augmentation index corrected to a heart rate of 75/min, aging index (AI)], carotid-femoral pulse wave velocity [cfPWV], and endothelial function (EndoPAT). Multivariable linear regression and correlation analyses were performed.

Results: We included 47 BAV patients and 84 controls (age 8–65 years). Ascending aortic stiffness, pulse wave reflection (cAIx75, pAIx75, and AI) and central blood pressure were significantly increased in patients with BAV. However, PWV, cIMT, and endothelial function were not significantly different from controls. BAV patients had marginally reduced diastolic (E': β = −1.5, p < 0.001) but not systolic function compared to controls. Overall, all parameters of arterial stiffness had moderate-strong correlations with diastolic dysfunction and age. In the BAV group, ascending aortic distensibility had the strongest correlation with diastolic dysfunction.

Conclusions: BAV is associated with increased proximal arterial stiffness and wave reflection. However, PWV and cIMT are not increased, and endothelial function is preserved. This suggests that the mechanism of arterial and cardiac stiffening is different from patients with acquired heart diseases.
Developing an Online Tool to Promote Safe Sun Behaviors With Young Teenagers as Co-researchers
Authors: Nguyen Rebecca , Clare Isabelle M. , Gamage Nisali , Alvares Gail A. , Black Lucinda J. , Hart Prue H. , Lucas Robyn M. , Strickland Mark , Jaimangal Mohinder , White James , Gorman Shelley
Published: March 2021

Despite education about the risks of excessive sun exposure, teenagers in Australia are sun-seeking, with sunburn common in summer. Conversely, some regular (time-limited) exposure to sunlight (that avoids sunburn) is necessary for vitamin D and healthy bones and other molecules important for immune and metabolic health. New interventions are thus required to better support teenagers to make healthy and balanced decisions about their sun behaviors. This paper describes the development of a prototype online tool—a smartphone app—that aimed to foster safe sun practices in teenagers. We recruited young adolescents (aged 12–13 years, n = 24) as “co-researchers” to provide ongoing input into the nature and design of the online tool. This age group was selected, as it is a critical time when young people transition from primary education, where “SunSmart” behaviors are entrenched in Australian schools, to high school, where risky behaviors emerge. Through a series of interviews and workshops, we codesigned an Apple iOS smartphone app with the co-researchers, leading health promotion professionals, researchers, and app designers. The developed app, Sun Safe, contains educational content relevant to teenagers about safe sun behaviors, complemented by other features requested by co-researchers and stakeholders to help engage young people, including gamified quizzes to test their sun health knowledge, real-time weather data on the UV Index and temperature, a sunscreen application timer, and reminders to check the UV Index. The developed prototype app was rated well by co-researchers, suggesting it is suitable for further feasibility and efficacy testing as an intervention tool to improve knowledge and promote safe sun behaviors by young adolescents.
Climate Change in Rwanda: The Observed Changes in Daily Maximum and Minimum Surface Air Temperatures during 1961–2014
Authors: Ngarukiyimana Jean Paul , Fu Yunfei , Sindikubwabo Celestin , Nkurunziza Idrissa Fabien , Ogou Faustin Katchele , Vuguziga Floribert , Ogwang Bob Alex , Yang Yuanjian
Published: March 2021

Rwanda has experienced high temperature rising phenomena over the last decades and hence, highly vulnerable to climate change. This paper examined the spatial and temporal variations of daily maximum and minimum surface air temperature (Tmin and Tmax) and diurnal temperature range (DTR). It studied variables at monthly, seasonal and annual time-scales from 1961 to 2014. The study applied various statistical methods such as ordinary least-square fitting, Mann-Kendall, Sen’ slope and Sequential Mann-Kendall statistical test to the new reconstructed ENACTS dataset that cover the period from 1983 to 2014 while pre-1983s recorded data from 24 meteorological stations have been added to complete the lengthiness of ENACTS data. The January to February season did not show a significant trend at seasonal time-scales. The authors decided only to consider March-to-May, June-to-August and October-to-December seasons for further analyses. Topography impacts on temperature classified stations into three regions: region one (R1) (1,000–1,500 m), region two (R2) (1,500–2,000 m) and region three (R3) (≥2,000 m). With high confidence, the results indicate a significant positive trend in both Tmin and Tmax in all three regions during the whole study period. However, the magnitude rate of temperatures change is different in three regions and it varies in seasonal and annual scale. The spatial distributions of Tmax and Tmin represent a siginificant warming trend over the whole country notably since the early 1980s. Surprisingly, Tmin increased at a faster rate than Tmax in R3 (0.27 vs. 0.07°C/decade in March-to-May) and (0.29 vs. 0.04°C/decade in October-to-December), resulting in a significant decrease in the DTR. This is another confirmation of warming in Rwanda. The mutation test application exhibited most of the abrupt changes in the seasonal and annual Tmax and Tmin trends between 1984 and 1990. The present work mainly focus on the spatial and temporal variability of Tmin, Tmax and DTR in Rwanda and their relationship with elevation change, leaving a gap in other potential cause factors explored in the future.
Civic Learning: A Sine Qua Non of Service Learning
Authors: Bringle Robert G. , Clayton Patti H.
Published: March 2021

Civic learning is an essential element of service learning, but one that is often underdeveloped in practice. This article surveys various conceptualizations of civic learning that are in use in higher education around the world, discusses approaches to designing service learning courses to generate civic learning outcomes, and proposes two methods for assessing student attainment of them. The intent is to build instructors’ capacities to cultivate the knowledge, skills, dispositions, and behaviors that lie at the very heart of civic learning and of public life in the ever-more complex and interconnected 21st century.
Dancing With Non-duality for Healing Through the Shadows of the COVID-19 Pandemic
Authors: Bai Heesoon , Berry Kevin , Haber Jesse , Cohen Avraham
Published: March 2021

The COVID-19 pandemic has unleashed torrents of global suffering at a devastating scale, necessitating a strong response to alleviating suffering. This paper begins with noting that the conventional approach to suffering in North America is to be positive and not to be negative. The paper summarily explores the philosophy of positive psychology underlying the first- and the second-wave of positive psychology, commenting on the evolution from dualism and a binary conceptualization in the first wave (PP 1.0) to a non-dualism of integrating binaries in the second wave (PP 2.0). PP 2.0’s enhanced therapeutic efficacy is noted for its non-dual framework. The paper then explores and suggests a different conceptualization possibility of non-duality,fundamental non-duality, that is related to but distinct from the one in PP 2.0. A case is made that fundamental non-duality has a radical possibility of therapeutic efficacy. Being consistent with the philosophy of non-duality, further suggestions are made that non-duality of PP 2.0 and fundamental non-duality can be therapeutically deployed together for greatest efficacy. The exploration contained in the paper is largely philosophical, arts-based, and autobiographical, creating an enacted and lived experience of applying theory to practice.
Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management
Authors: Lenschow Christina , Fuss Carmina Teresa , Kircher Stefan , Buck Andreas , Kickuth Ralph , Reibetanz Joachim , Wiegering Armin , Stenzinger Albrecht , Hübschmann Daniel , Germer Christoph Thomas , Fassnacht Martin , Fröhling Stefan , Schlegel Nicolas , Kroiss Matthias
Published: March 2021

Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.
Systems Biology Guided Gene Enrichment Approaches Improve Prediction of Chronic Post-surgical Pain After Spine Fusion
Authors: Chidambaran Vidya , Pilipenko Valentina , Jegga Anil G. , Geisler Kristie , Martin Lisa J.
Published: March 2021

Objectives

Incorporation of genetic factors in psychosocial/perioperative models for predicting chronic postsurgical pain (CPSP) is key for personalization of analgesia. However, single variant associations with CPSP have small effect sizes, making polygenic risk assessment important. Unfortunately, pediatric CPSP studies are not sufficiently powered for unbiased genome wide association (GWAS). We previously leveraged systems biology to identify candidate genes associated with CPSP. The goal of this study was to use systems biology prioritized gene enrichment to generate polygenic risk scores (PRS) for improved prediction of CPSP in a prospectively enrolled clinical cohort.

Methods

In a prospectively recruited cohort of 171 adolescents (14.5 ± 1.8 years, 75.4% female) undergoing spine fusion, we collected data about anesthesia/surgical factors, childhood anxiety sensitivity (CASI), acute pain/opioid use, pain outcomes 6–12 months post-surgery and blood (for DNA extraction/genotyping). We previously prioritized candidate genes using computational approaches based on similarity for functional annotations with a literature-derived “training set.” In this study, we tested ranked deciles of 1336 prioritized genes for increased representation of variants associated with CPSP, compared to 10,000 randomly selected control sets. Penalized regression (LASSO) was used to select final variants from enriched variant sets for calculation of PRS. PRS incorporated regression models were compared with previously published non-genetic models for predictive accuracy.

Results

Incidence of CPSP in the prospective cohort was 40.4%. 33,104 case and 252,590 control variants were included for association analyses. The smallest gene set enriched for CPSP had 80/1010 variants associated with CPSP (p < 0.05), significantly higher than in 10,000 randomly selected control sets (p = 0.0004). LASSO selected 20 variants for calculating weighted PRS. Model adjusted for covariates including PRS had AUROC of 0.96 (95% CI: 0.92–0.99) for CPSP prediction, compared to 0.70 (95% CI: 0.59–0.82) for non-genetic model (p < 0.001). Odds ratios and positive regression coefficients for the final model were internally validated using bootstrapping: PRS [OR 1.98 (95% CI: 1.21–3.22); β 0.68 (95% CI: 0.19–0.74)] and CASI [OR 1.33 (95% CI: 1.03–1.72); β 0.29 (0.03–0.38)].

Discussion

Systems biology guided PRS improved predictive accuracy of CPSP risk in a pediatric cohort. They have potential to serve as biomarkers to guide risk stratification and tailored prevention. Findings highlight systems biology approaches for deriving PRS for phenotypes in cohorts less amenable to large scale GWAS.
A Comparison for Dimensionality Reduction Methods of Single-Cell RNA-seq Data
Authors: Xiang Ruizhi , Wang Wencan , Yang Lei , Wang Shiyuan , Xu Chaohan , Chen Xiaowen
Published: March 2021

Single-cell RNA sequencing (scRNA-seq) is a high-throughput sequencing technology performed at the level of an individual cell, which can have a potential to understand cellular heterogeneity. However, scRNA-seq data are high-dimensional, noisy, and sparse data. Dimension reduction is an important step in downstream analysis of scRNA-seq. Therefore, several dimension reduction methods have been developed. We developed a strategy to evaluate the stability, accuracy, and computing cost of 10 dimensionality reduction methods using 30 simulation datasets and five real datasets. Additionally, we investigated the sensitivity of all the methods to hyperparameter tuning and gave users appropriate suggestions. We found that t-distributed stochastic neighbor embedding (t-SNE) yielded the best overall performance with the highest accuracy and computing cost. Meanwhile, uniform manifold approximation and projection (UMAP) exhibited the highest stability, as well as moderate accuracy and the second highest computing cost. UMAP well preserves the original cohesion and separation of cell populations. In addition, it is worth noting that users need to set the hyperparameters according to the specific situation before using the dimensionality reduction methods based on non-linear model and neural network.
The Translational Relevance of Human Circulating Memory Cutaneous Lymphocyte-Associated Antigen Positive T Cells in Inflammatory Skin Disorders
Authors: de Jesús-Gil Carmen , Sans-de SanNicolàs Lídia , García-Jiménez Irene , Ferran Marta , Celada Antonio , Chiriac Anca , Pujol Ramon M. , Santamaria-Babí Luis F.
Published: March 2021

Circulating memory T cells are heterogeneous in their tissue tropism. The skin-seeking T cell subset expresses the cutaneous lymphocyte-associated antigen (CLA) on their surface. CLA+ memory T cells not only migrate from blood to skin but also recirculate between blood and skin. Studying CLA+ memory T cells in cutaneous diseases has allowed a better understanding of immune-inflammatory mechanisms that take place. The analysis of the phenotypical features of these cells, their antigen specificity, cytokine production profile, and changes in relationship to clinical status and therapies among other characteristics have led to the concept that they constitute peripheral cellular biomarkers in T cell-mediated cutaneous conditions. CLA+ memory T cells are of relevance in the pathogenesis of several cutaneous diseases, such as psoriasis (PSO), atopic dermatitis, vitiligo, and drug-induced allergic reactions, to name a few. The interaction of circulating CLA+ T cells with skin-resident cells has been investigated in different ex vivo coculture models made out of clinical samples. Interestingly, microbes that are present in the skin or related with human skin diseases are preferentially recognized by CLA+ T cells. Thus, the interaction of Streptococcus pyogenes with CLA+ T cells in PSO is providing novel concepts that help to understand disease immunopathogenesis. The goal of this review is to present latest results in the field of CLA+ T cells in T cell-mediated inflammatory skin diseases and their translational relevance for human immunodermatology.
Interleukin-1 and Systemic Sclerosis: Getting to the Heart of Cardiac Involvement
Authors: De Luca Giacomo , Cavalli Giulio , Campochiaro Corrado , Bruni Cosimo , Tomelleri Alessandro , Dagna Lorenzo , Matucci-Cerinic Marco
Published: March 2021

Systemic sclerosis (SSc) is rare, severe connective tissue disease characterized by endothelial and vascular damage, immune activation, and resulting in inflammation and fibrosis of skin and internal organs, including the heart. SSc is associated with high morbidity and mortality. Cardiac involvement is frequent in SSc patients, even though often asymptomatic at early stages, and represents one of the major causes of SSc-related mortality. Heart involvement has a variable clinical presentation, and its pathogenesis is not completely understood. Myocardial fibrosis is traditionally considered the immunopathologic hallmark of heart involvement in SSc. This unique histological feature is paralleled by distinctive clinical and prognostic features. The so-called “vascular hypothesis” represents the most credited hypothesis to explain myocardial fibrosis. More recently, the prominent role of an inflammatory myocardial process has been identified as a cardinal event in the evolution to fibrosis, thus also delineating an “inflammation-driven pathway to fibrosis”. The pro-inflammatory cytokine interleukin (IL)-1 has an apical and cardinal role in the myocardial inflammatory cascade and in cardiac dysfunction. The primary aim of this perspective article is: to present the emerging evidence on the role of IL-1 and inflammasome in both SSc and heart inflammation, to review the complex interplay between cellular metabolism and inflammasome activation, and to discuss the rationale for targeted inhibition of IL-1 for the treatment of SSc-heart involvement, providing preliminary experimental and clinical data to support this hypothesis.
Fine-Scale Heterogeneity of a Cold-Water Coral Reef and Its Influence on the Distribution of Associated Taxa
Authors: Price David M. , Lim Aaron , Callaway Alexander , Eichhorn Markus P. , Wheeler Andrew J. , Lo Iacono Claudio , Huvenne Veerle A. I.
Published: March 2021

Benthic fauna form spatial patterns which are the result of both biotic and abiotic processes, which can be quantified with a range of landscape ecology descriptors. Fine- to medium-scale spatial patterns (<1–10 m) have seldom been quantified in deep-sea habitats, but can provide fundamental ecological insights into species’ niches and interactions. Cold-water coral reefs formed byDesmophyllum pertusum(syn.Lophelia pertusa) andMadrepora oculataare traditionally mapped and surveyed with multibeam echosounders and video transects, which limit the ability to achieve the resolution and/or coverage to undertake fine-scale, centimetric quantification of spatial patterns. However, photomosaics constructed from imagery collected with remotely operated vehicles (ROVs) are becoming a prevalent research tool and can reveal novel information at the scale of individual coral colonies. A survey using a downward facing camera mounted on a ROV traversed the Piddington Mound (Belgica Mound Province, NE Atlantic) in a lawnmower pattern in order to create 3D reconstructions of the reef with Structure-from-Motion techniques. Three high resolution orthorectified photomosaics and digital elevation models (DEM) >200 m2were created and all organisms were geotagged in order to illustrate their point pattern. The pair correlation function was used to establish whether organisms demonstrated a clustered pattern (CP) at various scales. We further applied a point pattern modelling approach to identify four potential point patterns: complete spatial randomness (CSR), an inhomogeneous pattern influenced by environmental drivers, random clustered point pattern indicating biologically driven clustering and an inhomogeneous clustered point pattern driven by a combination of environmental drivers and biological effects. Reef framework presence and structural complexity determined inhabitant distribution with most organisms showing a departure from CSR. These CPs are likely caused by an affinity to local environmental drivers, growth patterns and restricted dispersion reproductive strategies within the habitat across a range of fine to medium scales. These data provide novel and detailed insights into fine-scale habitat heterogeneity, showing that non-random distributions are apparent and detectable at these fine scales in deep-sea habitats.
Detection of Coral Reef Bleaching Based on Sentinel-2 Multi-Temporal Imagery: Simulation and Case Study
Authors: Xu Jingping , Zhao Jianhua , Wang Fei , Chen Yanlong , Lee Zhongping
Published: March 2021

Sentinel-2 mission has been shown to have promising applications in coral reef remote sensing because of its superior properties. It has a 5-day revisit time, spatial resolution of 10 m, free data, etc. In this study, Sentinel-2 imagery was investigated for bleaching detection through simulations and a case study over the Lizard Island, Australia. The spectral and image simulations based on the semianalytical (SA) model and the sensor spectral response function, respectively, confirmed that coral bleaching cannot be detected only using one image, and the change analysis was proposed for detection because there will be a featured change signal for bleached corals. Band 2 of Sentinel-2 is superior to its other bands for the overall consideration of signal attenuation and spatial resolution. However, the detection capability of Sentinel-2 is still limited by the water depth. With rapid signal attenuation due to the water absorption effect, the applicable water depth for bleaching detection was recommended to be less than 10 m. The change analysis was conducted using two methods: one radiometric normalization with pseudo invariant features (PIFs) and the other with multi-temporal depth invariant indices (DII). The former performed better than the latter in terms of classification. The bleached corals maps obtained using the PIFs and DII approaches had an overall accuracy of 88.9 and 57.1%, respectively. Compared with the change analysis based on two dated images, the use of a third image that recorded the spectral signals of recovered corals or corals overgrown by algae after bleaching significantly improved the detection accuracy. All the preliminary results of this article will aid in the future studies on coral bleaching detection based on remote sensing.
Meta-Analysis of Salmon Trophic Ecology Reveals Spatial and Interspecies Dynamics Across the North Pacific Ocean
Authors: Graham Caroline , Pakhomov Evgeny A. , Hunt Brian P. V.
Published: March 2021

We examined spatial patterns in diet, trophic niche width and niche overlap for chum, pink and sockeye salmon across the North Pacific during 1959–1969. This is a baseline period before major hatchery enhancement occurred coinciding with a negative phase of the Pacific Decadal Oscillation. Large-scale (between regions) and fine-scale (within regions) spatial and interspecies differences were apparent. In the Western Subarctic, all species tended to consume zooplankton. In the Bering Sea, chum consumed zooplankton, while sockeye and pink alternated between zooplankton and micronekton. In the Gulf of Alaska/Eastern Subarctic, chum and sockeye specialized on gelatinous zooplankton and cephalopod prey, respectively, while pink consumed a mixture of zooplankton and micronekton. The highest diet overlap across the North Pacific was between pink and sockeye (46.6%), followed by chum and pink (31.8%), and chum and sockeye (30.9%). Greater diet specialization was evident in the Gulf of Alaska/Eastern Subarctic compared to the Western Pacific. Generally, species had higher niche width and overlap in areas of high prey availability, and this was particularly evident for chum salmon. In addition to the large-scale trophic patterns, our data revealed novel fine-scale spatial patterns, including latitudinal, onshore-offshore, and cross-gyre gradients. Our results showed that pink tended to be more generalist consumers, and their diets may be a better reflection of overall prey presence and abundance in the environment. Conversely, chum and sockeye tended to be more specialist consumers, and their diets may provide a better reflection of interspecies dynamics or prey availability. This study provides a baseline for comparison with current and future changes in salmon marine ecology and North Pacific ecosystems. Finally, we identify two important data gaps that need addressing, that of improved taxonomic resolution diet data for Pacific salmon and focused research on sub-mesoscale oceanographic features that may play an important role in salmon health and productivity.
The Higher the Needs, the Lower the Tolerance: Extreme Events May Select Ectotherm Recruits With Lower Metabolic Demand and Heat Sensitivity
Authors: Vajedsamiei Jahangir , Wahl Martin , Schmidt Andrea Lee , Yazdanpanahan Maryam , Pansch Christian
Published: March 2021

Ongoing climate warming demands a better understanding of whether or how the ectotherms that evolved in response to fluctuating stress regimes may acquire increased heat tolerance. Using blue mussels, Mytilus spp., a globally important and well-studied species, we provide empirical evidence supporting that (i) extremely warm (future) summer conditions may select rare recruits that are more capable of expressing metabolic (feeding and respiration) suppression and recovery in response to daily thermal fluctuations in mild to critical temperature range, (ii) this higher heat tolerance can be mediated by lower baseline metabolic demand, possibly decreasing the risks of heat-induced supply and demand mismatch and its associated stress during thermal fluctuations, and (iii) the capacity to acquire such heat tolerance through acclimation is minor. We discuss our results, methodological limitations and offer a perspective for future research. Further evaluation of mechanistic hypotheses such as the one tested here (based on the role of metabolic demand) is needed to generalize the significance of drivers of fast warm adaptation in ectothermic metazoan populations.
N,Cu-CD-Decorated Mesoporous WO3 for Enhanced Photocatalysis Under UV–Vis–NIR Light Irradiation
Authors: Ni Tianjun , Li Qiansheng , Yan Yunhui , Yang Zhijun , Chang Kaiwen , Liu Guoguang
Published: March 2021

Research on the design of semiconductor photocatalysts with rapid electron transfer efficiencies and broad-spectrum responses for environmental remediation remains a pressing challenge. Herein, we described the fabrication of a novel broad-spectrum nitrogen and copper codoped carbon dots/mesoporous WO3 nanocomposite (N,Cu-CDs/m-WO3), which exhibited complete UV–vis–NIR spectrum response, light harvesting capabilities, rich oxygen vacancies, rapid electron-transfer ability, low electron–hole (e−/h+) pair recombination rate, and extensive specific surface area. After 2 h of photocatalytic reaction, it showed excellent photoactivities for the degradation of rhodamine B, methylene blue, tetracycline hydrochloride, oxytetracycline, ciprofloxacin, and bisphenol A. Moreover, we found that the conversion between Cu (II) and Cu (I) played a key role in accelerating electron transfer and inhibiting the recombination of e−/h+ pairs. This work provides an efficient strategy for the utilization of solar light and enhancing the charge-transfer capacity in the semiconductor photocatalysis field.
Validation of a Quick Flow Cytometry-Based Assay for Acute Infection Based on CD64 and CD169 Expression. New Tools for Early Diagnosis in COVID-19 Pandemic
Authors: Comins-Boo Alejandra , Gutiérrez-Larrañaga Maria , Roa-Bautista Adriel , Guiral Foz Sandra , Renuncio García Mónica , González López Elena , Irure Ventura Juan , Fariñas-Álvarez María Carmen , San Segundo David , López Hoyos Marcos
Published: March 2021

Objectives: Several parameters aid in deciphering between viral and bacterial infections; however, new tools should be investigated in order to reduce the time to results and proceed with an early target-therapy. Validation of a biomarker study, including CD64 and CD169 expression, was conducted.

Material and Methods: Patients with active SARS-CoV-2 infection (ACov-2), bacterial infection (ABI), healthy controls, and antiretroviral-controlled chronic HIV infection were assessed. Whole blood was stained and, after lysing no-wash protocol, acquired by flow cytometry. The median fluorescence intensity (MFI) of CD64 and CD169 was measured in granulocytes, monocytes, and lymphocytes. The CD64 MFI ratio granulocytes to lymphocytes (CD64N) and CD169 MFI ratio monocytes to lymphocytes (CD169Mo) were evaluated as biomarkers of acute bacterial and viral infection, respectively.

Results: A CD64N ratio higher than 3.3 identified patients with ABI with 83.3 and 85.9% sensitivity and specificity, with an area under the curve (AUC) of 83.5%. In contrast, other analytic or hematological parameters used in the clinic had lower AUC compared with the CD64N ratio. Moreover, a CD169Mo ratio higher than 3.3 was able to identify ACov-2 with 91.7 and 89.8 sensitivity and specificity, with the highest AUC (92.0%).

Conclusion: This work confirms the previous data of CD64N and CD169Mo ratios in an independent cohort, including controlled chronic viral HIV infection patients as biomarkers of acute bacterial and viral infections, respectively. Such an approach would benefit from quick pathogen identification for a direct-therapy with a clear application in different Health Care Units, especially during this COVID pandemic.
Development of Rice Stripe Tenuivirus Minireplicon Reverse Genetics Systems Suitable for Analyses of Viral Replication and Intercellular Movement
Authors: Zhang Xiaoyan , Sun Kai , Liang Yan , Wang Shuo , Wu Kaili , Li Zhenghe
Published: March 2021

Rice stripe virus (RSV), a tenuivirus with four negative-sense/ambisense genome segments, is one of the most devastating viral pathogens affecting rice production in many Asian countries. Despite extensive research, our understanding of RSV infection cycles and pathogenesis has been severely impaired by the lack of reverse genetics tools. In this study, we have engineered RSV minireplicon (MR)/minigenome cassettes with reporter genes substituted for the viral open reading frames in the negative-sense RNA1 or the ambisense RNA2-4 segments. After delivery to Nicotiana benthamiana leaves via agroinfiltration, MR reporter gene expression was detected only when the codon-optimized large viral RNA polymerase protein (L) was coexpressed with the nucleocapsid (N) protein. MR activity was also critically dependent on the coexpressed viral suppressors of RNA silencing, but ectopic expression of the RSV-encoded NS3 silencing suppressor drastically decreased reporter gene expression. We also developed intercellular movement-competent MR systems with the movement protein expressed either in cis from an RNA4-based MR or in trans from a binary plasmid. Finally, we generated multicomponent replicon systems by expressing the N and L proteins directly from complementary-sense RNA1 and RNA3 derivatives, which enhanced reporter gene expression, permitted autonomous replication and intercellular movement, and reduced the number of plasmids required for delivery. In summary, this work enables reverse genetics analyses of RSV replication, transcription, and cell-to-cell movement and provides a platform for engineering more complex recombinant systems.
Transcriptomic Profiling Identifies DCBLD2 as a Diagnostic and Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma
Authors: Feng Zengyu , Li Kexian , Wu Yulian , Peng Chenghong
Published: March 2021

Background: Accumulating evidence shows that the elevated expression of DCBLD2 (discoidin, CUB and LCCL domain-containing protein 2) is associated with unfavorable prognosis of various cancers. However, the correlation of DCBLD2 expression value with the diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated. Methods: Univariate Cox regression analysis was used to screen robust survival-related genes. Expression pattern of selected genes was investigated in PDAC tissues and normal tissues from multiple cohorts. Kaplan–Meier (K–M) survival curves, ROC curves and calibration curves were employed to assess prognostic performance. The relationship between DCBLD2 expression and immune cell infiltrates was conducted by CIBERSORT software. Biological processes and KEGG pathway enrichment analyses were adopted to clarify the potential function of DCBLD2 in PDAC. Results: Univariate analysis, K–M survival curves and calibration curves indicated that DCBLD2 was a robust prognostic factor for PDAC with cross-cohort compatibility. Upregulation of DCBLD2 was observed in dissected PDAC tissues as well as extracellular vesicles from both plasma and serum samples of PDAC patients. Both DCBLD2 expression in tissue and extracellular vesicles had significant diagnostic value. Besides, DCBLD2 expression was correlated with infiltrating level of CD8+ T cells and macrophage M2 cells. Functional enrichment revealed that DCBLD2 might be involved in cell motility, angiogenesis, and cancer-associated pathways. Conclusion: Our study systematically analyzed the potential diagnostic, prognostic and therapeutic value of DCBLD2 in PDAC. All the findings indicated that DCBLD2 might play a considerably oncogenic role in PDAC with diagnostic, prognostic and therapeutic potential. These preliminary results of bioinformatics analyses need to be further validated in more prospective studies.
Patient and Public Involvement for Dementia Research in Low- and Middle-Income Countries: Developing Capacity and Capability in South Asia
Authors: Miah Jahanara , Sheikh Saima , Francis Rachel C. , Nagarajan Gayathri , Antony Sojan , Tahir Maryam , Sattar Rabia , Naz Anum , Tofique Sehrish , Billah Mostazir , Saha Sajib , Leroi Iracema
Published: March 2021

Background: Patient and public involvement (PPI) is an active partnership between the public and researchers in the research process. In dementia research, PPI ensures that the perspectives of the person with “lived experience” of dementia are considered. To date, in many lower- and middle-income countries (LMIC), where dementia research is still developing, PPI is not well-known nor regularly undertaken. Thus, here, we describe PPI activities undertaken in seven research sites across South Asia as exemplars of introducing PPI into dementia research for the first time.

Objective: Through a range of PPI exemplar activities, our objectives were to: (1) inform the feasibility of a dementia-related study; and (2) develop capacity and capability for PPI for dementia research in South Asia.

Methods: Our approach had two parts. Part 1 involved co-developing new PPI groups at seven clinical research sites in India, Pakistan and Bangladesh to undertake different PPI activities. Mapping onto different “rings” of the Wellcome Trust's “Public Engagement Onion” model. The PPI activities included planning for public engagement events, consultation on the study protocol and conduct, the adaptation of a study screening checklist, development and delivery of dementia training for professionals, and a dementia training programme for public contributors. Part 2 involved an online survey with local researchers to gain insight on their experience of applying PPI in dementia research.

Results: Overall, capacity and capability to include PPI in dementia research was significantly enhanced across the sites. Researchers reported that engaging in PPI activities had enhanced their understanding of dementia research and increased the meaningfulness of the work. Moreover, each site reported their own PPI activity-related outcomes, including: (1) changes in attitudes and behavior to dementia and research involvement; (2) best methods to inform participants about the dementia study; (3) increased opportunities to share knowledge and study outcomes; and (4) adaptations to the study protocol through co-production.

Conclusions: Introducing PPI for dementia research in LMIC settings, using a range of activity types is important for meaningful and impactful dementia research. To our knowledge, this is the first example of PPI for dementia research in South Asia.