bluuebunny/crossref_metadata_2025 huggingface dataset:
A Survey of Patient-Relevant Outcomes in Pediatric Craniopharyngioma: Focus on Hypothalamic Obesity
Authors: Craven Meghan , Crowley Julia H. , Chiang Lucas , Kline Cassie , Malbari Fatema , Hocking Matthew C. , McCormack Shana E.
Published: May 2022

Context

Individuals treated for pediatric craniopharyngioma, a rare, grade 1 brain tumor, frequently develop hypothalamic obesity, a complication often recalcitrant to intervention. Although hypothalamic obesity is known to adversely impact quality of life, less is known about how caregivers and patients experience this condition.

Objective

Our goal was to examine the approaches that families take towards weight management and the impact on social function in individuals with craniopharyngioma and obesity. Individuals with craniopharyngioma without obesity were included as a comparison.

Subjects and Methods

Adult caregivers of children <18y with craniopharyngioma completed a web-based survey posted by a patient advocacy organization between February and July 2020. Questions related to the child’s diagnosis, medications, lifestyle modifications, and social function along with research priorities. Descriptive statistics were generated. Linear regression was used to assess the independent effects of obesity and other covariates on social function.

Results

Of 106 respondents, 60 (57%) reported their child had obesity at the time of survey completion. In contrast, only 6 (5.7%) had obesity prior to craniopharyngioma diagnosis. A majority (92%) of those with obesity had tried limiting calories or carbohydrates; 31% and 69% found these helpful, respectively. Thirty-eight percent had tried weight loss medications (stimulants, metformin, GLP1R-agonists, and topiramate) and 48% found at least one helpful. Both stimulant and anti-depressant use were reported more frequently with obesity. An index (T-score) reflecting social function was lower in the cohort than a population reference, 41 (SD 11) vs. 50 (SD 10), p<0.001. In a linear model, both older age and obesity were independently associated with greater social impairment. Ninety-four percent of respondents caring for a child with obesity (and 79% of all respondents) identified “improving treatments and prevention for hypothalamic obesity” as a key research priority.

Conclusions

Only a minority of individuals with hypothalamic obesity had trialed medication, even though many reported that lifestyle modification was inadequate. Furthermore, social function was significantly impaired overall in survivors compared to a reference cohort, and even more so in individuals with obesity. These findings highlight the opportunity to improve social functioning as an additional potential benefit of improved treatments for hypothalamic obesity.
Association Between Indices of Body Composition and Metabolically Unhealthy Phenotype in China: A Cross-Sectional Study
Authors: Lv Fang , Cai Xiaoling , Li Yufeng , Fu Zuodi , Zhang Xiuying , Zhou Xianghai , Han Xueyao , Ji Linong
Published: May 2022

Introduction

Body composition is closely related to metabolic health status. Visceral adipose tissue (VAT) dysfunction contributes to metabolic syndrome. However, results regarding subcutaneous adipose tissue (SAT) and skeletal muscle are controversial. We aimed to determine the association of indices of body composition with abnormal metabolic phenotype in China.

Methods

A total of 3, 954 subjects (age 50.2 ± 11.7 years) with body mass index (BMI) more than 18.5 kg/m2 from Pinggu Metabolic Disease Study were analyzed. Quantitative computed tomography (QCT) was performed to measure total adipose tissue (TAT), VAT, SAT area, and lumbar skeletal muscle area (SMA). Participants were divided into six groups on the basis of BMI category (normal weight/overweight/obesity) and metabolic status (healthy/unhealthy), as defined by the presence or absence of components of the metabolic syndrome by Chinese Diabetes Society criteria.

Results

63.4%, 39.5%, and 23.3% participants were classified as metabolically healthy phenotype in individuals with normal weight, overweight and obese, respectively. Individuals in the highest TAT, VAT, and VAT/TAT ratio category had higher risk of being metabolically unhealthy than individuals in the lowest group (all p<0.01). While, risk for metabolically unhealthy was reduced significantly in the highest SMA/TAT ratio category when compared with the lowest category in individuals with normal wight and overweight (both p<0.05). Risk for metabolically unhealthy was reduced significantly in the highest SAT category when compared with the lowest category (OR=0.555, 95%CI: 0.360-0.856, p=0.008) in individuals with obese after adjustment for age, sex and BMI. However, skeletal muscle index (SMI) showed no significant association with the metabolically healthy status in different BMI categories (p>0.05). The VAT and VAT/TAT ratio were better diagnostic values of indicators to differentiate metabolically unhealthy subjects from controls compared with other indicators, such as TAT, SAT, SMI, SMA/TAT ratio.

Conclusions

Higher visceral adipose tissue was closely associated with metabolically unhealthy phenotype in Chinese adults. Subcutaneous adipose tissue might be a protective factor for metabolic health status only in obese individuals.
Comparative Study of the Internal Dynamic Failures of Grid-Connected Solar PVs: The Case of the Oman Power Network
Authors: Okedu Kenneth E. , Al Ghaithi Ahmed Sultan Salim
Published: May 2022

Solar Photovoltaic (PV) offers hope toward environmental sustainability in terms of carbon and global heat reduction. The harvested energy from solar PV depends on the solar radiation, temperature of the cells, and the voltage generated in the PV modules. With the recent proliferation of solar PV projects in Oman, it is imperative to carry out new studies on the causes and effects of failures of these grid connected PVs, for effective and reliable performance. This study serves as a prototype to evaluate the performance of solar PV installations in Oman, considering the possible failures that may occur. These failures could lead to poor performance of the solar PV systems during operation. The performance analysis of a 6.2 MW grid-connected solar photovoltaic system in Muscat car parking, Oman is presented in this paper. The electrical parameters, and data analysis of the PV system were evaluated by monitoring the voltage, frequency, power factor, and total output power variables. The analysis of the PV performance was based on three internal dynamic failures; dust accumulation, inverter malfunction, and faulty protection schemes. When the solar PV cells were exposed to high percentage of contamination and dust, the plant performance dropped sharply to lower power generation by 43.5%. Furthermore, Inverters failure data analysis show that the average power generation degraded by 34%, and the average power generation degradation of 1% in the same period due to protection schemes failure. The results demonstrated that dust accumulation and inverter malfunction are the two major shortcomings that could lead to low power efficiency of solar PVs during operation.
High-Gain Seven-Level Switched-Capacitor Two-Stage Multi-Level Inverter
Authors: Ahmed Hassan Yousif , Abdel-Rahim Omar , Ali Ziad M.
Published: May 2022

Due to the low voltage of the PV module and to enable AC module technology, where every PV module has its own DC-AC converter, this paper introduces a new high step-up seven-level two-stage multilevel inverter for a grid-connected Photovoltaic (PV) system. The introduced schematic consists of two stages. The first stage is a switched capacitor boost converter and the second stage is a seven-level seven-switches multilevel inverter. The first stage is designed to extract the maximum power of PV module and step-up its input voltage. The proposed seven-level seven-switches topology generates seven levels with only seven switches. Thus, the number of switches is reduced. The proposed inverter has eight valid switching states. In each switching state only three switches are ON at the same time. The proposed topology has some distinct features such as reduced number of switches and reduced conduction; total harmonic distortion (THD) of the current is 23% in case of pure resistive and with no filtration at the output and less than 3% using a small filter with integration into the grid. Due to the high boosting ability of the switched capacitor boost converter, a wide voltage gain is easily achievable. In this paper the system is tested at different voltage gains and the highest simulated efficiency was around 96%. The developed system is simulated in MATLAB/SIMULINK and in real time using DSPACE1202. Both simulation and real-time results are consistent with the theoretical analysis.
When to Use Transdisciplinary Approaches for Environmental Research
Authors: Kiatkoski Kim Milena , Douglas Michael M. , Pannell David , Setterfield Samantha A. , Hill Rosemary , Laborde Sarah , Perrott Laura , Álvarez-Romero Jorge G. , Beesley Leah , Canham Caroline , Brecknell Anthea
Published: May 2022

Transdisciplinary research (TDR) can help generate solutions to environmental challenges and enhance the uptake of research outputs, thus contributing to advance sustainability in social-ecological systems. Our aim is to support investment decisions in TDR; more specifically, to help funders, researchers, and research users to decide when and why it is most likely to be worth investing in TDR approaches. To achieve our aim, we: 1) define TDR and use a decision tree comparing it with alternative modes of research (i.e., basic, applied, disciplinary, multi-disciplinary, and interdisciplinary research) to help researchers and funders distinguish TDR from other research modes; 2) identify features of the research problem and context (complexity, diverse knowledge systems, contestation, power imbalance, and disagreement on the need for transformative change) where a TDR approach could be more appropriate than the alternative research modes; and 3) explore the idea that the intensity of the contextual features in (2), together with the problem at hand, will help determine where a research project stands in a continuum from low- to high-TDR. We present five studies exemplifying lower- to higher-TDR approaches that are distinguished by: 1) the number and variety of research participants engaged; 2) the strength of involvement of non-academic actors; and 3) the number and variety of disciplines and knowledge systems involved in the research.
Molecular Taxonomy of Systemic Lupus Erythematosus Through Data-Driven Patient Stratification: Molecular Endotypes and Cluster-Tailored Drugs
Authors: Garantziotis Panagiotis , Nikolakis Dimitrios , Doumas Stavros , Frangou Eleni , Sentis George , Filia Anastasia , Fanouriakis Antonis , Bertsias George , Boumpas Dimitrios T.
Published: May 2022

Objectives

Treatment of Systemic Lupus Erythematosus (SLE) is characterized by a largely empirical approach and relative paucity of novel compound development. We sought to stratify SLE patients based on their molecular phenotype and identify putative therapeutic compounds for each molecular fingerprint.

Methods

By the use of whole blood RNA-seq data from 120 SLE patients, and in a data-driven, clinically unbiased manner, we established modules of commonly regulated genes (molecular endotypes) and re-stratified patients through hierarchical clustering. Disease activity and severity were assessed using SLEDAI-2K and Lupus Severity Index, respectively. Through an in silico drug prediction pipeline, we investigated drugs currently in use, tested in lupus clinical trials, and listed in the iLINCS prediction databases, for their ability to reverse the gene expression signatures in each molecular endotype. Drug repurposing analysis was also performed to identify perturbagens that counteract group-specific SLE signatures.

Results

Molecular taxonomy identified five lupus endotypes, each characterized by a unique gene module enrichment pattern. Neutrophilic signature group consisted primarily of patients with active lupus nephritis, while the B-cell expression group included patients with constitutional features. Patients with moderate severity and serologic activity exhibited a signature enriched for metabolic processes. Mild disease was distributed in two groups, exhibiting enhanced basic cellular functions, myelopoiesis, and autophagy. Bortezomib was predicted to reverse disturbances in the “neutrophilic” cluster, azathioprine and ixazomib in the “B-cell” cluster, and fostamatinib in the “metabolic” patient subgroup.

Conclusion

The clinical spectrum of SLE encompasses distinct molecular endotypes, each defined by unique pathophysiologic aberrancies potentially reversible by distinct compounds.
Pharmacological Inhibition of MALT1 Ameliorates Autoimmune Pathogenesis and Can Be Uncoupled From Effects on Regulatory T-Cells
Authors: Biswas Subhabrata , Chalishazar Aditi , Helou Ynes , DiSpirito Joanna , DeChristopher Brian , Chatterjee Devin , Merselis Leidy , Vincent Benjamin , Monroe John G. , Rabah Dania , Long Andrew J.
Published: May 2022

MALT1 forms part of a central signaling node downstream of immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors, across a broad range of immune cell subsets, and regulates NF-κB driven transcriptional responses via dual scaffolding-protease activity. Allosteric inhibition of MALT1 activity has demonstrated benefit in animal models of inflammation. However, development of MALT1 inhibitors to treat autoimmune and inflammatory diseases (A&ID) has been hindered by reports linking MALT1 inhibition and genetic loss-of-function to reductions in regulatory T-cell (Treg) numbers and development of auto-inflammatory syndromes. Using an allosteric MALT1 inhibitor, we investigated the consequence of pharmacological inhibition of MALT1 on proinflammatory cells compared to regulatory T-cells. Consistent with its known role in ITAM-driven responses, MALT1 inhibition suppressed proinflammatory cytokine production from activated human T-cells and monocyte-derived macrophages, and attenuated B-cell proliferation. Oral administration of a MALT1 inhibitor reduced disease severity and synovial cytokine production in a rat collagen-induced arthritis model. Interestingly, reduction in splenic Treg numbers was less pronounced in the context of inflammation compared with naïve animals. Additionally, in the context of the disease model, we observed an uncoupling of anti-inflammatory effects of MALT1 inhibition from Treg reduction, with lower systemic concentrations of inhibitor needed to reduce disease severity compared to that required to reduce Treg numbers. MALT1 inhibition did not affect suppressive function of human Tregs in vitro. These data indicate that anti-inflammatory efficacy can be achieved with MALT1 inhibition without impacting the number or function of Tregs, further supporting the potential of MALT1 inhibition in the treatment of autoimmune disease.
Defining Delayed Perihematomal Edema Expansion in Intracerebral Hemorrhage: Segmentation, Time Course, Risk Factors and Clinical Outcome
Authors: Chen Yihao , Qin Chenchen , Chang Jianbo , Liu Yixun , Zhang Qinghua , Ye Zeju , Li Zhaojian , Tian Fengxuan , Ma Wenbin , Wei Junji , Feng Ming , Chen Shengpan , Yao Jianhua , Wang Renzhi
Published: May 2022

We attempt to generate a definition of delayed perihematomal edema expansion (DPE) and analyze its time course, risk factors, and clinical outcomes. A multi-cohort data was derived from the Chinese Intracranial Hemorrhage Image Database (CICHID). A non-contrast computed tomography (NCCT) -based deep learning model was constructed for fully automated segmentation hematoma and perihematomal edema (PHE). Time course of hematoma and PHE evolution correlated to initial hematoma volume was volumetrically assessed. Predictive values for DPE were calculated through receiver operating characteristic curve analysis and were tested in an independent cohort. Logistic regression analysis was utilized to identify risk factors for DPE formation and poor outcomes. The test cohort’s Dice scores of lesion segmentation were 0.877 and 0.642 for hematoma and PHE, respectively. Overall, 1201 patients were enrolled for time-course analysis of ICH evolution. A total of 312 patients were further selected for DPE analysis. Time course analysis showed the growth peak of PHE approximately concentrates in 14 days after onset. The best cutoff for DPE to predict poor outcome was 3.34 mL of absolute PHE expansion from 4-7 days to 8-14 days (AUC=0.784, sensitivity=72.2%, specificity=81.2%), and 3.78 mL of absolute PHE expansion from 8-14 days to 15-21 days (AUC=0.682, sensitivity=59.3%, specificity=92.1%) in the derivation sample. Patients with DPE was associated with worse outcome (OR: 12.340, 95%CI: 6.378-23.873, P<0.01), and the larger initial hematoma volume (OR: 1.021, 95%CI: 1.000-1.043, P=0.049) was the significant risk factor for DPE formation. This study constructed a well-performance deep learning model for automatic segmentations of hematoma and PHE. A new definition of DPE was generated and is confirmed to be related to poor outcomes in ICH. Patients with larger initial hematoma volume have a higher risk of developing DPE formation.
SAR Satellite Imagery Reveals the Impact of the Covid-19 Crisis on Ship Frequentation in the French Mediterranean Waters
Authors: Pita Ignacio , Seguin Raphael , Shin Yunne-Jai , Viguier Pauline , Catry Thibault , Devillers Rodolphe , Mouillot David
Published: May 2022

The Covid-19 pandemic is the latest example in a growing number of health, social, economic, and environmental crises humanity is facing. The multiple consequences of this pandemic crisis required strong responses from governments, including strict lockdowns. Yet, the impact of lockdowns on coastal ecosystems and maritime activities is still challenging to quantify over large spatial scales in comparison to the pre-Covid period. In this study, we used an object detection algorithm on Synthetic Aperture Radar (SAR) images acquired by the two Sentinel-1 satellites to assess the impact of the Covid-19 crisis on the presence of boats before, during and after lockdown periods in the French Mediterranean Exclusive Economic Zone. During the French most severe lockdown period (March – May 2020), we observed that ship frequentation remained at the same level from March to July 2020, instead of rising towards the summer peak like in previous years. Then, ship frequentation increased rapidly to a normal level in August 2020 when restrictions were lifted. By comparing morning and evening (7:00 am and 7:00 pm) ship frequentation during this period to pre-Covid years, we observed contrasting patterns. On the one hand, morning detections were particularly high, while on the other hand evening detections were significantly lower and less concentrated in coastal touristic waters than in previous years. Overall, we found a 9% decrease in ship frequentation between the year 2020 and the 2017-2019 period, with a maximum of 43% drop in June 2020 due to the lockdown. So, the Covid -19 crisis induced only a very short-term reduction in maritime activities but did not markedly reduce the annual ship frequentation in the French Mediterranean waters. The satellite imagery approach is an alternative method that improves our understanding of the pandemic impacts at an unprecedented spatiotemporal scale and resolution.
First Record of the Silverspot Squirrelfish Sargocentron caudimaculatum (Rüppell, 1838) in Mediterranean Waters
Authors: Ghanem Raouia , Rjiba Bahri Wafa , Chaffai Amani , Zaouali Jeanne , Hassen Bilel , Karray Sahar , El Bour Monia , Ben Souissi Jamila , Azzurro Ernesto
Published: May 2022

On 14th October 2021, a single specimen of Sargocentron caudimaculatum was captured in the locality of Cape Bon, Eastern Tunisia, by a local fisher using gillnets at 60 m depth, on rocky bottom. This observation represents the first record of this species in the Mediterranean Sea. General information on the squirrelfishes and the importance of molecular tools for the proper identification of morphologically challenging non-indigenous organisms were raised and discussed.
Spatio-Temporal Variation of Economic Drivers of Urban Heat Island Effect in Yangtze River Delta
Authors: Yan Yongzhe , Sun Yanwei , Tian Peng , Li Jialin
Published: May 2022

It is not deep enough that the theoretical and empirical analysis of economic drivers on the urban heat island (UHI) effect have been researched. Consequently, the study of economic drivers of the UHI effect is not only conducive to the governance of the UHI problem but also conducive to deepening the study of related issues in the economic field. The Yangtze River Delta (YRD) region of China has developed economic status and the special geography of estuaries and coasts. Therefore, 26 central cities in the YRD region are selected as research samples, and the period from 2003 to 2017 is taken as the observation period. The Spatio-temporal variability of UHI intensity caused by industrialization and urbanization is analyzed by using MODIS land surface temperature (LST) data and related yearbook data. The conclusions are as follows:(1) The UHI intensity of cities in the YRD region is significant and fluctuates to a certain extent. (2) Empirical analysis shows that the agglomeration of single economic factors in the process of industrialization and urbanization does correlate with the UHI intensity in the YRD region, but the correlation may show a downward trend due to the influence of exogenous factors suc0h as physical geography. (3) In terms of economic drivers, the combination of multiple factors can produce a greater UHI intensity. The model of their impacts on UHI intensity is increasingly-changed, which is from a model of Fixed Asset Investment and the Motor Vehicle Population as dominant factors to a model of multiple overlapping economic factors, and the latter has a greater impact.
Use of Traditional, Complementary and Integrative Medicine During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis
Authors: Kim Tae-Hun , Kang Jung Won , Jeon Sae-Rom , Ang Lin , Lee Hye Won , Lee Myeong Soo
Published: May 2022

Background

Traditional, Complementary and Integrative Medicine (TCIM) has been reported to use for symptom management of coronavirus disease 2019 (COVID-19). The objective of this review was to identify the overall usage prevalence of TCIM interventions for COVID-19.

Methods

Surveys on the general population and observational studies on the COVID-19 patient chart review were located in the search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases in September 2021. Observational studies, such as cross-sectional studies, surveys, cohort studies and hospital-based patient case reviews, published in any language, reporting the usage of TCIM in the patients with COVID-19 or the general population during the COVID-19 pandemic were included in this review. Data screening and extraction were performed independently by two reviewers. The reporting quality of the included studies was assessed with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement. To conduct a meta-analysis of the usage prevalence of various TCIM interventions, the effect size of the proportion for each intervention was calculated with the inverse variance method. The main outcome was usage prevalence of TCIM interventions among patients with COVID-19 or the general population during the COVID-19 pandemic.

Results

A total of 62 studies were included in this review. The overall TCIM usage prevalence was estimated to be 0.64 (95% CI 0.54–0.73). The overall prevalence did not differ between the population-based survey (0.65, 95% CI 0.48–0.81) and the hospital-based patient case review (0.63, 95% CI 0.52–0.73). Statistical heterogeneity and comparatively low quality in reporting were observed, which should be cautiously considered when interpreting the results.

Conclusion

Various TCIM interventions were reported to be used with comparatively high frequency. Future international collaborative research might overcome the main limitation of this study, i.e., the heterogeneity of the included data.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278452, identifier: CRD42021278452.
Efficacy of Physiotherapy Interventions on Weaning in Mechanically Ventilated Critically Ill Patients: A Systematic Review and Meta-Analysis
Authors: Lippi Lorenzo , de Sire Alessandro , D’Abrosca Francesco , Polla Biagio , Marotta Nicola , Castello Luigi Mario , Ammendolia Antonio , Molinari Claudio , Invernizzi Marco
Published: May 2022

Mechanical ventilation (MV) is currently considered a life-saving intervention. However, growing evidence highlighted that prolonged MV significantly affects functional outcomes and length of stay. In this scenario, controversies are still open about the optimal rehabilitation strategies for improving MV duration in ICU patients. In addition, the efficacy of physiotherapy interventions in critical ill patients without positive history of chronic respiratory conditions is still debated. Therefore, this systematic review of randomized controlled trials (RCTs) with meta-analysis aimed at characterizing the efficacy of a comprehensive physiotherapy intervention in critically ill patients. PubMed, Scopus, and Web of Science databases were systematically searched up to October 22, 2021 to identify RCTs assessing acute patients mechanical ventilated in ICU setting undergoing a rehabilitative intervention. The primary outcomes were MV duration, extubation, and weaning time. The secondary outcomes were weaning successful rate, respiratory function, ICU discharge rate and length of stay. Out of 2503 records, 12 studies were included in the present work. The meta-analysis performed in 6 RCTs showed a significant improvement in terms of MV duration (overall effect size: −3.23 days; 95% CI = −5.79, −0.67, p = 0.01; Z = 2.47) in patients treated with a comprehensive physiotherapy intervention including early mobilization, positioning, airway clearance techniques, lung expansion and respiratory muscle training. The quality assessment underlined 9 studies (75%) of good quality and 3 studies of fair quality according to the PEDro scale. In conclusion, our results provided previously unavailable data about the role of comprehensive physiotherapy intervention in improving MV duration in critical ill patients without chronic respiratory conditions. Further studies are needed to better characterize the optimal combination of rehabilitation strategies enhancing the improvements in critical ill patients without chronic respiratory disorders.
Seasonal and Spatial Variations in Synechococcus Abundance and Diversity Throughout the Gullmar Fjord, Swedish Skagerrak
Authors: Laber Christien P. , Pontiller Benjamin , Bunse Carina , Osbeck Christofer M. G. , Pérez-Martínez Clara , Di Leo Danilo , Lundin Daniel , Legrand Catherine , Pinhassi Jarone , Farnelid Hanna
Published: May 2022

The picophytoplanktonSynechococcusis a globally abundant autotroph that contributes significantly to primary production in the oceans and coastal areas. These cyanobacteria constitute a diverse genus of organisms that have developed independent niche spaces throughout aquatic environments. Here, we use the 16S V3–V4 rRNA gene region and flow cytometry to explore the diversity ofSynechococcuswithin the picophytoplankton community in the Gullmar Fjord, on the west coast of Sweden. We conducted a station-based 1-year time series and two transect studies of the fjord. Our analysis revealed that within the large number ofSynechococcusamplicon sequence variants (ASVs; 239 in total), prevalent ASVs phylogenetically clustered with clade representatives in both marine subcluster 5.1 and 5.2. The near-surface composition of ASVs shifted from spring to summer, when a 5.1 subcluster dominated community developed along with elevatedSynechococcusabundances up to 9.3 × 104cells ml–1. This seasonal dominance by subcluster 5.1 was observed over the length of the fjord (25 km), where shifts in community composition were associated with increasing depth. Unexpectedly, the community shift was not associated with changes in salinity.Synechococcusabundance dynamics also differed from that of the photosynthetic picoeukaryote community. These results highlight how seasonal variations in environmental conditions influence the dynamics ofSynechococcusclades in a high latitude threshold fjord.
Microbiome of Penaeus vannamei Larvae and Potential Biomarkers Associated With High and Low Survival in Shrimp Hatchery Tanks Affected by Acute Hepatopancreatic Necrosis Disease
Authors: Reyes Guillermo , Betancourt Irma , Andrade Betsy , Panchana Fanny , Román Rubén , Sorroza Lita , Trujillo Luis E. , Bayot Bonny
Published: May 2022

Acute hepatopancreatic necrosis disease (AHPND) is an emerging bacterial disease of cultured shrimp caused mainly by Vibrio parahaemolyticus, which harbors the lethal PirAB toxin genes. Although Penaeus vannamei (P. vannamei) postlarvae are susceptible to AHPND, the changes in the bacterial communities through the larval stages affected by the disease are unknown. We characterized, through high-throughput sequencing, the microbiome of P. vannamei larvae infected with AHPND-causing bacteria through the larval stages and compared the microbiome of larvae collected from high- and low-survival tanks. A total of 64 tanks from a commercial hatchery were sampled at mysis 3, postlarvae 4, postlarvae 7, and postlarvae 10 stages. PirAB toxin genes were detected by PCR and confirmed by histopathology analysis in 58 tanks. Seven from the 58 AHPND-positive tanks exhibited a survival rate higher than 60% at harvest, despite the AHPND affectation, being selected for further analysis, whereas 51 tanks exhibited survival rates lower than 60%. A random sample of 7 out of these 51 AHPND-positive tanks was also selected. Samples collected from the selected tanks were processed for the microbiome analysis. The V3–V4 hypervariable regions of the 16S ribosomal RNA (rRNA) gene of the samples collected from both the groups were sequenced. The Shannon diversity index was significantly lower at the low-survival tanks. The microbiomes were significantly different between high- and low-survival tanks at M3, PL4, PL7, but not at PL10. Differential abundance analysis determined that biomarkers associated with high and low survival in shrimp hatchery tanks affected with AHPND. The genera Bacillus, Vibrio, Yangia, Roseobacter, Tenacibaculum, Bdellovibrio, Mameliella, and Cognatishimia, among others, were enriched in the high-survival tanks. On the other hand, Gilvibacter, Marinibacterium, Spongiimonas, Catenococcus, and Sneathiella, among others, were enriched in the low-survival tanks. The results can be used to develop applications to prevent losses in shrimp hatchery tanks affected by AHPND.
Characterization of Rhizosphere Microbial Communities for Disease Incidence and Optimized Concentration of Difenoconazole Fungicide for Controlling of Wheat Dwarf Bunt
Authors: Jia Huanyu , Muhae-Ud-Din Ghulam , Zhang Han , Zong Qianqian , Zhao Sifeng , Guo Qingyuan , Chen Wanquan , Gao Li
Published: May 2022

Rhizosphere soil microorganisms have great agricultural importance. To explore the relationship between rhizosphere microorganisms and the disease incidence, and to optimize the concentration of difenoconazole fungicide for the control of wheat dwarf bunt, caused by Tilletia controversa Kühn, the rhizosphere microorganisms were characterized based on sequencing methods. We found that the disease incidence correlated with the relative abundance of some microbial communities, such as Acidobacteria, Nocardioides, Roseiflexaceae, Pyrinomonadaceae, and Gemmatimonadaceae. Actinobacteria showed significant differences in the infected soils when compared to the control soils, and the relative abundance of Acidobacteria, Pyrinomonadaceae, Gemmatimonadaceae, and Saccharimonadales populations was distinctly higher in the T. controversa-inoculated group than in the control group. The members of Dehalococcoidia, Nitrosomonadaceae, and Thermomicrobiales were found only in T. controversa-inoculated soils, and these taxa may have potential effects against the pathogen and contribute to disease control of wheat dwarf bunt. In addition, for T. controversa-infected plants, the soil treated with difenoconazole showed a high relative abundance of Proteobacteria, Actinobacteria, Ascomycota, Basidiomycota, Mortierellomycota, and Olpidiomycota based on the heatmap analysis and ANOVA. Our findings suggest that the optimized concentration of fungicide (5% recommended difenoconazole) exhibits better control efficiency and constant diversity in the rhizosphere soil.
Mutational Switch-Backs Can Accelerate Evolution of Francisella to a Combination of Ciprofloxacin and Doxycycline
Authors: Mehta Heer H. , Ibarra David , Marx Christopher J. , Miller Craig R. , Shamoo Yousif
Published: May 2022

Combination antimicrobial therapy has been considered a promising strategy to combat the evolution of antimicrobial resistance.Francisella tularensisis the causative agent of tularemia and in addition to being found in the nature, is recognized as a threat agent that requires vigilance. We investigated the evolutionary outcome of adapting the Live Vaccine Strain (LVS) ofF. tularensissubsp.holarcticato two non-interacting drugs, ciprofloxacin and doxycycline, individually, sequentially, and in combination. Despite their individual efficacies and independence of mechanisms, evolution to the combination arose on a shorter time scale than evolution to the two drugs sequentially. We conducted a longitudinal mutational analysis of the populations evolving to the drug combination, genetically reconstructed the identified evolutionary pathway, and carried out biochemical validation. We discovered that, after the appearance of an initial weak generalist mutation (FupA/B), each successive mutation alternated between adaptation to one drug or the other. In combination, these mutations allowed the population to more efficiently ascend the fitness peak through a series of evolutionary switch-backs. Clonal interference, weak pleiotropy, and positive epistasis also contributed to combinatorial evolution. This finding suggests that the use of this non-interacting drug pair againstF. tularensismay render both drugs ineffective because of mutational switch-backs that accelerate evolution of dual resistance.
Molecular Mingling: Multimodal Predictions of Ligand Promiscuity in Pentameric Ligand-Gated Ion Channels
Authors: Koniuszewski Filip , Vogel Florian D. , Bampali Konstantina , Fabjan Jure , Seidel Thomas , Scholze Petra , Schmiedhofer Philip B. , Langer Thierry , Ernst Margot
Published: May 2022

Background: Human pentameric ligand-gated ion channels (pLGICs) comprise nicotinic acetylcholine receptors (nAChRs), 5-hydroxytryptamine type 3 receptors (5-HT3Rs), zinc-activated channels (ZAC), γ-aminobutyric acid type A receptors (GABAARs) and glycine receptors (GlyRs). They are recognized therapeutic targets of some of the most prescribed drugs like general anesthetics, anxiolytics, smoking cessation aids, antiemetics and many more. Currently, approximately 100 experimental structures of pLGICs with ligands bound exist in the protein data bank (PDB). These atomic-level 3D structures enable the generation of a comprehensive binding site inventory for the superfamily and the in silico prediction of binding site properties.

Methods: A panel of high throughput in silico methods including pharmacophore screening, conformation analysis and descriptor calculation was applied to a selection of allosteric binding sites for which in vitro screens are lacking. Variant abundance near binding site forming regions and computational docking complement the approach.

Results: The structural data reflects known and novel binding sites, some of which may be unique to individual receptors, while others are broadly conserved. The membrane spanning domain, comprising four highly conserved segments, contains ligand interaction sites for which in vitro assays suitable for high throughput screenings are critically lacking. This is also the case for structurally more variable novel sites in the extracellular domain. Our computational results suggest that the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) can utilize multiple pockets which are likely to exist on most superfamily members.

Conclusion: With this study, we explore the potential for polypharmacology among pLGICs. Our data suggest that ligands can display two forms of promiscuity to an extent greater than what has been realized: 1) Ligands can interact with homologous sites in many members of the superfamily, which bears toxicological relevance. 2) Multiple pockets in distinct localizations of individual receptor subtypes share common ligands, which counteracts efforts to develop selective agents. Moreover, conformational states need to be considered for in silico drug screening, as certain binding sites display considerable flexibility. In total, this work contributes to a better understanding of polypharmacology across pLGICs and provides a basis for improved structure guided in silico drug development and drug derisking.
Hypoxic/Ischemic Inflammation, MicroRNAs and δ-Opioid Receptors: Hypoxia/Ischemia-Sensitive Versus-Insensitive Organs
Authors: Chen Yimeng , He Yichen , Zhao Shuchen , He Xiaozhou , Xue Dong , Xia Ying
Published: May 2022

Hypoxia and ischemia cause inflammatory injury and critically participate in the pathogenesis of various diseases in various organs. However, the protective strategies against hypoxic and ischemic insults are very limited in clinical settings up to date. It is of utmost importance to improve our understanding of hypoxic/ischemic (H/I) inflammation and find novel therapies for better prevention/treatment of H/I injury. Recent studies provide strong evidence that the expression of microRNAs (miRNAs), which regulate gene expression and affect H/I inflammation through post-transcriptional mechanisms, are differentially altered in response to H/I stress, while δ-opioid receptors (DOR) play a protective role against H/I insults in different organs, including both H/I-sensitive organs (e.g., brain, kidney, and heart) and H/I-insensitive organs (e.g., liver and muscle). Indeed, many studies have demonstrated the crucial role of the DOR-mediated cyto-protection against H/I injury by several molecular pathways, including NLRP3 inflammasome modulated by miRNAs. In this review, we summarize our recent studies along with those of others worldwide, and compare the effects of DOR on H/I expression of miRNAs in H/I-sensitive and -insensitive organs. The alternation in miRNA expression profiles upon DOR activation and the potential impact on inflammatory injury in different organs under normoxic and hypoxic conditions are discussed at molecular and cellular levels. More in-depth investigations into this field may provide novel clues for new protective strategies against H/I inflammation in different types of organs.
Deciphering the Link Between ERUPR Signaling and MicroRNA in Pathogenesis of Alzheimer’s Disease
Authors: Yasmeen Nusrath , Datta Manali , Kumar Vikram , Alshehri Fahad S. , Almalki Atiah H. , Haque Shafiul
Published: May 2022

Alzheimer’s disease (AD) is a neurodegenerative proteinopathic disease. The deposits of misfolded Amyloid β and Tau proteins in the brain of patients with AD suggest an imbalance in endoplasmic reticulum (ER) proteostasis. ER stress is due to accumulation of aberrant proteins in the ER lumen, which then leads to activation of three sensor protein pathways that ultimately evokes the adaptive mechanism of the unfolded protein response (UPR). The UPR mechanism operates via adaptive UPR and the apoptotic UPR. Adaptive UPR tries to restore imbalance in ER hemostasis by decreasing protein production, enhanced chaperone involvement to restore protein folding, misfolded protein decay by proteasome, and suppression of ribosomal translation ultimately relieving the excessive protein load in the ER. Subsequently, apoptotic UPR activated under severe ER stress conditions triggers cell death. MicroRNAs (miRNAs) are small non-coding protein causing dysregulated translational of mRNAs in a sequential manner. They are considered to be critical elements in the maintenance of numerous cellular activities, hemostasis, and developmental processes. Therefore, upregulation or downregulation of miRNA expression is implicated in several pathogenic processes. Evidence from scientific studies suggest a strong correlation between ERUPR signaling and miRNA dysregulation but the research done is still dormant. In this review, we summarized the cross-talk between ER stress, and the UPR signaling processes and their role in AD pathology by scrutinizing and collecting information from original research and review articles.
From the Sea for the Sight: Marine Derived Products for Human Vision
Authors: Brillante Simona , Galasso Christian , Lauritano Chiara , Carrella Sabrina
Published: May 2022

Visual impairment, at different degrees, produce a reduction of patient wellness which negatively impact in many aspects of working and social activities. Eye diseases can have common cellular damages or dysfunctions (e.g., inflammation, oxidative stress, neuronal degeneration), and can target several eye compartments, primarily cornea and retina. Marine organisms exhibit high chemical diversity due to the wide range of marine ecosystems where they live; thus, molecules of marine origin are gaining increasing attention for the development of new mutation-independent therapeutic strategies, to reduce the progression of retina pathologies having a multifactorial nature and characterized by high genetic heterogeneity. This review aims to describe marine natural products reported in the recent literature that showed promising therapeutic potential for the development of new drugs to be used to contrast the progression of eye pathologies. These natural compounds exhibited beneficial and protective properties on different in vitro cell systems and on in vivo models, through different mechanisms of action, including anti-inflammatory, antioxidant, antiangiogenic/vasoprotective or cytoprotective effects. We report compounds produced by several marine source (e.g., sponges, algae, shrimps) that can be administrated as food or with target-specific strategies. In addition, we describe and discuss the uses of opsin family proteins from marine organisms for the optimization of new optogenetic therapeutic strategies.
Environmentally Friendly and Roll-Processed Flexible Organic Solar Cells Based on PM6:Y6
Authors: Fernández-Castro Marcial , Truer Jean , Espindola-Rodriguez Moises , Andreasen Jens Wenzel
Published: May 2022

Organic Solar Cells (OSCs) have reached the highest efficiencies using lab-scale device manufacturing on active areas far below 0.1 cm2. The most used fabrication technique is spin-coating, which has poor potential for upscaling and substantial material waste. This tends to widen the so-called “lab-to-fab gap”, which is one of the most important challenges to make OSCs competitive. Other techniques such as blade or slot-die coating are much more suitable for roll-to-roll manufacturing, which is one of the advantages the technology presents due to the huge potential for fast and low-cost fabrication of flexible OSCs. However, only a few studies report solar cells using these fabrication techniques, especially applied on a roll-platform. Additionally, for environmentally friendly large area OSCs, inks based on non-hazardous solvent systems are needed. In this work, slot-die coating has been chosen to coat a PM6:Y6 active layer, using o-xylene, a more environmentally friendly alternative than halogenated solvents, and without additives. The optimal coating process is defined through fine-tuning of the coating parameters, such as the drying temperature and solution concentration. Moreover, ternary devices with PCBM, and fully printed devices are also fabricated. Power conversion efficiencies of 6.3% and 7.2% are achieved for binary PM6:Y6 and ternary PM6:Y6:PCBM devices measured with an aperture area of ∼0.4 cm2 (total device area ∼0.8 cm2).
A Schema-Based Robot Controller Complying With the Constraints of Biological Systems
Authors: Lagriffoul Fabien
Published: May 2022

This article reports on the early stages of conception of a robotic control system based on Piaget's schemas theory. Beyond some initial experimental results, we question the scientific method used in developmental robotics (DevRob) and argue that it is premature to abstract away the functional architecture of the brain when so little is known about its mechanisms. Instead, we advocate for applying a method similar to the method used in model-based cognitive science, which consists in selecting plausible models using computational and physiological constraints. Previous study on schema-based robotics is analyzed through the critical lens of the proposed method, and a minimal system designed using this method is presented.
Case Report: Fremitus Nystagmus in Superior Canal Dehiscence Syndrome
Authors: Morrison Miranda , Korda Athanasia , Wagner Franca , Caversaccio Marco Domenico , Mantokoudis Georgios
Published: May 2022

Superior canal dehiscence syndrome (SCDS) is a structural bony defect of the roof of the superior semi-circular canal into the middle cranial fossa and is responsible for the creation of a third window, which alters the dynamics of the inner ear. During humming, vibratory waves entering the vestibulum and cochlea are re-routed through the dehiscence, leading to stimulation of the otolithic and ampullary vestibular organs. This is responsible for the torsional-vertical nystagmus known as “fremitus nystagmus”. In this case report, we video-document a rare case of fremitus nystagmus and its resolution after plugging of the superior semi-circular canal.
Alpha-Synuclein Targeting Therapeutics for Parkinson's Disease and Related Synucleinopathies
Authors: Menon Sindhu , Armstrong Sabrina , Hamzeh Amir , Visanji Naomi P. , Sardi Sergio Pablo , Tandon Anurag
Published: May 2022

α-Synuclein (asyn) is a key pathogenetic factor in a group of neurodegenerative diseases generically known as synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Although the initial triggers of pathology and progression are unclear, multiple lines of evidence support therapeutic targeting of asyn in order to limit its prion-like misfolding. Here, we review recent pre-clinical and clinical work that offers promising treatment strategies to sequester, degrade, or silence asyn expression as a means to reduce the levels of seed or substrate. These diverse approaches include removal of aggregated asyn with passive or active immunization or by expression of vectorized antibodies, modulating kinetics of misfolding with small molecule anti-aggregants, lowering asyn gene expression by antisense oligonucleotides or inhibitory RNA, and pharmacological activation of asyn degradation pathways. We also discuss recent technological advances in combining low intensity focused ultrasound with intravenous microbubbles to transiently increase blood-brain barrier permeability for improved brain delivery and target engagement of these large molecule anti-asyn biologics.