bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges in the Development of Soft Sensors for Bioprocesses: A Critical Review
Authors: Brunner Vincent , Siegl Manuel , Geier Dominik , Becker Thomas
Published: August 2021

Among the greatest challenges in soft sensor development for bioprocesses are variable process lengths, multiple process phases, and erroneous model inputs due to sensor faults. This review article describes these three challenges and critically discusses the corresponding solution approaches from a data scientist’s perspective. This main part of the article is preceded by an overview of the status quo in the development and application of soft sensors. The scope of this article is mainly the upstream part of bioprocesses, although the solution approaches are in most cases also applicable to the downstream part. Variable process lengths are accounted for by data synchronization techniques such as indicator variables, curve registration, and dynamic time warping. Multiple process phases are partitioned by trajectory or correlation-based phase detection, enabling phase-adaptive modeling. Sensor faults are detected by symptom signals, pattern recognition, or by changing contributions of the corresponding sensor to a process model. According to the current state of the literature, tolerance to sensor faults remains the greatest challenge in soft sensor development, especially in the presence of variable process lengths and multiple process phases.
Hypoxia in Bone and Oxygen Releasing Biomaterials in Fracture Treatments Using Mesenchymal Stem Cell Therapy: A Review
Authors: Teh Seoh Wei , Koh Avin Ee-Hwan , Tong Jia Bei , Wu Xiaoyun , Samrot Antony V. , Rampal Sanjiv , Mok Pooi Ling , Subbiah Suresh Kumar
Published: August 2021

Bone fractures have a high degree of severity. This is usually a result of the physical trauma of diseases that affect bone tissues, such as osteoporosis. Due to its highly vascular nature, the bone is in a constant state of remodeling. Although those of younger ages possess bones with high regenerative potential, the impact of a disrupted vasculature can severely affect the recovery process and cause osteonecrosis. This is commonly seen in the neck of femur, scaphoid, and talus bone. In recent years, mesenchymal stem cell (MSC) therapy has been used to aid in the regeneration of afflicted bone. However, the cut-off in blood supply due to bone fractures can lead to hypoxia-induced changes in engrafted MSCs. Researchers have designed several oxygen-generating biomaterials and yielded varying degrees of success in enhancing tissue salvage and preserving cellular metabolism under ischemia. These can be utilized to further improve stem cell therapy for bone repair. In this review, we touch on the pathophysiology of these bone fractures and review the application of oxygen-generating biomaterials to further enhance MSC-mediated repair of fractures in the three aforementioned parts of the bone.
The Primary Cilium on Cells of Developing Skeletal Rudiments; Distribution, Characteristics and Response to Mechanical Stimulation
Authors: Shea Claire A. , Murphy Paula
Published: August 2021

Embryo movement is important for tissue differentiation and the formation of functional skeletal elements during embryonic development: reduced mechanical stimulation results in fused joints and misshapen skeletal rudiments with concomitant changes in the signaling environment and gene expression profiles in both mouse and chick immobile embryos. Despite the clear relationship between movement and skeletogenesis, the precise mechanisms by which mechanical stimuli influence gene regulatory processes are not clear. The primary cilium enables cells to sense mechanical stimuli in the cellular environment, playing a crucial mechanosensory role during kidney development and in articular cartilage and bone but little is known about cilia on developing skeletal tissues. Here, we examine the occurrence, length, position, and orientation of primary cilia across developing skeletal rudiments in mouse embryos during a period of pronounced mechanosensitivity and we report differences and similarities between wildtype and muscle-less mutant (Pax3Spd/Spd) rudiments. Strikingly, joint regions tend to have cilia positioned and oriented away from the joint, while there was a less obvious, but still significant, preferred position on the posterior aspect of cells within the proliferative and hypertrophic zones. Regions of the developing rudiments have characteristic proportions of ciliated cells, with more cilia in the resting and joint zones. Comparing wildtype to muscle-less mutant embryos, cilia are shorter in the mutant with no significant difference in the proportion of ciliated cells. Cilia at the mutant joint were also oriented away from the joint line.
A Novel Azaphilone Muyophilone A From the Endophytic Fungus Muyocopron laterale 0307-2
Authors: Yuan Chao , Guo Yuhua , Wang Ke , Wang Zhunian , Li Longfei , Zhu Huajie , Li Gang
Published: August 2021

Two known azaphilone derivatives, 4,6-dimethylcurvulinic acid (1) and austdiol (2), and their novel heterotrimer, muyophilone A (3), were isolated and identified from an endophytic fungus, Muyocopron laterale 0307-2. Their structures and stereochemistry were established by extensive spectroscopic analyses including HRMS, NMR spectroscopy, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectroscopic methods, as well as single crystal X-ray diffraction. In the structure of 3, two compound 2-derived azaphilone units were connected through an unprecedented five-membered carbon bridge which was proposed to be originated from compound 1. Compound 3 represents the first example of azaphilone heterotrimers.
Self-Radiopaque Markers Guiding Physician-Modified Fenestration (S-Fenestration) in Aortic Arch Endovascular Repair
Authors: Li Xin , Shu Chang , Li Quanming , He Hao , Li Ming , Wang Lunchang , Li Jiehua , Liu Dingxiao , Du Mingyuan
Published: August 2021

Backgrounds and Objectives: Thoracic endovascular aortic repair (TEVAR) has currently become the “first-line choice” for descending aortic pathologies. For pathologies located at the aortic arch, TEVAR with physician-modified fenestration (PMF) has been gained popularity as an alternative choice. However, stent fenestration is an experience-dependent technique and comes with possible adverse events such as misalignment. This study aims to introduce the self-radiopaque PMF (SF), which uses the radiopaque marker as a guiding indicator.

Methods: This is a single-center retrospective study of 125 patients who underwent the SF-TEVAR in Second Xiangya Hospital from December 2015 to December 2020. Data include basic clinical information and technique records of SF-TEVAR with follow-up results.

Results: According to the SF-TEVAR protocol, we have performed the procedures on 125 patients and obtained an instant success rate of 98.4%. A total of 140 aortic stent-grafts and 44 bridging stents have been implanted in this study. The operation time is 64.6 ± 19.3 min, X-ray exposure time (from first digital subtraction angiography (DSA) to last DSA) is 25.6 ± 14.3 min, and contrast volume is 82.2 ± 22.6 ml. The success rate of PMF alignment is 98.4%. One bailout stent-graft was implanted into the left subclavian artery (LSA) by the chimney technique (0.8%). One fenestration was successfully and immediately corrected after misalignment (0.8%). Large simultaneous fenestration was performed in six patients (4.8%) for the left common carotid artery (LCCA) and LSA and in two patients (1.6%) for IA, LCCA, and LSA. One hundred twenty-two out of 125 patients' LSAs have been kept patent by the technique during the follow-up. The bridging stent group consists of 44 patients who received LSA stents, while the non-bridging stent group includes the other 81 patients. Type I endoleak has occurred in seven patients (5.6%) 1 week after the procedure. During follow-up (23 ± 18 months), survival rate is 95.7% and branch artery patent rate is 97.4%.

Conclusions: The SF-TEVAR technique, which utilizes the radiopaque marker in stent-graft as an indication for PMF in TEVAR, seems a likely safe, effective, and efficient procedure that brings acceptable survival rate and branch artery patency rate. SF-TEVAR serves as a progressive alternative method to keep the branch artery patent in aortic arch endovascular reconstruction.
Oral, Tongue-Coating Microbiota, and Metabolic Disorders: A Novel Area of Interactive Research
Authors: Li Yiwen , Cui Jing , Liu Yanfei , Chen Keji , Huang Luqi , Liu Yue
Published: August 2021

Interactions between colonizing microbiota and the host have been fully confirmed, among which the tongue-coating microbiota have a moderate rate of renewal and disease sensitivity and are easily obtained, making them an ideal research subject. Oral microbiota disorders are related to diabetes, obesity, cardiovascular disease, cancer, and other systemic diseases. As an important part of the oral cavity, tongue-coating microbiota can promote gastritis and digestive system tumors, affecting the occurrence and development of multiple chronic diseases. Common risk factors include diet, age, and immune status, among others. Metabolic regulatory mechanisms may be similar between the tongue and gut microbiota. Tongue-coating microbiota can be transferred to the respiratory or digestive tract and create a new balance with local microorganisms, together with the host epithelial cells forming a biological barrier. This barrier is involved in the production and circulation of nitric oxide (NO) and the function of taste receptors, forming the oral-gut-brain axis (similar to the gut-brain axis). At present, the disease model and mechanism of tongue-coating microbiota affecting metabolism have not been widely studied, but they have tremendous potential.
The Potential of a Smartphone as an Urban Weather Station—An Exploratory Analysis
Authors: Cabrera Aly Noyola , Droste Arjan , Heusinkveld Bert G. , Steeneveld Gert-Jan
Published: August 2021

The ongoing urbanization requires enhanced understanding of the local meteorological and climatological conditions within the urban environment for multiple applications, concerning energy demand, human health, and spatial planning. Identifying areas with harmful meteorological conditions enables citizens and local authorities to take actions to optimize quality of life for urban dwellers. At the moment cities have (in general) limited networks of meteorological monitoring stations. To overcome this lack of observations, the use of non-traditional data sources is rapidly increasing. However, the use of such data sources without enough prior verification has become a controversial topic in the scientific community. This study aims to verify and assess one of the main non-traditional data sources, i.e. smartphones. The goal is to research the potential of smartphones (using the Samsung Galaxy S4 as an example phone model) to correctly sense air temperature, relative humidity, and solar radiation, and to determine to what extent environmental conditions negatively affect their performance. The smartphone readings were evaluated against observations from reference instrumentation at a weather station and a mobile measurement platform. We test the response time of the smartphone thermometer and hygrometer, and the light sensor’s cosine response. In a lab setting, we find that a smartphone can provide reliable temperature information when it is not exposed to direct solar radiation. The smartphone’s hygrometer performs better at low relative humidity levels while it can over-saturate at higher levels. The light sensor records show substantial correlation with global radiation observations, and short response times. Measurements along an urban transect of 10 km show the smartphone’s ability to react to fast changes of temperature in the field, both in time and space. However, a bias correction (dependent on wind speed and radiation) is required to represent the reference temperature. Finally we show that after such a bias correction, a smartphone record can successfully capture spatial variability over a transect as well.
Forests Without Frugivores and Frugivores Without Forests – An Investigation Into the Causes of a Paradox in One of the Last Archipelagos Colonized by Humans
Authors: Albert Sébastien , Flores Olivier , Ah-Peng Claudine , Strasberg Dominique
Published: August 2021

The Mascarenes are sadly famous worldwide for the massive extinction of their native vertebrates since recent human colonization. However, extinction patterns show astonishing disparities between the two main islands and between lineages of forest vertebrates. On Réunion (2,512 km2, 3,070 m) where about a third of native habitats remains, most large-bodied vertebrates, especially frugivores, collapsed by the first half of the 18th century, while several have survived longer and some still exist on Mauritius (1,865 km2, 828 m) where more than 95% of native habitats have been transformed. Considering lineages of forest vertebrates shared by both islands (23 genera, 53 species), we test the hypothesis that differing patterns of lowland suitable habitat destruction is the main cause behind this paradox. Before that, we assess the potential impact of other major drivers of extinctions since first contact with humans. Firstly, Mauritius shows earlier and more numerous introductions of mammal predators known for their devastating impact (except northern islets which have thus become important sanctuaries for several squamates). Secondly, settlers were inveterate hunters on both islands, but while Réunion was overhunted before Mauritius, the burst of human population in the latter in late 18th century has not led to the rapid extinction of all large native vertebrates. These two factors alone therefore cannot explain the observed paradox. Rather, the early destruction of lowland habitats (<400 m) on Réunion is concomitant with most extinctions of forest vertebrate, notably frugivores that rapidly lost most lowland habitats dominated by large fleshy-fruited plants. Moreover, landform-induced fragmentation has likely decreased the ability of adjacent habitats to act as effective refuges. Conversely, Mauritius retained suitable low-fragmented habitats until the late 19th which probably allowed, at least for a time, several native vertebrates to escape from multiple human-induced disturbances. Despite the almost total destruction of native habitats since then on Mauritius, conservation actions have saved several threatened vertebrate species that play a fundamental role in the functioning of native ecosystems. The fact that there are now more favorable habitats on Réunion than on Mauritius argues for the rewilding of Réunion with these extant large vertebrates.
Spatially Variable Effects of Artificially-Created Physical Complexity on Subtidal Benthos
Authors: O’Shaughnessy Kathryn A. , Perkol-Finkel Shimrit , Strain Elisabeth M. A. , Bishop Melanie J. , Hawkins Stephen J. , Hanley Mick E. , Lunt Paul , Thompson Richard C. , Hadary Tomer , Shirazi Raviv , Yunnie Anna L. E. , Amstutz Axelle , Milliet Laura , Yong Clara L. X. , Firth Louise B.
Published: August 2021

In response to the environmental damage caused by urbanization, Nature-based Solutions (NbS) are being implemented to enhance biodiversity and ecosystem processes with mutual benefits for society and nature. Although the field of NbS is flourishing, experiments in different geographic locations and environmental contexts have produced variable results, with knowledge particularly lacking for the subtidal zone. This study tested the effects of physical complexity on colonizing communities in subtidal habitats in two urban locations: (1) Plymouth, United Kingdom (northeast Atlantic) and (2) Tel Aviv, Israel (eastern Mediterranean) for 15- and 12-months, respectively. At each location, physical complexity was manipulated using experimental tiles that were either flat or had 2.5 or 5.0 cm ridges. In Plymouth, biological complexity was also manipulated through seeding tiles with habitat-forming mussels. The effects of the manipulations on taxon and functional richness, and community composition were assessed at both locations, and in Plymouth the survival and size of seeded mussels and abundance and size of recruited mussels were also assessed. Effects of physical complexity differed between locations. Physical complexity did not influence richness or community composition in Plymouth, while in Tel Aviv, there were effects of complexity on community composition. In Plymouth, effects of biological complexity were found with mussel seeding reducing taxon richness, supporting larger recruited mussels, and influencing community composition. Our results suggest that outcomes of NbS experiments are context-dependent and highlight the risk of extrapolating the findings outside of the context in which they were tested.
Metafounders May Reduce Bias in Composite Cattle Genomic Predictions
Authors: Kluska Sabrina , Masuda Yutaka , Ferraz José Bento Sterman , Tsuruta Shogo , Eler Joanir Pereira , Baldi Fernando , Lourenco Daniela
Published: August 2021

Metafounders are pseudo-individuals that act as proxies for animals in base populations. When metafounders are used, individuals from different breeds can be related through pedigree, improving the compatibility between genomic and pedigree relationships. The aim of this study was to investigate the use of metafounders and unknown parent groups (UPGs) for the genomic evaluation of a composite beef cattle population. Phenotypes were available for scrotal circumference at 14 months of age (SC14), post weaning gain (PWG), weaning weight (WW), and birth weight (BW). The pedigree included 680,551 animals, of which 1,899 were genotyped for or imputed to around 30,000 single-nucleotide polymorphisms (SNPs). Evaluations were performed based on pedigree (BLUP), pedigree with UPGs (BLUP_UPG), pedigree with metafounders (BLUP_MF), single-step genomic BLUP (ssGBLUP), ssGBLUP with UPGs for genomic and pedigree relationship matrices (ssGBLUP_UPG) or only for the pedigree relationship matrix (ssGBLUP_UPGA), and ssGBLUP with metafounders (ssGBLUP_MF). Each evaluation considered either four or 10 groups that were assigned based on breed of founders and intermediate crosses. To evaluate model performance, we used a validation method based on linear regression statistics to obtain accuracy, stability, dispersion, and bias of (genomic) estimated breeding value [(G)EBV]. Overall, relationships within and among metafounders were stronger in the scenario with 10 metafounders. Accuracy was greater for models with genomic information than for BLUP. Also, the stability of (G)EBVs was greater when genomic information was taken into account. Overall, pedigree-based methods showed lower inflation/deflation (regression coefficients close to 1.0) for SC14, WWM, and BWD traits. The level of inflation/deflation for genomic models was small and trait-dependent. Compared with regular ssGBLUP, ssGBLUP_MF4 displayed regression coefficient closer to one SC14, PWG, WWM, and BWD. Genomic models with metafounders seemed to be slightly more stable than models with UPGs based on higher similarity of results with different numbers of groups. Further, metafounders can help to reduce bias in genomic evaluations of composite beef cattle populations without reducing the stability of GEBVs.
Comparative Analysis of Genomic and Transcriptome Sequences Reveals Divergent Patterns of Codon Bias in Wheat and Its Ancestor Species
Authors: Yang Chenkang , Zhao Qi , Wang Ying , Zhao Jiajia , Qiao Ling , Wu Bangbang , Yan Suxian , Zheng Jun , Zheng Xingwei
Published: August 2021

The synonymous codons usage shows a characteristic pattern of preference in each organism. This codon usage bias is thought to have evolved for efficient protein synthesis. Synonymous codon usage was studied in genes of the hexaploid wheat Triticum aestivum (AABBDD) and its progenitor species, Triticum urartu (AA), Aegilops tauschii (DD), and Triticum turgidum (AABB). Triticum aestivum exhibited stronger usage bias for G/C-ending codons than did the three progenitor species, and this bias was especially higher compared to T. turgidum and Ae. tauschii. High GC content is a primary factor influencing codon usage in T. aestivum. Neutrality analysis showed a significant positive correlation (p<0.001) between GC12 and GC3 in the four species with regression line slopes near zero (0.16–0.20), suggesting that the effect of mutation on codon usage was only 16–20%. The GC3s values of genes were associated with gene length and distribution density within chromosomes. tRNA abundance data indicated that codon preference corresponded to the relative abundance of isoaccepting tRNAs in the four species. Both mutation and selection have affected synonymous codon usage in hexaploid wheat and its progenitor species. GO enrichment showed that GC biased genes were commonly enriched in physiological processes such as photosynthesis and response to acid chemical. In some certain gene families with important functions, the codon usage of small parts of genes has changed during the evolution process of T. aestivum.
Analysis of Bulk RNA Sequencing Data Reveals Novel Transcription Factors Associated With Immune Infiltration Among Multiple Cancers
Authors: Liu Lei , Zhao Qiuchen , Cheng Chao , Yi Jingwen , Sun Hongyan , Wang Qi , Quan Weili , Xue Yaqiang , Sun Luguo , Cong Xianling , Zhang Yi
Published: August 2021

Tumor-infiltrating immune cells shape the tumor microenvironment and are closely related to clinical outcomes. Several transcription factors (TFs) have also been reported to regulate the antitumor activity and immune cell infiltration. This study aimed to quantify the populations of different immune cells infiltrated in tumor samples based on the bulk RNA sequencing data obtained from 50 cancer patients using the CIBERSORT and the EPIC algorithm. Weighted gene coexpression network analysis (WGCNA) identified eigengene modules strongly associated with tumorigenesis and the activation of CD4+ memory T cells, dendritic cells, and macrophages. TF genesFOXM1,MYBL2,TAL1, andERGare central in the subnetworks of the eigengene modules associated with immune-related genes. The analysis of The Cancer Genome Atlas (TCGA) cancer data confirmed these findings and further showed that the expression of these potential TF genes regulating immune infiltration, and the immune-related genes that they regulated, was associated with the survival of patients within multiple cancers. Exome-seq was performed on 24 paired samples that also had RNA-seq data. The expression quantitative trait loci (eQTL) analysis showed that mutations were significantly more frequent in the regions flanking the TF genes compared with those of non-TF genes, suggesting a driver role of these TF genes regulating immune infiltration. Taken together, this study presented a practical method for identifying genes that regulate immune infiltration. These genes could be potential biomarkers for cancer prognosis and possible therapeutic targets.
Brief Episodes of Nocturnal Hypoxia and Acidification Reduce Survival of Economically Important Blue Crab (Callinectes sapidus) Larvae
Authors: Tomasetti Stephen J. , Kraemer Jeffrey R. , Gobler Christopher J.
Published: August 2021

Many shallow coastal systems experience diel fluctuations in dissolved oxygen (DO) and pH that can intensify throughout the summer season and expose estuarine organisms to repeated episodes of coastal hypoxia and acidification. In temperate regions, larval release of the economically important blue crab Callinectes sapidus occurs in the summer, and while the earliest stage (zoea I) larvae are susceptible to persistent low DO and low pH conditions, their sensitivity to diel fluctuations is unknown. Here, a series of short-term (≤96 h) experiments were conducted to investigate the survival of C. sapidus zoea I larvae exposed to a range of diel cycling hypoxic and acidified conditions and durations. Two experiments comparing a diel cycling DO/pH treatment (fluctuating from ∼30% air saturation to ∼103% averaging ∼66%/and from pH ∼7.26 to ∼7.80 averaging ∼7.53) to a static low DO/pH treatment (∼43%/∼7.35), a static moderate DO/pH treatment (∼68%/∼7.59), and a static control treatment (∼106%/∼7.94) indicated that survival in the diel cycling treatment was significantly lower than the moderate treatment (p < 0.05) by 75 and 48% over 96 and 48 h, respectively, despite comparable mean experimental DO/pH values. Three other experiments aimed at identifying the effective minimum duration of low DO/low pH to significantly depress larval survival under diel cycling conditions revealed that 8 h of low DO/low pH (∼28%/∼7.43) over a 24-h diel cycle consistently decreased survival (p < 0.05) relative to control conditions by at least 55% regardless of experimental duration (72-, 48-, and 24-h experiments). An increase in DO beyond saturation to supersaturation (160%) and pH beyond normocapnic to highly basified (8.34) conditions during the day phase of the diel cycle did not improve survival of larvae exposed to nocturnal hypoxia and acidification. Collectively, these experiments demonstrate that diel cycling does not provide newly hatched C. sapidus larvae a temporal refuge capable of ameliorating low DO/pH stress, but rather is more lethal than chronic exposure to comparable average DO/pH conditions. Given that larvae exposed to a single nocturnal episode of moderate hypoxia and acidification experience significantly reduced survival, such occurrences may depress larval recruitment.
Safe Limits of Contrast Media for Contrast-Induced Nephropathy: A Multicenter Prospective Cohort Study
Authors: Nie Zhiqiang , Liu Yong , Wang Chao , Sun Guoli , Chen Guo , Lu Zuxun
Published: August 2021

Background: The safe level of contrast media volume (CV) is an important modifiable risk factor for contrast-induced nephropathy (CIN). The safe limit of CV remains unclear and is limited to single-center studies. Our objective was to determine the association between the ratio of contrast volume-to-glomerular filtration (CV/GFR) and CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI).

Methods: We assessed the association between CV/GFR and the risk of CIN in 4,254 patients undergoing CAG or PCI from the year 2013 to 2016 and enrolled in the REICIN (REduction of rIsk for Contrast-Induced Nephropathy), a prospective, multicenter, observational cohort study. CV/GFR was calculated at the five primary GFR equation.

Results: Sixty-nine (1.7%) patients with a median contrast volume-to-chronic kidney disease epidemiology collaboration (CV/CKD-EPI) ratio of 2.16 (1.30–3.93) have suffered from CIN. The CV/CKD-EPI demonstrated the best performance of model fit, discrimination (area under curve = 0.736), calibration, reclassification, and equation conciseness (1 variable). The CV/CKD-EPI ≥1.78 was the statistical significance associated with CIN [adjusted odds ratio, 4.64 (2.84–7.56); p < 0.001]. Furthermore, similar results were found in the subgroup analyses.

Conclusions: The CV/CKD-EPI showed the best performance in patients undergoing CAG or PCI. CV/CKD-EPI ≥1.78 could be a more reliable and convenient predictor of CIN. Intraprocedural preventive measures should include a priori calculation of CV/GFR to limit contrast volume.
Comparison of Success Rate and Complications of Totally Percutaneous Decannulation in Patients With Veno-Arterial Extracorporeal Membrane Oxygenation and Endovascular Aneurysm Repair
Authors: Liu Zhenjie , Xu Yongshan , Xu Xin , He Minzhi , Han Pan , Shao Changming , Pan Yifeng , Zhang Libin , Yin Li , Li Zhenhua , Huang Man , Chen Bing
Published: August 2021

Background: Total percutaneous closure for the site of femoral arterial puncture using Perclose ProGlide (PP) has become prevalent post-percutaneous endovascular aortic repair (EVAR) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

Objective: To evaluate the safety and efficacy of total percutaneous closure of the femoral artery access site post-EVAR compared with VA-ECMO.

Methods: This was a retrospective observational study conducted over 4 years, including 88 patients who underwent EVAR (64 patients) and VA-ECMO (24 patients). Perclose ProGlide devices were used in the femoral artery puncture sites closed percutaneously. In this study, technical success was defined as successful arterial closure of the common femoral artery (CFA) without additional surgical or endovascular procedures to prevent vessel leaking. Access site complications, including overt bleeding requiring transfusion or surgical intervention, minor bleeding, tinea cruris, pseudoaneurysm, and lymphocele, were recorded 24 h and 30 days after arterial closure.

Results: Each group's technical success rates were 95.8% (VA-ECMO) and 92.2% EVAR, respectively. There were no differences in the periprocedural complications of major bleeding, pseudoaneurysm, minor bleeding, acute limb ischemia, and groin infection. Furthermore, we did not observe any complications such as arterial thrombosis, dissection, stenosis, arteriovenous fistula, hematoma, groin infection, or lymphocele at the access site by following-up an ultrasound examination. There was no significant difference in the technical success rate of percutaneous closure by the PP device in the EVAR and VA-ECMO oxygenation groups. Also, no periprocedural or 30-day complications were observed at the access site of the EVAR and VA-ECMO patients.
Evaluating the Assembly Dynamics in the Human Vaginal Microbiomes With Niche-Neutral Hybrid Modeling
Authors: Ma Zhanshan (Sam)
Published: August 2021

Using 2,733 longitudinal vaginal microbiome samples (representing local microbial communities) from 79 individuals (representing meta-communities) in the states of healthy, BV (bacterial vaginosis) and pregnancy, we assess and interpret the relative importance of stochastic forces (e.g., stochastic drifts in bacteria demography, and stochastic dispersal) vs. deterministic selection (e.g., host genome, and host physiology) in shaping the dynamics of human vaginal microbiome (HVM) diversity by an integrated analysis with multi-site neutral (MSN) and niche-neutral hybrid (NNH) modeling. It was found that, when the traditional “default”P-value = 0.05 was specified, the neutral drifts were predominant (≥50% metacommunities indistinguishable from the MSN prediction), while the niche differentiations were moderate (<20% from the NNH prediction). The study also analyzed two challenging uncertainties in testing the neutral and/or niche-neutral hybrid models, i.e., lack of full model specificity – non-unique fittings of same datasets to multiple models with potentially different mechanistic assumptions – and lack of definite rules for setting theP-value thresholds (also noted asPt-value when referring to the threshold ofP-value in this article) in testing null hypothesis (model). Indeed, the two uncertainties can be interdependent, which further complicates the statistical inferences. To deal with the uncertainties, the MSN/NNH test results under a series ofP-values ranged from 0.05 to 0.95 were presented. Furthermore, the influence ofP-value threshold-setting on the model specificity, and the effects of woman’s health status on the neutrality level of HVM were examined. It was found that with the increase ofP-value threshold from 0.05 to 0.95, the overlap (non-unique) fitting of MSN and NNH decreased from 29.1 to 1.3%, whereas the specificity (uniquely fitted to data) of MSN model was kept between 55.7 and 82.3%. Also with the risingP-value threshold, the difference between healthy and BV groups become significant. These findings suggested that traditional singleP-value threshold (such as thede factostandardP-value = 0.05) might be insufficient for testing the neutral and/or niche neutral hybrid models.
Packpred: Predicting the Functional Effect of Missense Mutations
Authors: Tan Kuan Pern , Kanitkar Tejashree Rajaram , Kwoh Chee Keong , Madhusudhan Mallur Srivatsan
Published: August 2021

Predicting the functional consequences of single point mutations has relevance to protein function annotation and to clinical analysis/diagnosis. We developed and tested Packpred that makes use of a multi-body clique statistical potential in combination with a depth-dependent amino acid substitution matrix (FADHM) and positional Shannon entropy to predict the functional consequences of point mutations in proteins. Parameters were trained over a saturation mutagenesis data set of T4-lysozyme (1,966 mutations). The method was tested over another saturation mutagenesis data set (CcdB; 1,534 mutations) and the Missense3D data set (4,099 mutations). The performance of Packpred was compared against those of six other contemporary methods. With MCC values of 0.42, 0.47, and 0.36 on the training and testing data sets, respectively, Packpred outperforms all methods in all data sets, with the exception of marginally underperforming in comparison to FADHM in the CcdB data set. A meta server analysis was performed that chose best performing methods of wild-type amino acids and for wild-type mutant amino acid pairs. This led to an increase in the MCC value of 0.40 and 0.51 for the two meta predictors, respectively, on the Missense3D data set. We conjecture that it is possible to improve accuracy with better meta predictors as among the seven methods compared, at least one method or another is able to correctly predict ∼99% of the data.
Cholesterol Is a Dose-Dependent Positive Allosteric Modulator of CCR3 Ligand Affinity and G Protein Coupling
Authors: van Aalst Evan , Wylie Benjamin J.
Published: August 2021

Cholesterol as an allosteric modulator of G protein-coupled receptor (GPCR) function is well documented. This quintessential mammalian lipid facilitates receptor–ligand interactions and multimerization states. Functionally, this introduces a complicated mechanism for the homeostatic modulation of GPCR signaling. Chemokine receptors are Class A GPCRs responsible for immune cell trafficking through the binding of endogenous peptide ligands. CCR3 is a CC motif chemokine receptor expressed by eosinophils and basophils. It traffics these cells by transducing the signal stimulated by the CC motif chemokine primary messengers 11, 24, and 26. These behaviors are close to the human immunoresponse. Thus, CCR3 is implicated in cancer metastasis and inflammatory conditions. However, there is a paucity of experimental evidence linking the functional states of CCR3 to the molecular mechanisms of cholesterol–receptor cooperativity. In this vein, we present a means to combine codon harmonization and a maltose-binding protein fusion tag to produce CCR3 from E. coli. This technique yields ∼2.6 mg of functional GPCR per liter of minimal media. We leveraged this protein production capability to investigate the effects of cholesterol on CCR3 function in vitro. We found that affinity for the endogenous ligand CCL11 increases in a dose-dependent manner with cholesterol concentration in both styrene:maleic acid lipid particles (SMALPs) and proteoliposomes. This heightened receptor activation directly translates to increased signal transduction as measured by the GTPase activity of the bound G-protein α inhibitory subunit 3 (Gαi3). This work represents a critical step forward in understanding the role of cholesterol-GPCR allostery in regulation of signal transduction.
Microglial TREM2 Mitigates Inflammatory Responses and Neuronal Apoptosis in Angiotensin II-Induced Hypertension in Middle-Aged Mice
Authors: Xu Xiaotian , Du Lin , Jiang Jianxiong , Yang Ming , Wang Zhaoxia , Wang Yingge , Tang Tieyu , Fu Xuetao , Hao Jiukuan
Published: August 2021

Growing evidence suggests that hypertension and aging are prominent risk factors for the development of late-onset Alzheimer’s disease (LOAD) by inducement of neuroinflammation. Recent study showed that neuroinflammation via activated microglia induces reactive astrocytes, termed A1 astrocytes, that highly upregulate numerous classical complement cascade genes that are destructive to neurons in neurodegeneration diseases. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) is considered as one of the strongest single-allele genetic risk factors and plays important roles in neuroinflammation for LOAD. However, the mechanisms of microglia in the regulation of A1 astrocytic activation are still not clear. We introduced angiotensin II-induced hypertension in middle-aged mice and found that hypertension-upregulated TREM2 expression and A1 astrocytic activation were involved in neuroinflammation in the animal models used in this study. The in vitro results revealed that overexpression of microglial TREM2 not only mitigated microglial inflammatory response but also had salutary effects on reverse A1 astrocytic activation and neuronal toxicity.
Pathogenic Variants in ABHD16A Cause a Novel Psychomotor Developmental Disorder With Spastic Paraplegia
Authors: Yahia Ashraf , Elsayed Liena E. O. , Valter Remi , Hamed Ahlam A. A. , Mohammed Inaam N. , Elseed Maha A. , Salih Mustafa A. , Esteves Typhaine , Auger Nicolas , Abubaker Rayan , Koko Mahmoud , Abozar Fatima , Malik Hiba , Adil Rawaa , Emad Sara , Musallam Mhammed Alhassan , Idris Razaz , Eltazi Isra Z. M. , Babai Arwa , Ahmed Elhami A. A. , Abd Allah Amal S. I. , Mairey Mathilde , Ahmed Ahmed K. M. A. , Elbashir Mustafa I. , Brice Alexis , Ibrahim Muntaser E. , Ahmed Ammar E. , Lamari Foudil , Stevanin Giovanni
Published: August 2021

Introduction: Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common feature. Abnormalities in multiple cellular processes are implicated in their pathogenesis, including lipid metabolism; but still 40% of the patients are undiagnosed. Our goal was to identify the disease-causing variants in Sudanese families excluded for known genetic causes and describe a novel clinico-genetic entity.

Methods: We studied four patients from two unrelated consanguineous Sudanese families who manifested a neurological phenotype characterized by spasticity, psychomotor developmental delay and/or regression, and intellectual impairment. We applied next-generation sequencing, bioinformatics analysis, and Sanger sequencing to identify the genetic culprit. We then explored the consequences of the identified variants in patients-derived fibroblasts using targeted-lipidomics strategies.

Results and Discussion: Two homozygous variants in ABHD16A segregated with the disease in the two studied families. ABHD16A encodes the main brain phosphatidylserine hydrolase. In vitro, we confirmed that ABHD16A loss of function reduces the levels of certain long-chain lysophosphatidylserine species while increases the levels of multiple phosphatidylserine species in patient's fibroblasts.

Conclusion:ABHD16A loss of function is implicated in the pathogenesis of a novel form of complex hereditary spastic paraplegia.
Mental Workload Estimation Based on Physiological Features for Pilot-UAV Teaming Applications
Authors: Singh Gaganpreet , Chanel Caroline P. C. , Roy Raphaëlle N.
Published: August 2021

Manned-Unmanned Teaming (MUM-T) can be defined as the teaming of aerial robots (artificial agents) along with a human pilot (natural agent), in which the human agent is not an authoritative controller but rather a cooperative team player. To our knowledge, no study has yet evaluated the impact of MUM-T scenarios on operators' mental workload (MW) using a neuroergonomic approach (i.e., using physiological measures), nor provided a MW estimation through classification applied on those measures. Moreover, the impact of the non-stationarity of the physiological signal is seldom taken into account in classification pipelines, particularly regarding the validation design. Therefore this study was designed with two goals: (i) to characterize and estimate MW in a MUM-T setting based on physiological signals; (ii) to assess the impact of the validation procedure on classification accuracy. In this context, a search and rescue (S&R) scenario was developed in which 14 participants played the role of a pilot cooperating with three UAVs (Unmanned Aerial Vehicles). Missions were designed to induce high and low MW levels, which were evaluated using self-reported, behavioral and physiological measures (i.e., cerebral, cardiac, and oculomotor features). Supervised classification pipelines based on various combinations of these physiological features were benchmarked, and two validation procedures were compared (i.e., a traditional one that does not take time into account vs. an ecological one that does). The main results are: (i) a significant impact of MW on all measures, (ii) a higher intra-subject classification accuracy (75%) reached using ECG features alone or in combination with EEG and ET ones with the Adaboost, Linear Discriminant Analysis or the Support Vector Machine classifiers. However this was only true with the traditional validation. There was a significant drop in classification accuracy using the ecological one. Interestingly, inter-subject classification with ecological validation (59.8%) surpassed both intra-subject with ecological and inter-subject with traditional validation. These results highlight the need for further developments to perform MW monitoring in such operational contexts.
Progress of Acupuncture Therapy in Diseases Based on Magnetic Resonance Image Studies: A Literature Review
Authors: Zhang Jinhuan , Li Zihan , Li Zhixian , Li Jiaying , Hu Qingmao , Xu Jinping , Yu Haibo
Published: August 2021

The neural mechanisms of acupuncture are not well-understood. Over the past decades, an increasing number of studies have used MRI to investigate the response of the brain to acupuncture. The current review aims to provide an update on acupuncture therapy in disease. The PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception to January 31, 2021. Article selection and data extraction were conducted by two review authors. A total of 107 publications about MRI in acupuncture were included, the collective findings of which were as follows: (1) stroke and GB34 (Yanglingquan) are the most studied disease and acupoint. Related studies suggested that the mechanism of acupuncture treatment for stroke may associate with structural and functional plasticity, left and right hemispheres balance, and activation of brain areas related to movement and cognition. GB34 is mainly used in stroke and Parkinson's disease, which mainly activates brain response in the premotor cortex, the supplementary motor area, and the supramarginal gyrus; (2) resting-state functional MRI (rs-fMRI) and functional connectivity (FC) analysis are the most frequently used approaches; (3) estimates of efficacy and brain response to acupuncture depend on the type of sham acupuncture (SA) used for comparison. Brain processing after acupuncture differs between patients and health controls (HC) and occurs mainly in disorder-related areas. Factors that influence the effect of acupuncture include depth of needling, number and locations of acupoints, and deqi and expectation effect, each contributing to the brain response. While studies using MRI have increased understanding of the mechanism underlying the effects of acupuncture, there is scope for development in this field. Due to the small sample sizes, heterogeneous study designs, and analytical methods, the results were inconsistent. Further studies with larger sample sizes, careful experimental design, multimodal neuroimaging techniques, and standardized methods should be conducted to better explain the efficacy and specificity of acupuncture, and to prepare for accurate efficacy prediction in the future.
The Antifungal Activity of Loquat (Eriobotrya japonica Lindl.) Leaves Extract Against Penicillium digitatum
Authors: Shen Yuting , Chen Chuying , Cai Nan , Yang Ruopeng , Chen Jinyin , Kahramanoǧlu İbrahim , Okatan Volkan , Rengasamy Kannan R. R. , Wan Chunpeng
Published: August 2021

This study was performed to determine the antifungal activity of loquat (Eriobotrya japonica Lindl) leaf extract (LLE) against the citrus postharvest pathogen Penicillium digitatum (P. digitatum). The LLE exhibited an antifungal activity against P. digitatum, with a minimum inhibitory concentration (MIC) of 0.625 mg/ml and a minimum fungicidal concentration (MFC) of 1.25 mg/ml. Significant inhibitory effects of LLE on mycelial growth and spore germination of P. digitatum were seen in a dose-dependent manner. Simultaneously, to investigate possible antifungal mechanisms by LLE, we analyzed their influence on morphological changes, cell membrane permeability, cell wall and cell membrane integrity, and adenosine phosphates (ATP, ADP, and AMP) levels. Alterations, such as sunken surface and malformation, occurred in the LLE-treated P. digitatum spores. Furthermore, intracellular inclusion content decreased after LLE treatment, indicating an increase in cell membrane permeability. Besides, the LLE treatment induced a significant decline in the level of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) with a noticeable addition of extracellular ATP, ADP, and AMP during the entire treatment period. Overall, the results manifested that the antifungal activity of LLE against P. digitatum can be attributed to the derangement of cell membrane permeability and disordered energy metabolism. This is the first report on the mechanism of antifungal activity of LLE and could be useful in the development of targeted fungicides from natural origin.
Metaproteomic Insights Into the Microbial Community in Pozol
Authors: Rizo Jocelin , Guillén Daniel , Díaz-Ruiz Gloria , Wacher Carmen , Encarnación Sergio , Sánchez Sergio , Rodríguez-Sanoja Romina
Published: August 2021

Pozol is an acidic, refreshing, and non-alcoholic traditional Mayan beverage made with nixtamalized corn dough that is fermented spontaneously. The extensive analysis of the microbiology, biochemistry and metaproteomics of pozol allowed the construction of a comprehensive image of the fermentation system. The main changes in both the substrate and the microbiota occurred in the first 9 h of fermentation. The increase in microorganisms correlated with the drop in pH and with the decrease in the contents of carbohydrates, lipids, and nitrogen, which shows that this stage has the highest metabolic activity. Bacterial proteins were mainly represented by those of lactic acid bacteria, and among them, the proteins from genus Streptococcus was overwhelmingly the most abundant. Yeast proteins were present in all the analyzed samples, while proteins from filamentous fungi increased up to 48 h. The metaproteomic approach allowed us to identify several previously unknown enzyme complexes in the system. Additionally, enzymes for hydrolysis of starch, hemicellulose and cellulose were found, indicating that all these substrates can be used as a carbon source by the microbiota. Finally, enzymes related to the production of essential intermediates involved in the synthesis of organic acids, acetoin, butanediol, fatty acids and amino acids important for the generation of compounds that contribute to the sensorial quality of pozol, were found.