bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Bioprinted Implants for Cartilage Repair in Intervertebral Discs and Knee Menisci
Authors: Perera Kalindu , Ivone Ryan , Natekin Evelina , Wilga Cheryl. A. , Shen Jie , Menon Jyothi U.
Published: October 2021

Cartilage defects pose a significant clinical challenge as they can lead to joint pain, swelling and stiffness, which reduces mobility and function thereby significantly affecting the quality of life of patients. More than 250,000 cartilage repair surgeries are performed in the United States every year. The current gold standard is the treatment of focal cartilage defects and bone damage with nonflexible metal or plastic prosthetics. However, these prosthetics are often made from hard and stiff materials that limits mobility and flexibility, and results in leaching of metal particles into the body, degeneration of adjacent soft bone tissues and possible failure of the implant with time. As a result, the patients may require revision surgeries to replace the worn implants or adjacent vertebrae. More recently, autograft – and allograft-based repair strategies have been studied, however these too are limited by donor site morbidity and the limited availability of tissues for surgery. There has been increasing interest in the past two decades in the area of cartilage tissue engineering where methods like 3D bioprinting may be implemented to generate functional constructs using a combination of cells, growth factors (GF) and biocompatible materials. 3D bioprinting allows for the modulation of mechanical properties of the developed constructs to maintain the required flexibility following implantation while also providing the stiffness needed to support body weight. In this review, we will provide a comprehensive overview of current advances in 3D bioprinting for cartilage tissue engineering for knee menisci and intervertebral disc repair. We will also discuss promising medical-grade materials and techniques that can be used for printing, and the future outlook of this emerging field.
Dynamic Gesture Recognition Using Surface EMG Signals Based on Multi-Stream Residual Network
Authors: Yang Zhiwen , Jiang Du , Sun Ying , Tao Bo , Tong Xiliang , Jiang Guozhang , Xu Manman , Yun Juntong , Liu Ying , Chen Baojia , Kong Jianyi
Published: October 2021

Gesture recognition technology is widely used in the flexible and precise control of manipulators in the assisted medical field. Our MResLSTM algorithm can effectively perform dynamic gesture recognition. The result of surface EMG signal decoding is applied to the controller, which can improve the fluency of artificial hand control. Much current gesture recognition research using sEMG has focused on static gestures. In addition, the accuracy of recognition depends on the extraction and selection of features. However, Static gesture research cannot meet the requirements of natural human-computer interaction and dexterous control of manipulators. Therefore, a multi-stream residual network (MResLSTM) is proposed for dynamic hand movement recognition. This study aims to improve the accuracy and stability of dynamic gesture recognition. Simultaneously, it can also advance the research on the smooth control of the Manipulator. We combine the residual model and the convolutional short-term memory model into a unified framework. The architecture extracts spatiotemporal features from two aspects: global and deep, and combines feature fusion to retain essential information. The strategy of pointwise group convolution and channel shuffle is used to reduce the number of network calculations. A dataset is constructed containing six dynamic gestures for model training. The experimental results show that on the same recognition model, the gesture recognition effect of fusion of sEMG signal and acceleration signal is better than that of only using sEMG signal. The proposed approach obtains competitive performance on our dataset with the recognition accuracies of 93.52%, achieving state-of-the-art performance with 89.65% precision on the Ninapro DB1 dataset. Our bionic calculation method is applied to the controller, which can realize the continuity of human-computer interaction and the flexibility of manipulator control.
RETRACTED: NR2F1-AS1/miR-190a/PHLDB2 Induces the Epithelial–Mesenchymal Transformation Process in Gastric Cancer by Promoting Phosphorylation of AKT3
Authors: Lv Jinqi , Zhang Simeng , Liu Yang , Li Ce , Guo Tianshu , Zhang Shuairan , Li Zenan , Jiao Zihan , Sun Haina , Zhang Ye , Xu Ling
Published: October 2021

The median survival time of patients with advanced gastric cancer (GC) who received radiotherapy and chemotherapy was <1 year. Epithelial–mesenchymal transformation (EMT) gives GC cells the ability to invade, which is an essential biological mechanism in the progression of GC. The long non-coding RNA (lncRNA)-based competitive endogenous RNA (ceRNA) system has been shown to play a key role in the GC-related EMT process. Although the AKT pathway is essential for EMT in GC, the relationship between AKT3 subtypes and EMT in GC is unclear. Here, we evaluated the underlying mechanism of ceRNA involving NR2F1-AS1/miR-190a/PHLDB2 in inducing EMT by promoting the expression and phosphorylation of AKT3. The results of bioinformatics analysis showed that the expression of NR2F1-AS1/miR-190a/PHLDB2 in GC was positively associated with the pathological features, staging, poor prognosis, and EMT process. We performed cell transfection, qRT-PCR, western blot, cell viability assay, TUNEL assay, Transwell assay, cell morphology observation, and double luciferase assay to confirm the regulation of NR2F1-AS1/miR-190a/PHLDB2 and its effect on EMT transformation. Finally, GSEA and GO/KEGG enrichment analysis identified that PI3K/AKT pathway was positively correlated to NR2F1-AS1/miR-190a/PHLDB2 expression. AKT3 knockout cells were co-transfected with PHLDB2-OE, and the findings revealed that AKT3 expression and phosphorylation were essential for the PHLDB2-mediated EMT process. Thus, our results showed that NR2F1-AS1/miR-190a/PHLDB2 promoted the phosphorylation of AKT3 to induce EMT in GC cells. This study provides a comprehensive understanding of the underlying mechanism involved in the EMT process as well as the identification of new EMT markers.
Highly Efficient Synthetic CRISPR RNA/Cas9-Based Mutagenesis for Rapid Cardiovascular Phenotypic Screening in F0 Zebrafish
Authors: Quick Rachael E. , Buck Luke D. , Parab Sweta , Tolbert Zane R. , Matsuoka Ryota L.
Published: October 2021

The zebrafish is a valuable vertebrate model to study cardiovascular formation and function due to the facile visualization and rapid development of the circulatory system in its externally growing embryos. Despite having distinct advantages, zebrafish have paralogs of many important genes, making reverse genetics approaches inefficient since generating animals bearing multiple gene mutations requires substantial efforts. Here, we present a simple and robust synthetic CRISPR RNA/Cas9-based mutagenesis approach for generating biallelic F0 zebrafish knockouts. Using a dual-guide synthetic CRISPR RNA/Cas9 ribonucleoprotein (dgRNP) system, we compared the efficiency of biallelic gene disruptions following the injections of one, two, and three dgRNPs per gene into the cytoplasm or yolk. We show that simultaneous cytoplasmic injections of three distinct dgRNPs per gene into one-cell stage embryos resulted in the most efficient and consistent biallelic gene disruptions. Importantly, this triple dgRNP approach enables efficient inactivation of cell autonomous and cell non-autonomous gene function, likely due to the low mosaicism of biallelic disruptions. In support of this finding, we provide evidence that the F0 animals generated by this method fully phenocopied the endothelial and peri-vascular defects observed in corresponding stable mutant homozygotes. Moreover, this approach faithfully recapitulated the trunk vessel phenotypes resulting from the genetic interaction between two vegfr2 zebrafish paralogs. Mechanistically, investigation of genome editing and mRNA decay indicates that the combined mutagenic actions of three dgRNPs per gene lead to an increased probability of frameshift mutations, enabling efficient biallelic gene disruptions. Therefore, our approach offers a highly robust genetic platform to quickly assess novel and redundant gene function in F0 zebrafish.
Mosmo Is Required for Zebrafish Craniofacial Formation
Authors: Camacho-Macorra Carlos , Sintes Marcos , Tabanera Noemí , Grasa Irene , Bovolenta Paola , Cardozo Marcos J.
Published: October 2021

Hedgehog (Hh) signaling is a highly regulated molecular pathway implicated in many developmental and homeostatic events. Mutations in genes encoding primary components or regulators of the pathway cause an array of congenital malformations or postnatal pathologies, the extent of which is not yet fully defined. Mosmo (Modulator of Smoothened) is a modulator of the Hh pathway, which encodes a membrane tetraspan protein. Studies in cell lines have shown that Mosmo promotes the internalization and degradation of the Hh signaling transducer Smoothened (Smo), thereby down-modulating pathway activation. Whether this modulation is essential for vertebrate embryonic development remains poorly explored. Here, we have addressed this question and show that in zebrafish embryos, the two mosmo paralogs, mosmoa and mosmob, are expressed in the head mesenchyme and along the entire ventral neural tube. At the cellular level, Mosmoa localizes at the plasma membrane, cytoplasmic vesicles and primary cilium in both zebrafish and chick embryos. CRISPR/Cas9 mediated inactivation of both mosmoa and mosmob in zebrafish causes frontonasal hypoplasia and craniofacial skeleton defects, which become evident in the adult fish. We thus suggest that MOSMO is a candidate to explain uncharacterized forms of human congenital craniofacial malformations, such as those present in the 16p12.1 chromosomal deletion syndrome encompassing the MOSMO locus.
Mechanisms of TLR4-Mediated Autophagy and Nitroxidative Stress
Authors: Zhang Kunli , Huang Qiuyan , Deng Shoulong , Yang Yecheng , Li Jianhao , Wang Sutian
Published: October 2021

Pathogenic infections have badly affected public health and the development of the breeding industry. Billions of dollars are spent every year fighting against these pathogens. The immune cells of a host produce reactive oxygen species and reactive nitrogen species which promote the clearance of these microbes. In addition, autophagy, which is considered an effective method to promote the destruction of pathogens, is involved in pathological processes. As research continues, the interplay between autophagy and nitroxidative stress has become apparent. Autophagy is always intertwined with nitroxidative stress. Autophagy regulates nitroxidative stress to maintain homeostasis within an appropriate range. Intracellular oxidation, in turn, is a strong inducer of autophagy. Toll-like receptor 4 (TLR4) is a pattern recognition receptor mainly involved in the regulation of inflammation during infectious diseases. Several studies have suggested that TLR4 is also a key regulator of autophagy and nitroxidative stress. In this review, we describe the role of TLR4 in autophagy and oxidation, and focus on its function in influencing autophagy-nitroxidative stress interactions.
Virtual (Computed) Fractional Flow Reserve: Future Role in Acute Coronary Syndromes
Authors: Haley Hazel Arfah , Ghobrial Mina , Morris Paul D. , Gosling Rebecca , Williams Gareth , Mills Mark T. , Newman Tom , Rammohan Vignesh , Pederzani Giulia , Lawford Patricia V. , Hose Rodney , Gunn Julian P.
Published: October 2021

The current management of acute coronary syndromes (ACS) is with an invasive strategy to guide treatment. However, identifying the lesions which are physiologically significant can be challenging. Non-invasive imaging is generally not appropriate or timely in the acute setting, so the decision is generally based upon visual assessment of the angiogram, supplemented in a small minority by invasive pressure wire studies using fractional flow reserve (FFR) or related indices. Whilst pressure wire usage is slowly increasing, it is not feasible in many vessels, patients and situations. Limited evidence for the use of FFR in non-ST elevation (NSTE) ACS suggests a 25% change in management, compared with traditional assessment, with a shift from more to less extensive revascularisation. Virtual (computed) FFR (vFFR), which uses a 3D model of the coronary arteries constructed from the invasive angiogram, and application of the physical laws of fluid flow, has the potential to be used more widely in this situation. It is less invasive, fast and can be integrated into catheter laboratory software. For severe lesions, or mild disease, it is probably not required, but it could improve the management of moderate disease in 'real time' for patients with non-ST elevation acute coronary syndromes (NSTE-ACS), and in bystander disease in ST elevation myocardial infarction. Its practicability and impact in the acute setting need to be tested, but the underpinning science and potential benefits for rapid and streamlined decision-making are enticing.
The Epidemiological Boehringer Ingelheim Employee Study (Part 3): Association of Elevated Fasting Insulin Levels but Not HOMA-IR With Increased Intima Media Thickness and Arteriosclerosis in Middle-Aged Persons
Authors: Röhling Martin , Kempf Kerstin , Kolb Hubert , Martin Tobias , Schneider Michael , Martin Stephan
Published: October 2021

Background:Recently published genetic studies have indicated a causal link between elevated insulin levels and cardiovascular disease (CVD) risk. We, therefore, hypothesized that increased fasting insulin levels are also associated with precursors of CVD such as endothelial lesions.

Methods:Middle-aged (≥40 years,n= 1,639) employees were followed up for the occurrence of increased intima media thickness (IMT ≥ 1 mm) or plaques in abdominal or cervical arteries (arteriosclerosis). Multivariable logistic regression analyses determined the incidence of increased IMT or arteriosclerosis. Adjusted relative risk (ARR) for increased IMT and arteriosclerosis was calculated by using Mantel-Haenszel analysis.

Results:Increased IMT was diagnosed in 238 participants (15 %) and 328 (20 %) developed arteriosclerosis after 5 years of follow-up. Logistic regression analysis identified fasting insulin, BMI and smoking as risk factors for both cardiovascular endpoints (allp< 0.05), whereas age and diastolic blood pressure were risk factors for increased IMT only, and male sex was associated with incident arteriosclerosis only (allp< 0.01). Additional adjustment for BMI change during follow-up did not modify these associations (including fasting insulin), but adjustment for fasting insulin change during follow-up removed BMI as risk factor for both cardiovascular endpoints. Fasting insulin change during follow-up but not BMI change associated with increased IMT and arteriosclerosis (bothp< 0.001). ARR analysis indicated that high fasting insulin and BMI added to age and sex as risk factors. Homeostatic model assessment of insulin resistance (HOMA-IR) did not associate with either cardiovascular endpoint in any model and smoking did not increase the risk conferred by high fasting insulin levels.

Conclusions:Higher fasting insulin levels and increases in fasting insulin over time are associated with atherogenic progression and supersede BMI as well as HOMA-IR as risk factors.
Modelling Representative Population Mobility for COVID-19 Spatial Transmission in South Africa
Authors: Potgieter A. , Fabris-Rotelli I. N. , Kimmie Z. , Dudeni-Tlhone N. , Holloway J. P. , Janse van Rensburg C. , Thiede R. N. , Debba P. , Manjoo-Docrat R. , Abdelatif N. , Khuluse-Makhanya S.
Published: October 2021

The COVID-19 pandemic starting in the first half of 2020 has changed the lives of everyone across the world. Reduced mobility was essential due to it being the largest impact possible against the spread of the little understood SARS-CoV-2 virus. To understand the spread, a comprehension of human mobility patterns is needed. The use of mobility data in modelling is thus essential to capture the intrinsic spread through the population. It is necessary to determine to what extent mobility data sources convey the same message of mobility within a region. This paper compares different mobility data sources by constructing spatial weight matrices at a variety of spatial resolutions and further compares the results through hierarchical clustering. We consider four methods for constructing spatial weight matrices representing mobility between spatial units, taking into account distance between spatial units as well as spatial covariates. This provides insight for the user into which data provides what type of information and in what situations a particular data source is most useful.
A Charge Balanced Neural Stimulator Silicon Chip for Human-Machine Interface
Authors: Liu Xu , Li Juzhe , Mao Wei , Chen Zhuangguang , Chen Zhijie , Wan Peiyuan , Yu Hao
Published: October 2021

This paper proposes a neural stimulator silicon chip design with an improved charge balancing technology. The proposed neural stimulation integrated circuit (IC) uses two charge balancing modules including synchronous charge detection module and short-time pulse insertion module. The synchronous charge detection module is designed based on a current splitter with ultra-small output current and an integrator circuit for neural stimulation pulse width control, which greatly reduces the residual charge remained on the electrode-tissue interface. The short-time pulse insertion module is designed based on the electrode voltage detection and compensation current control, which further reduces the accumulated residual charge and keeps the electrode voltage within a safety range of ±25 mV during multiple stimulation cycles. Finally, this neural stimulator is implemented in TSMC 0.18-μm CMOS process technology, and the chip function is tested and verified in both experiments with the electrode-tissue RC model and the PBS saline solution environment. The measurement result shows the neural stimulator chip achieves improved charge balancing with the residual charge smaller than 0.95 nC, which is the lowest compared to the traditional neural stimulator chips.
Growth Hormone Deficiency and Treatment in Childhood Cancer Survivors
Authors: Pollock Netanya I. , Cohen Laurie E.
Published: October 2021

Growth hormone (GH) deficiency is a common pituitary hormone deficiency in childhood cancer survivors (CCS). The identification, diagnosis, and treatment of those individuals at risk are important in order to minimize associated morbidities that can be ameliorated by treatment with recombinant human GH therapy. However, GH and insulin-like growth factor-I have been implicated in tumorigenesis, so there has been concern over the use of GH therapy in patients with a history of malignancy. Reassuringly, GH therapy has not been shown to increase risk of tumor recurrence. These patients have an increased risk for development of meningiomas, but this may be related to their history of cranial irradiation rather than to GH therapy. In this review, we detail the CCS who are at risk for GHD and the existing evidence on the safety profile of GH therapy in this patient population.
Computationally Accelerated Discovery and Experimental Demonstration of Gd0.5La0.5Co0.5Fe0.5O3 for Solar Thermochemical Hydrogen Production
Authors: Park James Eujin , Bare Zachary J. L. , Morelock Ryan J. , Rodriguez Mark A. , Ambrosini Andrea , Musgrave Charles B. , McDaniel Anthony H. , Coker Eric N.
Published: October 2021

Solar thermochemical hydrogen (STCH) production is a promising method to generate carbon neutral fuels by splitting water utilizing metal oxide materials and concentrated solar energy. The discovery of materials with enhanced water-splitting performance is critical for STCH to play a major role in the emerging renewable energy portfolio. While perovskite materials have been the focus of many recent efforts, materials screening can be time consuming due to the myriad chemical compositions possible. This can be greatly accelerated through computationally screening materials parameters including oxygen vacancy formation energy, phase stability, and electron effective mass. In this work, the perovskite Gd0.5La0.5Co0.5Fe0.5O3 (GLCF), was computationally determined to be a potential water splitter, and its activity was experimentally demonstrated. During water splitting tests with a thermal reduction temperature of 1,350°C, hydrogen yields of 101 μmol/g and 141 μmol/g were obtained at re-oxidation temperatures of 850 and 1,000°C, respectively, with increasing production observed during subsequent cycles. This is a significant improvement from similar compounds studied before (La0.6Sr0.4Co0.2Fe0.8O3 and LaFe0.75Co0.25O3) that suffer from performance degradation with subsequent cycles. Confirmed with high temperature x-ray diffraction (HT-XRD) patterns under inert and oxidizing atmosphere, the GLCF mainly maintained its phase while some decomposition to Gd2-xLaxO3 was observed.
Cardiac Fibrosis Is a Risk Factor for Severe COVID-19
Authors: Mustroph Julian , Hupf Julian , Baier Maria J. , Evert Katja , Brochhausen Christoph , Broeker Katharina , Meindl Christine , Seither Benedikt , Jungbauer Carsten , Evert Matthias , Maier Lars S. , Wagner Stefan
Published: October 2021

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor β1 (TGF-β1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-β1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-β1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-β1 mRNA performed at the time of first medical contact.
Nociceptive Sensory Fibers Drive Interleukin-23 Production in a Murine Model of Psoriasis via Calcitonin Gene-Related Peptide
Authors: Zhang Xuan , Cao Jiali , Zhao Siqi , Yang Xutong , Dong Jie , Tan Yaqi , Yu Teng , He Yanling
Published: October 2021

Neuroimmunity is involved in the pathogenesis of psoriasis, but the mechanism underlying the interaction between the nervous system and the interleukin (IL)-23/IL-17 immune axis is yet unclear. This study reveals the essential role of the sensory neuron-derived calcitonin gene-related peptide (CGRP) in imiquimod (IMQ)-induced expression of IL-23. First, we show that the increased nociceptive behavior was consistent with the development of psoriasiform dermatitis, which requires intact sensory innervation. Systemic ultrapotent Transient receptor potential vanilloid 1 (TRPV1) agonist (resiniferatoxin, RTX) treatment-induced sensory denervation resulted in a significant decrease in IL-23 expression in this model, while the recombinant IL-23 treatment induced IL-17A expression was intact after RTX treatment. In addition, IMQ exposure induced a transient increase in CGRP expression in the dorsal root ganglion. The neuron-derived CGRP expression was completely abolished by sensory denervation, thereby downregulating IL-23 expression, which could be reversed through the introduction of CGRP into the denervated dorsal skin. Our results suggest that nociceptive sensory neurons may drive the production of IL-23, resulting in IL-17A production from γδ T cells via the neuropeptide CGRP in the pathology of psoriasis.
Association Between Infections and Risk of Ankylosing Spondylitis: A Systematic Review and Meta-Analysis
Authors: Zhang Xiao , Sun Zhe , Zhou Aihong , Tao Lei , Chen Yingxin , Shi Xinyu , Yin Jia , Sun Zheng , Ding Guoyong
Published: October 2021

Background

Previous literature on the association between infections and the risk of developing ankylosing spondylitis (AS) presented controversial results. This meta-analysis aimed to quantitatively investigate the effect of infections on the risk of AS.

Methods

We searched the PubMed, Embase, and Web of Science databases until March 26, 2021 for analytical epidemiological studies on the association between infections and the risk of AS. Fixed or random effect models were used to calculate total risk estimates based on study heterogeneity. Subgroup analysis, and sensitivity analysis were also performed. Publication bias was estimated using funnel plots and Begg’s test.

Results

Six case-control articles (n=1,296,239) and seven cohort articles (n=7,618,524) were incorporated into our meta-analysis. The pooled odds ratio (OR) from these case-control studies showed that infections were associated with an increased risk of AS (OR=1.46, 95% confidence interval [CI], 1.23–1.73), and the pooled relative risk (RR) from the cohort studies showed the same findings (RR=1.35, 95% CI, 1.12–1.63). Subgroup analysis showed that infections in participants with unadjusted comorbidities (OR=1.66, 95% CI, 1.35–2.03), other types of infection (OR=1.40, 95% CI, 1.15–1.70), and infection of the immune system (OR=1.46, 95% CI, 1.42–1.49) were associated with the risk of AS in case-control studies. In cohort studies, infections with adjusted comorbidities (RR=1.39, 95% CI, 1.15–1.68), viral infection (RR=1.43, 95% CI, 1.22–1.66), other types of infection (RR=1.44, 95% CI, 1.12–1.86), and other sites of infection (RR=1.36, 95% CI, 1.11–1.67) were associated with an increased risk of AS.

Conclusions

The findings of this meta-analysis confirm that infections significantly increase the risks of AS. This is helpful in providing an essential basis for the prevention of ASviathe avoidance of infections.
Novel Insights Into the Genetic Population Connectivity of Transient Whale Sharks (Rhincodon typus) in Pacific Panama Provide Crucial Data for Conservation Efforts
Authors: Guzmán Héctor M. , Beaver Caitlin E. , Díaz-Ferguson Edgardo
Published: October 2021

The whale shark (Rhincodon typus) is an endangered and highly migratory species, of which solitary individuals or aggregations are observed in oceans worldwide and for which conservation efforts are hindered by a lack of comprehensive data on genetic population connectivity. Tissue samples were collected from wandering whale sharks in Pacific Panama to determine genetic diversity, phylogeographic origin, and possible global and local connectivity patterns using a 700–800 bp fragment of the mitochondrial control region gene. Genetic diversity among samples was high, with five new haplotypes and nine polymorphic sites identified among the 15 sequences. Haplotype diversity (Hd= 0.83) and nucleotide diversity (π = 0.00516) were similar to those reported in other studies. Our sequences, in particular haplotypesPTY1andPTY2, were similar to those previously reported in the Arabian Gulf and the Western Indian Ocean populations (a novel occurrence in the latter case). HaplotypesPTY3,PTY4, andPTY5were similar to populations in Mexico and the Gulf of California. In contrast, the only populations to which our Panamanian sequences were genetically dissimilar were those from the Atlantic Ocean. The absence of reference sequences in GenBank from southern sites in the Eastern Tropical Pacific, such as Galapagos (Ecuador), Gorgona and Malpelo Islands (Colombia), and Coco Island (Costa Rica), reduced our capacity to genetically define regional patterns. Genetic differentiation and connectivity were also assessed using an analysis of molecular variance (AMOVA), which showed a similar population structure (five groups) to the neighbor-joining tree. Other population features based on neutrality tests, such as Tajima’s D and Fu’sFsstatistics, showed positive values for Panama of 0.79 and 1.61, respectively. Positive values of these statistics indicate a lack of evidence for population expansion among the sampled individuals. Our results agree with previous reports suggesting that whale sharks can travel over long distances and that transboundary conservation measures may be effective for species protection.
Sediment Coarsening in Tidal Flats and Stable Coastline of the Abandoned Southern Yellow River Sub-Delta in Response to Fluvial Sediment Flux Decrease During the Past Decades
Authors: Zeng Lin , Zhan Chao , Wang Qing , Liu Xianbin , Wang Longsheng , Li Xueyan , Wang Xin , Yu Xiang , Zhang Jinzhi , Cui Buli
Published: October 2021

Due to remarkable reduction of sediment supply, the vulnerability of Yellow River deltaic system increased and ecological impacts occurred to some extent. To have a comprehensive and quantitative understanding of the morphological evolution of deltas, surficial sediments of tidal flat along the abandoned southern Yellow River sub-delta and two adjacent coastal units were systematically collected and evaluated by grain-size analysis in the study. The results reveal that surficial sediments of the abandoned southern Yellow River sub-delta have been coarsening significantly since the 1980s, as characterized by a decrease in both the mud content and the clay/mud ratio. In particular, the transition from cohesive to non-cohesive sediment was completed between 2007 and 2013. With a sharp decrease in sediment flux from the Yellow River estuary, the flood currents from the submarine coastal slope carry few fine particles into the tidal zone, whereas the ebb currents with reverse direction remove some fine particles from the tidal flat. This is a major cause of sediment coarsening in the tidal flat. As sediment coarsening, the coastline of the abandoned southern Yellow River sub-delta has remained stable. The significant change in the grain size of the tidal flat surficial sediments may have a profound impact on the future coastal geomorphic evolution.
Molecular Hydrogen: A Promising Adjunctive Strategy for the Treatment of the COVID-19
Authors: Li Yingning , Wang Zhen , Lian Naqi , Wang Yuzun , Zheng Weiqiang , Xie Keliang
Published: October 2021

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has no specific and effective treatment. The pathophysiological process of the COVID-19 is an excessive inflammatory response after an organism infects with a virus. Inflammatory storms play an important role in the development of the COVID-19. A large number of studies have confirmed that hydrogen has a therapeutic effect on many diseases via inhibiting excessive inflammatory cells and factors. Recently, a study led by the Academician Zhong Nanshan in China on the treatment of the patients with the COVID-19 by inhalation of a mixed gas composed of hydrogen and oxygen has attracted widespread international attention and hydrogen therapy has also been included in a new treatment plan for the COVID-19 in China. This study mainly describes the mechanism of occurrence of the COVID-19, summarizes the therapeutic effects and underlying mechanisms of hydrogen on the critical disease, and analyzes the feasibility and potential therapeutic targets of hydrogen for the treatment of the COVID-19.
Host-Related Laboratory Parameters for Leprosy Reactions
Authors: Luo Yuqian , Kiriya Mitsuo , Tanigawa Kazunari , Kawashima Akira , Nakamura Yasuhiro , Ishii Norihisa , Suzuki Koichi
Published: October 2021

Leprosy reactions are acute inflammatory episodes that complicate the course of aMycobacterium lepraeinfection and are the major cause of leprosy-associated pathology. Two types of leprosy reactions with relatively distinct pathogenesis and clinical features can occur: type 1 reaction, also known as reversal reaction, and type 2 reaction, also known as erythema nodosum leprosum. These acute nerve-destructive immune exacerbations often cause irreversible disabilities and deformities, especially when diagnosis is delayed. However, there is no diagnostic test to detect or predict leprosy reactions before the onset of clinical symptoms. Identification of biomarkers for leprosy reactions, which impede the development of symptoms or correlate with early-onset, will allow precise diagnosis and timely interventions to greatly improve the patients' quality of life. Here, we review the progress of research aimed at identifying biomarkers for leprosy reactions, including its correlation with not only immunity but also genetics, transcripts, and metabolites, providing an understanding of the immune dysfunction and inflammation that underly the pathogenesis of leprosy reactions. Nevertheless, no biomarkers that can reliably predict the subsequent occurrence of leprosy reactions from non-reactional patients and distinguish type I reaction from type II have yet been found.
Translation of Preclinical PET Imaging Findings: Challenges and Motion Correction to Overcome the Confounding Effect of Anesthetics
Authors: Miranda Alan , Bertoglio Daniele , Stroobants Sigrid , Staelens Steven , Verhaeghe Jeroen
Published: October 2021

Preclinical brain positron emission tomography (PET) in animals is performed using anesthesia to avoid movement during the PET scan. In contrast, brain PET scans in humans are typically performed in the awake subject. Anesthesia is therefore one of the principal limitations in the translation of preclinical brain PET to the clinic. This review summarizes the available literature supporting the confounding effect of anesthesia on several PET tracers for neuroscience in preclinical small animal scans. In a second part, we present the state-of-the-art methodologies to circumvent this limitation to increase the translational significance of preclinical research, with an emphasis on motion correction methods. Several motion tracking systems compatible with preclinical scanners have been developed, each one with its advantages and limitations. These systems and the novel experimental setups they can bring to preclinical brain PET research are reviewed here. While technical advances have been made in this field, and practical implementations have been demonstrated, the technique should become more readily available to research centers to allow for a wider adoption of the motion correction technique for brain research.
Muscle Physiopathology in Parathyroid Hormone Disorders
Authors: Romagnoli Cecilia , Brandi Maria Luisa
Published: October 2021

Parathyroid hormone disorders are a group of diseases in which secretion of parathormone (PTH) is impaired. The disorders that result are characterized by signs and symptoms associated with the persistent presence of high blood calcium levels (hypercalcemia) related to hyperparathyroidism (PHPT), or reduced blood calcium levels (hypocalcemia) associated with hypoparathyroidism (HypoPT). In addition to the resulting alteration in bone microarchitecture and mass for both pathologies, patients also report problems with skeletal muscle due to a decrease in muscular strength, muscular dysfunction, and myopathies, which can be responsible for an increased risk of instability and fracture. Although the effect of PTH on bone is well established, and numerous studies suggest that PTH has an effect on skeletal muscle, knowledge about cellular e molecular mechanisms of action on skeletal muscle is very limited. Skeletal muscle is a tissue well known for its structural and mechanical actions and is endowed with an extraordinary ability to adapt to physiological changes. Research in skeletal muscle has increased over the last decade, its importance as an endocrine tissue also emerging, becoming itself a target of numerous substances and hormones. Parathyroid hormone disorders represent a starting point to understand whether PTH may have an effect on skeletal muscle. This review analyzes the basic research data reported to date on PTH and skeletal muscle, highlighting the importance of increasing our knowledge in this field of research.
Bayesian Augmented Clinical Trials in TB Therapeutic Vaccination
Authors: Kiagias Dimitrios , Russo Giulia , Sgroi Giuseppe , Pappalardo Francesco , Juárez Miguel A.
Published: October 2021

We propose a Bayesian hierarchical method for combining in silico and in vivo data onto an augmented clinical trial with binary end points. The joint posterior distribution from the in silico experiment is treated as a prior, weighted by a measure of compatibility of the shared characteristics with the in vivo data. We also formalise the contribution and impact of in silico information in the augmented trial. We illustrate our approach to inference with in silico data from the UISS-TB simulator, a bespoke simulator of virtual patients with tuberculosis infection, and synthetic physical patients from a clinical trial.
Comparative Analysis of 16S rRNA Gene and Metagenome Sequencing in Pediatric Gut Microbiomes
Authors: Peterson Danielle , Bonham Kevin S. , Rowland Sophie , Pattanayak Cassandra W. ,   RESONANCE Consortium, Klepac-Ceraj Vanja
Published: October 2021

The colonization of the human gut microbiome begins at birth, and over time, these microbial communities become increasingly complex. Most of what we currently know about the human microbiome, especially in early stages of development, was described using culture-independent sequencing methods that allow us to identify the taxonomic composition of microbial communities using genomic techniques, such as amplicon or shotgun metagenomic sequencing. Each method has distinct tradeoffs, but there has not been a direct comparison of the utility of these methods in stool samples from very young children, which have different features than those of adults. We compared the effects of profiling the human infant gut microbiome with 16S rRNA amplicon vs. shotgun metagenomic sequencing techniques in 338 fecal samples; younger than 15, 15–30, and older than 30 months of age. We demonstrate that observed changes in alpha-diversity and beta-diversity with age occur to similar extents using both profiling methods. We also show that 16S rRNA profiling identified a larger number of genera and we find several genera that are missed or underrepresented by each profiling method. We present the link between alpha diversity and shotgun metagenomic sequencing depth for children of different ages. These findings provide a guide for selecting an appropriate method and sequencing depth for the three studied age groups.
Protein Biomarker Identification for the Discrimination of Brucella melitensis Field Isolates From the Brucella melitensis Rev.1 Vaccine Strain by MALDI-TOF MS
Authors: Kornspan David , Brendebach Holger , Hofreuter Dirk , Mathur Shubham , Blum Shlomo Eduardo , Fleker Marcelo , Bardenstein Svetlana , Al Dahouk Sascha
Published: October 2021

Brucella melitensis Rev.1 is a live attenuated vaccine strain that is widely used to control brucellosis in small ruminants. For successful surveillance and control programs, rapid identification and characterization of Brucella isolates and reliable differentiation of vaccinated and naturally infected animals are essential prerequisites. Although MALDI-TOF MS is increasingly applied in clinical microbiology laboratories for the diagnosis of brucellosis, species or even strain differentiation by this method remains a challenge. To detect biomarkers, which enable to distinguish the B. melitensis Rev.1 vaccine strain from B. melitensis field isolates, we initially searched for unique marker proteins by in silico comparison of the B. melitensis Rev.1 and 16M proteomes. We found 113 protein sequences of B. melitensis 16M that revealed a homologous sequence in the B. melitensis Rev.1 annotation and 17 of these sequences yielded potential biomarker pairs. MALDI-TOF MS spectra of 18 B. melitensis Rev.1 vaccine and 183 Israeli B. melitensis field isolates were subsequently analyzed to validate the identified marker candidates. This approach detected two genus-wide unique biomarkers with properties most similar to the ribosomal proteins L24 and S12. These two proteins clearly discriminated B. melitensis Rev.1 from the closely related B. melitensis 16M and the Israeli B. melitensis field isolates. In addition, we verified their discriminatory power using a set of B. melitensis strains from various origins and of different MLVA types. Based on our results, we propose MALDI-TOF MS profiling as a rapid, cost-effective alternative to the traditional, time-consuming approach to differentiate certain B. melitensis isolates on strain level.
Bacterial Communities Present Distinct Co-occurrence Networks in Sediment and Water of the Thermokarst Lakes in the Yellow River Source Area
Authors: Ren Ze , Zhang Cheng , Li Xia , Ma Kang , Zhang Zhe , Feng Kexin , Cui Baoshan
Published: October 2021

Thermokarst lakes are a ubiquitous and important landscape feature in cold regions and are changing tremendously due to the accelerated climate change. In thermokarst lakes, sediment and water are two distinct but highly interconnected habitats, harboring different bacterial communities in terms of taxonomic composition. However, the co-occurrence networks of these bacterial communities remain unclear. Here, we investigate the co-occurrence ecological networks of sediment and water bacterial communities for thermokarst lakes in the Yellow River Source Area on the Qinghai-Tibet Plateau. The results show that the bacterial communities construct distinct co-occurrence networks in sediment and water. The metacommunity network was parsed into four major modules formed by the operational taxonomic units (OTUs) enriched in sediment or water independently, and water-enriched OTUs exhibited much closer interconnections than sediment-enriched OTUs. When considering the sediment and water bacterial networks separately, different topological properties and modular patterns present: the sediment bacterial network was more clustered while the modules less responded to the environmental variables. On the contrary, the water bacterial network was more complex with the OTUs more interconnected and its modules more responded to the environmental variables. Moreover, the results of the structural equation model suggest that, by the influence of environmental variations on individual modules, the water bacterial communities would be more vulnerable under the fact of accelerating climate change. This study provides insights beyond a conventional taxonomic perspective, adding our knowledge of the potential mechanisms structuring bacterial community assembly and improving our prediction of the responses of this fast-changing ecosystem to future climate change.
Flavobacterium flabelliforme sp. nov. and Flavobacterium geliluteum sp. nov., Two Multidrug-Resistant Psychrotrophic Species Isolated From Antarctica
Authors: Králová Stanislava , Busse Hans-Jürgen , Bezdíček Matěj , Sandoval-Powers Megan , Nykrýnová Markéta , Staňková Eva , Krsek Daniel , Sedláček Ivo
Published: October 2021

Despite unfavorable Antarctic conditions, such as cold temperatures, freeze-thaw cycles, high ultraviolet radiation, dryness and lack of nutrients, microorganisms were able to adapt and surprisingly thrive in this environment. In this study, eight cold-adapted Flavobacterium strains isolated from a remote Antarctic island, James Ross Island, were studied using a polyphasic taxonomic approach to determine their taxonomic position. Phylogenetic analyses based on the 16S rRNA gene and 92 core genes clearly showed that these strains formed two distinct phylogenetic clusters comprising three and five strains, with average nucleotide identities significantly below 90% between both proposed species as well as between their closest phylogenetic relatives. Phenotyping revealed a unique pattern of biochemical and physiological characteristics enabling differentiation from the closest phylogenetically related Flavobacterium spp. Chemotaxonomic analyses showed that type strains P4023T and P7388T were characterized by the major polyamine sym-homospermidine and a quinone system containing predominantly menaquinone MK-6. In the polar lipid profile phosphatidylethanolamine, an ornithine lipid and two unidentified lipids lacking a functional group were detected as major lipids. These characteristics along with fatty acid profiles confirmed that these species belong to the genus Flavobacterium. Thorough genomic analysis revealed the presence of numerous cold-inducible or cold-adaptation associated genes, such as cold-shock proteins, proteorhodopsin, carotenoid biosynthetic genes or oxidative-stress response genes. Genomes of type strains surprisingly harbored multiple prophages, with many of them predicted to be active. Genome-mining identified biosynthetic gene clusters in type strain genomes with a majority not matching any known clusters which supports further exploratory research possibilities involving these psychrotrophic bacteria. Antibiotic susceptibility testing revealed a pattern of multidrug-resistant phenotypes that were correlated with in silico antibiotic resistance prediction. Interestingly, while typical resistance finder tools failed to detect genes responsible for antibiotic resistance, genomic prediction confirmed a multidrug-resistant profile and suggested even broader resistance than tested. Results of this study confirmed and thoroughly characterized two novel psychrotrophic Flavobacterium species, for which the names Flavobacterium flabelliforme sp. nov. and Flavobacterium geliluteum sp. nov. are proposed.
Biofilm-Related Infections in Gram-Positive Bacteria and the Potential Role of the Long-Acting Agent Dalbavancin
Authors: Oliva Alessandra , Stefani Stefania , Venditti Mario , Di Domenico Enea Gino
Published: October 2021

Infections caused by Gram-positive bacteria are a major public health problem due to their increasing resistance to antibiotics. Staphylococcus and Enterococcus species’ resistance and pathogenicity are enhanced by their ability to form biofilm. The biofilm lifestyle represents a significant obstacle to treatment because bacterial cells become highly tolerant to a wide range of antimicrobial compounds normally effective against their planktonic forms. Thus, novel therapeutic strategies targeting biofilms are urgently needed. The lipoglycopeptide dalbavancin is a long-acting agent for treating acute bacterial skin and skin structure infections caused by a broad range of Gram-positive pathogens. Recent studies have shown promising activity of dalbavancin against Gram-positive biofilms, including methicillin-resistant S. aureus (MRSA), methicillin-resistant S. epidermidis (MRSE), and vancomycin-susceptible enterococci. This review outlines the mechanisms regulating biofilm development in Staphylococcus and Enterococcus species and the clinical impact of biofilm-related infections. In addition, it discusses the clinical implications and potential therapeutic perspectives of the long-acting drug dalbavancin against biofilm-forming Gram-positive pathogens.