bluuebunny/crossref_metadata_2025 huggingface dataset:
Hülle Cells of Aspergillus nidulans with Nuclear Storage and Developmental Backup Functions Are Reminiscent of Multipotent Stem Cells
Authors: Troppens Danielle M. , Köhler Anna M. , Schlüter Rabea , Hoppert Michael , Gerke Jennifer , Braus Gerhard H.
Published: August 2020

The
in vivo
identification of Hülle cells in cases of aspergillosis infections in animals and humans illustrates their biological relevance and suggests that they might be involved in pathogenicity. It is striking that aspergilli have developed and maintained a multinucleate nurse cell that is presumably energy-intensive to produce and is usually found only in higher eukaryotes. Our findings shed light on how the understudied Hülle cells might contribute to the success of aspergilli by acting not only as nurse cells under detrimental conditions (sexual development) but also as fungal backup stem cells with the capacity to produce genetically diverse spores in an accelerated manner, thereby substantially contributing to survival in response to predator attack or under otherwise severely destructive conditions. Our study solved the 90-year-old puzzle of Hülle cell germination and provides easy, reproducible methods that will facilitate future studies on biological and ecological roles of Hülle cells in aspergilli.
Rethinking Gain-of-Function Experiments in the Context of the COVID-19 Pandemic
Authors: Imperiale Michael J. , Casadevall Arturo
Published: August 2020

Proponents of the use of gain-of-function (GOF) experiments with pathogens with pandemic potential (PPP) have argued that such experiments are necessary because they reveal important facets of pathogenesis and can be performed safely. Opponents of GOF experiments with PPP have argued that the risks outweigh the knowledge gained. The COVID-19 pandemic demonstrates the vulnerability of human societies to a new PPP, while also validating some arguments of both camps, questioning others, and suggesting the need to rethink how we approach this class of experiments.
Enterobacterial Common Antigen: Synthesis and Function of an Enigmatic Molecule
Authors: Rai Ashutosh K. , Mitchell Angela M.
Published: August 2020

The outer membrane (OM) of Gram-negative bacteria poses a barrier to antibiotic entry due to its high impermeability. Thus, there is an urgent need to study the function and biogenesis of the OM. InEnterobacterales, an order of bacteria with many pathogenic members, one of the components of the OM is enterobacterial common antigen (ECA). We have known of the presence of ECA on the cell surface ofEnterobacteralesfor many years, but its properties have only more recently begun to be unraveled.
Development of a Counterselectable Transposon To Create Markerless Knockouts from an 18,432-Clone Ordered Mycobacterium bovis Bacillus Calmette-Guérin Mutant Resource
Authors: Borgers Katlyn , Vandewalle Kristof , Van Hecke Annelies , Michielsen Gitte , Plets Evelyn , van Schie Loes , Vanmarcke Sandrine , Schindfessel Laurent , Festjens Nele , Callewaert Nico
Published: August 2020

While speeding up research for many fields of biology (e.g., yeast, plant, and
Caenorhabditis elegans
), genome-wide ordered mutant collections are still elusive in mycobacterial research. We developed methods to generate such resources in a time- and cost-effective manner and developed a newly engineered transposon from which unmarked mutants can be efficiently generated. Our library in the WHO reference vaccine strain of
Mycobacterium bovis
BCG Danish targets 83% of all nonessential genes and was made publicly available via the BCCM/ITM Mycobacteria Collection. This resource will speed up
Mycobacterium
research (e.g., drug resistance research and vaccine development) and paves the way to similar genome-wide mutant collections in other strains of the
Mycobacterium tuberculosis
complex. The stretch to a full collection of mutants in all nonessential genes is now much shorter, with just 17% remaining genes to be targeted using gene-by-gene approaches, for which highly effective methods have recently also been described.
Microbial Strategies for Survival in the Glass Sponge
Vazella pourtalesii
Authors: Bayer Kristina , Busch Kathrin , Kenchington Ellen , Beazley Lindsay , Franzenburg Sören , Michels Jan , Hentschel Ute , Slaby Beate M.
Published: August 2020

We investigated the microbial community of
V. pourtalesii
that forms globally unique, monospecific sponge grounds under low-oxygen conditions on the Scotian Shelf, where it plays a key role in its vulnerable ecosystem. The microbial community was found to be concentrated within biomass patches and is dominated by small cells (<1 μm). MAG analyses showed consistently small genome sizes and low GC contents, which is unusual compared to known sponge symbionts. These properties, as well as the (facultatively) anaerobic metabolism and a high degree of interdependence between the dominant symbionts regarding amino acid and vitamin synthesis, are likely adaptations to the unique conditions within the syncytial tissue of their hexactinellid host and the low-oxygen environment.
Rates and causes of mortality among children and young people with and without intellectual disabilities in Scotland: a record linkage cohort study of 796 190 school children
Authors: Smith Gillian S , Fleming Michael , Kinnear Deborah , Henderson Angela , Pell J P , Melville Craig , Cooper Sally-Ann
Published: August 2020

Objectives

To investigate mortality rates and causes in children and young people with intellectual disabilities.

Design

Retrospective cohort; individual record linkage between Scotland’s annual pupil census and National Records of Scotland death register.

Setting

General community.

Participants

Pupils receiving local authority-funded schooling in Scotland, 2008 to 2013, with an Additional Support Need due to intellectual disabilities, compared with other pupils.

Main outcome measures

Deaths up to 2015: age of death, age-standardised mortality ratios (age-SMRs); causes of death including cause-specific age-SMRs; avoidable deaths as defined by the UK Office of National Statistics.

Results

18 278/947 922 (1.9%) pupils had intellectual disabilities. 106 died over 67 342 person-years (crude mortality rate=157/100 000 person-years), compared with 458 controls over 3 672 224 person-years (crude mortality rate=12/100 000 person-years). Age-SMR was 11.6 (95% CI 9.6 to 14.0); 16.6 (95% CI 12.2 to 22.6) for female pupils and 9.8 (95% CI 7.7 to 12.5) for male pupils. Most common main underlying causes were diseases of the nervous system, followed by congenital anomalies; most common all-contributing causes were diseases of the nervous system, followed by respiratory system; most common specific contributing causes were cerebral palsy, pneumonia, respiratory failure and epilepsy. For all contributing causes, SMR was 98.8 (95% CI 69.9 to 139.7) for congenital anomalies, 76.5 (95% CI 58.9 to 99.4) for nervous system, 63.7 (95% CI 37.0 to 109.7) for digestive system, 55.3 (95% CI 42.5 to 72.1) for respiratory system, 32.1 (95% CI 17.8 to 57.9) for endocrine and 14.8 (95% CI 8.9 to 24.5) for circulatory system. External causes accounted for 46% of control deaths, but the SMR for external-related deaths was still higher (3.6 (95% CI 2.2 to 5.8)) for pupils with intellectual disabilities. Deaths amenable to good care were common.

Conclusion

Pupils with intellectual disabilities were much more likely to die than their peers, and had a different pattern of causes, including amenable deaths across a wide range of disease categories. Improvements are needed to reduce amenable deaths, for example, epilepsy-related and dysphagia, and to support families of children with life-limiting conditions.
Fluoroquinolones as a potentially novel class of antidiabesity and antiproliferative compounds: synthesis and docking studies
Authors: Kasabri Violet , Arabiyat Shereen , Al-Hiari Yusuf , Zalloum Hiba , Almaliti Jehad , Telfah Ahmad , Bustanji Yasser K. , Alalawi Sundus
Published: August 2020

Intense efforts by the pharmaceutical industry have been made to identify new targets for obesity diabetes (diabesity). Pancreatic triacylglycerol lipase (PL) inhibition is an interesting putative target for obesity management. Fluoroquinolones (FQs) have been identified as potent inhibitors of PL. The aim of this research was to synthesize novel FQs and evaluate their in vitro antilipolytic and antiproliferative properties. Characterization of the synthesized FQs was carried out with NMR, MS, IR, and EA. Like orlistat, potential FQs’ modulation of PL was quantified colorimetrically (n = 3) and was further supported by docking studies. Compared with cisplatin, FQs’ antiproliferative propensities against a panel of obesity related colorectal cancer cell lines were investigated with Sulforhodamine B assay. Twelve novel FQs (2A–5A, 2B–5B, and 2C–5C) were synthesized and characterized. The PL-IC50 values of tested FQs were in the range of 6.8–165.7 μmol/L. FQ 4A was the most active antiproliferative compound against HCT116 with an IC50 value of 3.5 μmol/L. Their selectivity of growth inhibition for safety examination using normal periodontal ligament fibroblasts (PDL) in comparison with cisplatin’s lack of differential cytotoxicity was reported. Lipophilicity and hydrogen bonding were found essential for both activities. Conclusively, FQs are robustly proven for their emerging in vitro anti-obesity and antiproliferative activities.
Lactobacillus rhamnosus cell-free extract targets virulence and antifungal drug resistance in Candida albicans
Authors: Dube Yvonne , Khan Amber , Marimani Musa , Ahmad Aijaz
Published: August 2020

Candidiasis caused by multidrug-resistant Candida species continues to be difficult to eradicate. The use of live probiotic bacteria has gained a lot of interest in the treatment of candidiasis; however, whole-cell probiotic use can often be associated with a high risk of sepsis. Strategies manipulating cell-free methods using probiotic strains could lead to the development of novel antifungal solutions. Therefore, we evaluated the effect of three probiotic cell-free extracts (CFEs) on the growth, virulence traits, and drug efflux pumps in C. albicans. On the basis of its minimum inhibitory concentration, Lactobacillus rhamnosus was selected and assessed against various virulence traits and drug resistance mechanisms. The results showed that L. rhamnosus CFE significantly inhibited hyphae formation and reduced secretion of proteinases and phospholipases. Moreover, L. rhamnosus inhibited the drug efflux proteins in resistant C. albicans strains thus reversing drug resistance. Gene expression data confirmed downregulation of genes associated with microbial virulence and drug resistance following treatment of C. albicans with L. rhamnosus CFE. Through gas chromatography – mass spectrometry chemical characterization, high contents of oleic acid (24.82%) and myristic acid (13.11%) were observed in this CFE. Collectively, our findings indicate that L. rhamnosus may potentially be used for therapeutic purposes to inhibit C. albicans infections.
Constraining the tidal charge of brane black holes using their shadows
Authors: Neves Juliano C. S.
Published: August 2020

A constraint on the tidal charge generated within a brane world is shown. Using the shadow of a rotating black hole in a brane context in order to describe the M87* parameters recently announced by the Event Horizon Telescope Collaboration, the deviation from circularity of the reported shadow produces an upper bound on the bulk’s nonlocal effect, which is conceived of as a tidal charge in the four-dimensional brane induced by the five-dimensional bulk. Therefore, a deviation from circularity $$\lesssim 10\%$$≲10% leads to an upper bound on the tidal charge $$\lesssim 0.004M^2$$≲0.004M2.
Toward Better Understanding and Management of CAR-T Cell–Associated Toxicity
Authors: Schmidts Andrea , Wehrli Marc , Maus Marcela V.
Published: August 2020

Adoptive transfer of T cells modified with chimeric antigen receptors (CAR-T cells) has changed the therapeutic landscape of hematological malignancies, particularly for acute lymphoblastic leukemia and large B cell lymphoma, where two different CAR-T products are now considered standard of care. Furthermore, intense research efforts are under way to expand the clinical application of CAR-T cell therapy for the benefit of patients suffering from other types of cancers. Nevertheless, CAR-T cell treatment is associated with toxicities such as cytokine release syndrome, which can range in severity from mild flu-like symptoms to life-threatening vasodilatory shock, and a neurological syndrome termed ICANS (immune effector cell–associated neurotoxicity syndrome), which can also range in severity from a temporary cognitive deficit lasting only a few hours to lethal cerebral edema. In this review, we provide an in-depth discussion of different types of CAR-T cell–associated toxicities, including an overview of clinical presentation and grading, pathophysiology, and treatment options. We also address future perspectives and opportunities, with a special focus on hematological malignancies.
Synthesis of Bimetal Doped Metal-Organic Framework (MOF-5): An Electrocatalyst with Low Noble Metal Content and High Electrochemical Activity
Authors: Parkash Anand
Published: August 2020

The challenge to developing a rechargeable metal-air battery is designing and developing an oxygen reduction reaction (ORR) electrocatalyst that is reliable, low cost, and high-performance. Herein, a novel approach for the synthesis of ORR electrocatalysts presented, where Pt-Ni alloys, with ultra-low Pt contents (<1 wt%), are encapsulated in MOF-5 and then carbonized at 900 °C. Benefiting from its hierarchically porous structure and strong synergetic coupling among all prepared catalysts, the Pt/Ni/NPC-900 exhibits a positive onset potential (Eo) 1.01 V and half-wave potential (E1/2) of 0.89 V, as well as superior stability than commercial Pt/C (20 wt%) in alkaline media for ORR. This work will open up a novel route for the next generation of metal-air batteries to develop advanced bifunctional electrocatalysts.
Bismuth Vanadate Encapsulated with Reduced Graphene Oxide for Hydrogen Peroxide Generation
Authors: Dhabarde Nikhil , Tian Siyu , Xiong Guoping , Misra Mano , Subramanian Vaidyanathan
Published: August 2020

Hydrogen peroxide (H2O2), a strong oxidant, is considered as a highly value-added chemical due to its diverse applications. The conventional process for H2O2 production currently pursued is energy intensive, using reactants of explosive nature, and involves using expensive catalysts. However, a photocatalytic H2O2 production is a sustainable and eco-friendly process, requiring mostly water, oxygen, and sunlight. The role of the photocatalyst is to provide electrons for the reduction of O2 and holes for the release of hydrogen ion in water. Bismuth vanadate (BVO), a semiconductor with a low band gap energy (~2.4 eV), is known to be a promising photocatalyst. Moreover, reduced graphene oxide is well-known for its role in promoting the separation and transport of charges, preventing the recombination of photogenerated electron−hole pairs. This study proposes a method of synthesizing a composite catalyst by functionalizing BVO, via the encapsulation with RGO and utilizing the composite for production of H2O2.
Testosterone supplementation upregulates androgen receptor expression and translational capacity during severe energy deficit
Authors: Howard Emily E. , Margolis Lee M. , Berryman Claire E. , Lieberman Harris R. , Karl J. Philip , Young Andrew J. , Montano Monty A. , Evans William J. , Rodriguez Nancy R. , Johannsen Neil M. , Gadde Kishore M. , Harris Melissa N. , Rood Jennifer C. , Pasiakos Stefan M.
Published: August 2020

Testosterone supplementation during energy deficit promotes whole body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before, 1 h, and 6 h after exercise and a mixed meal (40 g protein, 1 h postexercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active nonobese men treated with 200 mg testosterone enanthate/wk (TEST) or placebo (PLA) during the ED. Participants ( n = 10/group) exhibiting substantial increases in leg lean mass and total testosterone (TEST) were compared with those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 gene expression was lower in TEST vs. PLA during ED relative to WM ( P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA ( P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.
Gene expression of the IGF hormones and IGF binding proteins across time and tissues in a model reptile
Authors: Beatty Abby E. , Schwartz Tonia S.
Published: August 2020

The insulin and insulin-like signaling (IIS) network regulates cellular processes including pre- and postnatal growth, cellular development, wound healing, reproduction, and longevity. Despite their importance in the physiology of vertebrates, the study of the specific functions of the top regulators of the IIS network, insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs), has been mostly limited to a few model organisms. To expand our understanding of this network, we performed quantitative gene expression of IGF hormones in liver and qualitative expression of IGFBPs across tissues and developmental stages in a model reptile, the brown anole lizard ( Anolis sagrei). We found that lizards express IGF2 across all life stages (preoviposition embryos to adulthood) and at a higher level than IGF1, which is opposite to patterns seen in laboratory rodents but similar to those seen in humans and other vertebrate models. IGFBP expression was ubiquitous across tissues (brain, gonad, heart, liver, skeletal muscle, tail, and regenerating tail) in adults, apart from IGFBP5, which was variable. These findings provide an essential foundation for further developing the anole lizard as a physiological and biomedical reptile model, as well as expanding our understanding of the function of the IIS network across species.
Metabolomics analysis of annual killifish (Austrofundulus limnaeus) embryos during aerial dehydration stress
Authors: Zajic Daniel E. , Podrabsky Jason E.
Published: August 2020

The annual killifish, Austrofundulus limnaeus, survives in ephemeral ponds in the coastal deserts of Venezuela. Persistence through the dry season is dependent on drought-resistant eggs embedded in the pond sediments during the rainy season. The ability of these embryos to enter drastic metabolic dormancy (diapause) during normal development enables A. limnaeus to survive conditions lethal to most other aquatic vertebrates; critical to the survival of the species is the ability of embryos to survive months and perhaps years without access to liquid water. Little is known about the molecular mechanisms that aid in survival of the dry season. This study aims to gain insight into the mechanisms facilitating survival of dehydration stress due to aerial exposure by examining metabolite profiles of dormant and developing embryos. There is strong evidence for unique metabolic profiles based on developmental stage and length of aerial exposure. Actively developing embryos exhibit more robust changes; however, dormant embryos respond in an active manner and significantly alter their metabolic profile. A number of metabolites accumulate in aerial-exposed embryos that may play an important role in survival, including the identification of known antioxidants and neuroprotectants. In addition, a number of unique metabolites not yet discussed in the dehydration literature are identified, such as lanthionine and 2-hydroxyglutarate. Despite high oxygen availability, embryos accumulate the anaerobic end product lactate. This paper offers an overview of the metabolic changes occurring that may support embryonic survival during dehydration stress due to aerial incubation, which can be functionally tested using genetic and pharmacological approaches.
A Modified Spatiotemporal Mixed-Effects Model for Interpolating Missing Values in Spatiotemporal Observation Data Series
Authors: Shi Qiang , Dai Wujiao , Santerre Rock , Liu Ning
Published: August 2020

Missing values in data series is a common problem in many research and applications. Most of existing interpolation methods are based on spatial or temporal interpolation, without considering the spatiotemporal correlation of observation data, resulting in poor interpolation effect. In this paper, a Modified Spatiotemporal Mixed-Effects (MSTME) model for interpolation of spatiotemporal data series is proposed. Experiments with simulated data and real SCIGN data are performed to assess the validity of the proposed model in comparison with Kriged Kalman Filter (KKF) model and Spatiotemporal Mixed-Effects (STME) model. The average improvements of simulated data and SCIGN data for observed stations are around 46% and 19% over the KKF model and 62% and 21% over the STME model, and those for unobserved stations are around 23% and 34% over the KKF model and 41% and 16% over the STME model, respectively, indicating that the proposed MSTME model can achieve better accuracy for interpolating missing values.
Clinical Characteristics of COVID-19 Patients with and without Diabetes in Wuhan Red Cross Hospital
Authors: Li Guozhen , Deng Qin , Feng Jiali , Li Fang , Xiong Nian , He Qiong
Published: August 2020

Background. Since the end of December 2019, novel coronavirus- (SARS-CoV-2-) infected pneumonia (COVID-19) has spread rapidly in China. The study was designed to describe the clinical characteristics of COVID-19 patients with and without diabetes in Wuhan. Methods. 199 COVID-19 patients were admitted to Wuhan Red Cross Hospital in China from January 24th to March 15th. The cases were divided into the diabetic and nondiabetic groups according to the history of taking antidiabetic drugs or by plasma fasting blood glucose level at admission, and the differences between the groups were compared. A multivariable analysis of independent risk factors for in-hospital death was performed. Results. Among 199 COVID-19 patients, 76 were diabetic and 123 were nondiabetic. Compared with nondiabetics, patients with diabetes were older and had high levels of fasting plasma glucose (FPG), D-dimer, white blood cells, blood urea nitrogen (BUN), and total bilirubin (TBIL) and lower levels of lymphocytes, albumin and oxygen saturation (SaO2), and higher mortality (

P
<
0.05

). The two groups showed no difference in clinical symptoms. Diabetes (odds ratio (OR): 10.816, 95% CI (confidence interval): 1.895-61.741,

P
=
0.007

), higher level of D-dimer at admission (OR: 1.094, 95% CI: 1.017-1.178,

P
=
0.016

), and a

lymphocyte
 
count
<
0.6
×

10

9

/
L

at admission (OR: 7.609, 95% CI: 1.087-32.049,

P
=
0.006

) were associated with increasing odds of death. Antidiabetic drugs were associated with decreasing odds of death. Treatment with low molecular weight heparin was not related to odds of death. Conclusion. The mortality rate of COVID-19 patients with diabetes was significantly higher than those without diabetes. Diabetes, higher level of D-dimer, and a

lymphocyte
 
count
<
0.6
×

10

9

/
L

at admission were the risk factors associated with in-hospital death.
Effective Algorithms for Solving Trace Minimization Problem in Multivariate Statistics
Authors: Li Jiao-fen , Wen Ya-qiong , Zhou Xue-lin , Wang Kai
Published: August 2020

This paper develops two novel and fast Riemannian second-order approaches for solving a class of matrix trace minimization problems with orthogonality constraints, which is widely applied in multivariate statistical analysis. The existing majorization method is guaranteed to converge but its convergence rate is at best linear. A hybrid Riemannian Newton-type algorithm with both global and quadratic convergence is proposed firstly. A Riemannian trust-region method based on the proposed Newton method is further provided. Some numerical tests and application to the least squares fitting of the DEDICOM model and the orthonormal INDSCAL model are given to demonstrate the efficiency of the proposed methods. Comparisons with some latest Riemannian gradient-type methods and some existing Riemannian second-order algorithms in the MATLAB toolbox Manopt are also presented.
The Abnormal Expression of miR‐205‐5p, miR‐195‐5p, and VEGF‐A in Human Cervical Cancer Is Related to the Treatment of Venous Thromboembolism
Authors: Wang Yuting , Zhang Zegao , Tao Pengcai , Reyila Maimaitiyimin , Qi Xiaoli , Yang Jie
Published: August 2020

Background. Low molecular heparin (LWMH) therapy can prevent the occurrence of VTE in tumor patients and may have a direct antitumor effect. However, the expression pattern of VEGF‐A and microRNAs was less reported in cervical cancer subjects who received concurrent chemoradiotherapy (CCRT) or received anticoagulant treatment with low molecular weight heparin (LWMH) after CCRT (CCRT+LWMH). Methods. In this study, 30 cervical cancer subjects treated with CCRT and 30 cervical cancer patients treated with CCRT+LWMH were enrolled. We screened five miRNAs (miR‐15a‐5p, miR‐16‐5p, miR‐29a‐3p, miR‐195‐5p, and miR‐205‐5p), which have multiple binding sites with VEGF‐A and are highly expressed in serum of patients with cervical cancer, by RT‐qPCR. The expression level of VEGF‐A was also detected by RT‐qPCR and ELISA. Statistical methods were used for difference and correlation analyses. Results. We observed the curative effect in the two treatment methods. In the CCRT group, the total effective rate was 60.00%, and in the CCRT+LWMT group, the total effective rate was 83.33% (P = 0.013, χ2 = 6.129). Additionally, the serum levels of VEGF‐A in the CCRT+LWMH group were downregulated, relative to the CCRT group (P < 0.05), and VEGF‐A in serum was significantly positively correlated with venous thromboembolism (VTE) (r = 2.134, P = 0.035). Only miR‐205‐5p and miR‐195‐5p were upregulated in CCRT+LWMH, relative to CCRT (P < 0.05). In serum of patients with cervical cancer after CCRT+LWMH treatment, there was no significant correlation between VEGF‐A and miR‐15a‐5p (r = −0.132, P = 0.209), miR‐16‐5p (r = −0.205, P = 0.311), or miR‐29a‐3p (r = −0.029, P = 0.662), but VEGF‐A was significantly negatively correlated with miR‐195‐5p (r = −0.396, P = 0.040) and miR‐205‐5p (r = −0.315, P = 0.032). Furthermore, VTE was also significantly negatively correlated with miR‐195‐5p (r = −0.412, P = 0.031) and miR‐205‐5p (r = −0.123, P = 0.044). Conclusion. These data revealed roles for VEGF‐A and these miRNAs as potential biomarkers in cervical cancer patients with VTE, which exhibited usage potential in the treatment of venous thromboembolism.
A Prospective, Randomized, Placebo-Controlled Study of a Combination of Simvastatin and Chemotherapy in Metastatic Breast Cancer
Authors: Alarfi Hiba , Youssef Lama A. , Salamoon Maher
Published: August 2020

Preclinical studies support the anticancer activity of statins; however, the existing clinical evidence is inconsistent and not definitive. Our study aimed at evaluating a postulated cancer chemo-sensitizing effect of statin (simvastatin) in a cohort of metastatic breast cancer (MBC) patients. We designed a prospective, single-centered, randomized, double blinded, placebo-controlled trial that encompassed MBC patients with an ECOG Performance Status Scale ≤2 and scheduled to be treated with a chemotherapy regimen consisting of carboplatin and vinorelbine every 3 weeks at Al-Baironi Hospital, Damascus, Syria. Patients were enrolled between August 2011 and July 2012 and randomly allocated to receive a 15-day course of either simvastatin (40 mg) or placebo seven days prior to the first day of each chemotherapy cycle and then continued for eight days in each individual cycle. Primary endpoints were objective response rate (ORR) and toxicity, and the secondary endpoint was overall survival (OS). Eighty-two patients met the inclusion criteria and consented. ORR (35% vs. 32.5%) and predominant toxicity and grade ≥3 neutropenia (occurred in 30% vs. 40% of the patients) were not significantly different between simvastatin and placebo groups, respectively. Over a median follow-up of 44 months (range, 10–60), median OS was 15 months in the simvastatin group and 17 the in placebo group (hazard ratio (HR) = 1.16, 95% CI (0.70–1.91), P=0.57). Elevated baseline values of high-sensitivity C-reactive protein (hsCRP >10 mg/l), lactate dehydrogenase (LDH >480 U/L), and chemotherapy being ≥2nd line were significantly associated with shorter OS for the total cohort in both Univariate and multivariate analyses. Our data prove a safe profile of simvastatin at 40 mg per day combined with carboplatin and vinorelbine in MBC patients but without any beneficial increase of tumor sensitivity to chemotherapy. Moreover, we demonstrated a strong clinical advantage of baseline values of hsCRP and LDH as useful prognostic tools in MBC patients. This trial is registered with ISRCTN12964275.
Modeling and Simulation of Collaborative Dispatching of Disaster Relief Materials Based on Urgency
Authors: Guan Gaofeng , Lin Zijun , Gong Yu , Jiang Zhijuan
Published: August 2020

In order to address the lack of collaborative decision and failure to notice the emergency and fairness of relief after disasters have occurred, a collaborative decision-making system for emergency relief materials dispatching is established. According to the forecast of the demand for postdisaster relief materials, the entropy weight-TOPSIS method is applied to measure the urgency of the disaster area; then, a “Hub-and-Spoke” dispatching network is constructed. In this paper, a multiobjective collaborative relief material dispatching model is built, which has great performance in terms of minimal distribution cost and maximal fairness, and the objective of fairness requires minimizing the penalty cost caused by unsatisfied demands. Based on the urgency of demand points, the simulated annealing algorithm is designed to solve the Pareto disaggregation of multiobjective optimization model. The performance of the model is verified with the case of Wenchuan Earthquake. The results indicate that if the fair distribution of supplies is emphasized, it will increase the number of rescue vehicles and the number of distribution batches. On the other hand, a variety of relief material dispatching plans can be provided based on calculation of the Pareto front for policy-makers.
Discovery and Validation of a CT‐Based Radiomic Signature for Preoperative Prediction of Early Recurrence in Hypopharyngeal Carcinoma
Authors: Li Wenming , Wei Dongmin , Wushouer Aihemaiti , Cao Shengda , Zhao Tongtong , Yu Dexin , Lei Dapeng
Published: August 2020

Purpose. In the clinical management of hypopharyngeal squamous cell carcinoma (HSCC), preoperative identification of early recurrence (≤2 years) after curative resection is essential. Thus, we aimed to develop a CT‐based radiomic signature to predict early recurrence in HSCC patients preoperatively. Methods. In total, 167 HSCC patients who underwent partial surgery were enrolled in this retrospective study and divided into two groups, i.e., the training cohort (n = 133) and the validation cohort (n = 34). Each individual was followed up for at least for 2 years. Radiomic features were extracted from CT images, and the radiomic signature was built with the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model. The associations of preoperative clinical factors with early recurrence were evaluated. A radiomic signature‐combined model was built, and the area under the curve (AUC) was used to explore their performance in discriminating early recurrence. Results. Among the 1415 features, 335 of them were selected using the variance threshold method. Then, the SelectKBest method was further used for the selection of 31 candidate features. Finally, 11 out of 31 optimal features were identified with the LASSO algorithm. In the LR classifier, the AUCs of the training and validation sets in discriminating early recurrence were 0.83 (95% CI: 0.76‐0.90) (sensitivity 0.8 and specificity 0.83) and 0.83 (95% CI: 0.67‐0.99) (sensitivity 0.69 and specificity 0.71), respectively. Conclusions. Using the radiomic signature, we developed a radiomic signature to preoperatively predict early recurrence in patients with HSCC, which may serve as a potential noninvasive tool to guide personalized treatment.
H∞ Time-Delayed Fractional Order Adaptive Sliding Mode Control for Two-Wheel Self-Balancing Vehicles
Authors: Xue Han , Fang Qionglin , Zhong Jifeng , Shao Zhe-ping
Published: August 2020

In this paper, a time-delayed fractional order adaptive sliding mode control algorithm is proposed for a two-wheel self-balancing vehicle system. The closed-loop system is proved based on the Lyapunov-Razumikhin function. The switching function is designed to make the system robust when facing uncertainties and external disturbances. It is designed to avoid monotonically increasing gains and can handle state-dependent uncertainties without a prior bound. The two-wheel self-balancing vehicle used in the experiment consists of a gyroscope MPU-6050 and accelerometer, a motor driving circuit composed of a motor driving chip TB6612FNG, and STM32F103x8B that is selected as the control core. The experimental results show that the time-delayed fractional order adaptive sliding mode control algorithm can make the vehicle achieve autonomous balance and quickly restore its stable state while appropriate disturbance is introduced.
Modeling and Simulation of an Unpowered Lower Extremity Exoskeleton Based on Gait Energy
Authors: Wang Yongfeng , Kong Xiangzhan , Yang Jing , Li Guanglin , Zhao Guoru
Published: August 2020

Aiming at the problem of how to store/release gait energy with high efficiency for the conventional unpowered lower extremity exoskeletons, an unpowered lower-limb exoskeleton is proposed. In the current study, the human motion model is established, and the change rule and recovery/utilization mechanism of gait energy are illustrated. The stiffness and metabolic cost of relevant muscles in lower extremity joints are obtained based on OpenSim software. The results show that stiffness of muscle is increased when muscle concentric contraction generates positive work, but it is reverse when muscle eccentric contraction generates negative work. Besides, metabolic cost of the soleus, gastrocnemius, and tibialis anterior decreased about 31.5%, 34.7%, and 40%, respectively. Metabolic cost of the rectus femoris, tensor fascia lata, and sartorius decreased about 36.3%, 7%, and 5%, respectively, and the total metabolic cost of body decreased about 15.5%, under the exoskeleton conditions. The results of this study can provide a theoretical basis for the optimal design of unpowered lower extremity exoskeleton.
Role of RING-Type E3 Ubiquitin Ligases in Inflammatory Signalling and Inflammatory Bowel Disease
Authors: Zhu Liguo , Li Ying , Zhou Longyuan , Yang Guang , Wang Ying , Han Jing , Li Li , Zhang Shenghong
Published: August 2020

Ubiquitination is a three-step enzymatic cascade for posttranslational protein modification. It includes the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). RING-type E3 ubiquitin ligases catalyse the posttranslational proteolytic and nonproteolytic functions in various physiological and pathological processes, such as inflammation-associated signal transduction. Resulting from the diversity of substrates and functional mechanisms, RING-type ligases regulate microbe recognition and inflammation by being involved in multiple inflammatory signalling pathways. These processes also occur in autoimmune diseases, especially inflammatory bowel disease (IBD). To understand the importance of RING-type ligases in inflammation, we have discussed their functional mechanisms in multiple inflammation-associated pathways and correlation between RING-type ligases and IBD. Owing to the limited data on the biology of RING-type ligases, there is an urgent need to analyse their potential as biomarkers and therapeutic targets in IBD in the future.
Low Bone Turnover Markers in Young and Middle-Aged Male Patients with Type 2 Diabetes Mellitus
Authors: Liu X. X. , Jiang L. , Liu Q. , Zhang J. , Niu W. , Liu J. , Zhang Q.
Published: August 2020

Accumulating evidence has supported an increased risk of osteoporotic fracture in postmenopausal women and elderly men diagnosed with diabetes mellitus. However, it is not uncommon for young and middle-aged male patients diagnosed with type 2 diabetes mellitus (T2DM) to suffer from osteopenia or osteoporosis. Few studies focused on this population group are available. The aim of this study is to evaluate bone metabolic status and investigate the influence of T2DM on bone metabolism in 30-50-year-old men. Anthropometric assessment and blood samples were obtained from 160 patients with T2DM and 69 nondiabetic volunteers. Serum parathyroid hormone (PTH) and bone turnover markers (BTMs), including serum procollagen type I N-terminal peptide (PINP), osteocalcin (OC), and β-cross-linked C-telopeptide of type I collagen (β-CTX), were analysed. No significant differences were observed based on age, body mass index, systolic blood pressure, serum calcium, phosphorus, creatinine, total protein, and albumin levels when comparing T2DM and control groups. Fasting blood glucose, HbA1c, triglyceride (TG), total cholesterol, and low-density lipoprotein cholesterol were significantly increased, while high-density lipoprotein cholesterol was significantly decreased in the T2DM group. Compared with controls, diabetic patients showed lower serum PINP, OC, and PTH levels, whereas serum β-CTX levels were similar between the two groups. Moreover, HbA1c levels were positively correlated with PINP and inversely associated with PTH levels. TG levels were negatively correlated with OC or β-CTX levels. Furthermore, multiple linear regression revealed a positive correlation between HbA1c and PINP levels. These results also revealed a negative association between HbA1c and PTH, and between TG and OC levels, even after adjusting for expected confounder factors. Collectively, these findings indicated that young and middle-aged male patients with T2DM showed a lower turnover state resulting from bone formation inhibition. Glucose and lipid metabolic disorders may affect bone formation through different pathways.
Period Family of Clock Genes as Novel Predictors of Survival in Human Cancer: A Systematic Review and Meta-Analysis
Authors: Deng Fan , Yang Kai , Zheng Gang
Published: August 2020

Background. Period genes are important core clock genes, including PER1, PER2, and PER3. A number of studies have demonstrated that the abnormal expression of the PER gene family of clock genes is associated with the survival and prognosis of patients with cancer; however, the sample sizes included in the majority of these studies were small, and the reported results were inconsistent. This study was the first to collect the relevant publications to systematically evaluate the value of the expression of the PER gene family in the prediction of survival and prognosis of human tumors. Methods. The PubMed, Cochrane Library, Embase, and Web of Science databases were searched systematically, and a meta-analysis was performed. Results. A total of 12 eligible publications met the inclusion criteria for the meta-analysis, including 1,369 patients and 9 different types of cancer. The pooled hazard ratio for overall survival indicated that the overall survival of patients in the high PER1, PER2, and PER3 protein expression group was significantly higher than that in the low-expression group, respectively. The sensitivity analysis revealed that the result was stable and reliable. The association between PER1 and PER3 mRNA expression levels and cancer prognosis was not meta-analyzed as the number of experimental studies was <3. There was no significant association between the expression of PER2 mRNA and the overall survival of patients with cancer. Conclusion. PER1, PER2, and PER3 protein expression levels can be used as novel potential biomarkers for predicting cancer prognosis.
The Efficacy of Traditional Chinese Medicine Shoutai Pill Combined with Western Medicine in the First Trimester of Pregnancy in Women with Unexplained Recurrent Spontaneous Abortion: A Systematic Review and Meta‐Analysis
Authors: Li Hui-fang , Shen Qi-hong , Li Xiao-qing , Feng Zhang-feng , Chen Wei-min , Qian Jia-hua , Shen Li , Yu Li-ying , Yang Yi
Published: August 2020

Background. Shoutai Pill (STP), a famous classic herbal formula documented in traditional Chinese medicine (TCM), is widely available in China for treating unexplained recurrent spontaneous abortion (URSA). This systematic review and meta‐analysis aims at evaluating the efficacy and safety of STP in the first trimester of pregnancy in women with a history of unexplained recurrent spontaneous abortion. Methods. The following eight databases were searched from their establishment to Dec 31, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results. A total of 12 studies (916 patients) with URSA were contained in this meta‐analysis. The forest plot showed that patients treated with Shoutai Pill and western medicine had a significantly lower incidence of early pregnancy loss (RR: 0.42; 95% CI: 0.34–0.52; P < 0.01, I2 = 0%). Subgroup analysis revealed that different types of TCM syndrome differentiation had the similar results. Also, in the combined group, patients had a lower TCM syndromes and symptoms and serum D‐dimer level, while higher incidence of live birth. Conclusions. Our findings suggest that cotreatment with STP and western medicine might be superior to western medicine alone in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent spontaneous abortion, and there was no adverse event in the experimental group reported. However, the methodological quality of included RCTs was unsatisfactory; it is necessary to verify its effectiveness with further more standardized researches of rigorous design.
Multifractal Analysis of Acoustic Emissions during Hydraulic Fracturing Experiments under Uniaxial Loading Conditions: A Niutitang Shale Example
Authors: Tan Jingqiang , Xie Jun , Li Lei , Lyu Qiao , Han Jianqiang , Zhao Zhengguang
Published: August 2020

Fracture characterization is essential for estimating the stimulated reservoir volume and guiding subsequent hydraulic fracturing stimulations in shale reservoirs. Laboratory fracturing experiments can help provide theoretical and technical guidance for field operations. In this study, hydraulic fracturing experiments on the shale samples from Niutitang Formation in Hunan Province (China) under a uniaxial loading condition are conducted. The multifractal method is used to analyze the acoustic emission (AE) signals and characterize fracture initiation and propagation. The hydraulic fracturing process can be divided into three stages based on the characteristics of AE signals: the initial stage, the quite stage, and the fracturing stage. The multifractal analysis results showed that: (1) the value of the spectrum width, Δα, continues to increase as the energy accumulates until the fracturing stage starts; and (2) the difference in the multifractal spectrum values, Δf, reflects the relationship between small and large signal frequencies and can quantify the fracture scale, i.e., the lower the Δf, the larger the fracture scale and vice versa. The results were further verified using a time-frequency analysis of the AE signals and micro-CT scanning of the samples. This study demonstrates that the multifractal method is feasible for quantitatively characterizing hydraulic fractures and can aid field hydraulic fracturing operations.
Image Target Recognition via Mixed Feature-Based Joint Sparse Representation
Authors: Wang Xin , Tang Can , Li Ji , Zhang Peng , Wang Wei
Published: August 2020

An image target recognition approach based on mixed features and adaptive weighted joint sparse representation is proposed in this paper. This method is robust to the illumination variation, deformation, and rotation of the target image. It is a data-lightweight classification framework, which can recognize targets well with few training samples. First, Gabor wavelet transform and convolutional neural network (CNN) are used to extract the Gabor wavelet features and deep features of training samples and test samples, respectively. Then, the contribution weights of the Gabor wavelet feature vector and the deep feature vector are calculated. After adaptive weighted reconstruction, we can form the mixed features and obtain the training sample feature set and test sample feature set. Aiming at the high-dimensional problem of mixed features, we use principal component analysis (PCA) to reduce the dimensions. Lastly, the public features and private features of images are extracted from the training sample feature set so as to construct the joint feature dictionary. Based on joint feature dictionary, the sparse representation based classifier (SRC) is used to recognize the targets. The experiments on different datasets show that this approach is superior to some other advanced methods.