bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational Design of a Dual‐Reactivity‐Based Fluorescent Probe for Visualizing Intracellular HSNO
Authors: Chen Wei , Matsunaga Tetsuro , Neill Deshka L. , Yang Chun‐tao , Akaike Takaaki , Xian Ming
Published: September 2019

Thionitrous acid (HSNO), the smallest S‐nitrosothiol, is emerging as a potential key intermediate in cellular redox regulation linking two signaling molecules H2S and NO. However, the chemical biology of HSNO remains poorly understood. A major hurdle is the lack of methods for selective detection of HSNO in biological systems. Herein, we report the rational design, synthesis, and evaluation of the first fluorescent probe TAP‐1 for HSNO detection. TAP‐1 showed high selectivity and sensitivity to HSNO in aqueous media and cells, providing a useful tool for understanding the functions of HSNO in biology.
Exploration of the structure–activity relationship and druggability of novel oxazolidinone‐based compounds as Gram‐negative antibacterial agents
Authors: Ding Shi , Ji Jing‐Chao , Zhang Ming‐Juan , Yang Yu‐She , Wang Rui , Zhu Xing‐Long , Wang Li‐Hong , Zhong Yi , Gao Le , Lu Man , Liu Ju , Chen Ye
Published: September 2019

To gain further knowledge of the structure–activity relationship and druggability of novel oxazolidinone‐based UDP‐3‐O‐acyl‐N‐acetylglucosamine deacetylase (LpxC) inhibitors as Gram‐negative antibacterial agents, compounds containing the hydrophobic tails with different lengths and terminal substitutions were synthesized and their antibacterial activities against standard and clinically isolated Gram‐negative strains were evaluated. We summarized their structure–activity relationships and found that oxazolidinone‐based compounds exhibited a narrower antibacterial spectrum compared with threonine‐based compounds. Furthermore, we parallelly compared the metabolic stabilities of the compounds with the classic threonine scaffold and the novel oxazolidinone scaffold in liver microsomes. The results indicated that the druggability of the oxazolidinone scaffold may be inferior to the classic threonine scaffold in the design of LpxC inhibitors.
The responsible parent and networks of support: A case study of school engagement in a challenging environment
Authors: Wyness Michael
Published: September 2019

Research, policy and practice on education in recent years has focused attention on the mediating role that parents play in children's schooling. Parents have been constructed as responsible agents; as consumers, investors and partners in the performance‐oriented educational project. Much of the literature has looked at parent–school relations from the vantage point of parents, particularly parents in disadvantaged areas. Less has been written on how parent–school relations look from a school's perspective. In this article we draw on data from a case study English school in a socio‐economically deprived area and explore the nature of the construct ‘responsible parent’ from the perspectives of teaching staff. We utilise data from semi‐structured interviews with teaching staff in one case study school located on the outskirts of an English city. Through the data we outline teachers’ conceptions of parents and an emerging network of engagement incorporating parents as part of a broader social and education project in schools. We argue that a dominant construct, the responsible parent, has resonances with the ways that teachers conceptualise parents. At the same time, the case study school inhabits a dual institutional space: it is captured within a neo‐liberal discourse on the responsible parent as a key conduit for an outcomes‐oriented education project and also goes beyond the narrow confines of formal educational structures in offering ‘challenging’ parents social and emotional support in connecting with their children and their schooling.
The impact on the cost of equity capital in the effects of integrated reporting quality
Authors: Vitolla Filippo , Salvi Antonio , Raimo Nicola , Petruzzella Felice , Rubino Michele
Published: September 2019

Integrated reporting is a new reporting tool that includes financial and nonfinancial information, which represents a natural evolution of the corporate reporting movement. Although this practice has gained increasing attention in recent years, both from an academic and professional perspective, the quality of the reports still represents a critical aspect due to inadequate investigation. Only a few studies have focused on integrated reporting quality, and contributions on the effects of quality have been even rarer. This study aims to investigate on the impact of integrated reporting quality on the firm's cost of equity capital, owing to the paramount importance of this parameter for firms and investors. Our results highlight that integrated reporting quality has a significantly negative association with the cost of equity capital, suggesting that integrated reporting quality represents an innovative way to reduce the cost of equity. To our knowledge, this is the first study that examines the relationship between integrated reporting quality and a firm's cost of equity.
Size‐Dependent Cellular Uptake of RGD Peptides
Authors: Kemker Isabell , Feiner Rebecca C. , Müller Kristian M. , Sewald Norbert
Published: September 2019

Monomeric RGD peptides show unspecific fluid‐phase uptake in cells, whereas multimeric RGD peptides are thought to be internalized by integrin‐mediated endocytosis. However, a potential correlation between uptake mechanism and molecular mass has been neglected so far. A dual derivatization of peptide c(RGDw(7Br)K) was performed to investigate this. A fluorescent probe was installed by chemoselective Suzuki–Miyaura cross‐coupling of the 7‐bromotryptophan and a poly(ethylene glycol) (PEG) linker was attached to the lysine residue. Flow cytometry and live cell imaging confirmed unspecific uptake of the small, non‐PEGylated peptide, whereas the PEG5000 peptide conjugate unveiled a selective internalization by M21 cells overexpressing αvβ3 and no uptake in αv‐deficient M21L cells.
Impact of age and comorbidities on the effect of transcatheter versus surgical mitral valve repair on inpatient outcomes
Authors: Jogu Hanumantha R. , Arora Sameer , Strassle Paula D. , Patel Chinmay , Patil Nikita , Venkatesh Sanjay , Alkhaimy Haytham , Ramm Cassandra J. , Qamar Arman , Kim Sun M. , Yeung Michael , Vavalle John P.
Published: September 2019

Background

Transcatheter mitral valve repair (TMVR) has shown to be a safe and effective treatment option for symptomatic severe mitral regurgitation (MR) in patients who are at prohibitive surgical risk. Whether age and comorbidities impact the inpatient safety outcomes of TMVR versus surgical mitral valve repair (SMVR) is unknown.

Methods

Using the national inpatient sample, patients undergoing either elective TMVR or SMVR between 2012 and 2015 were analyzed. Logistic, generalized logistic, and linear regression were used to compare inpatient complications, discharge disposition, and length of stay (LOS). Heterogeneity in the effect of TMVR versus SMVR across Charlson comorbidity index (CCI, categorized as <2 and ≥2) and age (categorized as <75 years old and ≥75 years old) were assessed for effect modification.

Results

Overall, 8,716 hospitalizations were included, 7,950 (91%) SMVR and 766 (9%) TMVR. Compared with SMVR, patients undergoing TMVR were older (median age 79 vs. 62 years) and more likely to be female (45% vs. 40%) with a higher CCI score (median CCI 2 vs. 1). Despite being older with a higher comorbidity burden, patients undergoing TMVR had a lower incidence of permanent pacemaker implantation (OR 0.23, 95% CI: 0.11, 0.50), cerebrovascular accidents (OR 0.37, 95% CI: 0.15, 0.92), and major bleeding (OR 0.39, 95% CI: 0.32, 0.47). TMVR patients were also discharged 3 days earlier (CIE −3.26; 95% CI: −3.72, −2.80) and were less likely to be discharged to a skilled nursing facility (OR 0.72, 95% CI 0.55, 0.93). Additionally, the relative reduction in complications after TMVR versus SMVR was significantly higher in older (age ≥75 years) and more comorbid (CCI ≥2) patients (p for interaction <.05 for both).

Conclusion

Patients treated with TMVR, as compared with SMVR, were older and had more comorbidities, but had a lower incidence of inpatient complications, shorter LOS, and better discharge disposition. Therefore, TMVR may be a safer option than SMVR in older patients and those with a higher burden of comorbidities.
Delocalization of π‐Electron in Graphitic Carbon Nitride to Promote its Photocatalytic Activity for Hydrogen Evolution
Authors: Guan Hai‐Xin , Zhang Wei‐De
Published: September 2019

Polymers with a large π‐electron conjugated system have aroused extensive concern in photocatalysis due to their appropriate bandgap and high stability. In order to overcome such drawbacks as its inadequate visible light absorption and rapid recombination of the photogenerated electron‐hole pairs of graphic carbon nitride (g‐C3N4), a facile strategy is proposed to tune its electronic structure by grafting small molecules. The conjugated photocatalysts were prepared by attaching 3‐Aminobenzoic acid (AB) and 6‐Aminopyridine‐2‐carboxylic acid (APy) to the framework of g‐C3N4 via low‐temperature condensation. The obtained catalysts UCN‐AB and UCN‐APy possess higher visible light absorption that results from the modified band structure by extending π‐electron delocalization. Additionally, AB and APy worked as the electron acceptors which further enhance transport of the photogenerated electrons. The optimal UCN‐AB and UCN‐APy accomplished remarkable photocatalytic hydrogen evolution rates of 104.0 and 133.2 μmol/h, respectively, which are nearly four or five times of that over g‐C3N4. This work provides a simple and feasible modification approach to extend π‐electron delocalization in g‐C3N4 with a stronger visible light response and accelerated charge transfer for high photocatalytic hydrogen evolution.
Discovering Expert Perspectives on Dispositions and Remediation: A Qualitative Study
Authors: Freeman Brenda J. , Garner Curtis M. , Scherer Rebecca , Trachok Kerstin
Published: September 2019

The authors used a qualitative approach to discover the perceptions of 19 experts on dispositions and remediation for counseling students. Analysis revealed 4 dispositional domains related to context, severity, amenability to change, and cultural sensitivity. Counselor educators should consider dispositions at admission and examine their program’s ability to remediate severe tenacious dispositions.
Photolytic and Reductive Activations of 2‐Arsaethynolate in a Uranium–Triamidoamine Complex: Decarbonylative Arsenic‐Group Transfer Reactions and Trapping of a Highly Bent and Reduced Form
Authors: Magnall Rosie , Balázs Gábor , Lu Erli , Kern Michal , van Slageren Joris , Tuna Floriana , Wooles Ashley J. , Scheer Manfred , Liddle Stephen T.
Published: September 2019

Little is known about the chemistry of the 2‐arsaethynolate anion, but to date it has exclusively undergone fragmentation reactions when reduced. Herein, we report the synthesis of [U(TrenTIPS)(OCAs)] (2, TrenTIPS=N(CH2CH2NSiiPr3)3), which is the first isolable actinide‐2‐arsaethynolate linkage. UV‐photolysis of 2 results in decarbonylation, but the putative [U(TrenTIPS)(As)] product was not isolated and instead only [{U(TrenTIPS)}2(μ‐η2:η2‐As2H2)] (3) was formed. In contrast, reduction of 2 with [U(TrenTIPS)] gave the mixed‐valence arsenido [{U(TrenTIPS)}2(μ‐As)] (4) in very low yield. Complex 4 is unstable which precluded full characterisation, but these photolytic and reductive reactions testify to the tendency of 2‐arsaethynolate to fragment with CO release and As transfer. However, addition of 2 to an electride mixture of potassium‐graphite and 2,2,2‐cryptand gives [{U(TrenTIPS)}2{μ‐η2(OAs):η2(CAs)‐OCAs}][K(2,2,2‐cryptand)] (5). The coordination mode of the trapped 2‐arsaethynolate in 5 is unique, and derives from a new highly reduced and bent form of this ligand with the most acute O‐C‐As angle in any complex to date (O‐C‐As
≈128°). The trapping rather than fragmentation of this highly reduced O‐C‐As unit is unprecedented, and quantum chemical calculations reveal that reduction confers donor–acceptor character to the O‐C‐As unit.
Benzyltriethylammonium Chloride Electrolyte for High‐Performance Al‐Ion Batteries
Authors: Xu Cheng , Li Jialin , Chen Haixia , Zhang Jianxin
Published: September 2019

Aluminum ion batteries have attached more attention because of inherent advantages such as abundant Al source, low flammability, three‐electron‐redox property and high theoretical capacity. However, many problems exist in the electrolyte system of aluminum ion battery, such as high price, low capacity. We prepare a novel AlCl3/Benzyltriethylammonium chloride electrolyte for aluminum ion battery. The battery displays a good performance at high current densities: 102 mA h g−1 at 5 A g−1 with a coulombic efficiency of ∼98% and 91 mA h g−1 at 10 A g−1 after 1500 cycles. It only takes 13 seconds to be fully charged/discharged at the current density of 25 A g−1. The mechanism of intercalation/de‐intercalation of chloroaluminate anions is confirmed by characterization and we believe AlCl3/Benzyltriethylammonium chloride will be a promising electrolyte for aluminum ion batteries.
Electronic Modulation of Terrylene Diimides Leading to Core‐Twisting, Tunable Emission and Intermolecular Interactions
Authors: Regar Ramprasad , Mehra Kundan Singh , Bhowal Rohit , Sankar Jeyaraman
Published: September 2019

Three new symmetrically para‐phenylethynylene‐substituted terrylene diimide derivatives namely, TDI‐Ph, TDI‐PhCN and TDI‐PhNMe2 were synthesized to study the electronic effects on the structure and properties. The solid‐state single‐crystal structures for TDI‐Ph and TDI‐PhCN as well as for the precursor TDI‐Br4 are presented. The X‐ray diffraction studies revealed twisting in the bay‐area of terrylene core, which improved the solubility as well, despite of having some of the shortest intermolecular Br···Br and C‐H···O interactions in TDI‐Br4. All the compounds exhibited near infra‐red absorption and emission except for TDI‐PhNMe2; especially TDI‐PhNMe2 showed interesting broad absorption ranging from 300 to 970 nm. Further, the effects of electron‐donating and accepting unit on electrochemical and optical properties have been investigated.
Field and numerical investigations of gateroad system failure under an irregular residual coal pillar in close‐distance coal seams
Authors: Shang Hefu , Ning Jianguo , Hu Shanchao , Yang Shang , Qiu Pengqi
Published: September 2019

The Gaojialiang Coal Mine in Inner Mongolia in China was used as an example to investigate the process of chain pillar and gateroad failure in the lower coal seam under the effect of an irregular residual coal pillar in the upper close‐distance coal seam. The results indicated that after the longwall face in the lower coal seam retreated through the area under the large irregular residual coal pillar in the upper coal seam, the bearing area of the residual coal pillar decreased and the roof pressure continuously concentrated in the elastic core area of the residual coal pillar. Isolated triangular slab rock was formed above the triangular residual coal pillar, and the weight of the overlying strata was transferred downward through the triangular slab rock. When the chain pillar under the residual coal pillar was destroyed due to loading that exceeded its carrying capacity, the upper triangular slab rock rotated and sank, which resulted in the intensification of the concentrated stress in the solid rib of the gateroad in the lower coal seam. Based on the analysis, it is suggested that in the design of a longwall system, a gateroad under an isolated residual coal pillar in the upper coal seam should be avoided when mining in close‐distance coal seams.
Trigonometric transforms and precoding strategies for OFDM‐based uplink hybrid multi‐carrier nonorthogonal multiple access
Authors: Trivedi Vinay Kumar , Ramadan Khaled , Kumar Preetam , Dessouky Moawad Ibrahim , Abd El‐Samie Fathi E.
Published: September 2019

An uplink hybrid nonorthogonal multiple access (h‐NOMA) scheme utilizing power domain multiplexing is adopted in this paper for orthogonal frequency–division multiplexing (OFDM)–based systems. The OFDM‐based NOMA systems can achieve high spectral efficiency with resilience to wireless multipath fading. The h‐NOMA maintains a low interference level per resource block or low complexity of multiuser detection (MUD) implementation at the receiver and also achieves consistent fairness performance by restricting the maximum number of users per resource block. An improved user clustering algorithm for OFDM‐based h‐NOMA system under the assumption of user's distinct data rate requirement is presented here. The proposed algorithm takes into consideration both the channel gain of all activated users and the different data rate requirements of weak channel gain users. High peak‐to‐average power ratio (PAPR) and performance degradation due to strict frequency synchronization requirements are the main drawbacks of such an OFDM‐based uplink h‐NOMA system. High PAPR of multicarrier NOMA is addressed here with precoding techniques. An enhanced minimum mean square error (MMSE) receiver performing joint equalization and carrier frequency offset (CFO) compensation using low‐complexity banded‐matrix implementation is proposed to cancel interference in the frequency domain. The MUD is implemented with low‐complexity successive interference cancellation (SIC) using bandedmatrix approximation of the interference matrix in the presence of CFO. Moreover, the possibility of utilizing efficient trigonometric transforms to implement OFDM‐based NOMA is studied with CFO and estimation errors. For OFDM‐based h‐NOMA system, an efficient combination of different trigonometric transform configurations to constitute the multicarrier basis for OFDM with a suitable precoding strategy for PAPR reduction is studied.
LightCert: On designing a lighter certificate for resource‐limited Internet‐of‐Things devices
Authors: Kwon Hyuksang , Ahn Jeongseob , Ko JeongGil
Published: September 2019

Internet‐of‐Things (IoT) devices are typically resource constrained in terms of computing capabilities and battery power. Despite the efforts from the Internet Engineering Task Force (IETF) to established standards for IoT such as IPv6 over low‐power wireless personal area networks (6LoWPAN), routing protocol for low‐power lossy networks (RPL), and constrained application protocol (CoAP), certificate‐based Internet security protocols have not been fully addressed yet.

We see the main cause of this being the size of the X.509‐based Internet certificates. Typically being 1 to 2 kB, the large size of these certificates can cause IEEE 802.15.4‐based IoT nodes to fragment the certificate into many smaller packet‐size chunks, which causes many packet transmissions to occur in the network. This work presents LightCert, a lightweight scheme to compress the size of the security certificates using the similarity of contents in X.509 certificates. Specifically, LightCert identifies common fields in a certificate and suppresses the transmission of these contents within the IoT subnet scope. This allows LightCert nodes to minimize the packet transmission overhead for supporting certificate‐based security mechanisms such as datagram transport layer security (DTLS), by as much as ∼37%. The added overhead of exchanging certificates when using LightCert is kept low to as much as ∼5 mJ of energy and ∼0.48 seconds of latency.
Clonal evolution of acute myeloid leukemia from diagnosis to relapse
Authors: Vosberg Sebastian , Greif Philipp A.
Published: September 2019

Based on the individual genetic profile, acute myeloid leukemia (AML) patients are classified into clinically meaningful molecular subtypes. However, the mutational profile within these groups is highly heterogeneous and multiple AML subclones may exist in a single patient in parallel. Distinct alterations of single cells may be key factors in providing the fitness to survive in this highly competitive environment. Although the majority of AML patients initially respond to induction chemotherapy and achieve a complete remission, most patients will eventually relapse. These points toward an evolutionary process transforming treatment‐sensitive cells into treatment‐resistant cells. As described by Charles Darwin, evolution by natural selection is the selection of individuals that are optimally adapted to their environment, based on the random acquisition of heritable changes. By changing their mutational profile, AML cell populations are able to adapt to the new environment defined by chemotherapy treatment, ultimately leading to cell survival and regrowth. In this review, we will summarize the current knowledge about clonal evolution in AML, describe different models of clonal evolution, and provide the methodological background that allows the detection of clonal evolution in individual AML patients. During the last years, numerous studies have focused on delineating the molecular patterns that are associated with AML relapse, each focusing on a particular genetic subgroup of AML. Finally, we will review the results of these studies in the light of Darwinian evolution and discuss open questions regarding the molecular background of relapse development.
The Silurian red beds of Tarim Basin: Signals of palaeoenvironment, palaeoclimate, and sea‐level change
Authors: Liu Jingyan , Ma Xiao , Lin Changsong , Yang Haijun , Shu Zhenzhen , Fu Chao , Schulte Lothar
Published: September 2019

The Silurian red beds of the Tarim Basin were formed in a coastal tidal and fluvial delta environment. They consist of red mudstone layers of the lower Tataaiertag Formation and separate the grey‐green muddy sandstones of the Kalpintag Formation from the red sandstones of the upper Tataaiertag Formation. These mudstones are regarded as the most important regional seal for Silurian oil reservoirs. They contain a significant record of palaeoenvironmental and palaeoclimate changes which is related to global sea‐level changes. Based on a systematic and continuous sedimentary study and multiple geochemistry analyses of samples taken from the Sishichang outcrop profile in west of the Tarim Basin, the Early–Middle Silurian palaeoclimate and sea‐level curve have been reconstructed. The Early–Middle Silurian Tarim Basin encountered five intervals of climate change, from humid transitioning to semi‐humid and dry–hot climate which shows signs of generally increasing oxidation. The reconstructed sea‐level curve indicates five sea‐level cycles throughout the Early–Middle Silurian succession. The most significant sea‐level drop occurred during the early Telychian stage, which represents the onset of the red mudstone section of the Tataaiertag Formation. This new sea‐level curve shows some differences compared with the earlier proposed global sea‐level curves. The dry–hot climate occurred during the late Telychian stage and the beginning of Wenlock age. The Early–Middle Silurian sea‐level change of the Tarim Basin was mostly synchronical to the eustacy. However, regional tectonic activities during the early Telychian stage further enhanced the effect of the global sea‐level fall and lead to a dry–hot climate trend which also caused the creation of the red beds of the Silurian period.
Relationship between protein biomarkers of chemotherapy response and microsatellite status, tumor mutational burden and PD‐L1 expression in cancer patients
Authors: Nikanjam Mina , Arguello David , Gatalica Zoran , Swensen Jeff , Barkauskas Donald A. , Kurzrock Razelle
Published: September 2019

Chemotherapy and checkpoint inhibitor immunotherapies are increasingly used in combinations. We determined associations between the presence of anti‐PD‐1/PD‐L1 therapeutic biomarkers and protein markers of potential chemotherapy response. Data were extracted from a clinical‐grade testing database (Caris Life Sciences; February 2015 through November 2017): immunotherapy response markers (microsatellite instability‐high [MSI‐H], tumor mutational burden‐high [TMB‐H], and PD‐L1 protein expression) and protein chemotherapy response markers (excision repair complementation group 1 [ERCC1], topoisomerase 1 [TOPO1], topoisomerase 2 [TOP2A], thymidylate synthase [TS], tubulin beta 3 [TUBB3], ribonucleotide reductase regulatory subunit M1 [RRM1] and O‐6‐methyl guanine DNA methyltransferase [MGMT]). Relationships were determined by the Mantel‐Haenszel chi‐squared test or Fischer's exact tests. Overall, 28,034 patients representing a total of 40 tumor types were assessed. MSI‐H was found in 3.3% of patients (73% were also TMB‐H), TMB‐H, 8.4% (28.3% were also MSI‐H) and PD‐L1 expression in 11.0% of patients (5.1% were also MSI‐H; 16.4% were also TMB‐H). Based on concurrent biomarker expression, combinations of immunotherapy with platinum (ERCC1 negativity) or with doxorubicin, epirubicin or etoposide (TOP2A positivity) have a higher probability of response, whereas combinations with irinotecan or topotecan (TOPO1 positivity), with gemcitabine (RRM1 negativity), and fluorouracil, pemetrexed or capecitabine (TS negativity) may be of less benefit. The potential for immunotherapy and taxane (TUBB3 negativity) combinations is present for MSI‐H but not TMB‐H or PD‐L1‐expressing tumors; for temozolomide and dacarbazine (MGMT negative), PD‐L1 is frequently coexpressed, but MSI‐H and TMB‐H are not associated. Protein markers of potential chemotherapy response along with next‐generation sequencing for immunotherapy response markers can help support rational combinations as part of an individualized, precision oncology approach.
Comprehensive analysis of lncRNA‐TF crosstalks and identification of prognostic regulatory feedback loops of glioblastoma using lncRNA/TF‐mediated ceRNA network
Authors: Ji Yang , Gu Yaqin , Hong Shuai , Yu Bo , Zhang Jian‐Hua , Liu Jin‐Na
Published: September 2019

Glioblastoma (GBM) has become the most aggressive primary brain tumor in the world. Patients with GBM usually have a poor prognosis. The median survival times of GBM patients retain less than 2 years. Thus, it is urgent to investigate the molecular mechanism of GBM. Recently, studies have demonstrated that transcription factors (TFs) participate in cancer pathology by regulating long noncoding RNAs (lncRNAs). However, the functional and regulatory roles of TF‐lncRNA crosstalks are still unclear. In this study, we constructed a global lncRNA‐TF network (GLTN) based on competing endogenous RNA. As a result, some topological features of GLTN were identified. A known GBM lncRNA MCM3AP‐AS1 showed multiple central topological features in GLTN. Furthermore, we identified hub genes and extracted the hub‐hub pairs from GLTN to form a hub associated lncRNA‐TF network (HALTN). Results showed that a risk model combined with multiple hubs had a significant effect on prognosis. Additionally, we performed module searching and two functional modules from HALTN were identified, which were confirmed as risk factors of GBM. More importantly, we also identified some core lncRNA‐TF crosstalks that might form feedback loops to control the biological processes in GBM. Our results demonstrated that the synergistic, competitive lncRNA‐TF crosstalks played an important role in pathological processes of GBM, and had strong effect on prognosis. All these results can help us to uncover the molecular mechanism and provide a new therapeutic target for GBM.
New sights on the associations between the XRCC1 gene polymorphisms and hepatocellular carcinoma susceptibility
Authors: Cai Wenjuan , Liu Xinhua , Li Yan , Bi Bowen , Liu Lei , Wang Zhenglu
Published: September 2019

Studies investigating the relationships between the polymorphisms in the X‐ray repair cross complementing 1 (XRCC1) gene and the susceptibility of hepatocellular carcinoma (HCC) remained controversial, therefore, we assessed this associations by metaanalysis and trial sequential analysis (TSA). PubMed, Embase, Google Scholar, Chinese National Knowledge Infrastructure and Baidu Scholar were comprehensively screened to retrieve relevant studies up to May 20, 2019. A total of 32 studies was included. Significant associations were discovered in the overall and subgroup analysis in these three polymorphisms. Interestingly, the decreased risk of HCC was detected in the Indians for the rs24587 polymorphism. TSA indicated the required information size for the rs25487 polymorphism were reached, but for the rs25489 and rs1799782 polymorphisms, more well‐designed trials were required. Sensitivity analysis implied our results were stable; no publication bias was observed in the rs25487 and rs1799782 polymorphisms. The bioinformatic analysis indicate that the rs1799782 polymorphism is probably damaging and has an influence on the XRCC1 protein function. Our study indicated that the XRCC1 rs25487 was a risk factor for the susceptibility of HCC, which was verified by the TSA. In addition, the rs25489 and rs1799782 polymorphisms were associated with increased risk of HCC. In the subgroup analysis, increased risks were detected in some subgroups (in accordance with Hardy‐Weinberg equilibrium, Chinese groups, Mongoloid subgroup, polymerase chain reaction‐restriction fragment length polymorphisms and more than 300 subgroups), moreover, decreased HCC risk of the rs25487 polymorphism was firstly observed, which required further studies to verify.
TAZ promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells via the p‐SMAD3
Authors: Gu Ke , Fu Xucheng , Tian Hui , Zhang Yafei , Li Aonan , Wang Ying , Wen Yong , Gu Weiting
Published: September 2019

Objective

This study aims to offer insights about the biological influence of TAZ, which is a transcriptional coactivator containing a PDZ‐binding motif, upon the apoptosis, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (h‐PDLSCs).

Methods

We used the green fluorescence protein lentivirus infection system to knockdown or overexpress TAZ in h‐PDLSCs. 5‐ethynyl‐2’‐deoxyuridine (EdU) staining detected the proliferative activity, and h‐PDLSC apoptosis was analyzed by Annexin V‐APC staining. TAZ knockdown or overexpression was performed to determine the osteogenic differentiation function of TAZ during the osteogenic induction of h‐PDLSCs. The molecular mechanism of TAZ in the promotion of h‐PDLSC osteogenesis was also explored. The chemical inhibitor of SMAD2/3 SIS3 HCL was used to identify the effects in vitro osteogenic differentiation and bone formation in h‐PDLSCs overexpressing TAZ.

Results

TAZ overexpression resulted in enhanced cell rapid multiplication, which increased the expression of messenger RNA in stemness‐related genes. By comparison, TAZ knockdown reduced proliferative activity and increased the apoptosis of h‐PDLSCs. After the 7‐day osteogenic induction period, alkaline phosphatase activity in the TAZ‐overexpression group was significantly increased, and mineralized nodules increased significantly after osteogenic induction for 21 days. Similarly, osteoblast differentiation of h‐PDLSCs was impaired after TAZ knockdown. However, the osteogenic potential of the group exposed to the p‐SMAD3 inhibitor was restored to its original level.

Conclusion

Hippo/TAZ plays a positive role inside the proliferation, stemness maintenance, and osteogenic specialization of h‐PDLSCs, and the specific downstream factor of osteogenic differentiation is SMAD3.
Serine peptidase inhibitor Kazal type III (SPINK3) promotes BRL‐3A cell proliferation by targeting the PI3K–AKT signaling pathway
Authors: Chang Cuifang , Xie Junjie , Yang Qingdan , Yang Jing , Luo Yaru , Xi Lingling , Guo Jianlin , Yang Ganggang , Jin Wei , Wang Gaiping
Published: September 2019

The serine protease inhibitor, Kazal type III (SPINK3), is a trypsin inhibitor associated with liver disease, which highly overexpresses in a variety of cancers. In one of our previous studies of our laboratory, Spink3 was observed to be significantly upregulated in rat liver regeneration (LR) via a gene expression profile. For the current study, rat hepatocyte BRL‐3A cells were treated by gene addition/interference, and the addition of the exogenous rat recombinant protein SPINK3. It was revealed that both the overexpression of endogenous Spink3 and addition of exogenous rat recombinant SPINK3 (rrSPINK3) significantly promoted the cell proliferation of BRL‐3A cells, whereas cell proliferation was inhibited when Spink3 was interfered. Furthermore, quantitative reverse transcription polymerase chain reaction and western blot results revealed that three signaling pathways, including extracellular‐signal‐regulated kinase 1/2 (ERK1/2), Janus kinase (JAK)–signal transducer and activator of transcription (STAT), and phosphatidylinositol‐3‐kinase (PI3K)–protein kinase B (AKT), as well as their related genes, were altered following endogenous Spink3 addition/interference. Also, the PI3K–AKT and SRC‐p38 pathways and their related genes were modified following exogenous SPINK3 treatment. Among them, the common signaling pathway was PI3K–AKT pathway. We concluded that SPINK3 could activate the PI3K–AKT pathway by enhancing the expression of AKT1 to regulate the proliferation of BRL‐3A cells. This study may contribute to shedding light on the potential mechanisms of SPINK3 that regulate the proliferation of BRL‐3A cells.
Treatment with DNases rescues hidden neutrophil elastase from aggregated NETs
Authors: Podolska Malgorzata J , Mahajan Aparna , Hahn Jonas , Knopf Jasmin , Maueröder Christian , Petru Lenka , Ullmann Marc , Schett Georg , Leppkes Moritz , Herrmann Martin , Muñoz Luis E , Schauer Christine
Published: September 2019

The release of neutrophil extracellular traps (NETs) is one of the weapons neutrophils have in their armory. NETs consist of extracellular chromatin fibers decorated with a plethora of cytoplasmic and granular proteins, such as the antimicrobial serine protease neutrophil elastase (NE). Because the first description of NETs as beneficial to the host, reports on their double-faced role in health and disease have considerably increased recently. On one hand, NETs reportedly trap and kill bacteria and also participate in the resolution of the acute inflammation associated with infection and with tissue damage. On the other hand, numerous negative aspects of NETs contribute to the etiopathogenesis of autoimmune disorders. Employing soluble and solid fluorescent substrates, we demonstrate the interaction of NE with aggregated NETs (aggNETs), the limitation of its enzymatic activity and the containment of the enzyme from surrounding tissues. These events prevent the spread of inflammation and tissue damage. The detection of DNase 1-dependent elevation of NE activity attests the continuous presence of patrolling neutrophils forming NETs and aggNETs even under conditions physiologic conditions.
Parametric Presburger arithmetic: complexity of counting and quantifier elimination
Authors: Bogart Tristram , Goodrick John , Nguyen Danny , Woods Kevin
Published: September 2019

We consider an expansion of Presburger arithmetic which allows multiplication by k parameters . A formula in this language defines a parametric set as varies in , and we examine the counting function as a function of t. For a single parameter, it is known that can be expressed as an eventual quasi‐polynomial (there is a period m such that, for sufficiently large t, the function is polynomial on each of the residue classes mod m). We show that such a nice expression is impossible with 2 or more parameters. Indeed (assuming ) we construct a parametric set such that is not even polynomial‐time computable on input . In contrast, for parametric sets with arbitrarily many parameters, defined in a similar language without the ordering relation, we show that is always polynomial‐time computable in the size of t, and in fact can be represented using the gcd and similar functions.
TFG: At the crossroads of motor neuron disease and myopathy
Authors: Nicolau Stefan , Liewluck Teerin
Published: September 2019

See article on pages 739–744 in this issue.
Employment in refractory myasthenia gravis: A Myasthenia Gravis Foundation of America Registry analysis
Authors: Harris Linda , Aban Inmaculada B. , Xin Haichang , Cutter Gary
Published: September 2019

Introduction

Labor‐market participation is potentially very difficult for patients with refractory myasthenia gravis (MG). In this study, employment status and work absences are compared between refractory and nonrefractory MG.

Methods

Adults (aged 18–64 years, all diagnosed ≥2 years previously) were included if enrolled in the Myasthenia Gravis Foundation of America Patient Registry during July 2013 to February 2018.

Results

Seventy‐six patients (9.2%) had refractory and 749 (90.8%) had nonrefractory disease; demographic data did not differ between groups. Relative to the nonrefractory group, the refractory group patients were more than twice as likely to work fewer hours per week (odds ratio [95% confidence interval]: currently employed, 2.777 [1.640–4.704]; employed over previous 6 months, 2.643 [1.595–4.380]), but those employed were not more likely to be absent from work.

Discussion

Because absence from the labor market adversely affects quality of life and personal finances, these findings reaffirm the considerable disease burden associated with refractory MG.
Multiple scales analysis of the undular hydraulic jump over horizontal surfaces
Authors: Murschenhofer Dominik , Schneider Wilhelm
Published: September 2019

The basic equations for near‐critical stationary turbulent open‐channel flow over horizontal surfaces are solved by means of a multiple scales analysis. The multiple scales solution describing the first‐order perturbation of the free‐surface elevation is compared with the numerical solution of an extended steady‐state version of the Korteweg–de Vries (KdV) equation, confirming the uniform validity of this non‐linear third‐order ODE. In comparison with experimental data the numerical solution of the extended KdV equation shows strong dependence on the initial curvature in terms of wavelength and amplitude.
Does sperm DNA fragmentation correlate with semen parameters?
Authors: Le Minh Tam , Nguyen Tam An Thi , Nguyen Hiep Tuyet Thi , Nguyen Thai Thanh Thi , Nguyen Van Trung , Le Dinh Duong , Nguyen Vu Quoc Huy , Cao Ngoc Thanh
Published: September 2019

Purpose

This study aimed to investigate the association between sperm quality assessed by routine semen analysis and sperm DNA integrity assay.

Methods

In our cross‐sectional study, a total of 318 men from the infertile couples were enrolled from December 2017 to March 2019 at the Hue Center for Reproductive Endocrinology and Infertility, Vietnam. General characteristics and semen parameters were detected. The sperm DNA fragmentation index (DFI) was estimated by the sperm chromatin dispersion (SCD) assay. A threshold of DFI 30% was applied to classify normal (DFI < 30%) or abnormal (DFI ≥ 30%) groups. The correlations between DFI and semen parameters were analyzed by Spearman's rank correlation coefficient.

Results

In the correlation analysis, DFI was significantly correlated with abnormal head and progressive motility, with a positive correlation with abnormal head (ρ = .202, P = .0003) and a weak negative correlation with progressive motility (ρ = −.168, P = .0027), respectively. In the bivariate analysis, DFI was associated with male age, smoking, and alcohol consumption with P < .05.

Conclusions

The sperm DFI was not strongly correlated with conventional semen parameters. Therefore, a sperm DNA fragmentation assay should be performed as an additional step in the investigation of male fertility.
Open and Endovascular Management of Acute Mesenteric Ischaemia: A Systematic Review
Authors: Murphy B. , Dejong C. H. C. , Winter D. C.
Published: September 2019

Background

Acute mesenteric ischaemia (AMI) is a life‐threatening surgical emergency resulting from thromboembolic occlusion of the mesenteric vasculature. Traditional management of AMI has been open revascularisation with or without bowel resection—a procedure which carries considerable morbidity and mortality in an already unwell, compromised patient. Endovascular and more minimally invasive management approaches to AMI have been reported. Proponents of endovascular management suggest this approach may be associated with reduced morbidity and mortality compared with open surgery.

Objectives

To assess the impact of endovascular approach for AMI on mortality and need for subsequent laparotomy and/or bowel resection.

Data Sources

The search bodies PubMed and Medline were interrogated.

Eligibility Criteria, Participants and Interventions

All studies in English with greater than 10 patients examining outcomes for patients undergoing endovascular intervention for acute mesenteric ischaemia were included. All patients over 18 years presenting with a diagnosis of acute mesenteric ischaemia secondary to an arterial thromboembolic source were included. Studies examining endovascular intervention alone or endovascular and open intervention were selected.

Results

The 30‐day mortality for endovascular approach from all 13 studies was 16–42%. Of the 7 comparative studies including results of open revascularisation, the 30‐day mortality for patient treated with an endovascular approach was 15–39% versus 33–50% for open revascularisation. Laparotomy rates post‐initial endovascular intervention ranged from 13 to 73%. Bowel resection post‐endovascular therapy ranged from 14 to 40% among studies. Concerning 7 comparative studies for open versus endovascular revascularisation, the rate of bowel resection in the endovascular group ranged 14–28% and 33–63% in the open cohort. Endovascular intervention also demonstrated lower median length (s) of bowel resected.

Limitations

Heterogeneity of studies and patient populations studied including selection bias.

Conclusions and implications of findings

Endovascular management may be associated with reduced mortality and need for/length of bowel resection compared with the traditional open approach, but there remains a paucity of robust data to support this. The available literature illustrates that a subgroup of patients without haemodynamic compromise and more insidious onset may garner benefit from endovascular intervention.
Effects of long-term magnesium sulfate crystallisation tests on abrasion and durability of andesite aggregates
Authors: Czinder Balázs , Török Ákos
Published: September 2019

The durability of aggregates against salt weathering is calculated after five cycles of immersion in a magnesium sulfate solution followed by drying according to the relevant European standard (EN 1367–2: 2010). The aim of the study is to investigate the long-term durability of aggregates by increasing the number of cycles of the salt crystallization test from the standardized five to a maximum of 35. Three andesite types from Hungarian quarries were tested representing three different localities. The weight loss of the specimens was determined after every 5-cycle set. Results were documented for three size-fractions 10.0/11.2 mm, 11.2/14.0 mm and the 10.0/14.0 mm, respectively. Relationships between immersion-drying cycles and magnesium sulfate values were described by the Pearson-coefficient. According to the test results, the magnesium sulfate values followed linearly increasing tendencies in the course of the long-term salt crystallization tests. Parallel to the salt-weathering tests, the changes in the mechanical properties of the salt-attacked aggregates were also detected by micro-Deval tests (EN 1097–1: 2012). The changes in micro-Deval coefficients were calculated in the form of a decay factor as a function of sulfate cycles. The results suggest that the micro-Deval coefficient does not rise after a certain salt cycle; i.e. higher number of salt-crystallisation cycles does not necessarily reduce the micro-Deval coefficient of studied andesite lithologies.
Profile of women with anal neoplasia associated with cervical neoplasia receiving care at a tertiary healthcare facility in northeastern Brazil
Authors: Almeida Gian Francisco , Heráclio Sandra , Souza Alex Sandro Rolland , Amorim Melania M.
Published: September 2019

Objective To describe the epidemiological, clinical and laboratory profiles of women with anal neoplasia associated with cervical neoplasia attending a tertiary healthcare facility in northeastern Brazil.

Methods This epidemiological, descriptive study was conducted using a database from a cross-sectional study carried out between December 2008 and January 2016. Women with a diagnosis of cervical neoplasia associated with anal neoplasia were included in the present study.

Results Of the women with cervical neoplasia, 14% were found to have an anal intraepithelial lesion or anal cancer. Median age was 33 years, 68% were non-white, and 70% were from urban regions, had little schooling and low income. Most reported having had anoreceptive (73%) and unprotected intercourse (84%). Regarding symptoms, 7% reported bleeding and 11% pruritus. Overall, 10% of the sample tested positive for the human immunodeficiency virus. Anal cytology was abnormal in 92%. High-resolution anoscopy was abnormal in all cases. Histopathology revealed three cases of invasive carcinoma and high-grade lesions in 32% of the cases.

Conclusion Women with a diagnosis of anal and cervical neoplasia are often young, non-white women, who initiated their sexual life at an early age, were exposed to unprotected anoreceptive intercourse, live in urban centers, have little schooling and a low-income level.
The exact asymptotics of the large deviation probabilities in the multivariate boundary crossing problem
Authors: Pan Yuqing , Borovkov Konstantin A.
Published: September 2019

For a multivariate random walk with independent and identically distributed jumps satisfying the Cramér moment condition and having mean vector with at least one negative component, we derive the exact asymptotics of the probability of ever hitting the positive orthant that is being translated to infinity along a fixed vector with positive components. This problem is motivated by and extends results of Avram et al. (2008) on a two-dimensional risk process. Our approach combines the large deviation techniques from a series of papers by Borovkov and Mogulskii from around 2000 with new auxiliary constructions, enabling us to extend their results on hitting remote sets with smooth boundaries to the case of boundaries with a ‘corner’ at the ‘most probable hitting point’. We also discuss how our results can be extended to the case of more general target sets.