bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissipationsenergie bei Ermüdungsversuchen an Betonprobekörpern
Authors: Bode Matthias , Marx Steffen , Vogel Albert , Völker Conrad
Published: March 2019

Aufgrund des visko‐elasto‐plastischen Materialverhaltens von Beton wird Probekörpern und Bauteilen infolge zyklischer Beanspruchungen Energie zugeführt. Die entsprechenden Energiegrößen werden durch Hystereseflächen der Spannungs‐Dehnungslinien beschrieben. In der Literatur finden sich dabei unterschiedliche Ansätze, wofür diese Energie verwendet wird. Erste Untersuchungen zeigen, dass zumindest ein Teil dieser dissipierten Energie in thermische Energie umgewandelt wird. Mithilfe der in diesem Beitrag beschriebenen Methodik lassen sich diese Energiegrößen für jeden Lastwechsel eines Ermüdungsversuchs schnell und zuverlässig bestimmen. Anschließend wurden mit dem implementierten Algorithmus die dissipierten Energien von insgesamt 27 zyklischen Versuchen ausgewertet. Analog zu der Dehnungsentwicklung und der Steifigkeitsdegradation weisen auch die Verläufe der dissipierten Energie über die Lastwechselzahl einen dreiphasigen Verlauf auf. Die Auswertung zeigt außerdem eine Korrelation zwischen der Bruchlastwechselzahl und der dissipierten Energie. Auch der Zusammenhang zwischen Probekörpererwärmung und dissipierter Energie konnte bestätigt werden.
Cox regression model with randomly censored covariates
Authors: Atem Folefac D. , Matsouaka Roland A. , Zimmern Vincent E.
Published: March 2019

This paper deals with a Cox proportional hazards regression model, where some covariates of interest are randomly right‐censored. While methods for censored outcomes have become ubiquitous in the literature, methods for censored covariates have thus far received little attention and, for the most part, dealt with the issue of limit‐of‐detection. For randomly censored covariates, an often‐used method is the inefficient complete‐case analysis (CCA) which consists in deleting censored observations in the data analysis. When censoring is not completely independent, the CCA leads to biased and spurious results. Methods for missing covariate data, including type I and type II covariate censoring as well as limit‐of‐detection do not readily apply due to the fundamentally different nature of randomly censored covariates. We develop a novel method for censored covariates using a conditional mean imputation based on either Kaplan–Meier estimates or a Cox proportional hazards model to estimate the effects of these covariates on a time‐to‐event outcome. We evaluate the performance of the proposed method through simulation studies and show that it provides good bias reduction and statistical efficiency. Finally, we illustrate the method using data from the Framingham Heart Study to assess the relationship between offspring and parental age of onset of cardiovascular events.
Cardioprotective effects of omega‐3 fatty acids and ascorbic acid improve regenerative capacity of embryonic stem cell‐derived cardiac lineage cells
Authors: Shabani Parisa , Ghazizadeh Zaniar , Gorgani‐Firuzjaee Sattar , Molazem Mohammad , Rajabi Sarah , Vahdat Sadaf , Azizi Yaser , Doosti Mahmood , Aghdami Nasser , Baharvand Hossein
Published: March 2019

One of the major issues in cell therapy of myocardial infarction (MI) is early death of engrafted cells in a harsh oxidative stress environment, which limits the potential therapeutic utility of this strategy in the clinical setting. Increasing evidence implicates beneficial effects of omega‐3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and ascorbic acid (AA) in cardiovascular diseases, in particular their role in ameliorating fibrosis. In the current study, we aim to assess the cytoprotective role of EPA + DHA and AA in protecting embryonic stem cell (ESC)‐derived cardiac lineage cells and amelioration of fibrosis. Herein, we have shown that preincubation of the cells with EPA + DHA + AA prior to H2O2 treatment attenuated generation of reactive oxygen species (ROS) and enhanced cell viability. Gene expression analysis revealed that preincubation with EPA + DHA + AA followed by H2O2 treatment, upregulated heme oxygenase‐1 (HO‐1) along with cardiac markers (GATA4, myosin heavy chain, α isoform [MYH6]), connexin 43 [CX43]) and attenuated oxidative stress‐induced upregulation of fibroblast markers (vimentin and collagen type 1 [Col1]). Alterations in gene expression patterns were followed by marked elevation of cardiac troponin (TNNT2) positive cells and reduced numbers of vimentin positive cells. An injection of EPA + DHA + AA‐pretreated ESC‐derived cardiac lineage cells into the ischemic myocardium of a rat model of MI significantly reduced fibrosis compared to the vehicle group. This study provided evidence that EPA + DHA + AA may be an appropriate preincubation regimen for regenerative purposes. © 2019 BioFactors, 45(3):427–438, 2019
Prognostic impact of repeat sentinel lymph node biopsy in patients with ipsilateral breast tumour recurrence
Authors: Poodt I G M , Vugts G , Schipper R J , Roumen R M H , Rutten H J T , Maaskant-Braat A J G , Voogd A C , Nieuwenhuijzen G A P , Luiten E J T , Rutgers E J T , Vrancken-Peeters M T F D , Bessems M , Klaase J M , Muller S , Francken A B , Van Dalen T , Jansen L , Koopal S A , Vissers Y L J , Smidt M L , Merkus J W S , Contant C M E , Veldman P H , Linthorst-Niers E M H , van der Sijp J R , Guicherit O R , Koppert L B , Bosch A M , Strobbe L J A , Schlooz-Vries M S , Arntz I E , van Essen J A , de Waard J W D , Vrouenraets B C , van Ooijen B
Published: March 2019

Background

Ipsilateral breast tumour recurrence (IBTR) has an unfavourable prognosis, with a significant subsequent risk of distant recurrence. Repeat sentinel lymph node biopsy (rSLNB) has recently been demonstrated to be technically feasible and useful in tailoring adjuvant treatment plans in patients with IBTR. The prognostic impact of rSLNB in patients with IBTR remains unclear. This study analysed the risk of distant recurrence after IBTR, and evaluated the prognostic impact of rSLNB and other patient and tumour characteristics on distant recurrence-free survival.

Methods

Data were obtained from the SNARB (Sentinel Node and Recurrent Breast Cancer) study. Cox proportional hazards analyses were performed to assess the prognostic effect of tumour, patient and treatment factors on distant recurrence-free survival.

Results

Of the 515 included patients, 230 (44·7 per cent) had a tumour-negative rSLNB and 46 (8·9 per cent) a tumour-positive rSLNB. In 239 patients (46·4 per cent) the rSLNB procedure was unsuccessful. After a median follow-up of 5·1 years, 115 patients (22·3 per cent) had developed a recurrence. The overall 5-year distant recurrence-free survival rate was 84·2 (95 per cent c.i. 80·7 to 87·7) per cent. An interval of less than 2 years between primary breast cancer treatment and ipsilateral recurrence (P = 0·018), triple-negative IBTR (P = 0·045) and absence of adjuvant chemotherapy after IBTR (P = 0·010) were independently associated with poor distant recurrence-free survival. The association between the outcome of rSLNB and distant recurrence-free survival was not statistically significant (P = 0·682).

Conclusion

The outcome of rSLNB is not an important prognostic factor for distant recurrence, and its value as a staging tool in patients with IBTR seems disputable.
SALL4 induces radioresistance in nasopharyngeal carcinoma via the ATM/Chk2/p53 pathway
Authors: Nie Xin , Guo Ergang , Wu Cheng , Liu Dongbo , Sun Wei , Zhang Linli , Long Guoxian , Mei Qi , Wu Kongming , Xiong Huihua , Hu Guoqing
Published: March 2019

Radiotherapy is the mainstay and primary curative treatment modality in nasopharyngeal carcinoma (NPC), whose efficacy is limited by the development of intrinsic and acquired radioresistance. Thus, deciphering new molecular targets and pathways is essential for enhancing the radiosensitivity of NPC. SALL4 is a vital factor in the development and prognosis of various cancers, but its role in radioresistance remains elusive. This study aimed to explore the association of SALL4 expression with radioresistance of NPC. It was revealed that SALL4 expression was closely correlated with advanced T classification of NPC patients. Inhibition of SALL4 reduced proliferation and sensitized cells to radiation both in vitro and in vivo. Furthermore, SALL4 silencing increased radiation‐induced DNA damage, apoptosis, and G2/M arrest in CNE2 and CNE2R cells. Moreover, knockdown of SALL4 impaired the expression of p‐ATM, p‐Chk2, p‐p53, and anti‐apoptosis protein Bcl‐2, while pro‐apoptosis protein was upregulated. These findings indicate that SALL4 could induce radioresistance via ATM/Chk2/p53 pathway and its downstream proteins related to apoptosis. Targeting SALL4 might be a promising approach for the development of novel radiosensitizing therapeutic agents for radioresistant NPC patients.
Heroes on the Hill: A qualitative study of the psychosocial benefits of an intercultural arts programme for youth in Northern Ireland
Authors: Scrantom Katharine , McLaughlin Katrina
Published: March 2019

The current study investigates the psychosocial benefits of a cross‐community, intercultural dance programme for youth in Northern Ireland. Psychological theories, including contact theory and the ecology of childhood development, underpin the study, and results are discussed in relation to the programme's aims. The present study used qualitative, inductive methods; data consisted of interviews before and after the programme with facilitators (n = 2) and 10 (n = 10) programme participants (11–15 years old) of diverse races and nationalities. Latent themes were identified using thematic analysis. Findings reveal that participants have complex senses of identity. Worryingly, they also reported many instances of bullying, relating both to themselves and others. Results reveal three main psychosocial benefits of the programme, all of which promote positive mental health in adolescents. The benefits are increased self‐confidence, the formation of new cross‐community friendships, and improved intercultural awareness and pride. It is argued that the programme is an exemplar of how the arts can promote peace as well as resilience in the face of adversity. Recommendations for future research are included.
TAK1 is a druggable kinase for diffuse large B‐cell lymphoma
Authors: Wu Yuanyuan , Yang Riyun , Ming Yue , Xu Yuanpei , Chen Hao , Yao Min , Chen Xia , Mao Renfang , Fan Yihui
Published: March 2019

Diffuse large B‐cell lymphoma (DLBCL) is the most common form of lymphoma, and up to 30% DLBCL patients eventually died by using first‐line chemotherapy regimens. Currently, Bruton tyrosine kinase (BTK) inhibitor (ibrutinib) is one of the most promising medicine in clinical trials for DLBCL, to which about 25% of patients with relapsed or refractory DLBCL are responsive. Thus, it is urgent to discover new druggable targets for DLBCL, especially for patients who are unresponsive to first‐line chemotherapy and ibrutinib. Here, we found that MAP 3K7 (TAK1) is required for DLBCL survival. Inhibition of TAK1 by small molecule 5Z7 or genetic silence could massively induce deaths of DLBCL cells. Mechanistically, TAK1 inhibition could dramatically reduce the nuclear factor kappa B (NF‐κB) activity. Notably, ibrutinib‐resistant DLBCL cells also respond to TAK1 inhibition. Database analysis showed that high expression of TAK1 in patients with DLBCL shows poor survival. A subtype of DLBCL patients showed that high expression of both TAK1 and BTK1 is poorly responsive to the current chemotherapy. Moreover, DLBCL cell line with high expression of both TAK1 and BTK1 is resistant to Dox. Simultaneously targeting TAK1 and BTK not only increases cellular toxicity of individual drug but also enhances the sensitivity to Dox. Taken together, we provide convincing evidence to show that kinase TAK1 is a druggable target in DLBCL.

Significance of the study

Currently, there is still a significant portion of patients with DLBCL who are unresponsive to first‐line chemotherapy. Thus, identification of novel druggable targets such as kinase is critical important. Here, we found that TAK1 inhibition promotes death of DLBCL cells through inhibition of chronic NF‐κB signalling. Importantly, TAK1 inhibition overcomes ibrutinib resistance in DLBCL cells. Finally, DLBCL patients with high expression of both TAK1 and BTK showed extremely poor survival. In summary, we provide convincing results to demonstrate a potential important druggable kinase in DLBCL.
Fatty Acid Biosynthesis: Chain‐Length Regulation and Control
Authors: Heil Christina S. , Wehrheim S. Sophia , Paithankar Karthik S. , Grininger Martin
Published: March 2019

De novo biosynthesis of fatty acids is an iterative process requiring strict regulation of the lengths of the produced fatty acids. In this review, we focus on the factors determining chain lengths in fatty acid biosynthesis. In a nutshell, the process of chain‐length regulation can be understood as the output of a chain‐elongating C−C bond forming reaction competing with a terminating fatty acid release function. At the end of each cycle in the iterative process, the synthesizing enzymes need to “decide” whether the growing chain is to be elongated through another cycle or released as the “mature” fatty acid. Recent research has shed light on the factors determining fatty acid chain length and has also achieved control over chain length for the production of the technologically interesting short‐chain (C4–C8) and medium‐chain (C10–C14) fatty acids.
Incomplete coronary sinus reducer endothelialization as potential mechanism of clinical failure
Authors: Zivelonghi Carlo , Vermeersch Gaelle , Verheye Stefan , Agostoni Pierfrancesco
Published: March 2019

The number of patients suffering from refractory angina is constantly increasing. Moreover, these patients are considered at higher risk for new hospitalizations and increased incidence of adverse cardiac events. The coronary sinus reducer was recently introduced as a new therapeutic option in patients with refractory angina and no possibilities for coronary revascularization. However, a consistent percentage of patients, ranging from 15 to 30%, reports no clinical benefits after coronary sinus reducer implantation. The reasons for this lack of effectiveness are at present unknown. We suggest here a possible explanation to this phenomenon.
A Rechargeable Aqueous Sodium‐Ion Battery
Authors: Thimmappa Ravikumar , Gautam Manu , Aralekallu Shambhulinga , Devendrachari Mruthunjayachari Chattanahalli , Kottaichamy Alagar Raja , Bhat Zahid Manzoor , Thotiyl Musthafa Ottakam
Published: March 2019

We report a rechargeable sodium‐ion battery in an aqueous environment with hydrophobic few‐layer graphene as the capacitive anode and hexacyanometallate as the insertion cathode. Owing to the lack of hydrophilic functionalities, sodium‐ion adsorption is selectively favored over H+ adsorption at the hydrophobic anode/electrolyte interface without the complexity of widely encountered hydrogen‐ion insertion/H2 evolution. Hydrophobicity precludes chemical bond formation with sodium ions, thereby improving reversibility and extended cyclability during charge discharge chemistry.
SO‐CovSel: A novel method for variable selection in a multiblock framework
Authors: Biancolillo Alessandra , Marini Federico , Roger Jean‐Michel
Published: March 2019

With the development of technology and the relatively higher availability of new instrumentations, having multiblock data sets (eg, a set of samples analyzed by different analytical techniques) is becoming more and more common and, as a consequence, how to handle this kind of outcomes is a widely discussed topic. In such a context, where the number of involved variables is relatively high, selecting the most significant features is obviously relevant. For this reason, the possibility of joining a multiblock regression method, the sequential and orthogonalized partial least‐squares (SO‐PLS), with a variable selection approach called covariance selection (CovSel), has been investigated. The resulting method, sequential and orthogonalized covariance selection (SO‐CovSel) is similar to SO‐PLS, but the feature reduction provided by PLS is performed by CovSel. Finally, predictions are made by applying multiple linear regression on the subset of selected variables. The novel approach has been tested on different multiblock data sets both in regression and in classification (by combination with LDA), and it has been compared with another state‐of‐the‐art multiblock method. SO‐CovSel has demonstrated to be suitable for its purpose: It has provided good predictions (both in regression and in classification) and, from the interpretation point of view, it has led to a meaningful selection of the original variables.
3D Single Bubble Breakup Tracking in a Stirred Tank
Authors: Krakau Frederic , Kraume Matthias
Published: March 2019

A detailed understanding of turbulent fluid particle breakup mechanisms is essential for the accurate modeling of gas/liquid and liquid/liquid dispersions. The design of a fully automated setup for the three‐dimensional serial examination of the single bubble breakup process in a stirred tank, ensuring high repetition rates necessary for the additionally automated statistical analysis, is described. The implementation of a three‐dimensional automatic bubble breakup tracking tool is illustrated. At last, exemplary bubble breakup trajectories that show the benefits and limitations of the developed system and method are discussed.
Left atrial function in elite athletes: A meta‐analysis of two‐dimensional speckle tracking echocardiographic studies
Authors: Cuspidi Cesare , Tadic Marijana , Sala Carla , Gherbesi Elisa , Grassi Guido , Mancia Giuseppe
Published: March 2019

Background

We sought to investigate left atrial (LA) volume, function, and strain in elite athletes by a meta‐analysis including echocardiographic studies that provided volumetric and strain analysis of LA phasic function.

Methods

The OVID‐MEDLINE, PubMed, and Cochrane CENTRAL databases were searched for English‐language articles without time restriction up to February 2018 through focused and high sensitive search strategies. Studies were identified by crossing the following search terms: “athletes,” “left atrial size,” “left atrial volume,” “atrial function,” “atrial strain,” “atrial strain rate,” “echocardiography,” “2D speckle echocardiography.”

Results

Meta‐analysis included 403 athletes and 314 active but not trained healthy controls from 9 studies. Pooled data showed that average LA volume index was higher in athletes than in healthy controls (28.0 ± 1.0 vs 20.7 ± 0.8 mL/m2, P < 0.001). Global LA longitudinal strain, showing LA reservoir function, was lower in the athletes than in healthy controls with borderline significance (37.0 ± 1.2 vs 38.3 ± 1.5%, P = 0.044). Late diastolic LA strain rate, resembling LA contractile function, was also lower in elite athletes than in control group (−1.56 ± 0.08 vs −1.74 ± 0.09 seconds −1, P = 0.007).

Conclusions

Our meta‐analysis shows that LA volume is higher, while LA reservoir and contractile functions are impaired in elite athletes during active training compared to untrained controls. Whether these changes persist during deconditioning periods remains to be determined. These alterations may be related to the higher risk of arrhythmias, in particular atrial fibrillation, reported among middle/old aged athletes.
“The Missing Link”: The Tubulin Mutation Database Connects Over 1500 Missense Mutations With Phenotypes Across Eukaryotes
Authors: Hussey Shane P , Fritz‐Laylin Lillian K
Published: March 2019

As outlined in their recent paper (A Tubulin Mutation Database: A Resource for the Cytoskeletal Community), Catherine Pham and Naomi Morrissette from the University of California, Irvine, scoured the literature and catalogued data for 489 point mutations for 𝛂‐tubulin, 729 for β‐tubulin, and 343 for 𝛄, ẟ, 𝛆, and 𝛇 tubulins to create the tubulin mutation database (http://tubulinmutations.bio.uci.edu). The database is a searchable catalog of missense mutations and phenotypes that is expected to grow with biannual updates. Data entries regarding the species and isoform, as well as links to available sequences and the original study which characterized the mutant are intuitively displayed and color coded (Pham & Morrissette, 2019). This database represents a unique opportunity for clinicians and cell biologists to rapidly connect sequence data to mutant phenotypes and gather primary literature which promises to facilitate discoveries on topics including microtubule dynamics, antimitotic drug use and resistance, and evolution. We expect that many researchers will find this tool of great use to their research.

This article is protected by copyright. All rights reserved.
Examining Acid Formation During the Selective Dehydration of Fructose to 5‐Hydroxymethylfurfural in Dimethyl Sulfoxide and Water
Authors: Whitaker Mariah R. , Parulkar Aamena , Ranadive Pinaki , Joshi Rutuja , Brunelli Nicholas A.
Published: March 2019

Sustainable conversion of biomass, including fructose dehydration to 5‐hydroxymethylfurfural (HMF), remains a challenge. Fructose can be selectively dehydrated to HMF in dimethyl sulfoxide (DMSO) without addition of an acid catalyst. The role of DMSO is examined starting with either fructose or HMF in DMSO/water. With increasing DMSO content, it is observed that fructose conversion, HMF selectivity, and post‐reaction solution acidity increase. Although DMSO degradation to sulfuric acid is a potential source of acidity and reactivity, a barium chloride precipitation test demonstrates that sulfate ions are not detectable after reaction, suggesting that DMSO is stable during reaction at 120 °C and 150 °C with oxygen present. Instead, the majority of the acidic species produced are formic acid, levulinic acid, and humins. These acids have a minimal effect on fructose conversion in DMSO. These results suggest that DMSO promotes fructose conversion mainly through solvation effects and not as an origin of acid catalysis. For HMF stabilization, the optimal molar fraction of DMSO in water is 0.20–0.43. Overall, these results indicate that DMSO can promote fructose dehydration to HMF at 120 °C.
Standards of medical care for type 2 diabetes in China 2019
Authors: Jia Weiping , Weng Jianping , Zhu Dalong , Ji Linong , Lu Juming , Zhou Zhiguang , Zou Dajin , Guo Lixin , Ji Qiuhe , Chen Li , Chen Liming , Dou Jingtao , Guo Xiaohui , Kuang Hongyu , Li Ling , Li Qifu , Li Xiaoying , Liu Jing , Ran Xingwu , Shi Lixin , Song Guangyao , Xiao Xinhua , Yang Liyong , Zhao Zhigang ,   On behalf of Chinese Diabetes Society
Published: March 2019

The prevalence of diabetes in China has increased rapidly from 0.67% in 1980 to 10.4% in 2013, with the aging of the population and westernization of lifestyle. Since its foundation in 1991, the Chinese Diabetes Society (CDS) has been dedicated to improving academic exchange and the academic level of diabetes research in China. From 2003 to 2014, four versions of Chinese diabetes care guidelines have been published. The guidelines have played an important role in standardizing clinical practice and improving the status quo of diabetes prevention and control in China. Since September 2016, the CDS has invited experts in cardiovascular diseases, psychiatric diseases, nutrition, and traditional Chinese medicine to work with endocrinologists from the CDS to review the new clinical research evidence related to diabetes over the previous 4 years. Over a year of careful revision, this has resulted in the present, new version of guidelines for prevention and care of type 2 diabetes in China. The main contents include epidemiology of type 2 diabetes in China; diagnosis and classification of diabetes; primary, secondary, and tertiary diabetes prevention; diabetes education and management support; blood glucose monitoring; integrated control targets for type 2 diabetes and treatments for hyperglycaemia; medical nutrition therapy; exercise therapy for type 2 diabetes; smoking cessation; pharmacologic therapy for hyperglycaemia; metabolic surgery for type 2 diabetes; prevention and treatment of cardiovascular and cerebrovascular diseases in patients with type 2 diabetes; hypoglycaemia; chronic diabetic complications; special types of diabetes; metabolic syndrome; and diabetes and traditional Chinese medicine.
Microfluidic device fabricated by three‐dimensional lithography for observation of cancer cell invasion process
Authors: Tachikawa Saeko , Kaneda Shohei , Kumemura Momoko , Sato Rui , Tsukamoto Takuya , Fujii Teruo , Suzuki Takaaki , Fujita Hiroyuki
Published: March 2019

This paper describes a microfluidic device for observation of cancer cell invasion induced by chemotaxis. The developed device has two main channels, the channel filled with cell suspension and the channel filled with solution containing chemotactic factor. These channels are connected via tapered orifice structures to capture multiple cancer cells in it to form cell clusters. Observation of cell invasions affected by cell adhesions is possible with this device. The devices were fabricated by using three‐dimensional lithography and PDMS (polydimethylsiloxane) molding. Invasion cells leaving the cell clusters and moving to the channel containing chemotactic factors through the orifices were successfully observed on the device.
Synthesis and Characterization of Two Cationic Silver Quinoxaline Coordination Polymers
Authors: Soe Eaindar , Kim Judith S. , Chakraborty Indranil , Oliver Scott R. J.
Published: March 2019

We report two cationic silver‐based coordination polymers with N‐donating quinoxaline as the linker. [Ag(quinoxaline)+] [–O3S(CH2)2SO3–]0.5·2H2O (which we denote as SLUG‐37 for University of California, Santa Cruz, structure No. 37; quinoxaline = C8H6N2) and [Ag(quinoxaline)+][CH3CO2–] (SLUG‐38) were solved by single‐crystal X‐ray diffraction and further characterized by several solid‐state techniques. Both structures consist of cationic 1D Ag‐quinoxaline chains arranged into π‐stacked layers, with charge‐balancing anions residing in the interlamellar space. The materials can be synthesized hydrothermally as well as in higher yield by reflux or room temperature conditions. The luminescent behavior of SLUG‐37 exhibits a strong white emission making it potentially useful as white LEDs.
Synthesis and Characterization of Cyclometalated NHC Platinum Complexes with Chelating Carboxylate Ligands
Authors: Zábranský Martin , Soellner Johannes , Horký Filip , Císařová Ivana , Štěpnička Petr , Strassner Thomas
Published: March 2019

Platinum(II) complexes [Pt(C^C*)(acac)], where C^C* = 3‐R‐1‐(phenyl‐κC2)‐1H‐benzimidazol‐2‐ylidene‐κC2 (R = Me, Ph) and acac = pentane‐2,4‐dionate, reacted with functionalized acetic acids YCH2CO2H (Y = NMe2, SMe and PPh2) with elimination of acetylacetone to produce the bis‐chelate complexes of the type [Pt(C^C*)(YCH2CO2)]. Whereas the Pt(II) precursor with the less bulky methyl substituent (R) gave rise to single products having trans‐C(NHC),Y geometry, its phenyl congener reacted less selectively, affording exclusively the product with trans‐S,C(Ph) configuration for Y = SMe and mixtures of cis and trans isomers for Y = NMe2 and PPh2. These observations were well reproduced by different DFT functionals at the double‐ξ level of theory, which suggested rather small energy differences between the geometric isomers. The photophysical measurements showed that complexes [Pt(C^C*)(YCH2CO2)] are emissive in the blue region (λem 460–490 nm) with photoluminescence quantum yields up to 36 % and emission lifetimes in the range of 3–5 µs.
Halogenated Allyl Alcohol Derivatives ‐ Versatile Electrophiles for Palladium‐Catalyzed Allylic Alkylations
Authors: Kohr Michael , Kazmaier Uli
Published: March 2019

Brominated and iodinated allylic substrates can be subjected to palladium‐catalyzed allylic alkylation of amino acid and peptide ester enolates. The incorporation of a vinylic halide functionality into the allylic substrate allows a direct modification of the allylated peptide via cross coupling chemistry. Therefore, the direct introduction of a vinylhalide side chain into a peptide is an interesting alternative to the stannylallylation/halogenation approach. However, the haloallylation is not as trivial as normal allylic alkylations, because the incorporation of a second, competitive electrophilic center into the allyl moiety requires careful optimization of the reaction conditions.
Partial characteristics for marked spatial point processes
Authors: Eckardt M. , Mateu J.
Published: March 2019

This paper introduces a new class of partial summary characteristics for two types of marked planar point processes. We consider purely qualitatively marked spatial point processes and multitype spatial point processes with quantitative marks. After a survey of classical functional summary characteristics for qualitatively and quantitatively marked point processes, the class of partial characteristics is presented. These characteristics are defined through the periodogram, which makes the computations efficient. We demonstrate the application of our method in the analysis of a multispecies tree data recorded in the City of Melbourne.
Breakage law and fractal characteristics of broken coal and rock masses with different mixing ratios during compaction
Authors: Li Bo , Liang Yunpei , Zhang Lei , Zou Quanle
Published: March 2019

Broken coal and rock masses are the major part of the goaf. The compaction characteristics of coal and rock masses and the breakage law of whose particles during compaction exert an important influence on various aspects including control of strata motion, prediction of surface subsidence, and backfill mining. In this paper, the triaxial compaction experiment on broken coal‐rock masses with different mixing ratios was carried out. The test results showed that with the increase of stresses, the strain of coal‐rock masses gradually rose while the porosity, bulking factor, and degree of compaction gradually declined. During the compaction of coal‐rock masses, the fitting curves of the strain, porosity, bulking factor, and degree of compaction with stresses of coal samples all appeared as a cubic function of stresses. The breakage behavior of coal particles underwent three stages: structure re‐arrangement and breakage of particles, particle breakage, and compression‐induced deformation of particles. With increasing stress, the crushing amount of particles gradually grew while the increase rate of the crushed particles gradually decreased and the larger the particle strength was, the lower the increase rate of the crushing amount. Additionally, in the compaction process of samples, particle breakage mainly appeared before the stress reached to 8 MPa while the coal and rock particles were hardly crushed after the stress was larger than 8 MPa. With increasing stresses, the particle size gradation of samples gradually became reasonable and the lower the particle strength of samples was, the more reasonable the particle size gradation of compacted samples. The particle size gradation of various compacted and crushed samples showed a favorable fractal characteristic. In the stage with a low stress, the value of fractal dimension D rapidly grew and the fractal dimensions D of various samples tended to be stabilized after the stress reached to a high level.
Intermittent antipsychotic medication and mortality in institutionalized older adults: A scoping review
Authors: Randle Jason M. , Heckman George , Oremus Mark , Ho Joanne
Published: March 2019

Objective/Background

Antipsychotic use appears to increase mortality risk among older adults with dementia. Whether this risk is similar for regular or intermittent use is unknown. This scoping review aims to explore the temporal association between antipsychotic use and mortality risk for older institutionalized adults.

Method

We conducted a scoping review using Medline (PubMed), EMBASE, CINAHL, and the Cochrane libraries between October 2018 and January 2019.

Results

Twenty‐eight articles met review criteria. We found that different antipsychotic medications present different safety profiles. The risk of mortality was highest with conventional antipsychotic use and within 40 days of antipsychotic initiation.

Conclusions

Conventional antipsychotic use increases mortality for older institutionalized adults. The evidence for atypical antipsychotics is less clear. Mortality risk appears highest within 30 to 40 days of initiating antipsychotic treatment. This temporal association suggests increased mortality may actually be the result of some previously unrecognized illness, comorbidity, change in health status, or increased frailty, rather than an idiosyncrasy of the antipsychotic itself.
LncRNA CACNA1G‐AS1 facilitates hepatocellular carcinoma progression through the miR‐2392/C1orf61 pathway
Authors: Yang Jinghui , Li Chunsheng , Li Hang , E Changyong
Published: March 2019

Emerging studies have indicated that long noncoding RNAs (lncRNAs) possess various functions in initiating human cancers. However, the role of lncRNAs in hepatocellular carcinoma (HCC) still remains ill understood. In this study, we sought to investigate the role of lncRNA CACNA1G‐AS1 in HCC progression. Through bioinformatics analysis, we found that CACNA1G‐AS1 expression was significantly upregulated in HCC tissues compared with that in the adjacent normal tissues. Moreover, CACNA1G‐AS1 upregulation indicated poor prognosis in HCC patients. Knockdown of CACNA1G‐AS1 attenuated the proliferation, migration, and invasion of HCC cells. Additionally, decreased expression of CACNA1G‐AS1 prevented epithelial–mesenchymal transition. In vivo assay also showed that CACNA1G‐AS1 silencing HCC cells have smaller tumor volumes and weights. Further investigations demonstrated that CACNA1G‐AS1 worked as a competing endogenous RNA to bind microRNA‐2392 (miR‐2392) and thereby alleviate the repression of the downstream target C1orf61. Collectively, CACNA1G‐AS1 promotes HCC progression through regulating the miR‐2392/C1orf61 pathway.
Antibody‐drug therapeutic conjugates: Potential of antibody‐siRNAs in cancer therapy
Authors: Yarian Fatemeh , Alibakhshi Abbas , Eyvazi Shirin , Arezumand Roghaye , Ahangarzadeh Shahrzad
Published: March 2019

Codelivery is a promising strategy of targeted delivery of cytotoxic drugs for eradicating tumor cells. This rapidly growing method of drug delivery uses a conjugate containing drug linked to a smart carrier. Both two parts usually have therapeutic properties on the tumor cells. Monoclonal antibodies and their derivatives, such as Fab, scFv, and bsAb due to targeting high potent have now been attractive candidates as drug targeting carrier systems. The success of some therapeutic agents like small interfering RNA (siRNA), a small noncoding RNAs, with having problems such as enzymatic degradation and rapid renal filtration need to an appropriate carrier. Therefore, the aim of this study is to review the recent enhancements in development of antibody drug conjugates (ADCs), especially antibody–siRNA conjugates (SRCs), its characterizations and mechanisms in innovative cancer therapy approaches.
Ability to understand and correctly follow HIV self‐test kit instructions for use: applying the cognitive interview technique in Malawi and Zambia
Authors: Simwinga Musonda , Kumwenda Moses K , Dacombe Russell J , Kayira Lusungu , Muzumara Agness , Johnson Cheryl C , Indravudh Pitchaya , Sibanda Euphemia L , Nyirenda Lot , Hatzold Karin , Corbett Elizabeth L , Ayles Helen , Taegtmeyer Miriam
Published: March 2019

Introduction

The ability to achieve an accurate test result and interpret it correctly is critical to the impact and effectiveness of HIV self‐testing (HIVST). Simple and easy‐to‐use devices, instructions for use (IFU) and other support tools have been shown to be key to good performance in sub‐Saharan Africa and may be highly contextual. The objective of this study was to explore the utility of cognitive interviewing in optimizing the local understanding of manufacturers’ IFUs to achieve an accurate HIVST result.

Methods

Functionally literate and antiretroviral therapy‐naive participants were purposefully selected between May 2016 and June 2017 to represent intended users of HIV self‐tests from urban and rural areas in Malawi and Zambia. Participants were asked to follow IFUs for HIVST. We then conducted cognitive interviews and observed participants while they attempted to complete the HIVST steps using a structured guide, which mirrored the steps in the IFU. Qualitative data were analysed using a thematic approach.

Results

Of a total of 61 participants, many successfully performed most steps in the IFU. Some had difficulties in understanding these and made errors, which could have led to incorrect test results, such as incorrect use of buffer and reading the results prematurely. Participants with lower levels of literacy and inexperience with standard pictorial images were more likely to struggle with IFUs. Difficulties tended to be more pronounced among those in rural settings. Ambiguous terms and translations in the IFU, unfamiliar images and symbols, and unclear order of the steps to be followed were most commonly linked to errors and lower comprehension among participants. Feedback was provided to the manufacturer on the findings, which resulted in further optimization of IFUs.

Conclusions

Cognitive interviewing identifies local difficulties in conducting HIVST from manufacturer‐translated IFUs. It is a useful and practical methodology to optimize IFUs and make them more understandable.
Detection and assignment of inorganic aqueous polymers relevant to environmental nanogeoscience by direct infusion electrospray ionization mass spectrometry
Authors: Becerra‐Herrera Mercedes , Moraga Sergio D. , Cruz‐Hernández Pablo , Molinas Rodrigo , Richter Pablo , Caraballo Manuel A.
Published: March 2019

Inorganic polymers in aqueous solutions are being proposed as essential components in new theories concerning nonclassical nucleation and growth of nanominerals relevant to environmental nanogeosciences. The study of those complex natural processes requires multi‐technique analytical approaches able to characterize the solutions and their constituents (solutes, oligomers, polymers, clusters and nanominerals) from atomic to micrometric scales. A novel analytical approach involving an electrospray ionization source (ESI) coupled to time‐of‐flight mass spectrometry (TOF/MS) was developed to identify inorganic polymers in aqueous solution. To this end, the presence of initial Al oligomers and their polymerization processes was studied during a nanomineral aqueous synthesis (hydrobasaluminte, Al4SO4(OH)10·12‐36H2O). Ensuring the feasibility and robustness of the methodology as well as the stability of the polymers under study (avoiding undesirable fragmentation), a meticulous study of the ESI‐TOF MS working conditions was performed. Precision of the methodology was evaluated obtaining relative standard deviations below 3.3%. For the first time in the study of inorganic polymers in the earth sciences, the mass accuracy error (ppm) has been reported and the use of significant decimal figures of the m/z signal has been taken into account. Complementary to this, a four‐step polymer assignment methodology and a database with the Al− and Al‐SO42− polymers assigned were created. Several polymers have been assigned for the first time, including Al (SO4)+·H2O, Al2O(SO4)2+·H2O, Al5O4(OH)52+·2H2O, and Al3O5(OH)2−·4H2O, among others. The results obtained in the present study help create a foundation to include mass spectrometry as a routine analytical technique to study mineral formation in aqueous solution.
Molecular and serological characterization of occult hepatitis B virus infection among patients with hemophilia
Authors: Javanmard Davod , Namaei Mohammad Hasan , Farahmand Mohammad , Ziaee Arash , Amini Elham , Ziaee Masood
Published: March 2019

Background

The occult hepatitis B virus infection (OBI) is a health concern among high‐risk groups and immunosuppressed individuals. There is still a paucity of data regarding the occult hepatitis B virus infection among hemophilic patients. With this in mind, we aimed to evaluate the molecular prevalence of OBI among clients with hemophilia.

Methods

Totally, 87 hemophilic patients were selected to be studied. To detect OBI, nested polymerase chain reaction test was used to amplify HBV‐S, X, and Core regions. Viral load was determined using an in‐house real‐time PCR assay. Finally, sequence of S gene was used for genotyping and analysis of mutations.

Results

The mean age of patients was 28.4 ± 5.3 years old, with 90.7% of whom were men. HBV‐DNA was detected in eight subjects (9.3%). The rate of OBI was much higher in anti‐HBs seronegative subjects than that in other patients (P = 0.019). All OBI cases had HBV genotype D, subgenotype D1. In addition, five out of eight cases (62.5%) showed detectable viral loads (a mean viral load of 4.5 × 10
2 copies/mL). sR73H, sI110L, sP120A, sP127T, sQ129H, sG130R, and sC137S were shown to be the most determinant escape mutation and OBI‐relevant mutants.

Conclusion

The rate of OBI among the studied population of hemophilia seems to be remarkable. Therefore, screening for OBI must be a routine practice in patients with hemophilia and also patients undergoing immunosuppressive treatments. Amino acid substitutions were observed in the major hydrophilic region. However further investigations are needed for analysis of exact function.
Relative contribution of epiphyseal tubercle and peripheral cupping to capital femoral epiphysis stability during daily activities
Authors: Kiapour Ata M. , Kiapour Ali , Maranho Daniel A. , Kim Young‐Jo , Novais Eduardo N.
Published: March 2019

Epiphyseal tubercle and peripheral cupping can influence the development of slipped capital femoral epiphysis (SCFE) and Cam morphology. During normal skeletal growth, epiphyseal tubercle shrinks while the peripheral cupping grows. We hypothesized that epiphyseal tubercle act as the primary stabilizer of the head‐neck junction at early stages and this role is gradually transferred to epiphyseal cupping as the tubercle shrinks and cupping grows. From a cohort of 80 boys and girls (8–15 years old) with normal hips, CT scans of 5 subjects corresponding to minimum, 25th percentile, median, 75th percentile and maximum relative tubercle and cupping height were used to develop 3D finite element models. In vivo measured hip loads were used to study load sharing between the tubercle and peripheral cupping under combined and uniaxial loads exerted on femoral head during a range of daily activities. Lower epiphyseal tubercle height, larger epiphyseal cupping height and bigger differences in tubercle and cupping heights were strongly associated with increased epiphyseal cupping to epiphyseal tubercle stress ratios (R2 > 0.7). We found lower peripheral cupping stresses relative to the tubercle (cupping to tubercle stress ratio <1) in hips with larger tubercle and smaller cupping. The relative decreases in tubercle size along with increased in peripheral cupping in our models gradually shifted the load distribution to higher stresses in the periphery compared to the epiphyseal tubercle area (cupping to tubercle stress ratio >1). Both tubercle and cupping play a substantial role in sharing the generated stresses across the head‐neck junction under all tested loading conditions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1571–1579, 2019.
Bone resorption triggered by high radial stress: The mechanism of screw loosening in plate fixation of long bone fractures
Authors: Feng Xiaoreng , Lin Guanghu , Fang Christian X. , Lu William W. , Chen Bin , Leung Frankie K. L.
Published: March 2019

Screw loosening is a common complication in plate fixation. However, the underlying mechanism is unclear. This study investigated screw loosening mechanisms by finite element analysis (FEA) simulation and clinical X‐ray feature analysis. Two FEA models incorporated bone heterogeneity and orthotropy, representing fracture fixation using dynamic compression plate (DCP) and locking compression plate (LCP), were developed. These models were used to examine the volume of bone exceeding a certain stress value around each screw under physiologically‐relevant loading conditions. These damaged bone was then separated and compared by the axial stress and radial stress of each screw. In addition, features of patients’ X‐ray images showing screw loosening were analyzed to validate the loosening features simulated by the models. The FEA study showed that more damaged bone was found at the central two screws which gradually decreased toward the two end screws in all groups. More bone was damaged by the radial stress of each screw than by the axial stress. The radiological analysis of screw loosening showed that bone loss occurred at the screw closest to the fracture line first then subsequent bone loss at the screws further away from the fracture line occurred. This study found that the two screws nearest to the fracture line are more vulnerable to loosening. The radial stress of the screw plays a larger role in screw loosening than the axial stress. Bone resorption triggered by the high radial stress of screws is indicated as the mechanism of screw loosening in the diaphyseal plate fixation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1498–1507, 2019.
Effect of cavity preparation and bone mineral density on bone‐interface densification and bone‐implant contact during press‐fit implantation of hip stems
Authors: Bätz Johanna , Messer‐Hannemann Philipp , Lampe Frank , Klein Anke , Püschel Klaus , Morlock Michael M. , Campbell Graeme M.
Published: March 2019

Implant loosening and periprosthetic fracture are two major revision causes for uncemented hip stems. The chosen method of cavity preparation could play a key role for both failure mechanisms. The aim of this study was to determine the dependence of the broach type as well as patient bone mineral density (BMD) on densification and contact conditions at the bone‐implant interface. Hip stems were implanted into cadaveric femora using compaction, blunt extraction or sharp extraction broaches with computed tomography scans performed prior to broaching, after broaching and after stem implantation. Proximal periprosthetic bone densification as well as press‐fit, contact area and stem seating relative to the last broach were determined. Median bone densification was higher with the compaction and blunt extraction broaches compared to sharp extraction broaches (181% and 177%, respectively, p = 0.002). The bone densification of femora prepared with compaction broaching increased with higher BMD (R2 = 0.183, p = 0.037), while stem seating decreased with higher BMD for all broach types (R2 = 0.259, p = 0.001). Incomplete seated prostheses were associated with smaller press‐fit and bone‐implant contact area (R2 = 0.249, p = 0.001; R2 = 0.287, p < 0.001).

Clinical Significance: The results suggest that compaction broaching maximizes bone densification in patients with higher bone density. However, there appears to be an increased risk of insufficient stem seating in high‐density bone that could limit the benefits for primary stability. For lower quality bone, the broach type appears to play a lesser role, but care must be taken to limit extensive stem seating which might increase periprosthetic fracture risk. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1580–1589, 2019.