bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of olfactory training on odor identification in patients with traumatic anosmia
Authors: Jiang Rong‐San , Twu Chih‐Wen , Liang Kai‐Li
Published: August 2019

Background

This study investigates the effect of olfactory training on odor identification in patients with traumatic anosmia.

Methods

Patients with a clear history of loss of smell after head injury, and whose phenyl ethyl alcohol (PEA) odor detection thresholds remained at –1 after steroid and zinc treatment, were included in this study between July 2016 and July 2018. They were randomly divided into 2 groups, with patients in the 4‐odorant group given 4 bottles of PEA, lemon, eucalyptus, and clove oils and those in the PEA group given a bottle of PEA for 6‐month olfactory training. After 3‐month and 6‐month training, the olfactory function was evaluated by both the PEA threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT‐TC). Magnetic resonance imaging was performed to measure the volume of olfactory bulbs after training.

Results

There were 45 patients completing 4‐odorant training and another 45 completing PEA training. The birhinal PEA threshold decreased significantly in both groups after 6‐month training, but the decrease was not significantly different between the 2 groups. The UPSIT‐TC score increased significantly in the PEA group but not in the 4‐odorant group. The volume of olfactory bulbs was not significantly different between these 2 groups.

Conclusion

Our results show that olfactory training can slightly improve odor threshold levels in patients with traumatic anosmia, but did not improve the odor identification ability. Nevertheless, clinical improvement or benefit in quality of life from olfactory training needs further investigation.
Aromatic Chemistry in the Excited State: Facilitating Metal‐Free Substitutions and Cross‐Couplings
Authors: Liu Wenbo , Li Jianbin , Huang Chia‐Yu , Li Chao‐Jun
Published: August 2019

Transition‐metal‐catalyzed cross‐couplings between aromatic electrophiles and nucleophiles have revolutionized modern chemical syntheses. Nevertheless, transition‐metal‐free approaches are preferable, considering the various issues caused by metal catalysts. This Minireview summarizes the recent progress in the light‐enabled transition‐metal‐free formation of carbon–carbon and carbon–heteroatom bonds in aromatics, which opens a new avenue in aromatic reactions. From the mechanistic perspective, it classifies different reaction types of aryl electrophiles in an excited state with various nucleophiles. We believe this will provide more rationales for metal‐free aromatic substitutions and cross‐couplings with light, and guide the development of novel transformations of aromatic compounds facilitated by light.
Layer‐Defining Strategy to Grow Two‐Dimensional Molecular Crystals on a Liquid Surface down to the Monolayer Limit
Authors: Yao Jiarong , Zhang Yu , Tian Xinzi , Zhang Xiali , Zhao Huijuan , Zhang Xiaotao , Jie Jiansheng , Wang Xinran , Li Rongjin , Hu Wenping
Published: August 2019

Two‐dimensional molecular crystals (2DMCs) open a new door for the controllable growth of 2D materials by molecular design with a energy gap and solution processability. However, the growth of 2DMCs with defined molecular layers remains full of challenges. Herein, we report a novel method to produce various 2DMCs with a defined number of molecular layers. When the surface tension and viscosity are tuned to control the spreading of the solution on the liquid surface, large‐area quasi‐freestanding 2DMCs from bulk size down to the monolayer limit are obtained, which makes it possible to probe the intrinsic layer‐dependent optoelectronic properties of organic semiconductors down to the physical limit, and paves the way for the application of 2DMCs in new optoelectronic devices and technologies.
Stable 2D Heteroporous Covalent Organic Frameworks for Efficient Ionic Conduction
Authors: Xie Zhen , Wang Bo , Yang Zongfan , Yang Xiao , Yu Xiang , Xing Guolong , Zhang Yinghui , Chen Long
Published: August 2019

Two‐dimensional (2D) covalent organic frameworks (COFs) feature open and ordered one‐dimensional column nanochannels which offer immense possibilities for incorporation of various guests for specific functions. However, the relatively low chemical stability of most COFs originating from the dynamic covalent linkages hinders their practical application. In this work, a highly crystalline and heteroporous dibenzo[g,p]chrysene‐based COF (DBC‐2P) was synthesized and served as a host material for ionic conduction. DBC‐2P exhibits excellent stability both in strong acid and base due to the large conjugated DBC‐based knot that reinforces the interlayer interactions. Subsequent encapsulation of linear polyethylene glycol (PEG) and PEG‐LiBF4 salt into the nanochannels of DBC‐2P affords a hybrid material with a high ionic conductivity of 2.31×10−3 S cm−1. This work demonstrates an efficient post‐synthetic strategy for the development of new COF–polymer composites with intriguing properties.
Spontaneous Crystallization of Perovskite Nanocrystals in Nonpolar Organic Solvents: A Versatile Approach for their Shape‐Controlled Synthesis
Authors: Huang He , Li Yanxiu , Tong Yu , Yao En‐Ping , Feil Maximilian W. , Richter Alexander F. , Döblinger Markus , Rogach Andrey L. , Feldmann Jochen , Polavarapu Lakshminarayana
Published: August 2019

The growing demand for perovskite nanocrystals (NCs) for various applications has stimulated the development of facile synthetic methods. Perovskite NCs have often been synthesized by either ligand‐assisted reprecipitation (LARP) at room temperature or by hot‐injection at high temperatures and inert atmosphere. However, the use of polar solvents in LARP affects their stability. Herein, we report on the spontaneous crystallization of perovskite NCs in nonpolar organic media at ambient conditions by simple mixing of precursor–ligand complexes without application of any external stimuli. The shape of the NCs can be controlled from nanocubes to nanoplatelets by varying the ratio of monovalent (e.g. formamidinium+ (FA+) and Cs+) to divalent (Pb2+) cation–ligand complexes. The precursor–ligand complexes are stable for months, and thus perovskite NCs can be readily prepared prior to use. Moreover, we show that this versatile synthetic process is scalable and generally applicable for perovskite NCs of different compositions.
In‐situ Electrochemical X‐ray Diffraction: A Rigorous Method to Navigate within Phase Diagrams Reveals β‐Fe1+xSe as Superconductor for All x
Authors: Rasche Bertold , Yang Minjun , Nikonow Lothar , Cooper Joshaniel F. K. , Murray Claire A. , Day Sarah J. , Kleiner Karin , Clarke Simon J. , Compton Richard G.
Published: August 2019

We report the precise postsynthetic control of the composition of β‐Fe1+xSe by electrochemistry with simultaneous tracking of the associated structural changes via in situ synchrotron X‐ray diffraction. We access the full phase width of 0.01<x<0.04 and identify the superconducting state below 8 K, which in contrast to earlier reports is independent of the composition. However, in a second set of in situ X‐ray diffraction experiments, we demonstrate that β‐Fe1+xSe forms a new phase in the presence of oxygen above a 100 °C which has the same anti‐PbO type structure but is not superconducting down to 1.8 K. The latter process can be reversed electrochemically to reinstate the superconducting state. These observations exploit the exquisite control afforded by electrochemistry in contrast with classical approaches of chemical synthesis.
Sutural Morphology in the Craniofacial Skeleton: A Descriptive Microcomputed Tomography Study in a Swine Model
Authors: Savoldi Fabio , Tsoi James K. H. , Paganelli Corrado , Matinlinna Jukka P.
Published: August 2019

Sutures are greatly involved in both normal craniofacial growth and developmental anomalies. Having clear parameters for defining their morphology is fundamental to properly investigate their physiological or pathological development. However, the current literature is lacking of well‐defined methods for the assessment of these structures. This study performed a comprehensive microcomputed tomography (μCT) analysis of a swine model evaluating morphological variation of sutures in different skull regions. Seventy‐two suture samples were removed from one swine (Sus scrofa), approximately 9–12‐month‐old. Each sample was analyzed with μCT in the parallel (PAR) and perpendicular (PER) plane with respect to the bone surface. Suture width (S
w), linear obliteration index (LOI), and linear interdigitation index (LII) were calculated in each of the two reference planes, and sutures were categorized in four types (S
t). Parameters were compared among the facial, craniofacial, and cranial region. Description of the main morphological parameters was provided, and differences were found between the parallel and perpendicular planes. S
t varied depending on the skull region, with simple sutures more represented in the cranial region. LII in the perpendicular plane decreased from facial to craniofacial and cranial region. S
w in the parallel plane decreased from facial and craniofacial to cranial region. In the swine model, the sutural width, linear interdigitation, and suture type were related to distinct skull regions. The suture type was introduced to allow a better morphological characterization of sutures as 3D structures. Clear definition of sutural parameters is important for appropriate description of these complex structures. Anat Rec, 302:2156–2163, 2019. © 2019 American Association for Anatomy
Aflatoxin B1 removal by three bacterial strains and optimization of fermentation process parameters
Authors: Ning Mengge , Zhang Shujie , Xie Yanli , Wang Wei , Gao Yajun
Published: August 2019

Aflatoxin B1 (AFB1) removing bacterial strains were isolated from different habitats that were easily contaminated by AFB1. Furthermore, the composition of the fermentation medium and conditions of fermentation process were optimized, including carbon source, nitrogen source, metal ions, temperature, initial pH value, inoculation volume, and culture broth volume. Using coumarin as the sole carbon and energy source, we primarily screened 31 strains, and 10 strains were found to be capable to remove AFB1. Among them, the highest removal rate of 71.91% appeared in those isolated from rotten wood (poplar). Strains XY1, XY3, and T6 were carried out to identify, and the results were Klebsiella sp., Klebsiella pneumonia, and Pantoea sp., respectively. Corn cob powder and tryptone can significantly increase the AFB1 removal activity of these strains. The AFB1 removal activity of Klebsiella sp.XY1 and K. pneumonia XY3 can be enhanced by Ca2+, and those of Pantoea sp. T6 can be enhanced by Cu2+. Temperature and initial pH were positively correlated with the AFB1 removal activity of these strains in a certain range. This study not only provides reference for the screening and application of AFB1 removing bacteria, but also provides a basis for possible application in the food and feed industry.
Geotechnische Herausforderungen bei der Planung der Filstalbrücke als semiintegrales Bauwerk auf der Neubaustrecke Wendlingen–Ulm
Authors: Boley Conrad , Wilfing Lisa , Raithel Marc , Zimmerer Martin , Hierl Martin , Zaidman Igor
Published: August 2019

Für die Eisenbahn‐Hochgeschwindigkeitsstrecke im Projektabschnitt „Albaufstieg“ des Großprojekts Stuttgart 21 wird die Filstalbrücke als semiintegrales Bauwerk ausgeführt, bei welchem die Pfeiler ohne Fugen und Lager kraftschlüssig mit dem Überbau gekoppelt werden. Der Entwurf sah flach gegründete Widerlager und kombinierte Pfahl‐Plattengründungen für die Pfeiler in den teilweise karstigen Jurakalken vor. Auf der Grundlage der konsequenten Ausweisung von Tragwerksreserven durch Anwendung hochwertiger numerischer Bemessungsmodelle in Verbindung mit der Durchführung von Pfahlprobebelastungen konnte die Gründung so optimiert werden, dass gegenüber dem ursprünglichen Entwurf ca. 50 % der Pfahlmeter eingespart werden konnten.

Während der Bauausführung wurde im Bereich des Widerlagers komplexer und sehr heterogener Baugrund angetroffen. Als Folge wurde eine Vielzahl an Vergütungsmaßnahmen geplant und ausgeführt.
Reducing Staphylococcus aureus resistance to lysostaphin using CRISPR‐dCas9
Authors: Wu Xia , Zha Jian , Koffas Mattheos A. G. , Dordick Jonathan S.
Published: August 2019

Bacteriolytic enzymes (cell lytic enzymes) are promising alternatives to antibiotics especially in killing drug‐resistant bacteria. However, some bacteria slowly become resistant to various classes of peptidoglycan hydrolases, for reasons not well studied, in the presence of growth‐supporting nutrients, which are prevalent at sites of infection. Here, we show that Staphylococcus aureus, a human and animal pathogen, while susceptible to the potent staphylolytic enzyme lysostaphin (Lst) in buffered saline, is highly resistant in the rich medium tryptic soy broth (TSB). Through a series of biochemical analysis, we identified that the resistance was due to prevention of Lst‐cell binding mediated by the wall teichoic acids (WTAs) present on the cell surface. Inhibition or deletion of the gene tarO responsible for the first step of WTA biosynthesis greatly reduced S. aureus resistance to Lst in TSB. To overcome the resistance, we took advantage of the gene regulation potential of CRISPR‐dCas9 and demonstrated that downregulation of tarO, tarH, and/or tarG gene expression, the latter two encoding enzymes that anchor WTAs in the outer layer of cell wall peptidoglycan, sensitized S. aureus to Lst and enabled eradication of the bacterium in TSB in 24 hr. As a result, we elucidate a key mechanism of Lst resistance in metabolically active S. aureus and provide a potential approach for treating life‐threatening or hard‐to‐treat infections caused by Gram‐positive pathogens.
Substrate Flexibility of the Flavin‐Dependent Dihydropyrrole Oxidases PigB and HapB Involved in Antibiotic Prodigiosin Biosynthesis
Authors: Couturier Maxime , Bhalara Hiral D. , Chawrai Suresh R. , Monson Rita , Williamson Neil R. , Salmond George P. C. , Leeper Finian J.
Published: August 2019

In the biosynthesis of the tripyrrolic pigment prodigiosin, PigB is a predicted flavin‐dependent oxidase responsible for the formation of 2‐methyl‐3‐amylpyrrole (MAP) from a dihydropyrrole. To prove which dihydropyrrole is the true intermediate, both possibilities, 5‐methyl‐4‐pentyl‐3,4‐dihydro‐2H‐pyrrole (5 a, resulting from transamination of the aldehyde of 3‐acetyloctanal) and 2‐methyl‐3‐pentyl‐3,4‐dihydro‐2H‐pyrrole (6, resulting from transamination of the ketone), were synthesised. Only 5 a restored pigment production in a strain of Serratia sp. ATCC 39006 blocked earlier in MAP biosynthesis. PigB is membrane‐associated and inactive when its transmembrane domain was deleted, but HapB, its homologue in Hahella chejuensis, lacks the transmembrane domain and is active in solution. Two colourimetric assays for PigB and HapB were developed, and the HapB‐catalysed reaction was kinetically characterised. Ten analogues of 5 a were synthesised, varying in the C2 and C3 side chains, and tested as substrates of HapB in vitro and for restoration of pigment production in Serratia ΔpigD in vivo. All lengths of side chain tested at C3 were accepted, but only short side chains at C2 were accepted. The knowledge that 5 a is an intermediate in prodigiosin biosynthesis and the ease of synthesis of analogues of 5 a makes a range of prodigiosin analogues readily available by mutasynthesis.
Inner‐Sphere Oxygen Activation Promoting Outer‐Sphere Nucleophilic Attack on Olefins
Authors: Abril Paula , del Río M. Pilar , López José A. , Lledós Agustí , Ciriano Miguel A. , Tejel Cristina
Published: August 2019

Alkoxylation and hydroxylation reactions of 1,5‐cyclooctadiene (cod) in an iridium complex with alcohols and water promoted by the reduction of oxygen to hydrogen peroxide are described. The exo configuration of the OH/OR groups in the products agrees with nucleophilic attack at the external face of the olefin as the key step. The reactions also require the presence of a coordinating protic acid (such as picolinic acid (Hpic)) and involve the participation of a cationic diolefin iridium(III) complex, [Ir(cod)(pic)2]+, which has been isolated. Independently, this cation is also involved in easy alkoxy group exchange reactions, which are very unusual for organic ethers. DFT studies on the mechanism of olefin alkoxylation mediated by oxygen show a low‐energy proton‐coupled electron‐transfer step connecting a superoxide–iridium(II) complex with hydroperoxide–iridium(III) intermediates, rather than peroxide complexes. Accordingly, a more complex reaction, with up to four different products, occurred upon reacting the diolefin–peroxide iridium(III) complex with Hpic. Moreover, such hydroperoxide intermediates are the origin of the regio‐ and stereoselectivity of the hydroxylation/alkoxylation reactions. If this protocol is applied to the diolefin–rhodium(I) complex [Rh(pic)(cod)], free alkyl ethers ORC8H11 (R=Me, Et) resulted, and the reaction is enantioselective if a chiral amino acid, such as l‐proline, is used instead of Hpic.
BODIPY‐Labeled Cyclobutanes by Secondary C(sp3)−H Arylations for Live‐Cell Imaging
Authors: Virelli Matteo , Wang Wei , Kuniyil Rositha , Wu Jun , Zanoni Giuseppe , Fernandez Antonio , Scott Jamie , Vendrell Marc , Ackermann Lutz
Published: August 2019

Arylated cyclobutanes were accessed by a versatile palladium‐catalyzed secondary C(sp3)−H activation, exploiting chelation assistance by modular triazoles. The C−H arylation led to cyclobutane natural product derivatives in a highly regioselective fashion, setting the stage for the easy access to novel fluorogenic boron‐dipyrrin (BODIPY)‐labeled probes for live‐cell imaging.
“On‐Water” Palladium‐Catalyzed Tandem Cyclization Reaction for the Synthesis of Biologically Relevant 4‐Arylquinazolines
Authors: Yuan Shuo , Yu Bin , Liu Hong‐Min
Published: August 2019

The quinazoline scaffold is prevalent in pharmaceutically relevant molecules that show diverse biological activities. Herein, we report an efficient “on‐water” palladium‐catalyzed tandem cyclization reaction from commercially available arylboronic acids and benzonitriles that enable the rapid access to 4‐arylquinazoline scaffolds in good to excellent yields (45 examples, up to 98 % yield). This protocol has shown good functional group tolerance and broad substrate scope. The reaction was also performed on a gram scale and successfully applied to the synthesis of the highly potent and selective PI3Kδ inhibitor N11, showing the practicability and synthetic utility of the protocol. In this reaction, the quinazoline scaffold is efficiently constructed with the simultaneous formation of one C−C bond and one C−N bond. Collectively, the protocol could serve as an alternative strategy to synthesize biologically important quinazoline scaffolds.
Direct Dimesitylborylation of Benzofuran Derivatives by an Iridium‐Catalyzed C−H Activation with Silyldimesitylborane
Authors: Shishido Ryosuke , Sasaki Ikuo , Seki Tomohiro , Ishiyama Tatsuo , Ito Hajime
Published: August 2019

Direct dimesitylborylation of benzofuran derivatives by a C−H activation catalyzed by an iridium(I)/N‐heterocyclic carbene (NHC) complex in the presence of Ph2MeSi‐BMes2 afforded the corresponding dimesitylborylation products in good to high yield with excellent regioselectivity. This method provides a straightforward route to donor–(π‐spacer)–acceptor systems with intriguing solvatochromic luminescence properties.
Electrospun Cu‐Deposited Flexible Fibers as an Efficient Oxygen Evolution Reaction Electrocatalyst
Authors: Morinaga Asuka , Tsutsumi Hiromori , Katayama Yu
Published: August 2019

Developing oxygen evolution reaction (OER) catalysts with high activity, long‐term durability, and at low cost remains a great challenge. Herein, we report the high activity of fibrous Cu‐based catalysts. The synthesis process is simple and scalable. Electrospinning method was selected to synthesize fibrous polymer substrates (Poly(vinylidene fluoride‐co‐hexafluoropropylene, PVdF‐HFP), which are then covered by Cu via electroless deposition. Cu‐deposited PVdF‐HFP with different microstructures having smooth and roughened surfaces were also synthesized by drop‐casting and impregnation method, respectively, to emphasize the importance of the microstructures on OER activity. The OER activity and durability were studied by linear sweep voltammetry, chronoamperometry, and Tafel slope analysis. The Cu/PVdF‐HFP fibrous catalysts exhibit significantly improved OER activity and durability compared with Cu plate as well as Cu‐deposited PVdF‐HFP with different microstructures. The unique fibrous structure provides better mass transport, diffusion, and large active surface area. In addition to the advantages of the fibrous structure, attenuated total reflection infrared (ATR‐IR) and ex situ X‐ray photoelectron spectroscopy revealed that the improved specific activity for Cu/PVdF‐HFP fiber can be attributed to the synergistic effect between Cu and Cu/PVdF‐HFP (electron transfer from Cu to PVdF‐HFP) at the Cu|PVdF‐HFP interface, which results in optimized reaction energetics for the OER.
Impact of Hepatic Steatosis on Resting Metabolic Rate and Metabolic Adaptation in Response to Intentional Weight Loss
Authors: Rachakonda Vikrant P. , DeLany James P. , Kershaw Erin E. , Behari Jaideep
Published: August 2019

Weight loss is the primary intervention for nonalcoholic fatty liver disease (NAFLD). A decrease in resting metabolic rate (RMR) out of proportion to the degree of weight loss may promote weight regain. We aimed to determine the impact of hepatic steatosis on weight loss‐associated changes in RMR and metabolic adaptation, defined as the difference between predicted and measured RMR after weight loss. We retrospectively analyzed prospectively collected data from 114 subjects without diabetes (52 with NAFLD), with body mass index (BMI) >35, and who enrolled in a 6‐month weight loss intervention. Hepatic steatosis was determined by unenhanced computed tomography scans by liver:spleen attenuation ratio <1.1. RMR was measured by indirect calorimetry. At baseline, patients with hepatic steatosis had higher BMI, fat mass (FM), fat‐free mass (FFM), and RMR (RMR, 1,933 kcal/day; 95% confidence interval [CI], 841‐2,025 kcal/day; versus 1,696; 95% CI, 1,641‐1,751; P < 0.0001). After 6 months, the NAFLD group experienced larger absolute declines in weight, FM, and FFM, but percentage changes in weight, FFM, and FM were similar between groups. A greater decline in RMR was observed in patients with NAFLD (−179 kcal/day; 95% CI, −233 to −126 kcal/day; versus −100; 95% CI, −51 to −150; P = 0.0154) for the time × group interaction, and patients with NAFLD experienced greater metabolic adaptation to weight loss (−97 kcal/day; 95% CI, −143 to −50 kcal/day; versus −31.7; 95% CI, −74 to 11; P = 0.0218) for the prediction × group interaction. The change (Δ) in RMR was significantly associated with ΔFM, ΔFFM, and baseline RMR, while metabolic adaptation was significantly associated with female sex and ΔFM only. Conclusion: Hepatic steatosis is associated with a greater reduction in FM, which predicts RMR decline and a higher metabolic adaptation after weight loss, potentially increasing the risk of long‐term weight regain.
Investigating the effect of custom‐made insoles and exercises on lower limb and back discomfort in assembly‐line workers in a rubber tire factory: A randomized controlled trial
Authors: Mousavi Elahe , Zamanian Zahra , Hadadi Mohammad , Sobhani Sobhan
Published: August 2019

Many occupations require standing for prolonged periods, which can be a major contributor to musculoskeletal problems and cause disturbances in different parts of the body, especially the lower back and lower extremities. The aim of this study was to investigate the effect of custom‐made insoles and exercise training on the lower limb and lower back discomfort in workers on a production line at a rubber tire factory. One hundred male workers (mean age 35.96 years, work experience of 10.62 years, standing time 6.58 hr) participated in this randomized controlled trial. The men were randomly assigned to one of four groups: (a) custom‐made insole plus lower limb exercises, (b) insoles only, (c) lower limb exercises only, and (d) no intervention. Discomfort level was recorded with a visual analog scale and a body map. The data were analyzed with analysis of covariance. The results showed a significant difference in discomfort levels between groups in the lower back (p = .001), thigh (p = .001), and knee (p = .001) areas. The combined insole and exercise group had less discomfort in the lower back, thigh, and knee. In the group that used the insole only without exercises, the discomfort level in the lower back area was reduced. The results indicate that the simultaneous use of insoles and exercises might be an effective intervention to reduce discomfort in the lower limbs and lower back in workers who remain standing for prolonged periods.
Model‐Based Product Line Engineering to Plan and Track Submarine Configuration
Authors: Hause Matthew , Hallett Jon
Published: August 2019

One can measure the life of a class of submarines in decades. As such, the operational demands and expectations change both strategically and tactically over its lifetime. Coupling this adaptability with the length of time submarines take to design, build, and maintain, no two as‐built submarines in a class will ever be the same, even when constructed/maintained to the same build‐to design. Traditionally, we have accepted this as the standard, and in most cases the configuration management team managed the full information set at a class or batch level, but not at an individual submarine level. The team managed the configuration of an individual submarine in terms of agreed changes against the class or batch baseline. Advances in technology (hardware performance, software tools, and standards) now give us the opportunity to not only manage the full information set related to individual submarine system configuration baselines as they change over time, but also undertake rigorous model‐based trade‐off studies to plan the manner in which we can modify a class, a batch, an individual submarine (variant), or any combination thereof over time. This paper will explore the use of model‐based systems engineering (MBSE) coupled with recent developments of product line engineering (PLE)/orthogonal variability modelling (OVM) to provide a means to plan, track, manage, and evaluate an individual submarine's configuration over time in the context of the class, whilst simultaneously highlighting the wider application in the submarine enterprise and beyond.
Retracted: Silencing of keratin 1 inactivates the Notch signaling pathway to inhibit renal interstitial fibrosis and glomerular sclerosis in uremia
Authors: Chen Wen , Wang Zhi‐Kui , Ren Yue‐Qin , Zhang Lei , Sun Li‐Na , Man Yu‐Lin , Zhou Zhong‐Qi
Published: August 2019

Renal interstitial fibrosis is a key factor in the development of chronic renal diseases, possibly leading to uremia. The present study conducted aimed to assess the hypothesis whether keratin 1 (KRT1) silencing could suppress kidney interstitial fibrosis and glomerular sclerosis via the Notch pathway to alleviate uremic symptoms. Differentially expressed genes associated with uremia were identified using the gene expression omnibus (GEO) database. Uremic rat models were established, in which short hairpin‐RNA against KRT1, activators, and inhibitors of the Notch pathway were transfected. To further validate the mechanism of KRT1 in uremia, KRT1 expression, cell apoptosis, glomerular area (GA), and glomerular capillary volume (GV), the score of glomerular sclerosis, and tubulointerstitial injury were assayed and investigated. GEO database revealed that KRT1 was upregulated in uremia and regulated the Notch pathway. GA, GV, cell apoptosis, glomerular sclerosis, and tubulointerstitial injury were typically located in more elevated levels of uremia in rats. KRT1 silencing and Notch pathway inhibition decreased the expression of Jagged1, Notch1, NICD1, Hey1, Hes1, α‐SMA, and FN, which further resulted in decreased cell apoptosis, GA, GV, the score of glomerular sclerosis, and tubulointerstitial injury. Subsequently, the effect of KRT1 silencing on uremia was no longer evident once the Notch pathway was activated. The co‐localization of high expression KRT1 and Notch1 was found in uremia. In summary, the results identified KRT1 as a key regulator in uremia progression, and KRT1 silencing can suppress glomerular sclerosis and tubulointerstitial injury via inactivation of the Notch pathway in uremic rats.
RETRACTED: Silencing of tumor‐suppressive NR_023387 in renal cell carcinoma via promoter hypermethylation and HNF4A deficiency
Authors: Zhou Hui , Guo Liang , Yao Weimin , Shi Runlin , Yu Gan , Xu Hua , Ye Zhangqun
Published: August 2019

Dysregulation of the epigenetic status of long noncoding RNAs (lncRNAs) has been linked to diverse human diseases including human cancers. However, the landscape of the whole‐genome methylation profile of lncRNAs and the precise roles of these lncRNAs remain elusive in renal cell carcinoma (RCC). We first examined lncRNA expression profiles in RCC tissues and corresponding adjacent normal tissues (NTs) to identify the lncRNA signature of RCC, then lncRNA Promoter Microarray was performed to depict the whole‐genome methylation profile of lncRNAs in RCC. Combined analysis of the lncRNAs expression profiles and lncRNAs Promoter Microarray identified a series of downregulated lncRNAs with hypermethylated promoter regions, including NR_023387. Quantitative real‐time polymerase chain reaction (RT‐PCR) implied that NR_023387 was significantly downregulated in RCC tissues and cell lines, and lower expression of NR_023387 was correlated with shorter overall survival. Methylation‐specific PCR, MassARRAY, and demethylation drug treatment indicated that hypermethylation in the NR_023387 promoter contributed to its silencing in RCC. Besides, HNF4A regulated the expression of NR_023387 via transcriptional activation. Functional experiments demonstrated NR_023387 exerted tumor‐suppressive roles in RCC via suppressing the proliferation, migration, invasion, tumor growth, and metastasis of RCC. Furthermore, we identified MGP as a putative downstream molecule of NR_023387, which promoted the epithelial–mesenchymal transition of RCC cells. Our study provides the first whole‐genome lncRNA methylation profile in RCC. Our combined analysis identifies a tumor‐suppressive and prognosis‐related lncRNA NR_023387, which is silenced in RCC via promoter hypermethylation and HNF4A deficiency, and may exert its tumor‐suppressive roles by downregulating the oncogenic MGP.
Association between DIO2 polymorphism and the risk of Kashin–Beck disease in the Tibetan population
Authors: Jin Tianbo , Wang Li , He Xue , Liu Ming , Bai Mei , Rong Hao , He Yongjun , Yuan Dongya
Published: August 2019

Background

Kashin–Beck disease (KBD) is a local, multiple and deformable osteoarthropathy, mostly occurring in Tibet. Type 2 iodothyronine deiodinase (DIO2) is implicated in the activation of thyroid hormones to which the bones are very sensitive. Therefore, it is necessary to explore the association between KBD and DIO2 in the Tibetan population.

Methods

We carried out a case–control study among 316 cases and 320 controls from a Tibetan population. Seven single nucleotide polymorphisms in DIO2 were selected and genotyped using the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis. HaploReg (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php) and GTEx (http://www.gtexportal.org) databases were applied for functional assessment of the polymorphisms.

Results

The “A/C" genotype of rs1352815 (OR = 3.18, 95% CI = 1.14–8.85, p = 0.027) and the “A/G" genotype of rs1388382 (OR = 3.80, 95% CI = 1.30–11.11, p = 0.015) were associated with the susceptibility of KBD under the co‐dominant model. With gender stratification analysis, rs1388382 showed obvious evidence for correlation with an elevated risk of KBD in females under the co‐dominant model (OR = 3.32, 95% CI = 1.06–10.41, p = 0.039).

Conclusions

The results obtained in the present study indicate that DIO2 polymorphisms rs1352815 and rs1388382 were correlated with KBD susceptibility among Tibetans, which also sheds new light on the role of DIO2 in the development of KBD.
History of scoria‐cone eruptions on the eastern shoulder of the Kenya–Tanzania Rift revealed in the 250‐ka sediment record of Lake Chala near Mount Kilimanjaro
Authors: Martin‐Jones Catherine , Lane Christine , Van Daele Maarten , Meeren Thijs Van Der , Wolff Christian , Moorhouse Heather , Tomlinson Emma , Verschuren Dirk
Published: August 2019

Reconstructions of the timing and frequency of past eruptions are important to assess the propensity for future volcanic activity, yet in volcanic areas such as the East African Rift only piecemeal eruption histories exist. Understanding the volcanic history of scoria‐cone fields, where eruptions are often infrequent and deposits strongly weathered, is particularly challenging. Here we reconstruct a history of volcanism from scoria cones situated along the eastern shoulders of the Kenya–Tanzania Rift, using a sequence of tephra (volcanic ash) layers preserved in the ~250‐ka sediment record of Lake Chala near Mount Kilimanjaro. Seven visible and two non‐visible (crypto‐) tephra layers in the Lake Chala sequence are attributed to activity from the Mt Kilimanjaro (northern Tanzania) and the Chyulu Hills (southern Kenya) volcanic fields, on the basis of their glass chemistry, textural characteristics and known eruption chronology. The Lake Chala record of eruptions from scoria cones in the Chyulu Hills volcanic field confirms geological and historical evidence of its recent activity, and provides first‐order age estimates for seven previously unknown eruptions. Long and well‐resolved sedimentary records such as that of Lake Chala have significant potential for resolving regional eruption chronologies spanning hundreds of thousands of years.
Occurrence, risk factors, and outcomes of bone cement implantation syndrome after hemi and total hip arthroplasty in cancer patients
Authors: Schwarzkopf Eugenia , Sachdev Ridhi , Flynn Jessica , Boddapati Venkat , Padilla Roger E. , Prince Daniel E.
Published: August 2019

Background and Objectives

Patients undergoing cement fixation for hip arthroplasty are at increased risk of developing bone cement implantation syndrome (BCIS). We sought to determine: what is the occurrence of BCIS in patients with cancer after hip arthroplasty? What are the risk factors in patients with cancer for the development of this syndrome? What is the outcome for patients with cancer having BCIS?

Methods

We identified 374 patients with cancer who underwent cemented hip arthroplasty between 2010 and 2014. Patient characteristics, operative variables, and outcomes were collected.

Results

BCIS occurred in 279 (75%) patients. A total of 353 (94%) patients had bone metastases and 179 (48%) patients had lung metastases at the time of surgery. Age greater than 60 (hazard ratio [HR] 2.09, P = .02) and the presence of lung metastases (HR 1.77, P = .019) were associated with increased risk of BCIS. Increased perioperative use of vasopressors (HR 1.72, P = .023) and increased hospital stay beyond 10 days (HR 2.67, P = .003) was associated with BCIS.

Conclusions

BCIS is a frequent clinical event in patients with cancer undergoing femoral cemented arthroplasty with increased risk for patients over age 60 and those with compromised lung function due to lung metastases and lung cancer. Patients who develop BCIS are more likely to require longer postoperative hospitalization. Careful preoperative assessment and intraoperative communication are crucial steps to reduce the consequences of BCIS.
IRX5 promotes colorectal cancer metastasis by negatively regulating the core components of the RHOA pathway
Authors: Zhu Qiangqiang , Wu Yiqi , Yang Mengli , Wang Zhen , Zhang Hailing , Jiang Xinying , Chen Meng , Jin Tianyu , Wang Ting
Published: August 2019

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. As tumor metastasis is the leading cause of death in patients with CRC, it is important to elucidate the molecular mechanisms that drive CRC metastasis. Studies have shown a close relationship between Iroquois homeobox (IRX) family genes and multiple cancers, while the mechanism by which IRX5 promotes CRC metastasis is unclear. Therefore, we focused on the involvement of IRX5 in CRC metastasis. In this study, analyses of clinical data indicated that the expression of IRX5 was coincided with metastatic colorectal tumors tissues and was negatively correlated with the overall survival of patients with CRC. Functional analysis showed that IRX5 promoted the migration and invasion of CRC cells, accompanied by a large number of cellular protrusions. IRX5‐overexpressing cells were more likely to form metastatic tumors in nude mice. Further analysis demonstrated that the core components of the RHOA/ROCK1/LIMK1 pathway were significantly inhibited in IRX5‐overexpressing cells. Overexpression of LIMK1 effectively reversed the enhanced cellular motility caused by IRX5 overexpression. Moreover, we found that high levels of IRX5 in intestinal tissues were correlated with the inflammatory response. IRX5 was significantly increased in azoxymethane/dextran sodium sulfate intestinal tissue of mice and IRX5‐overexpressing may also enhance chemokines CXCL1 and CXCL8. In summary, our findings suggested that IRX5 promoted CRC metastasis by inhibiting the RHOA‐ROCK1‐LIMK1 axis, which correlates with a poor prognosis.
Probing Binding Landscapes and Molecular Recognition Mechanisms of Atypical Antipsychotic Drugs towards the Selective Targeting of D2 Dopamine Receptor
Authors: Appiah‐Kubi Patrick , Olotu Fisayo Andrew , Soliman Mahmoud E. S.
Published: August 2019

Dopamine receptors constitute a unique class of G‐protein coupled receptors that mediate the activities of dopamine, a neurotransmitter implicated in diverse neurological diseases when dysregulated. Over the years, antipsychotic drugs have been primarily directed towards D2 dopamine receptor (DRD2) while associable adverse effects have been centred on non‐selective targeting. The recent crystal structure of DRD2 in complex with atypical antipsychotic could further aid the structure‐based design of highly DRD2‐selective antipsychotics. Therefore, in this study, we comprehensively investigate the molecular recognition and differential binding landscapes of class‐I and II DRD2 atypical antipsychotics, using membrane‐bilayer molecular dynamics simulation and binding free energy techniques. Findings revealed that selected class‐I antipsychotics exhibited binding dynamics and poses dissimilar to the class‐II types with different interactive mechanisms at the binding cavity of DRD2. More interestingly, the class‐II drugs established a highly coordinated binding at the DRD2 active site with a pertinent and recurrent involvement of Asp114 via strong hydrogen interactions. Furthermore, while these compounds exert distinct effects on DRD2 structure, findings revealed that the class‐II types favourably engaged the deep hydrophobic pocket of DRD2 compared to the class‐I drugs. We speculate that these findings will be fundamental to the discovery of highly selective DRD2 antipsychotics.
Spontaneous voiding is surprisingly recoverable via outlet procedure in men with underactive bladder and documented detrusor underactivity on urodynamics
Authors: Dobberfuhl Amy D. , Chen Annie , Alkaram Ahmed F. , De Elise J.B.
Published: August 2019

Aims

To identify clinical and urodynamic factors leading to spontaneous voiding in men with detrusor underactivity (DU) and suspected bladder outlet obstruction who underwent an outlet de‐obstruction procedure.

Methods

We identified 614 men who underwent an outlet procedure at our institution from 2005 to 2014. Men were stratified by bladder contractility index (BCI). The primary outcome was spontaneous voiding after surgery. Data were analyzed in Statistical analysis system software.

Results

Of the 131 men who underwent preoperative urodynamics, 122 (mean age 68 years) had tracings available for review. DU (BCI < 100) was identified in 54% (66 of 122), of whom only 68% (45 of 66) voided spontaneously before surgery, compared with 82% (46 of 56) of men with BCI ≥ 100. At a mean follow‐up of 6.4 months postoperatively, 79% (52 of 66) of men with DU were able to void spontaneously, compared with 96% (54 of 56) of men with BCI ≥ 100. In men with a BCI < 100 unable to void before surgery, 57% (12 of 21) recovered spontaneous voiding after surgery. On logistic regression for the outcome postoperative spontaneous voiding, significant preoperative characteristics, and urodynamic factors included preoperative spontaneous voiding (odds ratio [OR] = 9.460; 95% confidence interval [CI] = 2.955‐30.289), increased maximum flow rate (Qmax; OR = 1.184; 95% CI = 1.014‐1.382), increased detrusor pressure at maximum flow (Pdet@Qmax; OR = 1.032; 95% CI = 1.012‐1.052), DU with BCI < 100 (OR = 0.138; 95% CI = 0.030‐0.635), and obstruction with bladder outlet obstruction index > 40 (OR = 5.595; 95% CI = 1.685‐18.575).

Conclusion

Outlet de‐obstruction improves spontaneous voiding in men with DU and may benefit men who do not meet the urodynamic threshold for obstruction.
The use of urethral bulking injections in post‐prostatectomy stress urinary incontinence: A narrative review of the literature
Authors: Nguyen Linh , Leung Lap Yan , Walker Roger , Nitkunan Tharani , Sharma Davendra , Seth Jai
Published: August 2019

Aims

Post‐prostatectomy stress urinary incontinence (PPI) is a common condition with significant impact on patient quality of life. With rising numbers of prostatectomies performed, recognition of incontinence during survivorship care is growing. With increasing hesitance of the use of suburethral mesh in females, urethral bulking injections in this patient population as a minimally invasive alternative to surgery are evaluated.

This review aims to evaluate the existing evidence base for urethral bulking therapy in PPI and provide a summary of its efficacy, durability, and side‐effect profile.

Methods

A literature search of Medline/Pubmed and Cochrane databases was conducted to identify publications reporting the clinical outcomes of urethral bulking injections in patients with PPI, up to and including October 1st, 2018. Case reports, letters and reviews were excluded.

Results

We identified 25 studies that fit our inclusion criteria, comprised of one RCT, two large retrospective cohort studies, and 22 case series. The success rates reported varying widely from 13%‐100% with reports of symptomatic control deterioration. Complication rates remain low. This review highlighted a poor performance using the more historic bulking agents (BA), and the lack of strong evidence with the more novel BA in PPI and discussed challenges regarding optimal patient selection and techniques.

Conclusions

There exists poor clinical evidence base concerning the use of urethral bulking in PPI with few high‐level studies and a significant lack of consistency between studies. Further study in this area is required to evaluate the role of BA in this patient population.
The discrepancy between the uroflowmetry parameters, curve patterns, and lower urinary tract symptoms of children with nocturnal enuresis according to the presence or absence of daytime urinary incontinence
Authors: Hyuga Taiju , Nakamura Shigeru , Kawai Shina , Tanabe Kazuya , Nakai Hideo
Published: August 2019

Aim

To evaluate the uroflowmetry (UFM), which reflects the urinary symptoms of children with nocturnal enuresis (NE).

Methods

This study retrospectively investigated 93 children who underwent UFM three times on the same day (≥8 years old; mean age: 9 years and 10 months; 66 boys and 27 girls). Children with the combination of daytime incontinence (DI) and NE (DI+NE group: n = 45) and NE alone (isolated NE group: n = 48) were compared. UFM curve patterns were classified into five types: bell (B), tower (T), staccato (S), plateau (P), and interrupted (I). An unclassified (U) curve pattern was designated when all three curve patterns differed. Patterns other than the B pattern were considered abnormal (A). Each score in the dysfunctional voiding symptom score (DVSS) was also compared between the two groups.

Results

The UFM curve pattern was B (n = 21), T (n = 15), S (n = 4), P (n = 1), U (n = 4) in the DI+NE group and B (n = 25), T (n = 10), S (n = 7), P (n = 2), U (n = 4) in the isolated NE group, indicating no significant difference (B vs A; P = .680). The two items of DVSS questionnaire were significantly greater in the DI+NE group than in the isolated NE group (voiding postponement: 0.93 ± 1.18 vs 0.23 ± 0.56, P = .001, urgency: 2.09 ± 1.06 vs 0.56 ± 0.85, P < .001).

Conclusion

The abnormal UFM curve patterns did not differ significantly between NE children with and without DI. However, the DVSS questionnaire scores differed significantly. UFM did not reflect the urinary symptoms of children with NE.
The role of WNT10B in normal prostate gland development and prostate cancer
Authors: Madueke Ikenna , Hu Wen‐Yang , Hu Danping , Swanson Steven M. , Vander Griend Donald , Abern Michael , Prins Gail S.
Published: August 2019

Background

WNT signaling is implicated in embryonic development, and in adult tissue homeostasis, while its deregulation is evident in disease. This study investigates the unique roles of canonical WNT10B in both normal prostate development and prostate cancer (PCa) progression.

Methods

Organ culture and rat ventral prostates (VPs) were used to study Wnt10b ontogeny and growth effect of WNT10B protein. PB‐SV40 LTag rat VPs were utilized for Wnt expression polymerase chain reaction (PCR) array and immunohistochemistry. Human localized PCa tissue microarrays (TMAs) were investigated for differential WNT10B expression. Human RNA‐seq data sets were queried for differential expression of WNT10B in metastatic and localized PCa. Knockdown of WNT10B in PC3 cells was utilized to study its effects on proliferation, stemness, epithelial to mesenchymal transition (EMT), and xenograft propagation.

Results

Wnt10b expression was highest at birth and rapidly declined in the postnatal rat VP. Exogenous WNT10B addition to culture developing VPs decreased growth suggesting an antiproliferative role. VPs from PB‐SV40 LTag rats with localized PCa showed a 25‐fold reduction in Wnt10b messenger RNA (mRNA) expession, confirmed at the protein level. Human PCa TMAs revealed elevated WNT10B protein in prostate intraepithelial neoplasia compared with normal prostates but reduced levels in localized PCa specimens. In contrast, RNA‐seq data set of annotated human PCa metastasis found a significant increase in WNT10B mRNA expression compared with localized tumors suggesting stage‐specific functions of WNT10B. Similarly, WNT10B mRNA levels were increased in metastatic cell lines PC3, PC3M, as well as in HuSLC, a PCa stem‐like cell line, as compared with disease‐free primary prostate epithelial cells. WNT10B knockdown in PC3 cells reduced expression of EMT genes, MMP9 and stemness genes NANOG and SOX2 and markedly reduced the stem cell‐like side population. Furthermore, loss of WNT10B abrogated the ability of PC3 cells to propagate tumors via serial transplantation.

Conclusions

Taken together, these results suggest a dual role for WNT10B in normal development and in PCa progression with opposing functions depending on disease stage. We propose that decreased WNT10B levels in localized cancer allow for a hyperproliferative state, whereas increased levels in advanced disease confer a stemness and malignant propensity which is mitigated by knocking down WNT10B levels. This raises the potential for WNT10B as a novel target for therapeutic intervention in metastatic PCa.