bluuebunny/crossref_metadata_2025 huggingface dataset:
Support groups address residents' personal development
Authors: Butler Ricahrd
Published: October 2018

Graduate medical education traditionally has emphasized the teaching of biomedical knowledge and technical skills. However, physicians-in-training also need opportunities to explore their emotional reactions that occur during the process of patient care and medical training. The promotion of personal growth and self-awareness should be important components of graduate medical education. Easily implemented, a resident support , group is one forum that addresses this obvious gap in medical education. This article reviews the goals and structure of support groups, with the hope that more training programs will implement them.
Standards for Pediatric Immunization Practices: An osteopathic physician's commentary and 'reality check'
Authors: Marino Ronald V.
Published: October 2018

The "Standards for Pediatric Immunization Practices," recommended by the National Vaccine Advisory Committee and approved by the US Public Health Service, provides guidance to clinicians as to what the National Vaccine Advisory Committee considers optimal practice. Each of the 18 recommendations reflects the ideal; unfortunately, life in the trenches is less than ideal. Providers must reflect on each point and consider how they might modify their own practices to help us to realize the goal of Healthy People 2000, that is, 90% immunization coverage by the child's second birthday. The Standards are clear. They are reprinted herein from MMWR (April 23, 1993;42[5]). Following each is a response, sort of a reality check, from the author, a practicing clinician and practice administrator.
Wehrmacht i Norge
Authors: Korsnes Kjetil , Dybvig Olve
Published: October 2018

Hvor mange tyskere var det i Norge under krigen? Denne rapporten søker å besvare dette spørsmålet ved å undersøke et stort kildemateriale fra den tyske overkommandoen i Norge. Tysk personell er inndelt i fire store grupper; hær, marine, luftforsvar og samlegruppene Sonstige (annet personell). I tillegg er det en stor gruppe med krigsfanger. Alle disse gruppene var omfattet av tysk forpleiningsansvar. Derfor finnes det i kildene oversikter over alt personell som okkupasjonsmakten brakte til landet. Tallene viser hovedtrekkene i utviklingen av antallet tysk personell fra april 1940 til mai 1945 for månedsvis. I tillegg er det gjort beregninger for å fordele totalantallet på de ulike personellgruppene. Det er første gangen en slik samlet fremstilling er laget.
BCG‐induced cytokine release in bladder cancer cells is regulated by Ca2+ signaling
Authors: Ibarra Cristián , Karlsson Marie , Codeluppi Simone , Varas‐Godoy Manuel , Zhang Songbai , Louhivuori Lauri , Mangsbo Sara , Hosseini Arad , Soltani Navid , Kaba Rahim , Kalle Lundgren T. , Hosseini Abolfazl , Tanaka Nobuyuki , Oya Mototsugu , Wiklund Peter , Miyakawa Ayako , Uhlén Per
Published: October 2018

Bacillus Calmette–Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca2+ (calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL‐8). A similar Ca2+ response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll‐like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL‐8, whereas exocytosis appeared to be controlled by global Ca2+ signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.
Circulating pancreatic cancer exosomal RNAs for detection of pancreatic cancer
Authors: Kitagawa Tatsuya , Taniuchi Keisuke , Tsuboi Makiko , Sakaguchi Masahiko , Kohsaki Takuhiro , Okabayashi Takehiro , Saibara Toshiji
Published: October 2018

Diagnostic biomarkers for the early diagnosis of pancreatic cancer are needed to improve prognosis for this disease. The aim of this study was to investigate differences in the expression of four messenger RNAs (mRNAs: CCDC88A, ARF6, Vav3, and WASF2) and five small nucleolar RNAs (snoRNAs: SNORA14B, SNORA18, SNORA25, SNORA74A, and SNORD22) in serum of patients with pancreatic cancer and control participants for use in the diagnosis of pancreatic cancer. Results were compared with the expression of sialylated Lewis (a) blood group antigen CA19‐9, the standard clinical tumor biomarker. Reverse transcription quantitative real‐time PCR showed that all of the mRNAs and snoRNAs, except CCDC88A, were encapsulated in exosomes and secreted from cultured pancreatic cancer cells, and present in cell culture medium. In a discovery‐stage clinical study involving 27 pancreatic cancer patients and 13 controls, the area under the receiver operating characteristic curve (AUC) of two mRNAs (WASF2 and ARF6) and two snoRNAs (SNORA74A and SNORA25) was > 0.9 for distinguishing pancreatic cancer patients from controls; the AUC of CA19‐9 was 0.897. Comparing serum levels of WASF2, ARF6, SNORA74A, SNORA25, and CA19‐9 revealed that levels of WASF2 were the most highly correlated with the risk of pancreatic cancer. The AUCs of WASF2, ARF6, SNORA74A, and SNORA25 in serum from patients in the early stages of pancreatic cancer (stages 0, I, and IIA) were > 0.9, compared with an AUC of 0.93 for the level of CA19‐9. The results of this study suggest that WASF2, ARF6, SNORA74A, and SNORA25 may be useful tools for the early detection of pancreatic cancer. Monitoring serum levels of WASF2 mRNA may be particularly useful, as it was the most highly correlated with pancreatic cancer risk.
Prediction of the lighting energy‐saving effect by human detection control with an office worker agent model
Authors: Togashi Eisuke , Watanabe Ken‐ichi , Honma Mutsuo
Published: October 2018

The energy‐saving effect of lighting control in the absence of workers in an office is predicted by using simulations. We divided an office space into meshes and constructed an agent model of an office worker who move between meshes by using the A* algorithm. By examining many office worker models, we calculated the time a worker spent in each office's mesh. We controlled the lighting fixtures in this virtual office room based on human sensors. We quantitatively evaluated the influence of conditions such as the occupancy rate, retention time, fade‐out time, and minimum output rate on the lighting rate of the lighting fixtures.
Atmospheric‐Pressure Synthesis of 2D Nitrogen‐Rich Tungsten Nitride
Authors: Yu Huimin , Yang Xin , Xiao Xu , Chen Ming , Zhang Qinghua , Huang Liang , Wu Jiabing , Li Tianqi , Chen Shuangming , Song Li , Gu Lin , Xia Bao Yu , Feng Guang , Li Jia , Zhou Jun
Published: October 2018

2D transition metal nitrides, especially nitrogen‐rich tungsten nitrides (WxNy, y > x), such as W3N4 and W2N3, have a great potential for the hydrogen evolution reaction (HER) since the catalytic activity is largely enhanced by the abundant WN bonding. However, the rational synthesis of 2D nitrogen‐rich tungsten nitrides is challenging due to the large formation energy of WN bonding. Herein, ultrathin 2D hexagonal‐W2N3 (h‐W2N3) flakes are synthesized at atmospheric pressure via a salt‐templated method. The formation energy of h‐W2N3 can be dramatically decreased owing to the strong interaction and domain matching epitaxy between KCl and h‐W2N3. 2D h‐W2N3 demonstrates an excellent catalytic activity for cathodic HER with an onset potential of −30.8 mV as well as an overpotential of −98.2 mV for 10 mA cm−2.
Efficient Charging of Lithium–Sulfur Batteries by Triboelectric Nanogenerator Based on Pulse Current
Authors: Yin Yingying , Zhang Xiuling , Du Xinyu , Zhou Tao , Li Nianwu , Xu Weihua , Li Congju
Published: October 2018

The pulsed output current of triboelectric nanogenerators (TENGs) has been used to charge the secondary battery recently. For a robust TENG with constant impetus, the output current will keep steady unless the external load resistance is changed. Therefore, the difference of charging current reflects the different charging resistance of the battery. Herein, the lithium–sulfur (Li–S) battery is charged by robust stable scale‐like structured TENG (SL‐TENG), and the real‐time charging current is recorded. The charging current increases with the initial potential rise, reflecting the oxidation process of the precipitated Li2S and Li2S2 with poor conductivity. Then the charging current keeps almost no change in flat charge plateau, accompanying with the main production of S8
2−, S7
2−, S6
2−, and S5
2−. Finally it shows a steep drop when the potential exceeds 2.4 V, accompanying with the second oxidation stage of the main production of S8. Moreover, under SL‐TENG charging protocol, the capacity of Li–S battery increases obviously, and Li ions tend to deposit as large grain with smooth surface. SL‐TENG charging protocol is beneficial to improve the performance of Li–S battery, as well as helping to understand the charging mechanism to some extent.
Thin Copper Flakes for Conductive Inks Prepared by Decomposition of Copper Formate and Ultrafine Wet Milling
Authors: Rosen Yitzchak , Marrach Roy , Gutkin Vitaly , Magdassi Shlomo
Published: October 2018

Fabrication of devices by printing conductive interconnections on plastic substrates is of growing interest. Currently, silver flakes are wildly used, however the high cost of silver prevents their wide use in many electrical devices. A new two‐step process for synthesizing thin copper flakes, and their utilization in conductive inks, is reported. In the first step, sub‐micrometer copper particles are formed by thermal decomposition and self‐reduction of copper formate. These copper particles are then milled in a wet bead mill that results in their transformation into thin flakes with an average thickness of 48 nm. X‐ray diffraction results indicate that the copper particles undergo plastic deformation in a mechanism similar to cold rolling. The effect of various process parameters and type of dispersing agents on the morphology and electrical performance is studied. The ink formulations result in printed patterns with 22% of bulk copper conductivity. The optimal ink is used to print functioning near field communication antennas on polyimide film, which is found to have a high bending durability.
Streaming Current Based Microtubular Enzymatic Sensor for Self‐Powered Detection of Urea
Authors: Yu Longteng , Shi Chen , Xi Wang , Yeo Joo Chuan , Soon Ren Hao , Chen Zhengkun , Song Peiyi , Lim Chwee Teck
Published: October 2018

The emergence of microfluidic techniques coupled with flow‐induced electrification has advanced the development of innovative self‐powered sensors. However, selective detection of target substances using these sensors is extremely challenging, owing to the lack of recognition elements in the flow pathway. To overcome this, catalytic enzymes are immobilized on the microfluidic channel and the concentration of targets is measured via monitoring the streaming current. As an example, a urease equipped self‐powered microtubular sensor is developed to selectively detect urea, a physiologically and industrially important molecule. The urease catalyzes the hydrolysis of urea into ions, increasing the pH of the fluid, which serves as the basis of the sensing mechanism. Remarkably, high sensitivity, wide detection range, short response time, and superior selectivity are reported for urinary urea detection. The accuracy and reliability of sensing in artificial urine are validated with the standard spectrophotometric method. The microtubular sensor features facile fabrication and operation and circumvents the need for sophisticated peripherals, highlighting its enormous potential in chemical and biomedical applications, such as pollutant detection, food quality assessment, disease diagnosis, and point‐of‐care testing.
Simulation Assisted Nanoscale Imaging of Single Live Cells with Scanning Electrochemical Microscopy
Authors: Filice Fraser P. , Li Michelle S. M. , Ding Zhifeng
Published: October 2018

Nanoelectrodes have become an area of significant interest in recent years, which provide a number of advantages for imaging with scanning electrochemical microscopy (SECM). Since the resolution of SECM imaging is directly dependent on the size of the electrode probe, the reduced surface area of nanoelectrodes allows for the imaging of smaller sample features, or more localized electrochemical reactivity. Nanoelectrodes with a radius of 130 nm are employed to image the surface of single live cells. The use of nanoscale imaging, however, introduces additional complexity into the simulation modeling of the cell surface geometry and electrochemical reactivity. The creation of tailored simulation models accounting for these specific physical conditions is utilized to overcome the additional challenges to the characterization of the electrochemical system. Methodologies for the experimental mapping and creation of 3D simulation models of single live cells have been well developed, which are presented herein. These developments include characterization of cell surface topography, tip‐to‐cell distance, as well as cell membrane permeability quantification. The advanced quantification of the complex nanoscale imaging of single live cells assisted by theoretical simulations provides increased versatility to SECM as an already powerful bioanalytical tool.
Improved Rechargeability of Lithium Metal Anode via Controlling Lithium‐Ion Flux
Authors: Xiang Jingwei , Yuan Lixia , Shen Yue , Cheng Zexiao , Yuan Kai , Guo Zezhou , Zhang Yi , Chen Xin , Huang Yunhui
Published: October 2018

Among all the possible anode materials for next‐generation rechargeable batteries, lithium (Li) metal stands out from the crowd for its high specific capacity and low redox potential. Unfortunately, the issues caused by Li dendrites limit the commercialization of the batteries based on Li metal anodes. Research in recent years has proved that the Li dendrites cannot be completely eliminated. Inspired by the Chinese legend, “King Yu Tamed the Flood,” the new strategy of combing dredge and block, to control the diversion of Li ions is proposed. Via Au modification on one side of the carbon fibers matrix (CFs@Au), selective deposition of Li ions on the back side of the current collector is successfully achieved. This is distant from the separator, and hence improves the safety effectively. As a result, the Coulombic efficiency of the CFs@Au–Li anode remains 99.2% throughout 400 cycles. What is more, the Li–S full cell paired with the composite anode also exhibits outstanding performance, even with limited Li. This backside‐deposition strategy provides new insight into safe Li metal anode design for high energy density battery systems such as Li–S and Li–O2.
Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency
Authors: Bianchi Paola , Fermo Elisa , Glader Bertil , Kanno Hitoshi , Agarwal Archana , Barcellini Wilma , Eber Stefan , Hoyer James D. , Kuter David J. , Maia Tabita Magalhães , Mañu‐Pereira Maria del Mar , Kalfa Theodosia A. , Pissard Serge , Segovia José‐Carlos , van Beers Eduard , Gallagher Patrick G. , Rees David C. , van Wijk Richard ,   with the endorsement of EuroBloodNet, the European Reference Network in Rare Hematological Diseases
Published: October 2018

Pyruvate kinase deficiency (PKD) is the most common enzyme defect of glycolysis and an important cause of hereditary, nonspherocytic hemolytic anemia. The disease has a worldwide geographical distribution but there are no verified data regarding its frequency. Difficulties in the diagnostic workflow and interpretation of PK enzyme assay likely play a role. By the creation of a global PKD International Working Group in 2016, involving 24 experts from 20 Centers of Expertise we studied the current gaps in the diagnosis of PKD in order to establish diagnostic guidelines. By means of a detailed survey and subsequent discussions, multiple aspects of the diagnosis of PKD were evaluated and discussed by members of Expert Centers from Europe, USA, and Asia directly involved in diagnosis. Broad consensus was reached among the Centers on many clinical and technical aspects of the diagnosis of PKD. The results of this study are here presented as recommendations for the diagnosis of PKD and used to prepare a diagnostic algorithm. This information might be helpful for other Centers to deliver timely and appropriate diagnosis and to increase awareness in PKD.
Characterization of speech and language phenotype in children with NRXN1 deletions
Authors: Brignell Amanda , St John Miya , Boys Amber , Bruce Amanda , Dinale Carla , Pigdon Lauren , Hildebrand Michael S. , Amor David J. , Morgan Angela T.
Published: October 2018

Neurexin 1 gene (NRXN1) deletions are associated with several neurodevelopmental disorders. Communication difficulties have been reported, yet no study has examined specific speech and language features of individuals with NRXN1 deletions. Here, we characterized speech and language phenotypes in 21 children (14 families), aged 1.8–17 years, with NRXN1 deletions. Deletions ranged from 74 to 702 kb and consisted mostly of either exons 1–3 or 1–5. Speech sound disorders were frequent (69%), although few were severe. The majority (57%) of children had difficulty with receptive and/or expressive language, although no homogeneous profiles of deficit were seen across semantic, morphological, or grammatical systems. Social language difficulties were seen in over half the sample (53%). All but two individuals with language difficulties also had intellectual disability/developmental delay. Overall, while speech and language difficulties were common, there was substantial heterogeneity in the severity and type of difficulties observed and no striking communication phenotype was seen. Rather, the speech and language deficits are likely part of broader concomitant neurodevelopmental profiles (e.g., intellectual disability, social skill deficits). Nevertheless, given the high rate of affectedness, it is important speech/language development is assessed so interventions can be applied during childhood in a targeted and timely manner.
Psychiatric genetics researchers' views on offering return of results to individual participants
Authors: Kostick Kristin M. , Brannan Cody , Pereira Stacey , Lázaro‐Muñoz Gabriel
Published: October 2018

In the middle of growing consensus that genomics researchers should offer to return clinically valid, medically relevant, and medically actionable findings identified in the course of research, psychiatric genetics researchers face new challenges. As they uncover the genetic architecture of psychiatric disorders through genome‐wide association studies and integrate whole genome and whole exome sequencing to their research, there is a pressing need for examining these researchers' views regarding the return of results (RoR) and the unique challenges for offering RoR from psychiatric genetics research. Based on qualitative interviews with 39 psychiatric genetics researchers from different countries operating at the forefront of their field, we provide an insider's view of researchers' practices regarding RoR and the most contentious issues in psychiatry researchers' decision‐making around RoR, including what are the strongest ethical, scientific, and practical arguments for and against offering RoR from this research. Notably, findings suggest that psychiatric genetics researchers (85%) overwhelmingly favor offering RoR of at least some findings, but only 22% of researchers are returning results. Researchers identified a number of scientific and practical concerns about RoR, and about how to return results in a responsible way to patients diagnosed with a severe psychiatric disorder. Furthermore, findings help highlight areas for further discussion and resolution of conflicts in the practice of RoR in psychiatric genetics research. As the pace of discovery in psychiatric genetics continues to surge, resolution of these uncertainties gains greater urgency to avoid ethical pitfalls and to maximize the positive impact of RoR.
Tolerance strategies revealed in tree peony (Paeonia suffruticosa; Paeoniaceae) ecotypes differentially adapted to desiccation
Authors: Guo Lili , Guo Dalong , Yin Weilun , Hou Xiaogai
Published: October 2018

Premise of the Study

Tree peony (Paeonia suffruticosa; Paeoniaceae) is well known for its ornamental value, edible oil, and medicinal properties. However, its growing area has been limited by drought that has been exacerbated by global climate change.

Methods

Gene expression profiles of a drought‐tolerant cultivar and a drought‐sensitive cultivar during dehydration and rehydration were investigated by transcriptome analysis. Expression patterns of unigenes related to drought and recovery response and unrelated to either cultivar were classified by hierarchical clustering and real‐time quantitative PCR (qPCR).

Results

A total of 81,725 unigenes with a mean length of 762 nucleotides that may play roles in drought response were identified. Unigenes were characterized as being involved in lipid transport metabolism, proline metabolism, and photosynthesis. In addition, plant hormone signaling pathway genes were also characterized as potentially being involved in drought response. Expression patterns of the 20 drought‐responsive unigenes verified by qPCR showed a differential expression pattern under either the drought or recovery treatment.

Discussion

This is the first report to identify and verify unigenes of tree peonies with differing water sensitivity during dehydration and rehydration. This study offers a valuable resource for candidate genes involved in drought and provides insight into the breeding of drought‐resistant tree peony cultivars.
Synthesis and anticancer activity of novel rapamycin C‐28 containing triazole moiety compounds
Authors: Huang Qingwen , Xie Lijun , Chen Xiaoming , Yu Hui , Lv Yubing , Huang XueHui , Ying Jiayin , Zheng Congshen , Cheng Yuanrong , Huang Jie
Published: October 2018

Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Its C‐43 semi‐synthetic derivatives temsirolimus and everolimus have been used as mTOR targeting anticancer drugs in the clinic. Following our previous research on antitumor rapalogs modified on the C‐43 position, 13 novel rapamycin triazole hybrids (6a–g, 7a–f) were designed and synthesized on the C‐28 position of rapamycin via Huisgen's reaction. Anticancer assays indicated that the targeted derivatives containing phenyl and 4‐methylphenyl groups showed an obvious raise in anticancer activity. On the contrary, the compounds with methoxyl, amine, and halogen groups on the benzene ring displayed lower anticancer activity. Compound 6c, as the most active compound, showed a stronger inhibition effect as compared with rapamycin for almost all of the tested cell lines (p < 0.01), except PC‐3. Meanwhile, the effect of 6c on inducing apoptosis and cell cycle arrest in A549 cells was more powerful than that of rapamycin. In addition, 6c inhibited the phosphorylation of mTOR and its downstream key kinases 4EBP1 and p70S6K1 in A549 cells, indicating that 6c also effectively inhibits the mTORC1 signaling pathway as rapamycin. On the basis of these findings, 6c may have the potential to be developed as a new mTOR inhibitor against specific cancers.
Surfactant‐driven Amphoteric Doping of Carbon Nanotubes
Authors: Nonoguchi Yoshiyuki , Tani Atsushi , Murayama Tomoko , Uchida Hideki , Kawai Tsuyoshi
Published: October 2018

Aqueous surfactant dispersion is the most typical starting step to functionalize materials consisting of carbon nanotubes, but the effects of surfactants on the electronic properties are still unclear. Here we report how the functional groups of surfactants affect the electronic properties of carbon nanotube films. Using spectroscopic and thermoelectric characterization, we demonstrate that anionic and non‐ionic surfactants contribute to the formation of p‐type and n‐type carbon nanotubes, respectively. Additionally, p‐type doping with oxygen adsorption is found to compete with surfactants’ doping. These findings are useful for designing the srarting carbon nanotube materials exhibiting desirable electronic properties.
Robust Tracking Control Of The Variable Stiffness Actuator Based On The Lever Mechanism
Authors: Guo Jishu , Tian Guohui
Published: October 2018

This paper is concerned with the design of a robust adaptive tracking control scheme for a class of variable stiffness actuators (VSAs) based on the lever mechanisms. For these VSAs based on the lever mechanisms, the AwAS‐II developed at Italian Institute of Technology (IIT) is chosen as the study object, and it is an enhanced version of the original realization AwAS (actuator with adjustable stiffness). Firstly, for the dynamic model of the AwAS‐II system in the presence of parametric uncertainties, unknown bounded friction torques, unknown bounded external disturbance and input saturation constraints, by using the coordinate transformations and the static state feedback linearization, the state space model of the AwAS‐II system with composite disturbances and input saturation constraints is transformed into an uncertain multiple‐input multiple‐output (MIMO) linear system with lumped disturbances and input saturation constraints. Subsequently, a combination of the feedback linearization, disturbance observer, sliding mode control and adaptive input saturation compensation law is adopted for the design of the robust tracking controller that simultaneously regulates the position and stiffness of the AwAS‐II system. Under the proposed controller, the semi‐global uniformly ultimately bounded stability of the closed‐loop system has been proved via Lyapunov stability analysis. Simulation results illustrate the effectiveness and the robustness of the proposed robust adaptive tracking control scheme.
Invariant Kalman Filter for Correlated Wide Band Noises
Authors: Bashirov Agamirza E. , Abuassba Kanda
Published: October 2018

Kalman filtering is a powerful estimation method. One of its weaknesses is related to the white or coloured nature of the disturbing noises in the Kalman filtering model. At the same time, real noises are rarely white or coloured. They are mostly wide band. In this regard, white or coloured noise Kalman filtering makes concessions on adequacy. This pushes system scientists to develop mathematical methods of estimation for systems corrupted by wide band noises. In applications, wide band noises are detected by their autocovariance and cross‐covariance functions, which do not allow to model them uniquely. Therefore, it becomes important to develop estimation methods which are independent of a class of wide band noises, but dependent on the unique autocovariance and cross‐covariance functions. Such results are called invariant results. In this paper, we prove a complete set of invariant equations for Kalman type filter for a linear signal‐observation system corrupted by correlated wide band noises. This filter has a ready form to be used in applications, just respective numerical methods must be developed.
Exponential Stabilization of Stochastic Memristive Recurrent Neural Networks Under Periodically Intermittent State Feedback Control
Authors: Li Xiaofan , Fang Jian‐an , Li Huiyuan
Published: October 2018

In this paper, the exponential stabilization problem is investigated for a class of memristive time‐varying delayed neural networks with stochastic disturbance via periodically intermittent state feedback control. First, a periodically intermittent state feedback control rule is designed for the exponential stabilization of stochastic memristive time‐varying delayed neural networks. Then, by adopting appropriate Lyapunov‐Krasovskii functionals in light of the Lyapunov stability theory, some novel stabilization criteria are obtained to guarantee exponential stabilization of stochastic memristive time‐varying delayed neural networks via periodically intermittent state feedback control. Compared with existing results on stabilization of stochastic memristive time‐varying delayed neural networks, the obtained stabilization criteria in this paper are not difficult to verify. Finally, an illustrative example is given to illustrate the validity of the obtained results.
Expanding the Chemical Palette of Industrial Microbes: Metabolic Engineering for Type III PKS‐Derived Polyketides
Authors: Palmer Claire M. , Alper Hal S.
Published: October 2018

Polyketides are a unique class of molecules with attractive bioactive and chemical properties. As a result, biorenewable production is being explored with these molecules as potential pharmaceutical, fuel, and material precursors. In particular, type III polyketide synthases enable access to a diverse class of chemicals using a relatively simple biochemical synthesis pathway. In this review, the recent advances in the engineering of microbial hosts for the production of type III PKS‐derived polyketides are highlighted. In particular, the field has moved beyond simple proof‐of‐concept and has been exploring engineering efforts that have led to improved production scales. This review details engineering progress for the production of acetyl‐CoA‐ and malonyl‐CoA‐derived polyketides including the products triacetic acid lactone and phloroglucinol as well as polyphenolic, phenylpropanoid‐derived compounds including flavonoids, stilbenoids, and curcuminoids. Specifically, the authors focus on enumerating the metabolic engineering strategies employed and product titers achieved for these molecules. Finally, the authors highlight tools and strategies that can be leveraged to realize the potential of microbial production and diversification of these molecules.
Cost-effectiveness of revascularization in patients with intermittent claudication
Authors: Djerf H , Falkenberg M , Jivegård L , Lindgren H , Svensson M , Nordanstig J
Published: October 2018

Background

Revascularization is a treatment option for patients with intermittent claudication. However, there is a lack of evidence to support its long-term benefits and cost-effectiveness. The aim of this study was to compare the cost-effectiveness of revascularization and best medical therapy (BMT) with that of BMT alone.

Methods

Data were used from the IRONIC (Invasive Revascularization Or Not in Intermittent Claudication) RCT where consecutive patients with mild-to-severe intermittent claudication owing to aortoiliac or femoropopliteal disease were allocated to either BMT alone (including a structured, non-supervised exercise programme) or to revascularization together with BMT. Inpatient and outpatient costs were obtained prospectively over 24 months of follow-up. Mean improvement in quality-adjusted life-years (QALYs) was calculated based on responses to the EuroQol Five Dimensions EQ-5D-3 L™ questionnaire. Cost-effectiveness was assessed as the cost per QALY gained.

Results

A total of 158 patients were randomized, 79 to each group. The mean cost per patient in the BMT group was €1901, whereas it was €8280 in the group treated with revascularization in addition to BMT, with a cost difference of €6379 (95 per cent c.i. €4229 to 8728) per patient. Revascularization in addition to BMT resulted in a mean gain in QALYs of 0·16 (95 per cent c.i. 0·06 to 0·24) per patient, giving an incremental cost-effectiveness ratio of €42 881 per QALY.

Conclusion

The costs associated with revascularization together with BMT in patients with intermittent claudication were about four times higher than those of BMT alone. The incremental cost-effectiveness ratio of revascularization was within the accepted threshold for public willingness to pay according to the Swedish National Guidelines, but exceeded that of the UK National Institute for Health and Care Excellence guidelines.
Liquid chromatographic enantioseparation of (RS)‐etodolac using (S)‐levofloxacin and determination of absolute configuration of the diastereomeric derivatives
Authors: Singh Manisha
Published: October 2018

(RS)‐Etodolac was isolated from commercial tablets and was purified and characterized to be used as racemic standard. A pair of diastereomeric derivatives was synthesized using (S)‐levofloxacin as a chiral derivatizing reagent. The derivatization reaction was carried out under conditions of stirring at room temperature (30°C for 1.5 h) as well as under microwave irradiation; the derivatives obtained by the two methods were compared. Reaction conditions for derivatization were optimized with respect to mole ratio of chiral derivatizing reagent and (RS)‐etodolac. No racemization was observed throughout the study. Separation of diastereomeric derivatives was successful using C18 column and a binary mixture of methanol and triethyl ammonium phosphate buffer of pH 4.5 (80:20, v/v) as mobile phase at a flow rate of 1 mL min−1 and UV detection at 223 nm. An efficient approach for recognizing chirality and determining the absolute configuration of the diastereomeric derivatives of (RS)‐etodolac is described, which in turn is a measure of the enantiomeric purity of (RS)‐etodolac since the diastereomeric derivatives were separated and isolated using preparative thin‐layer chromatography.
Proposition of zinc supplementation during levodopa–carbidopa intestinal gel treatment
Authors: Matsuyama Hirofumi , Matsuura Keita , Ishikawa Hidehiro , Hirata Yoshinori , Kato Natsuko , Niwa Atsushi , Narita Yugo , Tomimoto Hidekazu
Published: October 2018

Objectives

Levodopa–carbidopa intestinal gel (LCIG) infusion is a useful therapy for the wearing‐off phenomenon of advanced Parkinson's disease (PD) patients. Recently, we found three PD patients that may have had a zinc deficiency after the LCIG infusion, possibly due to the zinc‐chelating action of levodopa. This study aims to evaluate changes in serum zinc levels in three patients that received LCIG treatment and to determine possible remedies for zinc deficiency during treatment.

Materials and Methods

We performed a prospective blood analysis of serum zinc levels before, when possible, and after LCIG treatment in our three PD patients.

Results

The serum zinc levels of the first patient before treatment and 4 months after beginning LCIG treatment were 69 and 58 μg/dl, respectively. For the second patient, serum zinc levels before treatment and two months after starting LCIG treatment were 87 and 46 μg/dl, respectively. The baseline serum zinc level for the third patient was not examined, but was 48 μg/dl 5 months after starting the LCIG infusion.

Conclusions

Levodopa–carbidopa intestinal gel infusion might have caused a zinc deficiency through levodopa zinc chelation. Zinc deficiency with LCIG infusion has not yet been reported, though preventing zinc deficiency may be an important factor in future LCIG treatment strategies.
High levels of serum glypican‐1 indicate poor prognosis in pancreatic ductal adenocarcinoma
Authors: Zhou Cong‐ya , Dong Yi‐ping , Sun Xiao , Sui Xin , Zhu Hong , Zhao Ya‐qin , Zhang Yuan‐yuan , Mason Clifford , Zhu Qing , Han Su‐xia
Published: October 2018

Carbohydrate antigen 19‐9 (CA19‐9) fails to demonstrate the predictive value for early detection pancreatic ductal adenocarcinoma (PDAC). Glypican‐1 (GPC1+) exosomes may serve as a noninvasive diagnostic tool to detect early stages of PDAC. Therefore, it is necessary to explore the serum GPC1 levels and determine whether serum GPC1 serves as a novel biomarker for PDAC patients. Blood samples were collected from 156 patients with PDAC, 199 non‐cancer controls, and 240 patients with other cancers. Serological levels of GPC1 were examined by enzyme‐linked immunosorbent assay (ELISA). Finally, a 5‐year follow‐up was monitored to evaluate the correlation between serum GPC1 levels and overall survival in 156 patients with PDAC. The results suggested that levels of serum GPC1 and CA19‐9 were higher in PDAC patients than that of controls (P < 0.05). Serum GPC1 levels in PDAC were different from those in gallbladder carcinoma (P < 0.001), colorectal carcinoma (P < 0.001), gastric carcinoma (P < 0.001), and prostate cancer (P < 0.001), but not hepatocellular carcinoma (P = 0.395) and cholangiocarcinoma (P = 0.724). Receiver operating characteristic curve (ROC) analysis showed that serum CA19‐9 was significantly better than serum GPC1 in distinguishing PDAC patients from the controls (AUC, 95% CI: 0.908, 0.868‐0.947 vs 0.795, 0.749‐0.841, respectively). The serum GPC1 cannot be used as a serum diagnostic biomarker for PDAC patients. The level of serum GPC1 decreased 2 days after surgery (P = 0.001), which were not different from serum GPC1 levels in healthy control (P = 0.381). The overall survival rate was shorter in patients with high levels of serum GPC1 compared to those with low levels of serum GPC1 (log‐rank = 5.16, P = 0.023). Taken together, the results indicate that high levels of serum GPC1 predict poor prognosis in PDAC patients. Serum GPC1 may be a prognosis factor for PDAC patients.
Expression of CD81 and CD117 in plasma cell myeloma and the relationship to prognosis
Authors: Chen Fang , Hu Yanping , Wang Xiaohui , Fu Shuang , Liu Zhuogang , Zhang Jihong
Published: October 2018

In this study, the immunophenotype was retrospectively analyzed in 131 patients who received initial treatment for plasma cell myeloma (PCM) and the relationships of CD81 and CD117 with the clinicopathologic characteristics and prognosis were further evaluated. The Kaplan and Meier method and Cox regression survival analysis model were used to determine whether CD117 and CD81 were factors affecting the overall survival (OS) and progression‐free survival (PFS) of PCM patients. CD117 and CD81 positivity was demonstrated in 35.88% and 40.46% of the 131 patients, respectively. Kaplan‐Meier analysis showed that CD117 and CD81 were potential predictors of a patient's prognosis. Specifically, CD117(+) patients had longer PFS (P = 0.033) and OS (P = 0.002), while CD81(+) patients had shorter PFS (P = 0.001) and OS (P = 0.002). CD117(+) and CD81(−) patients had the longest PFS [P = 0.0183 compared to the CD117(−)CD81(−)/CD117(+)CD81(+) group;P = 0.0007 compared to the CD117(−)CD81(+) group] and the longest OS [P = 0.0331 compared to the CD117(−)CD81(−)/CD117(+)CD81(+) group;P = 0.0005 compared to the CD117(−)CD81(+) group]. Our results show that CD81 is an independent factor affecting the OS and PFS of PCM patients, and CD117 is an independent factor affecting the OS of PCM patients. CD117‐positive and CD81‐negative patients with PCM have a better prognosis.
Albocycline‐type Macrolides with Antibacterial Activities from Streptomyces sp. 4205
Authors: Gu Cheng‐Zhen , Yuan Sheng‐Hao , Lü Jing , Qiao Yi‐Jun , Song Yuan‐Yuan , Abdalla Elzaki Mohammed Esmail , Yang Chong‐Ren , Zhang Ying‐Jun , Zeng Ren‐Sen
Published: October 2018

The actinomycete genus Streptomyces is characterized by producing bioactive secondary metabolites, including antibiotics. In this study, chemical and biological investigations were carried out on Streptomyces strain 4205 isolated from the paddy soil, leading to the identification and characterization of 10 albocycline‐type macrolides, among which 4 compounds were new, namely albocyclines A–D (1–4). The structures of 1–10 were identified according to the 1D‐ and 2D‐NMR spectroscopic data. Furthermore, compounds 1–10 were evaluated for antimicrobial activity. Compounds 5–7 displayed antimicrobial activities against Candidaalbicans ATCC 90028 with the same MIC value of 10.0 mg/mL and the IC50 values of 1.5, 1.0, and 1.0 mg/mL, respectively. Thus, the research on Streptomyces sp. is of vital significance for developing new antibiotic agents.
Superior semicircular canal dehiscence with concomitant otosclerosis—A literature review and case discussion
Authors: Ungar Omer J. , Handzel Ophir , Cavel Oren , Oron Yahav
Published: October 2018

Key Clinical Massage

Computed tomography scan should be performed as a routine before every stapes surgery, in order to exclude concomitant superior semicircular canal dehiscence, since no other clinical, audiological, or electro‐physiological criteria are available to exclude concomitant superior semicircular canal dehiscence in the otosclerotic temporal bone.
Novel metabolic signatures of compound heterozygous Szt2 variants in a case of early‐onset of epileptic encephalopathy
Authors: Uittenbogaard Martine , Gropman Andrea , Brantner Christine A. , Chiaramello Anne
Published: October 2018

Key Clinical Message

Our study reports the case of a patient with early onset of epileptic encephalopathy harboring compound heterozygous Szt2 variants. We provide the first evidence that these Szt2 variants impair mitochondrial energy metabolism. Our results shed light on their pathogenic molecular mechanism and clinical implications for brain development and disease progression.
Oxidative Dehydrogenation on Nanocarbon: Revealing the Reaction Mechanism via In Situ Experimental Strategies
Authors: Wang Chao , Liu Wei , Wei Shimeng , Su Dangsheng , Qi Wei
Published: October 2018

Classical mechanistic analysis strategy, including active site chemical titration, kinetic measurement and corresponding isotopic effect and surface reaction of single reactant etc., were performed in oxidative dehydrogenation reactions on nanocarbon. The detailed reaction mechanism for non‐metallic carbon catalytic process was revealed via in situ experimental methods, which sheds light on the accurate quantitative description and structure‐function relations for carbon catalysis.
Boosting the Performance of BiVO4 Prepared through Alkaline Electrodeposition with an Amorphous Fe Co‐Catalyst
Authors: Saada Hiba , Abdallah Rawa , Fabre Bruno , Floner Didier , Fryars Stéphanie , Vacher Antoine , Dorcet Vincent , Meriadec Cristelle , Ababou‐Girard Soraya , Loget Gabriel
Published: October 2018

BiVO4 is a promising n‐type semiconductor for water‐splitting photoelectrochemical cells. We report here a new method to prepare BiVO4 photoanodes that is based on an alkaline electrodeposition process, which avoids chemical etching of Bi. In addition, we present a simple and general method to prepare coatings of amorphous FeOx that behave as a co‐catalyst on our BiVO4 material, improving the water splitting photocurrent.
Identifying optimal approaches to implement colorectal cancer screening through participation in a learning laboratory
Authors: Tangka Florence K.L. , Subramanian Sujha , DeGroff Amy S. , Wong Faye L. , Richardson Lisa C.
Published: October 2018

A total of 14 programs selected from among the 30 Centers for Disease Control and Prevention's Colorectal Cancer Control Program awardees are participating in the Colorectal Cancer Control Program learning laboratory to share information regarding the effectiveness and cost‐effectiveness of the interventions and lessons learned from the implementation processes. Herein, the authors
present findings from the first set of 4 awardee programs in a series of 4 articles along with a methods article describing the data collection and analytic procedures used to perform comprehensive assessments
Effectiveness and cost of multilayered colorectal cancer screening promotion interventions at federally qualified health centers in Washington State
Authors: Kemper Kathryn E. , Glaze Becky L. , Eastman Casey L. , Waldron Roxane C. , Hoover Sonja , Flagg T’Ronda , Tangka Florence K. L. , Subramanian Sujha
Published: October 2018

Background

It has been demonstrated that fecal immunochemical test (FIT) mailing programs are effective for increasing colorectal cancer (CRC) screening. The objectives of the current study were to assess the magnitude of uptake that could be achieved with a mailed FIT program in a federally qualified health center and whether such a program can be implemented at a reasonable cost to support sustainability.

Methods

The Washington State Department of Health’s partner HealthPoint implemented a direct‐mail FIT program at 9 medical clinics, along with a follow‐up reminder letter and automated telephone calls to those not up‐to‐date with recommended screening. Supplemental outreach events at selected medical clinics and a 50th birthday card screening reminder program also were implemented. The authors collected and analyzed process, effectiveness, and cost measures and conducted a systematic assessment of the short‐term cost effectiveness of the interventions.

Results

Overall, 5178 FIT kits were mailed with 4009 follow‐up reminder letters, and 8454 automated reminder telephone calls were made over 12 months. In total, 1607 FIT kits were returned within 3 months of the end of the implementation period: an overall return rate of 31% for the mailed FIT program. The average total intervention cost per FIT kit returned was $39.81, and the intervention implementation cost per kit returned was $18.76.

Conclusions

The mailed FIT intervention improved CRC screening uptake among HealthPoint’s patient population. This intervention was implemented for less than $40 per individual successfully screened. The findings and lessons learned can assist other clinics that serve disadvantaged populations to increase their CRC screening adherence.
Gene expression patterns determine the differential numbers of dorsocentral macrochaetes between Musca domestica and Drosophila melanogaster
Authors: Liang Qing , Peng Tingting , Sun Boyuan , Tu Jianbo , Cheng Xingyi , Tian Yuanliangzi , Fan Xiaolan , Yang Deying , Gaur Uma , Yang Mingyao
Published: October 2018

The evolutionary differences in sensory bristle patterns on the thorax of dipterans are an excellent model for studying the patterns of evolutionary development. We observed that Drosophila melanogaster has two pairs of the large bristles, called macrochaetes, in the dorsocentral (DC) region of the notum, while Musca domestica retains six DC macrochaetes. To explore possible mechanism by which these two dipteran species have different numbers of DC bristles, we compared the corresponding protein sequences, the gene expression levels and the spatial expression patterns of five genes (scute, pnr, ush, hairy, and emc) for bristle development between two species. We also checked the overexpression of scute and emc in transgenic flies. The results demonstrated a strong conservation of five protein sequences between these two species. The mRNA expression of the five genes differed significantly between D. melanogaster and M. domestica. The gene expression patterns exhibited a species‐specific pattern during the larval development stage. It suggests that the function of these genes has been conserved in regulating the development of macrocheates between housefly and fruit fly, whereas the gene expression levels, especially spatial expression patterns lead to species‐specificity in DC bristles.