bluuebunny/crossref_metadata_2025 huggingface dataset:
Modular and Reconfigurable Wireless E‐Tattoos for Personalized Sensing
Authors: Jeong Hyoyoung , Wang Liu , Ha Taewoo , Mitbander Ruchika , Yang Xiangxing , Dai Zhaohe , Qiao Shutao , Shen Linxiao , Sun Nan , Lu Nanshu
Published: May 2019

In the past few years, ultrathin and ultrasoft epidermal electronics (a.k.a. e‐tattoos) emerged as the next‐generation wearables for telemedicine, mobile health, performance tracking, human‐machine interface (HMI), and so on. However, it is not possible to build an all‐purpose e‐tattoo that can accommodate such a wide range of applications. Thus, the design, fabrication, and validation of modular and reconfigurable wireless e‐tattoos for personalized sensing are reported. Such e‐tattoos feature a multilayer stack of stretchable layers of distinct functionalities—a near field communication (NFC) layer capable of wireless power harvesting and data transmission, a functional circuit layer, and a passive electrode/sensor layer. These layers can be disassembled and swapped out multiple times to form different e‐tattoos of different sensing capabilities. Such modular and wireless e‐tattoos can be rapid‐prototyped via a dry, digital, and cost‐effective fabrication process—the “cut‐solder‐paste” process. They have been successfully applied to wirelessly measure a variety of biometrics.
In Situ Fine‐Tuning of Microfluidic Chips by Swelling and Its Application to Droplet Microfluidics
Authors: González‐Estefan Juan H. , Gonidec Mathieu , Vu Thi Thiet , Daro Nathalie , Chastanet Guillaume
Published: May 2019

Over the last two decades, polydimethylsiloxane (PDMS) has been widely used as the material of choice for fast‐throughput prototyping of microfluidic devices due to the ease of fabrication of PDMS devices by soft‐lithography replica molding methods. Nevertheless, PDMS is known to swell significantly in a variety of organic solvents which has sometimes limited its use in synthetic chemistry and has led the microfluidic community to consider PDMS as being “incompatible” with such solvents. Nevertheless, as shown here, when analyzed deeper and controlled properly, the solvent‐induced swelling of PDMS actually constitutes a potentially useful phenomenon that can become a simple tool to control and adjust finely and dynamically the geometry of microfluidic chips in situ. In this paper, this method is applied to the control of the behavior of a variety of droplet generators. The simplicity and efficiency of this approach make it a great asset for droplet microfluidics synthesis, for which microreactor sizes are a critical parameter that is often overlooked due to its complex implementation. In a more general sense, it is expected that integrating swelling into design should allow to adjust the function of many different types of chips exhibiting geometry‐driven functions.
Optimized‐Surface Wettability: A New Experimental 3D Modeling Approach Predicting Favorable Biomaterial–Cell Interactions
Authors: do Nascimento Rodney Marcelo , Sarig Udi , da Cruz Nilson Cristino , de Carvalho Vanessa Rafaela , Eyssartier Camille , Siad Larbi , Ganghoffer Jean‐François , Hernandes Antônio Carlos , Rahouadj Rachid
Published: May 2019

Despite several decades of research on biomedical implant materials, the identification of predictive and robust in vitro characteristics of cell support ability and viabilities—as indicators of biocompatibility and future implant‐tissue integration—remain elusive. This study addresses the phenomenology of cell–implant interfaces based on experimental, theoretical, and numerical analysis of cell response to functionalized bioceramic coatings of commercial titanium implants, cp‐Ti. A variable spectrum of coatings having differing surface wettabilities, with optimized solid tension values, is obtained. Measured values are modeled and correlated to cell support ability and viabilities. The contributions of different surface aspects to cell viability are decoupled, resulting in the identification of the polar component of the surface free energy as a significant and major cell–substrate effector. Furthermore, results of this study and the suggested model establish the thermodynamic interfacial free energy as an omnipotent measure that can be fully correlated to the morphology of an individual cell under numerical simulation matching empirical observations. Collectively, the 3D model reported herein can offer a new generic theoretical framework, using implementable mathematical simulation, toward the objective of rational biomaterial design that can improve next‐generation metal and ceramic implants.
Polyelemental, Multicomponent Perovskite Semiconductor Libraries through Combinatorial Screening
Authors: Saliba Michael
Published: May 2019

Recently, perovskites with multiple cations, metals, and anions have shown very high efficiencies and stabilities for perovskite solar cells. The novel materials frequently exhibit unexpected and beneficial properties, outperforming simpler counterparts. The trend of increasing material complexity requires a systematic strategy to explore polyelemental “multicomponent engineering.” Here, a combinatorial approach is introduced to generate all possible, unique combinations within a set of available components. Thus, with each new component, the combinatorial framework can generate the full theoretical parameter space. Based on reported components, the experimental parameter space can then be identified. The exceptional material versatility of perovskites is suited for high‐throughput screening, machine‐learning, or data mining, laying the foundation for a “perovskite genome project” that thoroughly catalogues the entire material family for desired properties. This can provide the framework for theoretical simulations toward understanding the fundamental working principles of perovskite materials enabling the “next big thing” after perovskites. Finally, informed by literature, a promising candidate list for future material exploration is presented including novel organic‐free, Pb‐free, and all‐inorganic perovskites. These compounds are primary contenders toward stable, high efficiency, and reproducible materials for rapid industrialization of perovskite solar cells, lasers, light‐emitting diodes, photo detectors, or particle detectors.
A Green and Sustainable Approach for Selective Halogenation of Anilides, Benzanilides, Sulphonamides and Heterocycles†
Authors: Lakshmireddy V. M. , Naga Veera Y. , Reddy T. J. , Rao V. J. , China Raju B.
Published: May 2019

An efficient green and sustainable protocol has been devised for the selective oxidative halogenation of acetanilides, benzanilides, sulphonamides, and heterocyclic compounds, using easily available NaX as a halogen source and Oxone as a powerful oxidant. Reaction products were analyzed by GC‐MS. Defined experimental conditions provided the mono and dihalo compounds. The present protocol is simple and environmentally benign to conduct the laboratory scale halogenations and can be extended to prepare industrially important compounds.
Individual acquisition of “stick pounding” behavior by naïve chimpanzees
Authors: Bandini Elisa , Tennie Claudio
Published: May 2019

Many studies investigating culture in nonhuman animals tend to focus on the inferred need of social learning mechanisms that transmit the form of a behavior to explain the population differences observed in wild animal behavioral repertoires. This research focus often results in studies overlooking the possibility of individuals being able to develop behavioral forms without requiring social learning. The disregard of individual learning abilities is most clearly observed in the nonhuman great ape literature, where there is a persistent claim that chimpanzee behaviors, in particular, require various forms of social learning mechanisms. These special social learning abilities have been argued to explain the acquisition of the relatively large behavioral repertoires observed across chimpanzee populations. However, current evidence suggests that although low‐fidelity social learning plays a role in harmonizing and stabilizing the frequency of behaviors within chimpanzee populations, some (if not all) of the forms that chimpanzee behaviors take may develop independently of social learning. If so, they would be latent solutions—behavioral forms that can (re‐)emerge even in the absence of observational opportunities, via individual (re)innovations. Through a combination of individual and low‐fidelity social learning, the population‐wide patterns of behaviors observed in great ape species are then established and stably maintained. This is the Zone of Latent Solutions (ZLS) hypothesis. The current study experimentally tested the ZLS hypothesis for pestle pounding, a wild chimpanzee behavior. We tested the reinnovation of this behavior in semi‐wild chimpanzees at Chimfunshi Wildlife Orphanage in Zambia, Africa, (N = 90, tested in four social groups). Crucially, all subjects were naïve to stick pounding before testing. Three out of the four tested groups reinnovated stick pounding—clearly demonstrating that this behavioral form does not require social learning. These findings provide support for the ZLS hypothesis alongside further evidence for the individual learning abilities of chimpanzees.
Nasal saline irrigation: a clinical update
Authors: Succar Eric F. , Turner Justin H. , Chandra Rakesh K.
Published: May 2019

Background

Nasal saline irrigation (NSI) plays an important role in the treatment of chronic rhinosinusitis (CRS). It is a beneficial low‐risk treatment that serves an adjunctive function in the medical and surgical management of CRS. NSI is hypothesized to function by thinning mucous, improving mucociliary clearance, decreasing edema, and reducing antigen load in the nasal and sinus cavities. Although its use in CRS is nearly universal, significant variety exists with regard to delivery volume, delivery pressure, frequency of use, duration of use, composition, and hygiene recommendations. Evidence is limited regarding the most optimal methods of NSI delivery. In addition, use of NSI has recently come under increasing scrutiny due to potential associations with cases of primary amebic meningoencephalitis.

Methods

In this review we provide a clinical update summarizing use of NSI for treatment of CRS, including current recommendations for use, and data regarding overall efficacy, available delivery devices, solution composition, and hygiene.

Results

Current evidence and recommendations for nasal saline delivery methods, composition, and hygiene are presented.

Conclusion

The most recent consensus statements and Cochrane Review recommend the use of NSI for CRS based on a preponderance of lower level evidence. A conclusion regarding the optimal method of delivery and solution composition cannot be drawn based on the current literature.
Topical antibiotic therapy in chronic rhinosinusitis: an update
Authors: Carlton Daniel A. , Beahm D. David , Chiu Alexander G.
Published: May 2019

Background

Topical antibiotic therapies have been investigated for their use in chronic rhinosinusitis (CRS). However, society guidelines and evidence‐based medicine reviews have recommended against the use of topical antibiotic therapy based on randomized controlled trials (RCTs). The purpose of this article is to review recent clinical research published since the aforementioned guidelines were published.

Methods

A structured literature review was performed on clinical studies published in the last 5 years investigating the use of topical antibiotic therapies.

Results

One double‐blinded, randomized controlled trial (DB‐RCT) supported the use of tobramycin using a vibrating aerosolizer; 1 non‐blinded non‐randomized controlled prospective trial lent support to use of topical ofloxacin for its anti‐biofilm properties; and 1 meta‐analysis found mupirocin irrigations to be beneficial in the short term. One Cochrane Review was unable to make a recommendation as no trial met the inclusion criteria. An additional systematic review found limited evidence to support the use of topical antibiotics with the exception of mupirocin irrigations that may be considered in Staphylococcus aureus infections. Two retrospective studies found that topical antibiotics change bacterial cultures of the sinuses.

Conclusion

There is additional evidence to support continuing investigation of topical antibiotic therapies. Further, larger RCTs are required to establish the efficacy of topical antibiotic therapies.
Sulfur‐Based Electrodes that Function via Multielectron Reactions for Room‐Temperature Sodium‐Ion Storage
Authors: Wang Yun‐Xiao , Lai Wei‐Hong , Wang Yun‐Xia , Chou Shu‐Lei , Ai Xinping , Yang Hanxi , Cao Yuliang
Published: May 2019

Emerging rechargeable sodium‐ion storage systems—sodium‐ion and room‐temperature sodium–sulfur (RT‐NaS) batteries—are gaining extensive research interest as low‐cost options for large‐scale energy‐storage applications. Owing to their abundance, easy accessibility, and unique physical and chemical properties, sulfur‐based materials, in particular metal sulfides (MSx) and elemental sulfur (S), are currently regarded as promising electrode candidates for Na‐storage technologies with high capacity and excellent redox reversibility based on multielectron conversion reactions. Here, we present current understanding of Na‐storage mechanisms of the S‐based electrode materials. Recent progress and strategies for improving electronic conductivity and tolerating volume variations of the MSx anodes in Na‐ion batteries are reviewed. In addition, current advances on S cathodes in RT‐NaS batteries are presented. We outline a novel emerging concept of integrating MSx electrocatalysts into conventional carbonaceous matrices as effective polarized S hosts in RT‐NaS batteries as well. This comprehensive progress report could provide guidance for research toward the development of S‐based materials for the future Na‐storage techniques.
miR‐455‐5p Overexpression Reduces Rat Lung Alveolar Type II Cell Proliferation by Downregulating STRA6
Authors: Zheng Jintao , He Qiuming , Tang Huajian , Xia Huimin
Published: May 2019

miR‐455‐5p and retinoid signaling pathway and its membrane receptor, STRA6, are associated with lung development. Software copredictions indicate that the miRNA upstream of the STRA6 gene is miR‐455‐5p. We hypothesized that miR‐455‐5p participates in rat lung alveolar Type II cell proliferation by targeting STRA6 and designed this study to investigate the effects of miR‐455‐5p overexpression on rat lung alveolar Type II cells. Dual luciferase reporter gene assay was utilized to confirm the relationship between miR‐455‐5p and STRA6. An miR‐455‐5p‐expressing adenoviral vector was constructed and transfected into rat lung alveolar Type II cells. STRA6 protein expression was detected in rat lung alveolar Type II cells by Western blotting at 72 hr posttransfection. Retinol concentration was detected by ELISA at 72 hr posttransfection. The cell proliferation was detected by CCK8 assay at 24, 48, and 72 hr posttransfection. Our results showed that STRA6 is a target gene of miR‐455‐5p. STRA6 protein expression was significantly lower in the miR‐455‐5p‐overexpression group than in the NC group (0.615 ± 0.131 vs. 0.958 ± 0.246, P = 0.029). Similar results were observed for retinol concentration (2.985 ± 0.061 vs. 3.949 ± 0.118, P = 0.000). Rat lung alveolar Type II cell proliferation was lower in the miR‐455‐5p‐overexpression group than in the NC group at 24, 48, and 72 hr posttransfection (24 hr: 0.280 ± 0.184 vs. 1.354 ± 0.169 P = 0.026; 48 hr: 0.881 ± 0.016 vs. 1.992 ± 0.050 P = 0.001; 72 hr: 2.105 ± 0.148 vs. 2.937 ± 0.079 P = 0.016). In summary, miR‐455‐5p is associated with lung development. miR‐455‐5p overexpression downregulates STRA6, leading to reduced retinol concentration and rat lung alveolar Type II cell proliferation. Anat Rec, 302:2062–2069, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
A standard procedure for lentiviral‐mediated labeling of murine mesenchymal stromal cells in vitro
Authors: Lupan Ana‐Mihaela , Preda Mihai Bogdan , Burlacu Alexandrina
Published: May 2019

Tracking of stem cells after transplantation is effectively performed in vivo with imaging systems, assuming the cells are adequately labeled to facilitate their recognition. This study aimed to optimize a protocol for fluorescent labeling of mesenchymal stromal cells (MSCs) in vitro, by using a third‐generation lentiviral system. Basically, 293T cells are seeded in high‐glucose Dulbecco's modified Eagle medium with 10% FBS one day before transfection. Transfection is done for 24 h using a mix of transfer, packaging, regulatory, and envelope plasmids, in molar ratio of 4:2:1:1, respectively. After transfection, the cells are further cultured for two days. During this period, the viral medium is harvested two times, at 24‐h intervals, with the first round being stored at 4°C until the second round is completed. The pooled viral medium is frozen in single‐use aliquots. MSCs are transduced with 25 multiplicity of infection (MOI) and one day later the cells are passaged at standard seeding density and further grown for three days, when the fluorescence reach the maximum level. Our protocol provides particular experimental details for permanent MSC labeling that makes the procedure highly effective for therapeutic purposes, without affecting the functional properties of stem cells.
Efficient and Innocuous Live‐Cell Delivery: Making Membrane Barriers Disappear to Enable Cellular Biochemistry
Authors: Pellois Jean‐Philippe
Published: May 2019

The confluence of protein engineering techniques and delivery protocols are providing new opportunities in cell biology. In particular, techniques that render the membrane of cells transiently permeable make the introduction of nongenetically encodable macromolecular probes into cells possible. This, in turn, can enable the monitoring of intracellular processes in ways that can be both precise and quantitative, ushering an area that one may envision as cellular biochemistry. Herein, the author reviews pioneering examples of such new cell‐based assays, provides evidence that challenges the paradigm that cell penetration is a necessarily damaging and stressful event for cells, and highlights some of the challenges that should be addressed to fully unlock the potential of this nascent field.
Response misclassification in studies on bilateral diseases
Authors: Günther Felix , Brandl Caroline , Heid Iris M. , Küchenhoff Helmut
Published: May 2019

Misclassification in binary outcomes can severely bias effect estimates of regression models when the models are naively applied to error‐prone data. Here, we discuss response misclassification in studies on the special class of bilateral diseases. Such diseases can affect neither, one, or both entities of a paired organ, for example, the eyes or ears. If measurements are available on both organ entities, disease occurrence in a person is often defined as disease occurrence in at least one entity. In this setting, there are two reasons for response misclassification: (a) ignorance of missing disease assessment in one of the two entities and (b) error‐prone disease assessment in the single entities. We investigate the consequences of ignoring both types of response misclassification and present an approach to adjust the bias from misclassification by optimizing an adequate likelihood function. The inherent modelling assumptions and problems in case of entity‐specific misclassification are discussed. This work was motivated by studies on age‐related macular degeneration (AMD), a disease that can occur separately in each eye of a person. We illustrate and discuss the proposed analysis approach based on real‐world data of a study on AMD and simulated data.
Did college radio station violate coach's contract?
Authors: Gelpi Aileen
Published: May 2019

The plaintiff became the head women's basketball coach and assistant athletic director at Northland College in 2009.
Relationship between self‐worrying and self‐critical messages in clients with generalised anxiety engaging in emotion‐focused worry dialogues
Authors: Toolan Rochelle , Devereux Megan , Timulak Ladislav , Keogh Daragh
Published: May 2019

Emotion‐focused therapy (EFT) has recently been adapted as a treatment for generalised anxiety disorder (GAD). One intervention used in this adaptation is a worry dialogue, in which the client enacts worry in one chair (“worrier”) and is facilitated to experience the impact of this worry in another chair (“experiencer”). Although not formally studied, anecdotal observations from therapists in the EFT for GAD treatment development study suggested that within worry dialogues there might be a link between client's self‐worrying and self‐critical messages. This study used data from 47 worry dialogues from fourteen study clients who received EFT for GAD. An observation based qualitative analysis of clients' self‐directed messages as present in in‐session worry dialogues was conducted using video/audio recordings of relevant sessions. Results indicate a relationship between self‐worrying and self‐critical messages. A total of 90 paired self‐worry and self‐critic messages across the 47 worry dialogues were logged. Six recurring clusters of themes/relationships were observed: (a) I need to be prepared for future negative events because… I'm weak and a failure; (b) I need to stop worrying… I'm flawed for being a worrier; (c) People will negatively judge me if I engage with them… because I'm not good enough; (d) If I don't worry, there will be negative consequences… and I will be responsible and will be unable to bear it; (e) I worry/ruminate that I cause(d) some damage… because I'm incompetent; and, (f) I must always be prepared against others taking advantage of me… because I'm weak. Given the observed close link between self‐critical and worry processes, it is important that therapists differentiate between these processes and remember to address both in therapy for GAD.
A Comprehensive View on (−)‐7‐Oxo‐ent‐kaur‐16‐en‐19‐oic Acid, the Major Constituent of Xylopia sericea Leaves Extract: Complete NMR Assignments, X‐Ray Crystallographic Structure, in Vitro Antimalarial Activity and Cytotoxicity
Authors: Costa Gontijo Douglas , Fernanda Alves do Nascimento Maria , Borgati Tatiane Freitas , Speziali Nivaldo Lúcio , Dias de Souza Filho José , Braga de Oliveira Alaíde
Published: May 2019

Bioguided fractionation of Xylopia sericea antiplasmodial dichloromethane leaves extract led to the isolation of (−)‐7‐oxo‐ent‐kaur‐16‐en‐19‐oic acid (C20H28O3) that was identified by a combination of 1D and 2D NMR experiments (COSY, HMBC, HSQC, HSQC‐TOCSY, HSQC‐NOESY and NOESY) and by X‐ray crystallography. A feature to be pointed out is its (4R) configuration that was inferred from the NOE experiments (HSQC‐NOESY and NOESY) and X‐ray crystallography. In vitro evaluation of this rare diterpene acid against the chloroquine‐resistant strain Plasmodium falciparum W2 by the PfLDH method showed it disclosed a low antiplasmodial activity and was not cytotoxic to HepG2 cells (CC50 862.6±6.7 μm) by the MTT assay. The unequivocal NMR signals assignments, the X‐ray crystallographic structure, the assessment to the bioactivities and the occurrence this diterpene in X. sericea are reported here for the first time.
Cover Picture: Electrochemical Oxidative Csp3—H/S—H Cross‐Coupling with Hydrogen Evolution for Synthesis of Tetrasubstituted Olefins (Chin. J. Chem. 6/2019)
Authors: Lu Fangling , Yang Zengzhuan , Wang Tao , Wang Tianhao , Zhang Yuying , Yuan Yong , Lei Aiwen
Published: May 2019

The inside cover picture shows an electrochemical oxidative Csp3‐H/S‐H activation with hydrogen evolution for the synthesis of tetrasubstituted olefins. This method features very high atom economy, besides hydrogen gas, under the base‐free, transition met‐al‐free, and oxidants‐free conditions, no other by‐products were generated. More details are discussed in the article by Lei et al. on page 547–551.

image
Ligand Effect on the Stability of Water‐Soluble Iridium Catalysts for High‐Pressure Hydrogen Gas Production by Dehydrogenation of Formic Acid
Authors: Iguchi Masayuki , Onishi Naoya , Himeda Yuichiro , Kawanami Hajime
Published: May 2019

The front cover artwork is provided by researchers from National Institute of Advanced Industrial Science and Technology (AIST) in Japan. The image shows the ligand effect on catalyst activity for the formic acid dehydrogenation and a durability of Cp*Ir complex under high‐pressure conditions. Read the full text of the Communication at 10.1002/cphc.201900137.
Interface Electronic Coupling in Hierarchical FeLDH(FeCo)/Co(OH)2 Arrays for Efficient Electrocatalytic Oxygen Evolution
Authors: Kong Fanhao , Zhang Wenwen , Sun Liping , Huo Lihua , Zhao Hui
Published: May 2019

The oxygen evolution reaction (OER) with sluggish kinetics is the key half‐cell reaction for several sustainable energy systems, such as electrochemical water splitting, fuel cells, and rechargeable metal–air batteries. Two‐dimensional transition‐metal hydroxides have good prospects for the OER. Herein, 2D hierarchical FeLDH(FeCo)/Co(OH)2 (LDH=layered double hydroxide) arrays were fabricated by growing 2D‐ZIF‐67 (ZIF=zeolitic imidazolate framework) on carbon cloth, transformation of 2D‐ZIF‐67 into Co(OH)2, and electrodeposition of FeLDH(FeCo) on Co(OH)2 at ambient temperature. The optimized hierarchical catalyst exhibits high OER activity that requires a small overpotential of only 242 mV to drive 10 mA cm−2 (279 mV for 100 mA cm−2) and prolonged durability for 100 h at 20 mA cm−2 in 1 m KOH. The FeLDH(FeCo)/Co(OH)2 interfaces are observed to be the electrocatalytically active centers for the OER. The interfaces contribute to accelerating the OER kinetics owing to fast transfer of intermediate oxygen species. Furthermore, the FeCo alloy promotes electron transfer among the newly formed interfaces related to CoOOH in the OER process, which leads to improved durability. This work gives insight into the design and synthesis of hierarchical bimetallic hydroxide arrays with high OER activity and durability, as well as understanding of the origin of the OER promotion by metals and metal hydroxides.
B cell‐intrinsic MyD88 signaling controls IFN‐γ‐mediated early IgG2c class switching in mice in response to a particulate adjuvant
Authors: Lee Michelle Sue Jann , Natsume‐Kitatani Yayoi , Temizoz Burcu , Fujita Yukiko , Konishi Aki , Matsuda Kyoko , Igari Yoshikatsu , Tsukui Toshihiro , Kobiyama Kouji , Kuroda Etsushi , Onishi Motoyasu , Marichal Thomas , Ise Wataru , Inoue Takeshi , Kurosaki Tomohiro , Mizuguchi Kenji , Akira Shizuo , Ishii Ken J , Coban Cevayir
Published: May 2019

Adjuvants improve the potency of vaccines, but the modes of action (MOAs) of most adjuvants are largely unknown. TLR‐dependent and ‐independent innate immune signaling through the adaptor molecule MyD88 has been shown to be pivotal to the effects of most adjuvants; however, MyD88's involvement in the TLR‐independent MOAs of adjuvants is poorly understood. Here, using the T‐dependent antigen NIPOVA and a unique particulate adjuvant called synthetic hemozoin (sHZ), we show that MyD88 is required for early GC formation and enhanced antibody class‐switch recombination (CSR) in mice. Using cell‐type‐specific MyD88 KO mice, we found that IgG2c class switching, but not IgG1 class switching, was controlled by B cell‐intrinsic MyD88 signaling. Notably, IFN‐γ produced by various cells including T cells, NK cells, and dendritic cells was the primary cytokine for IgG2c CSR and B‐cell intrinsic MyD88 is required for IFN‐γ production. Moreover, IFN‐γ receptor (IFNγR) deficiency abolished sHZ‐induced IgG2c production, while recombinant IFN‐γ administration successfully rescued IgG2c CSR impairment in mice lacking B‐cell intrinsic MyD88. Together, our results show that B cell‐intrinsic MyD88 signaling is involved in the MOA of certain particulate adjuvants and this may enhance our specific understanding of how adjuvants and vaccines work.
Gel electrophoresis in combination with laser ablation–inductively coupled plasma mass spectrometry to quantify the interaction of cisplatin with human serum albumin
Authors: Sullivan Matthew P. , Morrow Stuart J. , Goldstone David C. , Hartinger Christian G.
Published: May 2019

Cisplatin and its second and third generation analogues are widely used in the treatment of cancer. To study their reactions with proteins, we present a method based on SDS‐PAGE separation and laser ablation–inductively coupled plasma‐mass spectrometry (LA–ICP‐MS) for platinum detection in the reaction between human serum albumin (HSA) and cisplatin. We developed matrix‐matched standards of HSA/cisplatin mixtures and used them to quantify the amount of adducts formed at different HSA:cisplatin ratios. We noted that cisplatin incubation with HSA resulted in the formation of higher order HSA n‐mers, depending on the amount of cisplatin added. This caused a depletion of the HSA dimer bands, while the majority of HSA was present as the monomer. Inducing the formation of such higher molecular weight species may have an impact on the mode of action of metallodrugs.
High‐order curvilinear mesh generation technique based on an improved radius basic function approach
Authors: Zhao Zhong , Li Ming , He Lei , Shao Shuai , Zhang Laiping
Published: May 2019

A high‐order curvilinear hybrid mesh generation technique is developed for high‐order numerical method (eg, discontinuous Galerkin method) applications to improve the accuracy for problems with curve boundary. The grid generation technique is based on an improved radius basic function (RBF) approach by which the straight‐edge mesh is converted into high‐order curve mesh. Firstly, an initial straight‐edge mesh is prepared by traditional grid generation software. Then, high‐order interpolation points are inserted into the mesh entities such as edges, faces, and cells according to the final demand of mesh order. To preserve the original geometry, the inserted points on solid wall are then projected onto the CAD model using an open source tool “Open Cascade.” Finally, other inserted points in the field near the solid wall are moved to appropriate positions by the improved RBF approach to avoid tangled cells. If we use the original RBF approach, then the inserted points on the edge and face entities normal to the solid boundary in the region of boundary layer will move to improper positions. To overcome this problem, a weighting based on the local grid aspect ratio between normal direction and tangential direction is introduced into the baseline RBF approach. Three typical configurations are tested to validate the mesh generator. Meanwhile, a third‐order solution of subsonic flow over an analytical 3D body of revolution in the second International Workshop on High‐Order CFD Methods is supplied by a discontinuous Galerkin solver. These numerical tests demonstrate the potential capability of present technique for high‐order simulations of complex geometries.
Prognostic impact of tumor growth velocity in head and neck squamous cell carcinoma treated by radiotherapy: A pilot study
Authors: Delahaut Gilles , Témam Stéphane , Ambroise Jérôme , Tao Yungan , Janot Francois , Van der Vorst Sébastien
Published: May 2019

Background

When a patient is seen with a newly diagnosed oropharyngeal squamous cell carcinoma, it remains unclear to the treating physicians how fast the tumor growth rate is.

Methods

From patients with oropharynx squamous cell carcinoma treated by radiotherapy, the investigators selected comparable diagnostic CT‐scan (DiCT) and radiotherapy planning CT‐scan (RtCT). Tumor and pathological lymph node volumes were measured in order to calculate tumor progression.

Results

From the selection of 19 patients, the mean absolute tumor progression rate was 0.23 ± 0.2 cm3/d and mean relative progression rate was 1.84 ± 1.64%/d. Mean tumor doubling time is 286 days (range 7‐1282 days), demonstrating a wide range of tumor growth pattern. Significant tumor progression (>20%) between DiCT and RtCT was shown in 73% of patients, and 53% of the patients were seen a tumor progression of >50% within a mean waiting time of 42.1 days. Kaplan‐Meier curves showed a non‐significative link between fast progression tumors (>1%/d) and higher risk of recurrence (HR: 2.2; P = .23).

Conclusions

Tumor progression can be assessed based on DiCT and RtCT. Treatment delay should be avoided at all cost. Different growth patterns were evidenced. For the fast‐growing tumors subgroup, pejorative clinical outcomes were suggested. Prospective studies are needed to confirm a link between fast‐growing tumors and higher risk for recurrence.
Mapping the postgraduate year one pharmacy accreditation standards to the core entrustable professional activities
Authors: Moon Jean Y. , Lounsbery Jody L. , Schweiss Sarah K. , Pittenger Amy L.
Published: May 2019

Introduction

Postgraduate year one (PGY1) pharmacy residency is a common training path for pharmacy graduates. As the American Association of Colleges of Pharmacy (AACP) have published the Core Entrustable Professional Activities (EPAs) as a standard for new pharmacy graduates, mapping these competencies to the American Society of Health‐System Pharmacists (ASHP) PGY1 pharmacy residency standards may allow for progression tracking.

Methods

Using group consensus, the guidance documents from the ASHP PGY1 pharmacy residency standards and the AACP Core EPAs for new pharmacy graduates were compared and mapped.

Results

The ASHP PGY1 pharmacy residency standards included one additional tier (ie, goals) when evaluating structural levels compared with the AACP Core EPAs. All of the 15 AACP Core EPAs mapped to at least one ASHP educational objective. In addition, all of the ASHP educational objectives mapped to the Core EPAs except for one objective in Patient Care and four in the Leadership and Management competency areas.

Discussion

With only a slight difference in structure and a small gap between ASHP education objectives and AACP EPAs, tracking of progression from new pharmacy graduate to postgraduate pharmacy resident may be possible. Greater consensus around leveling and general use with EPAs will provide further insight.
Recent developments in polyetherimide membrane for gas separation
Authors: Alqaheem Yousef , Alomair Abdulaziz
Published: May 2019

Polyetherimide (PEI) is an extraordinary type of polyimide with excellent thermal and mechanical properties. The polymer is also gas permeable and is considered one of the best membranes for gas separation. Despite the high selectivity, PEI suffers from low permeability due to the trade‐off between phenomena in polymers. To overcome this limitation, fillers are added during the membrane preparation to create voids for better gas transport. In this paper, permeability and selectivity data of PEI membranes for the separation of oxygen, carbon dioxide, and helium are discussed. The paper also summarizes the reported studies for adding fillers to improve the membrane performance.
Physiologically Based Pharmacokinetic Modeling to Evaluate Formulation Factors Influencing Bioequivalence of Metoprolol Extended‐Release Products
Authors: Basu Sumit , Yang Haitao , Fang Lanyan , Gonzalez‐Sales Mario , Zhao Liang , Trame Mirjam N. , Lesko Lawrence , Schmidt Stephan
Published: May 2019

The University of Florida Center for Pharmacometrics and Systems Pharmacology and the Food and Drug Administration Office of Generic Drugs have collaborated on a research project to develop a mechanism‐ and risk‐based strategy that systematically investigates postmarketing reports of therapeutic inequivalence following the switch between brand and generic drug products. In this study we developed and qualified a physiologically based pharmacokinetic model to systematically investigate the influence of drug‐ and formulation‐related properties on the oral absorption and bioequivalence of modified‐release products using metoprolol as an example. Our findings show that the properties of the release‐controlling polymer are the critical attributes for in vitro dissolution, in vivo absorption, and systemic exposure (ie, pharmacokinetics) and, thus, the bioequivalence of metoprolol extended‐release products rather than the properties of the drug itself. Differences in dissolution rate can result in significant differences in maximum plasma concentration but not in area under the concentration‐time curve.
Enhanced low‐temperature activity for CO2 methanation over NiMgAl/SiC composite catalysts
Authors: Wang Yujiang , Xu Yang , Liu Qiankun , Sun Jinwei , Ji Shengfu , Wang Zhou‐jun
Published: May 2019

Background

Carbon dioxide (CO2) methanation is an important reaction in energy and environmental fields, which aims to convert CO2 into natural gas with hydrogen (H2) from renewable sources. One of the technical bottlenecks for CO2 methanation is the lack of feasible catalysts, especially the ones with satisfactory low‐temperature activity.

Results

The NiMgAl/SiC composite catalyst that was derived from hydrotalcite precursor on the SiC substrate possessed enhanced low‐temperature activity and excellent long‐term stability in CO2 methanation. For the low‐temperature activity, CO2 conversion reached 63.8% and 74.5% at 300 and 325 °C respectively. For the long‐term stability, CO2 conversion merely decreased from 78.4% to 76.9% after 50 h of reaction at 400 °C.

Conclusion

The NiMgAl/SiC composite catalyst was successfully synthesized by the co‐precipitation method, which exhibited enhanced low‐temperature methanation activity compared with the NiMgAl and Ni/SiC catalysts. The superior low‐temperature activity was mainly ascribed to two structural parameters. One was the small nickel (Ni) nanoparticle size, which was endowed by the unique structure of the hydrotalcite precursor. The other one was the high reducibility of Ni species, which was rendered by the appropriate metal‐support interactions. The present work provides guidelines for the synthesis of highly efficient composite catalysts for energy and environmental applications. © 2019 Society of Chemical Industry
Efficacy of using trimethoprim‐sulfamethoxazole prophylaxis in an adult patient with autoimmune neutropenia
Authors: Azuma Naoto , Sekiguchi Masahiro , Matsunaga Hitomi , Sano Hajime , Matsui Kiyoshi
Published: May 2019

A 63‐year‐old man was admitted for pneumonia with neutropenia. After the pneumonia resolved with administration of antibiotics and granulocyte colony‐stimulating factor, he was diagnosed with autoimmune neutropenia (AIN) on the basis of bone marrow findings and positive antineutrophil antibodies. He had recurring high fever once or twice a month with productive cough and an elevated serum C‐reactive protein level. However, after the initiation of treatment with oral trimethoprim‐sulfamethoxazole (TMP/SMX), the respiratory tract infection no longer recurred. The standard management for adults with AIN has not been established. In our case, the recurrent infection was resolved with TMP/SMX prophylaxis. Thus, TMP/SMX prophylaxis may be beneficial for managing adults with AIN.
Leptin in the regulation of the immunometabolism of adipose tissue-macrophages
Authors: Monteiro Lauar , Pereira Jéssica Aparecida da Silva , Palhinha Lohanna , Moraes-Vieira Pedro Manoel M
Published: May 2019

Obesity is a pandemic disease affecting around 15% of the global population. Obesity is a major risk factor for other conditions, such as type 2 diabetes and cardiovascular diseases. The adipose tissue is the main secretor of leptin, an adipokine responsible for the regulation of food intake and energy expenditure. Obese individuals become hyperleptinemic due to increased adipogenesis. Leptin acts through the leptin receptor and induces several immunometabolic changes in different cell types, including adipocytes and Mϕs. Adipose tissue resident Mϕs (ATMs) are the largest leukocyte population in the adipose tissue and these ATMs are in constant contact with the excessive leptin levels secreted in obese conditions. Leptin activates both the JAK2-STAT3 and the PI3K-AKT-mTOR pathways. The activation of these pathways leads to intracellular metabolic changes, with increased glucose uptake, upregulation of glycolytic enzymes, and disruption of mitochondrial function, as well as immunologic alterations, such as increased phagocytic activity and proinflammatory cytokines secretion. Here, we discuss the immunometabolic effects of leptin in Mϕs and how hyperleptinemia can contribute to the low-grade systemic inflammation in obesity.
Association between PR Interval, First‐degree atrioventricular block and major arrhythmic events in patients with Brugada syndrome – Systematic review and meta‐analysis
Authors: Pranata Raymond , Yonas Emir , Chintya Veresa , Deka Hadrian , Raharjo Sunu Budhi
Published: May 2019

Background

Risk stratification in patients with asymptomatic Brugada Syndrome is challenging, and despite recent advances, there is no clear evidence. The first‐degree atrioventricular block was hypothesized to be a predictor of arrhythmic events. Measurement of the PR interval and diagnosing atrioventricular block from surface ECG is easy, noninvasive, and cost‐effective. We aimed to assess the latest evidence on PR interval or first‐degree atrioventricular block and major arrhythmic events related to Brugada Syndrome.

Methods

We performed a comprehensive search in PubMed for “atrioventricular block” OR “PR interval” and “Brugada syndrome.” We included studies that have a component of PR interval and/or first‐degree atrioventricular block and major arrhythmic events related to Brugada Syndrome including syncope/VT/VF/appropriate ICD shocks/ICD implantation.

Results

We included 1526 subjects from 7 studies. Pooled mean difference of PR interval in 4 studies showed a significant difference [MD 10.77 ms (2.97‐18.57) P = 0.007, moderate‐high heterogeneity I2 = 53% P = 0.08]. On sensitivity analysis by removing a study, it became MD 6.50 ms [1.97‐11.03], P = 0.005, heterogeneity I2 = 0% P = 0.52. Indicating that PR interval was prolonged by small margin. Pooled analysis of the association between a first‐degree atrioventricular block and major arrhythmic events was significant [OR 3.33 (2.02‐5.50) P < 0.001, low heterogeneity I2 = 0% P = 0.57].

Conclusion

First‐degree AV block is associated with more frequent major arrhythmic events in Brugada syndrome patients. PR interval seemed to be prolonged but is yet to be determined whether the PR interval association is still significant if it did not cross the first‐degree AVB threshold.
Autosomal dominant mitochondrial membrane protein‐associated neurodegeneration (MPAN)
Authors: Gregory Allison , Lotia Mitesh , Jeong Suh Young , Fox Rachel , Zhen Dolly , Sanford Lynn , Hamada Jeff , Jahic Amir , Beetz Christian , Freed Alison , Kurian Manju A. , Cullup Thomas , van der Weijden Marlous C. M. , Nguyen Vy , Setthavongsack Naly , Garcia Daphne , Krajbich Victoria , Pham Thao , Woltjer Randy , George Benjamin P. , Minks Kelly Q. , Paciorkowski Alexander R. , Hogarth Penelope , Jankovic Joseph , Hayflick Susan J.
Published: May 2019

Background

Mitochondrial membrane protein‐associated neurodegeneration (MPAN) is caused by pathogenic sequence variants in C19orf12. Autosomal recessive inheritance has been demonstrated. We present evidence of autosomal dominant MPAN and propose a mechanism to explain these cases.

Methods

Two large families with apparently dominant MPAN were investigated; additional singleton cases of MPAN were identified. Gene sequencing and multiplex ligation‐dependent probe amplification were used to characterize the causative sequence variants in C19orf12. Post‐mortem brain from affected subjects was examined.

Results

In two multi‐generation non‐consanguineous families, we identified different nonsense sequence variations in C19orf12 that segregate with the MPAN phenotype. Brain pathology was similar to that of autosomal recessive MPAN. We additionally identified a preponderance of cases with single heterozygous pathogenic sequence variants, including two with de novo changes.

Conclusions

We present three lines of clinical evidence to demonstrate that MPAN can manifest as a result of only one pathogenic C19orf12 sequence variant. We propose that truncated C19orf12 proteins, resulting from nonsense variants in the final exon in our autosomal dominant cohort, impair function of the normal protein produced from the non‐mutated allele via a dominant negative mechanism and cause loss of function. These findings impact the clinical diagnostic evaluation and counseling.
Robust spatiotemporal fractionation schemes in the presence of patient setup uncertainty
Authors: Gaddy Melissa R. , Unkelbach Jan , Papp Dávid
Published: May 2019

Purpose

Spatiotemporal fractionation schemes for photon radiotherapy have recently arisen as a promising technique for healthy tissue sparing. Because spatiotemporally fractionated treatments have a characteristic pattern of delivering high doses to different parts of the tumor in each fraction, uncertainty in patient positioning is an even more pressing concern than in conventional uniform fractionation. Until now, such concerns in patient setup uncertainty have not been addressed in the context of spatiotemporal fractionation.

Methods

A stochastic optimization model is used to incorporate patient setup uncertainty to optimize spatiotemporally fractionated plans using expected penalties for deviations from prescription values. First, a robust uniform reference plan is optimized with a stochastic optimization model. Then, a spatiotemporal plan is optimized with a constrained stochastic optimization model that minimizes a primary clinical objective and constrains the spatiotemporal plan to be at least as good as the uniform reference plan with respect to all other objectives. A discrete probability distribution is defined to characterize the random setup error occurring in each fraction. For the optimization of uniform plans, the expected penalties are computed exactly by exploiting the symmetry of the fractions, and for the spatiotemporal plans, quasi‐Monte Carlo sampling is used to approximate the expectation.

Results

Using five clinical liver cases, it is demonstrated that spatiotemporally fractionated treatment plans maintain the same robust tumor coverage as a stochastic uniform reference plan and exhibit a reduction in the expected mean BED of the uninvolved liver. This is observed for a spectrum of probability distributions of random setup errors with shifts in the patient position of up to 5 mm from the nominal position. For probability distributions with small variance in the patient position, the spatiotemporal plans exhibit an 8–30% reduction in expected mean BED in the healthy liver tissue for shifts up to 2.5 mm and reductions of 5–25% for shifts up to 5 mm.

Conclusions

In the presence of patient setup uncertainty, spatiotemporally fractionated treatment plans exhibit the same robust tumor coverage as their uniformly fractionated counterparts and still retain the benefit in sparing healthy tissues.