bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer's disease
Authors: Ginsberg Stephen D. , Malek‐Ahmadi Michael H. , Alldred Melissa J. , Che Shaoli , Elarova Irina , Chen Yinghua , Jeanneteau Freddy , Kranz Thorsten M. , Chao Moses V , Counts Scott E. , Mufson Elliott J.
Published: September 2017

Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom‐designed microarray analysis, and qPCR of CA1 subregional dissections. Gene expression levels were correlated with cognitive test scores and AD neuropathology criteria. We found a significant downregulation of several neurotrophin genes (e.g., Gdnf, Ngfb, and Ntf4) in CA1 pyramidal neurons in MCI compared to NCI and AD subjects. In addition, the neurotrophin receptor transcripts TrkB and TrkC were decreased in MCI and AD compared to NCI. Regional hippocampal dissections also revealed select neurotrophic gene dysfunction providing evidence for vulnerability within the hippocampus proper during the progression of dementia. Downregulation of several neurotrophins of the NGF family and cognate neurotrophin receptor (TrkA, TrkB, and TrkC) genes correlated with antemortem cognitive measures including the Mini‐Mental State Exam (MMSE), a composite global cognitive score (GCS), and Episodic, Semantic, and Working Memory, Perceptual Speed, and Visuospatial domains. Significant correlations were found between select neurotrophic expression downregulation and neuritic plaques (NPs) and neurofibrillary tangles (NFTs), but not diffuse plaques (DPs). These data suggest that dysfunction of neurotrophin signaling complexes have profound negative sequelae within vulnerable hippocampal cell types, which play a role in mnemonic and executive dysfunction during the progression of AD.
Gold‐Catalyzed Synthesis of 1,3‐Diaminopyrazoles from 1‐Alkynyltriazenes and Imines
Authors: Jeanbourquin Loïc N. , Scopelliti Rosario , Tirani Farzaneh Fadaei , Severin Kay
Published: September 2017

A new procedure for the synthesis of highly substituted 1,3‐diaminopyrazoles is described. As substrates, we have employed 1‐alkynyltriazenes and imines. The formation of pyrazoles was achieved by two‐fold C–N coupling reactions in the presence of (JohnPhos)AuCl and AgNTf2 as catalyst precursors. The regioselectivity of the reaction was inferred from a crystallographic analysis of one reaction product.
Contemporary Issues in Women's Health
Authors: Boama Vincent , Guinto Valerie T. , Sosa Claudio G.
Published: September 2017

Effect of early tranexamic acid administration in women with primary post-partum hemorrhage

Maternal pertussis vaccination confers additional protection for infants

The global breastfeeding collective

Resources for Women's Health
Bioabsorbable nerve conduits coated with induced pluripotent stem cell‐derived neurospheres enhance axonal regeneration in sciatic nerve defects in aged mice
Authors: Yokoi Takuya , Uemura Takuya , Takamatsu Kiyohito , Shintani Kosuke , Onode Ema , Okada Mitsuhiro , Hidaka Noriaki , Nakamura Hiroaki
Published: September 2017

Aging influences peripheral nerve regeneration. Nevertheless, most basic research of bioabsorbable nerve conduits including commercial products have been performed in very young animals. Results from these studies may not provide information about axonal regeneration in aged tissue, because young nerve tissue holds sufficient endogenous potential for axonal regeneration. The clinical target age for nerve conduit application is most likely going to increase with a rapidly growing elderly population. In the present study, we examined axonal regeneration after sciatic nerve defects in aged and young mice. 5‐mm sciatic nerve defects in young (6 weeks old) and aged (92 weeks old) mice were reconstructed using nerve conduits (composed of a poly lactide and caprolactone) or autografts. In addition, in aged mice, sciatic nerve defects were reconstructed using nerve conduits coated with mouse induced pluripotent stem cell (iPSc)‐derived neurospheres. Using electrophysiological and histological techniques, we demonstrated axonal regeneration was significantly less effective in aged than in young mice both for nerve conduits and for nerve autografts. However, despite the low regenerative capacity of the peripheral nerve in aged mice, axonal regeneration significantly increased when nerve conduits coated with iPSc‐derived neurospheres, rather than nerve conduits alone, were used. The present study shows that aging negatively affects peripheral nerve regeneration based on nerve conduits in mice. However, axonal regeneration using nerve conduits was improved when supportive iPSc‐derived neurospheres were added in the aged mice. We propose that tissue‐engineered bioabsorbable nerve conduits in combination with iPSc‐derived neurospheres hold therapeutic potential both in young and elderly patients. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1752–1758, 2018.
Comparison of genome‐wide analysis techniques to DNA methylation analysis in human cancer
Authors: Soozangar Narges , Sadeghi Mohammad R. , Jeddi Farhad , Somi Mohammad H. , Shirmohamadi Masoud , Samadi Nasser
Published: September 2017

DNA methylation was the first epigenetic modification to be detected in human cancers with specific relation to aberrant gene expression. Herein, DNA methylation analysis explains how epigenetic patterns affect gene expression level. Hypermethylation at tumor suppressor gene loci leads to increased tumorigenesis due to tumor suppressor gene silencing, whereas global hypomethylation of CpG islands (CGIs) is followed by genomic instability and aberrant activation of multiple oncogenes. Therefore, characterization of the genes which silenced or activated epigenetically in human tumor cells can improve our understanding of cancer biology. Different genome‐wide methodologies are applied to evaluate methylation status. Various commonly conducted techniques for this evaluation are reviewed in this paper. We provided comparative description of the procedures, advantages, and drawbacks of genome‐wide DNA methylation analysis methods and biological applications, to give information on selecting the appropriate method for different methylation studies.
Small‐molecule inhibition of MuRF1 attenuates skeletal muscle atrophy and dysfunction in cardiac cachexia
Authors: Bowen Thomas Scott , Adams Volker , Werner Sarah , Fischer Tina , Vinke Paulien , Brogger Maria Noel , Mangner Norman , Linke Axel , Sehr Peter , Lewis Joe , Labeit Dittmar , Gasch Alexander , Labeit Siegfried
Published: September 2017

Background

Muscle ring finger 1 (MuRF1) is a muscle‐specific ubiquitin E3 ligase activated during clinical conditions associated with skeletal muscle wasting. Yet, there remains a paucity of therapeutic interventions that directly inhibit MuRF1 function, particularly in vivo. The current study, therefore, developed a novel compound targeting the central coiled coil domain of MuRF1 to inhibit muscle wasting in cardiac cachexia.

Methods

We identified small molecules that interfere with the MuRF1–titin interaction from a 130 000 compound screen based on Alpha Technology. A subset of nine prioritized compounds were synthesized and administrated during conditions of muscle wasting, that is, to C2C12 muscle cells treated with dexamethasone and to mice treated with monocrotaline to induce cardiac cachexia.

Results

The nine selected compounds inhibited MuRF1–titin complexation with IC50 values <25 μM, of which three were found to also inhibit MuRF1 E3 ligase activity, with one further showing low toxicity on cultured myotubes. This last compound, EMBL chemical core ID#704946, also prevented atrophy in myotubes induced by dexamethasone and attenuated fibre atrophy and contractile dysfunction in mice during cardiac cachexia. Proteomic and western blot analyses showed that stress pathways were attenuated by ID#704946 treatment, including down‐regulation of MuRF1 and normalization of proteins associated with apoptosis (BAX) and protein synthesis (elF2B‐delta). Furthermore, actin ubiquitinylation and proteasome activity was attenuated.

Conclusions

We identified a novel compound directed to MuRF1's central myofibrillar protein recognition domain. This compound attenuated in vivo muscle wasting and contractile dysfunction in cardiac cachexia by protecting de novo protein synthesis and by down‐regulating apoptosis and ubiquitin‐proteasome‐dependent proteolysis.
Comparison of anatomic and non‐anatomic hepatic resection for hepatocellular carcinoma
Authors: Kaibori Masaki , Kon Masanori , Kitawaki Tomoki , Kawaura Takayuki , Hasegawa Kiyoshi , Kokudo Norihiro , Ariizumi Shunichi , Beppu Toru , Ishizu Hiroyuki , Kubo Shoji , Kamiyama Toshiya , Takamura Hiroyuki , Kobayashi Tsuyoshi , Kim Dong‐Sik , Wang Hee Jung , Kim Jong Man , Han Dai Hoon , Park Sang‐Jae , Kang Koo Jeong , Hwang Shin , Roh Younghoon , You Young Kyung , Joh Jae‐Won , Yamamoto Masakazu
Published: September 2017

Background

The aim of the present study was to compare the prognostic impact of anatomic resection (AR) versus non‐anatomic resection (NAR) on patient survival after resection of a single hepatocellular carcinoma (HCC).

Methods

To control for confounding variable distributions, a 1‐to‐1 propensity score match was applied to compare the outcomes of AR and NAR. Among 710 patients with a primary, solitary HCC of <5.0 cm in diameter that was resectable by either AR or NAR from 2003 to 2007 in Japan and Korea, 355 patients underwent NAR and 355 underwent AR of at least one section with complete removal of the portal territory containing the tumor.

Results

Overall survival (OS) was better in the AR than NAR group (hazard ratio 1.67, 95% confidence interval 1.28–2.19, P < 0.001) while disease‐free survival showed no significant difference. Significantly fewer patients in the AR than NAR group developed intrahepatic HCC recurrence and multiple intrahepatic recurrences. Patients with poorly differentiated HCC who underwent AR had improved disease‐free survival and OS.

Conclusions

Anatomic resection decreases the risk of tumor recurrence and improves OS in patients with a primary, solitary HCC of <5.0 cm in diameter.
Tokyo Guidelines 2018: management strategies for gallbladder drainage in patients with acute cholecystitis (with videos)
Authors: Mori Yasuhisa , Itoi Takao , Baron Todd H. , Takada Tadahiro , Strasberg Steven M. , Pitt Henry A. , Ukai Tomohiko , Shikata Satoru , Noguchi Yoshinori , Teoh Anthony Yuen Bun , Kim Myung‐Hwan , Asbun Horacio J. , Endo Itaru , Yokoe Masamichi , Miura Fumihiko , Okamoto Kohji , Suzuki Kenji , Umezawa Akiko , Iwashita Yukio , Hibi Taizo , Wakabayashi Go , Han Ho‐Seong , Yoon Yoo‐Seok , Choi In‐Seok , Hwang Tsann‐Long , Chen Miin‐Fu , Garden O. James , Singh Harjit , Liau Kui‐Hin , Huang Wayne Shih‐Wei , Gouma Dirk J. , Belli Giulio , Dervenis Christos , de Santibañes Eduardo , Giménez Mariano Eduardo , Windsor John A. , Lau Wan Yee , Cherqui Daniel , Jagannath Palepu , Supe Avinash Nivritti , Liu Keng‐Hao , Su Cheng‐Hsi , Deziel Daniel J. , Chen Xiao‐Ping , Fan Sheung Tat , Ker Chen‐Guo , Jonas Eduard , Padbury Robert , Mukai Shuntaro , Honda Goro , Sugioka Atsushi , Asai Koji , Higuchi Ryota , Wada Keita , Yoshida Masahiro , Mayumi Toshihiko , Hirata Koichi , Sumiyama Yoshinobu , Inui Kazuo , Yamamoto Masakazu
Published: September 2017

Since the publication of the Tokyo Guidelines in 2007 and their revision in 2013, appropriate management for acute cholecystitis has been more clearly established. Since the last revision, several manuscripts, especially for alternative endoscopic techniques, have been reported; therefore, additional evaluation and refinement of the 2013 Guidelines is required. We describe a standard drainage method for surgically high‐risk patients with acute cholecystitis and the latest developed endoscopic gallbladder drainage techniques described in the updated Tokyo Guidelines 2018 (TG18). Our study confirmed that percutaneous transhepatic gallbladder drainage should be considered the first alternative to surgical intervention in surgically high‐risk patients with acute cholecystitis. Also, endoscopic transpapillary gallbladder drainage or endoscopic ultrasound‐guided gallbladder drainage can be considered in high‐volume institutes by skilled endoscopists. In the endoscopic transpapillary approach, either endoscopic naso‐gallbladder drainage or gallbladder stenting can be considered for gallbladder drainage. We also introduce special techniques and the latest outcomes of endoscopic ultrasound‐guided gallbladder drainage studies. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
Evaluation of loading parameters for murine axial tibial loading: Stimulating cortical bone formation while reducing loading duration
Authors: Sun David , Brodt Michael D. , Zannit Heather M. , Holguin Nilsson , Silva Matthew J.
Published: September 2017

Classic studies in bone mechanobiology have established the importance of loading parameters on the anabolic response. Most of these early studies were done using loading methods not currently in favor, and using non‐murine species. Our objective was to re‐examine the effects of several loading parameters on the response of cortical bone using the contemporary murine axial tibial compression model. We subjected tibias of 5‐month old, female C57Bl/6 mice to cyclic (4 Hz) mechanical loading and examined bone formation responses using dynamic and static histomorphometry. First, using a reference protocol of 1,200 cycles/day, 5 days/week for 2 weeks, we confirmed the significant influence of peak strain magnitude on periosteal mineralizing surface (Ps.MS/BS) and bone formation rate (Ps.BFR/BS) (p < 0.05, ANOVA). There was a significant induction of periosteal lamellar bone at a lower threshold of approx. −1,000 μϵ and a transition from lamellar‐woven bone near −2,000 μϵ. In contrast, on the endocortical surface, bone formation indices did not exhibit a load magnitude‐dependent response and no incidence of woven bone. Next, we found that reducing daily cycle number from 1,200 to 300 to 60 did not diminish the bone formation response (p > 0.05). On the other hand, reducing the daily frequency of loading from 5 consecutive days/week to 3 alternate days/week significantly diminished the periosteal response, from a loading‐induced increase in Ps.MS/BS of 38% (loaded vs. control) for 5 days/week to only 15% for 3 days/week (p < 0.05). Finally, we determined that reducing the study duration from 2 to 1 weeks of loading did not affect bone formation outcomes. In conclusion, cyclic loading to −1,800 μϵ peak strain, at 4 Hz and 60 cycles/day for 5 consecutive days (1 week) induces an increase in periosteal lamellar bone formation with minimal incidence of woven bone in 5‐month‐old C57Bl/6 female mice. Our results provide a basis for reduction of loading duration (daily cycles and study length) without loss of anabolic effect as measured by dynamic histomorphometry. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:682–691, 2018.
Ultrasound‐Guided Intratumoral Radiofrequency Ablation Coagulation to Facilitate Meningioma Resection: Preliminary Experience
Authors: Yan Li , Yang Junle , Zhou Xiaodong , He Guangbin , Zheng Yu , Zhu Yali , Liu Weiping , Luo Wen , Qin Haiying , Liu Haijing , Yi Xicai , Zhou Yin
Published: September 2017

Objectives

This study aimed to explore the feasibility and safety of intratumoral radiofrequency ablation (RFA) in meningioma resection.

Methods

This study was approved by the Xijing Ethics Committee, and informed consent was obtained from all of the patients. Thirteen patients with meningiomas were recruited in the Neurosurgery Department of Xijing Hospital. These patients were treated with intratumoral RFA and surgery. We also chose 13 patients with meningiomas treated with traditional surgery as the control group. Two‐dimensional ultrasound, color Doppler flow imaging, contrast‐enhanced ultrasound, and magnetic resonance imaging were used to identify the location, border, and blood supply of the meningiomas preoperatively and to assess the therapeutic effect intraoperatively. Finally, the meningiomas were dissected and removed by surgery.

Results

All procedures were technically successful without serious complications. Intraoperative ultrasound was able to provide a clear display of the location, shape, size, and boundary of the tumor and its relationship with other tissues and reveal the vascular distribution in and around the tumors. With intratumoral RFA, coagulative necrosis was induced, and the meningiomas became hard in texture with a decreased blood supply. Blood loss was significantly lower in the RFA group versus control group (320.0 ± 24.8 versus 390.4 ± 36.8 mL; P < .001). The RFA group spent fewer days in the hospital (6.0 ± 0.9 versus 7.0 ± 1.2 days; P = .022). However, the surgical time of the RFA group was relatively longer (3.5 ± 0.5 versus 3.0 ± 0.3 hours, P = .007).

Conclusions

The application of intratumoral RFA in meningioma resection is effective and safe. It may be a useful adjunct for meningioma treatment.
Determinants of HDL Cholesterol Efflux Capacity after Virgin Olive Oil Ingestion: Interrelationships with Fluidity of HDL Monolayer
Authors: Fernández‐Castillejo Sara , Rubió Laura , Hernáez Álvaro , Catalán Úrsula , Pedret Anna , Valls Rosa‐M , Mosele Juana I. , Covas Maria‐Isabel , Remaley Alan T. , Castañer Olga , Motilva Maria‐José , Solá Rosa
Published: September 2017

Scope

Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion.

Methods and results

Post‐hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3‐week changes in HDL‐related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A‐I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity.

Conclusions

HDL fluidity, ApoA‐I concentration, and oxidative status are major determinants for CEC after VOO. The impact on CEC of changes in free cholesterol and triglycerides in HDL, and those of small HDL or HDL mean size, could be mechanistically linked through HDL fluidity. Our work points out novel therapeutic targets to improve HDL functionality in humans through nutritional or pharmacological interventions.
Development of a patient‐specific atrial phantom model for planning and training of inter‐atrial interventions
Authors: Morais Pedro , Tavares João Manuel R. S. , Queirós Sandro , Veloso Fernando , D'hooge Jan , Vilaça João L.
Published: September 2017

Background

Several authors have presented cardiac phantoms to mimic the particularities of the heart, making it suitable for medical training and surgical planning. Although the initial models were mainly focused on the ventricles, personalized phantoms of the atria were recently presented. However, such models are typically rigid, the atrial wall is not realistic and they are not compatible with ultrasound (US), being sub‐optimal for planning/training of several interventions.

Methods

In this work, we propose a strategy to construct a patient‐specific atrial model. Specifically, the target anatomy is generated using a computed tomography (CT) dataset and then constructed using a mold‐cast approach. An accurate representation of the inter‐atrial wall (IAS) was ensured during the model generation, allowing its application for IAS interventions. Two phantoms were constructed using different flexible materials (silicone and polyvinyl alcohol cryogel, PVA‐C), which were then compared to assess their appropriateness for US acquisition and for the generation of complex anatomies.

Results

Two experiments were set up to validate the proposed methodology. First, the accuracy of the manufacturing approach was assessed through the comparison between a post‐production CT and the virtual references. The results proved that the silicone‐based model was more accurate than the PVA‐C‐based one, with an error of 1.68 ± 0.79, 1.36 ± 0.94, 1.45 ± 0.77 mm for the left (LA) and right atria (RA) and IAS, respectively. Second, an US acquisition of each model was performed and the obtained images quantitatively and qualitatively assessed. Both models showed a similar performance in terms of visual evaluation, with an easy detection of the LA, RA, and the IAS. Furthermore, a moderate accuracy was obtained between the atrial surfaces extracted from the US and the ideal reference, and again a superior performance of the silicone‐based model against the PVA‐C phantom was observed.

Conclusions

The proposed strategy proved to be accurate and feasible for the correct generation of complex personalized atrial models.
A universal parameterized gradient‐based method for photon beam field size determination
Authors: Lebron Sharon , Yan Guanghua , Li Jonathan , Lu Bo , Liu Chihray
Published: September 2017

Purpose

To propose a universal, parameterized gradient‐based method (PGM) for radiation field size determination.

Methods

The PGM locates the beam profile's edge by parameterizing its penumbra region with a modified sigmoid function where the inflection point can be determined in a closed form. The parametrization was validated with filter‐flattened (FF), flattening‐filter‐free (FFF) and wedged profiles measured on two Elekta linac models (Synergy and Versa HD). Gamma analysis with the delta dose function set to zero was used to quantitatively assess the parameterization accuracy. Field sizes of FF beams were calculated with the PGM and the full width at half maximum (FWHM) methods for comparison. To assess the consistency of the PGM and the FWHM method with geometric scaling across different depths, the calculated field size at a reference depth was scaled to other depths and compared with the field sizes calculated from the measured profiles. The method was also validated against a maximum‐slope method (MSM) with wedge and FFF profiles. We also evaluated the robustness of the three methods with respect to measurement noise, varying scanning step sizes, detector characteristics, and beam energy/modality.

Results

Small distance‐to‐agreement (0.02 ± 0.02 mm) between the measured and parameterized penumbra region was observed for all profiles. The differences between the field sizes calculated with the FWHM method and the PGM were consistent (0.9 ± 0.3 mm), with the FWHM method yielding larger values. With geometrical scaling, the PGM and the FWHM method produced maximum differences of 0.26 and 1.16 mm, respectively. For wedge and FFF beams, the mean differences relative to FF fields were 0.15 ± 0.09 mm and 0.57 ± 0.91 mm for the PGM and the MSM, respectively. The PGM was also found to produce more consistent results than the FWHM method and the MSM when measurement noise, scanning step size, detector characteristics, and beam energy/modality changed.

Conclusion

The proposed PGM is universally applicable to all beam modalities (FF, wedge and FFF) for accurate field size determination. Compared to the FWHM and the MSM, it is more robust to variations in measurement condition and detection system.
MYC drives overexpression of telomerase RNA (hTR/TERC) in prostate cancer
Authors: Baena‐Del Valle Javier A , Zheng Qizhi , Esopi David M , Rubenstein Michael , Hubbard Gretchen K , Moncaliano Maria C , Hruszkewycz Andrew , Vaghasia Ajay , Yegnasubramanian Srinivasan , Wheelan Sarah J , Meeker Alan K , Heaphy Christopher M , Graham Mindy K , De Marzo Angelo M
Published: September 2017

Telomerase consists of at least two essential elements, an RNA component hTR or TERC that contains the template for telomere DNA addition and a catalytic reverse transcriptase (TERT). While expression of TERT has been considered the key rate‐limiting component for telomerase activity, increasing evidence suggests an important role for the regulation of TERC in telomere maintenance and perhaps other functions in human cancer. By using three orthogonal methods including RNAseq, RT‐qPCR, and an analytically validated chromogenic RNA in situ hybridization assay, we report consistent overexpression of TERC in prostate cancer. This overexpression occurs at the precursor stage (e.g. high‐grade prostatic intraepithelial neoplasia or PIN) and persists throughout all stages of disease progression. Levels of TERC correlate with levels of MYC (a known driver of prostate cancer) in clinical samples and we also show the following: forced reductions of MYC result in decreased TERC levels in eight cancer cell lines (prostate, lung, breast, and colorectal); forced overexpression of MYC in PCa cell lines, and in the mouse prostate, results in increased TERC levels; human TERC promoter activity is decreased after MYC silencing; and MYC occupies the TERC locus as assessed by chromatin immunoprecipitation (ChIP). Finally, we show that knockdown of TERC by siRNA results in reduced proliferation of prostate cancer cell lines. These studies indicate that TERC is consistently overexpressed in all stages of prostatic adenocarcinoma and that its expression is regulated by MYC. These findings nominate TERC as a novel prostate cancer biomarker and therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Dielectric properties of continuous fiber reinforced polymer composites: Modeling, validation, and application
Authors: Zhou Jing , Li Yingguang , Cheng Libing , Hao Xiaozhong
Published: September 2017

Microwave curing technologies can realize a fast and energy saving curing process with less temperature gradients in the composite thickness compared with traditional autoclave curing techniques. A fundamental understanding and quantitative characterization for the dielectric properties of composites are crucial steps to ensure an effective microwave curing process. Herein, this study aims at providing a practical method to predict the effective complex permittivity of continuous fiber reinforced composites. A stochastic method was used to simulate the real distribution of fibers in the resin matrix. The huge scale factor between the micro architecture and macro structure of composites was balanced by using homogenization methods. Then the dielectric properties of composites in both longitudinal and transverse directions were computed by finite element analysis. The effectiveness of the proposed model was validated by various experimental measurements. Statistical analysis showed that the relative error was only 1.48–3.17% between model calculations and experimental results. Based on curing kinetics, the proposed model was further applied to investigate the permittivity of composites during microwave cure. POLYM. COMPOS., 39:4646–4655, 2018. © 2017 Society of Plastics Engineers
Epigenetic regulation – contribution to herbicide resistance in weeds?
Authors: Markus Catarine , Pecinka Ales , Karan Ratna , Barney Jacob N , Merotto Aldo
Published: September 2017

Continuous use of herbicides has resulted in the evolution of resistance to all major herbicide modes of action worldwide. Besides the well‐documented cases of newly acquired resistance through genetic changes, epigenetic regulation may also contribute to herbicide resistance in weeds. Epigenetics involves processes that modify the expression of specific genetic elements without changes in the DNA sequence, and play an important role in re‐programming gene expression. Epigenetic modifications can be induced spontaneously, genetically or environmentally. Stress‐induced epigenetic changes are normally reverted soon after stress exposure, although in specific cases they can also be carried over multiple generations, thereby having a selective benefit. Here, we provide an overview of the basis of epigenetic regulation in plants and discuss the possible effect of epigenetic changes on herbicide resistance. The understanding of these epigenetic changes would add a new perspective to our knowledge of environmental and management stresses and their effects on the evolution of herbicide resistance in weeds. © 2017 Society of Chemical Industry
The novel 19G endobronchial USS (EBUS) needle samples processed as tissue “core biopsies” facilitate PD‐L1 and other biomarker testing in lung cancer specimens: case report and the view point from the Respiratory Physician and the Pathologist
Authors: Herath Samantha , Cooper Wendy A
Published: September 2017

The immunohistochemical expression of Programmed Death Ligand (PD‐L1) predicts responses to PD‐1/PD‐L1 inhibitors in non‐small cell lung cancer (NSCLC). PD‐L1 testing is currently only recommended on tissue specimens; however, in many patients, cytology samples are the only specimens available. The introduction of the novel 19G “core‐biopsy” needle has revolutionized the utility of endobronchial USS‐guided biopsy (EBUS) by providing solid tissue “microbiopsies” rather than traditional liquid cytology samples. We report a case of metastatic adenocarcinoma with the only accessible site of biopsy being a hilar lymph node. Using the 19G core‐biopsy needle and processing the microbiopsy samples in formalin provided more material for predictive biomarker testing, including PD‐L1 immunohistochemistry, when traditional processing was inadequate. This case highlights the need for close multidisciplinary discussions between the pathologist and the respiratory physician regarding emerging biomarkers and novel biopsy techniques to obtain maximum utility of the tools and avoid repeated procedures for the patient.
Taxonomy of the Crisis and Disaster Literature: Themes and Types in 34 Years of Research
Authors: Kuipers Sanneke , Welsh Nicholas H.
Published: September 2017

This survey of the literature on crises and disasters reveals that crisis and disaster scholars remain focused on ‘classic’ natural disaster types and on our ability to prepare and respond to the threat they pose. The prevalence of natural disasters as a crisis type and the dominance of preparedness as a crisis theme indicates that the literature remains firmly linked to the world of practice, examining how best practices may be shared to prepare for future incidents. Yet interestingly, the three journals studied demonstrate modest interest in a number of issues that are only likely to increase in the coming years, all of which relate directly to an increasingly interconnected world. Most notably, the lack of attention on system interconnectedness or on advances in communication and cyber dependence (despite the rise of social media and internet use) is a surprising result, given how such systems and methods of communication are becoming so integrated into daily life. Such studies could help scholars and policymakers understand the unexpected turns crises can take and provide practitioners with a range of tools when preparing for or handling future crises.
Safety Profile of Good Manufacturing Practice Manufactured Interferon γ-Primed Mesenchymal Stem/Stromal Cells for Clinical Trials
Authors: Guess Adam J. , Daneault Beth , Wang Rongzhang , Bradbury Hillary , La Perle Krista M. D. , Fitch James , Hedrick Sheri L. , Hamelberg Elizabeth , Astbury Caroline , White Peter , Overolt Kathleen , Rangarajan Hemalatha , Abu-Arja Rolla , Devine Steven M. , Otsuru Satoru , Dominici Massimo , O'Donnell Lynn , Horwitz Edwin M.
Published: September 2017

Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon γ (IFNγ) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule. This protocol eliminates the need to infuse cryopreserved, just thawed cells which may reduce the immune modulatory activity. Moreover, using (IFNγ) as a prototypic cytokine, we demonstrate the feasibility of priming the cells with any biologic agent. We then characterized MSCs and IFNγ primed MSCs prepared with our protocol, by karyotype, in vitro potential for malignant transformation, biodistribution, effect on engraftment of transplanted hematopoietic cells, and in vivo toxicity in immune deficient mice including a complete post-mortem examination. We found no evidence of toxicity attributable to the MSC or IFNγ primed MSCs. Our data suggest that the clinical risk of infusing MSCs or IFNγ primed MSCs produced by our two-step protocol is not greater than MSCs currently in practice. While actual proof of safety requires phase I clinical trials, our data support the use of either cell product in new clinical studies.
Digital affordances, spatial affordances, and the genesis of entrepreneurial ecosystems
Authors: Autio Erkko , Nambisan Satish , Thomas Llewellyn D. W. , Wright Mike
Published: September 2017

Research Summary: Entrepreneurial ecosystems command increasing attention from policy makers, academics, and practitioners, yet the phenomenon itself remains under‐theorized. Specifically, the conceptual similarities and differences of entrepreneurial ecosystems relative to, for instance, clusters, “knowledge clusters,” regional systems of innovation, and “innovative milieus” remain unclear. Drawing on research on industrial districts and agglomerations, clusters, and systems of innovation, we suggest that entrepreneurial ecosystems differ from traditional clusters by their emphasis on the exploitation of digital affordances; by their organization around entrepreneurial opportunity discovery and pursuit; by their emphasis on business model innovation; by voluntary horizontal knowledge spillovers; and by cluster‐external locus of entrepreneurial opportunities. We highlight how these distinctive characteristics set entrepreneurial ecosystems apart from other cluster types, propose a structural model of entrepreneurial ecosystems, summarize the articles in this special issue, and suggest promising avenues for future research.

Managerial Summary: Entrepreneurial ecosystems command increasing attention from policy makers, academics, and practitioners. We suggest that entrepreneurial ecosystems differ from traditional clusters by their emphasis on the exploitation of digital affordances; by their organization around entrepreneurial opportunity discovery and pursuit; by their emphasis on business model innovation; by voluntary horizontal knowledge spillovers; and by cluster‐external locus of entrepreneurial opportunities. We highlight how these distinctive characteristics set entrepreneurial ecosystems apart from regional cluster phenomena discussed in received economic geography and innovation literatures. We suggest policy makers need to adopt novel approaches to stimulate entrepreneurial ecosystems that differ from those in place to develop industrial clusters or support already established small‐ and medium‐sized companies.
Fire in the belly? Employee motives and innovative performance in start‐ups versus established firms
Authors: Sauermann Henry
Published: September 2017

Research Summary: We examine whether start‐ups attract employees with different pecuniary and non‐pecuniary motives than small or large established firms. We then explore whether such differences in employee motives may lead to differences in innovative performance across firm types. Using data on more than 10,000 U.S. R&D employees, we find that start‐up employees (“joiners”) place lower importance on job security and salary but greater importance on independence and responsibility. Start‐up employees have higher patent output than employees in small and large established firms, and this difference is partly mediated by employee motives—especially joiners’ greater willingness to bear risk. We discuss implications for research as well as for managers and policy makers concerned with the supply of human capital to entrepreneurship and innovation.

Managerial Summary: Start‐ups and established firms play different roles in the economy and differ with respect to their organizational features. Recent research has started to also explore differences in their human capital. While prior work focuses on employees’ skills and experience, we broaden the notion of human capital to include motivational characteristics. We find that start‐up employees differ from those working in established firms with respect to their motives, most notably a weaker concern with job security. Moreover, such differences can partly explain higher innovative performance in start‐ups. Our findings suggest that founders may derive significant benefits from hiring “joiners” with entrepreneurial motives. Our findings also have implications for corporate managers who seek to acquire start‐ups or who consider creating entrepreneurial units that replicate features of young and small organizations.
Resource orchestration in start‐ups: Synchronizing human capital investment, leveraging strategy, and founder start‐up experience
Authors: Symeonidou Noni , Nicolaou Nicos
Published: September 2017

Research Summary: We examine the performance effects of resource orchestration in start‐ups by investigating three key contingencies of resource orchestration: human capital (HC) investment relative to rivals, leveraging strategy, and founder start‐up experience. We find that deviating from rivals' resource investments (either above or below the industry mean) negatively affects performance, while conforming to the norms set by rivals positively affects performance. However, we also find that a higher investment in HC relative to rivals is less detrimental when aligned with a leveraging strategy focused on innovation. In addition, we find evidence that this relationship is conditioned by the entrepreneurial experience of the founders themselves.

Managerial Summary: To create value, entrepreneurs need to assemble and manage various resources and capabilities. We explain how entrepreneurs can manage their resources to achieve higher performance. Using a sample of U.S. start‐ups, we find that deviations in human capital (HC) investments relative to rivals (either below or above) harm the performance of start‐ups. However, we also find that a higher investment in HC relative to rivals is less detrimental when the start‐up is focused on innovation. In addition, we find that experienced founders benefit from actively orchestrating HC investments relative to rivals with a strategy focused on innovation.
Prediction and control: An agent‐based simulation of search processes in the entrepreneurial problem space
Authors: Mauer René , Wuebker Robert , Schlüter Jan , Brettel Malte
Published: September 2017

Research Summary: This study seeks to understand the boundary conditions and successful application of search processes in the entrepreneurial problem space. To this end, we employ an agent‐based simulation approach to formally investigate the influence of environmental isotropy, unpredictability, and goal ambiguity on two distinct search processes, one prediction‐based and one control‐based. Specifically, we investigate the performance of effectuation as an example of non‐predictive, control‐based search and causation as an example of prediction‐based search. Results enhance theory by revealing a more nuanced relationship between the environment and entrepreneurial search than previous conceptual and empirical work has suggested.

Managerial Summary: Historically, entrepreneurship research has tended to view the external environment as given. The guidance for entrepreneurs given an immutable landscape sits on a continuum between “learn to plan better” and “learn to react faster.” These two approaches differ only in their suggestions about what entrepreneurs should do assuming the environment is given. A growing body of theoretical work questions this environment‐as‐given assumption and suggests an alternative entrepreneurial search process that seeks active control of environmental elements. To understand the successful applications as well as limitations of these entrepreneurial search processes, this study runs a simulation in which agents engage in different search processes. Practitioners receive more realistic guidance on how search for value needs a match between the idea, the context, and the search process.
Entrepreneurship in digital platforms: A network‐centric view
Authors: Srinivasan Arati , Venkatraman N.
Published: September 2017

Research summary

Research on entrepreneurship has focused primarily on the individual characteristics of founders in driving the success of new ventures offering stand‐alone products and/or services. In recent years, we have seen an increase in entrepreneurship in digital platforms—where success requires positioning products and services within dynamic digital networks that depict complex connections among platforms, complementary modules, and consumers. This article introduces key elements of a theory for settings where entrepreneurship success is intricately connected to the moves of other entrepreneurs and coordinated within and across platforms. We introduce a network‐centric view to understand how entrepreneurs occupying the role of third‐party developers support digital platforms by their choices to link to them. Furthermore, we develop propositions reflecting a dynamic perspective representing two key stages of competition in digital platforms, initial launch, and scale‐up. We hope this work guides further theorizing and empirical research in digital platforms and entrepreneurship in general.

Managerial summary

Over the last decade, we have seen a rise in digital entrepreneurs who support platforms such as Apple iOS, Google's Android, Facebook, Twitter, and others. The success of platforms requires support from applications, and entrepreneurs in such settings play a critical role in making some platforms succeed relative to others. Our study provides insight into how digital entrepreneurs can orchestrate strategic moves that allow them to navigate the complex landscape of linking and adapting to different platforms and how these linkage choices can lead to entrepreneurial success.
Unlocking the value of real options: How firm‐specific learning conditions affect R&D investments under uncertainty
Authors: Ross Jan‐Michael , Fisch Jan H. , Varga Emanuel
Published: September 2017

Research Summary

Why do some firms increase R&D investments in the face of uncertainty, while others do not? Contrary to common wisdom, this study posits that uncertainty prompts firms to invest in R&D. The value to invest under uncertainty is, however, bounded by a firm's learning conditions (i.e., human capital, relatedness of innovation activities, and industry maturity). An empirical test on a cross‐industry panel of 551 business divisions of manufacturing firms reveals how organization‐environment interactions determine the firm‐specific value to invest in learning prior to full‐scale commercialization. The insights help to bridge real options theory and the learning literature.

Managerial Summary

Uncertainty about the market environment makes investment decisions in R&D and the commercialization of new products a challenge: should firms “wait and see” until uncertainty resolves to avoid the risk of betting on the wrong product or commit further resources regardless? Our analysis suggests that manufacturing firms often take a mixed approach (“act and see”). While deferring investments in the commercialization of new products, they undertake further R&D to inform decision making by insights that would otherwise be unavailable. However, we find that the benefit of such practice depends on the learning conditions of the individual firm. What is risky for firms with disadvantages in human capital and technology development is value enhancing for firms with good foundations for learning through R&D.
Supporting girls’ and boys’ engagement in math and science learning: A mixed methods study
Authors: Fredricks Jennifer A. , Hofkens Tara , Wang Ming‐Te , Mortenson Elizabeth , Scott Paul
Published: September 2017

This study uses a mixed method sequential exploratory design to examine motivational and contextual influences on boys’ and girls’ engagement in math and science, paying particular attention to similarities and differences in the patterns by gender. First, interviews were conducted with 38 middle and high school students who varied in their level of math and science engagement about their perceptions of the motivational and contextual factors influencing their level of engagement. Both boys and girls discussed how their engagement was higher in classrooms with more student‐centered instructional practices and in classrooms with highly engaged peers. Girls were more likely to discuss teacher support and personally relevant instruction as being important to their engagement in math and science. In contrast, boys reported being more engaged in math and science when they were interested in pursuing a STEM‐related career. From these interviews, we identified factors that students described as important to their engagement and tested whether these factors were statistically significant in a socioeconomic and racially diverse sample of 3,833 middle and high school students. Specifically, we tested the associations between adolescents’ motivational beliefs (e.g., utility value, attainment value, and expectancy beliefs), social support from teachers and peers, and student‐centered and relevant instructional practices with engagement (e.g., cognitive, behavioral, emotional, and social) in math and science, paying particular attention to main effects and gender as a moderator. In the majority of the models, the motivational and contextual factors were significantly related to engagement and had comparable effects for girls and boys. We documented a few significant interactions by gender that tended to mirror the patterns found in the qualitative interviews. Implications of these findings for developing interventions to increase girls’ participation in math and science are discussed. © 2017 Wiley Periodicals, Inc. J Res Sci Teach 55: 271–298, 2018