bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteopathic Manipulative Therapy in Patients With Chronic Tension-Type Headache: A Pilot Study
Authors: Deodato Manuela , Guolo Franco , Monticco Antonella , Fornari Mauro , Manganotti Paolo , Granato Antonio
Published: August 2019

Context

Nonpharmacologic treatment, such as osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) may be a beneficial complementary treatment for tension-type headache. However, to the authors’ knowledge, the benefit of OMTh in the management of tension-type headache has not been explored, especially chronic tension-type headache (CTTH).

Objective

To investigate the effectiveness of OMTh compared with traditional treatment in reducing pain intensity, frequency, and duration of CTTH, and to evaluate the objective postural measurement of the forward head posture (FHP) as an integral parameter in the assessment of the effects of OMTh and traditional management of CTTH.

Methods

Patients with CTTH were registered at the Headache Centre of Trieste in Italy. At the time of the study, none of the patients had been taking any headache prophylaxis in the past 3 months. A 3-month baseline period was recorded by all patients with an ad hoc diary. Patients were randomly placed in the test or control group using a simple randomization program in Excel (Microsoft). Patients in the OMTh group underwent a 3-month period of OMTh, and patients in the control group were treated with amitriptyline. Pain intensity, frequency, and duration of headaches, as well as FHP were analyzed.

Results

The study enrolled 10 patients (mean [SD] age, 42.6 [15.2] years) in the OMTh group and 10 patients (51.4 [17.3] years) in the control group. The final assessment of OMTh patients showed statistically significant changes in all headache parameters: pain intensity decreased from a mean (SD) score of 4.9 (1.4) to 3.1 (1.1) (P=.002); frequency decreased from 19.8 (6) to 8.3 (6.2) days per month (P=.002); and the duration of headaches decreased from 10 (4.2) to 6 (3) hours (P=.01). Significant improvement of all parameters was found in the control group as well: pain intensity decreased from a mean (SD) score of 5.9 (0.7) to 4.2 (1.75) (P=.03); frequency decreased from 23.4 (7.2) to 7.4 (8.7) days per month (P=.003); and duration decreased from 7.8 (2.9) to 3.6 (2.1) hours (P=.002). Forward head posture significantly improved in OMTh patients (P=.003).

Conclusions

Our data suggested that OMTh may be an effective treatment to improve headaches in patients with CTTH. Our results also suggest that OMTh may reduce FHP.
Citation.js: a format-independent, modular bibliography tool for the browser and command line
Authors: Willighagen Lars G.
Published: August 2019

Background

Given the vast number of standards and formats for bibliographical data, any program working with bibliographies and citations has to be able to interpret such data. This paper describes the development of Citation.js (https://citation.js.org/), a tool to parse and format according to those standards. The program follows modern guidelines for software in general and JavaScript in specific, such as version control, source code analysis, integration testing and semantic versioning.

Results

The result is an extensible tool that has already seen adaption in a variety of sources and use cases: as part of a server-side page generator of a publishing platform, as part of a local extensible document generator, and as part of an in-browser converter of extracted references. Use cases range from transforming a list of DOIs or Wikidata identifiers into a BibTeX file on the command line, to displaying RIS references on a webpage with added Altmetric badges to generating ”How to cite this” sections on a blog. The accuracy of conversions is currently 27% for properties and 60% for types on average and a typical initialization takes 120 ms in browsers and 1 s with Node.js on the command line.

Conclusions

Citation.js is a library supporting various formats of bibliographic information in a broad selection of use cases and environments. Given the support for plugins, more formats can be added with relative ease.
Phosphorylation/dephosphorylation response to light stimuli of Symbiodinium proteins: specific light-induced dephosphorylation of an HSP-like 75 kDa protein from S. microadriaticum
Authors: Castillo-Medina Raúl E. , Islas-Flores Tania , Villanueva Marco A.
Published: August 2019

Background

Some genera of the family Symbiodiniaceae establish mutualistic endosymbioses with various marine invertebrates, with coral being the most important ecologically. Little is known about the biochemical communication of this association and the perception and translation of signals from the environment in the symbiont. However, specific phosphorylation/dephosphorylation processes are fundamental for the transmission of external signals to activate physiological responses. In this work, we searched phosphorylatable proteins in amino acids of Ser, Thr and Tyr from three species of the family Symbiodiniaceae, Symbiodinium kawagutii, Symbiodinium sp. Mf11 and Symbiodinium microadriaticum.

Methods

We used specific antibodies to the phosphorylated aminoacids pSer, pThr and pTyr to identify proteins harboring them in total extracts from three species of Symbiodinium in culture. Extractions were carried out on logarithmic phase growing cultures under a 12 h light/dark photoperiod. Various light/dark, nutritional and other stimuli were applied to the cultures prior to the extractions, and proteins were subjected to SDS-PAGE and western immunoblotting. Partial peptide sequencing was carried out by MALDI-TOF on specific protein spots separated by 2D electrophoresis.

Results

At 4 h of the light cycle, several Thr-phosphorylated proteins were consistently detected in the three species suggesting a genus-dependent expression; however, most Ser- and Tyr-phosphorylated proteins were species-specific. Analysis of protein extracts of S. microadriaticum cultures demonstrated that the level of phosphorylation of two Thr-phosphorylated proteins with molecular weights of 43 and 75 kDa, responded inversely to a light stimulus. The 43 kDa protein, originally weakly Thr-phosphorylated when the cells were previously adapted to their 12 h dark cycle, underwent an increase in Thr phosphorylation when stimulated for 30 min with light. On the other hand, the 75 kDa protein, which was significantly Thr-phosphorylated in the dark, underwent dephosphorylation in Thr after 30 min of the light stimulus. The phosphorylation response of the 43 kDa protein only occurred in S. microadriaticum, whereas the dephosphorylation of the 75 kDa protein occurred in the three species studied suggesting a general response. The 75 kDa protein was separated on 2D gels as two isoforms and the sequenced spots corresponded to a BiP-like protein of the HSP70 protein family. The presence of differential phosphorylations on these proteins after a light stimulus imply important light-regulated physiological processes in these organisms.
An enigmatic decoupling between heat stress and coral bleaching on the Great Barrier Reef
Authors: DeCarlo Thomas M. , Harrison Hugo B.
Published: August 2019

Ocean warming threatens the functioning of coral reef ecosystems by inducing mass coral bleaching and mortality events. The link between temperature and coral bleaching is now well-established based on observations that mass bleaching events usually occur when seawater temperatures are anomalously high. However, times of high heat stress but without coral bleaching are equally important because they can inform an understanding of factors that regulate temperature-induced bleaching. Here, we investigate the absence of mass coral bleaching on the Great Barrier Reef (GBR) during austral summer 2004. Using four gridded sea surface temperature data products, validated with in situ temperature loggers, we demonstrate that the summer of 2004 was among the warmest summers of the satellite era (1982–2017) on the GBR. At least half of the GBR experienced temperatures that were high enough to initiate bleaching in other years, yet mass bleaching was not reported during 2004. The absence of bleaching is not fully explained by wind speed or cloud cover. Rather, 2004 is clearly differentiated from bleaching years by the slow speed of the East Australian Current (EAC) offshore of the GBR. An anomalously slow EAC during summer 2004 may have dampened the upwelling of nutrient-rich waters onto the GBR shelf, potentially mitigating bleaching due to the lower susceptibility of corals to heat stress in low-nutrient conditions. Although other factors such as irradiance or acclimatization may have played a role in the absence of mass bleaching, 2004 remains a key case study for demonstrating the dynamic nature of coral responses to marine heatwaves.
Compras Sustentáveis: Proposta de Intervenção para as Compras Públicas Do IFPB – Campus Campina Grande
Authors: Cunha Silvan Freire , Araújo Maria Arlete Duarte
Published: August 2019

Essa proposta de intervenção objetivou construir um modelo de compras para o IFPB – Campus Campina Grande, em consonância com a legislação ambiental vigente e com os pressupostos da sustentabilidade e proteção ao meio ambiente.  Para construir um modelo de licitações sustentáveis adequado à realidade do IFPB – Campus Campina Grande, avaliou-se uma série de modelos implementados por instituições públicas federais e outros sugeridos por associações dedicadas à temática, além de uma ampla pesquisa na legislação federal que trata de licitações públicas. Como resultados, foram propostos a inclusão de critérios de sustentabilidade nos processos licitatórios, alterações nos editais licitatórios para adaptá-los à legislação ambiental, normas de implementação e métodos de avaliação dos resultados a serem alcançados para que as correções necessárias sejam efetuadas. Sugeriu-se a adoção de um modelo de edital licitatórios com critérios de sustentabilidade; criação de uma Comissão Gestora para o Plano de Gestão de Logística Sustentável; uma nova política de compras na instituição a partir de uma nova postura dos requisitantes; boa parte dos itens solicitados após as orientações, passaram a ser descritos com algumas características sustentáveis.
Cationic Photopolymerization by Polymeric Triphenyl Phosphonium Salts
Authors: Abu-Abdoun Ideisan I.
Published: August 2019

Phenacyl triphenylphosphonium and p-nitrobenzyl triphenylphosphonium polymer bound salts with SbF6- counter ions, have been synthesized and examined as polymeric photoinitiators for the cationic photopolymerization of epoxide monomers such as cyclohexene oxide and vinyl monomers such as N-vinyl carbazole and p-methyl styrene. The polymeric phosphonium salts utilized as photocatalysts and were found to be easy to handle and stable when stored far from normal light. Reaction of the nonpolymerizable epoxide compound trans-stilbene oxide with the polymeric phenacyl phosphonium was investigated in dichloromethane solvent and found to gives diphenyl acetaldehyde.
The Biosynthesis of Glucosinolates: Insights, Inconsistencies, and Unknowns
Authors: Bell Luke
Published: August 2019

Glucosinolates (GSLs) and their hydrolysis products (GHPs) are of great interest within the scientific community. Isothiocyanates (ITCs) are one type of hydrolysis product that have efficacy against some forms of cancer and prevention of some neurodegenerative disorders. They can also have potent effects upon pests and diseases of crops and give rise to the characteristic tastes and flavours of many commonly consumed Brassicales crops. The genetic mechanisms underlying GSL biosynthesis and regulation of GHPs are well elucidated in the model organismArabidopsis thaliana, and research over the last fifteen years has also greatly expanded knowledge withinBrassicaspp. There are, of course, many hundreds of GSL‐producing species within the Brassicales order, with potentially very different and/or advanced mechanisms of GSL biosynthesis, metabolism, and catabolism. This article summarises the current understanding of GSL biosynthesis and highlights areas of exploration beyond the ‘ArabidopsisandBrassicabubble’ of GSL research. Novel GSLs, and the gene encoding proteins that regulate their biosynthetic pathways, could greatly enhance our knowledge of Brassicales phytochemistry, evolution, and natural history if given more attention.
Mass Transfer and Reaction Kinetic Enhanced Electrode for High‐Performance Aqueous Flow Batteries
Authors: Mukhopadhyay Alolika , Yang Yang , Li Yifan , Chen Yong , Li Hongyan , Natan Avi , Liu Yuanyue , Cao Daxian , Zhu Hongli
Published: August 2019

A scalable and efficient process to modify electrodes with enhanced mass transfer and reaction kinetics is critical for redox flow batteries (RFBs). For the first time, this work introduces electrochemical exfoliation as a surface modification method of graphite felt (GF) to enhance the mass transfer and reaction kinetics in RFBs. Anion intercalation and subsequent gas evolutions at room temperature for one minute expand the graphite layers that increase the electrode surface area. Meanwhile, sufficient oxygen functional groups are introduced to the electrode, resulting in enhanced reaction kinetics and improved hydrophilicity. Further, spin‐polarized density functional theory is employed to reveal the role of oxygen functional groups in accelerating the vanadium redox reaction. Benefitting from sufficient oxygen groups, larger surface area, and superior wettability, the as‐prepared exfoliated GF (E‐GF) shows exceptional electrocatalytic activity with minimized overpotential, higher volumetric capacity, and improved energy efficiency. The redox flow battery assembled with the E‐GF electrode delivers voltage and energy efficiencies of 89.72% and 86.41% at the current density of 100 mA cm−2, respectively. Remarkably, compared to the traditional GF treatment method, the elimination of the high temperature and long‐time treatment processes make this approach much more energy and time efficient, scalable, and affordable for large‐scale manufacturing.
Tailoring Carbon Nanotube Microsphere Architectures with Controlled Porosity
Authors: Zhang Zishuai , Sadeghi Mohammad Amin , Jervis Rhodri , Ye Siyu , Gostick Jeff T. , Barralet Jake E , Merle Geraldine
Published: August 2019

Nanomaterials are at the core of fuel cell electrodes, providing high‐area catalytic, proton, and electron conducting surfaces, traditionally on carbon black supports. Other carbons, e.g., carbon nanotubes (CNTs) and graphene are less prone to oxidation; however, their handling is not trivial due to health risks associated with their size. Assembling them into microscale structures without jeopardizing their performance is ideal, but there are mass transfer limitations as thickness increases. In this work, a soluble acicular calcium carbonate (aragonite) is used as a porogen to create connected porosity in microspheres. Increasing macroporosity has a considerable positive impact on the mass transfer process. The experimental manipulation of porosity of the microspheres is combined with pore network modeling to better understand how pore distribution throughout the whole microsphere can optimize platinum utilization decorated onto the CNTs. Oxygen reduction reaction (ORR) activity is compared with the prepared composite materials and a commercial Pt/C catalyst for 4 weeks. The composite materials exhibit a highly interconnected network resulting in a 3.4 times higher ORR activity (at 0.9 V vs reversible hydrogen electrode) than that of the nanoporous spheres with no macroporosity.
Fused Cyclopentadithienothiophene Acceptor Enables Ultrahigh Short‐Circuit Current and High Efficiency >11% in As‐Cast Organic Solar Cells
Authors: He Qiao , Shahid Munazza , Wu Jiaying , Jiao Xuechen , Eisner Flurin D. , Hodsden Thomas , Fei Zhuping , Anthopoulos Thomas D. , McNeill Christopher R. , Durrant James R. , Heeney Martin
Published: August 2019

A new method to synthesize an electron‐rich building block cyclopentadithienothiophene (9H‐thieno‐[3,2‐b]thieno[2″,3″:4′,5′]thieno[2′,3′:3,4]cyclopenta[1,2‐d]thiophene, CDTT) via a facile aromatic extension strategy is reported. By combining CDTT with 1,1‐dicyanomethylene‐3‐indanone endgroups, a promising nonfullerene small molecule acceptor (CDTTIC) is prepared. As‐cast, single‐junction nonfullerene organic solar cells based on PFBDB‐T: CDTTIC blends exhibit very high short‐circuit currents up to 26.2 mA cm−2 in combination with power conversion efficiencies over 11% without any additional processing treatments. The high photocurrent results from the near‐infrared absorption of the CDTTIC acceptor and the well‐intermixed blend morphology of polymer donor PFBDB‐T and CDTTIC. This work demonstrates a useful fused ring extension strategy and promising solar cell results, indicating the great potential of the CDTT derivatives as electron‐rich building blocks for constructing high‐performance small molecule acceptors in organic solar cells.
Synthesis of Joint‐Welded Carbon Nanotube Foam @ Ni(OH)2 Nanosheet‐Based Core–Shell 3D Architecture for Freestanding Flexible Electrode for Supercapacitor Applications
Authors: Anwer Shoaib , Bin Ari Ahmed , Bharath G. , Cao Pei , Patole Shashikant P. , Luo Shaohong , Masood Hafiz Tariq , Cantwell Wesley J. , Liao Kin , Li Qingwen , Zheng Lianxi
Published: August 2019

Freestanding electrode 3D architectures, based on Ni(OH)2 nanosheets grown on a joint‐welded carbon nanotube foam network, are introduced via a unique and facile chemical bath synthesis strategy. As a result of the unique 3D core configuration of nanotubes and the nanostructural shell design of Ni(OH)2 nanosheets, the prepared electrode displays an excellent electrochemical performance. The electrode shows an outstanding specific capacitance of 1272 F g−1 at a scan rate of 2 A g−1, and it even retained a value of 517 F g−1 at a scan rate of 20 A g−1. The excellent electrochemical performance is due to the highly conductive nanotube network and the unique nanostructure of Ni(OH)2 nanosheets, which promote the ion transport in fast speed, while facilitate the charge storage via redox reactions in nanosheets. The large specific capacitance and superior rate performance of core–shell Ni nanosheets, combined with the elasticity of the welded‐nanotube network, render these 3D architectures as promising candidates of freestanding electrodes for high‐performance flexible supercapacitor applications.
3D Printing Ionogel Auxetic Frameworks for Stretchable Sensors
Authors: Wong Jitkanya , Gong Alex T. , Defnet Peter A. , Meabe Leire , Beauchamp Bruce , Sweet Robert M. , Sardon Haritz , Cobb Corie L. , Nelson Alshakim
Published: August 2019

Ionogels are an emerging class of soft materials that exhibit ionic conductivity and thermal stability without the need to replenish ions or the addition of conductive particle fillers. An ionogel ink is reported for direct‐write 3D printing to fabricate conductive structures that can vary in the printed object geometries. This approach relies on a shear‐thinning ionogel ink that can be extruded to afford self‐supporting constructs. After a brief UV cure, the printed construct is transformed into a mechanically tough, transparent structure that is ionically conductive. Upon application of stretching and twisting loads, the 3D‐printed objects exhibit detectable changes in conductivity. To demonstrate the versatility of rapid prototyping with the ionogel inks, an auxetic structure is 3D printed and tested as a strain sensor. The printed auxetic structure exhibits an electrical response to strain, but also demonstrates increased extensibility and operational range in comparison to a casted bulk film with the same outer dimensions.
Lenz–Majewski syndrome in a patient from Egypt
Authors: Afifi Hanan H. , Abdel‐Hamid Mohamed S. , Mehrez Mennat I. , El‐Kamah Ghada , Abdel‐Salam Ghada M. H.
Published: August 2019

Lenz–Majewski syndrome (LMS) is an extremely rare type of cutis laxa caused by dominant mutations in PTDSS1 gene. We report an Egyptian patient who presented with cutis laxa, brachydactyly, and progeroid features. LMS syndrome was suspected and a previously reported de novo heterozygous missense mutation (c.284G > T, p.R95L) in PTDSS1 was identified. To the best of our knowledge, nine molecularly proven patients with LMS from different ethnicities have been reported. Our patient is the first report from the Middle East and the tenth molecularly proven patient reported to date. His clinical features were in accordance with LMS syndrome. In addition, his hands X‐ray images showed hypoplastic or absent middle and proximal phalanges but sparing the thumbs. This hand patterning was similarly observed before. Further, he had relatively large and convex fingernails. Our report highlights this unique hand patterning and suggests these signs should be considered among the diagnostic criteria of LMS. Further reports of patients with PTDSS1 mutations are necessary to further elucidate the detailed clinical features of LMS syndrome.
Quantum‐Memory‐Assisted Entropic Uncertainty Relations
Authors: Wang Dong , Ming Fei , Hu Ming‐Liang , Ye Liu
Published: August 2019

Uncertainty relations take a crucial and fundamental part in the frame of quantum theory, and are bringing on many marvelous applications in the emerging field of quantum information sciences. Especially, as entropy is imposed into the uncertainty principle, entropy‐based uncertainty relations lead to a number of applications including quantum key distribution, entanglement witness, quantum steering, quantum metrology, and quantum teleportation. Herein, the history of the development of the uncertainty relations is discussed, especially focusing on the recent progress with regard to quantum‐memory‐assisted entropic uncertainty relations and dynamical characteristics of the measured uncertainty in some explicit physical systems. The aims are to help deepen the understanding of entropic uncertainty relations and prompt further explorations for versatile applications of the relations on achieving practical quantum tasks.
Enantiospecific Desorption Triggered by Circularly Polarized Light
Authors: Mortaheb Farinaz , Oberhofer Katrin , Riemensberger Johann , Ristow Florian , Kienberger Reinhard , Heiz Ulrich , Iglev Hristo , Kartouzian Aras
Published: August 2019

The interest in enantioseparation and enantiopurification of chiral molecules has been drastically increasing over the past decades, since these are important steps in various disciplines such as pharmaceutical industry, asymmetric catalysis, and chiral sensing. By exposing racemic samples of BINOL (1,1′‐bi‐2‐naphthol) coated onto achiral glass substrates to circularly polarized light, we unambiguously demonstrate that by controlling the handedness of circularly polarized light, preferential desorption of enantiomers can be achieved. There are currently no mechanisms known that would describe this phenomenon. Our observation together with a simplified phenomenological model suggests that the process of laser desorption needs to be further developed and the contribution of quantum mechanical processes should be revisited to account for these data. Asymmetric laser desorption provides us with a contamination‐free technique for the enantioenrichment of chiral compounds.
Switchable Solvatochromic Probes for Live‐Cell Super‐resolution Imaging of Plasma Membrane Organization
Authors: Danylchuk Dmytro I. , Moon Seonah , Xu Ke , Klymchenko Andrey S.
Published: August 2019

Visualization of the nanoscale organization of cell membranes remains challenging because of the lack of appropriate fluorescent probes. Herein, we introduce a new design concept for super‐resolution microscopy probes that combines specific membrane targeting, on/off switching, and environment sensing functions. A functionalization strategy for solvatochromic dye Nile Red that improves its photostability is presented. The dye is grafted to a newly developed membrane‐targeting moiety composed of a sulfonate group and an alkyl chain of varied lengths. While the long‐chain probe with strong membrane binding, NR12A, is suitable for conventional microscopy, the short‐chain probe NR4A, owing to the reversible binding, enables first nanoscale cartography of the lipid order exclusively at the surface of live cells. The latter probe reveals the presence of nanoscopic protrusions and invaginations of lower lipid order in plasma membranes, suggesting a subtle connection between membrane morphology and lipid organization.
Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis
Authors: Stellingwerf M E , Sahami S , Winter D C , Martin S T , D'Haens G R , Cullen G , Doherty G A , Mulcahy H , Bemelman W A , Buskens C J
Published: August 2019

Introduction

Appendicectomy may reduce relapses and need for medication in patients with ulcerative colitis, but long-term prospective data are lacking. This study aimed to analyse the effect of appendicectomy in patients with refractory ulcerative colitis.

Methods

In this prospective multicentre cohort series, all consecutive patients with refractory ulcerative colitis referred for proctocolectomy between November 2012 and June 2015 were counselled to undergo laparoscopic appendicectomy instead. The primary endpoint was clinical response (reduction of at least 3 points in the partial Mayo score) at 12 months and long-term follow-up. Secondary endpoints included endoscopic remission (endoscopic Mayo score of 1 or less), failure (colectomy or start of experimental medication), and changes in Inflammatory Bowel Disease Questionnaire (IBDQ) (range 32–224), EQ-5D™ and EORTC-QLQ-C30-QL scores.

Results

A total of 28 patients (13 women; median age 40·5 years) underwent appendicectomy. The mean baseline IBDQ score was 127·0, the EQ-5D™ score was 0·65, and the EORTC-QLQ-C30-QL score was 41·1. At 12 months, 13 patients had a clinical response, five were in endoscopic remission, and nine required a colectomy (6 patients) or started new experimental medical therapy (3). IBDQ, EQ-5D™ and EORTC-QLQ-C30-QL scores improved to 167·1 (P < 0·001), 0·80 (P = 0·003) and 61·0 (P < 0·001) respectively. After a median of 3·7 (range 2·3–5·2) years, a further four patients required a colectomy (2) or new experimental medical therapy (2). Thirteen patients had a clinical response and seven were in endoscopic remission. The improvement in IBDQ, EQ-5D™ and the EORTC-QLQ-C30-QL scores remained stable over time.

Conclusion

Appendicectomy resulted in a clinical response in nearly half of patients with refractory ulcerative colitis and a substantial proportion were in endoscopic remission. Elective appendicectomy should be considered before proctocolectomy in patients with therapy-refractory ulcerative colitis.
Research waste in surgical randomized controlled trials
Authors: Chapman S J , Aldaffaa M , Downey C L , Jayne D G
Published: August 2019

Background

Research waste is a major challenge for evidence-based medicine. It implicates misused resources and increased risks for research participants. The aim of this study was to quantify constituent components of waste in surgical RCTs and explore targets for improvement.

Methods

ClinicalTrials.gov was searched for RCTs registered between January 2011 and December 2012 using the keyword ‘surgery’. The primary outcome was research waste, defined as non-publication, inadequate reporting or presence of an avoidable design limitation. Serial systematic searches of PubMed and Scopus databases were performed to determine publication status. Adequacy of reporting was assessed using the CONSORT checklist. Avoidable design limitations were evaluated according to the presence of bias and/or the absence of a cited systematic review of the literature.

Results

Of 5617 registered RCTs, 304 met all eligibility criteria. Overall, 259 of 304 (85·2 per cent) demonstrated at least one feature of waste. Of these, 221 (72·7 per cent) were published in a peer-reviewed journal and 219 were accessible for full-text review. Only 73 of 131 (55·7 per cent) RCTs with a pharmacological intervention and 24 of 88 (27 per cent) with a non-pharmacological intervention were reported adequately, and 159 of 219 (72·6 per cent) demonstrated an avoidable design limitation. Multicentre (odds ratio 0·31, 95 per cent c.i. 0·11 to 0·88) and externally funded (OR 0·35, 0·15 to 0·82) RCTs were less associated with research waste.

Conclusion

This study identified a considerable burden of research waste in surgical RCTs. Future initiatives should target improvements in single-centre, poorly supported RCTs.
Development and Validation of an HPLC Method Using a Less Hazardous Mobile Phase for the Determination of some β‐Lactams
Authors: Pham Thuy‐Vy , Mai Xuan‐Lan , Le Thi‐Anh‐Tuyet , Lee Jae‐Yong , Lee Gunhee , Kim Dae‐Jung , Han Sang‐Beom , Kim Kyeong Ho
Published: August 2019

A simple, cost‐effective, and greener HPLC method was investigated to determine 14 β‐lactams. To achieve this, various strategies were implemented such as the use of an aqueous mobile phase, ionic liquids, or an alternative organic solvent. Preliminary experiments were conducted using “one‐factor‐at‐a‐time” to identify the significant factors affecting chromatographic performance. The experimental design (central composite design) was then applied to thoroughly examine the effects of the key factors and exploit them to achieve optimal HPLC condition. The developed method was less hazardous and improved the retention and peak shape, compared with other conventional methods. The optimized assay condition was validated according to the ICH guidelines and effectively applied for the quantification of some β‐lactams in various formulations. These results imply that this novel HPLC method can be employed for routine analyses of some β‐lactams in pure drug and commercial formulations.
Differences between male and female prostates in terms of physiology, sensitivity to chemicals and pathogenesis—A review in a rodent model
Authors: Sanches Bruno D. A. , Carvalho Hernandes F. , Maldarine Juliana S. , Biancardi Manoel F. , Santos Fernanda C. A. , Vilamaior Patricia S. L. , Taboga Sebastião R.
Published: August 2019

The prostate is a gland that is not exclusively present in males, being also found in females of several mammalian species, including humans. There is evidence that the prostate in both sexes is affected by the same pathologies such as prostatitis, benign alterations and even cancer. In view of the difficulties of manipulating the prostate gland, the Mongolian gerbil (Meriones unguiculatus), a rodent species with high incidence of functional prostates in females, is widely used in studies of the female prostate. However, despite knowing much about the similarities between the female and male prostate, little emphasis has been placed on the differences between them. This review investigates the intersex differences in prostate development, physiology and pathogenesis. The female prostate develops earlier than in males and studies indicate that it is more sensitive to oestrogens than the male prostate, as well as being more sensitive to exposure to xenoestrogens, such as Bisphenol A and methylparaben, with a higher susceptibility to benign lesions in the adult and senile prostate than in males. In addition, the female prostate is impacted by pregnancy and the oestrous cycle, and is also dependent on progesterone. The peculiarities of the female prostate raise concerns about the risk of it undergoing neglected changes as a result of environmental chemicals, since safe dosages are established exclusively for the male prostate.
Hashimoto's encephalopathy: Follow‐up data from neuropsychology, lumbar puncture, and FDG‐PET
Authors: Lagström Ronja Maria Birgitta , Østerbye Natascha Nellum , Henriksen Otto Mølby , Høgh Peter
Published: August 2019

Hashimoto's encephalopathy is a rare disease with nonspecific symptoms, associated with elevated levels of anti‐TPO and/or anti‐TG. It can be potentially fatal. However, it is responsive to steroid and treated in due time, it can be fully reversible.
Shape‐Controlled Synthesis of NiCo2O4‐rGO as Bifunctional Electrocatalyst for Zn‐Air Battery
Authors: Li Yao , Cheng Gao , Zhou Zihao , Liao Xiuhong , Han Shengbo , Ye Fei , Sun Ming , Yu Lin
Published: August 2019

The engineering of morphology and surface structure of electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is an effective strategy to improve their performance. Herein, we synthesized NiCo2O4 catalysts with different shape by controlling the reaction solvent and studied their morphology‐dependent ORR/OER activities by various characterizations and electrochemical measurements. The NiCo2O4 prepared using methanol as solvent displays three‐dimensional (3D)  hierarchical structure composed of interconnected nanosheets, and exhibits the best ORR/OER performance (a half‐wave potential of 0.78 V for ORR and an overpotential of 381 mV for OER). When used as catalyst for a rechargeable Zn‐air battery, it possesses a peak power density of 125.3 mW cm−2 with relatively superior durability.
Deracemization in a Complex Quaternary System with a Second‐Order Asymmetric Transformation by Using Phase Diagram Studies
Authors: Oketani Ryusei , Marin Francesco , Tinnemans Paul , Hoquante Marine , Laurent Anne , Brandel Clément , Cardinael Pascal , Meekes Hugo , Vlieg Elias , Geerts Yves , Coquerel Gérard
Published: August 2019

A productive deracemization process based on a quaternary phase diagram study of a naphthamide derivative is reported. New racemic compounds of an atropisomeric naphthamide derivative have been discovered, and a quaternary phase diagram has been constructed that indicated that four solids are stable in a methanol/H2O solution. Based on the results of a heterogeneous equilibria study showing the stable domain of the conglomerate, a second‐order asymmetric transformation was achieved with up to 97 % ee. Furthermore, this methodology showcases the chiral separation of a stable racemic compound forming system and does not suffer from any of the typical limitations of deracemization, although application is still limited to conglomerate‐forming systems. We anticipate that this present study will serve as a fundamental model for the design of sophisticated chiral separation processes.
Flexible NO2‐Functionalized N‐Heterocyclic Carbene Monolayers on Au (111) Surface
Authors: Dery Shahar , Kim Suhong , Tomaschun Gabriele , Haddad David , Cossaro Albano , Verdini Alberto , Floreano Luca , Klüner Thorsten , Toste F. Dean , Gross Elad
Published: August 2019

The formation of flexible self‐assembled monolayers (SAMs) in which an external trigger modifies the geometry of surface‐anchored molecules is essential for the development of functional materials with tunable properties. In this work, it is demonstrated that NO2‐functionalized N‐heterocyclic carbene molecules (NHCs), which were anchored on Au (111) surface, change their orientation from tilted into flat‐lying position following trigger‐induced reduction of their nitro groups. DFT calculations identified that the energetic driving force for reorientation was the lower steric hindrance and stronger interactions between the chemically reduced NHCs and the Au surface. The trigger‐induced changes in the NHCs′ anchoring geometry and chemical functionality modified the work function and the hydrophobicity of the NHC‐decorated Au surface, demonstrating the impact of a chemically tunable NHC‐based SAM on the properties of the metal surface.
Chiral Benzazaborole‐Catalyzed Regioselective Sulfonylation of Unprotected Carbohydrate Derivatives
Authors: Kuwano Satoru , Hosaka Yusei , Arai Takayoshi
Published: August 2019

Chiral benzazaborole‐catalyzed regioselective sulfonylations of unprotected carbohydrate derivatives have been developed. This methodology enables direct regioselective functionalization of the secondary OH group in carbohydrate in the presence of the primary OH group. By using the chiral organoboron catalysis, kinetic resolution of the carbohydrate derivatives was also achieved.
Peptide‐Driven Targeted Drug‐Delivery System Comprising Turn‐On Near‐Infrared Fluorescent Xanthene–Cyanine Reporter for Real‐Time Monitoring of Drug Release
Authors: Ebaston T. M. , Rozovsky Alex , Zaporozhets Alisa , Bazylevich Andrii , Tuchinsky Helena , Marks Vered , Gellerman Gary , Patsenker Leonid D.
Published: August 2019

Targeted drug delivery (TDD) is an efficient strategy for cancer treatment. However, the real‐time monitoring of drug delivery is still challenging because of a pronounced lack of TDD systems capable of providing a near‐infrared (NIR) fluorescence signal for the detection of drug‐release events. Herein, a new TDD system, comprising a turn‐on NIR fluorescent reporter attached to an anticancer drug and targeting peptide, is reported. This system provides both TDD and NIR fluorescence monitoring of drug‐release events in target tissue. In this TDD system, a new carboxy‐derivatized xanthene–cyanine (XCy) dye is attached to an anticancer drug, chlorambucil (CLB), through a hydrolytically cleavable ester linker and coupled to a targeting peptide, octreotide amide (OCTA), which is specific to somatostatin receptors SSTR‐2 and STTR‐5 overexpressed on many tumor cells. This OCTA‐G‐XCy‐CLB (G: γ‐aminobutyric acid) conjugate exhibits no detectable fluorescence, whereas, upon the hydrolytic cleavage of the ester linker, a bright NIR fluorescence appears at λ≈710 nm; this signals release of the drug. Real‐time TDD monitoring is demonstrated for the example of the human pancreatic cancer cell line overexpressing SSTR‐2 and STTR‐5, in comparison with the noncancerous Chinese hamster ovary cell line, which contains a reduced number of these receptors.
Prediagnosis aspirin use, DNA methylation, and mortality after breast cancer: A population‐based study
Authors: Wang Tengteng , McCullough Lauren E. , White Alexandra J. , Bradshaw Patrick T. , Xu Xinran , Cho Yoon Hee , Terry Mary Beth , Teitelbaum Susan L. , Neugut Alfred I. , Santella Regina M. , Chen Jia , Gammon Marilie D.
Published: August 2019

Background

The authors hypothesized that epigenetic changes may help to clarify the underlying biologic mechanism linking aspirin use to breast cancer prognosis. To the authors' knowledge, this is the first epidemiologic study to examine whether global methylation and/or tumor promoter methylation of breast cancer‐related genes interact with aspirin use to impact mortality after breast cancer.

Methods

Prediagnosis aspirin use was assessed through in‐person interviews within a population‐based cohort of 1508 women diagnosed with a first primary breast cancer in 1996 and 1997. Global methylation in peripheral blood was assessed by long interspersed elements‐1 (LINE‐1) and the luminometric methylation assay. Promoter methylation of 13 breast cancer‐related genes was measured in tumor by methylation‐specific polymerase chain reaction and the MethyLight assay. Vital status was determined by the National Death Index through December 31, 2014 (N = 202/476 breast cancer‐specific/all‐cause deaths identified among 1266 women with any methylation assessment and complete aspirin data). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs, and the likelihood ratio test was used to evaluate multiplicative interactions.

Results

All‐cause mortality was elevated among aspirin users who had methylated promotor of BRCA1 (HR, 1.67; 95% CI, 1.26‐2.22), but not among those with unmethylated promoter of BRCA1 (HR, 0.99; 95% CI, 0.67‐1.45; P for interaction ≤.05). Decreased breast cancer‐specific mortality was observed among aspirin users who had unmethylated promotor of BRCA1 and PR and global hypermethylation of LINE‐1 (HR, 0.60, 0.78, and 0.63, respectively; P for interaction ≤.05), although the 95% CIs included the null.

Conclusions

The current study suggests that the LINE‐1 global methylation and promoter methylation of BRCA1 and PR in tumor may interact with aspirin use to influence mortality after breast cancer.
Different routes of insulin administration do not influence serum free thiols in type 1 diabetes mellitus
Authors: van Dijk Peter R. , Waanders Femke , Logtenberg Susan J. J. , Groenier Klaas H. , Vriesendorp Titia M. , Kleefstra Nanne , van Goor Harry , Bilo Henk J. G.
Published: August 2019

Aims

Intraperitoneal (IP) insulin administration is a last‐resort treatment option for selected patients with type 1 diabetes mellitus (T1DM). As the IP route of insulin administration mimics the physiology more closely than the subcutaneous (SC) route, we hypothesized that IP insulin would result in less oxidative stress (expressed as systemic level of free sulphydryl (R‐SH) content) compared to SC insulin in subjects with T1DM.

Materials and methods

Prospective, observational case‐control study. Serum thiol measurements were performed at baseline and at 26 weeks in age‐ and gender‐matched patients with T1DM. Serum‐free thiols, compounds with a R‐SH group that are readily oxidized by reactive oxygen species, are considered to be a marker of systemic redox status.

Results

A total of 176 patients, 39 of which used IP and 141 SC insulin therapy were analysed. Mean baseline R‐SH concentration was 248 (31) μmol/L. In multivariable analysis, the route of insulin therapy had no impact on baseline R‐SH levels. The estimated geometric mean concentrations of R‐SH did not differ significantly between both groups: 264 (95% CI 257, 270) for the IP group and 258 (95% CI 254, 261) for the SC group with a difference of 6 (95% CI −2, 14) μmol/L.

Conclusions

Based on R‐SH as a marker of systemic oxidative stress, these findings demonstrate that the route of insulin administration, IP or SC, does not influence systemic redox status in patients with T1DM.
The role of TP53 in acute myeloid leukemia: Challenges and opportunities
Authors: Barbosa Karina , Li Sha , Adams Peter D. , Deshpande Aniruddha J.
Published: August 2019

The tumor suppressor gene TP53 is one of the most frequently mutated genes in human cancer. The central role of the TP53 protein in several fundamental processes such as cancer, aging, senescence, and DNA repair has ensured enormous attention. However, the role of TP53 in acute myeloid leukemia (AML) is enigmatic. Unlike many other human cancers, a vast majority of AMLs display no genomic TP53 alterations. There is now growing appreciation of the fact that the unaltered TP53 status of tumor cells can be exploited therapeutically. As most AMLs have an intact TP53 gene, its physiological tumor‐suppressive roles could be harnessed. Therefore, the use of pharmacological activators of the TP53 pathway may provide clinical benefit in AML. Conversely, even though the frequency of TP53 mutations in AML is substantially lower than in other human cancers, TP53 mutations are associated with chemoresistance and high risk of relapse. In patients with TP53 mutations, these alterations may lead to novel, selective vulnerabilities, creating opportunities for therapeutic targeting of TP53 mutant AML. The mutational status of TP53 therefore poses challenges and opportunities in terms of advancing effective treatment strategies in AML. An increasing armamentarium of small‐molecule activators of the TP53 pathway, and a growing understanding of molecular pathways triggered by mutant TP53 have accelerated efforts aimed at targeting TP53 function in AML. In combination with standard AML chemotherapy or emerging targeted therapies, pharmacological targeting of the TP53 pathway may provide therapeutic benefit in AML.
Classification of social anhedonia using temporal and spatial network features from a social cognition fMRI task
Authors: Krohne Laerke Gebser , Wang Yi , Hinrich Jesper L. , Moerup Morten , Chan Raymond C. K. , Madsen Kristoffer H.
Published: August 2019

Previous studies have suggested that the degree of social anhedonia reflects the vulnerability for developing schizophrenia. However, only few studies have investigated how functional network changes are related to social anhedonia. The aim of this fMRI study was to classify subjects according to their degree of social anhedonia using supervised machine learning. More specifically, we extracted both spatial and temporal network features during a social cognition task from 70 subjects, and used support vector machines for classification. Since impairment in social cognition is well established in schizophrenia‐spectrum disorders, the subjects performed a comic strip task designed to specifically probe theory of mind (ToM) and empathy processing. Features representing both temporal (time series) and network dynamics were extracted using task activation maps, seed region analysis, independent component analysis (ICA), and a newly developed multi‐subject archetypal analysis (MSAA), which here aimed to further bridge aspects of both seed region analysis and decomposition by incorporating a spotlight approach.We found significant classification of subjects with elevated levels of social anhedonia when using the times series extracted using MSAA, indicating that temporal dynamics carry important information for classification of social anhedonia. Interestingly, we found that the same time series yielded the highest classification performance in a task classification of the ToM condition. Finally, the spatial network corresponding to that time series included both prefrontal and temporal‐parietal regions as well as insula activity, which previously have been related schizotypy and the development of schizophrenia.
Treatment modality and outcomes in larynx cancer patients: A sex‐based evaluation
Authors: Li Hong , Li Eva Yujia , Kejner Alexandra Eva
Published: August 2019

Background

To evaluate the differences in treatment modality and outcomes between male and female patients with laryngeal squamous cell carcinoma (SCC) in the United States.

Methods

Data were extracted from the Surveillance, Epidemiology, and End Results Database for patients with laryngeal SCC (2004‐2013). Overall survival (OS), disease specific survival (DSS), and multivariate analyses were conducted.

Results

Among women, supraglottic cancers were the most prevalent (61.2%); whereas the majority of men developed glottic cancers (64.2%; P < .001). Women with T4 disease were more likely to undergo primary radiation (56.8% vs 45.3%; P < .001) and less likely to undergo open surgery were than men (37.1% vs 48.2%; P < .001). Women had significantly better OS in glottic and supraglottic cancers, and comparable survival in subglottic cancer. Sex remained an independent prognostic factor for both DSS and OS.

Conclusion

Sex is an independent prognostic factor for DSS and OS in patients with laryngeal SCC.
Facial features and recognition memory: Eye‐movement study on the encoding and retrieval of unfamiliar child faces in children and adults
Authors: Rollins Leslie , Bertero Erin , Hunter Laurie
Published: August 2019

This study examined eye movements to unfamiliar child faces as a function of memory in children and adults. Young adults (n = 30) and 7‐ to 11‐year‐old children (n = 30) performed a recognition memory task with neutral child faces. At encoding, fixating on internal features, especially the eye region, was associated with subsequently forgetting the face. During retrieval, children and adults fixated on internal features and the nose of correctly recognized faces more than novel faces. However, age‐related differences were present in fixations to individual facial features. Adults viewed the eye region of correctly recognized faces more than novel faces, whereas children's gaze behavior of the eye region did not differ as a function of viewing history. This finding suggests an increase in the reliance on the eye region, which provides critical information for social communication, for face recognition from middle childhood to young adulthood.

Highlights

Encoding of external features supports face recognition

Children and adults fixate less on external features of previously viewed than novel faces

Adults, but not children, view the eye region of previously viewed faces more than novel faces