bluuebunny/crossref_metadata_2025 huggingface dataset:
Cervical thyroid remnant consistent with papillary carcinoma as an incidental finding in a patient with benign total thyroidectomy ten years prior
Authors: Ruano Campos Adriana , Rivera Alonso Daniel , Ochagavía Cámara Santiago
Published: July 2019

Background: Differential diagnosis of a cervical lesion corresponding with papillary thyroid carcinoma (PTC) after benign total thyroidectomy can be a real challenge.
Methods: A cervical thyroid remnant compatible with papillary carcinoma was incidentally found ten years after total thyroidectomy for a non-functional multinodular goitre. Histological analysis of fine needle puncture aspiration (FNPA) was highly suggestive for PTC. Surgical excision of the cervical lesion was performed. Specimen study demonstrated a classic variant of PTC contacting a peripheral margin, applying ablative treatment with radioactive iodine postoperatively.
Results: The patient did not present signs of recurrence during follow-up. Small thyroid remnants after benign thyroidectomy are often left behind, although their risk of malignancy is exceptional.
Conclusions: It is important to individualize therapeutic approach when facing this rare entity. We decided to treat the patient by removing the lesion followed by ablation therapy with successful results.

PTC: Papillary thyroid carcinoma
FNPA: Fine needle puncture aspiration
THE IMPACT OF AUTHENTIC LEADERSHIP ON THE COMMITMENT OF EMPLOYEES IN TRAVEL AGENCIES IN THE REPUBLIC OF SERBIA
Authors: Dramićanin Sandra
Published: July 2019

Authentic leadership is the highest and most powerful level of leadership. An authentic leader is expected to create an atmosphere of security, loyalty and trust among members of the organization. Only under these circumstances can an individual and group within the organization progress. An authentic leader places his interest in the last place, and their environment and employees are motivated in the right way that what they know and love, can do in the best possible way. The purpose of the paper is to analyze the characteristics of the authentic leaders and their impact on the commitment of employees. The aim of the paper is to quantify the influence of authentic leaders on the commitment of employees in travel agencies. The results show that leaders' self-awareness, internalized moral and transparency directly affect the commitment of employees to travel agencies.
DIGITIZATION OF CULTURAL HERITAGE AS A POTENTIAL FOR INCREASING MUSEUM ATTENDANCE IN CENTRAL SERBIA
Authors: Radosavljević Zoran , Ljubisavljević Tijana
Published: July 2019

Serbian cultural institutions, including foundations and museums, are faced with various ongoing challenges. One of them is an increasing lack of interest in cultural events by cultural consumers. Each year, there is a significant decline in the number of cultural consumers interested in cultural and historical exhibitions and displays. The number of museum visitations in Central and Western Serbia has dropped more than 200.000 in just two years. The aim of this study is to find an answer to the following question: Can the digitization of material culture, supported by new technologies, lead to the development of cultural tourism? Over the past few years, many museums have started the process of digitizing their tangible and intangible cultural heritage. However, the number of visitations will not be increased solely by digitization. It is necessary to combine some digital tools with new technologies, and duly implement them in the marketing strategies of cultural institutions. The main challenge is the fact most people are not properly informed about the possibilities of the digitization application. This research shows that young people express some level of interest. However, the problem with young people is the fact they have limited knowledge about culture and history, especially when it comes to their own region. Some of the digital applications that can be used to increase people’s interest in cultural institutions are: virtual tours, augmented reality, video games, and storytelling. To increase the number of visitors, new technologies should be properly implemented into the marketing strategies as an instrument of integrated marketing communications.
OBIM I VISINA NAKNADE ŠTETE PRIČINJENE MOTORNIM VOZILOM INOSTRANE REGISTRACIJE
Authors: Krulj - Mladenović Milica
Published: July 2019

Ubrzanje dinamike svakodnevnog života i poslovanja, dovode do naglog porasta saobraćajnih nezgoda sa elementom inostranosti i do potrebe stvaranja posebnih pravila za takve specifične situacije. Iz tog razloga nacionalna zakonodavstva većine evropskih zemalja obavezno osiguranje proširuju i na vozila inostrane registracije, kako bi se zaštita oštećenih lica ostvarila što potpunije. U mnogim zakonima predviđeno je da se naknada štete oštećenim licima obezbeđuje, bez obzira da li su oštećeni vozilom domaće ili inostrane registracije.
Il libro della produzione dei cerchi di Ibn ʿArabī
Authors: Marconi Maurizio
Published: July 2019

Riassunto: Questo breve trattato di Ibn ʿArabī, redatto prima delle al-Futūḥāt al-Makkiyya, ha come tema principale l’Uomo, creato secondo la forma delle cose create e del Creatore. La peculiarità di questo testo è la presenza di alcune tabelle e figure, che vengono appunto richiamate nella prima parte del titolo, e l’indicazione grafica delle connessioni tra i vari elementi della figura mediante delle linee. Queste connessioni non sono però puramente concettuali, bensì sono reali, e vengono chiamate fini o minute realtà: non si tratta di una immagine statica di corrispondenze bensì di una rete dinamica di connessioni che canalizzano influenze, come è riportato nella seconda parte del titolo. Nel corso della trattazione vengono anche esposte i quattro gradi di esistenza, le classi dei non-esistenti, i tre gradi delle cose ed in particolare la “terza cosa”, che non è né esistente né non-esistente, le classi degli esistenti, le dieci categorie, le classi dei Nomi divini e la causa dell’inizio del Mondo e della sua genesi. La traduzione del trattato è stata effettuata sul più antico manoscritto disponibile, conservato a Manissa in Turchia, di cui è presentata anche l’edizione in arabo, ed è accompagnata dalla traduzione dei brani di altre opere di Ibn ʿArabī in cui essa è citata.Parole chiave: Uomo Universale. Esistenza e non-esistenza. Classi di cose esistenti e non esistenti. Cosmogonia. Nomi divini.Abstract: The main subject of this short treatise of Ibn ʿArabī, written before al-Futūḥāt al-Makkiyya, is the Man, created upon the form both of the creatures and of the Creator. The peculiarity of this work is the presence of tables and figures, quoted in the first part of the title, along with a graphic representation of the connections between the various elements of the figure through lines. These connections are not merely conceptual, they are real and are called fine or minute realities: this hasnothing to do with a picture of static correspondences, but with a dynamic network of connections which are channelling influences, as it is reported in the second part of the complete title.While dealing with the main subject Ibn ʿArabī also explains the four degrees of existence, the classes of non-existent things, the three degrees of things and particularly the “third thing” which is neitherexistent nor non-existent, the classes of existent things, the ten categories, the classes of Divine Names and the cause of the beginning of the World and of its genesis. The translation has been carried out on the oldest known manuscript, kept in the Manisa Library in Turkey and whose Arabic edition is here joined along with the translation of passages of other works of Ibn ʿArabī in which this treatise is mentioned.Keywords: Universal Man. Existence and non-existence. Classes of existing and non-existing things. Cosmogony. Divine Names.
El intérprete de los deseos de Ibn ʿArabī y la vita nova de Dante Alighieri
Authors: Paredi Riccardo
Published: July 2019

Resumen: El presente artículo se propone comparar y llevar a dialogar El Intérprete de los deseos de Ibn ʿArabī y la Vita Nova de Dante Alighieri bajo tres aspectos profundamente presentes a lo largo de los escritos: el concepto de Ausencia, de Memoria y de Indefinido. Según el presente análisis, la búsquedade la Amada en las dos obras presupone la Ausencia y valora la Presencia como meta final del Amante; en segundo lugar, el vacío causado en la Memoria, por la ausencia de Niẓām y de Beatrice, se llena con evocaciones y recuerdos; finalmente, es el Indefinido espacio-temporal lo que permite a las dos obras de ser tan universales, sin otras referencias concretas que la Amada o, aún más, labúsqueda espiritual misma.Palabras clave: Sufismo. Mística Islámica. Ibn ʿArabī. Dante Alighieri. Memoria. Ausencia. Presencia. Deseo divino. Amor cortés. Amor divino.Abstract: The following article aims to compare and to bring into dialogue the Interpreter of Desires by Ibn ʿArabī and the Vita Nova by Dante Alighieri, under three aspects which are deeply represented in these two works: the concept of Absence, of Memory and Indefinite. According to this analysis, the quest for the Beloved, in both works, implies the Absence and values the Presence as the finalaim of the Lover; secondly, the void caused by the absence of Niẓām and Beatrice is fulfilled by the mnemonic faculty, thanks to evocations, souvenirs and memories; lastly, the space-time indefiniteness allows the works to be considered universal. No other concrete references are found except the Beloved and her Spiritual Quest in itself.Key words: Sufism. Islamic Mysticism. Ibn ʿArabī. Dante Alighieri. Memory. Absence. Presence. Divine Desire. Courtly Love. Divine Love.
The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling
Authors: Brown D Garrett , Soto Raymond , Yandamuri Soumya , Stone Colleen , Dickey Laura , Gomes-Neto Joao Carlos , Pastuzyn Elissa D , Bell Rickesha , Petersen Charisse , Buhrke Kaitlin , Fujinami Robert S , O'Connell Ryan M , Stephens W Zac , Shepherd Jason D , Lane Thomas E , Round June L
Published: July 2019

Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.
Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology
Authors: Alex Amal , Piano Valentina , Polley Soumitra , Stuiver Marchel , Voss Stephanie , Ciossani Giuseppe , Overlack Katharina , Voss Beate , Wohlgemuth Sabine , Petrovic Arsen , Wu Yaowen , Selenko Philipp , Musacchio Andrea , Maffini Stefano
Published: July 2019

Delivery of native or chemically modified recombinant proteins into mammalian cells shows promise for functional investigations and various technological applications, but concerns that sub-cellular localization and functional integrity of delivered proteins may be affected remain high. Here, we surveyed batch electroporation as a delivery tool for single polypeptides and multi-subunit protein assemblies of the kinetochore, a spatially confined and well-studied subcellular structure. After electroporation into human cells, recombinant fluorescent Ndc80 and Mis12 multi-subunit complexes exhibited native localization, physically interacted with endogenous binding partners, and functionally complemented depleted endogenous counterparts to promote mitotic checkpoint signaling and chromosome segregation. Farnesylation is required for kinetochore localization of the Dynein adaptor Spindly. In cells with chronically inhibited farnesyl transferase activity, in vitro farnesylation and electroporation of recombinant Spindly faithfully resulted in robust kinetochore localization. Our data show that electroporation is well-suited to deliver synthetic and chemically modified versions of functional proteins, and, therefore, constitutes a promising tool for applications in chemical and synthetic biology.
Algae and fungi move from the past to the future
Authors: Bonfante Paola
Published: July 2019

The ability of photosynthetic algae to enter the hyphae of a soil fungus could tell us more about the evolution of these species and their potential for applications in the production of biofuel.
Climate change and forest plagues: assessing current and future impacts of diprionid sawflies on the pine forests of north-western Mexico
Authors: Aguilera-Molina Víctor M. , Munguía-Ortega Khutzy K. , López-Reyes Eulogio , Martínez-Aquino Andrés , Ceccarelli F. Sara
Published: July 2019

The imminent threat of climate change lies in its potential to disrupt the balance of ecosystems, particularly vulnerable areas such as mountain-top remnant forests. An example of such a fragile ecosystem is the Sierra San Pedro Mártir (SSPM) National Park of Mexico’s Baja California state, where high levels of endemism can be found, and which is home to one of the country’s few populations of the emblematic Jeffrey pine (Pinus jeffreyi). Recent outbreaks of pine-feeding sawfly larvae in SSPM increase the vulnerability of this forest ecosystem, calling for immediate assessments of the severity of this threat. Here, we present a thorough study of the sawfly’s biology and distribution, carrying out molecular and morphology-based identification of the species and creating model-based predictions of the species distribution in the area. The sawfly was found to belong to an undescribed species of the genus Zadiprion (family Diprionidae) with a one-year life-cycle. The distribution of this species appears to be restricted to the SSPM national park and it will probably persist for at least another 50 years, even considering the effects of climate change.
Sedimentological Analysis of Core Samples to Decipher Depositional Environments: A Case Study of ‘Valz-01’ Well Niger-Delta Basin, Nigeria
Authors: Maju-Oyovwikowhe G. E. , Lucas F. A.
Published: July 2019

Sedimentological studies of ninety-seven feet (97ft) of core, covering 1643 -1797.74 m from ‘Valz-01’ well Offshore Eastern Niger Delta was carried out using twenty-four (24) core slabbed samples with the aim of identifying the textural characterization of sediments from the various sectors of the lithologic unit and to determine the environment of deposition. Six lithofacies units were identified within the cored interval. They include: Muddy heterolith, laminated fine sandstone/siltstone, Fine sandstone/siltstone, Hummocky fine sandstone/siltstone, laminated shale sandy, and shale. Three depositional environments identified include marine environment, transitional and continental environment. The marine environment is characterized by the deposits of shale (1644.27 - 1709) m, while the continental environment is characterized by sandstone (1779 - 1781) m. The transitional environment is characterized by alternation of siltstone and shale (1643 – 1644.22 and 1781 – 1797.74) m. From the studies most of the analyzed samples are deposited in the delta influenced by fluvial and waves actions revealing beach sediments and turbidites.
Hybrid Precipitated Calcium Carbonate Containing Wood Flour for Paper Applications – A Comparative Handsheet Study
Authors: Dölle Klaus , Baumgartner Kilian F. , Goodman Neil F. , Klitsiotisoris Alexander
Published: July 2019

The main objective of this paper handsheet study is to investigate if a hybrid filler material containing wood flour and precipitated calcium carbonate can replace and/or supplement commercially available ground calcium carbonate and precipitated calcium carbonate mineral filler material for papermaking. The handsheet study contains 25 different furnish mixtures. Four different types of wood flour were used to manufacture the hybrid filler material, including two wood flour blends with a strengthening agent. All handsheet were manufactured with an 80% harwood and 20% softwood mix. The filler content varied between 10, 15 and 20%. The study showed that the hybrid filler material achieved a retention of up to 92.68% as well as a higher caliper of up to 208 μm compared to commercial ground and precipitated calcium carbonate of 120.4 μm and 145.6 μm respectively. Tensile and tear strength did not show an improvement. Elongation and tensile energy absorption did improve of up to 30% with the strength additive containing hybrid filler material. Opacity was improved of up to 10% with the hybrid filler material. Brightness and color values were lower due to the natural brow color of the wood flower material.
The Preferences of Dentists’ Attire among a Selected Population of Parents
Authors: Eigbobo Joycelyn O. , Etim Sylvia S.
Published: July 2019

Aim: To evaluate the preferences of the dentists' attire among parents.

Study Design: Descriptive cross-sectional study.

Methodology: A questionnaire was used to obtain socio-demographic information and their preferences from Parents that accompanied their children to the Paediatric dental clinic. Information was also elicited from photographs showing male and female dentists’ with different attires and protective wears. The data was analyzed using SPSS version 22 and the level of significance was set at <0.05.

Results: One hundred and fifty parents, comprising of 105(70%) females and 45(30%) males were assessed. The 40-49 year age-group were the majority [73(48.7%)], the female dentist was the preferred gender and there were statistically significant differences between the male and female subjects (p=0.047).  One hundred and forty-six (97.3%) wanted the dentists to wear name tags mostly for ease of identification 103(68.8%) and communication 20(13.3%). All parents wanted the dentist to don protective coat and gloves, while 123(82%) and 80(53.3%) parents preferred dentists' wearing facemasks and protective glasses, respectively. One hundred and twenty-eight (85.3%) preferred the white coats because it depicts purity/cleanliness (51.4%) and professionalism (45.7%). Dentists attire was important to 82% and there were statistical significant differences (p=0.01) between those with previous dental exposure and first-timers. There were statistically significant differences (p=0.03) between procedures [orthodontics and other procedures] done in the present visit and their perception of dentist attire.

Conclusion: The preferences of the parents on protective wears, use of name tags and gender of the dentist show that identification, safety, empathy and rapport were desired from the dentist by the parents. Previous exposure of their children to the dental setting had an influence on the parents’ preferences.
Control of Some Phytopathogenic Fungi Using Clove Essential Oil (Syzygium aromaticum L.)
Authors: Lima Tiago Silva , França Kevison Romulo da Silva , Azevedo Plinio Tércio Medeiros de , Paiva Yaroslávia Ferreira , Silva José Carlos Santos , Silva Kaique Oliveira , Santos Alex Béu , Galdino José Antônio Almeida de Sousa , Júnior Antônio Francisco de Mendonça , Cardoso Tiago Augusto Lima
Published: July 2019

Aims: This study evaluates the inhibitory potential of the clove essential oil (Syzygium aromaticum L.) on phytopathogenic fungi in vitro and on maize seeds.

Study Design: The experiments comprised completely randomized designs: Seven treatments with five replicates on in vitro test; and four treatments with five replicates each, on in vivo test.

Place and Duration of Study: The work was carried out at the Center for Agrifood Science and Technology of the Federal University of Campina Grande, Pombal, Brazil, from April to May 2018.

Methodology: In the in vitro test, the essential oil was incorporated into the PDA (Potato-Dextrose-Agar) culture medium. The treatments comprised five concentrations of the oil (0.0125, 0.025, 0.05, 0.1, and 0.2%), a negative control (0.0%), and a positive control (Tiram). Plates were inoculated with the tested fungi, Fusarium verticillioides, Macrophomina phaseolina, and Macrophomina pseudophaseolina, then incubated for seven days at 27±2°C. The percentage of mycelial growth inhibition (PGI) and mycelial growth rate index (MGRI) were estimated. In the in vivo test, maize seeds (AG1051 hybrid) were treated with the essential oil on concentrations equal or superior to the minimum inhibitory concentration found in the in vitro test, besides the negative and positive controls. The artificial inoculation was carried out in fungi colonies for 32 hours and the seed sanity test was performed. The percentage of seeds infected by the fungus was evaluated after seven days.

Results: In vitro conditions, clove oil totally inhibited the mycelial growth of F. verticillioides, M. phaseolina and M. pseudophaseolina at concentrations of 0.05, 0.1 and 0.1%, respectively. At 0.2% concentration significantly reduced the incidence of colonies of fungi M. phaseolina and M. pseudophaseolina in hybrid corn seeds AG 1051.

Conclusion: The clove essential oil had a fungitoxic effect on the phytopathogens evaluated, under in vitro and in the treatment of maize seeds.
Racial Disparities in Total Knee Replacement Failure As Related to Poverty
Authors: Bass Anne R. , Mehta Bella , Szymonifka Jackie , Finik Jackie , Lyman Stephen , Lai Emily Ying , Parks Michael , Figgie Mark , Mandl Lisa A. , Goodman Susan M.
Published: July 2019

Objective

To determine whether racial disparities in total knee replacement (TKR) failure are explained by poverty.

Methods

Black and white New York state residents, enrolled in a prospective single‐institution TKR registry January 1, 2008 to February 6, 2012, who underwent primary unilateral TKR (n = 4,062) were linked to the New York Statewide Planning and Research Cooperative System database (January 1, 2008 to December 31, 2014) to capture revisions performed at outside institutions. Patients were linked by geocoded addresses to residential census tracts. Multivariable Cox regression was used to assess predictors of TKR revision. Multivariable logistic regression was used to analyze predictors of TKR failure, defined as TKR revision in New York state ≤2 years after surgery, or as Hospital for Special Surgery (HSS) TKR quality of life score “not improved” or “worsened” 2 years after surgery.

Results

The mean ± SD age was 68.4 ± 10 years, 64% of patients were female, 8% lived in census tracts with >20% of the population under the poverty line, and 9% were black. Median follow‐up time was 5.3 years. A total of 3% of patients (122 of 4,062) required revision a median 454 days (interquartile range 215–829) after surgery. TKR revision risk was higher in blacks than whites, with a hazard ratio of 1.69 (95% confidence interval 1.01–2.81), but in multivariable analysis, only younger age, male sex, and constrained prosthesis were predictors of TKR revision. TKR failure occurred in 200 of 2,832 cases (7%) with 2‐year surveys. Risk factors for TKR failure were non‐osteoarthritis TKR indication, low surgeon volume, and low HSS Expectations Survey score, but not black race. Community poverty was not associated with TKR revision or failure.

Conclusion

There was a trend toward higher TKR revision risk in blacks, but poverty did not modify the relationship between race and TKR revision or failure.
Effect of Numbers of Turns of High‐Pressure Torsion on the Development of Exceptional Ductility in Pure Magnesium
Authors: Figueiredo Roberto B. , Pereira Pedro Henrique R. , Langdon Terence G.
Published: July 2019

The low ductility of magnesium at room temperature is usually attributed to an insufficient number of independent slip systems. Recent research has shown that refining the grain structure of pure magnesium promotes a breakdown in the Hall‐Petch relationship at low strain rates and may lead to the development of exceptional ductilities. This report describes the evolution of microstructure and the mechanical behaviour of pure magnesium using different amounts of imposed plastic deformation by high‐pressure torsion (HPT). It is shown that the initial coarse grains undergo twinning followed by a gradual grain refinement. The flow stress at low strain rates decreases as the grain size is reduced, thereby confirming an inverse Hall‐Petch behaviour. The elongation to failure increases with grain refinement and elongations over 300% are achieved after 1/2 turn of HPT. These experimental data agree with a model for the low temperature deformation behaviour of fine‐grained pure magnesium.
Wide Bandgap Perovskite Oxides with High Room‐Temperature Electron Mobility
Authors: Prakash Abhinav , Jalan Bharat
Published: July 2019

Perovskite oxides are ABO3‐type compounds with a crystal structure capable of accommodating a large number of elements at A‐ and B‐sites. Owing to their flexible structure and complex chemistry, they exhibit a wide range of functionalities as well as novel ground states at the interface. However, in comparison with conventional semiconductors such as silicon, they possess orders of magnitude lower room‐temperature electron mobilities limiting their room‐temperature electronic applications. For example, in a prototypical doped SrTiO3, the room‐temperature electron mobility remains below 10 cm2 V−1 s−1 regardless of the defect minimization. Discovery of high room‐temperature mobility in alkaline‐earth stannates such as BaSnO3 and SrSnO3 constitutes a significant advancement toward all‐perovskite electronic and spintronic devices. Alkaline‐earth stannates also possess wide‐to‐ultra wide bandgaps that make them potentially suitable candidate for transparent conductors, power electronic devices, and high electron mobility transistors. This article provides an overview of the recent progress made to these materials' electrical properties with particular emphasis on the advancements in the molecular beam epitaxy approaches for their synthesis, and defect control.
Metal‐Free Synthesis of 4‐Aryl‐2‐quinolone Derivatives by Iodine‐Mediated Intramolecular C−H Amidation
Authors: Ghosh Subhankar , Chattopadhyay Shital K.
Published: July 2019

A metal‐free synthesis of a range of 4‐aryl‐2‐quinolone derivatives has been developed which utilizes an iodine‐mediated intramolecular C−H amidation of 3,3‐diarylacryl amides as the key step. Electron‐withdrawing or ‐donating substituents in either of the aryl rings display marginal influence on the course of the reaction. However, the presence of the diarylalkene moiety has been found to be crucial for the success of the reaction. The reaction proceeds in very good yield and is applicable to a range of substrates. Moreover, the methodology overcomes some of the difficulties associated with metal‐mediated approaches such as regio‐isomeric product formation, and E‐Z isomerization. We propose a mechanism involving the in situ generation of hypoiodous acid as source of positive iodine.

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Photoredox‐Catalyzed Cyclopropanation of 1,1‐Disubstituted Alkenes via Radical‐Polar Crossover Process
Authors: Luo Wenping , Yang Yi , Fang Yewen , Zhang Xinxin , Jin Xiaoping , Zhao Guicai , Zhang Li , Li Yan , Zhou Wanli , Xia Tingting , Chen Bin
Published: July 2019

The photoredox‐neutral catalyzed cyclopropanation of 1,1‐disubstituted alkenes via radical addition‐anionic cyclization cascade has been successfully developed. Another new protocol based on photocatalytic allylation and cyclopropanation cascade was also described between allylic halide and halomethyl radical. In addition to the successful use of bis‐catecholato silicates as the alkyl radical precursors, the acyl and alkyl radicals derived from 1,4‐dihydropyridines were also engaged in this radical‐polar crossover process. The competing experiments displayed that the 3‐exo‐tet mode of cyclization preferred over 4‐exo and 5‐exo cyclization modes, allowing for the selective 3‐exo‐tet cyclization. The superior nucleofuge character of bromide over chloride and tosylate has been demonstrated in the reaction of bromomethyl radical with homoallylic (pseudo)halides. This new protocol is characterized by its redox‐neutral process, broad substrate scope, mild conditions, and good functional‐group compatibility.

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Clinical Applicability of Ultrasound in Systemic Large Vessel Vasculitides
Authors: Brkic Alen , Terslev Lene , Møller Døhn Uffe , Torp‐Pedersen Søren , Schmidt Wolfgang A. , Diamantopoulos Andreas P.
Published: July 2019

The systemic large vessel vasculitides consist mainly of giant cell arteritis and Takayasu arteritis. Both diseases affect the large blood vessels and can lead to ischemia and end‐organ damage. Ultrasound is an imaging technique that can depict inflammation of the vessel wall in large and medium vessel vasculitis. In this article, we critically review the current evidence for the clinical use of ultrasound for systemic large vessel vasculitides, regarding the clinical applicability, technical requirements, challenges, and cost. A roadmap for the development of a fast‐track ultrasound clinic for giant cell arteritis is also provided.
A multistate model for early decision‐making in oncology
Authors: Beyer Ulrich , Dejardin David , Meller Matthias , Rufibach Kaspar , Burger Hans Ulrich
Published: July 2019

The development of oncology drugs progresses through multiple phases, where after each phase, a decision is made about whether to move a molecule forward. Early phase efficacy decisions are often made on the basis of single‐arm studies based on a set of rules to define whether the tumor improves (“responds”), remains stable, or progresses (response evaluation criteria in solid tumors [RECIST]). These decision rules are implicitly assuming some form of surrogacy between tumor response and long‐term endpoints like progression‐free survival (PFS) or overall survival (OS). With the emergence of new therapies, for which the link between RECIST tumor response and long‐term endpoints is either not accessible yet, or the link is weaker than with classical chemotherapies, tumor response‐based rules may not be optimal. In this paper, we explore the use of a multistate model for decision‐making based on single‐arm early phase trials. The multistate model allows to account for more information than the simple RECIST response status, namely, the time to get to response, the duration of response, the PFS time, and time to death. We propose to base the decision on efficacy on the OS hazard ratio (HR) comparing historical control to data from the experimental treatment, with the latter predicted from a multistate model based on early phase data with limited survival follow‐up. Using two case studies, we illustrate feasibility of the estimation of such an OS HR. We argue that, in the presence of limited follow‐up and small sample size, and making realistic assumptions within the multistate model, the OS prediction is acceptable and may lead to better early decisions within the development of a drug.
The added value of fasting blood glucose to serum squamous cell carcinoma antigen for predicting oncological outcomes in cervical cancer patients receiving neoadjuvant chemotherapy followed by radical hysterectomy
Authors: Wu Miao‐Fang , Guan Mei‐Mei , Liu Chang‐Hao , Wu Jie‐Ying , Rao Qun‐Xian , Li Jing
Published: July 2019

Objective

To determine the combination of fasting blood glucose (FBG) with squamous cell carcinoma antigen (SCCA) assessments in the prediction of tumor responses to chemotherapy and pretreatment prognostication among patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC).

Methods

Data of 347 LACC patients were retrospectively reviewed. Receiver operating characteristic (ROC) curves were constructed, and areas under the curves (AUCs) were compared to evaluate the ability to predict complete response (CR) following NACT. Patients were stratified into groups with low and high levels of SCCA and FBG and combined into low‐ or high‐SCCA and low‐ or high‐FBG groups. Cox regression analysis was performed to identify determinants of recurrence‐free survival (RFS) and overall survival (OS).

Results

The AUCs were 0.70, 0.68, and 0.66 for SCCA, FBG, and a combination of SCCA and FBG for predicting CR following NACT, respectively; however, the differences among AUCs were not significant (P = .496). Pretreatment SCCA and FBG levels were identified as independent predictors of RFS and OS. The high‐SCCA/high‐FBG group showed significantly worse prognosis than the low‐SCCA/low‐FBG group. After adjusting for other variables, high‐SCCA/high‐FBG remained independently associated with an increased risk of tumor recurrence and death.

Conclusion

SCCA, FBG, and a combination of SCCA and FBG could acceptably predict CR following NACT. Pretreatment SCCA and FBG levels were independent prognostic factors. The combination of SCCA and FBG levels refined the prognostic stratification of LACC patients, which allowed the group of patients with the highest risk of recurrence and death to be identified.
Nucleotide Binding Modes in a Motor Protein Revealed by 31P‐ and 1H‐Detected MAS Solid‐State NMR Spectroscopy
Authors: Wiegand Thomas , Schledorn Maarten , Malär Alexander A. , Cadalbert Riccardo , Däpp Alexander , Terradot Laurent , Meier Beat H. , Böckmann Anja
Published: July 2019

Protein–nucleic acid interactions play important roles not only in energy‐providing reactions, such as ATP hydrolysis, but also in reading, extending, packaging, or repairing genomes. Although they can often be analyzed in detail with X‐ray crystallography, complementary methods are needed to visualize them in complexes, which are not crystalline. Here, we show how solid‐state NMR spectroscopy can detect and classify protein–nucleic interactions through site‐specific 1H‐ and 31P‐detected spectroscopic methods. The sensitivity of 1H chemical‐shift values on noncovalent interactions involved in these molecular recognition processes is exploited allowing us to probe directly the chemical bonding state, an information, which is not directly accessible from an X‐ray structure. We show that these methods can characterize interactions in easy‐to‐prepare sediments of the 708 kDa dodecameric DnaB helicase in complex with ADP:AlF4−:DNA, and this despite the very challenging size of the complex.
In Situ Measurement of Local pH at Working Electrodes in Neutral pH Solutions by the Rotating Ring‐Disk Electrode Technique
Authors: Yokoyama Yuko , Miyazaki Kohei , Miyahara Yuto , Fukutsuka Tomokazu , Abe Takeshi
Published: July 2019

When electrochemical reactions that generate/consume protons or hydroxide ions take place, the local pH in the vicinity of an electrode becomes considerably different from the bulk pH. However, measuring the local pH is very difficult, and the idea of using a rotating ring‐disk electrode (RRDE) is not applicable to solutions with neutral pH. Herein, we extend the theory of local pH measurement using a RRDE and make it applicable to solutions with a wide pH range. This extended theory is corroborated by measurements of hydrogen oxidation/evolution reactions in solutions with near‐neutral pH. In addition, the local pH change in a highly concentrated solution is also measured, and the results show that this local pH measurement method can be used regardless of the solution concentration.
Demonstrating a Metal‐Metal Battery System in Aprotic Electrolyte with Silver and Lithium
Authors: Wang Huimin , Gu Wenchuan , Yu Denis Y. W.
Published: July 2019

Metals are attractive materials for energy storage as they can undergo oxidation to accommodate charge transfer. However, traditional metal‐metal batteries such as Cu−Zn have low voltage because of the use of an aqueous electrolyte. Here, we propose a metal‐metal battery system with higher voltage in aprotic electrolyte with Ag/AgCl and Li/Li+ reactions on the cathode and anode, respectively. The Ag−Li cell gives a voltage of about 2.8 V and a capacity of close to 200 mAh g−1. X‐ray diffraction confirms the formation of AgCl during charging. The reduction of AgCl is faster than oxidation of Ag, so the battery has better discharge rate performance than charge. We also find that the solubility of the charge product (AgCl) in the electrolyte influences the cycle stability of the battery.
19F NMR Monitoring of Reversible Protein Post‐Translational Modifications: Class D β‐Lactamase Carbamylation and Inhibition
Authors: van Groesen Emma , Lohans Christopher T. , Brem Jürgen , Aertker Kristina M. J. , Claridge Timothy D. W. , Schofield Christopher J.
Published: July 2019

Bacterial production of β‐lactamases with carbapenemase activity is a global health threat. The active sites of class D carbapenemases such as OXA‐48, which is of major clinical importance, uniquely contain a carbamylated lysine residue which is essential for catalysis. Although there is significant interest in characterizing this post‐translational modification, and it is a promising inhibition target, protein carbamylation is challenging to monitor in solution. We report the use of 19F NMR spectroscopy to monitor the carbamylation state of 19F‐labelled OXA‐48. This method was used to investigate the interactions of OXA‐48 with clinically used serine β‐lactamase inhibitors, including avibactam and vaborbactam. Crystallographic studies on 19F‐labelled OXA‐48 provide a structural rationale for the sensitivity of the 19F label to active site interactions. The overall results demonstrate the use of 19F NMR to monitor reversible covalent post‐translational modifications.
Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications
Authors: Sasaki Clarence T. , Doukas Sotirios G. , Costa Jose , Vageli Dimitra P.
Published: July 2019

Background

Recent preclinical explorations strongly support the tumorigenic potential of bile on laryngopharyngeal mucosa. Herein, the authors describe, in bile‐related human hypopharyngeal squamous cell carcinoma (HSCC), NF‐κB–related messenger RNA (mRNA) and microRNA (miRNA) oncogenic phenotypes similar to those previously identified in acidic bile–exposed premalignant murine hypopharyngeal mucosa.

Methods

In this pilot study, the authors included human HSCC specimens paired with their adjacent normal tissue (ANT) derived from 3 representative patients with documented biliary laryngopharyngeal reflux (bile[+]) compared with 5 control patients without signs of bile reflux disease (bile[‐]). Immunohistochemical, quantitative polymerase chain reaction, and miRNA analyses were used to detect the levels of activated NF‐κB and expression levels of STAT3, EGFR, BCL2, WNT5A, IL‐6, IL‐1B, ΔNp63, cREL, TNF‐α, TP53, NOTCH1, NOTCH2, NOTCH3, miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375, miR‐451a, miR‐489, miR‐504, and miR‐99a.

Results

Bile(+) HSCC demonstrated an intense NF‐κB activation accompanied by significant overexpression of RELA(p65), EGFR, STAT3, BCL‐2, cREL, ΔNp63, WNT5A, IL‐6, and IL1B; upregulation of oncomir miR‐21; and downregulation of tumor suppressor miR‐375 compared with their respective ANTs. Bile(+) HSCC demonstrated significantly higher mRNA levels of all the analyzed genes, particularly RELA(p65), IL‐6, EGFR, and TNF‐α compared with bile(‐) tumors. The miR‐21/miR‐375 ratio, which previously has been linked to tumor aggressiveness, was found to be >260‐fold and >30‐fold higher, respectively, in bile(+) HSCCs compared with their ANTs and bile(‐) tumors.

Conclusions

Although limitations apply to this pilot study due to the small number of patients with HSCC, the novel findings suggest that a history of bile as a component of esophageal reflux disease may represent an independent risk factor for hypopharyngeal carcinogenesis.
Visual short‐term memory activation patterns in adult survivors of childhood acute lymphoblastic leukemia
Authors: Boulet‐Craig Aubree , Robaey Philippe , Barlaam Fanny , Laniel Julie , Oswald Victor , Jerbi Karim , Sultan Serge , Affret‐Bertout Laurence , Drouin Simon , Krajinovic Maja , Laverdière Caroline , Sinnett Daniel , Jolicoeur Pierre , Lippé Sarah
Published: July 2019

Background

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Treatments against ALL might lead to later cognitive effects and alterations in brain structure in survivors but to the authors' knowledge the observed variability in the severity of neurocognitive deficits is not fully understood. The objective of the current study was to investigate abnormalities in visual short‐term memory (VSTM) brain activation in survivors of childhood ALL using magnetoencephalography.

Methods

A VSTM task was completed by 40 survivors of ALL and 26 controls. VSTM capacity (Cowan K) and brain activation were assessed during the retention period of the task (400‐1400 milliseconds) using a standard minimum norm source localization method.

Results

Performance (Cowan K) was found to be similar between survivors of ALL and controls. Atypical brain activation was found in survivors of ALL during the task, including overactivation of regions usually involved in VSTM (lateral occipital, precentral gyrus, and postcentral gyrus), recruitment of regions that typically are not involved in VSTM (superior/middle temporal gyrus and supramarginal gyrus), and lower activation of frontal brain regions (inferior frontal gyrus). These patterns of activation were modulated by the age at the time of cancer onset (P = .01) because activity was found to be reduced in participants who were younger at diagnosis.

Conclusions

The results of the current study suggest a pattern of neural inefficiency and compensatory activity during VSTM in survivors of ALL.
Magnesium‐Based Clusters as Building Blocks of Electrolytes in Lithium‐Ion Batteries
Authors: Sikorska Celina
Published: July 2019

Superhalogens, owing to their large electron affinity (EA, exceeding those of any halogen atom), play an essential role in physical chemistry as well as new material design. They have applications in hydrogen storage and lithium‐ion batteries. Owing to the unique geometries and electronic features of magnesium‐based clusters, their potential to form a new class of lithium salts has been investigated here theoretically. The idea is assessed by conducting ab initio computations on Li+/MgnF2n+1‐2mOm− compounds (n=2, 3; m=0‐3) and analyzing their performance as potential Li‐ion battery electrolytes. The Mg3F7− cluster, with large electron binding energy (EA of 7.93 eV), has been proven to serve as a building block for lithium salts. It is shown that, apart from high electronic stability, the new superhalogen‐based electrolytes exhibit a set of desirable properties, including a large band gap, high electrolyte stability window, easy mobility of the Li+, and favorable insensitivity to water.
Hydroxylamine Oxidation on Polycrystalline Gold Electrodes in Aqueous Electrolytes: Quantitative On‐Line Mass Spectrometry under Forced Convection
Authors: Pozniak Boguslaw , Treufeld Imre , Scherson Daniel
Published: July 2019

Herein, a method is presented that allows quantitative determination of faradaic efficiencies for dinitrogen (N2) generation during the electrochemical oxidation of hydroxylamine (NH2OH),
, on a polycrystalline gold Au(poly) disk electrode in aqueous electrolytes over a wide pH range. This tactic involves the use of an impinging jet electrolyte configuration incorporating a gas porous ring connected in turn to a mass spectrometer. The actual amount of N2 generated at the Au(poly) disk was assayed using the oxidation of hydrazine (N2H4) in aqueous phosphate buffer (pH 7). This redox process yields N2 as the only product, allowing a direct correlation to be established between the changes in the partial pressures of N2 and the current flowing through the disk electrode. An analysis of the data collected revealed a strong dependence of
both on pH and the applied potential. Although values of
as high as 20 to 30 % were found in acid and neutral media over a narrow potential region, those in alkaline solution were far smaller in the entire potential range examined.
Synthesis of Poly(ADP‐ribose) Monomer Containing 2′‐O‐α‐D‐Ribofuranosyl Adenosine
Authors: Mikhailov Sergey N. , Drenichev Mikhail S. , Oslovsky Vladimir E. , Kulikova Irina V. , Herdewijn Piet
Published: July 2019

In this article, the earlier reported procedure for the synthesis of 2′‐O‐β‐D‐ribofuranosyl nucleosides was extended to the synthesis of 2′‐O‐α‐D‐ribofuranosyl adenosine, a monomeric unit of poly(ADP‐ribose). It consists in condensation of a small excess of 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐α,β‐D‐arabinofuranose activated with tin tetrachloride with 3′,5′‐O‐tetra‐isopropyldisiloxane‐1,3‐diyl‐ribonucleosides in 1,2‐dichloroethane. The following debenzoylation and silylation of arabinofuranosyl residue and inversion of configuration at C‐2ʹʹ atom of arabinofuranosyl residue and final removal of silyl protective groups gave 2′‐O‐α‐D‐ribofuranosyl adenosine in overall 13% to 21% yield. © 2019 by John Wiley & Sons, Inc.
Local parasite pressures and host genotype modulate epigenetic diversity in a mixed‐mating fish
Authors: Berbel‐Filho Waldir M. , Garcia de Leaniz Carlos , Morán Paloma , Cable Joanne , Lima Sergio M. Q. , Consuegra Sofia
Published: July 2019

Parasite‐mediated selection is one of the main drivers of genetic variation in natural populations. The persistence of long‐term self‐fertilization, however, challenges the notion that low genetic variation and inbreeding compromise the host's ability to respond to pathogens. DNA methylation represents a potential mechanism for generating additional adaptive variation under low genetic diversity. We compared genetic diversity (microsatellites and AFLPs), variation in DNA methylation (MS‐AFLPs), and parasite loads in three populations of Kryptolebias hermaphroditus, a predomintanly self‐fertilizing fish, to analyze the potential adaptive value of DNA methylation in relation to genetic diversity and parasite loads. We found strong genetic population structuring, as well as differences in parasite loads and methylation levels among sampling sites and selfing lineages. Globally, the interaction between parasites and inbreeding with selfing lineages influenced DNA methylation, but parasites seemed more important in determining methylation levels at the local scale.