bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Scenarios of Testosterone and Anabolic Androgenic Steroids Use in and Outside Medicine
Authors: Câmara Lucas Caseri
Published: November 2024

Anabolic hormones, particularly testosterone and anabolic androgenic steroids (AAS), serve a range of applications with distinct goals, benefits, and risks. This article aims to clarify four primary scenarios in which these hormones are used, to aid in reducing misunderstandings and promoting more evidence-based discussions. The first scenario, testosterone replacement therapy (TRT), is well-documented as a treatment for hypogonadism, offering improvements in body composition, metabolic health, and cardiovascular outcomes with proper supervision. The second scenario involves therapeutic use of AAS in cases of significant catabolism, muscle loss, or other clinical conditions requiring anabolic support. Here, controlled studies underscore the potential of AAS to improve muscle mass, bone density, and physical function, though clinical practice underutilizes these therapies.
A third, more debated scenario covers the controlled use of supraphysiological doses of testosterone and AAS for performance and aesthetics. Research, including randomized controlled trials (RCTs), has shown measurable benefits in body composition and physical strength with minimal adverse effects when appropriately monitored. However, such uses remain controversial and are not widely endorsed by medical organizations due to ethical and safety concerns.
The final scenario contrasts sharply with the others, detailing the risks associated with unregulated AAS abuse. This includes prolonged use, high dosages, poor-quality products from the underground market, and polypharmacy, which collectively heighten the risk of severe health consequences. This chaotic pattern of abuse complicates the assessment of AAS’s specific impact on health due to numerous confounding factors.
A clearer distinction between these scenarios could enhance academic and clinical discourse, leading to more precise recommendations. By acknowledging the varied contexts in which AAS and testosterone are used, healthcare providers and researchers may make better-informed decisions, advancing safer practices and more effective guidelines.
Genetic Diversity Studies in Local Germplasm of Sesame (Sesamum indicum L.)
Authors: Ghule Shubham K. , Bhavsar Vilas V. , Shaniware Yogesh A. , Patil Varad V. , Ghume Omkar G.
Published: November 2024

The objective of the current study was to determine the type and degree of genetic diversity between traits that contribute to seed yield. Using a Randomized Block Design with two replications, 36 sesame genotypes were assessed for 10 distinct features at the Botany section farm, College of Agriculture, Dhule, in the summer of 2023. The genotypes were divided into fourteen clusters based on the D2 value.  In addition to providing options for achieving a high heterotic effect and upgrading the base population, inter-crossing between them would also restore suitable transgressive segregants and a wide range of diversity in succeeding generations. The study found that local germplasm viz., JLS-1414-21-2 for number of primary branches per plant, number of seeds per capsule, oil content (%), and seed yield, and TS-14 for plant height, number of primary branches, number of capsules per plant, number of seeds per capsule, 1000 seed weight, and seed yield per plant found superior and can be used for further breeding methodologies. Genotypes JLT-408 and AVTS-2001 were shown to be superior for protein content, DS-10 for earliness, TKG-22 for oil content, TS-16 for earliness, and DLS-12 for plant height, number of capsules per plant, and 1000 seed weight.
Desigualdade Racial E Discriminação: O Impacto Do Racismo Estrutural Nas Oportunidades De Educação E Trabalho
Authors: Oliveira Diego Nascimento De , Silva Igor Talarico Da , Lima Agnaldo Braga , Dutra Yuri Fedrigo , Lima Odaíze Do Socorro Ferreira Cavalcante
Published: November 2024

O presente estudo aborda o impacto do racismo estrutural nas oportunidades de educação e trabalho para minorias raciais, com foco nas desigualdades enfrentadas pela população negra e indígena no Brasil. O racismo estrutural é caracterizado por um sistema de normas e práticas institucionais que, de forma intencional ou não, perpetua a desigualdade e a exclusão desses grupos em diversas esferas sociais. Na educação, as disparidades são evidentes desde os primeiros anos de formação, uma vez que as crianças de minorias raciais têm, frequentemente, acesso limitado a escolas com infraestrutura adequada e a recursos pedagógicos de qualidade. A segregação educacional e a falta de políticas inclusivas perpetuam a evasão escolar e o baixo desempenho acadêmico, limitando as possibilidades de ascensão social e acesso a empregos qualificados. No mercado de trabalho, as barreiras são igualmente desafiadoras. Profissionais de minorias raciais encontram dificuldades no processo de contratação e enfrentam discriminação salarial e restrição de mobilidade profissional. Estudos indicam que, mesmo com qualificações equivalentes, trabalhadores negros e indígenas têm menores chances de ocupar posições de liderança ou de altos salários. Essa situação é agravada pelo alto índice de informalidade e pela falta de proteção social entre esses grupos, O que reforça a exclusão econômica e limita o acesso a direitos básicos, como previdência e saúde. Este estudo também analisa o papel das políticas de ação afirmativa e de inclusão, que buscam promover a equidade racial em ambientes educacionais e laborais. Embora tais políticas sejam passos importantes para a redução das desigualdades, elas enfrentam resistência e críticas sociais, sendo frequentemente acusadas de criar “privilégios invertidos”. A pesquisa conclui que, para combater efetivamente o racismo estrutural, é necessário um esforço conjunto que envolva políticas públicas robustas, práticas inclusivas nas instituições educacionais e empresas, e uma transformação cultural ampla que valorize a diversidade e promova a igualdade de oportunidades
Critical observations that shaped our understanding of the function(s) of intracellular glycosylation (O‐GlcNAc)
Authors: Zachara Natasha E.
Published: November 2018

Almost 100 years after the first descriptions of proteins conjugated to carbohydrates (mucins), several studies suggested that glycoproteins were not restricted to the serum, extracellular matrix, cell surface, or endomembrane system. In the 1980s, key data emerged demonstrating that intracellular proteins were modified by monosaccharides of O‐linked β‐N‐acetylglucosamine (O‐GlcNAc). Subsequently, this modification was identified on thousands of proteins that regulate cellular processes as diverse as protein aggregation, localization, post‐translational modifications, activity, and interactions. In this Review, we will highlight critical discoveries that shaped our understanding of the molecular events underpinning the impact of O‐GlcNAc on protein function, the role that O‐GlcNAc plays in maintaining cellular homeostasis, and our understanding of the mechanisms that regulate O‐GlcNAc‐cycling.
The effectiveness of 4DCT in children and adults: A pooled analysis
Authors: Huijskens Sophie C. , van Dijk Irma W. E. M. , Visser Jorrit , Balgobind Brian V. , Rasch Coen R. N. , Alderliesten Tanja , Bel Arjan
Published: November 2018

Background

While four‐dimensional computed tomography (4DCT) is extensively used in adults, reluctance remains to use 4DCT in children. Day‐to‐day (interfractional) variability and irregular respiration (intrafractional variability) have shown to be limiting factors of 4DCT effectiveness in adults. In order to evaluate 4DCT applicability in children, the purpose of this study is to quantify inter‐ and intrafractional variability of respiratory motion in children and adults. The pooled analysis enables a solid comparison to reveal if 4DCT application for planning purposes in children could be valid.

Methods/materials

We retrospectively included 90 patients (45 children and 45 adults), for whom the diaphragm was visible on abdominal/thoracic free‐breathing cone beam CTs (480 pediatric, 524 adult CBCTs). For each CBCT, the cranial–caudal position of end‐exhale and end‐inhale positions of the right diaphragm dome were manually selected in the projection images. The difference in position between both phases defines the amplitude. Cycle time equaled inspiratory plus expiratory time. We analyzed the variability of the inter‐ and intrafractional respiratory‐induced diaphragm motion.

Results

Ranges of respiratory motion characteristics were large in both children and adults (amplitude: 4–17 vs 5–24 mm, cycle time 2.1–3.9 vs 2.7–6.5 s). The mean amplitude was slightly smaller in children than in adults (10.7 vs 12.3 mm; P = 0.06). Interfractional amplitude variability was statistically significantly smaller in children than in adults (1.4 vs 2.2 mm; P = 0.00). Mean cycle time was statistically significantly shorter in children (2.9 vs 3.6 s; P = 0.00). Additionally, intrafractional cycle time variability was statistically significantly smaller in children (0.5 vs 0.7 s; P = 0.00).

Conclusions

Overall variability is smaller in children than in adults, indicating that respiratory motion is more regular in children than in adults. This implies that a single pretreatment 4DCT could be a good representation of daily respiratory motion in children and will be at least equally beneficial for planning purposes as it is in adults.
Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy
Authors: Otero Maria G. , Tiongson Emmanuelle , Diaz Frank , Haude Katrina , Panzer Karin , Collier Ashley , Kim Jaemin , Adams David , Tifft Cynthia J. , Cui Hong , Millian Zamora Francisca , Au Margaret G. , Graham John M. , Buckley David J. , Lewis Richard , Toro Camilo , Bai Renkui , Turner Lesley , Mathews Katherine D. , Gahl William , Pierson Tyler Mark
Published: November 2018

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron‐one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron‐two. cDNA and protein analysis indicated that no full‐length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.
Pilomotor seizures marked by infraslow activity and acetazolamide responsiveness
Authors: Wennberg Richard , Maurice Catherine , Carlen Peter L. , Garcia Dominguez Luis
Published: November 2018

A patient with pilomotor seizures post anti‐LGI1 limbic encephalitis, refractory to immunotherapy and anti‐epileptic drugs, was investigated with electroencephalography and magnetoencephalography. Seizures occurred daily (14.9 ± 4.9/day), with catamenial exacerbation, inducible by hyperventilation. Anterior temporal ictal onsets were heralded (by ~15 sec) by high amplitude ipsilateral electromagnetic infraslow activity. The catamenial/ventilatory sensitivity and the infraslow activity (reflecting glial depolarization) suggested an ionic,CO2/pH‐related glioneuronal mechanism. Furosemide decreased seizure frequency by ~33%. Acetazolamide led to immediate seizure freedom, but lost efficacy with daily treatment. A cycling acetazolamide regimen (2 days on, 4 days off) plus low‐dose topiramate maintained >95% reduction (0.5 ± 0.9/day) in seizures.
Liar, liar: Consistent lying decreases belief in the truth
Authors: Polage Danielle C.
Published: November 2018

This study investigated the effects of lying on belief ratings for autobiographical childhood events. Participants lied by trying to convince the experimenter that likely events had not happened and that unlikely events had happened. Participants consistently lied, consistently told the truth, and alternated lying and truth telling across two sessions. Results showed that consistent false assents increased belief in those false events and that consistent false denials decreased belief in those true events. False denials had a larger influence on belief than did false assents. False assents that were told first were more likely to increase in belief than were false assents told in the second session. False denials decreased belief in the true event regardless of when they were told. These results suggest that lying influences confidence ratings both by increasing belief in a lied‐about event and by decreasing belief in a true event.
Disruption of writing by background speech: Does sound source location and number of voices matter?
Authors: Keus van de Poll Marijke , Sjödin Louise , Nilsson Mats E.
Published: November 2018

It is not unusual that people have to write in an environment where background speech is present. Background speech can vary in both speech intelligibility and location of the sound source. Earlier research has shown disruptive effects of background speech on writing performance. To expand and reinforce this knowledge, the present study investigated the role of number of voices and sound source location in the relation between background speech and writing performance. Participants wrote texts in quiet or in background speech consisting of one or seven voices talking simultaneously located in front of or behind them. Overall, one voice was more disruptive than seven voices talking simultaneously. Self‐reports showed that sound from the front was more disruptive compared with sound from behind. Results are in line with theory of interference‐by‐process, attentional capture, and the cross‐modal theory of attention. The relevance of the results for open‐office environments is discussed.
Do seductive details do their damage in the context of graph comprehension? Insights from eye movements
Authors: Strobel Benjamin , Grund Simon , Lindner Marlit Annalena
Published: November 2018

In educational research, interesting but irrelevant materials are often considered seductive details, which are suspected to have detrimental effects on learning. Although seductive details have been mostly examined in the context of text comprehension, such elements are also used in graphs (e.g., depicting data points). In the present experiment, we investigated both seductive text and seductive pictures in the context of graph comprehension as well as the interaction of seductive details with spatial working memory capacity (SWMC). We recordedN = 68 students' eye movements, while they analyzed bar graphs in a within‐subject design. Data were analyzed with linear mixed‐effects models. Results show that seductive details did not affect students' graph reading performance but prolonged the task processing time. Eye‐fixation measures revealed that additional processing time was best explained by attention distraction towards the seductive material. SWMC did not affect the presence or the extent of the seductive details effect.
Electroactive Soft Photonic Devices for the Synesthetic Perception of Color and Sound
Authors: Kim Do Yoon , Choi Sunglok , Cho Hyesung , Sun Jeong‐Yun
Published: November 2018

Color, as perceived through the eye, transcends mere information in the visible range of electromagnetism and serves as an agent for communication and entertainment. Mechanochromic systems have thus far only aimed at satisfying the sense of vision and have overlooked the possibility of generating acoustic vibrations in concert with their visual color responses that would enable the simultaneous satisfaction of the auditory system. Transcending the boundaries of the two senses (i.e., sound and color), herein a strategy for their concurrent and synesthetic fulfillment is elucidated by electrically actuating an organogel photonic device, controlled by a single input signal. This new class of devices that integrate a color module with a speaker is fabricated from a mechanochromic layer that comprises close‐packed photonic lattice with an organogel matrix pervading the void fraction. Exploiting a dielectric elastomer actuator, the system's mechanical response permits the simultaneous, yet independent, exploration of visible‐light reflection alongside audible sound‐wave generation. Large areal strains at low frequencies of actuation tune the photonic stop‐band, whereas the layer remains incompressible and exhibits negligible strain when actuated at higher frequencies (e.g., tens of Hz), thereby making it amenable to modulate sound and color simultaneously yet independently.
Ultrasensitive 2D Bi2O2Se Phototransistors on Silicon Substrates
Authors: Fu Qundong , Zhu Chao , Zhao Xiaoxu , Wang Xingli , Chaturvedi Apoorva , Zhu Chao , Wang Xiaowei , Zeng Qingsheng , Zhou Jiadong , Liu Fucai , Tay Beng Kang , Zhang Hua , Pennycook Stephen J. , Liu Zheng
Published: November 2018

2D materials are considered as intriguing building blocks for next‐generation optoelectronic devices. However, their photoresponse performance still needs to be improved for practical applications. Here, ultrasensitive 2D phototransistors are reported employing chemical vapor deposition (CVD)‐grown 2D Bi2O2Se transferred onto silicon substrates with a noncorrosive transfer method. The as‐transferred Bi2O2Se preserves high quality in contrast to the serious quality degradation in hydrofluoric‐acid‐assisted transfer. The phototransistors show a responsivity of 3.5 × 104 A W−1, a photoconductive gain of more than 104, and a time response in the order of sub‐millisecond. With back gating of the silicon substrate, the dark current can be reduced to several pA. This yields an ultrahigh sensitivity with a specific detectivity of 9.0 × 1013 Jones, which is one of the highest values among 2D material photodetectors and two orders of magnitude higher than that of other CVD‐grown 2D materials. The high performance of the phototransistor shown here together with the developed unique transfer technique are promising for the development of novel 2D‐material‐based optoelectronic applications as well as integrating with state‐of‐the‐art silicon photonic and electronic technologies.
Photoredox‐Initiated 1,2‐Difunctionalization of Alkenes with N‐Chloro S‐Fluoroalkyl Sulfoximines
Authors: Prieto Alexis , Diter Patrick , Toffano Martial , Hannedouche Jérôme , Magnier Emmanuel
Published: November 2018

We describe herein the photoredox‐initiated 1,2‐difunctionalization of alkene derivatives with N‐chloro S‐fluoroalkyl sulfoximines yielding novel fluoroalkyl sulfoximine scaffolds. The reaction is proposed to proceed through an atom‐transfer radical addition (ATRA) mechanism involving the generation of fluorinated nitrogen‐centered sulfoximidoyl radicals.

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Cycloaddition of Carbon Dioxide to Epoxides for the Synthesis of Cyclic Carbonates with a Mixed Catalyst of Layered Double Hydroxide and Tetrabutylammonium Bromide at Ambient Temperature
Authors: Chen Yanglin , Xu Ping , Arai Masahiko , Sun Jianmin
Published: November 2018

A series of nickel‐aluminium, cobalt‐aluminium and zinc‐aluminum layered double hydroxides were synthesized by urea hydrolysis (UH) and reverse micelle (RM) methods and then applied for the cycloaddition of carbon dioxide to propylene oxide (PO) under solvent‐free and ambient conditions. The most efficient catalyst was zinc‐aluminum layered double hydroxide prepared by RM (denoted as ZnAl‐RM) and it showed, in the presence of a co‐catalyst of tetrabutylammonium bromide, 96% propylene carbonate (PC) yield in 12 h at 25 °C and 1 MPa carbon dioxide. It is noteworthy for the same catalyst system that 74% PC yield was achieved in 24 h at room temperature (about 25 °C) and atmospheric carbon dioxide pressure. The high catalytic performance of the ZnAl‐RM and tetrabutylammonium bromide system should result from cooperative effects between zinc ion and bromine ion. Moreover, the ZnAl‐RM and tetrabutylammonium bromide system showed excellent versatility, which was also an active catalyst to the transformation of carbon dioxide and other epoxides into corresponding cyclic carbonates under mild temperature and pressure conditions.

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All Hierarchical Core–Shell Heterostructures as Novel Binder‐Free Electrode Materials for Ultrahigh‐Energy‐Density Wearable Asymmetric Supercapacitors
Authors: Li Qiulong , Zhang Qichong , Sun Juan , Liu Chenglong , Guo Jiabin , He Bing , Zhou Zhenyu , Man Ping , Li Chaowei , Xie Liyan , Yao Yagang
Published: November 2018

High‐performance fiber‐shaped energy‐storage devices are indispensable for the development of portable and wearable electronics. Composite pseudocapacitance materials with hierarchical core–shell heterostructures hold great potential for the fabrication of high‐performance asymmetric supercapacitors (ASCs). However, few reports concerning the assembly of fiber‐shaped ASCs (FASCs) using cathode/anode materials with all hierarchical core–shell heterostructures are available. Here, cobalt‐nickel‐oxide@nickel hydroxide nanowire arrays (NWAs) and titanium nitride@vanadium nitride NWAs are constructed skillfully with all hierarchical core–shell heterostructures directly grown on carbon nanotube fibers and are shown to exhibit ultrahigh capacity and specific capacitance, respectively. The specific features and outstanding electrochemical performances of the electrode materials are exploited to fabricate an FASC device with a maximum working voltage of 1.6 V, and this device exhibits a high specific capacitance of 109.4 F cm−3 (328.3 mF cm−2) and excellent energy density of 36.0 mWh cm−3 (108.1 µWh cm−2). This work therefore provides a strategy for constructing all hierarchical core–shell heterostructured cathode and anode materials with ultrahigh capacity for the fabrication of next‐generation wearable energy‐storage devices.
Opportunities of Covalent Organic Frameworks for Advanced Applications
Authors: Song Yanpei , Sun Qi , Aguila Briana , Ma Shengqian
Published: November 2018

Covalent organic frameworks (COFs) are an emerging class of functional nanostructures with intriguing properties, due to their unprecedented combination of high crystallinity, tunable pore size, large surface area, and unique molecular architecture. The range of properties characterized in COFs has rapidly expanded to include those of interest for numerous applications ranging from energy to environment. Here, a background overview is provided, consisting of a brief introduction of porous materials and the design feature of COFs. Then, recent advancements of COFs as a designer platform for a plethora of applications are emphasized together with discussions about the strategies and principles involved. Finally, challenges remaining for this type material for real applications are outlined.
Polycarbazole‐Sorted Semiconducting Single‐Walled Carbon Nanotubes for Incorporation into Organic Thin Film Transistors
Authors: Rice Nicole A. , Bodnaryk William J. , Mirka Brendan , Melville Owen A. , Adronov Alex , Lessard Benoît H.
Published: November 2018

The realization of organic thin film transistors (OTFTs) with performances that support low‐cost and large‐area fabrication remains an important and challenging topic of investigation. The unique electrical properties of single‐walled carbon nanotubes (SWNTs) make them promising building blocks for next generation electronic devices. Significant advances in the enrichment of semiconducting SWNTs, particularly via π‐conjugated polymers for purification and dispersal, have allowed the preparation of high‐performance OTFTs on a small scale. The intimate interaction of the conjugated polymer with both SWNTs and the dielectric necessitates the investigation of a variety of conjugated polymer derivatives for device optimization. Here, the preparation of polymer–SWNT composites containing carbazole moieties, a monomer unit that has remained relatively overlooked for the dispersal of large‐diameter semiconducting SWNTs, is reported. This polymer selectively discriminates semiconducting SWNTs using a facile procedure. OTFTs prepared from these supramolecular complexes are ambipolar, and possess superior mobilities and on/off ratios compared to homo poly(fluorene) dispersions, with hole mobilities from random‐network devices reaching 21 cm2 V−1 s−1. Atomic force microscopy measurements suggest the poly(carbazole)–SWNT composites form more uniform thin films compared to the poly(fluorene) dispersion. Additionally, treating the silicon dioxide dielectric with octyltrichlorosilane is a simple and effective way to reduce operational hysteresis in SWNT OTFTs.
Destination Critical Care: A Roadmap for Academic Clinicians, Educators, and Mentors
Authors: Hoffman Jean M. W. , Mayer Katherine
Published: November 2018

The purpose of this article is to provide a framework for academic clinicians, educators, and mentors to advise the emergency medicine (EM) resident with an interest in the field of critical care medicine. Prior articles have detailed the prerequisites and specific training curricula of the distinct critical care pathways, but an approach for the advising faculty member in this climate of increased interest in critical care training has yet to be disseminated. In this article, we assume a starting point of EM residency and focus on pivotal training and decision points that occur along the path to matriculation into a critical care fellowship program. These decision points are described in stepwise fashion with aligned questions to help the EM resident evaluate individual strengths and desires that may help the decision‐making process. We also describe considerations of the postfellowship job market, as this also plays a role in the fellowship decision‐making process.
Faculty Assessment of Emergency Medicine Resident Grit: A Multicenter Study
Authors: Olson Nathan , Olson Adriana Segura , Williamson Kelly , Hartman Nicholas , Branzetti Jeremy , Lank Patrick ,   the Emergency Medicine Education Research Alliance (EMERA)
Published: November 2018

Background

Assessment of trainees’ competency is challenging; the predictive power of traditional evaluations is debatable especially in regard to noncognitive traits. New assessments need to be sought to better understand affective areas like personality. Grit, defined as “perseverance and passion for long‐term goals,” can assess aspects of personality. Grit predicts educational attainment and burnout rates in other populations and is accurate with an informant report version. Self‐assessments, while useful, have inherent limitations. Faculty's ability to accurately assess trainees’ grit could prove helpful in identifying learner needs and avenues for further development.

Objective

This study sought to determine the correlation between EM resident self‐assessed and faculty‐assessed Grit Scale (Grit‐S) scores of that same resident.

Methods

Subjects were PGY‐1 to ‐4 EM residents and resident‐selected faculty as part of a larger multicenter trial involving 10 EM residencies during 2017. The Grit‐S Scale was administered to participating EM residents; an informant version was completed by their self‐selected faculty. Correlation coefficients were computed to assess the relationship between residents’ self‐assessed and the residents’ faculty‐assessed Grit‐S score.

Results

A total of 281 of 303 residents completed the Grit‐S, for a 93% response rate; 200 of 281 residents had at least one faculty‐assessed Grit‐S score. No correlation was found between residents’ self‐assessed and faculty‐assessed Grit‐S scores. There was a correlation between the two faculty‐assessed Grit‐S scores for the same resident.

Conclusion

There was no correlation between resident and faculty‐assessed Grit‐S scores; additionally, faculty‐assessed Grit‐S scores of residents were higher. This corroborates the challenges faculty face at accurately assessing aspects of residents they supervise. While faculty and resident Grit‐S scores did not show significant concordance, grit may still be a useful predictive personality trait that could help shape future training.
Kinematics of the fountain flow during pipe filling with a power‐law fluid
Authors: Borzenko Evgeny I. , Frolov Oleg Yu , Shrager Gennady R.
Published: November 2018

The fountain flow of a non‐Newtonian fluid during a circular pipe filling is investigated. Mathematical description of the process is based on the equations of motion and continuity. The system of equations is completed by the Ostwald‐de Waele rheological equation. The slip condition is used at the contact line. The numerical solution of the formulated problem is obtained using a computational technology based on the finite volume method, SIMPLE procedure, and invariant method, which is used for numerical realization of the boundary conditions on the free surface. The results of parametric studies of the flow kinematic characteristics are presented depending on the governing dimensionless criteria and power‐law index. © 2018 American Institute of Chemical Engineers AIChE J, 65: 850–858, 2019
Changes in health‐related quality of life with long‐term eltrombopag treatment in adults with persistent/chronic immune thrombocytopenia: Findings from the EXTEND study
Authors: Khelif Abderrahim , Saleh Mansoor N. , Salama Abdulgabar , Portella Maria do Socorro O. , Duh Mei Sheng , Ivanova Jasmina , Grotzinger Kelly , Roy Anuja N. , Bussel James B.
Published: November 2018

Patients with persistent/chronic immune thrombocytopenia (cITP) have low platelet counts, increased risk of bleeding and bruising, and often suffer from reduced health‐related quality of life (HRQoL). cITP treatments may either improve HRQoL by increasing platelet counts or decrease it because of side effects. The open‐label EXTEND study (June 2006 to July 2015) evaluated long‐term safety, tolerability, and efficacy of eltrombopag (an oral thrombopoietin‐receptor‐agonist) in adults with cITP who completed a previous eltrombopag ITP trial. The final results of EXTEND were published and used to assess changes in patient‐reported HRQoL over time and association between HRQoL and platelet response. Four validated HRQoL instruments were administered: SF‐36v2 including physical component summary (PCS) and Mental Component Summary; Motivation and Energy Inventory Short Form (MEI‐SF); Fatigue Subscale of FACIT (FACIT‐Fatigue); and FACT‐Thrombocytopenia Subscale Six‐Item Extract (FACT‐Th6). For the 302 patients enrolled, median duration of eltrombopag treatment was 2.37 years. All 4 HRQoL instruments demonstrated positive mean changes from baseline over time adjusted for patient baseline characteristics and rescue therapy use, and had positive association with platelet response (platelet count ≥30 × 109/L; ≥50 × 109/L; and ≥50 × 109/L and >2 times baseline). Improvements from baseline started within 3 months and persisted through 5 years of treatment for FACIT‐Fatigue and FACT‐Th6 (P <.05 for nearly all time points); through 2.5 years for SF‐36v2 PCS and less consistently for the MEI‐SF. In conclusion, in addition to eltrombopag increasing platelet counts and reducing bleeding/bruising, it also alleviated fatigue, concerns about bleeding and bruising, and improved physical function in many patients, especially responders.
Identification of the first Crocodylus siamensis cathelicidin gene and RN15 peptide derived from cathelin domain exhibiting antibacterial activity
Authors: Tankrathok Anupong , Punpad Arpaporn , Kongchaiyapoom Monrudee , Sosiangdi Sirinthip , Jangpromma Nisachon , Daduang Sakda , Klaynongsruang Sompong
Published: November 2018

Cathelicidins are effector molecules of vertebrate immunity that play vital roles against microbial invasion. They are widely identified in mammals, but few have been reported in Crocodilians, which are considered to be species with a powerful immune system. In the present study, we identified and characterized a novel cathelicidin from the blood of the Siamese crocodile, Crocodylus siamensis. A cDNA sequence (501 base pair) encoded a predicted 166‐residue prepropeptide of C. siamensis cathelicidin (Cs‐CATH), which comprised a 21‐residue signal peptide, a 109‐residue cathelin domain, and a 36‐residue mature cathelicidin peptide. Multiple sequence alignment and phylogenetic analysis demonstrated that Cs‐CATH shared a high degree of similarity with other crocodilian cathelicidins. Joint consideration of elastase cleavage site, physicochemical properties, and predicted secondary structure demonstrated that RN15 peptide is a candidate antimicrobial peptide derived from Cs‐CATH. The synthetic RN15 peptide demonstrates antimicrobial activity against Gram‐positive and Gram‐negative bacteria. Scanning electron microscopy illustrated RN15‐peptide‐induced bacteria cells exhibited morphological change. Besides, RN15 peptide demonstrates low hemolytic activity against human erythrocytes and low cytotoxic activity against normal human dermal fibroblasts. This is the first cathelicidin identified from C. siamensis, and it is highlighted that its derived peptide from cathelin domain promises potent novel peptide antibiotics templates.
Methylphenidate promotes the interaction between motor cortex facilitation and attention in healthy adults: A combined study using event‐related potentials and transcranial magnetic stimulation
Authors: Berger Christoph , Müller‐Godeffroy Juliane , Marx Ivo , Reis Olaf , Buchmann Johannes , Dück Alexander
Published: November 2018

Objective

This study investigated simultaneously the impact of methylphenidate (MPH) on the interaction of inhibitory and facilitative pathways in regions processing motor and cognitive functions.

Method

Neural markers of attention and response control (event‐related potentials) and motor cortical excitability (transcranial magnetic stimulation) and their pharmacological modulation by MPH were measured simultaneously in a sample of healthy adults (n = 31) performing a cued choice reaction test.

Results

Methylphenidate modulated attentional gating and response preparation processes (increased contingent negative variation) and response inhibition (increased nogo P3). N1, cue‐ and go‐P3 were not affected by MPH. Motor cortex facilitation, measured with long‐interval cortical facilitation, was increased under MPH in the nogo condition and was positively correlated with the P3 amplitude.

Conclusion

Methylphenidate seems particularly to enhance response preparation processes. The MPH‐induced increased motor cortex facilitation during inhibitory task demands was accompanied by increased terminal response inhibition control, probably as a compensatory process.
Imaging brain tissue slices with terahertz near‐field microscopy
Authors: Geng Guoshuai , Dai Guangbin , Li Dandan , Zhou Shengling , Li Zaoxia , Yang Zhongbo , Xu Yuehong , Han Jiaguang , Chang Tianying , Cui Hong‐Liang , Wang Huabin
Published: November 2018

Photoconductive antenna microprobe (PCAM)‐based terahertz (THz) near‐field imaging technique is promising for biomedical detection due to its excellent biocompatibility and high resolution; yet it is limited by its imaging speed and the difficulty in the control of the PCAM tip‐sample separation. In this work, we successfully realized imaging of mouse brain tissue slices using an improved home‐built PCAM‐based THz near‐field microscope. In this system, the imaging speed was enhanced by designing and applying a voice coil motor‐based delay‐line. The tip‐sample separation control was implemented by developing an image analysis‐based technique. Compared with conventional PCAM‐based THz near‐field systems, our improved system is 100 times faster in imaging speed and the tip‐sample separation can be controlled to a few micrometers (e.g., 3 μm), satisfying the requirements of THz near‐field imaging of biological samples. It took about ~30 min (not the tens of hours it took to acquire the same kind of image previously) to collect a THz near‐field image of brain tissue slices of BALb/c mice (500 μm × 500 μm) with pixel size of 20 μm × 20 μm. The results show that the mouse brain slices can be properly imaged and different regions in the slices (i.e., the corpus callosum region and the cerebrum region) can be identified unambiguously. Evidently, the work demonstrated here provides not only a convincing example but a useful technique for imaging biological samples with THz near‐field microscopy. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2741, 2019.
Insights into the Base‐Assisted Acrylate Formation from CO2/C2H4 Coupling by Pd‐ and Ni‐catalyst: A DFT Mechanistic Study
Authors: Li Yuanhui , Liu Zhen , Zhang Jialong , Cheng Ruihua , Liu Boping
Published: November 2018

In this work, seven base‐assisted reaction paths were designed focusing on the rate‐determining metallalactone deprotonation process to further promote our understanding on nickel‐ and palladium‐catalyzed acrylate formation by CO2/C2H4 coupling in the presence of bases. The deprotonation efficiency of the bases was in accordance to the corresponding basicity, with stronger bases showing higher activity. Besides, a novel two‐step β‐H elimination mechanism through directly deprotonating the β‐H agostic intermediate formed from the metallalactone cleavage proved to be most promising in both the nickel and palladium systems. Whereas the literature‐suggested direct β‐H elimination of the distorted five‐membered ring was relatively inferior. Meanwhile, the high H‐rotation energy barriers hindered the emerging of the cation‐stabilized four‐membered lactone. The effects of the ligand properties appeared to be different in the nickel and palladium systems, since the dcpe (1,2‐bis(dicyclohexylphosphino)ethane) ligand facilitated the Pd‐catalyzed β‐H elimination yet showed minute influence in the Ni‐system. In addition, the palladium center was more active than the nickel center under bulky environment during the base‐assisted β‐H elimination, while the nickel center behaved better in less hindered surroundings, owning to the high sensitivity of the nickel center towards the steric factor.
Hierarchical MoS2@N‐Doped Carbon Hollow Spheres with Enhanced Performance in Sodium Dual‐Ion Batteries
Authors: Li Zhongyu , Yang Liwen , Xu Guobao , Liu Xiong , Wei Xiaolin , Cao Juexian , Chu Paul K.
Published: November 2018

Sodium dual‐ion batteries (S‐DIBs) are attracting increasing interest in large‐scale electrical energy storage, owing to low‐cost and abundant sodium resources and the crucial need to develop high‐performance anode materials to spur the large‐scale application of S‐DIBs. In this work, hierarchical hollow spheres assembled from interconnected few‐layer MoS2 nanosheets with an N‐doped carbon coating (designated as MoS2@NC HHSs) are designed and synthesized. An S‐DIBs full cell is fabricated with MoS2@NC HHSs as the anode, expanded graphite as the cathode, and 1.0 M NaPF6 in EC/DMC/EMC (1 : 1 : 1, volume ratio) as the electrolyte. The combined effects rendered by the ultrathin MoS2 subunits, hollow interior, and N‐doped carbon coating not only promote the reaction kinetics and capacitive‐controlled Na storage, but also guarantee outstanding mechanical stability during Na+ intercalation/deintercalation. The MoS2@NC HHSs‐based S‐DIBs deliver a high reversible capacity of 45 mAhg−1 at 2 Ag−1 and exhibit good cycling performance with a stable reversible capacity of 40 mAhg−1 and high coulombic efficiency beyond 90 % at 1 Ag−1 for 500 cycles. The MoS2@NC HHSs have great potential in high‐performance S‐DIBs.
Growth of E. coli on Solid Media
Authors: Elbing Karen L. , Brent Roger
Published: November 2018

We provide protocols for titering and isolating bacterial colonies from single cells by serial dilutions, for streaking agar plates, and for spreading suspensions of cells on plates. Support protocols describe replica plating and methods for storing strains as agar stabs and frozen stocks. © 2018 by John Wiley & Sons, Inc.
Generating Model Integrated Evidence for Generic Drug Development and Assessment
Authors: Zhao Liang , Kim Myong‐Jin , Zhang Lei , Lionberger Robert
Published: November 2018

Quantitative methods and modeling (QMM) covers a broad spectrum of tool sets, of which physiologically based models and quantitative clinical pharmacology are most critical for generic drugs. QMM has been increasingly applied by the US Food and Drug Administration (FDA) to facilitating generic drug development and review, and has played a critical role in the modernization of bioequivalence (BE) assessment, especially for locally acting drug products, complex products of other types, and modified‐release solid oral dosage forms. QMM has aided the development of novel BE methods, in vitro–only BE approaches, and risk‐based evaluations. The future of QMM is model integrated evidence or virtual BE studies that can potentially provide pivotal information for generic drug approval. In summary, QMM is indispensable in modernizing generic drug development, BE assessment, and regulatory decision makings. Regulatory examples demonstrate how QMM can be used in modernizing generic drug development, addressing challenges in BE assessment, and supporting regulatory decision making.
Diagnostic role of cytology in serous effusions of patients with hematologic malignancies
Authors: Savvidou Kyriaki , Dimitrakopoulou Aglaia , Kafasi Nikolitsa , Konstantopoulos Konstantinos , Vassilakopoulos Theodore , Angelopoulou Maria , Siakantaris Marina , Korkolopoulou Penelope , Kanavaros Panagiotis , Mikou Panagiota
Published: November 2018

Background

We investigated serous effusions occurring during the course of an already known hematologic neoplasia or as a first manifestation of it. We correlated cytology results with flow cytometry results, when available. In the absence of flow cytometry, our correlation was based on clinical follow up information obtained retrospectively. We evaluated our results in relation to the data of the literature and we considered some new suggestions for the improvement of cytology service.

Methods

Serous effusions in hematologic patients were retrieved from the files of the Department of Cytology, Laiko Hospital, for a period of 2 years. All patients had enrolled either a previous hematologic history, or a suspicious clinical and imaging status. Seventy‐three serous effusions were included. Cytology reports consisting of morphology and immunocytochemistry assessment were correlated to flow cytometry results and, occasionally, to clinical follow‐up.

Results

In the group of patients with previous history, sensitivity was 82.76%, positive predictive value was 100%, specificity 100%, and negative predictive value was 58.33%. In the group of patients without previous history, sensitivity and positive predictive value were both 91%, whereas specificity and negative predictive value could not be estimated.

Conclusion

We provide evidence that the diagnostic accuracy of cytology with the adjunct of immunocytochemistry is high compared to flow cytometry for detecting hematologic malignancies. In order to improve clinical performance, it is suggested that a cytology triage of serous effusions in all patients with hematologic malignancy must be implemented.
Intraoperative liquid‐based cytology of rinsed tissue fragments from head and neck lesions
Authors: Kinoshita Yuichi , Inaba Mayumi , Kobayashi Tadao K. , Murata Shin‐ichi
Published: November 2018

Background

Intraoperative diagnosis is an essential tool for the rapid diagnostic assessment of clinically critical head and neck lesions. Thus, we assumed that a combination of frozen section histological and cytological diagnoses may be preferable. Here, we investigated a relatively new method called liquid‐based cytology of rinsed tissue fragments (LBC‐RTF) and compared this method with intraoperative histological diagnosis.

Methods

We used 68 tissue biopsies (9 brains, 8 lymph nodes, 22 salivary glands, and 29 thyroid samples). Samples submitted for intraoperative consultation were divided into two‐halves: one was used to prepare frozen sections, and the other was prepared for LBC‐RTF by washing with PreservCyt. We then compared the final diagnosis obtained from permanent sections with the intraoperative histological diagnosis based on frozen sections and examination of LBC‐RTF preparations.

Results

The accuracy of LBC‐RTF was higher than that of intraoperative histological diagnosis alone, based on frozen sections of every organ (LBC‐RTF: 91.2% vs intraoperative histological diagnosis: 80.9%). With LBC‐RTF, artifacts that are commonly observed in frozen sections were not present. In addition, even with challenging cases from which it is impossible to prepare frozen sections, intraoperative diagnosis was possible using the LBC‐RTF technique.

Conclusion

Both histological and cytological intraoperative diagnoses were possible during a surgery if the LBC‐RTF technique was used. Moreover, our findings suggest that LBC‐RTF improved the diagnostic accuracy of traditional intraoperative diagnosis.
Comparative foliar metabolomics of a tropical and a temperate forest community
Authors: Sedio Brian E. , Parker John D. , McMahon Sean M. , Wright S. Joseph
Published: November 2018

Plant enemies that attack chemically similar host species are thought to mediate competitive exclusion of chemically similar plants and select for chemical divergence among closely related species. This hypothesis predicts that plant defenses should diverge rapidly, minimizing phylogenetic signal. To evaluate this prediction, we quantified metabolomic similarity for 203 tree species that represent >89% of all individuals in large forest plots in Maryland and Panama. We constructed molecular networks based on mass spectrometry of all 203 species, quantified metabolomic similarity for all pairwise combinations of species, and used phylogenetically independent contrasts to evaluate how pairwise metabolomic similarity varies phylogenetically. Leaf metabolomes exhibited clear phylogenetic signal for the temperate plot, which is inconsistent with the prediction. In contrast, leaf metabolomes lacked phylogenetic signal for the tropical plot, with particularly low metabolomic similarity among congeners. In addition, community‐wide variation in metabolomes was much greater for the tropical community, with single tropical genera supporting greater metabolomic variation than the entire temperate community. Our results are consistent with the hypothesis that stronger plant‐enemy interactions lead to more rapid divergence and greater metabolomic variation in tropical than temperate plants. Additional community‐level foliar metabolomes will be required from tropical and temperate forests to evaluate this hypothesis.
Synthesis of Glycosylated 1‐Deoxynojirimycins Starting from Natural and Synthetic Disaccharides
Authors: Liu Bing , van Mechelen Jeanine , van den Berg Richard J. B. H. N. , van den Nieuwendijk Adrianus M. C. H. , Aerts Johannes M. F. G. , van der Marel Gijsbert A. , Codée Jeroen D. C. , Overkleeft Herman S.
Published: November 2018

Iminosugars are an important class of natural products and have been subject to extensive studies in organic synthesis, bioorganic chemistry and medicinal chemistry, yet only a limited number of these studies are on glycosylated iminosugars. Here, a general route of synthesis is presented towards glycosylated 1‐deoxynojirimycin derivatives based on the oxidation–reductive amination protocol that in the past has also been shown to be a versatile route towards 1‐deoxynojirimycin. The strategy can be applied on commercial disaccharides, as shown in four examples, as well as on disaccharides that are not commercially available and are synthesized for this purpose, as shown by a fifth example.