bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of Residual Dipolar Couplings of Organic Molecules in Multiple Solvent Systems Using a Liquid‐Crystalline‐Based Medium
Authors: Qin Si‐Yong , Jiang Yan , Sun Han , Liu Han , Zhang Ai‐Qing , Lei Xinxiang
Published: June 2020

Residual dipolar coupling (RDC), a robust anisotropic NMR parameter for structural elucidation of organic molecules, is only accessible in an anisotropic environment. Herein, we introduce a novel alignment medium based on the molecular self‐assembly of oligopeptide amphiphile (OPA). This medium is compatible with different intermediate and polar solvent systems, such as CD3OD, [D6]DMSO, and D2O. The preparation of the OPA‐based medium is simple and rapid, while only very weak background signals were observed from OPAs. Furthermore, we show that the purity of OPA has only a minor influence on the quality of the RDC data. These advantages allow RDC measurements of organic molecules with different polarities and solubilities with high efficiency and accuracy.
Enantiodivergent Cyclization by Inversion of the Reactivity in Ambiphilic Molecules
Authors: Rodríguez‐López Julio , Brovetto Margarita , Martín Víctor S. , Martín Tomás
Published: June 2020

Inverting the reactivity of the functional groups in ambiphilic molecules provides a new synthetic strategy to perform late‐stage enantiodivergence. Both enantiomers of the final compound can be obtained from a common chiral precursor. As a proof of concept, the synthesis of substituted five‐ and six‐membered oxacycles is described. The key step is the cyclization of an ambiphilic linear precursor bearing a propargylic alcohol and an epoxide linked through an alkyl chain. Through a slight modification of these linear precursors and employing different reaction conditions, these functional groups can inverse their chemical reactivity, producing one enantiomer or another of the final product. This enantiodivergent cyclization involves three stereogenic centers that can undergo fully controlled retention or inversion of their configuration depending on the cyclization pathway that is activated. The cyclization provides late‐stage enantiodivergence, enabling the synthesis of either enantiomers of the oxacycles from a common chiral substrate with total transfer of the enantiomeric purity.
Constructing E. coli Co‐Cultures for De Novo Biosynthesis of Natural Product Acacetin
Authors: Wang Xiaonan , Shao Alan , Li Zhenghong , Policarpio Lizelle , Zhang Haoran
Published: June 2020

Modular co‐culture engineering is an emerging approach for biosynthesis of complex natural products. In this study, microbial co‐cultures composed of two and three Escherichia coli strains, respectively, are constructed for de novo biosynthesis of flavonoid acacetin, a value‐added natural compound possessing numerous demonstrated biological activities, from simple carbon substrate glucose. To this end, the heterologous biosynthetic pathway is divided into different modules, each of which is accommodated in a dedicated E. coli strain for functional expression. After the optimization of the inoculation ratio between the constituent strains, the engineered co‐cultures show a 4.83‐fold improvement in production comparing to the mono‐culture controls. Importantly, cultivation of the three‐strain co‐culture in shake flasks result in the production of 20.3 mg L−1 acacetin after 48 h. To the authors' knowledge, this is the first report on acacetin de novo biosynthesis in a heterologous microbial host. The results of this work confirm the effectiveness of modular co‐culture engineering for complex flavonoid biosynthesis.
The maturation of the P1m component in response to voice from infancy to 3 years of age: A longitudinal study in young children
Authors: Yoshimura Yuko , Hasegawa Chiaki , Ikeda Takashi , Saito Daisuke N. , Hiraishi Hirotoshi , Takahashi Tetsuya , Kumazaki Hirokazu , Kikuchi Mitsuru
Published: June 2020

Introduction

In the early development of human infants and toddlers, remarkable changes in brain cortical function for auditory processing have been reported. Knowing the maturational trajectory of auditory cortex responses to human voice in typically developing young children is crucial for identifying voice processing abnormalities in children at risk for neurodevelopmental disorders and language impairment. An early prominent positive component in the cerebral auditory response in newborns has been reported in previous electroencephalography and magnetoencephalography (MEG) studies. However, it is not clear whether this prominent component in infants less than 1 year of age corresponds to the auditory P1m component that has been reported in young children over 2 years of age.

Methods

To test the hypothesis that the early prominent positive component in infants aged 0 years is an immature manifestation of P1m that we previously reported in children over 2 years of age, we performed a longitudinal MEG study that focused on this early component and examined the maturational changes over three years starting from age 0. Five infants participated in this 3‐year longitudinal study.

Results

This research revealed that the early prominent component in infants aged 3 month corresponded to the auditory P1m component in young children over 2 years old, which we had previously reported to be related to language development and/or autism spectrum disorders.

Conclusion

Our data revealed the development of the auditory‐evoked field in the left and right hemispheres from 0‐ to 3‐year‐old children. These results contribute to the elucidation of the development of brain functions in infants.
Sufficiency economy philosophy: Buddhism‐based sustainability framework in Thailand
Authors: Song Hee‐Chan
Published: June 2020

Drawing upon institutional theory, sustainability scholars have demonstrated that various institutional factors, such as environmental regulations, national business systems, and global sustainability standards, shape legitimate sustainability frameworks. However, most of the studies have focused on formal institutions that have law‐like regulations and procedures. Owing to the skewed attention, the role of informal institutions in shaping sustainability frameworks has remained largely unexplored. The present study suggests that an informal institution, particularly religion, can play a significant role in developing a locally driven sustainability framework. In particular, this study investigates Thai context where Buddhism has shaped people's mindset, moral principles and day‐to‐day economic activity. For the past few decades, Thailand has theorized its own unique sustainability framework—sufficiency economy philosophy—based on Buddhist worldview on interrelationships of economy, society, and environment. By shedding light on how religion is formalized as a sustainability framework, this research contributes to institutional approach to sustainability.
Walking the tightrope and stirring things up: Exploring the institutional work of sustainable entrepreneurs
Authors: Arenas Daniel , Strumińska‐Kutra Marta , Landoni Paolo
Published: June 2020

Sustainable entrepreneurs (SEs) operate under different institutional pressures, but they also aim to provoke changes in their institutional environment in order to advance the goals of sustainability. These changes are not always large‐scale, successful transformations. This article adopts the concept of institutional work to explore how SEs engage in purposive, mundane activities to both fit in and influence the prevailing institutional environment. In particular, our findings allow us to introduce and discuss four specific types of work: making sustainability convenient, politicizing economic action, maneuvering around regulation, and relational work. At the end, we suggest that SEs may find themselves in a situation where they aim to transform the prevailing commercial institutional logic in order to promote sustainability goals while also trying to adapt to, and hence reproducing, this same logic they would like to transform.
Implications of a cap‐and‐trade system for emission reductions under an asymmetric duopoly
Authors: Chen Zi‐rui , Nie Pu‐yan
Published: June 2020

Climate change is a global problem causing wide concern and requiring workable solutions. The cap‐and‐trade system is recommended as a workable mechanism to reduce the emissions of enterprises and a popular policy affecting production and the environment. This article considers market power and studies the effects of a cap‐and‐trade system on the performance of companies and environmental protection under an asymmetric duopoly. A two‐step model was established to analyze the outputs, prices, and emission under the cap‐and‐trade system. The result indicates that the cap‐and‐trade system has significant implications for cleaner production. More precisely, the optimal emission cap is feasible with the function of social welfare. Both a low emission cap and high emission trading price are beneficial for promoting the development of sustainability. Moreover, the market value of the cap‐and‐trade system offers a huge incentive to companies emitting carbon dioxide. In particular, inefficient firms have a greater stimulus than efficient ones to reduce emissions to economize the cost of production. In summary, the cap‐and‐trade system makes a great contribution to the development of smart business.
Assessment of expression levels of leptin and leptin receptor as potential biomarkers for risk of prostate cancer development and aggressiveness
Authors: Kamel Hala Fawzy Mohamed , Nassir Anmar M. , Al refai Abeer A.
Published: June 2020

Background

Prostate cancer (PCa) is one of the most frequently diagnosed cancers worldwide. Despite the growing evidence associating obesity and adipokines, particularly leptin and its receptors, with cancer development and progression, it is still a debatable matter in PCa.

Objectives

We aimed to assess the role of leptin and its receptors as potential biomarkers for the risk of PCa development and aggressiveness.

Methods

In this study, 176 men were included and categorized according to an established histopathological diagnosis into three age‐ and BMI‐matched groups. The PCa group included 56 patients while the BPH group and the control group comprised 60 men each. Serum levels of total PSA (tPSA) were assessed by ELISA and mRNA expression levels of leptin and leptin receptors were assessed by RT‐PCR.

Results

Leptin and leptin receptor mRNA expression levels were significantly higher in PCa patients relative to BPH and to healthy control men. Both were overexpressed in PCa patients with aggressive and distantly metastasizing tumors compared to patients with confined tumors. Leptin receptor mRNA was an independent predictor of high Gleason score ≥ 7, distant metastasis, LN, and seminal vesicles invasion.

Conclusion

Leptin and its receptors are suggested to be potential biomarkers for PCa; leptin receptor mRNA might predict risk and aggressiveness of PCa.
Mechanisms of Epstein‐Barr virus nuclear antigen 1 favor Tregs accumulation in nasopharyngeal carcinoma
Authors: Wang Jie , Luo Yunfan , Bi Pei , Lu Juan , Wang Fan , Liu Xiong , Zhang Bao , Li Xiangping
Published: June 2020

Background

Documented reports proved that Epstein‐Barr virus (EBV) infection increased infiltration of Tregs in malignancy. However, the mechanism of EBV recruitment Tregs into nasopharyngeal carcinoma (NPC) tissues has not been detailed discussion.

Methods

Expression of EBV nuclear antigen 1 (EBNA1) and Foxp3 in NPC tissue samples was detected by immunohistochemistry. EBNA1+ NPC cell lines were used to coculture with PBMC, naïve T cells, Tregs, and monocytes. Percent of Treg was detected by flow cytometry.

Results

EBNA1 protein was overexpressed in NPC tissues, and was associated with a number of infiltrated Tregs. EBNA1+ NPC cells converted naïve T cells into Tregs by up‐regulated TGF‐β1. Enhanced CCL20 production in EBNA1‐expressed tumor cells increased Tregs migration. Polarized‐M2 macrophages by EBNA1 expression cells converted naïve T cells into Tregs.

Conclusions

EBNA1 favors accumulation of Tregs in NPC through: (a) upregulated TGF‐β1 converted naïve T cell into Treg; (b) upregulated CCL20 increased Treg migration; and (c) polarized‐M2 macrophage converted naïve T cell into Treg.
Self‐regeneration of an extensive bony defect following mandibular resection
Authors: Hasheminasab Mahboube , Sharifi Reza , Mortazavi Mahsa , Javani Arezoo
Published: June 2020

Spontaneous bone regeneration is a rapid and uncommon formation of new bone in a previous bone defect. Preservation of periosteum as the main source of osteogenesis, young age, and genetics are possible important factors related to this phenomenon.
Sarcoma and the 100,000 Genomes Project: our experience and changes to practice
Authors: Prendergast Sophie C , Strobl Anna‐Christina , Cross William , Pillay Nischalan , Strauss Sandra J , Ye Hongtao , Lindsay Daniel , Tirabosco Roberto , Chalker Jane , Mahamdallie Shazia S , Sosinsky Alona ,   RNOH Pathology Laboratory and Biobank Team,   Genomics England Research Consortium, Flanagan Adrienne M , Amary Fernanda
Published: June 2020

The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5 years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. Herein, we recount the lessons learned by a specialist sarcoma centre that recruited close to 1000 patients to the project, so that we and others may learn from our experience. WGS data was generated from 597 patients, but samples from the remaining approximately 400 patients were not sequenced. This was largely accounted for by unsuitability due to extensive necrosis, secondary to neoadjuvant radiotherapy or chemotherapy, or being placed in formalin. The number of informative genomes produced was reduced further by a PCR amplification step. We showed that this loss of genomic data could be mitigated by sequencing whole genomes from needle core biopsies. Storage of resection specimens at 4 °C for up to 96 h overcame the challenge of freezing tissue out of hours including weekends. Removing access to formalin increased compliance to these storage arrangements. With over 70 different sarcoma subtypes described, WGS was a useful tool for refining diagnoses and identifying novel alterations. Genomes from 350 of the cohort of 597 patients were analysed in this study. Overall, diagnoses were modified for 3% of patients following review of the WGS findings. Continued refinement of the variant‐calling bioinformatic pipelines is required as not all alterations were identified when validated against histology and standard of care diagnostic tests. Further research is necessary to evaluate the impact of germline mutations in patients with sarcoma, and sarcomas with evidence of hypermutation. Despite 50% of the WGS exhibiting domain 1 alterations, the number of patients with sarcoma who were eligible for clinical trials remains small, highlighting the need to revaluate clinical trial design.
Alterations in driver genes are predictive of survival in patients with resected pancreatic ductal adenocarcinoma
Authors: McIntyre Caitlin A. , Lawrence Sharon A. , Richards Allison L. , Chou Joanne F. , Wong Winston , Capanu Marinela , Berger Michael F. , Donoghue Mark T. A. , Yu Kenneth H. , Varghese Anna M. , Kelsen David P. , Park Wungki , Balachandran Vinod P. , Kingham T. Peter , D’Angelica Michael I. , Drebin Jeffrey A. , Jarnagin William R. , Iacobuzio‐Donahue Christine A. , Allen Peter J. , O’Reilly Eileen M.
Published: June 2020

Background

KRAS, TP53, CDKN2A, and SMAD4 are established driver genes in pancreatic ductal adenocarcinoma (PDAC). This study was aimed at determining whether the mutational status of driver genes and those involved in DNA repair pathways are associated with clinical outcomes for individuals who undergo resection.

Methods

Eligible individuals were those who underwent resection of PDAC and consented to targeted sequencing of their primary tumor via Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK‐IMPACT). Genomic alterations were determined on the basis of MSK‐IMPACT results from formalin‐fixed, paraffin‐embedded samples. Associations between genomic alterations and clinical outcomes were assessed.

Results

Targeted sequencing was performed on 283 primary tumors resected between 2004 and 2017. The median follow‐up was 23 months among survivors. Alterations in KRAS and TP53 were associated with worse overall survival (OS) in comparison to wild type (median for KRAS, 38.8 months [95% CI, 33.0‐45.5 months] vs 91.0 months [95% CI, 34.8 months to not available (NA)]; P = .043; median for TP53, 37.4 months [95% CI, 32.1‐42.8 months] vs 65.0 months [95% CI, 33.0 months to NA]; P = .035). KRAS G12D mutations were associated with worse OS (median, 31.6 months [95% CI, 25.3‐45.5 months] vs 39.2 months [95% CI, 37.4‐75.2 months]; P = .012). TP53 truncating mutations (median, 39.6 months [95% CI, 32.4‐75.2 months] vs 33.9 months [95% CI, 24.0‐39.0 months]; P = .020) and those associated with loss of heterozygosity (median, 26.6 months [95% CI, 21.6‐44.2 months] vs 39.2 months [95% CI, 34.5‐49.1 months]; P = .048) had decreased OS. TP53 alterations were independently associated with OS in a multivariate analysis (hazard ratio, 1.54; 95% CI, 1.01‐2.33; P = .042). Individuals with germline alterations in homologous recombination deficiency (HRD) genes had improved OS in comparison with those without them (median, not reached vs 37.0 months; 95% CI, 33.0‐49.8 months; P = .035).

Conclusions

In patients with resected PDAC, genomic alterations in KRAS and TP53 are associated with worse outcomes, whereas alterations in HRD genes are associated with a favorable prognosis. Further studies are needed to better define these alterations as biomarkers in resected PDAC.
QuoVadoPro, an Autonomous Tool for Measuring Intracellular Dynamics Using Temporal Variance
Authors: Basu Himanish , Schwarz Thomas L.
Published: June 2020

Trafficking of intracellular cargo is essential to cellular function and can be defective in pathological states including cancer and neurodegeneration. Tools to quantify intracellular traffic are thus necessary for understanding this fundamental cellular process, studying disease mechanisms, and testing the effects of therapeutic pharmaceuticals. In this article we introduce an algorithm called QuoVadoPro that autonomously quantifies the movement of fluorescently tagged intracellular cargo. QuoVadoPro infers the extent of intracellular motility based on the variance of pixel illumination in a series of time‐lapse images. The algorithm is an unconventional approach to the automatic measurement of intracellular traffic and is suitable for quantifying movements of intracellular cargo under diverse experimental paradigms. QuoVadoPro is particularly useful to measure intracellular cargo movement in non‐neuronal cells, where cargo trafficking occurs as short movements in mixed directions. The algorithm can be applied to images with low temporal or spatial resolutions and to intracellular cargo with varying shapes or sizes, like mitochondria or endoplasmic reticulum: situations in which conventional methods such as kymography and particle tracking cannot be applied. In this article we present a stepwise protocol for using the QuoVadoPro software, illustrate its methodology with common examples, discuss critical parameters for reliable data analysis, and demonstrate its use with a previously published example. © 2020 Wiley Periodicals LLC.

Basic Protocol: QuoVadoPro, an autonomous tool for measuring intracellular dynamics using temporal variance
In Silico Design of Cylindrophanes: The Role of Functional Groups in a Fluoride Selective Host
Authors: Østrøm Ina , Ortolan Alexandre O. , Caramori Giovanni F. , Mascal Mark , Muñoz‐Castro Alvaro , Parreira Renato L. T.
Published: June 2020

Molecular recognition is the key driver in the formation of supramolecular complexes, enabling the selective encapsulation of specific guests. Here, we explore the delicate balance between different energetic terms in the formation of an efficient host for fluoride anions based on a cylindrophane structure, which can be achieved by the incorporation of ligand sites into a cyanuric acid based cyclophane framework, resulting a close proximity between the ammonium hydrogens and the anion. This study describes the character and contribution of different energetic and repulsive terms that favor the efficient inclusion of fluoride. Our findings are useful for further rational design and synthesis of efficient and highly selective fluoride hosts, which have been generally less well described than complexing agents for other halides.
Negative Ion Formation by Thermal Surface Ionization of Sulfur Dioxide
Authors: Marciszuk Karolina , Pieńkos Tomasz , Gontarz Patryk , Pelc Andrzej
Published: June 2020

The generation of negative ions from SO2 in the gas phase was studied using the thermal surface ionization method. Six anion types were measured: O−, S−, SO−, and SO2− and anions with m/z=96 and m/z=128. The most abundant anion formed was S− and the formation routes are discussed for each of the six anions. O−, S−, and SO− are formed via dissociative electron attachment to the molecule, whereas the generation of SO2− and anions with m/z=96 and m/z=128 are probably associated with the formation of H2SO4 in the gas inlet system and the ion source. Using statistical thermodynamics the dissociation temperatures of SO2 and SO in the gas phase are calculated and values of above 1800 °C are obtained for both molecules. We also estimated the optimal filament temperatures for the formation of all anions measured, indicating that for SO2 the optimal temperature is related to the electron affinity of the molecules: the optimal temperature increases with decreasing value of the electron affinity for the molecule corresponding to the respective anion.
Politically connected firms and corporate social responsibility implementation expenditure in sub‐Saharan Africa: Evidence from Ghana
Authors: Adomako Samuel , Nguyen Nguyen P.
Published: June 2020

While previous research has emphasized the role of stakeholder pressures, firm‐specific factors, as well as CEO characteristics as important drivers of corporate social responsibility (CSR) implementation, our understanding of how political connections impact small and medium‐sized enterprises' (SMEs') CSR implementation expenditure is quite limited. In this study, we contribute to filling this gap by investigating the effects of political connections and CSR expenditure and explain the conditions that impact this relationship. Using data from 473 SMEs in Ghana, we find that political connections negatively influence CSR implementation expenditure. However, the negative effect is weakened when a firms' reputation and competitive CSR implementation pressures are high. Implications for theory and practice are discussed.
The National Institutes of Health Chemical Countermeasures Research Program (NIH CCRP): A collaborative opportunity to develop effective and accessible chemical medical countermeasures for the American people
Authors: Yeung David T. , Harper Jill R. , Platoff Gennady E.
Published: June 2020

The United States Department of Health and Human Services (HHS) leads the nation in preventing, preparing for, and responding to the adverse health effects of public health emergencies and disasters. In addition to biological, radiological and nuclear agents, the risk of a high consequence public health emergency due to the intentional and/or accidental release of chemical agents is a major growing concern of the US government. As such, the federal government is fully committed to address public health security threats posed by chemicals. To enhance chemical emergency preparedness and response, HHS oversees the interdepartmental research, advanced development, regulatory review and approval, procurement, and stockpiling of medical countermeasures (MCMs). Within the National Institute of Health (NIH/HHS), the National Institute of Allergy and Infectious Diseases (NIAID) is responsible for the fundamental research and early development of MCMs to prevent deaths and/or treat injuries during and after emergencies due to large scale chemical exposure. This commentary provides an overview of the NIAID/NIH Chemical Countermeasures Research Program (CCRP) and resources to facilitate the research, discovery, and early development of chemical MCMs. Available product development resources include research funding opportunities, expert advice from the NIH, and preclinical and efficacy service support cores to reduce opportunity costs and entry barriers for prospective developers interested in entering or accelerating the development of chemical MCMs.
Scalable Synthesis of LiF‐rich 3D Architected Li Metal Anode via Direct Lithium‐Fluoropolymer Pyrolysis to Enable Fast Li Cycling
Authors: Shang Yuanyuan , Chu Tiankuo , Shi Baohui , Fu Kun (Kelvin)
Published: June 2020

Lithium metal anode holds an important position in fast‐charging batteries. But lithium dendrite issues tend to exacerbate at high currents. LiF can be considered as an effective way to improve the Li metal surface electrochemical stability to achieve high power and high energy. However, most of reported work are relying on in situ formation of a 2D LiF on Li metal in liquid electrolyte, which limits the scalability and plated Li quantity. Here, we address this challenge and report a scalable synthesis of LiF‐rich 3D architected Li metal anode via a direct pyrolysis of molten lithium and fluoropolymer to enable fast Li charging with high current density (20 mA cm−2) and high areal capacity (20 mAh cm−2). The 3D structure is synthesized by the pyrolysis of fluoropolymer with Li metal and results show high similarity to the pristine electrolyte‐derived solid‐electrolyte‐interphase (SEI). This concept using pyrolysis of fluoropolymer with Li‐containing active materials could be also extended to modify Li metal oxide cathode (e.g., LiNi0.5Mn1.5O4) for mixed conductive interphase and engineer Li solid ion conductors (e.g., Li garnet‐type oxides) for interface stabilization and framework design.
Cushing syndrome cardiomyopathy: an unusual manifestation of small‐cell lung cancer
Authors: Pingle Srinath‐Reddi , Shah Tanvi , Mosleh Wassim , Kim Agnes S.
Published: June 2020

Cushing syndrome is a rare cause of dilated cardiomyopathy and heart failure with reduced ejection fraction. Cases describing this association are scarce. We describe a patient presenting with acute heart failure, new cardiomyopathy, refractory hypokalaemia, severe hyperglycaemia, and uncontrolled hypertension who was found to have hypercortisolism secondary to an ectopic adrenocorticotropic hormone‐secreting primary lung neoplasm. This case highlights the effects of hypercortisolism on the myocardium. The finding of a non‐dilated cardiomyopathy in this case is unique because the majority of previously reported Cushing syndrome cardiomyopathy cases have described left ventricular dilatation or significant left ventricular hypertrophy. In addition, small‐cell lung cancer with adrenocorticotropic hormone production causing Cushing syndrome cardiomyopathy is rare.
Synthesis of Metal Oxide Inverse Opals from Metal Nitrates by PMMA Colloidal Crystal Templating
Authors: Zhang Xuyang , Weinberger Christian , Amrehn Sabrina , Wu Xia , Tiemann Michael , Wagner Thorsten
Published: June 2020

Metal oxide inverse opals are interesting for various applications. To achieve highly ordered inverse opal structures, one important issue during the colloidal crystal templating procedure is to form a stable precursor network before the template loses its structural integrity at high temperature. Using poly(methyl methacrylate), PMMA, colloidal crystal templates, it is essential to consider the physical and chemical changes of the precursors induced by the changes of PMMA during the thermal conversion. For a systematic investigation of this matter, we synthesized a variety of metal oxide inverse opals from the respective metal nitrates, including Cr2O3, Ga2O3, Fe2O3, In2O3, CuO, CeO2, and ZnO, to compare the effect of various modifications of precursors on the structural and optical properties. When the nitrate precursors have a lower thermal stability than the PMMA template, we have modified the metal nitrates by chelating or by polyacrylamide gelation to form more stable precursor networks.
Crying out in pain—A systematic review into the validity of vocalization as an indicator for pain
Authors: Helmer Loreine M.L. , Weijenberg Roxane A.F. , de Vries Ralph , Achterberg Wilco P. , Lautenbacher Stefan , Sampson Elizabeth L. , Lobbezoo Frank
Published: June 2020

Background

Vocalization is often used to assess pain, sometimes combined with other behaviours such as facial expressions. Contrary to facial expressions, however, for vocalization, there is little evidence available on the association with pain. The aim of this systematic review was to critically analyse the association between vocalization and pain, to explore if vocalizations can be used as a “stand‐alone” indicator for pain.

Methods

The search was performed according to the Prisma Guidelines for systematic reviews and meta‐analysis. The following terms were used: “Pain Measurement,” “Vocalization” and “Verbalization.” The study population included verbal and non‐verbal individuals, including older people and children. The search was performed in three different databases: PubMed, Embase and CINAHL. A total of 35 studies were selected for detailed investigation. Quality assessments were made using two grading systems: Grading of Recommendations Assessment Development and Evaluation system and the Newcastle‐Ottawa scale.

Results

An association between vocalization and pain was found in most studies, particularly when different types of vocalizations were included in the investigation. Different types of vocalization, but also different types of pain, shape this association. The association is observed within all groups of individuals, although age, amongst others, may have an influence on preferred type of vocalization.

Conclusions

There is an association between vocalization and pain. However, vocalization as a “stand‐alone” indicator for pain indicates only a limited aspect of this multifactorial phenomenon. Using vocalization as an indicator for pain may be more reliable if other pain indicators are also taken into account.

Significance

Vocalizations are frequently used in pain scales, although not yet thoroughly investigated as a “single indicator” for pain, like, e.g. facial expression. This review confirms the role of vocalizations in pain scales, and stresses that vocalizations might be more reliable if used in combination with other pain indicators.
Flexible Polyester Screen‐printed Electrode Modified with Carbon Nanofibers for the Electrochemical Aptasensing of Cadmium (II)
Authors: Fakude Colani T , Arotiba Omotayo A , Arduini Fabiana , Mabuba Nonhlangabezo
Published: June 2020

An aptasensor was prepared by immobilising a biotinylated aptamer selected for Cd(II) on an activated carbon nanofiber (CNF) and streptavidin modified a screen‐printed electrode. The acid activated CNF was characterised by FTIR, CHNS elemental analysis and electron microscopy. Cyclic voltammetry, square wave voltammetry and electrochemical impedance spectroscopy (EIS) were used to characterise each step in the aptasensor preparation electrochemically. A detection limit of 0.11 ppb and a linear range of 2–100 ppb were obtained for Cd(II) with tolerance for other interfering species. The aptasensor was applied in real water samples and validated with ICPOES.
The extended evolutionary synthesis and human origins: Archaeological perspectives
Authors: Murray John K. , Benitez Robert Acio , O'Brien Michael J.
Published: June 2020

Recent developments in evolutionary biology have led to a call for an extension of standard evolutionary theory, with its emphasis on processes such as selection and drift, into a much larger theoretical framework that includes processes such as niche construction, developmental plasticity, inclusive inheritance, and developmental bias. Skeptics argue that these processes are already subsumed within the standard theory and thus an extension is not required. Here, we outline what this evolutionary “rethink” might mean for the study of human origins. Specifically, can paleoanthropologists benefit from an extended theoretical toolkit? The papers in this special issue suggest it can be useful but may not be necessary, depending on the kinds of questions that are being asked.
A causal model for short‐term time series analysis to predict incoming Medicare workload
Authors: Mizan Tasquia , Taghipour Sharareh
Published: June 2020

We have investigated methodologies for predicting radiologists' workload in a short time interval by adopting a machine learning technique. Predicting for shorter intervals requires lower execution time combined with higher accuracy. To deal with this issue, an ensemble model is proposed with the fixed‐batch‐training method. To excel in the execution time, a fixed‐batch‐training method is used. On the other hand, the ensemble of multiple machine learning algorithms provides higher accuracy. The experimental result shows that this predictive model can produce at least 10% higher accuracy in comparison with the other available widely used short‐term time series forecasting models. In the studied medical system, this gain in accuracy for the earlier prediction of workload can reduce the Medicare relative value unit cost by $1.1 million annually, which we have formulated and shown in this paper. The proposed batch‐trained ensemble of experts model has also provided at least a 6% improvement in execution time compared with the other studied models.
Delineating effect of corn microRNAs and matrix, ingested as whole food, on gut microbiota in a rodent model
Authors: Huang Haiqiu , Pham Quynhchi , Davis Cindy D. , Yu Liangli , Wang Thomas T.Y.
Published: June 2020

Dietary microRNAs (miRNAs) are thought to regulate a wide range of biological processes, including the gut microbiota. However, it is difficult to separate specific effect(s) of miRNA from that of the food matrix. This study aims to elucidate the specific effect(s) of dietary corn miRNAs, ingested as a whole food, on the gut microbiota. We developed an autoclave procedure to remove 98% of miRNA from corn. A mouse feeding study was conducted comparing autoclaved corn to nonautoclaved corn and purified corn miRNA. Compared to nonspecific nucleotides and corn devoid of miRNAs, feeding purified corn miRNAs or corn to C57BL/6 mice via gavage or diet supplementation for two weeks lead to a decrease in total bacteria in the cecum. The effect appeared to be due to changes in Firmicutes. Additionally, corn matrix minus miRNA and processing also affected gut bacteria. In silico analysis identified corn miRNAs that aligned to Firmicutes genome sequences lending further support to the interaction between corn miRNAs and this bacterium. These data support interactions between plant food miRNA, as well as matrix, and the gut microbiota exist but complex. However, it provides additional support for mechanism by which bioactive dietary components interact with the gut microbiota.
Oligocene Ailanthus from northwestern Qaidam Basin, northern Tibetan Plateau, China and its implications
Authors: Yang Tao , Jia Jingwei , Chen Hongyu , Zhang Yuxin , Wang Yong , Wang Haojian , Bao Lin , Zhang Li , Li Wenjia , Xie Sanping , Yan Defei
Published: June 2020

As the largest inland basin in the northeastern Tibetan Plateau, Qaidam Basin has traditionally been thought of as the key region to study the Cenozoic climatic changes in the plateau; however, the information from a palaeobotanic respect is still lacking because of the paucity of the fossil plants. Fossil fruits and foliage of Ailanthus (Simaroubaceae) are reported from the Oligocene Shangganchaigou Formation in the northwestern Qaidam Basin, Qinghai Province, China. All the characters suggest that the fossil materials should be assigned to A. confucii, which is one widely distributed fossil species in the Cenozoic, regarded as the analogue of extant A. altissima. Current materials represent the first fossil record of Simaroubaceae in the northern Tibetan Plateau. Based on the climate requirements of the living A. altissima, the ranges of mean annual temperature (MAT) and mean annual precipitation (MAP) reflected by current fossils from Qaidamare 6.9–17.0°C, and 376–1,383 mm, respectively, compared with the current climate at the fossil site with MAT of −1.03°C and MAP of 60.5 mm. The results indicate that the climate conditions of the fossil site during the Early Oligocene were much warmer and more humid than that of the current. We hereby suggest the warm and moist air could approach the northwestern Qaidam and to accommodate the ecological environment in Early Oligocene.
The same, but different: Preserved distractor suppression in old age is implemented through an age‐specific reactive ventral fronto‐parietal network
Authors: Ashinoff Brandon K. , Mayhew Stephen D. , Mevorach Carmel
Published: June 2020

Previous studies have shown age‐related impairments in the ability to suppress salient distractors. One possibility is that this is mediated by age‐related impairments in the recruitment of the left intraparietal sulcus (Left IPS), which has been shown to mediate the suppression of salient distractors in healthy, young participants. Alternatively, this effect may be due to a shift in engagement from proactive control to reactive control, possibly to compensate for age‐related impairments in proactive control. Another possibility is that this is due to changes in the functional specificity of brain regions that mediate salience suppression, expressed in changes in spontaneous connectivity of these regions. We assessed these possibilities by having participants engage in a proactive distractor suppression task while in an fMRI scanner. Although we did not find any age‐related differences in behavior, the young (N = 15) and older (N = 15) cohorts engaged qualitatively distinctive brain networks to complete the task. Younger participants engaged the predicted proactive control network, including the Left IPS. On the other hand, older participants simultaneously engaged both a proactive and a reactive network, but this was not a consequence of reduced network specificity as resting state functional connectivity was largely comparable in both age groups. Furthermore, improved behavioral performance for older adults was associated with increased resting state functional connectivity between these two networks. Overall, the results of this study suggest that age‐related differences in the recruitment of a left lateralized ventral fronto‐parietal network likely reflect the specific recruitment of reactive control mechanisms for distractor inhibition.
Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta‐analysis
Authors: de la Cour Cecilie Dovey , Sperling Cecilie Dyg , Belmonte Federica , Syrjänen Stina , Verdoodt Freija , Kjaer Susanne Krüger
Published: June 2020

The purpose of this systematic review and meta‐analysis was to estimate the overall and type‐specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16INK4a overexpression in relation to HPV‐status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16INK4a overexpression in relation to HPV‐status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6‐38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16INK4a. This meta‐analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.
Liver Transplantation in the Time of COVID19: Barriers and Ethical Considerations for Management and Next Steps
Authors: Jaffe Ariel , Schilsky Michael L. , Deshpande Ranjit , Batra Ramesh
Published: June 2020

The recent outbreak of the novel virus severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), which causes the corona virus disease of 2019 (COVID19), has spread globally and affects millions of people. This pandemic has taxed our health care system and disrupted normal operations, even life‐saving procedures, such as liver transplants. During these unprecedented times, providers and patients are imperiled and resources for diagnosis and care may be limited. Continuing to perform resource‐intense advanced procedures is challenging, as is caring for patients with end‐stage liver disease or patients with urgent needs for liver tumor control. Liver transplantation, in particular, requires critical resources, like blood products and critical care beds, which are fairly limited in the COVID19 pandemic. The potential of COVID19 infections in posttransplant recipients on immunosuppression and staff contacts further adds to the complexity. Therefore, transplant programs must reevaluate the ethicality, feasibility, and safety of performing liver transplants during this pandemic. Herein, we discuss the clinical and ethical challenges posed by performing liver transplants and offer guidance for managing patients with end‐stage liver disease during the COVID19 pandemic.
Structural Diversity‐Oriented Synthesis of Orthogonally Protected Cyclic Amino Acid Derivatives with Multiple Stereogenic Centers
Authors: Nonn Melinda , Remete Attila M. , Kiss Loránd
Published: June 2020

The synthesis of three‐dimensional cyclopentane amino acid derivatives with multiple stereocenters and with high regiochemical and diastereochemical diversity has been achieved starting from cyclopentadiene‐derived β‐aminocyclopentenecarboxylic acid. The small‐molecular design was based on stereo‐ and regiocontrolled functionalization of the starting cyclopentene β‐amino acid through stereoselective oxirane formation/regioselective oxirane opening and resulted in regio‐ and diastereoisomers of novel orthogonally protected aminocyclopentanecarboxylates.
The genomic profile of parathyroid carcinoma based on whole‐genome sequencing
Authors: Hu Ya , Zhang Xiang , Wang Ou , Bi Yalan , Xing Xiaoping , Cui Ming , Wang Mengyi , Tao Wei , Liao Quan , Zhao Yupei
Published: June 2020

Parathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Although some mutations such as CDC73 have been found in patients, the molecular mechanism of PC still needs extensive data to clarify. Whole‐genome sequencing (WGS) was performed with frozen samples from 23 PC patients. Peripheral leukocytes were collected from 14 patients and served as controls. Somatic and germline gene alterations, copy number abnormalities and structural variants were detected. Inactivating CDC73 mutations were identified in 39.1% of patients, but only one germline inactivating mutation was found. Other cancer‐related mutations identified in more than one case were MAF (2/23), NEB (6/23), NCOR1 (2/23), TTK (2/23), GRIN3A (4/23), TRIO (2/23), MAP1B (2/23), TJP2 (2/23) and FAM20A (2/23). In the seven wild‐type CDC73 samples, the mutated genes were enriched in pathways involving antigen presentation, allograft rejection or autoimmune disease. More copy number variants were found in patients with cancer recurrence (P = .006) and CDC73 mutations (P = .022) than in those without these characteristics. PIK3CA loss was found in one sample, which also harboured a CDC73 mutation. Gene alterations in the PI3K/AKT/mTOR pathway were found in 78.3% (18/23) of tumours. The most prominent cancer‐predisposing mutations were PDE4DIP (15/23), MAP3K1 (13/23) and CDC42EP1 (10/23). In conclusion, the PI3K/AKT/mTOR pathway may be pivotal in PC. CDC73 mutation correlated with an increased mutational burden and tumour relapse. PC patients with wild‐type CDC73 harboured mutations relevant to antigen presentation and autoimmune diseases. A molecular classification based on the CDC73 mutation may help to manage follow‐up and therapy for PC patients.
A pre‐existing coordinated inflammatory microenvironment is associated with complete response of vulvar high‐grade squamous intraepithelial lesions to different forms of immunotherapy
Authors: Abdulrahman Ziena , de Miranda Noel F. C. C. , Hellebrekers Bart W. J. , de Vos van Steenwijk Peggy J. , van Esch Edith M. G. , van der Burg Sjoerd H. , van Poelgeest Mariette I. E.
Published: June 2020

Immunotherapy of vulvar high‐grade squamous intraepithelial lesion (vHSIL) is investigated as an alternative for surgery, because of high comorbidity and risk of recurrence. Limited evidence exists on the role and composition of the immune microenvironment in current immunotherapeutic approaches for vHSIL. The vHSIL of 29 patients biopsied before treatment with imiquimod were analyzed by two multiplex seven‐color immunofluorescence panels to investigate the pre‐existing T‐cell and myeloid cell composition in relation to treatment response. The samples were scanned with the Vectra multispectral imaging system. Cells were automatically phenotyped and counted with inForm advanced image analysis software. Cell counts and composition were compared to that of vHSIL patients before therapeutic vaccination (n = 29) and to healthy vulva (n = 27). Our data show that the immune microenvironment of complete responders (CR) to imiquimod resembled the coordinated infiltration with type 1 CD4+ and CD8+ T cells and CD14+ inflammatory myeloid cells also found in healthy vulva. However, more CD8+ T cells and FoxP3+ regulatory T cells were present in CR. The lesions of partial responders (PR) lacked such a coordinated response and displayed an impaired influx of CD14+ inflammatory myeloid cells. Importantly, complete responses after imiquimod or therapeutic vaccination showed the same dependency on a pre‐existing coordinated type 1 T‐cell and CD14+ myeloid cell infiltration. In conclusion, a good clinical outcome after two different forms of immunotherapy for vHSIL is associated with the presence of a primary inflammatory process resulting in the coordinated influx of several types of immune cells which is then amplified.