bluuebunny/crossref_metadata_2025 huggingface dataset:
The eastern shores of the Baltic Sea in the Early Holocene according to natural and cultural relict data
Authors: Žulkus Vladas , Girininkas Algirdas
Published: February 2020

Exploration of the underwater landscape in Lithuanian waters, in the eastern part of the Baltic Sea, allowed identification of trees stumps in growth position, peat sediments, and traces of people that were living in the now flooded landscape. The exploration has been concentrated on localisation of the former Early Holocene coasts. Based on new data about sediment layers of the Preboreal‒Atlantis I, palynological and dendrohronological analysis, identified vegetation species, and dating of wood and peat samples by radiocarbon methods the Baltic Sea water level dynamics during the stages Yoldia Sea‒Early Litorina Sea could be identified. There are traces of the eroded coasts of the Yoldia Sea at a depth of 39–43 m, which were also observed at depths of 44 and 47 m. During the Ancylus Lake transgression, the RF‐I lagoons and small lakes with the peat layer and the surrounding forests were submerged. The water level could have even risen to 10–9 m below present sea level. The water drop during the Ancylus Lake regression is evidenced by a peat layer dated to 9,150–8,520 cal BP, and similar radiocarbon dating of an oak stump. The changes of the species composition of trees are indicative of the noticeable climate changes during the period 11,410–7,900 cal BP. Litorina transgression is marked by a tree stump found at a depth of 14.5 m dated to 7,900–7,660 cal BP. The preference of the Early Holocene population to the coastal zone is evidenced by poles driven into the seabed (one was dated to 9,510–9,460 cal BP) that were detected at a depth of 11 m and the T‐shaped antler axes dated to the Early Neolithic, washed ashore from the Litorina Sea coastal Stone Age settlements.
How protected classes in Medicare Part D influence U.S. drug sales, utilization, and price
Authors: Yarbrough Courtney R.
Published: February 2020

When the Medicare Part D prescription drug benefit was implemented in 2006, six drug classes were designated “protected classes.” Because responsibility for obtaining favorable drug prices depends on private insurers' abilities to negotiate with pharmaceutical manufacturers using the threat of formulary exclusion, the protected class designation could undermine the insurers' ability to control spending and utilization of drugs in these six classes. I estimate the effect of the protected class policy on U.S. national drug sales, utilization, and price using 2001–2010 IMS Health National Sales Perspectives data and Verispan Vector One: National data and controlling for drug and year fixed effects. I find that protected status beginning in 2006 led to $112–121 million per drug per year higher U.S. sales for drugs in protected classes relative to unprotected drugs. Greater sales were driven by the antidepressant, antipsychotic, anticonvulsant, and antineoplastic classes. Subsequent analyses on a subset of drugs reveal that increases in both price and quantity are responsible for the growth of sales in protected class drugs. These results are important for informing the recent and ongoing deliberation by the Medicare program over whether to remove several classes from protection.
Low‐dimensional metal halide perovskites and related optoelectronic applications
Authors: Zhu Pengchen , Zhu Jia
Published: February 2020

Low‐dimensional materials have pivotal significance in modern photonic, electronic, and optoelectronic areas due to their unique properties of the scale effect. Metal halide perovskites have revived in the optoelectronic fields recently, drawing intensive attention in photovoltaic devices, light‐emitting diodes, lasers, photodetectors, and so on. Compared to their three‐dimensional counterparts, the role of low‐dimensional perovskites is becoming crucial, requiring a comprehensive understanding and exploration unceasingly. In this review, we examine low‐dimensional perovskite of different forms and clarify various synthesis methods with morphological and dimensional control. Additionally, we also summarize potential optoelectronic applications based on their advantageous optical/electrical properties and enhanced mechanical integrity and stability. Finally, we propose a future perspective and possible developing directions in the exploration of novel perovskite‐derived materials, new physics, and promising applications.

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INFILTRATION CHARACTERISTICS OF FILM HOLE IRRIGATION UNDER THE INFLUENCE OF MULTIPLE FACTORS
Authors: Zhong Yun , Fei Liangjun , Li Yibo
Published: February 2020

Film hole irrigation is a new type of film‐mulched irrigation technology. To investigate the influences of five factors—bulk density, initial soil water content, irrigation depth, film hole diameter and infiltration time—on the infiltration characteristics of film hole irrigation, 12 experiments were conducted. The infiltration characteristics considered were the cumulative infiltration (I), infiltration rate (i) and average increment of soil water content (∆θ). Two empirical models were established that describe the relationship of I with ∆θ and various influential factors. The proposed models of I and ∆θ had a root mean square error of 5.82 ml and 0.003 cm3 cm−3, respectively. The results revealed that the effects of initial soil water content and irrigation depth on I were not significant (P > 0.05) and that the ranking of factors according to degree of influence, from large to small, was infiltration time, soil bulk density and film hole diameter. Soil bulk density, initial soil moisture, irrigation depth and film hole diameter had highly significant effects on ∆θ (P < 0.01), and their ranking according to degree of influence, from large to small, was initial moisture content, soil bulk density, irrigation depth and film hole diameter. © 2020 John Wiley & Sons, Ltd.
Targeting vasculogenic mimicry by phytochemicals: A potential opportunity for cancer therapy
Authors: Haiaty Sanya , Rashidi Mohammad‐Reza , Akbarzadeh Maryam , Maroufi Nazila F. , Yousefi Bahman , Nouri Mohammad
Published: February 2020

Vasculogenic mimicry (VM) is regarded as a process where very aggressive cancer cells generate vascular‐like patterns without the presence of endothelial cells. It is considered as the main mark of malignant cancer and has pivotal role in cancer metastasis and progression in various types of cancers. On the other hand, resistance to the antiangiogenesis therapies leads to the cancer recurrence. Therefore, development of novel chemotherapies and their combinations is urgently needed for abolition of VM structures and also for better tumor therapy. Hence, identifying compounds that target VM structures might be superior therapeutic factors for cancers treatment and controlling the recurrence and metastasis. In recent times, naturally occurring compounds, especially phytochemicals have obtained great attention due to their safe properties. Phytochemicals are also capable of targeting VM structure and also their main signaling pathways. Consequently, in this review article, we illustrated key signaling pathways in VM, and the phytochemicals that affect these structures including curcumin, genistein, lycorine, luteolin, columbamine, triptolide, Paris polyphylla, dehydroeffusol, jatrorrhizine hydrochloride, grape seed proanthocyanidins, resveratrol, isoxanthohumol, dehydrocurvularine, galiellalactone, oxacyclododecindione, brucine, honokiol, ginsenoside Rg3, and norcantharidin. The recognition of these phytochemicals and their safety profile may lead to new therapeutic agents' development for VM elimination in different types of tumors.
KinCon: Cell‐based recording of full‐length kinase conformations
Authors: Enzler Florian , Tschaikner Philipp , Schneider Rainer , Stefan Eduard
Published: February 2020

The spectrum of kinase alterations displays distinct functional characteristics and requires kinase mutation‐oriented strategies for therapeutic interference. Besides phosphotransferase activity, protein abundance, and intermolecular interactions, particular patient‐mutations promote pathological kinase conformations. Despite major advances in identifying lead molecules targeting clinically relevant oncokinase functions, still many kinases are neglected and not part of drug discovery efforts. One explanation is attributed to challenges in tracking kinase activities. Chemical probes are needed to functionally annotate kinase functions, whose activities may not always depend on catalyzing phospho‐transfer. Such non‐catalytic kinase functions are related to transitions of full‐length kinase conformations. Recent findings underline that cell‐based reporter systems can be adapted to record conformation changes of kinases. Here, we discuss the possible applications of an extendable kinase conformation (KinCon) reporter toolbox for live‐cell recording of kinase states. KinCon is a genetically encoded bioluminescence‐based biosensor platform, which can be subjected for measurements of conformation dynamics of mutated kinases upon small molecule inhibitor exposure. We hypothesize that such biosensors can be utilized to delineate the molecular modus operandi for kinase and pseudokinase regulation. This should pave the path for full‐length kinase‐targeted drug discovery efforts aiming to identify single and combinatory kinase inhibitor therapies with increased specificity and efficacy.
Implementation and evaluation of comprehensive medication management in telehealth practices
Authors: Badowski Melissa E. , Wright Eric A. , Bainbridge Jacquelyn , Michienzi Sarah M. , Nichols Stephanie D. , Turner Kyle M. , Wicke Christine , Awad John , Thompkins April , Martin Randy D.
Published: February 2020

The American College of Clinical Pharmacy (ACCP) endorses comprehensive medication management (CMM) as an essential element of team‐based care and advocates CMM inclusion in value‐based health care reform. Remote delivery of CMM through telehealth platforms is expanding and has the potential to become one of the most common clinical pharmacy services. Building on a previous ACCP publication, “Providing Comprehensive Medication Management in Telehealth,” the 2019 ACCP Clinical Practice Affairs A Committee provides insights and guidance on developing, implementing, evaluating, and improving CMM telehealth practices in this white paper.
Synthesis and discovery of N‐(1‐methyl‐4‐oxo‐4,5‐dihydro‐1H‐imidazol‐2‐yl)‐[1,1′‐biphenyl]‐2‐carboxamide derivatives as antimicrobial agents
Authors: Ashok S. R. , Shivananda M. K. , Shet Prakash M. , Sreenivasa S. , Manikandan Alagumuthu
Published: February 2020

Novel dihydro‐1H‐imidazole‐2‐yl)‐[1,1′‐biphenyl]‐2‐carboxamides (4a‐l) was achieved using a three‐step synthesis process and evaluated as antimicrobial agents. These compounds were characterized through FTIR, NMR, LCMS and evaluated for DNA gyrase inhibition potentials and antimicrobial properties against Gram‐negative bacteria Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424), Klebsiella pneumoniae MTCC 530 and Gram‐positive bacteria Staphylococcus aureus (MTCC 3160), Corynebacterium diphtheriae (MTCC 116) and Streptococcus pyogenes (MTCC 442). Excellent DNA gyrase inhibition exhibited by compound 4f (IC50 0.2 μM and relative percentage activity 96.24%). A broad spectrum of antimicrobial activity showed by compounds 4d, 4f and 4 k with a Minimal Inhibitory Constant (MIC) of 1.05, 1.35 and 1.25 μg mL−1, respectively.
Studies on the photocyclization reaction of 8‐styryl‐substituted coralyne derivatives
Authors: Pithan Phil Marvin , Ihmels Heiko
Published: February 2020

The photoreactivity of four 8‐styryl‐substituted coralyne derivatives was examined by UV/VIS‐ and 1H‐NMR‐spectroscopy. Except for the dimethylamino‐substituted derivative, these cationic azoniaheterocyclic dyes undergo photocyclization that most likely proceeds through an initial E‐Z‐isomerization of the double bond. Subsequent oxidation of the intermediates under aerobic conditions gave the pyrrolo‐annelated quinolizinium derivatives as final products, thus providing a useful synthetic route to polycyclic azoniahetarene derivatives. The 6‐(4‐chlorophenyl)‐substituted pyrroloquinolizinium derivative was isolated on a preparative scale, and the investigation of its photophysical properties revealed significantly red‐shifted absorption (λabs = 465–480 nm) and emission bands (λfl = 550–562 nm) in comparison to the parent coralyne and the styryl‐substituted derivatives.
Targeted Approaches for In Situ Gut Microbiome Manipulation
Authors: Cresci Gail A. M. , Lampe Johanna W. , Gibson Glenn
Published: February 2020

The 2019 Dudrick Research Symposium, entitled “Targeted Approaches for In Situ Gut Microbiome Manipulation,” was held on March 25, 2019, at the American Society for Parenteral and Enteral Nutrition (ASPEN) 2019 Nutrition Science & Practice Conference in Phoenix, AZ. The Dudrick Symposium honors the many pivotal and innovative contributions to the development and advancement of parenteral nutrition (PN) made by Dr Stanley J. Dudrick, physician scientist, academic leader, and a founding member of ASPEN. As the 2018 recipient of the Dudrick award, Dr Gail Cresci organized and chaired the symposium. The symposium addressed the evolving field of nutrition manipulation of the gut microbiome as a means to mitigate disease and support health. Presentations focused on (1) the role of prebiotics as a means to beneficially support gut microbiome composition and function and health; (2) designer synbiotics targeted to support metabolic by‐products altered by ethanol exposure and microbial effectors that manipulate host metabolic outcomes; and, lastly, (3) types of intervention designs used to study diet–gut microbiome interactions in humans and a review of findings from recent interventions, which tested the effects of diet on the microbiome and the microbiome's effect on dietary exposures. New molecular techniques and multiomic approaches have improved knowledge of the structure and functional activity of the gut microbiome; however, challenges remain in establishing causal relationships between changes in the gut microbial–community structure and function and health outcomes in humans.
Comparative Survey on Nutrition Risk and Nutrition Support Among Hospitalized General Surgery Patients Over a 7‐Year Period
Authors: Zhou Xue , Wu Xiaona , Deng Bo , Huang Lujiao
Published: February 2020

Background

In China, the trend of the prevalence of nutrition risk and malnutrition among the patients in hospitals has changed dramatically in the past few years. The aim of this study was to compare the prevalence of nutrition risk, undernutrition, and the application of nutrition support among hospitalized general surgery patients over a 7‐year period from 2010 to 2017.

Methods

A total of 810 consecutive inpatients who met the inclusion criteria upon admission and provided informed consent were recruited from March to December 2017. Nutrition risk was screened using the Nutritional Risk Screening 2002 tool. All the data collected in 2017 were compared with the data collected in 2010.

Results

The prevalence of undernutrition among the surgical patients in 2017 (12.8%) was lower than that in 2011 (15.5%) (P < .05), whereas the prevalence of nutrition risk in 2017 (42.6%) was higher than that in 2011 (30.4%) (P < .01). The application of nutrition support, including parenteral nutrition and enteral nutrition, among the patients in 2017 was higher than that in 2010 (P < .05). In 2017, 70.7% of the patients who were at nutrition risk received nutrition support, whereas only 48.9% of patients at nutrition risk did in 2010 (P < .05). Moreover, 26.9% of patients without nutrition risk received nutrition support in 2017 compared with 18.0% of patients in 2010.

Conclusions

The nutrition statuses among surgical inpatients changed from 2010 to 2017. The prevalence of undernutrition was reduced, whereas the prevalence of nutrition risk increased. The application of nutrition support increased significantly, whereas inappropriate application of nutrition support still existed in our hospital. More attention should be paid to the nutrition‐related issues of general surgery inpatients in the future.
Parenteral Nutrition in Moderately Preterm, Otherwise Healthy Neonates Is Not Associated With Improved Short‐Term Growth Outcomes
Authors: Prusakov Pavel , Speaks Sunday , Magers Jacqueline S.
Published: February 2020

Background

Parenteral nutrition (PN) serves a crucial role in providing nutrition to extremely premature infants who are at high risk for malnutrition. However, little is known about the impact of PN on short‐term growth outcomes in moderately preterm infants.

Methods

In this retrospective cohort analysis, patients were included in the study if they were born at ≥32 but <34 weeks gestational age and had no major comorbidities. The primary outcome of this study was to determine whether initiation of early PN for these patients has any effect on daily weight gain compared with standard dextrose‐containing fluids (DCFs). Secondary outcomes were to evaluate the differences in time to regain birth weight, length of stay, and change in weight, length, and head circumference percentiles from birth to discharge. Incidence of necrotizing enterocolitis, antibiotic usage, or supplemental oxygen utilization was also evaluated.

Results

There were 89 patients in the PN group and 35 patients in the DCF group. The mean daily weight gain was not different between PN and DCF groups when calculated from birth to discharge (11.8 vs 10 g/kg/d, respectively; P = .09). There were also no differences when weight gain was calculated from nadir to discharge: 16.8 vs 15.2 g/kg/d, respectively (P = .1). Lack of differences persisted even when propensity matching was performed.

Conclusion

Based on the study findings, neonates born ≥32 weeks of gestational age without any major comorbidities are unlikely to benefit from PN supplementation.
Optimization extraction and purification of biological activity curcumin from Curcuma longa L by high‐performance counter‐current chromatography
Authors: Pan Yan , Ju Ronghui , Cao Xueli , Pei Hairun , Zheng Tianhao , Wang Wei
Published: February 2020

The extraction condition of curcumin from Curcuma longa L was optimized through four factors and three levels orthogonal experiment based on the results of single factor tests. Under the optimal conditions: the concentration of ethanol  80%, extraction temperature 70°C, the ratio of liquid to material 20, and extraction time 3 h, a crude extract with the yield of curcumin 56.8 mg/g could be obtained. The isolation and purification of curcuminoids from the crude extract was performed on high performance counter current chromatography employing an optimized solvent system n‐hexane/ethyl acetate/methanol/water (2/3/3/1, v/v/v/v). From 97 mg crude sample (in which the purity of curmumin was 68.56%), 67 mg curmumin, 18 mg demethoxycurcumin, and 9.7 mg bisdemethoxycurcumin with a high‐performance liquid chromatography purity of 98.26, 97.39, and 98.67%, respectively, were obtained within 70 min. The antioxidant activities and cytotoxicity of purified curcumin was comparable to that of the commercial product, indicating that the biological activity of curcumin could be maintained by this method.
Secondary Tracheoesophageal Puncture After Laryngectomy Increases Complications With Shunt and Voice Prosthesis
Authors: Scherl Claudia , Kauffels Julia , Schützenberger Anne , Döllinger Michael , Bohr Christopher , Dürr Stephan , Fietkau Rainer , Haderlein Marlen , Koch Michael , Traxdorf Maximilian , Mantsopoulos Konstantinos , Müller Sarina , Iro Heinrich
Published: February 2020

Objectives/Hypothesis

To evaluate the demographics, clinical features, management, and prognostic indicators of tracheoesophageal puncture complications in patients undergoing placement of voice prosthesis following cancer treatment.

Study Design

Retrospective analysis.

Methods

A retrospective analysis was conducted of cases from a tertiary referral center diagnosed between 1996 and 2015. Multivariate logistic regression was used to determine factors associated with tracheoesophageal puncture (TEP) and voice prostheses–complication‐free survival (TEP/VP‐CFS).

Results

One hundred fourteen cases were identified. Most patients were males (92.9%) with pT3 (26.8%) or pT4 (58.1%) N+ (53.6%) tumors. All patients received laryngectomy as the primary treatment, with 75% of patients receiving adjuvant radiation therapy or chemoradiotherapy. Complications with TEP were common (65.2%). The most frequent problem was salivary leakage (50.0%), which at the same time was the most common reason for changing the prosthesis. On univariate regression analysis, prosthesis placement time after adjuvant radiotherapy (hazard ratio [HR]: 4.17, 95% confidence interval [CI]: 2‐8.69), secondary prosthesis placement after primary surgery (HR: 3.97, 95% CI: 1.99‐7.9), and laryngectomy with flap reconstruction (HR: 1.96, 95% CI: 0.99‐3.89) were significant prognosticators for complications. Multivariate regression analysis revealed secondary prosthesis placement after adjuvant radiotherapy (HR: 3.66, 95% CI: 1.39‐9.68) or after primary surgery (HR: 2.57, 95% CI: 0.92‐7.2) to be the strongest predictors of reduced TEP/VP‐CFS.

Conclusions

Secondary prosthesis placement after primary surgery, placement after previous irradiation, and laryngectomy with flap reconstruction are predictors of poor TEP/VP‐CFS. Planned adjuvant radiotherapy is not a contraindication for TEP with prosthetic placement, but it is very important to place the prosthesis during the primary surgery or at least before scheduled radiotherapy.

Level of Evidence

4 Laryngoscope, 2020
Soil properties alter plant and microbial communities to modulate denitrification rates in subtropical riparian wetlands
Authors: Ma Lin , Xiong Ziqian , Yao Lunguang , Liu Guihua , Zhang Quanfa , Liu Wenzhi
Published: February 2020

The capacity of riparian wetlands to remove nitrogen from upland runoff through the denitrification process is mainly controlled by soil properties and biological communities. However, the pathways or mechanisms by which soil properties and biological communities may regulate riparian denitrification rates are still largely unknown. Here, we measured the potential and unamended denitrification rates in sediments from riverine wetlands along a nitrogen‐rich river in subtropical China. We also investigated the plant richness, vegetation cover, and abundance of denitrifying microorganisms in wetland soils. The results show that both potential and unamended denitrification rates presented strong seasonality, and were found to be significantly associated with nitrogen concentration in soils, implying that denitrification process in riparian wetlands is probably nitrogen limited. Moreover, potential and unamended denitrification rates were positively related to denitrifier abundance, plant richness, and vegetation cover. Using structural equation modeling, we found that moisture and nitrogen concentration could influence denitrification rates directly; the indirect effects of these factors on denitrification rates mediated through modulating the structure of plant and microbial communities. These findings suggest that denitrification rates and nitrogen removal capacities in riparian wetlands are jointly modulated by soil properties and biological communities.
Interactive effects of iron and light limitation on the molecular physiology of the Southern Ocean diatom Fragilariopsis kerguelensis
Authors: Moreno Carly M. , Gong Weida , Cohen Natalie R. , DeLong Kimberly , Marchetti Adrian
Published: February 2020

The polar diatom Fragilariopsis kerguelensis is ubiquitous in Southern Ocean waters and is a major responder to iron fertilization, encountering large gradients in iron concentrations and light availability. We performed a comparative transcriptomic analysis of F. kerguelensis grown under varying iron and light conditions in order to investigate the molecular underpinnings that may explain its physiological response to iron and light limitation. Low iron reduced growth rates more than low light, but there was not an additive effect of low iron and low light on growth rate. Low iron treatments (saturating and low light) had the largest transcriptomic response; however, expression patterns were more similar in low light treatments (high and low iron). Under iron and light limitation, carbon fixation and amino acid, ribosome, and sulfur metabolisms were overrepresented relative to the control (iron replete, saturating light). Transcripts of genes encoding for the proteins aquaporin, proteorhodopsin, plastocyanin, and flavodoxin were overrepresented to the greatest extent in the low iron/low light treatment, indicating there may be an additive effect of iron/light colimitation at the molecular level. Iron and light replete cells demonstrated increased expression of genes encoding for the proteins ferritin, carbonic anhydrase, and numerous iron‐dependent proteins relative to the growth‐limiting treatments. This transcriptome analysis reveals mechanisms that may underpin the ecological success of this diatom in low iron and light environments, highlighting the important role of diversified photosynthetic isoforms, iron acquisition, unique detoxification mechanisms of reactive oxygen species, and metabolic shifts in amino acid recycling and carbon metabolism.
Nonlinear Nanophotonic Circuitry: Tristable and Astable Multivibrators and Chaos Generator
Authors: Ma Pujuan , Gao Lei , Ginzburg Pavel , Noskov Roman E.
Published: February 2020

The concept of lumped optical nanoelements (or metactronics), wherein nanometer‐scale structures act as nanoinductors, nanocapacitors, and nanoresistors, has attracted a great deal of attention as a simple toolbox for engineering different nanophotonic devices in analogy with microelectronics. While recent studies of the topic have been predominantly focused on linear functionalities, nonlinear dynamics in microelectronic devices plays a crucial role and provides a majority of functions, employed in modern applications. Here, the metactronics paradigm is extended and nonlinear dynamical modalities are added to those nanophotonic devices that have never been associated with optical nanoantennas. Specifically, it is shown that nonlinear dimer nanoantennae can operate in the regimes of tristable and astable multivibrators as well as chaos generators. The physical mechanism behind these modalities relies on the Kerr‐type nonlinearity of nanoparticles in the dimer enhanced by a dipolar localized surface plasmon resonance. This allows one to provide a positive nonlinear feedback at moderate optical intensities, leading to the desired dynamical behavior via tuning the driving field parameters. The findings shed light on a novel class of nonlinear nanophotonic devices with a tunable nonlinear dynamical response.
Elimination of Re‐excitation in Stimulated Emission Depletion Nanoscopy Based on Photon Extraction in a Phasor Plot
Authors: Chen Yue , Wang Luwei , Yan Wei , Peng Xiao , Qu Junle , Song Jun
Published: February 2020

Stimulated emission depletion (STED) nanoscopy can achieve super‐resolution imaging of microstructures at the nanoscale by confining the fluorescence emission of a diffraction‐limited focusing spot. The depletion wavelength is typically at the red tail of the emission spectrum of the fluorophore to avoid re‐excitation; however, inefficient fluorescence inhibition on account of the small stimulated emission cross‐section results in a huge demand for the depletion of laser power. Here, an accurate photon extraction method is proposed to eliminate re‐excitation caused by blue shift of the depletion wavelength. After only extracting the photons unaffected by a donut‐shaped depletion laser in the phasor plot, both the resolution and signal‐to‐noise ratio of the STED images are significantly improved. As a result, the increased depletion efficiency at a blue shifted depletion wavelength reduces the power demand for achieving a certain resolution. This approach, with flexible wavelength selectivity owing to the independence of depletion power, made more fluorophores applicable for STED super‐resolution imaging, thereby offering more convenient and efficient service to researchers.
Identification of a synergistic combination of dimethylaminoparthenolide and shikonin alters metabolism and inhibits proliferation of pediatric precursor‐B cell acute lymphoblastic leukemia
Authors: Sweeney Shannon R. , Collins Meghan , Pandey Renu , Chiou Jennifer , Lodi Alessia , Tiziani Stefano
Published: February 2020

Exploiting metabolic vulnerabilities of cancer cells with nontoxic, plant derived compounds constitutes a novel strategy for both chemoprevention and treatment. A high‐throughput screening approach was used to evaluate a library of natural products to determine the most synergistic combination in precursor‐B cell acute lymphoblast leukemia. Dimethylaminoparthenolide and shikonin effectively inhibited proliferation resulting in cell death in primary and immortalized leukemia cells, while having negligible effects on normal cells. Dimethylaminoparthenolide and shikonin have been shown separately to inhibit cell survival and proliferative signaling and activate tumor suppressors and proapoptotic pathways. Untargeted metabolomics and metabolic flux analysis with stable isotopically labeled glucose and glutamine exhibited a global shift in metabolism following treatment. Pathway analysis indicated significant differences in amino acid, antioxidant, tricarboxylic acid cycle, and nucleotide metabolism. Together, dimethylaminoparthenolide and shikonin reduced the shunting of glycolytic intermediates into the pentose phosphate pathway for biosynthetic purposes. Similarly, the incorporation of glutamine and glutamine‐derived metabolites into purine and pyrimidine synthesis was inhibited by the combination of dimethylaminoparthenolide and shikonin, effectively impeding biosynthetic pathways critical for leukemia cell survival. This approach demonstrates that a synergistic pair of compounds with malignant cell specificity can effectively target metabolic pathways crucial to leukemia cell proliferation and induce apoptosis.
Control of Energy Transfer Between Pyrene‐ and Perylene‐Nucleosides by the Sequence of DNA‐Templated Supramolecular Assemblies
Authors: Müller Sara , Fritz Yannic , Wagenknecht Hans‐Achim
Published: February 2020

DNA was used as supramolecular scaffold to order chromophores and control their optical properties. Ethynylpyrene as energy donor was attached to 2′‐desoxy‐2‐aminoadenosine that binds selectively to thymidines (T) in the template. Ethynylperylene as acceptor was attached to 2′‐desoxyuridine that is complementary to 2′‐desoxyadenosine (A). This donor‐acceptor pair was assembled along single‐stranded DNA templates of different A−T sequences to investigate the sequence control of the energy transfer between the chromophores. The fluorescence intensities increase in the mixed assemblies along the DNA templates from A10T10 over (AATT)5 to (AT)10, although these templates provide equal numbers of potential binding sites for the two different nucleoside chromophore conjugates and exhibit similar absorbances. This shows that the sequence selective assembly of the two building blocks along DNA templates is programmable and alters the fluorescence readout. Such sequence‐controlled supramolecular chemistry represents the key element for future functional π‐systems in materials for light harvesting of solar energy.
Can PROMIS domains of pain and physical functioning detect changes in health over time for children with sickle cell disease?
Authors: Singh Ashima , Dasgupta Mahua , Simpson Pippa M. , Brousseau David C. , Panepinto Julie A.
Published: February 2020

Background

The Patient‐Reported Outcomes Measurement Information System (PROMIS) includes multiple domains that measure pain and physical functioning which are valid and reliable for use in children with sickle cell disease. The responsiveness of these measures to detect changes in health status over time among children with sickle cell disease is unknown.

Procedure

We conducted a prospective cohort study of children presenting to emergency department (ED) with vaso‐occlusive crises. Children completed PROMIS surveys in the ED and at two follow‐up time points (7‐10 days and 1‐3 months) after their acute care visit. Linear mixed models were used to determine if there were significant changes in PROMIS T scores over time. We used a patient's global assessment of change in pain question to anchor the changes in PROMIS scores (mean and 95% confidence interval). A change was considered statistically significant if the 95% CI did not include 0.

Results

We found that patients improved significantly in all domains 1 to 3 months after discharge from an acute care visit for pain. In addition, the pain and physical stress experience domains were responsive to change 7 to 10 days after discharge. Using the anchor of change in pain, for children who had considerable improvement in pain, there were significant changes in PROMIS T scores ranging from 6 to 15.

Conclusions

Relevant PROMIS domains detect changes in children experiencing acute vaso‐occlusive crises. These domains can be used in research and clinic settings to measure clinically relevant change in children with sickle cell disease.
Exercising with an automated insulin delivery system: qualitative insight into the hopes and expectations of people with type 1 diabetes
Authors: Collard Sarah S , Regmi Pramod R , Hood Korey K , Laffel Lori , Weissberg‐Benchell Jill , Naranjo Diana , Barnard‐Kelly Katharine
Published: February 2020

For people with type 1 diabetes (T1DM), regular exercise can be highly beneficial. Although exercise has been shown to improve quality of life and health for people living with T1DM, there are common barriers. To examine such issues, we explored the perceived impact that automated insulin delivery systems could have on people with T1DM and their families. One common theme found was hopes, expectations and impact on sports and exercise. Four sites (United States: three; UK: one) were involved in this study. Two hundred and eighty‐four participants were recruited across all sites; participants comprised: children (9–11 years); adolescents (12–18 years); parents/caretakers of children and adolescents with T1DM; adults with T1DM (18–77 years); and their significant others/partners. Between May and December 2015, focus groups and semi‐structured interviews were conducted and analysed using content analysis. Three themes found related to the benefits of automated insulin delivery systems: (a) more freedom and spontaneity in the individual's ability to exercise; (b) relief from worry of hypoglycaemia as a result of exercise; (c) removing the ‘guesswork’ of adjusting insulin for exercise. Two further themes emerged relating to potential concerns with regard to safely exercising while wearing an automated insulin delivery system. Further research is encouraged with a view to providing accurate algorithms and increasing confidence for those using automated insulin delivery systems and, in turn, for their exercise colleagues and loved ones.
The moderating role of dissociation in the relation between borderline features and factors of self‐injury in adolescents
Authors: Sumlin Eric , Wall Kiana , Sharp Carla
Published: February 2020

Background

Self‐injurious behaviours (SIB) occur frequently in individuals with borderline personality disorder (BPD). While multiple factors may explain the association between SIB and BPD, studies in adults have pointed to dissociation as factor worth considering. However, this relationship has not been examined in adolescents.

Aims

The current study investigated the role of dissociation as a potential moderator between borderline features and SIB, with the expectation that this association would be stronger in the presence of dissociation.

Methods

One hundred forty‐four adolescent inpatients were compared on measures of BPD, non‐suicidal self‐injury (NSSI) and suicidal behaviour. The relationships between borderline features and self‐injury outcomes were evaluated using linear and logistic regression with dissociation as a moderator.

Results

Borderline features and dissociation were found to be significantly associated with history of NSSI, history of suicide attempt, suicidal ideation (SI) intensity and SI severity. However, dissociation was a significant moderator only in the relationship between borderline features and SI intensity.

Conclusion

Higher levels of dissociation were associated with more engagement with suicidal thoughts but did not necessarily contribute to SIB. Further research into differential patterns of association of self‐injury in patients with BPD may investigate other models where dissociation may more strongly factor into outcomes. © 2020 John Wiley & Sons, Ltd.
Theoretical study of concerted hydroamination‐fragmentation reactions to alkenes and alkynes
Authors: Byers Philip , Doyle Patrick , Augusta Alexandra
Published: February 2020

A new type of concerted cycloaddition‐fragmentation reaction utilizing carbamic acid as the amine source is herein reported. This method will require the use of carbamic acid for these reactions that are driven forward by elimination of a highly stable small molecule (CO2). The formation of this gaseous by‐products would make this type of concerted reaction irreversible, driving the reaction to completion. A theoretical study was completed at the B3LYP/6‐31G(d,p) level, providing evidence of the feasibility of this reaction. Additional computation work was done to show how adding electron donating groups to carbamic acid and electron withdrawing groups, such as fluorine, to the alkyne can additionally lower the activation energy of this reaction. This potential new methodology of unsaturated systems would allow for hydroaminations without the need for transition metal catalysts.
Dysbiosis of the Oral Ecosystem in Severe Congenital Neutropenia Patients
Authors: Zaura Egija , Brandt Bernd W. , Buijs Mark J. , Emingil Gülnur , Ergüz Merve , Karapinar Deniz Yilmaz , Pekpinarli Burç , Bao Kai , Belibasakis Georgios N. , Bostanci Nagihan
Published: February 2020

Purpose

To decipher the underlying immunological mechanisms in predisposition to oral microbial dysbiosis in severe congenital neutropenia (SCN) patients.

Experimental Design

Ten SCN patients (5–23 years old) and 12 healthy controls (5–22 years old) are periodontally examined and provided saliva, subgingival plaque, and gingival crevicular fluid (GCF) samples. The SCN patients received oral hygiene therapy and are re‐evaluated after 6 months. Antimicrobial peptides HPN1‐3 and LL‐37 are assessed in saliva by ELISA. Concentration of 30 cytokines is measured in saliva and GCF by human 30‐plex panel, while bacterial profiles of saliva and subgingival plaque are assessed using 16S rDNA amplicon sequencing.

Results

There is no significant difference in salivary HPN1‐3 and LL‐37 concentration between the SCN patients and controls. At baseline, clinical, immunological, and microbiological parameters of the patients are indicative of oral ecological dysbiosis. The SCN patients have significantly higher bleeding on probing (BOP)%, GCF volume, and cytokine levels, high bacterial load with low bacterial diversity in saliva. The associations between the microbiome and immunological parameters in the SCN patients differ from those in the healthy individuals.

Conclusions and Clinical Relevance

SCN patients have a dysregulated immune response toward commensal oral microbiota, which could be responsible for the observed clinical and microbiological signs of dysbiosis.
Hormetic effect of glyphosate persists during the entire growth period and increases sugarcane yield
Authors: Pincelli‐Souza Renata P , Bortolheiro Fernanda PAP , Carbonari Caio A , Velini Edivaldo D , Silva Marcelo de A
Published: February 2020

BACKGROUND

Stimulation of plant growth by low doses of a toxic compound is defined as a hormetic effect. Exposure of plants to low doses of glyphosate can cause stimulatory effects on growth or other variables. Sugarcane is the major biofuel and sugar‐production crop cultivated in Brazil, but its expansion to new areas is limited; therefore, there is a demand for new technologies to improve sugarcane production per unit area. The use of pesticides to stimulate growth through the hormetic effect might be a suitable strategy to increase sugarcane yields. The purpose of this research was to investigate the effect of a low dose of glyphosate on metabolic compound accumulation, leaf phosphorus (P) concentration, and morphological variables across a one‐year sugarcane cycle, as well as to determine whether the glyphosate effect was sustained and effective in improving the yield and technological quality of the sugarcane at harvest.

RESULTS

The application of a low dose of glyphosate led to higher concentrations of shikimic acid and quinic acid, higher leaf P concentrations, and improved plant growth, yield, and technological quality of the sugarcane, by increasing the Brix% juice, pol% cane, total recoverable sugar, tons of culms per hectare, and tons of pol per hectare, relative to the results for an untreated control.

CONCLUSIONS

The increased growth stimuli, observed through several variables, promoted an improvement in sugarcane yield. Therefore, the application of a low dose of glyphosate to sugarcane is a promising practice for crop management. © 2020 Society of Chemical Industry
Moving beyond immobility: Spatial stories of undergraduate mobility at the “local” college
Authors: Henderson Holly
Published: February 2020

In the English higher education context, “going to” university is commonly associated with leaving the familial home at the age of 18 and moving to a new city. This article sets out to problematise dominant narratives of student mobilities, by focusing on the everyday and imagined mobilities of students who stay in place for their degree education. On the basis of data from a case study of undergraduate education in further education colleges in England, the article sets out three challenges to the binary opposition between student mobilities and immobilities. First, the simple association between immobility, disadvantage, and deficit is challenged. The second challenge complicates perceptions of traditionally mobile undergraduates. Finally, the imagined “other lives” of local students challenge their characterisation as unable or unwilling to imagine student mobility. The article both highlights and seeks to resist powerful popular understandings of mobilities and undergraduate education.
Primary resistance to osimertinib despite acquired T790M
Authors: Chang Ling‐Kai , Chang Yih‐Leong , Shih Jin‐Yuan
Published: February 2020

Current National Comprehensive Cancer Network (NCCN) guidelines suggest plasma‐based testing (liquid biopsy) for T790M in epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung carcinoma (NSCLC) with acquired resistance to first‐/second‐generation EGFR tyrosine kinase inhibitors (TKIs). Positivity for resistant mutation on liquid biopsy may obviate the need for invasive tissue biopsy. We report a rare case of primary resistance to osimertinib, although liquid biopsy revealed EGFR T790M positivity. A 63‐year‐old male, never smoker, was diagnosed with stage IV lung adenocarcinoma with EGFR exon 19 deletion. Treatment started with erlotinib and was continued for 15 months until disease progression. Osimertinib was initiated when liquid biopsy showed EGFR T790M positivity. However, primary resistance to osimertinib was noted on follow‐up imaging. Re‐biopsy revealed small cell lung cancer. Detection of T790M via liquid biopsy among NSCLC patients with acquired resistance to EGFR‐TKI might miss other possible resistant mechanisms. Tissue biopsy should be considered to exclude small cell lung carcinoma (SCLC) transformation.
Soil sample timing, nitrogen fertilization, and incubation length influence anaerobic potentially mineralizable nitrogen
Authors: Clark Jason D. , Veum Kristen S. , Fernández Fabián G. , Kitchen Newell R. , Camberato James J. , Carter Paul R. , Ferguson Richard B. , Franzen David W. , Kaiser Daniel E. , Laboski Carrie A. M. , Nafziger Emerson D. , Rosen Carl J. , Sawyer John E. , Shanahan John F.
Published: February 2020

Understanding the variables that affect the anaerobic potentially mineralizable N (PMNan) test should lead to a standard procedure of sample collection and incubation length, improving PMNan as a tool in corn (Zea mays L.) N management. We evaluated the effect of soil sample timing (preplant and V5 corn development stage [V5]), N fertilization (0 and 180 kg ha−1) and incubation length (7, 14, and 28 d) on PMNan (0–30 cm) across a range of soil properties and weather conditions. Soil sample timing, N fertilization, and incubation length affected PMNan differently based on soil and weather conditions. Preplant vs. V5 PMNan tended to be greater at sites that received < 183 mm of precipitation or < 359 growing degree‐days (GDD) between preplant and V5, or had soil C/N ratios > 9.7:1; otherwise, V5 PMNan tended to be greater than preplant PMNan. The PMNan tended to be greater in unfertilized vs. fertilized soil in sites with clay content > 9.5%, total C < 24.2 g kg−1, soil organic matter (SOM) < 3.9 g kg−1, or C to N ratios < 11.0:1; otherwise, PMNan tended to be greater in fertilized vs. unfertilized soil. Longer incubation lengths increased PMNan at all sites regardless of sampling methods. Since PMNan is sensitive to many factors (sample timing, N fertilization, incubation length, soil properties, and weather conditions), it is important to follow a consistent protocol to compare PMNan among sites and potentially use PMNan to improve corn N management.
Brachiopods from the Byrd Group (Cambrian Series 2, Stage 4) Central Transantarctic Mountains, East Antarctica: biostratigraphy, phylogeny and systematics
Authors: Claybourn Thomas M. , Skovsted Christian B. , Holmer Lars E. , Pan Bing , Myrow Paul M. , Topper Timothy P. , Brock Glenn A.
Published: February 2020

Brachiopods from Cambrian Series 2, Stage 4 carbonate strata of the Byrd Group in the Central Transantarctic Mountains, East Antarctica, are described for the first time. These include six lingulate, one paterinate and one rhynchonelliform taxon, including the new lingulate brachiopod Plicarmus wildi gen. et sp. nov. The biostratigraphy correlates closely to the brachiopods recently reported from the Xinji Formation (Shuiyu section) in North China, as well as brachiopods recovered from the Dailyatia odyssei Zone across the Arrowie Basin of South Australia. These findings also support the previously identified close palaeobiogeography of these regions. The first unambiguous example of the acrotretid brachiopod Eohadrotreta zhenbaensis Li & Holmer outside South China is also identified in the context of its ontogenetic stages. Well‐preserved specimens of the acrotheloid Schizopholis yorkensis (Holmer & Ushatinskaya) facilitate a new reconstruction of its musculature and visceral region. These data are synthesized into a new cladistic analysis that resolves Acrotheloidea as a well‐supported monophyletic clade and supports previous hypotheses of a morphocline in acrotheloid evolution.
Rapid numerical approximation method for integrated covariance functions over irregular data regions
Authors: Simonson Peter , Nychka Douglas , Bandyopadhyay Soutir
Published: February 2020

In many practical applications, spatial data are often collected at areal levels (i.e., block data), and the inferences and predictions about the variable at points or blocks different from those at which it has been observed typically depend on integrals of the underlying continuous spatial process. In this paper, we describe a method based on Fourier transforms by which multiple integrals of covariance functions over irregular data regions may be numerically approximated with the same level of accuracy as traditional methods, but at a greatly reduced computational expense.