bluuebunny/crossref_metadata_2025 huggingface dataset:
Near Neutral pH Redox Flow Battery with Low Permeability and Long‐Lifetime Phosphonated Viologen Active Species
Authors: Jin Shijian , Fell Eric M. , Vina‐Lopez Lucia , Jing Yan , Michalak P. Winston , Gordon Roy G. , Aziz Michael J.
Published: April 2020

A highly stable phosphonate‐functionalized viologen is introduced as the redox‐active material in a negative potential electrolyte for aqueous redox flow batteries (ARFBs) operating at nearly neutral pH. The solubility is 1.23 m and the reduction potential is the lowest of any substituted viologen utilized in a flow battery, reaching −0.462 V versus SHE at pH = 9. The negative charges in both the oxidized and the reduced states of 1,1′‐bis(3‐phosphonopropyl)‐[4,4′‐bipyridine]‐1,1′‐diium dibromide (BPP−Vi) effect low permeability in cation exchange membranes and suppress a bimolecular mechanism of viologen decomposition. A flow battery pairing BPP−Vi with a ferrocyanide‐based positive potential electrolyte across an inexpensive, non‐fluorinated cation exchange membrane at pH = 9 exhibits an open‐circuit voltage of 0.9 V and a capacity fade rate of 0.016% per day or 0.00069% per cycle. Overcharging leads to viologen decomposition, causing irreversible capacity fade. This work introduces extremely stable, extremely low‐permeating and low reduction potential redox active materials into near neutral ARFBs.
Carbon‐Microcuboid‐Supported Phosphorus‐Coordinated Single Atomic Copper with Ultrahigh Content and Its Abnormal Modification to Na Storage Behaviors
Authors: Li Yifan , Kong Minhong , Hu Junping , Zhou Jisheng
Published: April 2020

Carbon‐supported single atomic metals (SAMs) have aroused great interest in energy conversion and storage fields. However, metal content has to date, been far below expectation. Additionally, theoretical calculations show that SAMs are superb anchoring sites for alkali metal‐ion storage, but the experimental research remains untouched. Herein, a metal–organophosphine framework derived strategy is proposed to prepare carbon microcuboids‐supported single atomic Cu with a high content of 26.3 wt%. Atomic Cu is stabilized mainly by P moieties, exhibiting robust stability even in concentrated HCl and HNO3. Interestingly, experimental investigations and first‐principle calculations indicate that Cu atoms can alter the Na storage behavior and enable Na to maintain an ionic state at a fully discharging state for sodium‐ion batteries, which may be a new pathway to mitigate safety concerns of dendrite formation. The Cu atoms also enhance electron transfer and diffusion kinetics. As a result, the carbon cuboids can deliver a high capacity of 107.7 mAh g−1 at 5 A g−1 and show a long life of 1000 cycles for Na storage. This strategy offers a new possibility for fabricating high‐content P‐coordinated atomic metals for energy conversion and storage.
Recessive congenital myasthenic syndrome caused by a homozygous mutation in SYT2 altering a highly conserved C‐terminal amino acid sequence
Authors: Maselli Ricardo A. , van der Linden Hélio , Ferns Michael
Published: April 2020

Defects in the gene encoding synaptotagmin 2 (SYT2) have been linked to a presynaptic congenital myasthenic syndrome (CMS) and motor neuropathies. However, to date only dominant forms of the disease have been described. We report here a consanguineous patient with a severe recessive form of presynaptic CMS and denervation atrophy caused by the homozygous mutation c.1191delG, p.Arg397Serfs*37 in SYT2. The affected 2‐year‐old girl had profound weakness and areflexia with moderate bulbar deficit. Repetitive nerve stimulation revealed an extreme reduction of compound muscle action potential amplitudes at rest, with a striking facilitation followed by a progressive decline at fast stimulation rates. These findings were reminiscent, but not identical to those seen in the Lambert–Eaton myasthenic syndrome. 3,4 diaminopyridine and pyridostigmine were effective to ameliorate muscle fatigue, but albuterol was ineffective. Modeling of the mutation using the rat Syt1 C2B x‐ray structure revealed that Arg397Serfs*37 disrupts a highly conserved amino acid sequence at the bottom face of the C2B domain not directly involved in calcium binding, but crucial for synaptotagmin‐SNARE interaction and exocytosis. Thus, this report describes a recessive form of synaptotagmin 2‐CMS and highlights the importance of the synaptotagmin C‐terminal on synaptic vesicle fusion and exocytosis.
N‐Heterocyclic Carbene Copper(I) Rotaxanes Mediate Sequential Click Ligations with All Reagents Premixed
Authors: Hsueh Fang‐Che , Tsai Chi‐You , Lai Chien‐Chen , Liu Yi‐Hung , Peng Shie‐Ming , Chiu Sheng‐Hsien
Published: April 2020

We have prepared NHC‐CuIcomplexes with a rotaxane structure and used them as sterically sensitive catalysts for one‐pot sequential copper‐catalyzed azide/alkyne cycloadditions in solutions containing all of the coupling partners premixed in unprotected form. Most notably, a photolabile and sterically encumbered complex first catalyzed the coupling of a less bulky azide/alkyne pair; after removing the protective macrocyclic component from the rotaxane structure, through irradiation with light, the exposed dumbbell‐shaped NHC‐CuIcomplex catalyzed the second click reaction of a bulkier azide/alkyne pair. Using this approach, we obtained predominantly, from a single sealed pot, a bis‐triazole product (84 %) from a mixture of two sterically distinct azides and a diyne.
Biocompatible polymeric electrospun matrices: Micro–nanotopography effect on cell behavior
Authors: Pisani Silvia , Genta Ida , Dorati Rossella , Kavatzikidou Paraskevi , Angelaki Despoina , Manousaki Aleka , Karali Kanelina , Ranella Anthi , Stratakis Emmanuel , Conti Bice
Published: April 2020

This work reports a preliminary biological study performed on nanofibrous biocompatible polylactidecopolycaprolactone (PLA‐PCL) scaffolds intended for tissue regeneration. The aim was to evaluate how matrix surface topography affects cell adhesion and proliferation. Scaffolds prepared by electrospinning either equipped with plane or rotating mandrel collectors, were characterized for their surface topography and nanofiber size. Cell culture studies were carried out using mouse embryonic fibroblast cells lines (NIH‐3T3), as model for skin, murine neuroblastoma neuro‐2α cell line, as model for neuronal tissue, and mouse mesenchymal stem cells (MSCs), because of their differentiation ability. Imaging analysis by scanning electron microscope and laser scanning confocal microscopy together with cell viability (MTT, L 3‐(4,5‐dymethiltiazol‐2‐y)‐2,5 diphenyltetrazolium bromide) test, were performed on cell cultures at fixed time laps. The results showed that electrospun nanofibers supported growth and proliferation of the tested cell lines, but electrospun matrices obtained with rotating mandrel showed significantly higher cell viability that follows the orientation of electrospun nanofibers.
Modulation of Hedgehog Signaling by Kappa Opioids to Attenuate Osteoarthritis
Authors: Weber Alexander E. , Jalali Omid , Limfat Sean , Shkhyan Ruzanna , Van Der Horst Robert , Lee Siyoung , Lin Yucheng , Li Liangliang , Mayer Erik N. , Wang Liming , Liu Nancy Q. , Petrigliano Frank A. , Lieberman Jay R. , Evseenko Denis
Published: April 2020

Objective

Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease‐modifying activity in OA.

Methods

Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee OA in rats was used. A novel automated 3‐dimensional indentation tester (Mach‐1) was used to quantify the thickness and stiffness properties of the articular cartilage.

Results

Inhibition of HH signaling through KOR activation was achieved with a selective peptide agonist, JT09, which reduced HH signaling via the cAMP/CREB pathway in OA human articular chondrocytes (P = 0.002 for treated versus untreated OA chondrocytes). Moreover, JT09 markedly decreased matrix degeneration induced by an HH agonist, SAG, in pig articular chondrocytes and cartilage explants (P = 0.026 versus untreated controls). In vivo application of JT09 via intraarticular injection into the rat knee joint after PMM surgery significantly attenuated articular cartilage degeneration (60% improvement in the tibial plateau; P = 0.021 versus vehicle‐treated controls). In JT09‐treated rats, cartilage content, structure, and functional properties were largely maintained, and osteophyte formation was reduced by 70% (P = 0.005 versus vehicle‐treated controls).

Conclusion

The results of this study define a novel mechanism for the role of KOR in articular cartilage homeostasis and disease, providing a potential unifying mechanistic basis for the overlap in disease processes and features involving opioid and HH signaling. Moreover, this study identifies a potential novel therapeutic strategy in which KOR modulation can improve outcomes in patients with OA.
High‐throughput protein precipitation method with 96‐well plate for determination of doxepin and nordoxepin in human plasma using LC–MS/MS
Authors: Margaryan Tigran , Sargsyan Mariam , Gevorgyan Arpine , Zakaryan Hasmik , Aleksanyan Armine , Harutyunyan Armen , Armoudjian Yeghig , Mikayelyan Astghik
Published: April 2020

The aim of this study was to establish a high‐throughput and sensitive LC–MS/MS method for the determination of doxepin and its major active metabolite nordoxepin in human plasma. It has been designed for bioequivalence study for formulations containing 25 mg of doxepin. Doxepin and nordoxepin were extracted from human plasma samples by protein precipitation with acetonitrile by using protein precipitation 96‐well plates. The analyte was separated using a Phenomenex Kinetex Biphenyl column (100 × 2.1 mm, 2.6 μm) using isocratic elution with a mobile phase of 20 mM ammonium formate (30%) and acetonitrile:methanol 3:7 v:v (70%) at a flow rate of 0.5 mL/min and an injection volume of 10 μL. The detection was performed using a triple quadrupole mass spectrometer by multiple reaction monitoring mode to monitor the precursor‐to‐product ion transitions ofm/z280.4 → 107.0 and 283.4 → 235.0 for doxepin and doxepin‐D3, respectively, and 266.3 → 106.9 and 269.3 → 235.0 for nordoxepin and nordoxepin‐D3, respectively, in positive electrospray ionization mode. The total run time was 3.5 min. The method was validated over a concentration range of 50–10,000 pg/mL using a Triple Quad 4500 MS System (Sciex) for both analytes. The developed and validated method can be successfully used to study the bioequivalence/pharmacokinetics of doxepin and nordoxepin.
Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients
Authors: Shen Chong , Wu Zhouliang , Wang Yujie , Gao Shen , Da La , Xie Linguo , Qie Yunkai , Tian Dawei , Hu Hailong
Published: April 2020

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in multiple biological processes. However, alterations in circRNA profiles during bladder cancer progression and the clinical significance thereof remain unclear. Therefore, high‐throughput RNA sequencing was conducted to identify circRNA and mRNA profiles in five pairs of bladder cancer tissues and adjacent noncancerous tissues. A total of 87 differentially expressed circRNAs and 2756 mRNAs were detected in above bladder cancer samples compared with paired noncancerous samples. Functional enrichment analyses, circRNA‐microRNA‐mRNA, and protein‐protein interaction networks revealed that these dysregulated circRNAs were potentially involved in carcinogenesis and evolution of bladder cancer. Subsequently, the differential expression of eight circRNAs was detected by real‐time qPCR. Hsa_circ_0003141 and hsa_circ_0008039 were significantly upregulated as well as hsa_circ_0026782, hsa_circ_0077837, hsa_circ_0004826, and hsa_circ_0001946 were significantly downregulated among validation of 70 matched bladder cancer tissues (≥75%). Moreover, hsa_circ_0077837 and hsa_circ_0004826 were also verified as markedly downregulated in four bladder cancer cells (100%). Naturally, hsa_circ_0077837 and hsa_circ_0004826 were also demonstrated using RNase‐R+ resistance experiments. In addition, Fisherʹs exact test, Kaplan‐Meier plots, Cox regression analyses, and receiver operating characteristic curve was performed to assess their clinical value. Downregulation of hsa_circ_0077837 and hsa_circ_0004826 all was significantly correlated with worse clinicopathological features and poor prognosis of bladder cancer patients. The area under the receiver operating characteristic curve of them was 0.775 (P < .0001) and 0.790 (P < .0001), respectively. Not surprisingly, in vitro functional experiments also demonstrated that the overexpression of hsa_circ_0077837 and hsa_circ_0004826 significantly weakened the proliferation, migration, and invasion of bladder cancer cells. Overall, hsa_circ_0077837 and hsa_circ_0004826 might act as tumor suppressors in the bladder cancer progression and serve as a potential biomarker for the diagnosis, prognosis, and therapy of bladder cancer.
Toxicity and efficacy of Gamma Knife radiosurgery for brain metastases in melanoma patients treated with immunotherapy or targeted therapy—A retrospective cohort study
Authors: Gatterbauer Brigitte , Hirschmann Dorian , Eberherr Nadine , Untersteiner Helena , Cho Anna , Shaltout Abdallah , Göbl Philipp , Fitschek Fabian , Dorfer Christian , Wolfsberger Stefan , Kasprian Gregor , Höller Christoph , Frischer Josa M.
Published: April 2020

Background

Few safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available. The aim of the study was to evaluate the outcome of melanoma patients with brain metastases (MBM) after Gamma Knife Radiosurgery (GKRS) in relation to IT/TT.

Methods

We evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era.

Results

The median time between the initial melanoma diagnosis and occurrence of MBM was 2.4 years. The median overall survival time was 5.4 years after melanoma diagnosis. The estimated median survival after the initial diagnosis of MBM was 1.0 year (95% CI = 0.7‐1.2 years). Patients treated with anti‐PD‐1 or a combination of anti‐CTLA‐4/PD‐1 showed a significantly longer survival after first GKRS compared to all other forms of treatment. In addition, patients treated with anti‐PD‐1, anti‐CTLA‐4, or a combination of anti‐CTLA‐4/PD‐1 showed a significantly longer time to new MBM after GKRS1 compared to patients treated with other forms and combinations of the oncological therapy. The occurrence of hemorrhage or radiation reaction/necrosis after GKRS did not show any statistically significant differences in relation to IT/TT.

Conclusion

In MBM patients, complications after GKRS are not significantly increased if IT/TT treatment is performed at the time of or after radiosurgery. Further, a clear benefit in distant control and survival is seen in MBM patients treated with GKRS and checkpoint inhibitors. Thus, concomitant treatment of MBM with GKRS and IT/TT seems to be a safe and powerful treatment option although further prospective studies should be conducted.
Reflective‐verbal language and reverie in a qualitative interview
Authors: McVey Lynn , Lees John , Nolan Greg
Published: April 2020

Background

In contrast to dominant approaches to therapy research that look at outcomes and focus on large samples, another primary strand of research considers microphenomenal processes and focuses on small samples. This study contributes to the latter genre in regard to the implicit impact of language.

Aim

This study aims to apply relational psychotherapeutic thinking about empathic dialogue, specifically the concepts of reflective‐verbal language and reverie, to qualitative interviewing.

Methodology

An example from a small‐scale study about emotionally evocative language is reviewed in detail, focusing on the interviewer's phenomenological experience of her conversation with a participant in a qualitative interview.

Findings

The authors argue that the interviewer's reflexive awareness of her reveries and the reflective‐verbal nature of the research dialogue gave her an alternative perspective on the participant's (and her own) experience.

Implications

The study highlights the value within research and practice of maintaining awareness of language at a microphenomenal level, using techniques based on the principles of psychological therapy.
Mindsets, shopping motivations and compulsive buying: Insights from China
Authors: Japutra Arnold , Song Zening
Published: April 2020

This study investigates how mindsets (i.e., the beliefs that individuals have about the nature of human characteristics) are associated with compulsive buying behavior (i.e., the tendency to buy impulsively and obsessively). In particular, we test the relationships between consumer mindsets, three shopping motivations (deal proneness, social comparison, and hedonic motives) and compulsive buying. Based on a survey of 421 respondents conducted in China, our findings reveal the mechanism through which mindsets affect compulsive buying. The results show that when consumers believe in the consistency of personal traits (fixed mindset), they tend to be more vulnerable to deal offers and social comparison. These motivations increase the desire to seek hedonic pleasure, which is associated with a greater propensity for compulsive buying. However, when consumers believe that personal traits can be changed and developed (growth mindset), they seek hedonic pleasure in shopping, which result in a greater tendency to engage in compulsive buying. The present study adds to the existing body of knowledge by unveiling how different mindsets are associated with compulsive buying. In terms of practical implications, this study provides policy makers and marketers with a better understanding of the different motivations that lead to compulsive buying.
Triage considerations for patients referred for structural heart disease intervention during the COVID‐19 pandemic: An ACC/SCAI position statement
Authors: Shah Pinak B. , Welt Frederick G. P. , Mahmud Ehtisham , Phillips Alistair , Kleiman Neal S. , Young Michael N. , Sherwood Matthew , Batchelor Wayne , Wang Dee Dee , Davidson Laura , Wyman Janet , Kadavath Sabeeda , Szerlip Molly , Hermiller James , Fullerton David , Anwaruddin Saif
Published: April 2020

The coronavirus disease‐2019 (COVID‐19) pandemic has strained health care resources around the world, causing many institutions to curtail or stop elective procedures. This has resulted in an inability to care for patients with valvular and structural heart disease in a timely fashion, potentially placing these patients at increased risk for adverse cardiovascular complications, including CHF and death. The effective triage of these patients has become challenging in the current environment, as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID‐19 pandemic against the risk of delaying a needed procedure. In this document, the authors suggest guidelines for how to triage patients in need of structural heart disease interventions and provide a framework for how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, the authors address the triage of patients in need of transcatheter aortic valve replacement and percutaneous mitral valve repair. The authors also address procedural issues and considerations for the function of structural heart disease teams during the COVID‐19 pandemic.
Antioxidant, anti‐inflammatory, and antitumor activities of phenolic compounds from white, red, and black Chenopodium quinoa seed
Authors: Liu Mengjie , Zhu Kaili , Yao Yang , Chen Yinhuan , Guo Huimin , Ren Guixing , Yang Xiushi , Li Jincai
Published: April 2020

Background and objectives

Quinoa (Chenopodium quinoa Willd.) is a promising nutritious cereal known for its rich nutrition and diverse physiological activities. In order to further investigate the profiles and physiological activities of phenolic compounds from quinoa, the composition of free and bound phenolic extracts from white, red, and black quinoa were analyzed, as well as their antioxidant, anti‐inflammatory, and antitumor activities.

Findings

Total phenolic content (TPC) and total flavonoid content (TFC) ranged from 514.03 to 1,409.54 mg gallic acid equivalent (GAE)/100g and 177.49 to 407.75 mg rutin equivalent (RE)/100 g, respectively. TPC existed mainly in bound form in red and black quinoa, but free form in white quinoa. Eight individual phenolic acids were detected, with the total acids amount ranging from 86.21 to 188.76 µg/g. Protocatechuic acid was the dominant phenolic acid both in red and black quinoa. Red quinoa showed the highest TPC and TFC, while black quinoa had the highest phenolic acids concentration. Red quinoa also showed the best ABTS and DPPH radical scavenging activities. Positive correlations were found among antioxidant activity and phenolic components. Besides, phenolics from red and black quinoa showed better anti‐inflammatory and antitumor activity by down‐regulating the NO production and inhibiting the proliferation of MCF‐7 cells.

Conclusions

Quinoa seed is rich in phenolic components, especially the red and black one. Higher phenolic contents in red and black quinoa can be responsible for their superior antioxidant, anti‐inflammatory, and antitumor activities. With potential health benefits, quinoa phenolics may be used as ingredients for functional food.

Significance and novelty

Findings of this study revealed useful information on phenolics and bioactivity of quinoa for its cultivation and breeding with functional oriented purpose. The results could be also applied in health food industry for quinoa material selection and processing.
Spray‐Flame‐Prepared LaCo1–xFexO3 Perovskite Nanoparticles as Active OER Catalysts: Influence of Fe Content and Low‐Temperature Heating
Authors: Alkan Baris , Medina Danea , Landers Joachim , Heidelmann Markus , Hagemann Ulrich , Salamon Soma , Andronescu Corina , Wende Heiko , Schulz Christof , Schuhmann Wolfgang , Wiggers Hartmut
Published: April 2020

Spray‐flame synthesis was used to produce high‐surface‐area perovskite electrocatalysts with high phase purity, minimum surface contamination, and high electrochemical stability. In this study, as‐prepared LaCo1–xFexO3 perovskite nanoparticles (x=0.2, 0.3, and 0.4) were found to contain a high degree of combustion residuals, and mostly consist of both, stoichiometric and oxygen‐deficient perovskite phases. Heating them at moderate temperature (250 °C) in oxygen could remove combustion residuals and increases the content of stoichiometric perovskite while preventing particle growth. A higher surface crystallinity was observed with increasing iron content coming along with a rise in oxygen deficient phases. With heat treatment, OER activity and stability of perovskites improved at 30 and 40 at.% Fe while deteriorating at 20 at.% Fe. This study highlights spray‐flame synthesis as a promising technique to synthesize highly active nanoscale perovskite catalysts with improved OER activity.
Chemistry of NOx and HNO3 Molecules with Gas‐Phase Hydrated O.− and OH− Ions
Authors: Lengyel Jozef , Ončák Milan , Beyer Martin K.
Published: April 2020

The gas‐phase reactions of O.−(H2O)n and OH−(H2O)n, n=20–38, with nitrogen‐containing atmospherically relevant molecules, namely NOx and HNO3, are studied by Fourier transform ion cyclotron resonance (FT‐ICR) mass spectrometry and theoretically with the use of DFT calculations. Hydrated O.− anions oxidize NO. and NO2. to NO2− and NO3− through a strongly exothermic reaction with enthalpy of −263±47 kJ mol−1 and −286±42 kJ mol−1, indicating a covalent bond formation. Comparison of the rate coefficients with collision models shows that the reactions are kinetically slow with 3.3 and 6.5 % collision efficiency. Reactions between hydrated OH− anions and nitric oxides were not observed in the present experiment and are most likely thermodynamically hindered. In contrast, both hydrated anions are reactive toward HNO3 through proton transfer from nitric acid, yielding hydrated NO3−. Although HNO3 is efficiently picked‐up by the water clusters, forming (HNO3)0–2(H2O)mNO3− clusters, the overall kinetics of nitrate formation are slow and correspond to an efficiency below 10 %. Combination of the measured reaction thermochemistry with literature values in thermochemical cycles yields ΔHf(O−(aq.))=48±42 kJ mol−1 and ΔHf(NO2−(aq.))=−125±63 kJ mol−1.
A Single‐Dose, Open‐Label, Randomized, Two‐Way Crossover Study in Healthy Japanese Participants to Evaluate the Bioequivalence and the Food Effect on the Pharmacokinetics of Daprodustat
Authors: Yamada Masanori , Osamura Minori , Ogura Hirofumi , Onoue Tomohiro , Wakamatsu Akira , Numachi Yotaro , Caltabiano Stephen , Mahar Kelly M.
Published: April 2020

Daprodustat is a prolyl hydroxylase inhibitor that stimulates erythropoiesis in a manner similar to the natural response to hypoxia, whereby inhibition of hypoxia inducible factor (HIF) prolyl‐4‐hydroxylases by daprodustat ultimately results in increased levels of HIF‐responsive genes. Daprodustat is under development as an emerging new class of agents for the treatment of anemia associated with chronic kidney disease (CKD). This was a single‐center, single‐dose, open‐label, randomized, 2‐way crossover study in healthy Japanese male participants consisting of 2 parts. The primary objective was to evaluate the bioequivalence (BE) between daprodustat tablet strengths (part 1) and to evaluate the food effect on the pharmacokinetics (PK) of daprodustat (part 2). A total of 64 healthy Japanese male participants were enrolled; 52 participants were included in part 1 and 12 in part 2. BE was demonstrated between the daprodustat 2‐mg tablet and the daprodustat 4‐mg tablet. A standard CKD meal did not have a large effect on the PK parameters of daprodustat after a single oral dose of daprodustat 4 mg. Administration of single oral doses of daprodustat 4 mg was generally well tolerated in the healthy Japanese participants, and no new safety signals were identified without regard to food.
Influence of TMAO as co‐solvent on the gelation of silica‐PNIPAm core‐shell nanogels at intermediate volume fractions
Authors: Frenzel Lara , Lokteva Irina , Koof Michael , Narayanan Suresh , Grübel Gerhard , Lehmkühler Felix
Published: April 2020

We study the structure and dynamics of poly(N‐isopropylacrylamide) (PNIPAm) core‐shell nanogels dispersed in aqueous trimethylamine N‐oxide (TMAO) solutions by means of small‐angle X‐ray scattering and X‐ray photon correlation spectroscopy (XPCS). Upon increasing the temperature above the lower critical solution temperature of PNIPAm at 33 °C, a colloidal gel is formed as identified by an increase of I(q) at small q as well as a slowing down of sample dynamics by various orders of magnitude. With increasing TMAO concentration the gelation transition shifts linearly to lower temperatures. Above a TMAO concentration of approximately 0.40 mol/L corresponding to a 1 : 1 ratio of TMAO and NIPAm groups, collapsed PNIPAm states are found for all temperatures without any gelation transition. This suggests that reduction of PNIPAm‐water hydrogen bonds due to the presence of TMAO results in a stabilisation of the collapsed PNIPAm state and suppresses gelation of the nanogel.
The Decay Mechanism Related to Structural and Morphological Evolution in Lithium‐Rich Cathode Materials for Lithium‐Ion Batteries
Authors: Liu Qiong , Zheng Wei , Lu Zhouguang , Zhang Xuan , Wan Kai , Luo Jiangshui , Fransaer Jan
Published: April 2020

Li‐rich oxides have garnered intense interest recently for their excellent capacity in rechargeable lithium‐ion batteries (LIBs). However, poor cycling stability and capacity degradation during the cycling process impede their practical application. Herein, two ball‐shaped cobalt‐free oxide materials, Li1.1Mg0.05Ni0.3Mn0.55O2 and Li1.1Zn0.05Ni0.3Mn0.55O2, which exhibit excellent cycling performance at a high current between 2 V and 4.8 V, are demonstrated. The two Li‐rich materials are prepared from hydrothermally synthesized carbonated precursors. Both oxides exhibit high reversible capacities of 237 and 231 mAh g−1 at 20 mA g−1, respectively, originating from the redox of Ni2+/Ni4+ and O2−/(O2)n−. Li1.1Mg0.05Ni0.3Mn0.55O2 presents excellent cycling stability after 200 cycles with 90 % capacity retention. Studies of the structural evolution upon electrochemical cycling implies the cathodes undergo a volume expansion, which results in continuous expanding, cracking, and crushing of the spherical particles, which further induces capacity fading in the cathodes.
Shifts in potential geographical distribution of Pterocarya stenoptera under climate change scenarios in China
Authors: Zhang Keliang , Liu Huina , Pan Haolei , Shi Wenhao , Zhao Yi , Li Silei , Liu Junchi , Tao Jun
Published: April 2020

Climate change poses a serious threat to biodiversity. Predicting the effects of climate change on the distribution of a species' habitat can help humans address the potential threats which may change the scope and distribution of species. Pterocarya stenoptera is a common fast‐growing tree species often used in the ecological restoration of riverbanks and alpine forests in central and eastern China. Until now, the characteristics of the distribution of this species' habitat are poorly known as are the environmental factors that influence its preferred habitat. In the present study, the Maximum Entropy Modeling (Maxent) algorithm and the Genetic Algorithm for Ruleset Production (GARP) were used to establish the models for the potential distribution of this species by selecting 236 sites with known occurrences and 14 environmental variables. The results indicate that both models have good predictive power. Minimum temperature of coldest month (Bio6), mean temperature of warmest quarter (Bio10), annual precipitation (Bio12), and precipitation of driest month (Bio14) were important environmental variables influencing the prediction of the Maxent model. According to the models, the temperate and subtropical regions of eastern China had high environmental suitability for this species, where the species had been recorded. Under each climate change scenario, climatic suitability of the existing range of this species increased, and its climatic niche expanded geographically to the north and higher elevation. GARP predicted a more conservative expansion. The projected spatial and temporal patterns of P. stenoptera can provide reference for the development of forest management and protection strategies.
Fractionation of hydrolysate from corn germ protein by ultrafiltration: In vitro antidiabetic and antioxidant activity
Authors: Karimi Amin , Azizi Mohammad Hossein , Ahmadi Gavlighi Hassan
Published: April 2020

In the present work, defatted corn germ was hydrolyzed by three proteases and further separated by sequential ultrafiltration with different molecular weight cutoff (100, 10, 2 kDa). Corn germ protein hydrolysate (CGPH) and their fractions were investigated for antioxidant activity, α‐glucosidase, α‐amylase, and DPP‐IV inhibitory activity. The degree of hydrolysis (DH) after 2 hr was 17.5%, 11.14%, and 2.05% for alcalase, trypsin, and flavourzyme, respectively. Trypsin hydrolysate showed the highest DPPH and ABTS+ radical scavenging and Fe2+ chelating activity, but a lower α‐glucosidase inhibitory activity. F1 fraction (<2 kDa) exhibited highest radical scavenging and α‐glucosidase inhibitory activity. While F2 fraction (2–10 kDa) showed the higher Fe2+ chelating and α‐amylase inhibitory activity, F1 fraction of flavourzyme showed the highest α‐glucosidase inhibitory and F2 fraction of alcalase and flavourzyme exhibited highest α‐amylase inhibitory activity. Hydrolysate and F1 fraction of alcalase and F2 fraction of trypsin showed the highest DPP‐IV inhibitory activity. RP‐HPLC results showed that trypsin hydrolysate had higher levels of high‐hydrophobic peptides. The amino acid composition of the F1 fractions showed high levels of hydrophobic amino acids. Thus, CGPHs may be used as a potential source of antioxidant and antidiabetic peptides in food industry and pharmaceutical application.
Plastic Debris in the Marine Environment: History and Future Challenges
Authors: Napper Imogen Ellen , Thompson Richard C.
Published: April 2020

The success of plastic as a material has shaped the development of modern society and challenged older materials in many of their established uses. However, plastic is now a major component of litter and is extensively reported within the marine environment. Impacts from plastic debris have been identified as a major global conservation issue with implications for maritime industries, tourism, marine life, and human health. Although there are many benefits of plastic, it is clear that society's relationship and reliance on plastics needs to be addressed. Conversely, alternative materials to replace plastic items, or solutions mitigating plastic release, also need to be critiqued to make sure their properties and environmental impacts are more beneficial. This review examines the history and impact of plastics in the marine environment. Current solutions that aim to mitigate plastics accumulation in the environment and the future challenges of plastic as a material are also discussed.
A comparison of robust Mendelian randomization methods using summary data
Authors: Slob Eric A. W. , Burgess Stephen
Published: April 2020

The number of Mendelian randomization (MR) analyses including large numbers of genetic variants is rapidly increasing. This is due to the proliferation of genome‐wide association studies, and the desire to obtain more precise estimates of causal effects. Since it is unlikely that all genetic variants will be valid instrumental variables, several robust methods have been proposed. We compare nine robust methods for MR based on summary data that can be implemented using standard statistical software. Methods were compared in three ways: by reviewing their theoretical properties, in an extensive simulation study, and in an empirical example. In the simulation study, the best method, judged by mean squared error was the contamination mixture method. This method had well‐controlled Type 1 error rates with up to 50% invalid instruments across a range of scenarios. Other methods performed well according to different metrics. Outlier‐robust methods had the narrowest confidence intervals in the empirical example. With isolated exceptions, all methods performed badly when over 50% of the variants were invalid instruments. Our recommendation for investigators is to perform a variety of robust methods that operate in different ways and rely on different assumptions for valid inferences to assess the reliability of MR analyses.
Progesterone loading as a strategy for treating postpartum depression
Authors: Barak Yoram , Glue Paul
Published: April 2020

Postpartum depression (PPD) is a severe disorder that adversely impacts both mothers and infants. It is associated with significant morbidity and mortality and reported prevalence is 11.5% (Ko, Rockhill, Tong, Morrow, & Farr. (2017). MMWR Morbidity and Mortality Weekly Report, 66(6), 153–158). Although PPD's fundamental pathophysiology remains to be fully illuminated, the influence of changes in perinatal hormones such as allopregnanolone (an endogenous progesterone metabolite) are most promising avenues of research. Conventional treatments for PPD are aligned with treatment strategies for depressive disorders. Brexanolone is a small molecule, neuroactive steroid GABAA receptor allosteric modulator consisting of synthetic allopregnanolone and a solubilizing agent. In early 2019, brexanolone received approval in the United States for the treatment of PPD. Brexanolone is only available through a restricted program and is costly. Animal models demonstrate that progesterone prevents depression‐like behaviors. However, studies of progesterone's effects in women suffering from PPD are few and inconclusive. We hypothesize that orally dosed progesterone will increase concentrations of allopregnanolone in the central nervous system, which should relieve symptoms of PPD.
Severity detection and infection level identification of tuberculosis using deep learning
Authors: Chithra R. S. , Jagatheeswari P.
Published: April 2020

Tuberculosis (TB) is a highly infectious disease and is one of the major health problems all over the world. The accurate detection of TB is a major challenge faced by most of the existing methods. This work addresses these issues and developed an effective mechanism for detecting TB using deep learning. Here, the color space transformation is applied for transforming the red green and blue image to LUV space, where L stands for luminance, U and V represent chromaticity values of color images. Then, adaptive thresholding is carried out for image segmentation and various features, like coverage, density, color histogram, area, length, and texture features, are extracted to enable effective classification. After the feature extraction, the size of the features is reduced using principal component analysis. The extracted features are subjected to fractional crow search‐based deep convolutional neural network (FC‐SVNN) for the classification. Then, the image level features, like bacilli count, bacilli area, scattering coefficients and skeleton features are considered to perform severity detection using proposed adaptive fractional crow (AFC)‐deep CNN. Finally, the inflection level is determined using entropy, density and detection percentage. The proposed AFC‐Deep CNN algorithm is designed by modifying FC algorithm using self‐adaptive concept. The proposed AFC‐Deep CNN shows better performance with maximum accuracy value as 0.935.
Trace‐based simulation for 6TiSCH
Authors: Tanaka Yasuyuki , Brun‐Laguna Keoma , Watteyne Thomas
Published: April 2020

Simulation is a powerful tool for development of wireless networks. One key drawback of simulation‐based studies for wireless networking is the need to use a radio propagation model. In this paper, we propose trace‐based simulation for 6TiSCH (IPv6 over the TSCH mode of IEEE802.15.4e). We make the 6TiSCH Simulator run against connectivity traces collected in a real‐world deployment. Our evaluation shows the trace‐based simulation can yield almost the same results as experiments, with 1200 times faster speed in execution
time.
Childhood Emotional Abuse and Maladaptive Coping in Adults Seeking Treatment for Substance Use Disorder
Authors: Watts Justin R. , O'Sullivan Deirdre , Panlilio Carlomagno , Daniels Aubrey D.
Published: April 2020

Little is understood about distinct traumatic exposures and their relationship to later coping strategies. Adults receiving treatment for substance use were assessed for experiential avoidance and a range of traumatic exposures. Only childhood emotional abuse significantly predicted experiential avoidance.
Murine Tissue-Resident PDGFRα+ Fibro-Adipogenic Progenitors Spontaneously Acquire Osteogenic Phenotype in an Altered Inflammatory Environment
Authors: Eisner Christine , Cummings Michael , Johnston Gabrielle , Tung Lin Wei , Groppa Elena , Chang Chihkai , Rossi Fabio MV
Published: April 2020

Acquired heterotopic ossifications (HO) arising as a result of various traumas, including injury or surgical interventions, often result in pain and loss of motion. Though triggers for HO have been identified, the cellular source of these heterotopic lesions as well as the underlying mechanisms that drive the formation of acquired HO remain poorly understood, and treatment options, including preventative treatments, remain limited. Here, we explore the cellular source of HO and a possible underlying mechanism for their spontaneous osteogenic differentiation. We demonstrate that HO lesions arise from tissue-resident PDGFRα+ fibro/adipogenic progenitors (FAPs) in skeletal muscle and not from circulating bone marrow–derived progenitors. Further, we show that accumulation of these cells in the tissue after damage due to alterations in the inflammatory environment can result in activation of their inherent osteogenic potential. This work suggests a mechanism by which an altered inflammatory cell and FAP interactions can lead to the formation of HO after injury and presents potential targets for therapeutics in acquired HO. © 2020 American Society for Bone and Mineral Research.
A pilot study of cdc6 as a biomarker for circulating tumor cells in patients with lung cancer
Authors: An Cheng , Liu Guijian , Cheng Shi , Pang Bo , Sun Shipeng , Zhang Yaying , Pan Zhongdai , Kang Xixiong
Published: April 2020

Background

Cell division cycle 6 (cdc6) is a key factor of DNA replication initiation license system and a proto‐oncogene. It has been detected in some tumor tissues to aid cancer diagnosis in many research projects. However, it remains unclear that if cdc6 could be detected in the peripheral blood, just like liquid biopsy, in solid tumor patients. The aim of this study is to investigate the possibility of cdc6 as a biomarker for circulating tumor cells in patients with lung cancer.

Methods

We first detected the expression of cdc6 in peripheral blood mononuclear cells (PBMCs) and tumor cells by in situ hybridization with cdc6 RNA probe. Then, we examined the expression of cdc6 in PBMCs from health individual, mononuclear cells from cord blood, or A549 cell line by RT‐qPCR. Furthermore, we used RT‐qPCR to test the cdc6 expression in PBMCs from tumor patients (test group) and non‐tumor individuals as a control group. Chi‐square test with Fisher's exact test was used to analyze the statistical significance of the difference. P < .05 is considered as statistically significant difference.

Results

When compared the cdc6 expression in cells from difference sources, we found that A549 tumor cell line had the strongest expression of cdc6, samples from cord blood showed the least expression level, indicating the detection strategy of RT‐qPCR is reasonable. Using this method, we studied whether cdc6 in Peripheral blood could be detected as a biomarker by examining cdc6 expression from PBMCs of patients with lung cancer. We found 20% of patients with lung cancer were cdc6 positive in PBMCs, whereas only 4.26% was found positive in the control group (P = .039, P < .05).

Conclusion

Cell division cycle 6 has a potential to be used as a circulating tumor cell biomarker for lung cancer. Further study in clinical application is still broad needed.
Enhancing inclusion of diverse populations in genomics: A competence framework
Authors: Sharif Saghira M. , Blyth Moira , Ahmed Mushtaq , Sheridan Eamonn , Saltus Roiyah , Yu Juping , Tonkin Emma , Kirk Maggie
Published: April 2020

Genomic knowledge and technology have developed rapidly over the last decade and increased our capabilities to diagnose and manage rare diseases. However, current genomic datasets lack ethnic diversity as many genomic studies have focused on participants of white European ancestry. Studies, such as the Deciphering Developmental Disorders study, have been available to participants of any ancestry but have been unsuccessful in recruiting diverse populations. The inclusion of diverse populations in exome and genome sequencing is important to ensure that clinical benefits of genomics advances are equally shared among all populations and to advance scientific knowledge. Our clinical and research experience with the British Pakistani population (the largest ethnic minority in Yorkshire and Humber, accounting for 4.3% of the population) has fostered the development of an innovative cultural competence framework to enhance the inclusion of diverse populations in clinical genomic research and service provision. The application of this framework has the potential to guide healthcare professionals to develop a wide range of competences, so they are ready to embrace genomic advances in order to improve health outcomes for all patients. This practice model will inform precision medicine and improve access of diverse populations to genomic studies. Although based upon work with the Pakistani population in the UK, it is anticipated that the model would be broadly applicable to all underrepresented populations across the world.
Rural–Urban Disparities in Otolaryngology: The State of Illinois
Authors: Urban Matthew J. , Wojcik Christopher , Eggerstedt Michael , Jagasia Ashok J.
Published: April 2020

Objectives/Hypothesis

To highlight rural–urban disparities in otolaryngology, and to quantify the disparities in access to otolaryngology specialist care across Illinois. Several studies across disciplines have shown increased prevalence and severity of disease in rural communities, relative to their urban counterparts. There is very little published quantifying a disparity in rural access to otolaryngologists.

Study Design

Population study.

Methods

Counties in Illinois were classified based on urbanization level on a scale from I (most urban) to VI (least urban) using the 2013 National Center for Health Statistics (NCHS) Urban–Rural Classification scheme. The six urbanization levels include four metropolitan (I–IV) and two nonmetropolitan levels (V and VI). The name and practice location of all registered otolaryngologists in Illinois were collected using the American Academy of Otolaryngology website (ENTnet.org). Population data were recorded from the most recent US Census (2010).

Results

Two hundred seventy‐eight academy‐registered otolaryngologists were identified in Illinois. One hundred fifty‐one of these providers were located in a single county categorized as a level I by the NCHS scheme. There are over 18,000 square miles and 600,000 persons living in NCHS level VI counties in Illinois with zero registered otolaryngologists. Overall, metropolitan counties (I–IV) averaged 1.32 otolaryngologists per 100,000 population, whereas nonmetropolitan counties (V and VI) averaged 0.46 otolaryngologists per 100,000 (P < .01).

Conclusions

There is a paucity of academy‐certified otolaryngologists with primary practice locations in rural counties of Illinois. There is a significant rural population and massive land area with limited spatial access to otolaryngologic specialist care.

Level of Evidence

NA Laryngoscope, 131:E70–E75, 2021
Polysaccharide Nanoparticles Bearing HDAC Inhibitor as Nontoxic Nanocarrier for Drug Delivery
Authors: Lindemann Henry , Kühne Marie , Grune Christian , Warncke Paul , Hofmann Susanne , Koschella Andreas , Godmann Maren , Fischer Dagmar , Heinzel Thorsten , Heinze Thomas
Published: April 2020

The histone deacetylase inhibitors (HDACi) are potent drugs in the treatment of inflammatory diseases and defined cancer types. However, major drawbacks of HDACi, such as valproic acid (VPA), are limited serum half‐life, side effects and the short circulation time. Thus, the immobilization of VPA in a polysaccharide matrix is used to circumvent these problems and to design a suitable nanocarrier system. Therefore, VPA is covalently attached to cellulose and dextran via esterification with degree of substitution (DS) values of up to 2.20. The resulting hydrophobic polymers are shaped to spherical nanoparticles (NPs) with hydrodynamic diameter between 138 to 221 nm and polydispersity indices from 0.064 to 0.094 by nanoprecipitation and emulsification technique. Lipase treatment of the NPs leads to in vitro release of VPA and hence to an inhibition of HDAC2 activity in a HDAC2 assay. NPs are rapidly taken up by HeLa cells and mainly localize in the cytoplasm. The NPs are hemocompatible and nontoxic as revealed by the shell‐less hen’s egg model.