bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Cortical Gyrification Patterns in Alzheimer's Disease and Impact on Memory Performance
Authors: Núñez Christian , Callén Antonio , Lombardini Federica , Compta Yaroslau , Stephan‐Otto Christian ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: April 2020

Objective

The study of cortical gyrification in Alzheimer's disease (AD) could help to further understanding of the changes undergone in the brain during neurodegeneration. Here, we aimed to study brain gyrification differences between healthy controls (HC), mild cognitive impairment (MCI) patients, and AD patients, and explore how cerebral gyrification patterns were associated with memory and other cognitive functions.

Methods

We applied surface‐based morphometry techniques in 2 large, independent cross‐sectional samples, obtained from the Alzheimer's Disease Neuroimaging Initiative project. Both samples, encompassing a total of 1,270 participants, were analyzed independently.

Results

Unexpectedly, we found that AD patients presented a more gyrificated entorhinal cortex than HC. Conversely, the insular cortex of AD patients was hypogyrificated. A decrease in the gyrification of the insular cortex was also found in older HC participants as compared with younger HC, which argues against the specificity of this finding in AD. However, an increased degree of folding of the insular cortex was specifically associated with better memory function and semantic fluency, only in AD patients. Overall, MCI patients presented an intermediate gyrification pattern. All these findings were consistently observed in the two samples.

Interpretation

The marked atrophy of the medial temporal lobe observed in AD patients may explain the increased folding of the entorhinal cortex. We additionally speculate regarding alternative mechanisms that may also alter its folding. The association between increased gyrification of the insular cortex and memory function, specifically observed in AD, could be suggestive of compensatory mechanisms to overcome the loss of memory function. ANN NEUROL 2020 ANN NEUROL 2020;88:67–80
Amplified Self‐Immolative Release of Small Molecules by Spatial Isolation of Reactive Groups on DNA‐Minimal Architectures
Authors: Prinzen Alexander L. , Saliba Daniel , Hennecker Christopher , Trinh Tuan , Mittermaier Anthony , Sleiman Hanadi F.
Published: April 2020

Triggering the release of small molecules in response to unique biomarkers is important for applications in drug delivery and biodetection. Due to low quantities of biomarker, amplifying release is necessary to gain appreciable responses. Nucleic acids have been used for both their biomarker‐recognition properties and as stimuli, notably in amplified small‐molecule release by nucleic‐acid‐templated catalysis (NATC). The multiple components and reversibility of NATC, however, make it difficult to apply in vivo. Herein, we report the use of the hybridization chain reaction (HCR) for the amplified, conditional release of small molecules from standalone nanodevices. We couple HCR with a DNA‐templated reaction resulting in the amplified, immolative release of small molecules. We integrate the HCR components into single nanodevices as DNA tracks and spherical nucleic acids, spatially isolating reactive groups until triggering. This could be applied to biosensing, imaging, and drug delivery.
A distribution‐based method to gauge market liquidity through scale invariance between investment horizons
Authors: Bianchi Sergio , Pianese Augusto , Frezza Massimiliano
Published: April 2020

A nonparametric method is developed to detect self‐similarity among the rescaled distributions of the log‐price variations over a number of time scales. The procedure allows to test the statistical significance of the scaling exponent that possibly characterizes each pair of time scales and to analyze the link between self‐similarity and liquidity, the core assumption of the fractal market hypothesis. The method can support financial operators in the selection of the investment horizons as well as regulators in the adoption of guidelines to improve the stability of markets. The analysis performed on the S&P500 reveals a very complex, time‐changing scaling structure, which confirms the link between market liquidity and self‐similarity.
Pulsed Electromagnetic Field Versus Whole Body Vibration on Cartilage and Subchondral Trabecular Bone in Mice With Knee Osteoarthritis
Authors: Ye Wenwen , Guo Hua , Yang Xiaotian , Yang Lin , He Chengqi
Published: April 2020

Pulsed electromagnetic field (PEMF) and whole body vibration (WBV) interventions are expected to be important strategies for management of osteoarthritis (OA). The aim of the study was to investigate the comparative effectiveness of PEMF versus WBV on cartilage and subchondral trabecular bone in mice with knee OA (KOA) induced by surgical destabilization of the medial meniscus (DMM). Forty 12‐week‐old male C57/BL mice were randomly divided into four groups (n = 10): Control, OA, PEMF, and WBV. OA was induced (OA, PEMF, and WBV groups) by surgical DMM of right knee joint. Mice in PEMF group received 1 h/day PEMF exposure with 75 Hz, 1.6 mT for 4 weeks, and the WBV group was exposed to WBV for 20 min/day with 5 Hz, 4 mm, 0.3 g peak acceleration for 4 weeks. Micro‐computed tomography (micro‐CT), histology, and immunohistochemistry analyses were performed to evaluate the changes in cartilage and microstructure of trabecular bone. The bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) increased, and bone surface/bone volume (BS/BV) decreased by micro‐CT analysis in PEMF and WBV groups. The Osteoarthritis Research Society International (OARSI) scores in PEMF and WBV groups were significantly lower than in the OA group. Immunohistochemical results showed that PEMF and WBV promoted expressions of Aggrecan, and inhibited expressions of IL‐1β, ADAMTS4, and MMP13. Superior results are seen in PEMF group compared with WBV group. Both PEMF and WBV were effective, could delay cartilage degeneration and preserve subchondral trabecular bone microarchitecture, and PEMF was found to be superior to WBV. Bioelectromagnetics. 2020;41:298–307 © 2020 Bioelectromagnetics Society
PASylation Enhances the Stability, Potency, and Plasma Half‐Life of Interferon α‐2a: A Molecular Dynamics Simulation
Authors: Shamloo Amir , Rostami Peyman , Mahmoudi Ashkan
Published: April 2020

In this study, the effectiveness of PASylation in enhancing the potency and plasma half‐life of pharmaceutical proteins has been accredited as an alternative technique to the conventional methods such as PEGylation. Proline, alanine, and serine (PAS) chain has shown some advantages including biodegradability improvement and plasma half‐life enhancement while lacking immunogenicity or toxicity. Although some experimental studies have been performed to find the mechanism behind PASylation, the detailed mechanism of PAS effects on the pharmaceutical proteins has remained obscure, especially at the molecular level. In this study, the interaction of interferon α‐2a (IFN) and PAS chain is investigated using molecular dynamics simulation method. Several important parameters including secondary structure, root‐mean‐square distance, and solvent accessible surface area to investigate the stability, bioavailability, and bioactivity of the PASylated protein are studied. The results demonstrate that IFN conformation is not affected critically through PASylation while it results in improvement of the protein stability and bioactivity. Therefore, PASylation can be considered as a proper biological alternative technique to increase the plasma half‐life of the biopharmaceutical proteins through enlarging apparent volume. The proposed simulation represents a computational approach that would provide a basis for the study of PASylated pharmaceutical proteins for different future applications.
Fluorescent indicators for continuous and lineage‐specific reporting of cell‐cycle phases in human pluripotent stem cells
Authors: Chang Yun , Hellwarth Peter B. , Randolph Lauren N. , Sun Yufei , Xing Yuxian , Zhu Wuqiang , Lian Xiaojun Lance , Bao Xiaoping
Published: April 2020

Proper cell‐cycle progression is essential for the self‐renewal and differentiation of human pluripotent stem cells (hPSCs). The fluorescent ubiquitination‐based cell‐cycle indicator (FUCCI) has allowed the dual‐color visualization of the G1 and S/G2/M phases in various dynamic models, but its application in hPSCs is not widely reported. In addition, lineage‐specific FUCCI reporters have not yet been developed to analyze complex tissue‐specific cell‐cycle progression during hPSC differentiation. Desiring a robust tool for spatiotemporal reporting of cell‐cycle events in hPSCs, we employed the CRISPR/Cas9 genome editing tool and successfully knocked the FUCCI reporter into the AAVS1 safe harbor locus of hPSCs for stable and constitutive FUCCI expression, exhibiting reliable cell‐cycle‐dependent fluorescence in both hPSCs and their differentiated progeny. We also established a cardiac‐specific TNNT2‐FUCCI reporter for lineage‐specific cell‐cycle monitoring of cardiomyocyte differentiation from hPSCs. This powerful and modular FUCCI system should provide numerous opportunities for studying human cell‐cycle activity, and enable the identification and investigation of novel regulators for adult tissue regeneration.
Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results
Authors: Kaaij R T , Wassenaar E C E , Koemans W J , Sikorska K , Grootscholten C , Los M , Huitema A , Schellens J H M , Veenhof A A F A , Hartemink K J , Aalbers A G J , Ramshorst B , Boerma D , Boot H , Sandick J W
Published: April 2020

Background

The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I–II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored.

Methods

Patients with resectable cT3–cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m2).

Results

Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m2 docetaxel), six at dose level 2 (50 mg/m2) and four at dose level 3 (75 mg/m2). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3).

Conclusion

Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m2 oxaliplatin and 50 mg/m2 normothermic docetaxel.
Total tumour volume as a prognostic factor in patients with resectable colorectal cancer liver metastases
Authors: Tai K , Komatsu S , Sofue K , Kido M , Tanaka M , Kuramitsu K , Awazu M , Gon H , Tsugawa D , Yanagimoto H , Toyama H , Murakami S , Murakami T , Fukumoto T
Published: April 2020

Background

Although total tumour volume (TTV) may have prognostic value for hepatic resection in certain solid cancers, its importance in colorectal liver metastases (CRLM) remains unexplored. This study investigated its prognostic value in patients with resectable CRLM.

Method

This was a retrospective review of patients who underwent hepatic resection for CRLM between 2008 and 2017 in a single institution. TTV was measured from CT images using three-dimensional construction software; cut-off values were determined using receiver operating characteristic (ROC) curve analyses. Potential prognostic factors, overall survival (OS) and recurrence-free survival (RFS) were determined using multivariable and Kaplan–Meier analyses.

Results

Some 94 patients were included. TTV cut-off values for OS and RFS were 100 and 10 ml respectively. Right colonic primary tumours, primary lymph node metastasis and bilobar liver metastasis were included in the multivariable analysis of OS; a TTV of 100 ml or above was independently associated with poorer OS (hazard ratio (HR) 6·34, 95 per cent c.i. 2·08 to 17·90; P = 0·002). Right colonic primary tumours and primary lymph node metastasis were included in the RFS analysis; a TTV of 10 ml or more independently predicted poorer RFS (HR 1·90, 1·12 to 3·57; P = 0·017). The 5-year OS rate for a TTV of 100 ml or more was 41 per cent, compared with 67 per cent for a TTV below 100 ml (P = 0·006). Corresponding RFS rates with TTV of 10 ml or more, or less than 10 ml, were 14 and 58 per cent respectively (P = 0·009). A TTV of at least 100 ml conferred a higher rate of unresectable initial recurrences (12 of 15, 80 per cent) after initial hepatic resection.

Conclusion

TTV was associated with RFS and OS after initial hepatic resection for CRLM; TTV of 100 ml or above was associated with a higher rate of unresectable recurrence.
Generation and characterization of Six2 conditional mice
Authors: Li Chaochang , Liu Han , Hu Yueh‐Chiang , Lan Yu , Jiang Rulang
Published: April 2020

Heterozygous deletion of Six2, which encodes a member of sine oculis homeobox family transcription factors, has recently been associated with the frontonasal dysplasia syndrome FND4. Previous studies showed that Six2 is expressed in multiple tissues during craniofacial development in mice, including embryonic head mesoderm, postmigratory frontonasal neural crest cells, and epithelial and mesenchymal cells of the developing palate and nasal structures. Whereas Six2
−/− mice exhibited cranial base defects but did not recapitulate frontonasal phenotypes of FND4 patients, Six1
−/‐Six2
−/− double mutant mice showed severe craniofacial defects including midline facial clefting. The complex phenotypes of FND4 patients and of Six1
−/‐Six2
−/− mutant mice indicate that Six2 plays crucial roles in distinct cell types at multiple stages of craniofacial morphogenesis. Here we report generation of mice carrying insertions of a pair of loxP sites flanking exon‐1 of the Six2 gene (Six2
f allele) using CRISPR/Cas9‐mediated genome editing. We show that the Six2
f allele functions normally and is effectively inactivated by Cre‐mediated recombination in vivo. Furthermore, we show that Six2
f/f;Wnt1‐Cre mice recapitulated cranial base defects but not neonatal lethality of Six2
−/− mice. These results indicate that Six2
f/f mice enable systematic investigation of cell type‐ and stage‐specific Six2 function in development and disease.
Simple embryo injection of long single‐stranded donor templates with the CRISPR/Cas9 system leads to homology‐directed repair in Xenopus tropicalis and Xenopus laevis
Authors: Nakayama Takuya , Grainger Robert M. , Cha Sang‐Wook
Published: April 2020

We report model experiments in which simple microinjection of fertilized eggs has been used to effectively perform homology‐directed repair (HDR)‐mediated gene editing in the two Xenopus species used most frequently for research: X. tropicalis and X. laevis. We have used long single‐stranded DNAs having phosphorothioate modifications as donor templates for HDR at targeted genomic sites using the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR‐associated protein 9 (CRISPR/Cas9) system. First, X. tropicalis tyr mutant (i.e., albino) embryos were successfully rescued: partially pigmented tadpoles were seen in up to 35% of injected embryos, demonstrating the potential for efficient insertion of targeted point mutations. Second, in order to demonstrate the ability to tag genes with fluorescent proteins (FPs), we targeted the melanocyte‐specific gene slc45a2.L of X. laevis to label it with the Superfolder green FP (sfGFP), seeing mosaic expression of sfGFP in melanophores in up to 20% of injected tadpoles. Tadpoles generated by these two approaches were raised to sexual maturity, and shown to successfully transmit HDR constructs through the germline with precise targeting and seamless recombination. F1 embryos showed rescue of the tyr mutation (X. tropicalis) and tagging in the appropriate pigment cell‐specific manner of slc45a2.L with sfGFP (X. laevis).
Improving emotion recognition in anorexia nervosa: An experimental proof‐of‐concept study
Authors: Preis Mira A. , Schlegel Katja , Stoll Linda , Blomberg Maximilian , Schmidt Hagen , Wünsch‐Leiteritz Wally , Leiteritz Andreas , Brockmeyer Timo
Published: April 2020

Objective

Previous research has found increasing evidence for difficulties in emotion recognition ability (ERA) and social cognition in anorexia nervosa (AN), and recent models consider these factors to contribute to the development and maintenance of the disorder. However, there is a lack of experimental studies testing this hypothesis. Therefore, the present proof‐of‐concept study examined whether ERA can be improved by a single session of a computerized training in AN, and whether this has short‐term effects on eating disorder symptoms.

Method

Forty inpatients (22.20 ± 7.15 years) with AN were randomly assigned to receive a single session of computerized training of ERA (TERA) or a sham training (training the recognition of different types of clouds). ERA, self‐reported eating disorder symptoms, and body mass index (BMI) were assessed within 3 days before and after training.

Results

After training, both groups showed improved ERA, reduced self‐reported eating disorder symptoms, and an increased BMI. As compared to patients in the control group, patients who received TERA showed greater improvements in ERA and self‐reported eating disorder symptoms.

Discussion

ERA can be effectively trained in patients with AN. Moreover, short‐term improvements in self‐reported eating disorder symptoms provide tentative support for the hypothesis that difficulties in ERA contribute to the maintenance of AN, and that specific trainings of ERA hold promise as an additional component in AN treatment. Future studies are needed to replicate these findings in larger samples, and to investigate long‐term effects and transfer into real‐world settings.
Magnitude and direction of stream–forest community interactions change with timescale
Authors: Marcarelli Amy M. , Baxter Colden V. , Benjamin Joseph R. , Miyake Yo , Murakami Masashi , Fausch Kurt D. , Nakano Shigeru
Published: April 2020

Networks of direct and indirect biotic interactions underpin the complex dynamics and stability of ecological systems, yet experimental and theoretical studies often yield conflicting evidence regarding the direction (positive or negative) or magnitude of these interactions. We revisited pioneering data sets collected at the deciduous forested Horonai Stream and conducted ecosystem‐level syntheses to demonstrate that the direction of direct and indirect interactions can change depending on the timescale of observation. Prior experimental studies showed that terrestrial prey that enter the stream from the adjacent forest caused positive indirect effects on aquatic invertebrates during summer by diverting fish consumption. Seasonal and annual estimates of secondary production and organic matter flows along food web pathways demonstrate that this seasonal input of terrestrial invertebrate prey increases production of certain fish species, reversing the indirect effect on aquatic invertebrates from positive at the seasonal timescale to negative at the annual timescale. Even though terrestrial invertebrate prey contributed 54% of the annual organic matter flux to fishes, primarily during summer, fish still consumed 98% of the aquatic invertebrate annual production, leading to top‐down control that is not revealed in short‐term experiments and demonstrating that aquatic prey may be a limiting resource for fishes. Changes in the direction or magnitude of interactions may be a key factor creating nonlinear or stabilizing feedbacks in complex systems, and these dynamics can be revealed by merging experimental and comparative approaches at different scales.
Solvent‐ and Catalyst‐Free Aza‐Michael Addition of Imidazoles and Related Heterocycles
Authors: Kodolitsch Katharina , Gobec Florian , Slugovc Christian
Published: April 2020

This work demonstrates the scope and limitations of the aza‐Michael addition of imidazoles and related heterocycles with electron deficient olefins under solvent‐ and catalyst‐free conditions. The reaction proceeds at 80 °C within hours towards completion as long as the azole derivative is sufficiently soluble in the Michael acceptor, which has been used in small excess. Workup only comprises evaporation of surplus Michael‐acceptor, and no additional solvents are necessary for purifying the products.
Prussian Blue Nanocubes‐SnO2 Quantum Dots‐Reduced Graphene Oxide Ternary Nanocomposite: An Efficient Non‐noble‐metal Electrocatalyst for Non‐enzymatic Detection of H2O2
Authors: Chauhan Seema , Sahoo Srikant , Satpati Ashis Kumar , Sharma Chhaya , Sahoo Prasanta Kumar
Published: April 2020

Developing non‐noble‐metal electrocatalyst for non‐enzymatic H2O2 sensing is highly attractive. A facile, two‐step approach has been utilized for the synthesis of PBNCs/SnO2 QDs/RGO ternary nanocomposite. TEM, SEM, XPS, and XRD techniques were used to the characterize the structural and morphological properties of synthesized ternary nanocomposite. The synthesized ternary nanocomposite has been examined as an electrode material for the electrochemical detection of H2O2 using the Amperometry technique. Under optimum conditions, PBNCs/SnO2 QDs/RGO ternary nanocomposite performed very well in the electrocatalytic reduction of H2O2 with a linear dynamic range from 25–225 μM (R2=0.996) with a low detection limit of 71 nM (S/N=3). Compared to the recent literature, PBNCs/SnO2QDs/RGO ternary nanocomposite based modified electrode exhibit a wider linear dynamic range with a low detection limit. Furthermore, PBNCs/SnO2 QDs/RGO ternary nanocomposite based modified electrode showed an excellent anti‐interference ability against various common interfering agents. The practical applicability of this ternary nanocomposite based modified electrode was further extended to determine the H2O2 in tap water with acceptable recovery. The present performance of PBNCs/SnO2 QDs/RGO ternary nanocomposite material towards H2O2 sensing might widen its application for developing a new type of non‐noble metal‐based non‐enzymatic electrochemical biosensors.
The metabolic response to inflammation in astrocytes is regulated by nuclear factor‐kappa B signaling
Authors: Robb Josephine L. , Hammad Nadia A. , Weightman Potter Paul G. , Chilton John K. , Beall Craig , Ellacott Kate L. J.
Published: April 2020

Inflammation and metabolism are intrinsically linked with inflammatory stimuli inducing metabolic changes in cells and, in turn, metabolic capacity determining cellular inflammatory responses. Although well characterized in peripheral immune cells there is comparatively less known about these “immunometabolic” responses in astrocytes. In this study, we tested the hypothesis that the astrocytic inflammatory response driven by nuclear factor‐kappa B (NF‐κB) signaling is dependent on glycolytic metabolism. Using mouse primary cortical astrocyte cultures, we assessed changes in cellular metabolism after exposure to lipopolysaccharide (LPS), with cytokine ELISAs and immunoblotting being used to measure inflammatory responses. Results indicate temporally distinct metabolic adaptations to pro‐inflammatory stimulation in astrocytes: 3 hr LPS treatment increased glycolysis but did not alter mitochondrial metabolism, while following 24 hr of LPS treatment we observed increased oxidative phosphorylation, and decreased glycolytic capacity and glucose uptake, partly due to reduced glucose transporter 1 expression. Inhibition of NF‐κB signaling with the IKK‐beta inhibitor TPCA‐1 prevented the LPS induced changes to glycolysis and oxidative phosphorylation. Furthermore, TPCA‐1 treatment altered both glycolysis and oxidative phosphorylation independently from inflammatory stimulation, indicating a role for NF‐κB signaling in regulation of basal metabolism in astrocytes. Inhibition of glycolysis with 2‐deoxyglucose significantly attenuated LPS‐induced cytokine release and NF‐κB phosphorylation, indicating that intact glycolysis is required for the full inflammatory response to LPS. Together our data indicate that astrocytes display immunometabolic responses to acute LPS stimulation which may represent a potential therapeutic target for neuroinflammatory disorders.
Hepatic Choline Transport Is Inhibited During Fatty Acid–Induced Lipotoxicity and Obesity
Authors: O’Dwyer Conor , Yaworski Rebecca , Katsumura Sakie , Ghorbani Peyman , Gobeil Odai Kaelan , Nunes Julia R.C. , LeBlond Nicholas D. , Sanjana Sabrin , Smith Tyler T.K. , Han Shauna , Margison Kaitlyn D. , Alain Tommy , Morita Masahiro , Fullerton Morgan D.
Published: April 2020

Choline is an essential nutrient and a critical component of the membrane phospholipid phosphatidylcholine (PC), the neurotransmitter acetylcholine, while also contributing to the methylation pathway. In the liver specifically, PC is the major membrane constituent and can be synthesized by the cytidine diphosphate–choline or the phosphatidylethanolamine N‐methyltransferase pathway. With the continuing global rise in the rates of obesity and nonalcoholic fatty liver disease, we sought to explore how excess fatty acids on primary hepatocytes and diet‐induced obesity affect choline uptake and metabolism. Our results demonstrate that hepatocytes chronically treated with palmitate, but not oleate or a mixture, had decreased choline uptake, which was associated with lower choline incorporation into PC and lower expression of choline transport proteins. Interestingly, a reduction in the rate of degradation spared PC levels in response to palmitate when compared with control. The effects of palmitate treatment were independent of endoplasmic reticulum stress, which counterintuitively augmented choline transport and transporter expression. In a model of obesity‐induced hepatic steatosis, male mice fed a 60% high‐fat diet for 10 weeks had significantly diminished hepatic choline uptake compared with lean mice fed a control diet. Although the transcript and protein expression of various choline metabolic enzymes fluctuated slightly, we observed reduced protein expression of choline transporter‐like 1 (CTL1) in the liver of mice fed a high‐fat diet. Polysome profile analyses revealed that in livers of obese mice, the CTL1 transcript, despite being more abundant, was translated to a lesser extent compared with lean controls. Finally, human liver cells demonstrated a similar response to palmitate treatment. Conclusion: Our results suggest that the altered fatty acid milieu seen in obesity‐induced fatty liver disease progression may adversely affect choline metabolism, potentially through CTL1, but that compensatory mechanisms work to maintain phospholipid homeostasis.
Tidal regime shift in Lingdingyang Bay, the Pearl River Delta: An identification and assessment of driving factors
Authors: Wang Heng , Zhang Ping , Hu Shuai , Cai Huayang , Fu Linxi , Liu Feng , Yang Qingshu
Published: April 2020

Both natural changes (e.g., tidal forcing from the ocean and global sea level rise) and human‐induced changes (e.g., dredging for navigation, sand excavation, and land reclamation) exert considerable influences on the long‐term evolution of tidal regimes in estuaries. Evaluating the impacts of these factors on tidal‐regime shifts is particularly important for the protection and management of estuarine environments. In this study, an analytical approach is developed to investigate the impacts of estuarine morphological alterations (mean water depth and width convergence length) on tidal hydrodynamics in Lingdingyang Bay, Southeast China. Based on the observed tidal levels from two tidal gauging stations along the channel, tidal wave celerity and tidal damping/amplification rate of different tidal constituents are computed using tidal amplitude and phase of tidal constituents extracted from a standard harmonic analysis. We show that the minimum mean water depth for the whole estuary occurred in 2006, whereas a shift in tidal wave celerity for the M2 tide component occurred in 2009. As such, the study period (1990–2016) could be separated into pre‐human (1990–2009) and post‐human (2010–2016) phases. Our results show that the damping/amplification rate and celerity of the M2 tide have increased by 31% (from 7 to 9.2 m−1) and 28% (from 7 to 9 m·s−1) respectively, as a consequence of the substantial impacts of human interventions. The proposed analytical method is subsequently applied to analyse the historical development of tidal hydrodynamics and regime shifts induced by human interventions, thus linking the evolution of estuarine morphology to the dominant tidal hydrodynamics along the channel. The observed tidal regime shift is primarily caused by channel deepening, which substantially enlarged the estuary and reduced effective bottom friction resulting in faster celerity and stronger wave amplification. Our proposed method for quantifying the impacts of human interventions on tidal regime shifts can inform evidence‐based guidelines for evaluating hydraulic responses to future engineering activities.
Influence of C4‐Dcu transporters on hydrogenase and formate dehydrogenase activities in stationary phase‐grown fermenting Escherichia coli
Authors: Karapetyan Lusine , Pinske Constanze , Sawers Gary , Trchounian Armen , Trchounian Karen
Published: April 2020

During mixed‐acid fermentation, Escherichia coli transports succinate mainly via transporters of the Dcu family. Here, we analyze the influence of Dcu transporters on hydrogenase (Hyd) and fermentative formate dehydrogenase (FDH‐H) activities and how this is affected by external pH and carbon source. Using selected dcu mutations, it was shown that Dcu carriers mainly affect Hyd and FDH‐H activities during glycerol but not glucose fermentation at acidic pH. During glycerol fermentation at pH 5.5, inactivation of either one or all Dcu carriers increased total Hyd activity by 60% compared with wild type. Under the same growth conditions, a dcuACBD mutant had a twofold higher FDH‐H activity. When glucose was fermented in dcuD single mutant at pH 5.5, the FDH‐H activity was also increased twofold compared with wild type. Interestingly, in dcuD or dcuACBD mutants at pH 7.5, Hyd activity was lowered by 20%. Taken together, it can be concluded that during glucose fermentation at pH 7.5, lack of DcuD affects Hyd enzyme activity, but at pH 5.5, it has a stronger effect on FDH‐H activity. During glycerol fermentation, lack of Dcu carriers increased Hyd and FDH‐H activities as revealed at pH 5.5. The results suggest that impairing Dcu transport function increases intracellular formate levels and thus affects H2 cycling and proton‐motive force generation.
Novel lactone‐layered double hydroxide ionomer powders for bone tissue repair
Authors: Zhou Tianhao , McCarthy Edward D. , Soutis Constantinos , Cartmell Sarah H.
Published: April 2020

This article describes the use of a novel lactone‐layered double hydroxide polymer network (PN), derived from a poly(lactide‐co‐caprolactone) copolymer, as a controlled ion‐release agent for artificial bone tissue regeneration. The osteogenic cell culture Saos‐2 is used as a test culture to investigate the PN's performance as an extracellular ion‐release agent. The compelling performance of this PN is demonstrated in both growth and osteogenic media compared with a control of cells grown on tissue culture plastic (TCP) without PN. Firstly, the PNs released concentration of magnesium ions over time ranging from 10 to 60 mM after 24 hr, depending on the PN sample. After incubation of Saos‐2 with the PN, while no difference was seen in cell number, there was significant upregulation of bone‐related gene expression at 14 days—~5fold increase in Bone Morphogenetic Protein 2, ~3fold increase in osteopontin and ~2fold increase in collagen Type I. In addition, normalized alkaline phosphatase activity was seen to significantly increase by ~2fold with PN presence. A ~4fold increase in collagen Type I protein expression (via Gomori Trichrome Stain) was observed with PN presence. In addition, a ~4fold increase in phosphate deposits (as seen with Von Kossa staining analysis) was seen with PN presence. It is found that this novel PN material has a significant potential for bone tissue regeneration.
Cover Image, Volume 95, Issue 5
Authors: Sánchez‐Trasviña Calef , Mayolo‐Deloisa Karla , Rito‐Palomares Marco
Published: April 2020

The cover image is based on the Original Article Ribonuclease A modification with poly[N‐(2‐hydroxypropyl)methacrylamide] copolymers: new route of synthesis and purification by Marco Rito‐Palomares, Calef Sanchz‐Trasviña, and Karla Mayolo‐Deloisa., https://doi.org/10.1002/jctb.6367.

image
Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma
Authors: Shigesawa Taku , Suda Goki , Kimura Megumi , Shimazaki Tomoe , Maehara Osamu , Yamada Ren , Kitagataya Takashi , Suzuki Kazuharu , Nakamura Akihisa , Ohara Masatsugu , Umemura Machiko , Kawagishi Naoki , Nakai Masato , Sho Takuya , Natsuizaka Mitsuteru , Morikawa Kenichi , Ogawa Koji , Sakamoto Naoya
Published: April 2020

Background

Sorafenib and lenvatinib are first‐line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear.

Methods

We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2–3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long‐SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated.

Results

Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib.

Conclusion

This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.
The narial musculature of Alligator mississippiensis: Can a muscle be its own antagonist?
Authors: Klassen Matthew , Adams James , Cramberg Michael , Knoche Lucas , Young Bruce A.
Published: April 2020

The crocodilian naris is regulated by smooth muscle. The morphology of this system was investigated using a combination of gross, light microscopic, and micro‐CT analyses, while the mechanics of narial regulation were examined using a combination of Hall Effect sensors, narial manometry, and electromyography. Alligator mississippiensis, like other crocodilians, routinely switches among multiple ventilatory mechanics and does not occlude the nares during any portion of the ventilatory cycle. In a complex that is unique among vertebrates, a single block of smooth muscle functions in dilation when active, and in constriction when passive. The alligator nares may include one of the best examples of a muscle that functions in “pushing” as well as “pulling.” The central muscle for narial regulation, the dilator naris, can legitimately be viewed as its own antagonist.
GlobalCO2emissions and global temperatures: Are they related
Authors: Gil‐Alana Luis A. , Monge Manuel
Published: April 2020

This paper deals with the analysis of the relationship between CO2emissions and temperatures. For this purpose, global CO2emissions and four measures of global temperatures (land, land and ocean, northern and southern temperatures) are used. We used techniques based on fractional integration and cointegration. The results indicate first that the orders of integration differ in the two variables. Thus, while emissions are I(1) or I(d) with d higher than 1, temperatures display orders of integration strictly smaller than 1 and thus invalidating the hypothesis of cointegration between the two variables. Due to this, another approach is conducted where we suppose that the emissions are weakly exogenous in relation to the temperatures. The results using this approach show a significantly positive relationship between the two variables with a long memory pattern.
Polyoxomolybdate368 /polyaniline nanocomposite as a novel fiber for solid‐phase microextraction of antidepressant drugs in biological samples
Authors: Amoli Hossein Salar , Yamini Yadollah , Darmani Hossein
Published: April 2020

A novel solid‐phase microextraction fiber was synthesized by coating a stainless steel wire with polyoxomolybdate368/polyaniline as a sorbent aimed at extraction of amitriptyline, nortriptyline, and doxepin as antidepressant drugs from urine and blood samples. The polyoxomolybdate368/polyaniline composite coating was applied using electropolymerization process under constant potential. This composition leads to enhanced extraction efficiency of the fiber. Scanning electron microscopy images show that huge three‐dimensional structures of polyoxomolybdate368 in composite induced more non‐smooth and porous fiber. In order to optimize of the extraction process, a series of variables including concentration of the composite materials, coating thickness, pH, extraction time, salt addition, and stirring rate was investigated and optimum conditions were determined. Analysis of surface morphology and chemical composition was performed. High‐performance liquid chromatography was used for separation and evaluation of mentioned antidepressant drugs from the matrixes. The experiments indicated a detection limits of <0.2 ng/L and a linear dynamic range of 0.3–100 ng/L (R2 > 0.994). The relative recovery values were found to be in the range of 92–98%. It was concluded that the purposed fiber is highly efficient in analyzing traces of antidepressant drugs in urine and blood.
Temperature‐programmed capillary high‐performance liquid chromatography with atmospheric pressure chemical ionization mass spectrometry for analysis of fatty acid methyl esters
Authors: Vrkoslav Vladimír , Rumlová Barbora , Strmeň Timotej , Cvačka Josef
Published: April 2020

A new capillary high‐performance liquid chromatography method with atmospheric pressure chemical ionization mass spectrometry was developed for the analysis of fatty acid methyl esters and long‐chain alcohols. The chromatographic separation was achieved using a Zorbax SB‐C18 HPLC column (0.3 × 150 mm, 3.5 μm) with a mobile phase composed of acetonitrile and formic acid and delivered isocratically at a flow rate of 10 μL/min. The column temperature was programmed simply, using a common column oven. Good reproducibility of the temperature profile and retention times were achieved. The temperature programming during the isocratic high‐performance liquid chromatography run had a similar effect as a solvent gradient; it reduced retention times of later eluting analytes and improved their detection limits. Two atmospheric pressure chemical ionization sources of the mass spectrometry detector were compared: an enclosed conventional ion source and an in‐house made ion source with a glass microchip nebulizer. The enclosed source provided better detectability of saturated fatty acid methyl esters and made it possible to determine the double bond positions using acetonitrile‐related adducts, while the open chip‐based source provided better analytical figures of merit for unsaturated fatty acid methyl esters. Temperature‐programmed capillary high‐performance liquid chromatography is a promising method for analyzing neutral lipids in lipidomics and other applications.
Development of a Tool to Predict Risk of Behavioral Health Evacuation From Combat
Authors: Thornquist Mary H. , Leonard James E. , Fraine Melissa C. , Loftis Christopher W. , Davison John W.
Published: April 2020

In the present study, we examined administrative data on 667,437 deployments of at least 30 days duration to Iraq and Afghanistan from 2011 through the end of 2016 to determine risk factors for evacuation from the combat zone for behavioral health reasons. Demographic data, military‐specific data, responses on predeployment mental health assessments, and presence of previous treatment for psychiatric conditions were entered into a logistic regression based on expert determination, distinguishing the 2,133 behavioral health evacuations from those deployments that either did not end in evacuation or included evacuations for reasons other than behavioral health. The model, derived from a random half of the sample (training set), was verified on the other half (validation set). Predictor variables used in the model were calendar year; gender; age; rank; marital status; parental status; number of prior war zone deployments; branch of service; screens for symptoms of posttraumatic stress disorder, depression, and hazardous alcohol use on the predeployment mental health assessment; and prior substance‐ and non–substance‐related behavioral health diagnoses. Odds ratios (range: 1.05–3.85) for selected variables that contributed to the model were used to assign risk scores in the Behavioral Health Evacuation Risk Tool, which can aid predicting which service members are more likely to be evacuated from combat for behavioral health reasons, thus indicating where resources can be allocated for behavioral health referrals and war zone care.
Efficacy of Psychological Intervention for Children with Concurrent Posttraumatic Stress Disorder and Mild Traumatic Brain Injury
Authors: Shorer Maayan , Segev Shira , Rassovsky Yuri , Fennig Silvana , Apter Alan , Peleg Tammy Pilowsky
Published: April 2020

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common conditions following motor vehicle accidents (MVAs). Mild TBI and PTSD not only share similar features but may also coexist and interact. Nonetheless, research on psychotherapeutic interventions for PTSD in patients with a history of mTBI, particularly regarding pediatric populations, is limited. The present study compared the efficacy of the prolonged exposure treatment protocol for children and adolescents (PE‐A) with PTSD and mTBI (n = 16) versus PTSD alone (n = 21); treatment commenced at least 3 months following an MVA. Emotional status and cognitive functioning were assessed pre‐ and postintervention using questionnaires and standardized neuropsychological tests. Participants from both groups benefitted from the intervention, as reflected in their emotional status via increased ratings of well‐being and decreased ratings of PTSD, anxiety, depression, and postconcussive symptoms, η2 = .21–.50. Ratings of cognitive function also improved for cognitive flexibility, η2 = .30; executive function in everyday life, η2 = .27; and attention and inhibition, η2 = .16. Parental PTSD was the strongest predictor of improvement after intervention, sr2 = .35. Thus, it appears that PE‐A is an effective intervention for children with MVA‐related PTSD regardless of its comorbidity with mTBI.
Therapists join national effort to help essential workers
Authors: Canady Valerie A.
Published: April 2020

Employees deemed “essential” workers (i.e., health care professionals, first responders, service industry employees, truck drivers, military and many others on the front line who are not able to work from their homes and risk exposure to COVID‐19 so that others could stay at home) can now have access to free or reduced‐fee online therapy sessions.
Design a 0.1 THz EIO with TM31 mode driven by sheet beam
Authors: Wu Zhenhua , Li Jielong , Wang Bo , Zhong Renbin , Zhao Tao , Gong Sen , Liu Diwei , Zhang Kaichun , Hu Min
Published: April 2020

In terahertz vacuum electronic devices, sheet beam can improve the interaction efficiency effectively. A rectangular cavity extended interaction oscillator driven by sheet beam in terahertz band is studied in this article. Specially, sheet beam can interact with higher mode in this structure such as TM31 mode. This will have the advantage of being able to operate at a higher frequency than fundamental mode. A 0.1 THz extended interaction oscillator (EIO) with TM31 mode driven by sheet beam is designed based on the dispersion characteristics, S parameters and particle‐in‐cell simulation calculation. The simulation results show that sheet beam with voltage of 12 kV and current of 0.6 A interacts with TM31 mode electromagnetic wave in the cavity under longitudinal magnetic field of 0.5 T. The output frequency is 0.1 THz, the power is 1 kW and the efficiency is 13.9%.
Efficient algorithms for flexible job shop scheduling with parallel machines
Authors: Kubiak Wieslaw , Feng Yanling , Li Guo , Sethi Suresh P. , Sriskandarajah Chelliah
Published: April 2020

Job shop scheduling with a bank of machines in parallel is important from both theoretical and practical points of view. Herein we focus on the scheduling problem of minimizing the makespan in a flexible two‐center job shop. The first center consists of one machine and the second has k parallel machines. An easy‐to‐perform approximate algorithm for minimizing the makespan with one‐unit‐time operations in the first center and k‐unit‐time operations in the second center is proposed. The algorithm has the absolute worst‐case error bound of k − 1, and thus for k = 1 it is optimal. Importantly, it runs in linear time and its error bound is independent of the number of jobs to be processed. Moreover, the algorithm can be modified to give an optimal schedule for k = 2.