bluuebunny/crossref_metadata_2025 huggingface dataset:
Wood by-Product as Storage Material for Post-Harvest Management of Tomato (Solanum lycopersicum L.) at Breaker Stage
Authors: Lawal Israel Oluwasanmi , Akande Samuel Adesayo , Adebayo Odunayo Benedicta , Ayanda Ifedapo Solomon , Ibrahim Adeola Saheed , Fashanu Titilope Abosede , Adediji Adetutu Yetunde
Published: March 2019

The study evaluated the effect of wood by-product on the storability of fresh breaker tomato. The samples (Kerewa variety) were harvested, cooled by aeration and divided into three lots (B0=control; B1=1: 1, tomato: wood by-product; B2=1: 2, tomato: wood by-product). They were kept in uniformly sized paper carton (170 mm×120 mm×140 mm) on the shelf for 28 days. The organoleptic properties of the stored tomatoes were assessed on 5-point hedonic scale, as well as the physicochemical properties (moisture, pH, acidity, and soluble solids), carotenoids, vitamin C content and mineral analysis. Result showed that; B1 and B2 were significantly (p<0.05) higher than control in colour, appearance and overall acceptability while no significant (p<0.05) difference was observed between B1 and the control in firmness and odour. Weight or moisture loss (%) and decay incidence were higher in control than both B1 and B2. Moisture content (MC) reduced significantly (p<0.05) in sample B2 while no significant (p>0.05) difference was observed in control and B1 after 28 days storage. The pH of B1 was significantly (p<0.05) lower than B2 and the control but the β-carotene and vitamin C of B1 was significantly (p<0.05) higher than B2 and control. Wood by-product had shown some potentials for post-harvest handling of fresh breaker tomato most especially when used at ratio 1: 1 (w/w %).
Superassembled Biocatalytic Porous Framework Micromotors with Reversible and Sensitive pH‐Speed Regulation at Ultralow Physiological H2O2 Concentration
Authors: Gao Song , Hou Jingwei , Zeng Jie , Richardson Joseph J. , Gu Zi , Gao Xiang , Li Dongwei , Gao Meng , Wang Da‐Wei , Chen Pu , Chen Vicki , Liang Kang , Zhao Dongyuan , Kong Biao
Published: March 2019

Synthetic nano/micromotors are a burgeoning class of materials with vast promise for applications ranging from environmental remediation to nanomedicine. The motility of these motors is generally controlled by the concentration of accessible fuel, and therefore, engineering speed‐regulation mechanisms, particularly using biological triggers, remains a continuing challenge. Here, control over the movement of superassembled porous framework micromotors via a reversible, biological‐relevant pH‐responsive regulatory mechanism is demonstrated. Succinylated β‐lactoglobulin and catalase are superassembled in porous framework particles, where the β‐lactoglobulin is permeable at neutral pH. This permeability allows the fuel (H2O2) to access catalase, leading to autonomous movement of the micromotors. However, at mild acidic pH, succinylated β‐lactoglobulin undergoes a reversible gelation process, preventing the access of fuel into the micromotors where the catalase resides. To one's knowledge, this study represents the first example of chemically driven motors with rapid, reversible pH‐responsive motility. Furthermore, the porous framework significantly enhances the biocatalytic activity of catalase, allowing ultralow H2O2 concentrations to be exploited at physiological conditions. It is envisioned that the simultaneous exploitation of pH and chemical potential of such nanosystems could have potential applications as stimulus‐responsive drug delivery vehicles that benefit from the complex biological environment.
A Dual‐Bioresponsive Drug‐Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade
Authors: Ruan Huitong , Hu Quanyin , Wen Di , Chen Qian , Chen Guojun , Lu Yifei , Wang Jinqiang , Cheng Hao , Lu Weiyue , Gu Zhen
Published: March 2019

Patients with advanced melanoma that is of low tumor‐associated antigen (TAA) expression often respond poorly to PD‐1/PD‐L1 blockade therapy. Epigenetic modulators, such as hypomethylation agents (HMAs), can enhance the antitumor immune response by inducing TAA expression. Here, a dual bioresponsive gel depot that can respond to the acidic pH and reactive oxygen species (ROS) within the tumor microenvironment (TME) for codelivery of anti‐PD1 antibody (aPD1) and Zebularine (Zeb), an HMA, is engineered. aPD1 is first loaded into pH‐sensitive calcium carbonate nanoparticles (CaCO3 NPs), which are then encapsulated in the ROS‐responsive hydrogel together with Zeb (Zeb‐aPD1‐NPs‐Gel). It is demonstrated that this combination therapy increases the immunogenicity of cancer cells, and also plays roles in reversing immunosuppressive TME, which contributes to inhibiting the tumor growth and prolonging the survival time of B16F10‐melanoma‐bearing mice.
Structure‐Guided Evolution of Aryl Alcohol Oxidase from Pleurotus eryngii for the Selective Oxidation of Secondary Benzyl Alcohols
Authors: Viña‐Gonzalez Javier , Jimenez‐Lalana Diego , Sancho Ferran , Serrano Ana , Martinez Angel T. , Guallar Victor , Alcalde Miguel
Published: March 2019

Aryl alcohol oxidase (AAO) is a fungal flavoenzyme capable of oxidizing aromatic primary alcohols into their correspondent aldehydes through a stereoselective hydride abstraction. Unfortunately, this enzyme does not act on secondary benzyl alcohols in racemic mixtures due to the strict control of substrate diffusion and positioning at the active site restricted to primary benzyl alcohols. Here we describe the engineering of AAO from Pleurotus eryngii to oxidize chiral benzyl alcohols with high enantioselectivity. The secondary benzyl alcohol oxidase was remodeled at the active site through four cycles of structure‐guided evolution, including a final step of in vivo site‐directed recombination to address the positive epistatic interactions between mutations. The final variant, with five substitutions and a renovated active site, was characterized at biochemical and computational level. The mutational sculpting helped position the bulkier (S)‐1‐(p‐methoxyphenyl)‐ethanol, improving the mutant's catalytic efficiency by three orders of magnitude relative to the native enzyme while showing a high enantioselectivity (ee >99%). As a promising candidate for racemic resolution, this evolved secondary benzyl alcohol oxidase maintained its natural stereoselective mechanism while displaying activity on several secondary benzyl alcohols.

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White Photoluminescent Ti3C2 MXene Quantum Dots with Two‐Photon Fluorescence
Authors: Lu Siyu , Sui Laizhi , Liu Yuan , Yong Xue , Xiao Guanjun , Yuan Kaijun , Liu Zhongyi , Liu Baozhong , Zou Bo , Yang Bai
Published: March 2019

A recently created class of inorganic 2D materials, MXenes, has become a subject of intensive research. Reducing their dimensionality from 2D to 0D quantum dots (QDs) could result in extremely useful properties and functions. However, this type of research is scarce, and the reported Ti3C2 MXene QDs (MQDs) have only shown blue fluorescence emission. This work demonstrates a facile, high‐output method for preparing bright white emitting Ti3C2 MQDs. The resulting product is two layers thick with a lateral dimension of 13.1 nm. Importantly, the as prepared Ti3C2 MQDs present strong two‐photon white fluorescence. Their fluorescence under high pressure is also investigated and it is found that the white emission is very stable and the pressure makes it possible to change from cool white emission to warm white emission. Hybrid nanocomposites are then fabricated by polymerizing Ti3C2 MQDs in polydimethylsiloxane (PDMS) solution, and the bright white emitting hybrid materials in white light‐emitting diodes are used. This work provides a facile and general approach to modulate various nanoscale MXene materials, and could further aid the wide development of applications for MXene materials in various optical‐related fields.
The effects of alcohol and cannabinoid exposure during the brain growth spurt on behavioral development in rats
Authors: Breit Kristen R. , Zamudio Brandonn , Thomas Jennifer D.
Published: March 2019

Cannabis is the most commonly used illicit drug among pregnant women. Moreover, over half of pregnant women who are consuming cannabis are also consuming alcohol; however, the consequences of combined prenatal alcohol and cannabis exposure on fetal development are not well understood. The current study examined behavioral development following exposure to ethanol (EtOH) and/or CP‐55,940 (CP), a cannabinoid receptor agonist. From postnatal days (PD) 4–9, a period of brain development equivalent to the third trimester, Sprague–Dawley rats received EtOH (5.25 g/kg/day) or sham intubation, as well as CP (0.4 mg/kg/day) or vehicle. All subjects were tested on open field activity (PD 18–21), elevated plus maze (PD 25), and spatial learning (PD 40–46) tasks. Both EtOH and CP increased locomotor activity in the open field, and the combination produced more severe overactivity than either exposure alone. Similarly, increases in thigmotaxis in the Morris water maze were caused by either EtOH or CP alone, and were more severe with combined exposure, although only EtOH impaired spatial learning. Finally, developmental CP significantly increased time spent in the open arms on the elevated plus maze. Overall, these data indicate that EtOH and CP produce some independent effects on behavior, and that the combination produces more severe overactivity in the open field. Importantly, these data suggest that prenatal cannabis disrupts development and combined prenatal exposure to alcohol and cannabis may be particularly damaging to the developing fetus, which has implications for the lives of affected individuals and families and also for establishing public health policy.
Polymorphism rs2395655 affects LEDGF/p75 binding activity and p21WAF1/CIP1 gene expression in esophageal squamous cell carcinoma
Authors: Guo Rong , Ma Yunan , Zhao Min , Zhang Wenlong , An Guo , Chen Baojun , Song Yiping , Xu Hui , Li Yong
Published: March 2019

p21WAF1/CIP1 (p21) plays critical roles in cell‐cycle regulation and DNA repair and is transcriptionally regulated through p53‐dependent or ‐independent pathways. Bioinformatic analysis predicated one stress‐response element (STRE) implicated in single nucleotide polymorphism (SNP) rs2395655 of the p21 promoter. Here, we investigated the transcriptional regulatory function of rs2395655 variant genotype and analyzed its associations with the p21 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC) patients. Luciferase assay results showed significantly increased transcriptional activity of the rs2395655 G allele‐containing p21 promoter compared with rs2395655 A allele‐containing counterpart, especially in ESCC cells with ectopic LEDGF/p75 expression. Furthermore electrophoretic mobility shift assay using the rs2395655 G or A allele‐containing probe and chromatin immunoprecipitation assay with specific anti‐LEDGF/p75 antibody indicated the potential binding activity of LEDGF/p75 with the STRE element implicated in rs2395655 G allele of the p21 promoter. Subsequent specific RNA interference‐mediated depletion or ectopic expression of LEDGF/p75 caused obviously down‐ or up‐regulated expression of p21 mRNA in ESCC cells harboring rs2395655 GG genotype but not cells with rs2395655 AA genotype. Furthermore, rs2395655 GG genotype carriers showed significantly elevated p21 protein expression and conferred survival advantage in both univariate and multivariate analyses in total 218 ESCC patients. Our findings suggest that LEDGF/p75 regulates the p21 expression in ESCC cells through interacting with STRE element implicated in polymorphism rs2395655 and the elevated p21 protein expression and rs2395655 GG genotype may serve as positive prognostic factors for ESCC patients.
Limb specific Acvr1‐knockout during embryogenesis in mice exhibits great toe malformation as seen in Fibrodysplasia Ossificans Progressiva (FOP)
Authors: Hildebrand Laura , Schmidt‐von Kegler Mareen , Walther Maria , Seemann Petra , Stange Katja
Published: March 2019

Purpose

This study analyzes Prx1‐specific conditional knockout of Acvr1 aiming to elucidate the endogenous role of Acvr1 during limb formation in early embryonic development. ACVR1 can exhibit activating and inhibiting function in BMP signaling. ACVR1 gain‐of‐function mutations can cause the rare disease fibrodysplasia ossificans progressiva (FOP), where patients develop ectopic bone replacing soft tissue, tendons and ligaments.

Methods

Whole‐mount in situ hybridization and skeletal preparations revealed that following limb‐specific conditional knockout of Acvr1, metacarpals and proximal phalanges were shortened and additional cartilage and bone elements were formed.

Results

The analysis of a set of marker genes including ligands and receptors of BMP signaling as well as genes involved in patterning and tendon and cartilage formation, revealed temporal disturbances with distinct spatial patterns. The most striking result was that in the absence of Acvr1 in mesoderm precursor cells, first digits were drastically malformed.

Conclusion

In FOP, malformation of big toes can serve as a first soft marker in diagnostics. The surprising similarities in phenotype between the described conditional knockout of Acvr1 and the FOP mouse model, indicates a natural inhibitory function of ACVR1. This represents a further step towards better understanding the role of Acvr1 and developing treatment options for FOP.
Transcranial direct current stimulation over the sensory‐motor regions inhibits gamma synchrony
Authors: Pellegrino Giovanni , Arcara Giorgio , Di Pino Giovanni , Turco Cristina , Maran Matteo , Weis Luca , Piccione Francesco , Siebner Hartwig Roman
Published: March 2019

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce plasticity phenomena. Although tDCS application has been spreading over a variety of neuroscience domains, the mechanisms by which the stimulation acts are largely unknown. We investigated tDCS effects on cortical gamma synchrony, which is a crucial player in cortical function. We performed a randomized, sham‐controlled, double‐blind study on healthy subjects, combining tDCS and magnetoencephalography. By driving brain activity via 40 Hz auditory stimulation during magnetoencephalography, we experimentally tuned cortical gamma synchrony and measured it before and after bilateral tDCS of the primary sensory‐motor hand regions (anode left, cathode right). We demonstrated that the stimulation induces a remarkable decrease of gamma synchrony (13 out of 15 subjects), as measured by gamma phase at 40 Hz. tDCS has strong remote effects, as the cortical region mostly affected was located far away from the stimulation site and covered a large area of the right centro‐temporal cortex. No significant differences between stimulations were found for baseline gamma synchrony, as well as early transient auditory responses. This suggests a specific tDCS effect on externally driven gamma synchronization. This study sheds new light on the effect of tDCS on cortical function showing that the net effect of the stimulation on cortical gamma synchronization is an inhibition.
Testing the myth of fee‐for‐service and overprovision in health care
Authors: Di Guida Sibilla , Gyrd‐Hansen Dorte , Oxholm Anne Sophie
Published: March 2019

Paying on the basis of fee‐for‐service (FFS) is often associated with a risk of overprovision. Policymakers are therefore increasingly looking to other payment schemes to ensure a more efficient delivery of health care. This study tests whether context plays a role for overprovision under FFS. Using a laboratory experiment involving medical students, we test the extent of overprovision under FFS when the subjects face different fee sizes, patient types, and market conditions. We observe that decreasing the fee size has an effect on overprovision under both market conditions. We also observe that patients who are harmed by excess treatment are at little risk of overprovision. Finally, when subjects face resource constraints but still have an incentive to overprovide high‐profit services, they hesitate to do so, implying that the presence of opportunity costs in terms of reduced benefits to other patients protects against overprovision. Thus, this study provides evidence that the risk of overprovision under FFS depends on fee sizes, patients' health profiles, and market conditions.
Weekly cisplatin chemotherapy dosing versus triweekly chemotherapy with concurrent radiation for head and neck squamous cell carcinoma
Authors: Morse Ryan T. , Ganju Rohit G. , TenNapel Mindi J. , Neupane Prakash , Kakarala Kiran , Shnayder Yelizaveta , Chen Allen M. , Lominska Christopher E.
Published: March 2019

Background

Triweekly high‐dose cisplatin (100 mg/m2) with concurrent radiation therapy is the current standard of care in the definitive or appropriate postoperative setting in head and neck squamous cell carcinoma (HNSCC). We compared triweekly 100 mg/m2 with alternative weekly 40 mg/m2 and weekly <40 mg/m2 cisplatin regimens.

Methods

From 2011 to 2016, 163 patients received concurrent cisplatin and intensity‐modulated radiotherapy for locally advanced HNSCC. Primary endpoints were overall survival (OS) and progression‐free survival.

Results

Cisplatin weekly <40 mg/m2 showed inferior OS outcomes when compared to weekly 40 mg/m2 (P = 0.084) and triweekly 100 mg/m2 (P = 0.04) regimens.

Conclusion

Our study displayed inferior outcomes with weekly cisplatin doses under 40 mg/m2, suggesting the inferiority of low‐dose weekly chemotherapy and the need for ongoing randomized trials to further explore 40 vs 100 mg/m2 chemotherapy regimens.
Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors: Functional analysis and expression of PD‐1 receptor
Authors: Tumino Nicola , Martini Stefania , Munari Enrico , Scordamaglia Francesca , Besi Francesca , Mariotti Francesca Romana , Bogina Giuseppe , Mingari Maria Cristina , Vacca Paola , Moretta Lorenzo
Published: March 2019

The tumor microenvironment (TM) contains a wide variety of cell types and soluble factors capable of suppressing immune responses. While the presence of NK cells in pleural effusions (PE) has been documented, no information exists on the presence of other innate lymphoid cell (ILC) subsets and on the expression of programmed cell death‐1 (PD‐1) in NK and ILC. The presence of ILC was assessed in PE of 54 patients (n = 33 with mesothelioma, n = 15 with adenocarcinoma and n = 6 with inflammatory pleural diseases) by cell staining with suitable antibody combinations and cytofluorimetric analysis. The cytokine production of ILC isolated from both PE and autologous peripheral blood was analyzed upon cell stimulation and intracytoplasmic staining. We show that, in addition to NK cells, also ILC1, ILC2 and ILC3 are present in malignant PE and that the prevalent subset is ILC3. PE‐ILC subsets produced their typical sets of cytokines upon activation. In addition, we analyzed the PD‐1 expression on NK/ILC by multiparametric flow‐cytometric analysis, while the expression of PD‐1 ligand (PD‐L1) was evaluated by immunohistochemical analysis. Both NK cells and ILC3 expressed functional PD‐1, moreover, both tumor samples and malignant PE‐derived tumor cell lines were PD‐L1+ suggesting that the interaction between PD‐1+ILC and PD‐L1+tumor cells may hamper antitumor immune responses mediated by NK and ILC.
Analysis of pseudo jahn–teller distortion based on natural bond orbital theory: Case study for silicene
Authors: Bhattacharjee Rameswar , Majumder Tirthick , Datta Ayan
Published: March 2019

Ground state (GS) instability of nondegenerate molecules in high symmetric structures is understood through Pseudo Jahn–Teller mixing of the electronic states through the vibronic coupling. The general approach involves setting up of a Pseudo Jahn–Teller (PJT) problem wherein one or more symmetry allowed excited states couple to the GS to create vibrational instability along a normal mode. This faces two major complications namely (1) estimating the adiabatic potential energy surfaces for the excited states which are often difficult to describe in case the excited states have charge‐transfer or multi‐excitonic (ME) character and (2) finding out how many such excited states (all satisfying the symmetry requirements for vibronic coupling) of increasing energies need to be coupled with the GS for a particular PJT problem. An analogous alternative approach presented here for the well‐known case of symmetry breaking of planar (D6h) hexasilabenzene (Si6H6) to the buckled (D3d) structure involves identifying the second‐order donor–acceptor, hyperconjugative interactions (E2i → j) that stabilize the distorted structure. Following the recent work of Nori‐Shargh and Weinhold, one observes that the orbitals involved in the vibronic coupling between the S0/Sn states and those for the donor (filled)–acceptor (empty) interactions are identical. In fact, deletion of any particular pair of E2i → j interaction creates vibrational instability in the buckled structure and as a corollary, deleting it for the planar structure removes its instability. The one‐to‐one correlation between the natural bond orbital theory and PJT theory assists in an intuitive identification of the relevant (few) excited states from a manifold of computed ones that cause symmetry breaking by vibronic coupling. © 2019 Wiley Periodicals, Inc.
Gas phase selective hydrogenation of phenylacetylene to styrene over Au/Al2O3
Authors: Wang Xiaodong , Keane Mark A
Published: March 2019

BACKGROUND

Trace quantities of phenylacetylene can poison styrene polymerisation catalysts. The phenylacetylene content must be less than 10 ppm and selective hydrogenation (to styrene) is viewed as a viable process solution. High styrene selectivities have been achieved in batch liquid phase operations while a switch from conventional batch liquid to continuous gas phase reaction presents process advantages in terms of higher throughput and enhanced productivity. We aim to provide the first direct comparison of Au/Al2O3 and Pd/Al2O3 in gas phase continuous catalytic hydrogenation of phenylacetylene.

RESULTS

Temperature programme reduction (TPR) generated metal particles at the nano‐scale (mean size = 3.0–4.3 nm), with evidence of electron donation from the aluminium oxide (Al2O3) carrier. Pd/Al2O3 exhibited a greater specific hydrogen (H2) uptake capacity than Au/Al2O3 under reaction conditions to deliver appreciably higher turnover frequencies (TOF) for reaction in excess H2. Stepwise hydrogenation predominated over Au/Al2O3 with 100% selectivity to styrene at 353 K where an increase in temperature favoured subsequent hydrogenation to ethylbenzene. Under the same conditions, Pd/Al2O3 was non‐selective, activating styrene to generate ethylbenzene with a greater contribution of direct phenylacetylene hydrogenation to ethylbenzene at higher temperature.

CONCLUSION

Kinetic analysis has revealed stepwise phenylacetylene hydrogenation in excess H2 over Au/Al2O3 with 100% selectivity to styrene. Stepwise hydrogenation also prevailed over Pd/Al2O3 at the lower temperature but surface activation of styrene coupled with enhanced H2 dissociation generated significant ethylbenzene. Decreasing inlet H2/phenylacetylene (to 1 mol/mol) over Pd/Al2O3 lowered rate where the activity/selectivity profile overlapped that exhibited by Au/Al2O3 in excess H2. © 2019 Society of Chemical Industry
Investigation of forward osmosis performance and anti‐fouling properties of the novel hydrophilic polymer brush‐grafted TFC‐type FO membranes
Authors: Wang Lin , Ma Fuqing , Jia Jizhen , Lei Xiaobin , Zhao Xinzhen , Liu Changkun
Published: March 2019

BACKGROUND

The concentration polarization and membrane fouling are two important factors, which can greatly reduce the forward osmosis (FO) performance and the service life of membranes. Optimizing the supporting layer structure and improving the hydrophilicity of the supporting layer are effective means to improve the FO performance and the anti‐fouling performance of thin‐film composite (TFC)‐type membranes.

RESULTS

A novel hydrophilic TFC‐type FO membrane with a macroporous polymer‐brush‐grafted polysulfone (PSf) supporting layer was fabricated. The prepared TFC‐type FO membrane (g‐FO‐3) showed remarkable FO and anti‐fouling performance. The water flux of g‐FO‐3 (43.0 L m−2 h−1) was nearly 2.6 times the conventional TFC‐type PSf‐based FO membrane (16.8 L m−2 h−1) and 1.8 times the TFC‐type FO membrane with macroporous PSf supporting layer but without polymer grafting (24 L m−2 h−1) in AL‐DS mode (the active layer facing the draw solution), with water as the feed solution and 2 mol L−1 sodium chloride as the draw solution. In addition, the low Js/Jw value of g‐FO‐3 indicated an excellent separation selectivity. Furthermore, the FO membrane kept a water flux recovery rate of 95% after the eight‐cycle fouling tests.

CONCLUSION

The hydrophilic polymer‐brush‐grafted PSf macroporous supporting layer of the FO membrane provides a convenient and efficient means to improve the FO and the anti‐fouling performance of the TFC‐type FO membranes. © 2019 Society of Chemical Industry
Long non‐coding RNA MIR22HG inhibits cell proliferation and migration in cholangiocarcinoma by negatively regulating the Wnt/β‐catenin signaling pathway
Authors: Hu Xiahong , Tan Zhaoxia , Yang Yijiang , Yang Pinghui
Published: March 2019

Background

Cholangiocarcinoma (CCA) is one of the most common primary biliary malignant tumors with a high mortality. MIR22HG has been reported to act as a tumor‐suppressor gene in several types of cancers. However, the role and molecular regulatory mechanism of MIR22HG in CCA still remains unclear. The present study aimed to investigate the role and underlying mechanism of MIR22HG in CCA.

Methods

The expression of MIR22HG was detected by RT‐qPCR assayin CCA tissues and cells. CCK‐8, colony formation and transwell assays were performed to study the biological function of MIR22HG in CCA. Western blot and immunofluorescence assays were performed to detect the expression ofWnt/β‐catenin signaling pathway markers. In vivo assays were conducted to explore the biological role of MIR22HG.

Results

We first found that MIR22HG expression was significantly down‐regulated in CCA tissues and cell lines. Moreover, MIR22HG expression was related to TNM stage and bore prognostic significance in CCA patients. Function experiments demonstrated that overexpression of MIR22HG inhibited cell proliferation, migration and invasion in CCA, whereas knockdown of MIR22HG caused the opposite result. It was found that MIR22HG negatively regulated mRNA and the expression levels of proteins in the Wnt/β‐catenin signaling pathway (β‐catenin, cyclin D1 and c‐myc). The effect of MIR22HG overexpression on CCA progression could be partly rescued by activating the Wnt/β‐catenin signaling pathway. MIR22HG suppressed CCA tumorigenesis in vivo.

Conclusions

In summary, the results of the present study show that MIR22HG repressed cell proliferation, migration and invasion in CCA by negatively regulating the Wnt/β‐catenin signaling pathway. MIR22HG may be a novel target for diagnosis and therapy in CCA.
Altered cortical morphology of visual cortex in adults with monocular amblyopia
Authors: Lu Lu , Li Qian , Zhang Lianqing , Tang Shi , Yang Xubo , Liu Longqian , Sweeney John A. , Gong Qiyong , Huang Xiaoqi
Published: March 2019

Background

The neural mechanism of amblyopia and its impact on the adult brain remain unclear. This hinders effective treatment for adults with this disease.

Purpose

To investigate neuroanatomical differences in cortical morphometry between amblyopic adults and healthy controls, and to explore the structural covariance of abnormal morphometric changes.

Study Type

Prospective.

Population

Twenty‐one amblyopic adults and 34 healthy controls.

Field Strength/Sequence

3T MRI, T1‐weighted, MPRAGE sequence.

Assessment

All participants completed ophthalmologic exams to confirm the diagnosis of amblyopia or its absence in the healthy controls, including tests of ocular motility and dilation, fundus exam, autorefraction and synoptophore tests. Cortical volume, thickness, and surface area measurements were obtained using FreeSurfer software.

Statistical Tests

Statistical differences of MRI measures between amblyopic adults and healthy controls were identified using a general linear model with intracranial volume and age as covariates. Monte Carlo simulations were used to correct for multiple comparisons. The structural covariance of abnormal morphometric changes and the relationship between morphometric abnormalities and visual acuity of the amblyopic eye were examined.

Results

Compared with healthy controls, amblyopic adults showed reduced cortical volume in left lateral occipital cortex, and decreased cortical thickness in bilateral inferior temporal gyrus and left precentral gyrus (P < 0.05; Monte Carlo corrected). Structural covariance between cortical volume of left lateral occipital cortex and cortical thickness of right inferior temporal gyrus in amblyopic adults was significantly less than in healthy controls (z = 1.73; P < 0.05).

Data Conclusion

Our study identified morphological abnormalities in occipital cortex and in temporal and frontal cortex which are projection fields of visual cortex important for processing of visual form and object location information, and disrupted structural covariance of visual cortex with other brain regions in amblyopic patients.

Level of Evidence: 2

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2019;50:1405–1412.
Aquaporin expression in the human and canine intervertebral disc during maturation and degeneration
Authors: Snuggs Joseph W. , Day Rebecca E. , Bach Frances C. , Conner Matthew T. , Bunning Rowena A. D. , Tryfonidou Marianna A. , Le Maitre Christine L.
Published: March 2019

The intervertebral disc (IVD) is a highly hydrated tissue, the rich proteoglycan matrix imbibes water, enabling the disc to withstand compressive loads. During aging and degeneration increased matrix degradation leads to dehydration and loss of function. Aquaporins (AQP) are a family of transmembrane channel proteins that selectively allow the passage of water in and out of cells and are responsible for maintaining water homeostasis in many tissues. Here, the expression of all 13 AQPs at gene and protein level was investigated in human and canine nondegenerate and degenerate IVDs to develop an understanding of the role of AQPs during degeneration. Furthermore, in order to explore the transition of notochordal cells (NCs) towards nucleus pulposus (NP) cells, AQP expression was investigated in canine IVDs enriched in NCs to understand the role of AQPs in IVD maturation. AQP0, 1, 2, 3, 4, 5, 6, 7, and 9 were expressed at gene and protein level in both nondegenerate and degenerate human NP tissue. AQP2 and 7 immunopositivity increased with degeneration in human NP tissue, whereas AQP4 expression decreased with degeneration in a similar way to AQP1 and 5 shown previously. All AQP proteins that were identified in human NP tissue were also expressed in canine NP tissue. AQP2, 5, 6, and 9 were found to localize to vacuole‐like membranes and cell membranes in NC cells. In conclusion, AQPs were abundantly expressed in human and canine IVDs. The expression of many AQP isotypes potentially alludes to multifaceted functions related to adaption of NP cells to the conditions they encounter within their microenvironment in health and degeneration. The presence of AQPs within the IVD may suggest an adaptive role for these water channels during the development and maintenance of the healthy, mature IVD.
Standardization of volumetric modulated arc therapy‐based frameless stereotactic technique using a multidimensional ensemble‐aided knowledge‐based planning
Authors: Sarkar Biplab , Munshi Anusheel , Ganesh Tharmarnadar , Manikandan Arjunan , Anbazhagan Satheesh Kumar , Mohanti Bidhu Kalyan
Published: March 2019

Purpose

Aim of this article is to describe a new knowledge‐based planning (KBP) methodology using volumetric modulated arc therapy (VMAT) for stereotactic radiosurgery (SRS) and radiotherapy (SRT) assisted by an ensemble mapping technique for use in a Monte Carlo planning system.

Methods

Libraries of 121 stereotactic patients were assembled on the basis of eight different parameters (a) tumor laterality, (b) whether planning target volume (PTV) dose coverage challenged by the presence of the organ at risk (OAR), (c) prescription dose and number of fractions, (d) number of PTVs, (e) tumor volume, (f) shortest distance between OAR and PTV (edge to edge distance, or EED), (g) center to center distance between OARs and PTV (CCD), and (h) lateral dimension of external contour (brain). For new patients, the most appropriate library plan was selected on the basis of the above categorization. A KBP plan was created based on this selected library plan with all parameters unchanged keeping the isocenter at the center of PTV. Using the same beam configuration, another independent treatment plan (IP) was generated by an experienced dosimetrist for comparison. IP and KBP were compared for 76 new patients.

Results

Of 197 patients (121 library and 76 new), 103 (52.3%) were placed in the OAR‐challenged category and 94 were placed in the OAR unchallenged category. The ensemble mapping technique shows that, for an OAR‐challenged patient, picking up the library plan is appropriate. IP was marginally better than KBP in PTV coverage and dose conformity (PCI). Library plans, IP, and KBP offer a mean PCI of 0.77 ± 0.2, 0.79 ± 0.2, and 0.78 ± 0.4, mean PTV‐V99% of 97.3 ± 22.0%, 98.9 ± 14.1%, and 98.2 ± 13.2%, and mean MU of 2403.8 ± 2403.8, 2344.0 ± 2423.6, and 2473.6 ± 2296.8, respectively. Statistically significant differences were observed in the planning time between the IP and KBP plans for both OAR‐challenged (P < 0.001) and ‐unchallenged (P < 0.002) categories. Comparison of optimization and dose calculation time showed a much lower average planning time of 111.0 ± 84.1 min for KBP as against 248.2 ± 96.6 min for IP.

Conclusion

Validation results for KBP plans indicate the multidimensional ensemble mapping mechanism can accurately pick up the most appropriate library plan. KBP plans, although slightly inferior in their dosimetric quality, fulfill all the required clinical conditions and dose constraints. KBP plans save considerable planning time and are nearly independent of the skill and knowledge of the treatment planner. KBP works well with a Monte Carlo planning system like Monaco.
Construction of patient‐specific computational models for organ dose estimation in radiological imaging
Authors: Xie Tianwu , Akhavanallaf Azadeh , Zaidi Habib
Published: March 2019

Purpose

Diagnostic imaging procedures require optimization depending on the medical task at hand, the apparatus being used, and patient physical and anatomical characteristics. The assessment of the radiation dose and associated risks plays a key role in safety and quality management for radiation protection purposes. In this work, we aim at developing a methodology for personalized organ‐level dose assessment in x‐ray computed tomography (CT) imaging.

Methods

Regional voxel models representing reference patient‐specific computational phantoms were generated through image segmentation of CT images for four patients. The best‐fitting anthropomorphic phantoms were selected from a previously developed comprehensive phantom library according to patient's anthropometric parameters, then registered to the anatomical masks (skeleton, lung, and body contour) of patients to produce a patient‐specific whole‐body phantom. Well‐established image registration metrics including Jaccard's coefficients for each organ, organ mass, body perimeter, organ‐surface distance, and effective diameter are compared between the reference patient model, registered model, and anchor phantoms. A previously validated Monte Carlo code is utilized to calculate the absorbed dose in target organs along with the effective dose delivered to patients. The calculated absorbed doses from the reference patient models are then compared with the produced personalized model, anchor phantom, and those reported by commercial dose monitoring systems.

Results

The evaluated organ‐surface distance and body effective diameter metrics show a mean absolute difference between patient regional voxel models, serving as reference, and patient‐specific models around 4.4% and 4.5%, respectively. Organ‐level radiation doses of patient‐specific models are in good agreement with those of the corresponding patient regional voxel models with a mean absolute difference of 9.1%. The mean absolute difference of organ doses for the best‐fitting model extracted from the phantom library and Radimetrics™ commercial dose tracking software are 15.5% and 41.1%, respectively.

Conclusion

The results suggest that the proposed methodology improves the accuracy of organ‐level dose estimation in CT, especially for extreme cases [high body mass index (BMI) and large skeleton]. Patient‐specific radiation dose calculation and risk assessment can be performed using the proposed methodology for both monitoring of cumulative radiation exposure of patients and epidemiological studies. Further validation using a larger database is warranted.
Solving partially observable agent‐intruder games with an application to border security problems
Authors: Laan Corine M. , Barros Ana Isabel , Boucherie Richard J. , Monsuur Herman , Timmer Judith
Published: March 2019

In this paper, we introduce partially observable agent‐intruder games (POAIGs). These games model dynamic search games on graphs between security forces (an agent) and an intruder given possible (border) entry points and high value assets that require protection. The agent faces situations with dynamically changing, partially observable information about the state of the intruder and vice versa. The agent may place sensors at selected locations, while the intruder may recruit partners to observe the agent's movement. We formulate the problem as a two‐person zero‐sum game, and develop efficient algorithms to compute each player's optimal strategy. The solution to the game will help the agent choose sensor locations and design patrol routes that can handle imperfect information. First, we prove the existence of ϵ‐optimal strategies for POAIGs with an infinite time horizon. Second, we introduce a Bayesian approximation algorithm to identify these ϵ‐optimal strategies using belief functions that incorporate the imperfect information that becomes available during the game. For the solutions of large POAIGs with a finite time horizon, we use a solution method common to extensive form games, namely, the sequence form representation. To illustrate the POAIGs, we present several examples and numerical results.
Forward‐in‐time goal‐oriented adaptivity
Authors: Muñoz‐Matute Judit , Pardo David , Calo Victor M. , Alberdi Elisabete
Published: March 2019

In goal‐oriented adaptive algorithms for partial differential equations, we adapt the finite element mesh to reduce the error of the solution in some quantity of interest. In time‐dependent problems, this adaptive algorithm involves solving a dual problem that runs backward in time. This process is, in general, computationally expensive in terms of memory storage. In this work, we define a pseudo‐dual problem that runs forward in time. We also describe a forward‐in‐time adaptive algorithm that works for some specific problems. Although it is not possible to define a general dual problem running forwards in time that provides information about future states, we provide numerical evidence via one‐dimensional problems in space to illustrate the efficiency of our algorithm as well as its limitations. Finally, we propose a hybrid algorithm that employs the classical backward‐in‐time dual problem once and then performs the adaptive process forwards in time.
Nanocomposites based on low density polyethylene filled with carbon nanotubes prepared by high energy ball milling and their potential antibacterial activity
Authors: Benigno Erika , Lorente Miguel A , Olmos Dania , González‐Gaitano Gustavo , González‐Benito Javier
Published: March 2019

Low density polyethylene (LDPE) based nanocomposites containing multi‐walled carbon nanotubes (MWCNTs) were prepared by a two‐step process consisting of a pre‐mixture using high energy ball milling (HEBM) and subsequent hot pressing. The effects of ball milling and the presence of the MWCNTs on some physical properties of the materials and the antimicrobial efficiency against DH5α Escherichia coli were studied. Fourier transform infrared spectroscopy revealed that the polymer structure did not change in the final materials after the addition of MWCNTs and mixing. Differential scanning calorimetry showed small differences in the LDPE thermal behavior as a function of the type of material due to small changes in the polymer crystallization. This result was mainly ascribed to the milling process rather than to the incorporation of the MWCNTs. The presence of 1% by weight of the nanofiller increased the rigidity and hydrophobicity of the nanocomposites with respect to neat LDPE. This effect was explained by the preferential location of the MWCNTs in the surface of the material as the main factor decreasing the polar contribution to the surface free energy. A correlation between hydrophobicity, biofilm development and the shape and size of DH5α E. coli was observed, indicating that the presence of MWCNTs leads to a biocide effect by decreasing cell adhesion and changing its metabolism. © 2019 Society of Chemical Industry
A test for the correct specification of marginal structural models
Authors: Sall Alioune , Aubé Karine , Trudel Xavier , Brisson Chantal , Talbot Denis
Published: March 2019

Marginal structural models (MSMs) allow estimating the causal effect of a time‐varying exposure on an outcome in the presence of time‐dependent confounding. The parameters of MSMs can be estimated utilizing an inverse probability of treatment weight estimator under certain assumptions. One of these assumptions is that the proposed causal model relating the outcome to exposure history is correctly specified. However, in practice, the true model is unknown. We propose a test that employs the observed data to attempt validating the assumption that the model is correctly specified. The performance of the proposed test is investigated with a simulation study. We illustrate our approach by estimating the effect of repeated exposure to psychosocial stressors at work on ambulatory blood pressure in a large cohort of white‐collar workers in Québec City, Canada. Code examples in SAS and R are provided to facilitate the implementation of the test.
The Legacy of Hypoxia: Tracking Carryover Effects of Low Oxygen Exposure in a Demersal Fish Using Geochemical Tracers
Authors: Altenritter Matthew E. , Walther Benjamin D.
Published: March 2019

The increasing prevalence of hypoxia in aquatic ecosystems emphasizes the need to understand sublethal effects on organisms to anticipate potential changes in population dynamics. Carryover effects of hypoxia exposure during early life stages on lifetime survival and growth performance are rarely known, which leaves major knowledge gaps about the long‐term impacts of sublethal exposures. Geochemical signatures incorporated into fish hard parts can track lifetime hypoxia exposure, thereby allowing sublethal carryover effects across age‐classes to be quantified. We examined the impact of hypoxia exposure on the Atlantic Croaker Micropogonias undulatus, a demersal fish inhabiting the northern Gulf of Mexico, which is one of the largest hypoxic systems in the world. Using an otolith‐based, dual‐proxy (Mn:Ca and Ba:Ca) geochemical method coupled with intracohort comparisons, we assessed changes in the traits of Atlantic Croakers that survived hypoxia exposure during their first year of life. We also investigated whether somatic growth was affected by exposure to sublethal hypoxia during the first year of life. Within three cohorts of Atlantic Croakers, there was no evidence that the otolith‐based traits of survivors changed from one year to the next. Additionally, somatic growth in individuals that had previously experienced sublethal hypoxia during the first year of life and survived was not depressed relative to somatic growth in individuals that did not experience hypoxic conditions. These results indicate that Atlantic Croakers are tolerant to hypoxia experienced during early life and that sublethal carryover effects do not manifest as reductions in survival or growth. Geochemical indicators of hypoxia exposure in fish otoliths can thus provide vital insight into the range of potential sublethal responses by fishes with variable sensitivities to this growing environmental stressor across the world.
Zero-Inflated Regime-Switching Stochastic Differential Equation Models for Highly Unbalanced Multivariate, Multi-Subject Time-Series Data
Authors: Lu Zhao-Hua , Chow Sy-Miin , Ram Nilam , Cole Pamela M.
Published: March 2019

In the study of human dynamics, the behavior under study is often operationalized by tallying the frequencies and intensities of a collection of lower-order processes. For instance, the higher-order construct of negative affect may be indicated by the occurrence of crying, frowning, and other verbal and nonverbal expressions of distress, fear, anger, and other negative feelings. However, because of idiosyncratic differences in how negative affect is expressed, some of the lower-order processes may be characterized by sparse occurrences in some individuals. To aid the recovery of the true dynamics of a system in cases where there may be an inflation of such “zero responses,” we propose adding a regime (unobserved phase) of “non-occurrence” to a bivariate Ornstein–Uhlenbeck (OU) model to account for the high instances of non-occurrence in some individuals while simultaneously allowing for multivariate dynamic representation of the processes of interest under nonzero responses. The transition between the occurrence (i.e., active) and non-occurrence (i.e., inactive) regimes is represented using a novel latent Markovian transition model with dependencies on latent variables and person-specific covariates to account for inter-individual heterogeneity of the processes. Bayesian estimation and inference are based on Markov chain Monte Carlo algorithms implemented using the JAGS software. We demonstrate the utility of the proposed zero-inflated regime-switching OU model to a study of young children’s self-regulation at 36 and 48 months.
A randomized clinical trial to evaluate home‐based assessment of people over 75 years old
Authors: Sano Mary , Zhu Carolyn W. , Kaye Jeffrey , Mundt James C. , Hayes Tamara L. , Ferris Steven , Thomas Ronald G. , Sun Chung‐Kai , Jiang Yanxin , Donohue Michael C. , Schneider Lon S. , Egelko Susan , Aisen Paul S. , Feldman Howard H. ,   for the Alzheimer Disease Cooperative Study Investigators
Published: March 2019

Introduction

There is an unmet need for effective methods for conducting dementia prevention trials.

Methods

Home‐based assessment study compared feasibility and efficiency, ability to capture change over time using in‐home instruments, and ability to predict cognitive conversion using predefined triggers in a randomized clinical trial in (1) mail‐in questionnaire/live telephone interviews, (2) automated telephone/interactive voice recognition, and (3) internet‐based computer Kiosk technologies. Primary endpoint was defined as cognitive conversion.

Results

Analysis followed a modified intent‐to‐treat principle. Dropout rates were low and similar across technologies but participants in Kiosk were more likely to dropout earlier. Staff resources needed were higher in Kiosk. In‐home instruments distinguished conversion and stable groups. Cognitively stable group showed improvement in cognitive measures. Triggering was associated with higher likelihood of conversion but statistically significant only in mail‐in questionnaire/live telephone interviews.

Discussion

Relatively low efficiency of internet‐based assessment compared with testing by live‐assessors has implications for internet‐based recruitment and assessment efforts currently proposed for diverse populations.