bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on risk stratification in the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology categories: 3‐Year, prospective, single‐institution experience
Authors: Sung Simon , Del Portillo Armando , Gonda Tamas A. , Kluger Michael D. , Tiscornia‐Wasserman Patricia G.
Published: November 2019

Background

Risk stratification is a critical element for the successful implementation of cytopathology reporting systems. To the authors' knowledge, there are limited prior studies regarding risk stratification for The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSCPC). In the current study, the authors reported on a single‐institution experience on 3‐year prospective PSCPC regarding risk of malignancy (ROM) and the overall risk of malignancy (OROM).

Methods

A computerized search was performed from August 2014 to December 2017 for all pancreatic fine‐needle aspiration (FNA) samples. Pathology from surgical resections and biopsies and relevant radiologic and clinical follow‐up data were collected. The ROM and the OROM were calculated. The OROM was based on the total number of FNA samples in each category.

Results

A total of 1017 pancreatic FNA cases were identified, with surgical and/or clinical follow‐up data available for 548 cases. The cytopathologic diagnoses included 242 nondiagnostic (category I), 162 benign (category II), 142 atypical (category III), 20 neoplastic‐benign (category IV: benign), 133 neoplastic‐other (category IV: other), 28 suspicious (category V), and 290 malignant (category VI) cases. A total of 364 malignancies were documented in 11 cases, 4 cases, 36 cases, 0 cases, 36 cases, 21 cases, and 255 cases, respectively, from categories I, II, III, IV: benign, IV:other, V, and VI. The ROM was 25%, 17.4%, 41.8%, 0%, 34.3% (95.2%), 95.5%, and 99.6%, respectively, and the OROM was 4.5%, 2.5%, 25.3%, 0%, 27.1% (83.3%), 75%, and 87.9%, respectively, for categories I, II, III, IV: benign, IV: other (with high‐grade dysplasia), V, and VI.

Conclusions

The true ROM for PSCPC is likely between the ROM and OROM for the benign and indeterminate categories. In the neoplastic‐other category (category IV: other), identifying high‐grade dysplasia is important for its association with malignancy and a higher ROM.
Deletion of the cannabinoid CB1 receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses
Authors: Buceta Ianire , Elezgarai Izaskun , Rico‐Barrio Irantzu , Gerrikagoitia Inmaculada , Puente Nagore , Grandes Pedro
Published: November 2019

The cannabinoid CB1 receptor localizes to the glutamatergic parallel fiber (PF) terminals of the cerebellar granule cells and participates in synaptic plasticity, motor control and learning that are impaired in CB1 receptor knockout (CB
1‐KO) mice. However, whether ultrastructural changes at the PF‐Purkinje cell (PC) synapses occur in CB
1‐KO remains unknown. We studied this in the vermis of the spinocerebellar lobule V and the vestibulocerebellar lobule X of CB
1‐KO and wild‐type (CB
1‐WT) mice by electron microscopy. Lobule V, but not lobule X, of CB
1‐KO had significantly less and longer synapses than in CB
1‐WT. PF terminals were significantly larger in both lobules of CB
1‐KO with no changes in PC dendritic spines. The PF terminals in lobule V of CB
1‐KO contained less synaptic vesicles and lower vesicle density; by contrast, vesicle density in lobule X of CB
1‐KO remained unchangeable relative to CB
1‐WT. There were as many vesicles in lobule V of CB
1‐KO as in CB
1‐WT, but their distribution decreased drastically at 300 nm of the active zone. In lobule X of CB
1‐KO, less vesicles were found within 150 nm from the presynaptic membrane; however, no vesicles were at 450–600 nm of the active zone. A significant higher amount of synaptic vesicles close to the active zone in lobule V and X of CB
1‐KO was observed. In conclusion, the absence of CB1 receptors strikingly and distinctively impacts on the ultrastructural architecture of the PF‐PC synapses located in cerebellar lobules that differ in vulnerability to damage and motor functions.
Characterization of striatal phenotypes in heterozygous Disc1 mutant mice, a model of haploinsufficiency
Authors: Baskaran Rathinasamy , Lai Chuan‐Ching , Li Wai‐Yu , Tuan Li‐Heng , Wang Chia‐Chuan , Lee Lukas J.‐H. , Liu Chih‐Min , Hwu Hai‐Gwo , Lee Li‐Jen
Published: November 2019

Disrupted‐in‐Schizophrenia 1 (DISC1) is a susceptibility gene for several psychiatric illnesses. To study the pathogenesis of these disorders, we generated Disc1 mutant mice by introducing the 129S6/SvEv 25‐bp deletion Disc1 variants into the C57BL/6J strain. In this study, we used heterozygous Disc1 mutant (Het) mice to evaluate the DISC1 haploinsufficiency model of schizophrenia. No changes in locomotor behaviors were observed in Het mice; however, after amphetamine injection, greater locomotor activity was observed in Het mice compared with wild‐type (WT) mice. Moreover, amphetamine‐induced elevations of c‐Fos expression and dopamine level in the striatum were greater in Het mice than in WT controls, suggesting an altered dopaminergic regulation in the striatum of Het mice. Compared with those in WTs, the striatal protein levels of dopamine transporter and D2 dopamine receptor were increased in Het mice, while D1 dopamine receptor level was decreased. DISC1 interacting proteins, GSK3α and GSK3β, were downregulated in Het mice, whereas the levels of PDE4B and CREB were not altered. Morphologically, the complexities of striatal median spiny neurons (MSNs), parvalbumin‐positive interneurons and Iba1‐positive microglia were all decreased in Het mice. The density and head diameter of dendritic spines in the MSNs of Het mice were also reduced. Our results indicate that mice lacking one WT Disc1 allele are more sensitive to psychostimulant amphetamine challenge, which might be attributed to the altered structure and function of the striatal dopaminergic system. Here, we demonstrated striatal phenotypes in heterozygous Disc1 mutant mice, which could be a promising model of DISC1 haploinsufficiency.
In Silico Evidence That Protein Unfolding is a Precursor of Protein Aggregation
Authors: Bianco Valentino , Franzese Giancarlo , Coluzza Ivan
Published: November 2019

We present a computational study on the folding and aggregation of proteins in an aqueous environment, as a function of its concentration. We show how the increase of the concentration of individual protein species can induce a partial unfolding of the native conformation without the occurrence of aggregates. A further increment of the protein concentration results in the complete loss of the folded structures and induces the formation of protein aggregates. We discuss the effect of the protein interface on the water fluctuations in the protein hydration shell and their relevance in the protein‐protein interaction.
Physiologically‐Based Pharmacokinetic Modeling for Optimal Dosage Prediction of Quinine Coadministered With Ritonavir‐Boosted Lopinavir
Authors: Saeheng Teerachat , Na‐Bangchang Kesara , Siccardi Marco , Rajoli Rajith K.R. , Karbwang Juntra
Published: November 2019

The coformulated lopinavir/ritonavir significantly reduces quinine concentration in healthy volunteers due to potential drug–drug interactions (DDIs). However, DDI information in malaria and HIV coinfected patients are lacking. The objective of the study was to apply physiologically‐based pharmacokinetic (PBPK) modeling to predict optimal dosage regimens of quinine when coadministered with lopinavir/ritonavir in malaria and HIV coinfected patients with different conditions. The developed model was validated against literature. Model verification was evaluated using the accepted method. The verified PBPK models successfully predicted unbound quinine disposition when coadministered with lopinavir/ritonavir in coinfected patients with different conditions. Suitable dose adjustments to counteract with the DDIs have identified in patients with various situations (i.e., a 7‐day course at 1,800 mg t.i.d. in patients with malaria with HIV infection, 648 mg b.i.d. in chronic renal failure, 648 mg t.i.d. in hepatic insufficiency except for severe hepatic insufficiency (324 mg b.i.d.), and 648 mg t.i.d. in CYP3A4 polymorphism).
Room‐Temperature Synthesis of High‐Entropy Perovskite Oxide Nanoparticle Catalysts through Ultrasonication‐Based Method
Authors: Okejiri Francis , Zhang Zihao , Liu Jixing , Liu Miaomiao , Yang Shize , Dai Sheng
Published: November 2019

In the present study, a sonochemical‐based method for one‐pot synthesis of entropy‐stabilized perovskite oxide nanoparticle catalysts with high surface area was developed. The high‐entropy perovskite oxides were synthesized as monodispersed, spherical nanoparticles with an average crystallite size of approximately 5.9 nm. Taking advantage of the acoustic cavitation phenomenon in the ultrasonication process, BaSr(ZrHfTi)O3, BaSrBi(ZrHfTiFe)O3 and Ru/BaSrBi(ZrHfTiFe)O3 nanoparticles were crystallized as single‐phase perovskite structures through ultrasonication exposure without calcination. Notably, the entropically‐driven stability of Ru/BaSrBi(ZrHfTiFe)O3 with excellent dispersion of Ru in the perovskite phase bestowed the nanoparticles of Ru/BaSrBi(ZrHfTiFe)O3 with good catalytic activity for CO oxidation.
Synthesis of Metal Phosphide Nanoparticles Supported on Porous N‐Doped Carbon Derived from Spirulina for Universal‐pH Hydrogen Evolution
Authors: Yang Ming , Feng Fan , Wang Kaizhi , Li Shuwen , Huang Xiaokang , Gong Li , Ma Lei , Li Rong
Published: November 2019

Transition metal phosphides (TMPs) are regarded as highly active electrocatalysts for the hydrogen evolution reaction (HER). However, traditional synthetic routes usually use expensive and dangerous precursors as P donors. The development of a low‐cost and ecofriendly method for the synthesis of TMPs is significant for sustainable energy development. Herein, cobalt phosphides anchored on or embedded in a spirulina‐derived porous N‐doped carbon matrix (Co2P/NC) was fabricated by two‐step hydrothermal treatment and carbonization method, which utilized the intrinsic C, N, and P of biomass cleverly as the sources of C, N, and P, respectively. As a result of the high surface area and porosity that enhance the mass‐transfer dynamics, Co2P/NC shows good electrocatalytic activity at all pH values in the HER. This work not only provides a facile and effective method for the fabrication of TMP nanoparticles loaded onto carbon materials but also opens a new strategy for the utilization of the intrinsic ingredients of biomass for the preparation of other functional electrocatalysts.
Appropriateness of action prompts for hypoglycaemia and hyperglycaemia in type 2 diabetes self‐management apps
Authors: Lum Elaine , Jimenez Geronimo , Huang Zhilian , Thai Linh , Car Josip
Published: November 2019

Background

Control of blood glucose levels is needed not only to alleviate symptoms of hypoglycaemia and hyperglycaemia, but also to prevent or delay diabetes‐related complications. Advice for glucose control is usually provided to patients by members of the health care team. However, many diabetes apps claim to enhance self‐management of blood glucose by providing decision support to patients when an out‐of‐range blood glucose level is recorded. In this study, we investigated the appropriateness of action prompts provided by diabetes apps for hypoglycaemia and hyperglycaemia against evidence‐based guidelines.

Methods

We used methods previously reported to identify and select diabetes apps, which were downloaded and assessed against the American Diabetes Association (ADA) guidelines. Screenshots of action prompts corresponding to low or high out‐of‐range blood glucose values were subjected to content analysis.

Results

Of 371 diabetes self‐management apps evaluated, only 217 and 216 apps alerted patients about hypoglycaemia and hyperglycaemia, respectively. Of these, 20.7% (45/217) and 15.3% (33/216) also provided action prompts. We found 5.1% of apps (hypoglycaemia: 11/217; hyperglycaemia: 11/216) provided prompts that were either too general to be helpful or not aligned with ADA guidelines. Overall, only 17.9% (39/217) and 14.8% (32/216) provided appropriate action prompts for hypoglycaemia and hyperglycaemia, respectively.

Conclusion

Less than one fifth of apps provided evidence‐based steps to guide patients through hypoglycaemia and hyperglycaemia. The majority of apps failed to provide just‐in‐time diabetes self‐management education to prevent frequent or severe episodes of hypoglycaemia and hyperglycaemia. Our findings emphasize the need for better design and quality assurance of diabetes apps.
Charge Redistribution Effects in Hexacyanometallates Evaluated from XPS Data
Authors: Cano Arely , Reguera Leslie , Avila Manuel , Velasco‐Arias Donaji , Reguera Edilso
Published: November 2019

The charge redistribution effects determine the physical and functional properties of transition metal hexacyanometallates. The π‐back bonding interaction between the CN ligand and the metal (M) linked at its C end and the σ donation from the N end to a second transition metal (T), when a coordination polymer is formed, are relevant features of such effects. The π‐back donation interaction contributes to the overlapping of the electron clouds of M and T metals in the ···–T–N≡C–M–C≡N–T‐··· chain. In this contribution, we demonstrate that XPS spectroscopy is a useful tool to sense the change in the electron density redistribution in hexacyanometallates related to these two mechanisms. The results herein discussed contribute to understand the physical and chemical properties of these materials. Initially, a series of potassium salts, Kn[M6–n(CN)6] (M = CrIII, FeII, RuII, OsII, CoIII, RhIII, IrIII, PtIV) is considered in order to evaluate the role of the π‐back donation on the electron density found at the N atom, which determines the strength for the T‐NC coordination bond and of the mentioned electron clouds overlapping. Then, a representative set of transition metal (T) hexacyanometallates, T2(1‐y)K2y[FeII(CN)6], is studied in order to shed light on the electron density redistribution when a coordination bond is formed at the N end. Within such coordination polymers, the copper (2+) salts are particularly attractive by the unique interaction between the copper atom and the hexacyanometallate ion, and the potential applications of these copper (2+) complexes in heterogeneous catalysis and other areas. From these reasons, the recorded XPS spectra for Cu (2+) hexacyanometallates were evaluated in detail. In accordance with a previous study of these copper (2+) coordination polymers using other techniques, XPS data is sensing an atypical strong bonding interaction with the CN ligand. The experimental XPS data herein discussed are relevant for the coordination chemistry of transition metal hexacyanometallates and for the research community involved in their applications.
Reactivity Studies of a Dipyridine Ethinyl Ligand with Zinc(II)
Authors: Egger Christiane M. , Jakob Christian H. G. , Kaiser Felix , Rindle Olivia , Altmann Philipp J. , Reich Robert M. , Kühn Fritz E.
Published: November 2019

Several dipyridine ethinyl ligands bearing a variety of functional groups (OMe, COOH, NH2, NHBoc, NBoc2) were synthesized and reacted with Zn(OTf)2 in CH3CN. Fundamental studies towards the reaction behavior between zinc and these ligands were conducted, showing that ligands with an amine group and its Boc protected derivatives (NBoc2 and NHBoc) lead to isolable defined products. SC‐XRD of the product derived from the amine ligand reveals a polymeric sandwich structure, showing that the NH2 moiety seems to be of vital importance for product formation. Depending on the reaction temperature, two novel coordination polymers are obtained upon reaction of the Boc protected amine ligands with Zn(OTf)2 in acetonitrile. SC‐XRD reveals for the NHBoc ligand an one‐dimensional CP with a layer structure, whereas the NBoc2 moiety possesses a two‐dimensional layer structure, with the NBoc2 moiety acting as a chelator for zinc(II) within the coordination polymer.
Metal‐Catalyzed Cyclization: Synthesis of (Benzo)morpholines and (Benzo)[1,4]dihydrooxazines
Authors: Aubineau Thomas , Cossy Janine
Published: November 2019

A review of the most recent metal‐catalyzed cyclizations to access morpholines and their unsaturated derivatives, from 1993 to 2019, is reported. The review is organized according to the bond(s) formed during the process. Special importance has been given to the mechanistic details of the reactions.
A high‐order nodal discontinuous Galerkin method to solve preconditioned multiphase Euler/Navier‐Stokes equations for inviscid/viscous cavitating flows
Authors: Hajihassanpour Mahya , Hejranfar Kazem
Published: November 2019

In this study, a high‐order accurate numerical method is applied and examined for the simulation of the inviscid/viscous cavitating flows by solving the preconditioned multiphase Euler/Navier‐Stokes equations on triangle elements. The formulation used here is based on the homogeneous equilibrium model considering the continuity and momentum equations together with the transport equation for the vapor phase with applying appropriate mass transfer terms for calculating the evaporation/condensation of the liquid/vapor phase. The spatial derivative terms in the resulting system of equations are discretized by the nodal discontinuous Galerkin method (NDGM) and an implicit dual‐time stepping method is used for the time integration. An artificial viscosity approach is implemented and assessed for capturing the steep discontinuities in the interface between the two phases. The accuracy and robustness of the proposed method in solving the preconditioned multiphase Euler/Navier‐Stokes equations are examined by the simulation of different two‐dimensional and axisymmetric cavitating flows. A sensitivity study is also performed to examine the effects of different numerical parameters on the accuracy and performance of the solution of the NDGM. Indications are that the solution methodology proposed and applied here is based on the NDGM with the implicit dual‐time stepping method and the artificial viscosity approach is accurate and robust for the simulation of the inviscid and viscous cavitating flows.
On the directional predictability of equity premium using machine learning techniques
Authors: Iworiso Jonathan , Vrontos Spyridon
Published: November 2019

This paper applies a plethora of machine learning techniques to forecast the direction of the US equity premium. Our techniques include benchmark binary probit models, classification and regression trees, along with penalized binary probit models. Our empirical analysis reveals that the sophisticated machine learning techniques significantly outperformed the benchmark binary probit forecasting models, both statistically and economically. Overall, the discriminant analysis classifiers are ranked first among all the models tested. Specifically, the high‐dimensional discriminant analysis classifier ranks first in terms of statistical performance, while the quadratic discriminant analysis classifier ranks first in economic performance. The penalized likelihood binary probit models (least absolute shrinkage and selection operator, ridge, elastic net) also outperformed the benchmark binary probit models, providing significant alternatives to portfolio managers.
LncRNA BC088259 promotes Schwann cell migration through Vimentin following peripheral nerve injury
Authors: Yao Chun , Chen Yanping , Wang Jing , Qian Tianmei , Feng Wei , Chen Yuanyuan , Mao Susu , Yu Bin
Published: November 2019

Schwann cell, the major glial cell in the peripheral nervous system, plays an essential role in peripheral nerve regeneration. However, the regulation of Schwann cell behavior following nerve injury is insufficiently explored. According to the development of high‐throughput techniques, long noncoding RNAs (lncRNAs) have been recognized. Accumulating evidence shows that lncRNAs take part in diverse biological processes and diseases. Here, by microarray analysis, we identified an upregulated lncRNA profile following sciatic nerve injury and focused on BC088259 for further investigation. Silencing or overexpression of BC088259 could affect Schwann cell migration. Mechanistically, BC088259 might exert this regulatory role by directly binding with Vimentin. Collectively, our study not only revealed a set of upregulated lncRNAs following nerve injury but also identified a new functional lncRNA, BC088259, which was important for Schwann cell migration, providing a therapeutic avenue toward peripheral nerve injury.
Predictors of online accountability practices in US hospitals: An exploratory investigation
Authors: Cooley Asya
Published: November 2019

The purpose of this research paper is to explore variations in online accountability practices in US hospitals and determine the factors that are associated with higher levels of online accountability practices. This project employed a quantitative content analysis of 240 US hospital websites. Additionally, secondary data were obtained from the American Hospital Association and the American Hospital Directory. The results show that the external environment somewhat impacted hospitals' online accountability practices, with hospital volume (measured through the number of annual admissions) as an unquestionable predictor. Another key finding is that some of the governance forms impacted online accountability practices. Particularly, hospitals with private ownership structures tended to disclose less accountability information in an online environment, compared with their public and nonprofit counterparts. The financial situation of hospitals did not have any significant impact on overall online accountability practices but was influencing performance disclosure practices. Online accountability studies have not been conducted in a health care setting. This research theoretically relates online accountability practices to organizational characteristics (such as size, volume, financial performance, system affiliation, ownership, and rurality). Knowledge of the online accountability landscape might benefit future policy decisions on accountability models.
Non‐performing loans and the harmonisation of extrajudicial collateral enforcement across Europe
Authors: Schuijling Ben , van Hoof Vincent , Hutten Tom
Published: November 2019

The European Union plans on partially harmonising the extrajudicial enforcement of collateral in order to reduce the stocks of nonperforming loans. This article discusses the proposed regime and its background. After examining its impact on the national secured transactions law of Austria, Belgium, France, Germany and The Netherlands, the authors comment on the appropriateness of the proposed harmonisation.
Social connectedness and mortality after prostate cancer diagnosis: A prospective cohort study
Authors: Wu Zimu , Nguyen Nga H. , Wang Dawei , Lynch Brigid M. , Hodge Allison M. , Bassett Julie K. , White Victoria M. , Borland Ron , English Dallas R. , Milne Roger L. , Giles Graham G. , Dugué Pierre‐Antoine
Published: November 2019

Men with prostate cancer experience side effects for which a supportive social environment may be beneficial. We examined the association between four measures of social connectedness and mortality after a prostate cancer diagnosis. Male participants in the Melbourne Collaborative Cohort Study in 1990–1994, who developed incident prostate cancer and attended follow‐up in 2003–2007, were eligible for the study. Information on social connectedness, collected at follow‐up, included (i) living arrangement; (ii) frequency of visits to friends/relatives and (iii) from friends/relatives; (iv) weekly hours of social activities. A total of 1,421 prostate cancer cases was observed (338 all‐cause deaths, 113 from prostate cancer), including 867 after follow‐up (150 all‐cause deaths, 55 from prostate cancer) and 554 before follow‐up (188 all‐cause deaths, 58 from prostate cancer). Cox models stratified by tumour Gleason score and stage, and sequentially adjusted for socioeconomic, health‐ and lifestyle‐related confounders, were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between social connectedness and all‐cause mortality after prostate cancer. Men who reported living alone before diagnosis had higher overall mortality (HR = 1.6, 95% CI: 1.0–2.5), after adjustment for socioeconomic, health and lifestyle confounders. Lower mortality was observed for men with more social activities (p‐trend = 0.07), but not in comprehensively adjusted models. Consistent with these findings, men living alone after prostate cancer diagnosis had higher mortality (HR = 1.3, 95% CI: 0.9–1.9). Lower mortality was observed with increasing socializing hours in the age‐adjusted model (p‐trend = 0.06) but not after more comprehensive adjustment. Our findings suggest that living with someone, but not other aspects of social connectedness, may be associated with decreased mortality for men with prostate cancer.
Optimizing deep belief network parameters using grasshopper algorithm for liver disease classification
Authors: Renukadevi Thangavel , Karunakaran Saminathan
Published: November 2019

Image processing plays a vital role in many areas such as healthcare, military, scientific and business due to its wide variety of advantages and applications. Detection of computed tomography (CT) liver disease is one of the difficult tasks in the medical field. Hand crafted features and classifications are the two types of methods used in the previous approaches, to classify liver disease. But these classification results are not optimal. In this article, we propose a novel method utilizing deep belief network (DBN) with grasshopper optimization algorithm (GOA) for liver disease classification. Initially, the image quality is enhanced by preprocessing techniques and then features like texture, color and shape are extracted. The extracted features are reduced by utilizing the dimensionality reduction method like principal component analysis (PCA). Here, the DBN parameters are optimized using GOA for recognizing liver disease. The experiments are performed on the real time and open source CT image datasets which embraces normal, cyst, hepatoma, and cavernous hemangiomas, fatty liver, metastasis, cirrhosis, and tumor samples. The proposed method yields 98% accuracy, 95.82% sensitivity, 97.52% specificity, 98.53% precision, and 96.8% F‐1 score in simulation process when compared with other existing techniques.
Step‐by‐step monitoring of a magnetic and SERS‐active immunosensor assembly for purification and detection of tau protein
Authors: Maurer Viktor , Frank Claudia , Porsiel Julian Cedric , Zellmer Sabrina , Garnweitner Georg , Stosch Rainer
Published: November 2019

We report a bottom‐up synthesis of iron oxide and gold nanoparticles, which are functionalized and combined to form a nanohybrid serving as an immune sensor, which selectively binds to tau protein, a biomarker for diagnosis of Alzheimer's disease. Detection of the target analyte is achieved by surface‐enhanced Raman scattering originating from the diagnostic part of the nanohybrid that was prepared from Au nanoparticles functionalized with 5,5′‐dithiobis‐(2‐nitrobenzoic acid) as a Raman reporter and monoclonal anti‐tau antibody. The magnetic part consists of FexOy nanoparticles functionalized with polyclonal anti‐tau antibody and is capable to separate tau protein from a complex matrix such as cerebrospinal fluid. We further identified and validated a set of analytical tools that allow monitoring the success of both nanoparticle preparation and each functionalization step performed during the assembly of the two binding sites by an immune reaction. By applying UV/Vis spectroscopy, dynamic light scattering, zeta potential measurements, X‐ray diffraction, small‐angle X‐ray scattering, and transmission electron microscopy, we demonstrate a proof‐of‐concept for a controlled and step‐by‐step traceable synthesis of a tau protein‐specific immune sensor.
LncRNA TDRG1 promotes the metastasis of NSCLC cell through regulating miR‐873‐5p/ZEB1 axis
Authors: Hu Xiufeng , Mu Yu , Wang Jiaojie , Zhao Yanqiu
Published: November 2019

Long noncoding RNAs (lncRNAs) are dysregulated in various malignancies and involved in the growth and aggressive phenotypes of cancer cells. Previous studies indicate that lncRNA testis development related 1 (TDRG1) plays critical roles in the development of several malignancies. Nevertheless, the molecular mechanism underlying TDRG1 contributes to non–small cell lung cancer (NSCLC) remains elusive. Here, we demonstrate that TDRG1 is significantly overregulated in NSCLC tissues and cell lines. Knockdown of TDRG1 inhibits the proliferation and metastatic‐related traits of NSCLC cell in vitro whereas overexpression of TDRG1 causes opposite results. In addition, TDRG1 silencing inhibits the growth and metastatic ability of NSCLC cell in vivo as demonstrated by xenograft tumor model and lung metastasis model. The binding capacity of TDRG1 with miR‐873‐5p is demonstrated by bioinformatics prediction tool and luciferase reporter gene assay. Additional, the rescue experiments indicate that TDRG1 interacts with miR‐873‐5p and its expression is positively associated with the target of miR‐873‐5p, zinc finger e‐box binding homeobox 1 (ZEB1). Altogether, lncRNA TDRG1 facilitates the progression of NSCLC via interacting with miR‐873‐5p and positively regulates the expression of ZEB1.
A Minimal Membrane Metal Transport System: Dynamics and Energetics of mer Proteins
Authors: Hwang Hyea , Hazel Anthony , Lian Peng , Smith Jeremy C. , Gumbart James C. , Parks Jerry M.
Published: November 2019

The mer operon in bacteria encodes a set of proteins and enzymes that impart resistance to environmental mercury toxicity by importing Hg2+ and reducing it to volatile Hg(0). Because the reduction occurs in the cytoplasm, mercuric ions must first be transported across the cytoplasmic membrane by one of a few known transporters. MerF is the smallest of these, containing only two transmembrane helices and two pairs of vicinal cysteines that coordinate mercuric ions. In this work, we use molecular dynamics simulations to characterize the dynamics of MerF in its apo and Hg2+‐bound states. We find that the apo state positions one of the cysteine pairs closer to the periplasmic side of the membrane, while in the bound state the same pair approaches the cytoplasmic side. This finding is consistent with the functional requirement of accepting Hg2+ from the periplasmic space, sequestering it on acceptance, and transferring it to the cytoplasm. Conformational changes in the TM helices facilitate the functional interaction of the two cysteine pairs. Free‐energy calculations provide a barrier of 16 kcal/mol for the association of the periplasmic Hg2+‐bound protein MerP with MerF and 7 kcal/mol for the subsequent association of MerF's two cysteine pairs. Despite the significant conformational changes required to move the binding site across the membrane, coarse‐grained simulations of multiple copies of MerF support the expectation that it functions as a monomer. Our results demonstrate how conformational changes and binding thermodynamics could lead to such a small membrane protein acting as an ion transporter. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
Long noncoding RNA NEAT1 correlates with higher disease risk, worse disease condition, decreased miR‐124 and miR‐125a and predicts poor recurrence‐free survival of acute ischemic stroke
Authors: Li Ping , Duan Shuyuan , Fu Adan
Published: November 2019

Objective

This study aimed to investigate the predictive value of long noncoding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) for acute ischemic stroke (AIS) risk and to explore the correlation of lncRNA NEAT1 with disease severity, inflammation, recurrence and target microRNAs in patients with AIS.

Methods

210 patients with AIS and 210 controls were enrolled, and their peripheral blood samples were collected within 24 hours after admission and collected on the enrollment, respectively. lncRNA NEAT1 expression was detected by quantitative polymerase chain reaction (qPCR). For patients with AIS, disease severity was evaluated by National Institute of Health Stroke Scale (NIHSS) score; plasma concentrations of inflammatory factors and lncRNA NEAT1 target microRNAs were measured by enzyme‐linked immune sorbent assay and qPCR, respectively; stroke recurrence and death were recorded; and recurrence‐free survival (RFS) was calculated.

Results

lncRNA NEAT1 expression was elevated in patients with AIS compared with controls, and it had a good predictive value for AIS risk (area under the curve [AUC]: 0.804 [95% confidence interval [CI]: 0.763‐0.845]). In patients with AIS, lncRNA NEAT1 expression positively correlated with NIHSS score and inflammatory factor levels including C‐reactive protein (CRP), tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, IL‐8, and IL‐22, while it negatively correlated with anti‐inflammatory cytokine IL‐10 level. Besides, lncRNA NEAT1 predicted increased recurrence/death risk (AUC: 0.641 [95% CI: 0.541‐0.741]), and its high expression correlated with worse RFS. Additionally, lncRNA NEAT1 expression negatively correlated with microRNA‐124 and microRNA‐125a expressions.

Conclusion

LncRNA NEAT1 may serve as a novel biomarker for assisting AIS management and prognosis.
Reduced expression of circRNA hsa_circ_0067582 in human gastric cancer and its potential diagnostic values
Authors: Yu Xiuchong , Ding Haixiang , Yang Liangwei , Yu Yu , Zhou Jiaming , Yan Zhilong , Guo Junming
Published: November 2019

Background

Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Circular RNAs (circRNAs) are an abundant kind of endogenous RNAs that recently are found play a crucial role in the cancer occurrence and development. Nevertheless, little is known with regard to the diagnostic values of these circRNAs for GC. In this article of research, we investigated the role of hsa_circ_0067582 in clinical diagnosis of GC.

Materials and Methods

We used divergent primers, and the expression levels of hsa_circ_0067582 in 93 fresh GC tissues and paired adjacent normal tissues from surgical patients were detected using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Then, a receiver operating characteristic (ROC) curve was established to assess the diagnostic significance of hsa_circ_0067582. The relationship between expression of hsa_circ_0067582 and clinicopathological factors of patients was made further explored.

Results

Hsa_circ_0067582 levels were significantly decreased in GC tissues contrasted with adjacent normal tissues (n = 93, P < .001). After that, we discovered that it was evidently downregulated in 81.7% (76/93) GC tissues. The area under the ROC curve (AUC) of hsa_circ_0067582 was up to 0.6937, the sensitivity was 66.67%, and the specificity was 61.29%. Moreover, the hsa_circ_0067582 levels were obviously associated with tumor diameter (P = .002) and carbohydrate antigen 19‐9 (CA19‐9, P = .01). Meanwhile, after operation, low‐level group of hsa_circ_0067582 of GC patients was associated with better prognosis.

Conclusion

Our data imply that hsa_circ_000067582 may be a potential biomarker for GC diagnosis and prognosis evaluation.
Modular cognitive‐behavioral therapy for affective symptoms in young individuals at ultra‐high risk of first episode of psychosis: Randomized controlled trial
Authors: Pozza Andrea , Dèttore Davide
Published: November 2019

Objectives: Individuals at ultra‐high risk of psychosis often present concurrent affective symptoms (depression/anxiety). This study investigated whether modular cognitive‐behavioral therapy (CBT) targeting both ultra‐high risk and affective symptoms (a) reduced/delayed risk of a first psychotic episode at posttreatment and 14‐month follow‐up compared with a supportive intervention, (b) was more effective than control condition in producing remission on depression/anxiety.

Methods: Fifty‐eight ultrahigh risk individuals were randomly assigned to CBT or control condition. CBT consisted of 30 sessions, including CBT for psychotic experiences and depression/anxiety.

Results: In the CBT group, the cumulative number of participants who developed a first psychotic episode (n = 3, 10.34%) at follow‐up was lower than in the control group (n = 8, 27.60%; logrank χ2(1) = 3.68, p = .05). In the CBT group, a higher number of participants achieved remission than in control condition on affective symptoms at posttreatment/follow‐up.

Conclusion: CBT can prevent psychosis risk and produce better outcomes on depression/anxiety than supportive intervention.
Hepatic hemangioma supplied by abnormal portal vein: A case report
Authors: Ogawa Masahiro , Matsumoto Naoki , Kaneko Masahiro , Kumagawa Mariko , Watanabe Yukinobu , Hirayama Midori , Moriyama Mitsuhiko , Higaki Tokio , Takayama Tadatoshi , Sugitani Masahiko
Published: November 2019

Hepatic hemangioma is the most common hepatic tumor with a prevalence of approximately 3%. It is typically supplied by the hepatic artery as evident from findings of abdominal angiography, contrast‐enhanced ultrasonography (CEUS), contrast‐enhanced computed tomography (CT), and contrast‐enhanced magnetic resonance imaging. However, few cases of hepatic hemangioma supplied by the portal vein have been reported. In this paper, we report a rare case of hepatic hemangioma supplied by the portal vein as shown on CEUS and CT arterioportography.
Exome sequencing identifies a FHOD3 p.S527del mutation in a Chinese family with hypertrophic cardiomyopathy
Authors: Huang Suqiu , Pu Tian , Wei Wei , Xu Rang , Wu Yurong
Published: November 2019

Background

Hypertrophic cardiomyopathy (HCM) is the most common inheritable cardiac disease and is characterised by unexplained ventricular myocardial hypertrophy. HCM is highly heterogeneous and is primarily caused by the mutation of genes encoding sarcomere proteins. As a result of its genetic basis, we investigated the underlying cause of HCM in a Chinese family by whole‐exome sequencing.

Methods

Whole‐exome sequencing was performed for seven clinically diagnosed HCM family members and the resulting single nucleotide variants associated with cardiac hypertrophy or heart development were analysed by a polymerase chain reaction and Sanger sequencing.

Results

A non‐frameshift deletion mutation (p.S527del) of Formin Homology 2 Domain Containing 3 (FHOD3) was detected in all of the affected family members and was absent in all unaffected members, with the exception of one young member. Moreover, three single nucleotide variants associated with heart development and morphogenesis were identified in the proband but were absent in the other affected subjects.

Conclusions

This is the first HCM family case of FHOD3 (p.S527del) variation in Asia. Additionally, RNF207 (p.Q268P), CCM2 (p. E233K) and SGCZ (p.Q134X) may be related to the clinical heterogeneity of the family. The present study could enable the provision of genetic counseling for this family and provide a basis for future genetic and functional studies.
Crosstalk between myeloid-derived suppressor cells and the immune system in prostate cancer
Authors: Sanaei Mohammad-Javad , Salimzadeh Loghman , Bagheri Nader
Published: November 2019

Prostate cancer is the second most common cancer and the fifth leading cause of cancer-associated death in men. Previous studies have revealed a surprising ability for an immature population of myeloid cells called myeloid-derived suppressor cells (MDSCs) in the commencement and development of many tumors, including those of prostate cancer. Herein, the molecular and cellular changes of MDSCs in prostate cancer in both human and nonhuman models are reviewed. The suppressive function of MDSCs are also discussed with a particular focus on the role of IL-6 and JAK/STAT3 signaling pathways in the induction of their suppressive activity. Ultimately, a brief review of MDSC-targeting approaches for potential cancer therapy is presented.
Sequential CCL2 Expression Profile After Disc Injury in Mice
Authors: Nakawaki Mitsufumi , Uchida Kentaro , Miyagi Masayuki , Inoue Gen , Kawakubo Ayumu , Kuroda Akiyoshi , Satoh Masashi , Takaso Masashi
Published: November 2019

Macrophages produce proinflammatory cytokines in injured intervertebral discs (IVDs). We recently showed that macrophage‐derived inflammatory cytokines contribute to the production of pain‐related factors. However, the mechanism by which macrophages are recruited to injured IVDs has not been fully clarified. Here, we examined the expression dynamics of the chemokine CCL2 in a mouse IVD injury model and the mechanisms of its regulation. The percentage of macrophages increased from day 1 after injury and persisted up until day 28. At 1 and 3 days after injury, the expression of both Ccl2 messenger RNA (mRNA) and CCL2 protein was elevated in the IVD injury group, after which expression decreased to basal levels. Consistent with the increase in CCL2 expression, Ccr2 and Tnfa expression and various types of macrophages were also immediately elevated following disc injury. Further, tumor necrosis factor‐α (TNF‐α) stimulated Ccl2 mRNA and CCL2 protein expression in IVD cells in vitro. The expressions of M1 (Cd86 and Nos2) and M2a (Ym1) macrophage markers were all significantly elevated from  day 1 following injury in injured compared with control mice. Meanwhile, the expression of Cd206 (M2a and M2c marker) was significantly elevated on days 3, 7, 14, and 28 following injury. These results suggest that in IVD injury, TNF‐α stimulates CCL2, which, in turn, mediates the recruitment of macrophages with the recruited macrophages subsequently differentiating into M1 and M2 subtypes. CCL2 signaling may, therefore, play an important role in IVD pathology via macrophage recruitment. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:895‐901, 2020
Cellular Plasticity in Musculoskeletal Development, Regeneration, and Disease
Authors: Kaji Deepak A. , Tan Zhijia , Johnson Gemma L. , Huang Wesley , Vasquez Kaetlin , Lehoczky Jessica A. , Levi Benjamin , Cheah Kathryn S. E. , Huang Alice H.
Published: November 2019

In this review, we highlight themes from a recent workshop focused on “Plasticity of Cell Fate in Musculoskeletal Tissues” held at the Orthopaedic Research Society's 2019 annual meeting. Experts in the field provided examples of mesenchymal cell plasticity during normal musculoskeletal development, regeneration, and disease. A thorough understanding of the biology underpinning mesenchymal cell plasticity may offer a roadmap for promoting regeneration while attenuating pathologic differentiation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:708‐718, 2020
Shedding light into the health‐beneficial properties of Corema album—A vibrational spectroscopy study
Authors: Martin D. , Marques J. , Amado A.M. , Barroca M.J. , Moreira da Silva A. , Batista de Carvalho L.A.E. , Marques M.P.M.
Published: November 2019

Corema album (L.) D. Don is a wild maritime shrub endemic to the Iberian Peninsula, which contains bioactive compounds with promising chemoprotective activity. The present work reports the first study of the edible fruits of this potentially health‐beneficial plant by complementary Raman and infrared techniques. Unique vibrational signatures were obtained for each part of the Corema album berries, revealing distinct chemical compositions for the skin (outer and inner) and the seeds, particularly regarding the content in phenolic derivatives, unsaturated fatty acids, and waxy polymers.
Photodynamic therapy may provide a benefit over systemic chemotherapy among non‐surgically managed patients with extrahepatic cholangiocarcinoma
Authors: Wu Lu , Merath Katiuscha , Farooq Ayesha , Hyer J. Madison , Tsilimigras Diamantis I , Paredes Anghela Z. , Mehta Rittal , Sahara Kota , Shen Feng , Pawlik Timothy M.
Published: November 2019

Background

Systemic chemotherapy is the standard treatment for patients with unresectable extrahepatic cholangiocarcinoma (ECC), however, the survival benefit of chemotherapy is limited. Photodynamic therapy (PDT) has been associated with improved survival among patients with advanced ECC, yet utilization of PDT remains low. We sought to compare the outcomes of patients with unresectable ECC following treatment with PDT versus chemotherapy.

Methods

A review of the National Cancer Database was conducted to identify patients with ECC who were nonsurgically managed between 2004 and 2013. Overall survival (OS) of patients receiving PDT vs systemic chemotherapy was compared using propensity score matching.

Results

After propensity matching (PDT, n = 59; chemotherapy, n = 177), 5‐year OS was 17.6% (95% confidence interval [CI], 9.0%‐28.6%) among patients who underwent PDT vs 3.8% (95%CI, 0.4%‐14.0%) among patients receiving chemotherapy (P < .001). On multivariable analysis PDT was associated with an OS benefit (hazard ratio, 0.72; 95%CI, 0.52‐0.998; P = .048). Subset analysis of patients receiving PDT only (n = 45) and patients receiving chemotherapy demonstrated similar results. In subset analysis of patients undergoing PDT‐only vs PDT‐chemotherapy, OS was comparable.

Conclusion

PDT was associated with a survival benefit compared with chemotherapy alone among patients with unresectable ECC.
The prognostic value of anterior commissure involvement in T1 glottic cancer: A systematic review and meta‐analysis
Authors: Tulli Michele , Re Massimo , Bondi Stefano , Ferrante Luigi , Dajko Marianxhela , Giordano Leone , Gioacchini Federico M. , Galli Andrea , Bussi Mario
Published: November 2019

Objective

The anterior commissure is considered a laryngeal subsite, but it is not taken into account in the current T‐staging system. The impact of anterior commissure involvement (ACI) on the oncologic outcomes of T1 glottic tumors has not been well defined and remains controversial. The aim of this study was to assess the influence of ACI in the prognosis of T1 glottic tumors.

Methods

A systematic review and meta‐analysis of observational studies was performed by including studies published up to July 2019. Studies were selected if they had investigated the local control rate (LCR) at 5 years of clinical stage I (T1 and N0) glottic squamous cell carcinoma with and without ACI. The difference in LCR at 5 years between T1 glottic tumors without and with ACI was evaluated.

Results

The meta‐analysis showed that the difference in LCR at 5 years between T1 glottic tumors without and with ACI is 12% (95% confidence interval: 8%‐16%, p < 0,0001, I2 = 34.81%).

Conclusions

Our study pointed out that the anterior commissure involvement is a negative prognostic factor in LCR at 5 years for T1 glottic tumors. Our results suggest the need to consider ACI in the T staging of glottic tumors. Laryngoscope, 130:1932–1940, 2020