bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in morphological traits affects dispersal and seedling emergence in dispersive diaspores of Geropogon hybridus
Authors: Chen Si‐Chong , Giladi Itamar
Published: February 2020

Premise

Intraspecific variation in diaspore characteristics could affect various aspects of plant performance at the population, individual plant, and seed levels. We quantified variation in dispersal traits in a wind‐dispersed annual, Geropogon hybridus (Asteraceae), focusing on continuous morphological traits of dispersive diaspores and their relationships to dispersal ability and seedling emergence.

Methods

We measured the morphological traits, terminal velocity, and seedling emergence of 1140 seeds from 10 populations in two successive years. We assessed the variation in traits among three hierarchical levels of organization and between years, and quantified their effects on diaspore terminal velocity and seedling emergence.

Results

Diaspore morphological traits varied substantially at the population, plant, and diaspore levels. Variables of pappus geometry, especially pappus width and pappus opening angle, were consistent between years and were found to be the best predictors of diaspore terminal velocity and seedling emergence. There was a significant negative relationship between diaspore terminal velocity and seedling emergence.

Conclusions

The intraspecific variation in diaspore traits is sufficiently large to substantially allow a dispersal–dormancy trade‐off of individual diaspores. Our results support the hypothesis that traits of dispersive diaspores evolve in concert to select for increased dispersal potential, and provide an avenue to predict plant offspring performance through simply measured traits.
A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma
Authors: Goldman‐Mazur Sarah , Jurczyszyn Artur , Castillo Jorge J. , Waszczuk‐Gajda Anna , Grząśko Norbert , Radocha Jakub , Bittrich Max , Kortüm K. Martin , Gozzetti Alessandro , Usnarska‐Zubkiewicz Lidia , Davila Valls Julio , Jayabalan David S. , Niesvizky Ruben , Kelman Julia , Coriu Daniel , Rosiñol Laura , Szukalski Łukasz , González‐Calle Veronica , Mateos Maria V. , Jamroziak Krzysztof , Hus Iwona , Avivi Irit , Cohen Yael , Suska Anna , Chappell Aimee , Madduri Deepu , Chhabra Saurabh , Kleman Ariel , Hari Parameswaran , Delforge Michel , Robak Paweł , Gentile Massimo , Kozłowska Izabela , Goldberg Stuart L. , Czepiel Jacek , Silbermann Rebecca , Olszewski Adam J. , Barth Peter , Mikala Gabor , Chim Chor S. , Długosz‐Danecka Monika , Grosicki Sebastian , Vesole David H.
Published: February 2020

The t(14;16) translocation, found in 3%‐5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real‐world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7‐18.7), the median progression‐free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5‐2.4) and 4.1 years (95% CI 3.3‐5.5), respectively. Worse OS was predicted by age > 60 years (HR = 1.65, 95% CI [1.05‐2.58]), as well as revised International Scoring System (R‐ISS) 3 (vs R‐ISS 2; HR = 2.59, 95% CI [1.59‐4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R‐ISS 3 predict poor survival.
A female with X‐linked Nephrogenic diabetes insipidus in a family with inherited central diabetes Insipidus: Case report and review of the literature
Authors: Ding Can , Beetz Rolf , Rittner Gabriele , Bartsch Oliver
Published: February 2020

There are two forms of diabetes insipidus, central (neurohypophyseal), and nephrogenic, caused by pathogenic variants in the AVP gene and the AVPR2 or AQP2 genes, respectively. We report on a four‐generation family, seven individuals had central diabetes insipidus (CDI) and the female index patient seen from age 16 to 26 years had (mild) nephrogenic diabetes insipidus. In her father with CDI, a known pathogenic heterozygous AVP variant c.232_234del p.(Glu78del) was identified, confirming the diagnosis of CDI in him and the other affected family members. In the proband, molecular analysis disclosed a novel heterozygous AVPR2 gene variant, c.962A > T p.(Asn321Ile) and an extremely skewed X‐inactivation, confirming X‐linked nephrogenic diabetes insipidus (XL‐NDI). Whole exome sequencing showed no further causative mutation. This is the first report on the co‐existence of CDI and NDI in one family. Our review of symptomatic female AVPR2 heterozygotes includes 23 families with at least one affected female (including this study). There were 21 different causative mutations. Mutation types in females did not differ from those in males. Both severe XL‐NDI and mild forms were reported in females. All six females with severe XL‐NDI had complete loss‐of‐function (null) mutations. The remaining 17 female probands had milder XL‐NDI caused by 14 missense variants and three null variants of the AVPR2 gene. X‐inactivation was studied in nine of these females; all showed extreme or slight skewing. The review underlines that XL‐NDI in female AVPR2 heterozygotes is always accompanied by skewed X‐inactivation, emphasizing a need for X‐inactivation studies in these females.
On the Binding of Congo Red to Amyloid Fibrils
Authors: Espargaró Alba , Llabrés Salomé , Saupe Sven J. , Curutchet Carles , Luque F. Javier , Sabaté Raimon
Published: February 2020

Amyloids are characterized by their capacity to bind Congo red (CR), one of the most used amyloid‐specific dyes. The structural features of CR binding were unknown for years, mainly because of the lack of amyloid structures solved at high resolution. In the last few years, solid‐state NMR spectroscopy enabled the determination of the structural features of amyloids, such as the HET‐s prion forming domain (HET‐s PFD), which also has recently been used to determine the amyloid–CR interface at atomic resolution. Herein, we combine spectroscopic data with molecular docking, molecular dynamics, and excitonic quantum/molecular mechanics calculations to examine and rationalize CR binding to amyloids. In contrast to a previous assumption on the binding mode, our results suggest that CR binding to the HET‐s PFD involves a cooperative process entailing the formation of a complex with 1:1 stoichiometry. This provides a molecular basis to explain the bathochromic shift in the maximal absorbance wavelength when CR is bound to amyloids.
Improvement of Intracellular Traffic System by Overexpression of KDEL Receptor 1 in Antibody‐Producing CHO Cells
Authors: Samy Andrew , Kaneyoshi Kohei , Omasa Takeshi
Published: February 2020

The localization of soluble endoplasmic reticulum (ER) chaperones in the cell organelle is mediated by the C‐terminal KDEL (lysine, aspartic acid, glutamic acid and leucine) motif. This motif is recognized by the KDEL receptor, a seven‐transmembrane protein that cycles between the ER and cis‐Golgi to capture missorted KDEL chaperones from post‐ER compartments in a pH‐dependent manner. The KDEL receptor's target chaperones have a substantial role in protein folding and assembly. In this study, the gene expression level of KDEL receptor 1 shows a moderate upregulation during either ER stress or growth of Chinese hamster ovary (CHO) cells in batch culture, while the ER chaperones show higher upregulation. This might indicate the possibility of saturation of the ER retention machinery or at least hindered retention during late stage batch culture in recombinant CHO cells. KDELR1 is overexpressed in a monoclonal antibody‐producing CHO cell line to improve the intracellular chaperone retention rate in the ER. An increase in the specific productivity of IgG1 by 13.2% during the exponential phase, and 23.8% in the deceleration phase of batch culture is observed. This is the first study to focus on the ER retention system as a cell engineering target for enhancing recombinant protein production.
Microstructural densification and alignment by aspiration‐ejection influence cancer cell interactions with three‐dimensional collagen networks
Authors: Huynh Ruby N. , Yousof Manal , Ly Khanh L. , Gombedza Farai C. , Luo Xiaolong , Bandyopadhyay Bidhan C. , Raub Christopher B.
Published: February 2020

Extracellular matrix microstructure and mechanics are crucial to breast cancer progression and invasion into surrounding tissues. The peritumor collagen network is often dense and aligned, features which in vitro models lack. Aspiration of collagen hydrogels led to densification and alignment of microstructure surrounding embedded cancer cells. Two metastasis‐derived breast cancer cell lines, MDA‐MB‐231 and MCF‐7, were cultured in initially 4 mg/ml collagen gels for 3 days after aspiration, as well as in unaspirated control hydrogels. Videomicroscopy during aspiration, and at 0, 1, and 3 days after aspiration, epifluorescence microscopy of phalloidin‐stained F‐actin cytoskeleton, histological sections, and soluble metabolic byproducts from constructs were collected to characterize effects on the embedded cell morphology, the collagen network microstructure, and proliferation. Breast cancer cells remained viable after aspiration‐ejection, proliferating slightly less than in unaspirated gels. Furthermore, MDA‐MB‐231 cells appear to partially relax the collagen network and lose alignment 3 days after aspiration. Aspiration‐ejection generated aligned, compact collagen network microstructure with immediate cell co‐orientation and higher cell number density apparently through purely physical means, though cell‐collagen contact guidance and network remodeling influence cell organization and collagen network microstructure during subsequent culture. This study establishes a platform to determine the effects of collagen density and alignment on cancer cell behavior, with translational potential for anticancer drug screening in a biomimetic three‐dimensional matrix microenvironment, or implantation in preclinical models.
Get real: Orbitofrontal cortex mediates the ability to sense reality in early adolescents
Authors: Liverani Maria Chiara , Freitas Lorena G. A. , Siffredi Vanessa , Mikneviciute Greta , Martuzzi Roberto , Meskaldij Djalel‐Eddine , Borradori Tolsa Cristina , Ha‐Vinh Leuchter Russia , Schnider Armin , Van De Ville Dimitri , Hüppi Petra Susan
Published: February 2020

Introduction

Orbitofrontal reality filtering (ORFi) is a memory mechanism that distinguishes whether a thought is relevant to present reality or not. In adults, it is mediated by the orbitofrontal cortex (OFC). This region is still not fully developed in preteenagers, but ORFi is already active from age 7. Here, we probe the neural correlates of ORFi in early adolescents, hypothesizing that OFC mediates the sense of reality in this population.

Methods

Functional magnetic resonance images (fMRI) were acquired in 22 early adolescents during a task composed of two runs: run 1 measuring recognition capacity; run 2 measuring ORFi; each containing two types of images (conditions): distractors (D: images seen for the first time in the current run) and targets (T: images seen for the second time in the current run). Group region of interest (ROI) analysis was performed in a flexible factorial design with two factors (run and condition) using SPM12.

Results

We found significant main effects for the experimental run and condition. The bilateral OFC activation was higher during ORFi than during the first run. Additionally, the OFC was more active while processing distractors than targets.

Conclusion

These results confirm, for the first time, the role of OFC in reality filtering in early adolescents.
Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: A multicenter retrospective study
Authors: Wang Lei , Deng Manjun , Ke Qiao , Lou Jianying , Zheng Shuguo , Bi Xinyu , Wang Jianming , Guo Wei , Li Fuyu , Wang Jian , Zheng Yamin , Li Jingdong , Cheng Shi , Zhou Weiping , Zeng Yongyi
Published: February 2020

Background and Aims

The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory; however, the clinical value of adjuvant therapy (AT) remains controversial. This multicenter study aimed to evaluate the clinical value of AT and identify potential patients who would be benefited from AT.

Methods

Data from ICC patients who underwent radical resection were retrospectively collected from 12 hepatobiliary centers in China between December 2012 and December 2015. Patients were divided into AT and non‐AT groups based on whether AT was administered or not. Overall survival (OS) and disease‐free survival (DFS) were analyzed using the Kaplan‐Meier method before and after 1:2 propensity score matching (PSM). Subgroup analyses were conducted based on the established staging systems.

Results

A total of 412 patients were enrolled in this study, and 77 patients (18.9%) received AT, including 32 (7.8%) patients who received transarterial chemoembolization (TACE), 21 (5.1%) patients who received chemotherapy, 10 (2.4%) patients who received radiotherapy, and 14 (3.4%) patients who received adjuvant chemoradiotherapy. The median OS and DFS were both longer in the AT group than in the non‐AT group (43.0 months vs 21.0 months, P = .015; 16.0 months vs 11.0 months, P = .045, respectively), and the advantage of AT was confirmed for both the OS and DFS (P = .023; P = .046, respectively) after 1:2 PSM. Furthermore, based on the established nomogram, only “middle‐risk” patients receiving AT cherished a longer median OS (43.0 months vs 20.0 months, P = .033). In subgroup analyses that were stratified by different AT strategies, patients receiving postoperative chemotherapy had a longer median OS (37.0 months vs 21.0 months, P = .039), while patients receiving postoperative TACE had a longer median DFS (50.0 months vs 11.0 months, P = .007).

Conclusion

With the current data, we conclude that AT benefits ICC patients following radical resection, especially those “middle‐risk” patients, as evaluated by the established nomogram. However, exactly which patients are the most suitable for AT requires further study and validation.
Utility of the long DrySeal sheath in facilitating transcatheter pulmonary valve implantation with the Edwards Sapien 3 valve
Authors: Fukuda Terunobu , Tan Weiyi , Sadeghi Soraya , Lin Jeannette , Salem Morris , Levi Daniel , Aboulhosn Jamil
Published: February 2020

Objective

To assess the utility of the 65‐cm‐long Gore DrySeal sheath when compared to the standard 36‐cm‐long Edwards expandable sheath (e‐sheath) for transcatheter pulmonary valve implantation (TPVI) with the Edwards Sapien 3 valve.

Methods

All patients who underwent TPVI with the Sapien 3 valve, excluding those performed via hybrid approach, at our center between September 2015 and November 2019 were retrospectively reviewed and compared between two groups.

Results

A total of 94 patients were enrolled; 29 patients underwent TPVI with the Sapien valve using the DrySeal sheath and 65 underwent TPVI using the e‐sheath. The height and body weight of patients implanted using the DrySeal sheath ranged from 137 to 193 cm and from 33 to 129 kg, respectively. Valve delivery time was significantly shorter in the DrySeal group (median time 4 min 33 s vs. 9 min 6 s, p = .002). There were no complications in the DrySeal group (0/27). Nine procedural complications occurred in the e‐sheath group (9/65), five of which were potentially directly related to sheath choice, including tricuspid valve injury in four and embolization of the tip of the e‐sheath during retrieval of a ruptured balloon in one patient.

Conclusions

TPVI with the Sapien 3 valve using the 65‐cm‐long DrySeal sheath facilitates faster and safer valve implantation when compared to the e‐sheath.
Percutaneous pulmonary valve implantation in a dysfunctional Trifecta® bioprothesis after high‐pressure balloon fracturing
Authors: Langhammer Florian , Lehner Anja , Haas Nikolaus A. , Jakob André
Published: February 2020

A percutaneous pulmonary valve‐in‐valve (PPVIV) implantation in small surgical tissue valves may be limited due to the valve's initial diameter. Fracturing of the valve's integrity by high‐pressure balloons may enhance the diameter and facilitate subsequent PPVIV with a large valve. To the best of our knowledge, the Trifecta® valve seemed not to be accessible for fracturing. We report a case of successful 19‐mm Trifecta valve fracturing, followed by PPVIV using a 26‐mm Edwards SAPIEN 3 valve in pulmonary position. By repetitively using a high‐pressure balloon 5 mm larger than the labeled valve size, we were able to fracture the valve's integrity and implant a 26‐mm valve thereafter. Therefore, Trifecta valve appears to be suitable for valve ring fracturing and subsequent PPVIV in certain patients.
One‐Pot Substitution of Aliphatic Alcohols Mediated by Sulfuryl Fluoride
Authors: Mo Jia Yi , Epifanov Maxim , Hodgson Jack W. , Dubois Rudy , Sammis Glenn M.
Published: February 2020

The Mitsunobu reaction is a powerful transformation for the one‐pot activation and substitution of aliphatic alcohols. Significant efforts have focused on modifying the classic conditions to overcome problems associated with purification from phosphine‐based byproducts. Herein, we report a phosphine free method for alcohol activation and substitution that is mediated by sulfuryl fluoride. This new method is effective for a wide range of primary alcohols using phthalimide, di‐tert‐butyl‐iminodicarboxylate, and aromatic thiol nucleophiles in 74 % average yield. Activated carbon nucleophiles and a deactivated phenol were also effective for this reaction in good yields. Secondary alcohols were also successful substrates using aryl thiols, affording the corresponding sulfides in 56 % average yield with enantiomeric ratios up to 99:1. This new protocol has a distinct synthetic advantage over many existing phosphine‐based methods as the byproducts are readily separable. This feature was exploited in several examples that did not require chromatography for purification. Furthermore, the mild reaction conditions enabled further in situ derivatization for the one‐pot conversion of alcohols to amines or sulfones. This method also provides a boarder nucleophile scope compared to existing phosphine‐free methods.
Le comportement d'achat organisationnel des emballages des produits périssables dans le secteur du commerce de détail
Authors: Afif Karima , Rebolledo Claudia , Roy Jacques
Published: February 2020

This qualitative study investigates the structure of the buying center, the buying process and the factors that influence the buying decision of perishable products packaging. This empirical investigation is based on the case study of a major Quebec food retailer. We show that the purchase of packaging changes significantly depending on whether the product is considered more or less strategic for the organization, which determines the required level of packaging customization. Buying center structure becomes more complex as packaging customization increases. Given the multifunctionality and the interdisciplinarity of packaging, we propose a multi‐criteria analysis grid to improve buying decision efficiency and streamline communication between the various levels of the buying center.
Studying Nicotinic Acetylcholine Receptors Using the IonFlux™ Microfluidic‐Based Automated Patch‐Clamp System with Continuous Perfusion and Fast Solution Exchange
Authors: Yehia Ali , Wei Haiyang
Published: February 2020

Automated patch‐clamp (APC) systems have become indispensable tools of drug‐discovery programs by allowing high‐throughput electrophysiology‐based screening of ion channel compounds. The recent development and introduction of microfluidics‐based APC systems have made it possible to study the interactions of ligand‐gated ion channels with pharmacological reagents, such as agonists, antagonists, or positive allosteric modulators (PAMs), with reliable pharmacological results comparable to those of the gold‐standard manual patch‐clamp technique while maintaining high‐throughput capacity. Many ligand‐gated ion channels exhibit rapid desensitization upon repetitive introduction of ligands; this loss of channel activity in the absence of pharmacological interaction poses a challenge for developing accurate, precise, and robust assays with high success rate, low run‐down, and reliable pharmacological results. Here we present procedures to study nicotinic acetylcholine receptors (nAChRs) with the IonFlux™, an automated patch‐clamp system with continuous flow and precise fluidic exchange; these procedures can also be generalized to the study of other ligand‐gated ion channels. We present protocols to study agonist, antagonist, and PAM activities on nAChRs, particularly the rapidly desensitizing nAChR α7 receptors. The data demonstrate that the IonFlux™ system is a fast, robust, and reliable platform for the study of nAChRs and other ligand‐gated ion channels, generating data that closely mimic those from manual patch‐clamp conditions. © 2020 by John Wiley & Sons, Inc.

Basic Protocol 1: Measuring agonist concentration‐dependent response

Basic Protocol 2: Measuring antagonist concentration‐dependent response

Basic Protocol 3: Measuring positive allosteric modulator (PAM) concentration‐dependent response

Support Protocol 1: Basic IonFlux system operation

Support Protocol 2: Plate care and filling

Support Protocol 3: Plate preparation for water rinsing

Support Protocol 4: Water rinsing of plates

Support Protocol 5: Plate priming

Support Protocol 6: General assay

Support Protocol 7: Editing the compound addition sequence (compound list)

Support Protocol 8: Creating compound list for agonist concentration‐dependent response

Support Protocol 9: Creating compound list for antagonist or PAM concentration‐dependent response

Support Protocol 10: Defining the different compounds used or compound list

Support Protocol 11: Maintenance

Support Protocol 12: Data analysis

Support Protocol 13: Cell culture
Natural killer cell activation by respiratory syncytial virus‐specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc‐glycosylation
Authors: van Erp Elisabeth A , Lakerveld Anke J , de Graaf Erik , Larsen Mads D , Schepp Rutger M , Hipgrave Ederveen Agnes L , Ahout Inge ML , de Haan Cornelis AM , Wuhrer Manfred , Luytjes Willem , Ferwerda Gerben , Vidarsson Gestur , van Kasteren Puck B
Published: February 2020

Objectives

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, and there is no vaccine available. In early life, the most important contributors to protection against infectious diseases are the innate immune response and maternal antibodies. However, antibody‐mediated protection against RSV disease is incompletely understood, as both antibody levels and neutralisation capacity correlate poorly with protection. Since antibodies also mediate natural killer (NK) cell activation, we investigated whether this functionality correlates with RSV disease.

Methods

We performed an observational case–control study including infants hospitalised for RSV infection, hernia surgery or RSV‐negative respiratory viral infections. We determined RSV antigen‐specific antibody levels in plasma using a multiplex immunoassay. Subsequently, we measured the capacity of these antibodies to activate NK cells. Finally, we assessed Fc‐glycosylation of the RSV‐specific antibodies by mass spectrometry.

Results

We found that RSV‐specific maternal antibodies activate NK cells in vitro. While concentrations of RSV‐specific antibodies did not differ between cases and controls, antibodies from infants hospitalised for severe respiratory infections (RSV and/or other) induced significantly less NK cell interferon‐γ production than those from uninfected controls. Furthermore, NK cell activation correlated with Fc‐fucosylation of RSV‐specific antibodies, but their glycosylation status did not significantly differ between cases and controls.

Conclusion

Our results suggest that Fc‐dependent antibody function and quality, exemplified by NK cell activation and glycosylation, contribute to protection against severe RSV disease and warrant further studies to evaluate the potential of using these properties to evaluate and improve the efficacy of novel vaccines.
Appropriate buffer sizes for Internet nodal devices: A networks' topologies–based solution
Authors: Eyinagho Monday Ofori , Falaki Samuel Oluwole
Published: February 2020

Switched networks' (including the Internet) nodal devices require buffers to hold packets during periods of congestion and when traffic streams on more than one input port need to access the same output port. Appropriately sizing the buffers has been a contentious issue among researchers over the last couple of years. Three main buffer sizing formulas have been reported in literature, which are: bandwidth‐delay product or BDP, small buffer, and the tiny buffer formulas. But researchers are largely agreed that the BDP formula results in unrealistically large and wasteful buffers, while a number of researchers have held with good reasons, that the small and tiny buffer formulas are theoretical formulations that cannot be generally and practically applied to real networks. Some researchers have even asserted that deriving a single, universal formula for sizing buffers may not be possible. The main purpose of this paper is to explain an approach, which we term “network topology point –of –view,” that we developed to derive a novel, empirical, generic, practical, easy‐to‐apply, closed‐form formula that can be used to obtain the buffer capacity that is optimal—in terms of the minimum capacity possible for lossless operation, for any switched network node, including nodes (switches and routers) in the Internet. The results obtained from utilizing the formula to specify typical nodal buffers' capacities are largely in agreement with the values of the tiny buffer formula in literature; but this paper's formula additionally specifies what we term “very tiny buffers.” The simple approach adopted for presenting this paper makes it a handy tutorial material that explains this “network topology point‐of‐view” concept.
Microglia in the developing retina couple phagocytosis with the progression of apoptosis via P2RY12 signaling
Authors: Blume Zachary I. , Lambert Jared M. , Lovel Anna G. , Mitchell Diana M.
Published: February 2020

Background

Microglia colonize the developing vertebrate central nervous system coincident with the detection of developmental apoptosis. Our understanding of apoptosis in intact tissue in relation to microglial clearance of dying cells is largely based on fixed samples, which is limiting given that microglia are highly motile and mobile phagocytes. Here, we used a system of microglial depletion and in vivo real‐time imaging in zebrafish to directly address microglial phagocytosis of apoptotic cells during normal retinal development, the relative timing of phagocytosis in relation to apoptotic progression, and the contribution of P2RY12 signaling to this process.

Results

The depletion of microglia resulted in accumulation of numerous apoptotic cells in the retina. Real‐time imaging revealed precise timing of microglial engulfment with the progression of apoptosis, and dynamic movement and displacement of engulfed apoptotic cells. Inhibition of P2RY12 signaling delayed microglial clearance of apoptotic cells.

Conclusions

Microglial engulfment of dying cells is coincident with apoptotic progression and requires P2RY12 signaling, indicating that microglial P2RY12 signaling is shared between development and injury response. Our work provides important in vivo insight into the dynamics of apoptotic cell clearance in the developing vertebrate retina and provides a basis to understand microglial phagocytic behavior in health and disease.
MMA Polymerization with Group 4 Alkyl‐Free 14‐Electron d0 Species
Authors: Londaitsbehere Addis M. , Sudupe María , Mosquera Marta E. G. , Cuenca Tomás , Cano Jesús
Published: February 2020

Cationic 1,2 and 1,3 doubly constrained geometry di(silylamido)cyclopentadienyl zirconium complexes, whilst being group 4 alkyl‐free 14‐electron d0 species, promote the polymerization of MMA. Different cocatalysts such as B(C6F5)3, Al(C6F5)3 and [CPh3][B(C6F5)4] have been employed to generate the catalytic species in order to collect experimental evidence to propose the polymerization mechanism that these cationic compounds may follow. By systematically studying the role of the active species, this study establishes that the mechanism may be different from the traditional coordination‐addition mechanism proposed for group 4 metal complexes in MMA polymerizations.
The Hidden Dimension: Context-Dependent Expression of Repeatable Behavior in Copepods
Authors: Heuschele Jan , Lode Torben , Andersen Tom , Titelman Josefin
Published: February 2020

In ecotoxicology and aquatic ecology, we often ignore responses of individuals and focus on average responses. However, both terrestrial and aquatic animals display consistent behavioral differences between individuals. The distribution of behavioral differences within a population contains vital information for predicting population responses to novel environmental challenges. Currently, individual data for behavioral and physiological traits of small marine invertebrates are few, partly because such variation is lost within published group means and assumed normality. We tested the combined effects of an inorganic contaminant (copper) and a biological stressor (i.e., chemical cues of a fish predator) on activity in a marine copepod. Although direct stress effects were weak, individuals behaved consistently differently, depending on the context. Individual differences in behavior were only expressed under the influence of kairomones, but not by copper exposure alone. This finding indicates that copepods express repeatable and context-dependent behavior. We also demonstrate how large variations in behavioral data can hide consistent differences between individuals. Environ Toxicol Chem 2020;39:1017–1026. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
The Effects of 17α-Ethinylestradiol on the Heart Rate of Embryonic Japanese Medaka (Oryzias latipes)
Authors: Anderson Jordan Christopher , Beyger Lindsay , Guchardi John , Holdway Douglas Alan
Published: February 2020

Estrogen toxicity has been an area of priority in aquatic toxicology over the last 20 yr. Currently, estrogen toxicity is primarily linked to classical estrogen signaling, the interaction of estrogen receptors alpha and beta (ERα and ERβ). Recent evidence has indicated that a rapid, nongenomic, nonclassical estrogen signaling pathway exists via the G protein–coupled estrogen receptor (GPER), which is expressed in many biological systems, with roles in the cardiovascular system. The objective of the present study was to investigate the effect of 17α-ethinylestradiol (EE2) on the heart rate of embryonic Japanese medaka (Oryzias latipes). A significant decrease (bradycardia) in embryonic heart rate was observed at all treatment concentrations (0.1, 1, 10, 100, and 1000 ng/L EE2) at 144, 168, and 192 h postfertilization (hpf; p ≤ 0.05), whereas 120 and 216 hpf embryos experienced a significant decrease from the control at 10, 100, and 1000 ng/L EE2 and 0.1, 100, and 1000 ng/L EE2, respectively (p ≤ 0.05). In addition, using select estrogen receptor modulators, it was demonstrated that estrogen-induced bradycardia appears to be linked to GPER and not ERα and ERβ. The present study highlights GPER as a novel and alternative mode of action for EE2 toxicity at environmentally relevant concentrations. Environ Toxicol Chem 2020;39:904–912. © 2020 SETAC
Survival of malignant mesothelioma and other rare thoracic cancers in Germany and the United States: A population‐based study
Authors: Sirri Eunice , Kieschke Joachim , Vohmann Claudia , Katalinic Alexander , Nennecke Alice , Ressing Meike , Eberle Andrea , Holleczek Bernd , Jansen Lina , Brenner Hermann ,   for the GEKID Cancer Survival Working Group
Published: February 2020

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000–2014. Patients diagnosed in 1997–2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5‐year relative survival (RS). During 2000–2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person‐years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5‐year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002–2007] vs. 13.0% [2008–2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020–2030 in Western countries.
SWI/SNF chromatin remodeling complex and glucose metabolism are deregulated in advanced bladder cancer
Authors: Stachowiak Malgorzata , Szymanski Michal , Ornoch Anna , Jancewicz Iga , Rusetska Natalia , Chrzan Alicja , Demkow Tomasz , Siedlecki Janusz A. , Sarnowski Tomasz J. , Sarnowska Elzbieta
Published: February 2020

Bladder cancer (BC) is a frequently diagnosed malignancy affecting predominantly adult and elderly populations. It is expected that due to the longer life time, BC will become even more frequent in the future; thus in consequence, it will represent serious health problem of older society part. The treatment of advanced BC is mostly ineffective due to its very aggressive behavior. So far, no effective targeted therapy is used for BC treatment. Here, we found that BC is characterized by lower protein levels of BRM, INI1, and BAF155 main subunits of SWI/SNF chromatin remodeling complex (CRC) which is involved in global control of gene expression and influences various important cellular processes like: cell cycle control, apoptosis, DNA repair, etc. Moreover, the expression of SMARCA2, a BRM encoding gene, strongly correlated with BC metastasis and expression of such metabolic genes as PKM2 and PRKAA1. Furthermore, the analysis of T24 and 5637 commonly used BC cell lines revealed different expression levels of metabolic genes including FBP1 gene encoding Frutose‐1,6‐Bisphosphatase, an enzyme controlling glycolysis flux and gluconeogenesis. The tested BC cell lines exhibited various molecular and metabolic alterations as well as differential glucose uptake, growth rate, and migration potential. We have shown that BRM subunit is involved in the transcriptional control of genes encoding metabolic enzymes. Moreover, we found that the FBP1 expression level and the SWI/SNF CRCs may serve as markers of molecular subtypes of BC. Collectively, this study may provide a new knowledge about the molecular and metabolic BC subtypes which likely will be of high importance for the clinic in the future.
Impact of a mental health trainee interdisciplinary program on a veteran population
Authors: Karst Allison , Colvard Michelle , Bean Jennifer , Patel Erin , Pate Rebecca , Lister Jonathan
Published: February 2020

Background

Less than half of adults with mental illness receive mental health services. Several barriers exist to accessing care including stigma and shortage of mental health clinicians. Due to the increasing demand for mental health services, the American health care system has begun moving toward an interprofessional approach.

Objective

The primary objective was to evaluate the impact of a trainee‐led interprofessional mental health team on treatment outcomes.

Methods

This single‐center, retrospective, observational analysis was conducted at a Veterans Affairs medical center from August 2013 through April 2019. Eligible patients were identified using the clinic roster and manual review was utilized to exclude patients based on defined criteria. Patient demographics, referral source, initial appointment date, enrollment status, psychiatric diagnoses, and mental health assessment measures were collected. The primary outcome was change in Patient Health Questionnaire (PHQ‐9), General Anxiety Disorder‐7 (GAD‐7), and Post‐Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (PCL‐5) total score from clinic intake to discharge.

Results

There was a statistically significant reduction in PHQ‐9 (−6.00; −38.54%; P < .001), GAD‐7 (−4.35; −33.38%; P < .001), and PCL‐5 (−19.33; −34.29%; P < .001) total scores. Additionally, there was a statistically significant change in PTSD remission rate per PCL‐5 (+33.3%; P = .001). There was a numerical reduction in mental health‐related emergency department visits (−3; P = .495), psychiatric hospitalizations (−7; P = .182), and psychiatric hospital days (−53; P = .229).

Conclusions

A trainee‐led interdisciplinary mental health team positively impacted depression, anxiety, and PTSD related outcomes in a Veteran population. Results support further study and incorporation of the interdisciplinary care model into outpatient mental health settings.
The miracle role of lattice imperfections in benzene alkylation with methanol over mordenite
Authors: Yun Hongfei , Meng Jiale , Li Guixian , Dong Peng
Published: February 2020

Mordenite (MOR) has demonstrated potential as a catalyst for alkylation due to high variability, intrinsic porosity, and outstanding stability. However, the contact probability of benzene and methanol has been limited by typical layered structures of MOR and there is no connection between layers. Here, we report the preparedness of H‐MOR via a sequential post‐treatment method based on a commercial MOR. H‐MOR sample had appeared lattice imperfections inferred from characterization means. The samples were tested with benezene methylation reaction. Results show that the high conversion of benzene and the high selectivity of toluene were obtained from the miracle role of lattice imperfections in the H‐MOR sample. Sequentially, based on the study of all catalyst structure and physical properties, a plausible reaction mechanism for the selectivity of the desired toluene was proposed.
Janus kinase inhibitors: A therapeutic strategy for cancer and autoimmune diseases
Authors: Hosseini Arezoo , Gharibi Tohid , Marofi Faroogh , Javadian Mahsa , Babaloo Zohreh , Baradaran Behzad
Published: February 2020

Many cytokines are crucial drivers of cancers and autoimmune conditions. These proteins bind to receptors and signal their responses through Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways. Genetic variations in the JAK–STAT pathway are correlated with the increased risk of cancers, autoimmunity as well as inflammatory diseases. Targeting JAKs and STATs can be a safe and efficacious strategy for treating these diseases. Tofacitinib, as the first JAK inhibitor, is approved for rheumatoid arthritis therapy. Also, many other JAK inhibitors have been proven or are in various phases of clinical trials for various diseases. At present, small‐molecule JAK inhibitors are considered as a novel category of drugs in the treatment of cancer and immune‐mediated diseases.
Ellis‐van Creveld syndrome: Report of a case and recurrent variant
Authors: Eftekhariyazdi Mitra , Meshkani Mahshid , Moslem Alireza , Hakimi Pooria , Safari Shamsi , Khaligh Ali , Zare‐Abdollahi Davood
Published: February 2020

Background

Ellis‐van Creveld syndrome (EvCS) is a rare autosomal recessive skeletal dysplasia that is characterized by short stature, short limbs, short ribs, polydactyly and structural heart defect. Despite locus heterogeneity, in the majority of the cases, the disorder segregates with mutations in the EVC and EVC2 genes, notably mutations with truncating protein as a final sequence. In the present study, we report the prenatal findings and genetic analysis of a terminated pregnancy affected by severe thoracic and skeletal dysplasia.

Methods

After detailed physical and clinical examination, whole exome sequencing (WES) was performed and the variant was confirmed by Sanger sequencing.

Results

One homozygote variant in EVC2 gene was identified in the fetus (NM_147127, c.942G>A, p.W314X). The EVC2 gene is strongly associated with EvCS, which is consistent with the sonographic findings of the fetus.

Conclusions

The homozygous p.W314X mutation found in this family was recently reported to be segregated in a consanguineous family originating from Pakistan. The occurrence of the p.W314X mutation in two unrelated families (Iranian and Pakistani) may be the result of an old founder effect or arose because of a mutational hotspot and is supporting evidence for the pathogenicity of this variant. Because skeletal dysplasia belongs to a broad spectrum of syndromes and therefore exhibits considerable background locus and allelic heterogeneity, our report highlights the need for appropriate genetic counseling and supports the feasibility of WES to determine an accurate diagnosis, as well as precise recurrence risk prediction.
Temperature‐dependent rate constants for the reactions of chlorine atom with methanol and Br2
Authors: Bedjanian Yuri
Published: February 2020

Kinetics of the reaction of Cl atoms with methanol has been investigated at 2 Torr total pressure of helium and over a wide temperature range 225‐950 K, using a discharge flow reactor combined with an electron impact ionization quadrupole mass spectrometer. The rate constant of the reaction Cl + CH3OH → products (1) was determined using both absolute measurements under pseudo‐first order conditions, monitoring the kinetics of Cl‐atom consumption in excess of methanol and relative rate method, k1 = (5.1 ± 0.8) × 10−11 cm3 molecule−1 s−1, and was found to be temperature independent over the range T = 225‐950 K. The rate constant of the reaction Cl + Br2 → BrCl + Br (3) was measured in an absolute way monitoring Cl‐atom decays in excess of Br2: k3 = 1.64 × 10−10 exp(34/T) cm3 molecule−1 s−1 at T = 225‐960 K (with conservative 15% uncertainty). The experimental data for k3 can also be adequately represented by the temperature independent value of k3 = (1.8 ± 0.3) × 10−10 cm3 molecule−1 s−1. The kinetic data from the present study are compared with previous measurements.
Rate constant of the BrO + BrO reaction over the temperature range 220‐950 K
Authors: Bedjanian Yuri
Published: February 2020

The kinetics of the self‐reaction of BrO radicals has been studied over a wide temperature range (T = 220‐950 K) at 2 Torr total pressure of He using a low‐pressure flow reactor combined with a quadrupole mass spectrometer: BrO + BrO → 2Br + O2 (1a) and BrO + BrO → Br2 + O2 (1b). The overall rate constant for this reaction (defined by d[BrO]/dt = –2k1[BrO]2) was found to be k1 = k1a +k1b = (1.32 ± 0.09) × 10−12 exp(182 ± 22/T) cm3 molecule−1 s−1 at T = 220‐950 K (where the uncertainties represent precision at the 2σ level). The channel‐specific rate constant for the Br2 + O2 forming channel (1b) was determined at T = 220‐450 K: k1b = (2.83 ± 0.35) × 10−13 exp(34 ± 36/T) cm3 molecule−1 s−1 (with 2σ uncertainties). As a result of the comparative analysis of the present data and those from the previous studies, the following Arrhenius expressions are recommended from the present work: k1 = 1.4 × 10−12 exp(200/T) at T = 220‐950 K (independent of pressure at least for T ≥ 250 K) and k1b = 3.2 × 10−13 exp(34/T) cm3 molecule−1 s−1 at T = 220‐450 K and total pressure of 2 Torr, with a conservative estimate of uncertainty of 25%, independent of temperature.
Effect of rare earth cerium on the impact toughness, corrosion and wear resistance of CrNiMnMo alloyed lining steel
Authors: Du X. , Lei X. , Wang J. , Zhao Q. , Ge H.
Published: February 2020

The effects of the addition of rare earth cerium on the impact corrosion and wear resistance of CrNiMnMo alloyed lining steel were studied using metallurgical microscopy, scanning electron microscope, x‐ray powder diffraction, a hardness tester, an impact tester, and an impact corrosion abrasion tester. The properties of CrNiMnMo alloyed lining steel with the addition of cerium were compared with that of CrNiMnMo steel without the addition of cerium after being heat treated by same processes. The results show that CrNiMnMo alloyed lining steel with the addition of rare earth cerium consisted of lath martensite with a low residual austenite phase after being quenched and tempered. The lath of the martensite was fine and uniform. The impact toughness and the corrosion resistance of the steel lining board improved greatly with the addition of cerium and the impact toughness increased by 22 % with the fracture mode of being ductile. The CrNiMnMo alloyed lining steel with cerium showed the highest resistance to impact corrosion abrasion compared with the alloy without cerium.
Service users' experiences of receiving a diagnosis of borderline personality disorder: A systematic review
Authors: Lester R. , Prescott L. , McCormack M. , Sampson M. ,   North West Boroughs Healthcare, NHS Foundation Trust
Published: February 2020

There is ongoing controversy regarding the borderline personality disorder (BPD) diagnosis. Whilst the experiences of people living with BPD have been widely acknowledged, the process of receiving the diagnosis is poorly described. This systematic review aimed to synthesize the existing research exploring people's experiences of receiving a diagnosis of BPD, as well as examining what is considered best practice in the diagnostic delivery process. The findings from 12 qualitative studies were synthesized using thematic analysis, generating two overarching themes: negative and positive experiences of receiving a diagnosis of BPD. These themes were described using the following sub‐themes: the communication of diagnosis and meaning made of it, validity around diagnosis and attitudes of others. Results indicate that there is a substantial difference between a well‐delivered and poorly delivered diagnosis. The diagnostic delivery process is fundamental to how people understand and interpret the BPD diagnosis. The way in which the BPD diagnosis is shared with people can ultimately shape their views about hope for recovery and their subsequent engagement with services. © 2020 John Wiley & Sons, Ltd.