bluuebunny/crossref_metadata_2025 huggingface dataset:
Alveolar Ridge Augmentation Around Exposed Mandibular Dental Implant With Histomorphometric Analysis
Authors: Ibraheem Ahmed Gamil , Blanchard Steven B.
Published: January 2020

Introduction

Alveolar ridge augmentation either before or during implant placement is a predictable procedure under certain conditions. A major complication during the healing phase is incision line opening and membrane exposure, which may result in reduced bone gain and reduced implant survival. This case report describes alveolar bone regeneration around three dental implants despite membrane exposure that developed during healing post‐surgically.

Case Presentation

A 72‐year‐old female presented requesting dental implants to replace tooth numbers 18, 19, and 20. A cone‐beam computed tomography (CBCT) scan showed loss of horizontal and vertical ridge dimensions. All implants were placed with a variable degree of implant thread exposure on their buccal surfaces, ranging from 3 to 4.5 mm. Simultaneous bone grafting was performed using freeze dried bone allograft and deproteinized bovine bone mineral that was covered by a d‐PTFE membrane that was secured with tacking screws. Primary closure was obtained, and flaps were sutured. Three weeks post‐surgically, membrane exposure occurred. Exposure was monitored and patient was instructed to follow strict oral hygiene instructions around the exposed membrane. Membrane exposure gradually increased without infection and was removed at 16 weeks. Membrane removal revealed dense fibrous tissues covering all implant surfaces. At the second stage surgery, new bone was seen covering all the implants coronal to the cover screws. A trephine core biopsy specimen revealed significant new bone formation and connective tissue around any residual grafted bone.

Conclusion

d‐PTFE membrane exposure does not necessarily lead to adverse healing outcomes for alveolar ridge augmentation if handled properly with close patient follow‐up.
Role of PKCζ‐NADPH oxidase signaling axis in PKCα‐mediated Giα2 phosphorylation for inhibition of adenylate cyclase activity by angiotensin II in pulmonary artery smooth muscle cells
Authors: Chowdhury Animesh , Sarkar Jaganmay , Kanti Pramanik Pijush , Chakraborti Tapati , Chakraborti Sajal
Published: January 2020

We sought to determine the mechanism by which angiotensin II (AngII) inhibits isoproterenol induced increase in adenylate cyclase (AC) activity and cyclic adenosine monophosphate (cAMP) production in bovine pulmonary artery smooth muscle cells (BPASMCs). Treatment with AngII stimulates protein kinase C‐ζ (PKC‐ζ), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and PKC‐α activities, and also inhibits isoproterenol induced increase in AC activity and cAMP production in the cells. Pertussis toxin pretreatment eliminates AngII caused inhibition of isoproterenol induced increase in AC activity without a discernible change in PKC‐ζ, NADPH oxidase, and PKC‐α activities. Treatment of the cells with AngII increases α2 isoform of Gi (Giα2) phosphorylation; while pretreatment with chemical and genetic inhibitors of PKC‐ζ and NADPH oxidase attenuate AngII induced increase in PKC‐α activity and Giα2 phosphorylation, and also reverse AngII caused inhibition of isoproterenol induced increase in AC activity. Pretreatment of the cells with chemical and genetic inhibitors of PKC‐α attenuate AngII induced increase in Giα2 phosphorylation and inhibits isoproterenol induced increase in AC activity without a discernible change in PKC‐ζ and NADPH oxidase activities. Overall, PKCζ‐NADPH oxidase‐PKCα signaling axis plays a crucial role in Giα2 phosphorylation resulting in AngII‐mediated inhibition of isoproterenol induced increase in AC activity in BPASMCs.
Motorized fractional flow reserve pullback: Accuracy and reproducibility
Authors: Sonck Jeroen , Collet Carlos , Mizukami Takuya , Vandeloo Bert , Argacha Jean F. , Barbato Emanuele , Andreini Daniele , Bartorelli Antonio , Cosyns Bernard , De Bruyne Bernard
Published: January 2020

Objectives

The present study aimed at determining the accuracy and reproducibility of motorized FFR pullbacks in patients with stable coronary artery disease.

Background

Fractional flow reserve (FFR) is recommended for decision making regarding myocardial revascularization. The distribution of epicardial resistance along coronary vessels can be assessed using FFR pullbacks.

Methods

Duplicated FFR pullbacks were acquired using a motorized device at a speed of 1 mm/s in intermediate coronary stenosis. In addition, a single FFR value was measured at an anatomical landmark. The agreement between FFR measurements was assessed using the Bland–Altman method, Pearson's correlation coefficient and area under the pullback curve (AUPC).

Results

In 20 vessels, 37,326 FFR values were obtained. The mean FFR from the pullbacks was 0.91 ± 0.08 whereas the mean FFR at the distal location was 0.85 ± 0.09. The mean difference between pullbacks was −0.002 (LOA −0.058 to 0.054). The difference in AUPC between the two FFR pullbacks was 2.1 ± 1.6%. At pre‐specified anatomical locations, the mean difference between the FFR derived from the pullback data and the measured FFR was 0 (LOA −0.040 to 0.039). The repeatability of the distal FFR measurement was high (bias −0.003, LOA −0.046 to 0.041).

Conclusion

A motorized FFR pullback was accurate to assess the distribution of epicardial resistance in patients with intermediate coronary artery disease. The reproducibility of the FFR pullback was high. Further studies are required to determine the potential usefulness of a hyperemic FFR pullback strategy for decision making and treatment planning.
Ulcerated gastrointestinal stromal tumor causing a gastrogastric intussusception
Authors: Vandereycken Jan , Michotte Naomi , Vandenbroucke Frederik , de Mey Johan
Published: January 2020

When a gastrointestinal intussusception is found, an underlying lesion should be excluded.
Overview on the Current Status of Hydrogen Energy Research and Development in India
Authors: Medisetty Venkata Manikanta , Kumar Ravinder , Ahmadi Mohammad Hossein , Vo Dai-Viet N. , Ochoa A. A. V. , Solanki Rajniesh
Published: January 2020

The energy demand for the automobile and industrial sectors is increasing drastically worldwide. Conventional sources will no longer fulfil the growing energy demand and environmental pollution is a big concern. Thus, an alternative fuel for vehicles is highly required. The focus is shifted on renewable energy sources like hydrogen, which is abundant in nature. This review examines the continuous progress of hydrogen regarding production and storage techniques in India. Current studies and ongoing projects are summarized projecting the status of production, storage, and application of hydrogen. Challenges like infrastructure development, distribution, policies, cost, and public acceptance as obstacles for the commercialization of hydrogen‐powered vehicles in the Indian market are analyzed.
Understanding the Driving Mechanisms of Enhanced Luminescence Emission of Oligo(styryl)benzenes and Tri(styryl)‐s‐triazine
Authors: Domínguez Rocío , Moral Mónica , Fernández‐Liencres M. Paz , Peña‐Ruiz Tomás , Tolosa Juan , Canales‐Vázquez Jesús , García‐Martínez Joaquín C. , Navarro Amparo , Garzón‐Ruiz Andrés
Published: January 2020

This work is focused on unraveling the mechanisms responsible for the aggregation‐induced enhanced emission and solid‐state luminescence enhancement effects observed in star‐shaped molecules based on 1,3,5‐tris(styryl)benzene and tri(styryl)‐s‐triazine cores. To achieve this, the photophysical properties of this set of molecules were analyzed in three states: free molecules, molecular aggregates in solution, and the solid state. Different spectroscopy and microscopy experiments and DFT calculations were conducted to scrutinize the causative mechanisms of the luminescence enhancement phenomenon observed in some experimental conditions. Enhanced luminescence emission was interpreted in the context of short‐ and long‐range excitonic coupling mechanisms and the restriction of intramolecular vibrations. Additionally, we found that the formation of π‐stacking aggregates could block E/Z photoisomerization through torsional motions between phenylene rings in the excited state, and hence, enhancing the luminescence of the system.
Acridinium Benzoates for Ratiometric Fluorescence Imaging
Authors: Wen Min , Wang Xijing , Wang Ting , Sun Yan , Fan Mengting , Li Min , Zhu Junru , Zhang Dazhi , Cui Xiaoyan , Shan Yongkui
Published: January 2020

Acridinium benzoate was developed as a unique ICT‐based fluorescent scaffold for both ratiometric and turn‐on fluorescence imaging through decaging of the phenolic hydroxyl groups. Two fluorescent probes, Acr1‐H2O2 and Acr1‐β‐gal, were developed for the fluorescence imaging of H2O2 and β‐galactosidase in vivo.
Patient familiarity with, understanding of, and preferences for clinical trial endpoints and terminology
Authors: von Itzstein Mitchell S. , Railey Elda , Smith Mary L. , White Carol B. , Sledge George W. , Howell John R. , Lawton Wendy , Marinucci Donna M. , Unni Nisha , Gerber David E.
Published: January 2020

Background

Although there is increased attention to designing and explaining clinical trials in ways that are clinically meaningful for patients, there is limited information on patient preferences, understanding, and perceptions of this content.

Methods

Maximum difference scaling (MaxDiff) methodology was used to develop a survey for assessing patients' understanding of 19 clinical terms and perceived importance of 9 endpoint surrogate phrases used in clinical trials and consent forms. The survey was administered electronically to individuals with metastatic breast cancer affiliated with the Metastatic Breast Cancer Alliance. Analyses were performed using Bayesian P values with statistical software.

Results

Among 503 respondents, 77% had a college degree, 70% were diagnosed with metastatic disease ≥2 years before survey completion, and 77% had received ≥2 lines of systemic therapy. Less than 35% of respondents reported understanding “fairly well” the terms symptomatic progression, duration of disease control, time to treatment cessation, and endpoints. Income level and time since onset of metastatic disease correlated with comprehension. Patients who had received ≥6 lines of therapy perceived that time until serious side effects (P < .001) and time on therapy (P < .001) were more important compared with those who had received only 1 line of therapy. Positively phrased parameters were associated with increased perceived importance.

Conclusions

Even among educated, heavily pretreated patients, many commonly used clinical research terms are poorly understood. Comprehension and the perceived importance of trial endpoints vary over the course of disease. These observations may inform the design, discussion, and reporting of clinical trials.
Chiroptical Spectroscopic Studies on Lanthanide Complexes with Valinamide Derivatives in Solution
Authors: Hasegawa Miki , Iwasawa Daichi , Kawaguchi Takuma , Koike Hikaru , Saso Akira , Ogata Shuhei , Ishii Ayumi , Ohmagari Hitomi , Iwamura Munetaka , Nozaki Koichi
Published: January 2020

Ligands based on 2,2’‐bipyridine and valinamide moieties induce circularly polarized luminescence in their europium complexes. Both the R and S enantiomers of the complexes were successfully obtained. Single‐crystal X‐ray analysis of the racemic crystal confirmed that the ligand is coordinated to the europium ion in a tetradentate fashion. The π‐electronic system of the ligand is co‐planar with the valinamide moiety, and acts as an efficient photoantenna to sensitize europium luminescence by UV excitation. The luminescence quantum yield (QY) of europium in the valinamide‐containing complex was 44 % in acetonitrile. The glum value to evaluate the circularly polarized luminescence was relatively high at |0.13| estimated from their magnetic dipole transitions around 593 nm. For comparison, we prepared hexadentate europium complexes in the S‐ and R‐forms derived from two bipyridine moieties linked by ethylenediamines. The determined QYs were 18 % (S) and 16 % (R), and the glum value |0.12| for the hexadentate complexes. The photophysical properties of the gadolinium complexes of the ligands were also evaluated.
Regioselective Bay‐Functionalization of Perylenes Toward Tailor‐Made Synthesis of Acceptor Materials for Organic Photovoltaics
Authors: Fujimoto Keisuke , Izawa Seiichiro , Arikai Yusaku , Sugimoto Shinya , Oue Hirona , Inuzuka Toshiyasu , Uemura Naohiro , Sakamoto Masami , Hiramoto Masahiro , Takahashi Masaki
Published: January 2020

The development of an efficient synthetic protocol for multiply bay‐functionalized perylenes and application of these products to photovoltaics are reported. Tetrabenzyl 1‐(4‐tert‐butylphenoxy)perylene‐3,4,9,10‐tetracarboxylate underwent a regioselective bromination at the 7‐position followed by a further bromination at the 12‐position to provide a 7,12‐dibromide in high 84% yield. This compound was transformed into a tetrasubstituted C2h‐symmetric dibromide by a controlled monoetherification and a final bromination. The synthetic versatility of the new brominated precursors was demonstrated by their application to cross‐coupling reactions, cyanation, and derivatization to the corresponding perylene diimide (PDI). Owing to the high solubility and the raised LUMO level, the obtained tetrasubstituted PDI showed significant advantages as an acceptor material for photovoltaic applications, exhibiting a remarkably high open‐circuit voltage (VOC) reaching 1.00 V. The observed high VOC could be understood by reduction of energy offset for charge separation and non‐radiative recombination loss.
Europium(III) Macrocyclic Chelates Appended with Tyrosine‐based Chromophores and Di‐(2‐picolyl)amine‐based Receptors: Turn‐On Luminescent Chemosensors Selective to Zinc(II) Ions
Authors: Wang Gaoji , Platas‐Iglesias Carlos , Angelovski Goran
Published: January 2020

Zinc ions play an important role in many biological processes in the human body. To selectively detect Zn2+, two EuDO3A‐based complexes (DO3A=1,4,7,10‐tetraazacyclododecane‐1,4,7‐tricarboxylic acid) appended with tyrosine as a chromophore and di‐(2‐picolyl)amine (DPA) as the Zn2+ recognition moiety were developed as suitable luminescent sensors. Their luminescence intensity is affected by the photoinduced electron transfer mechanism. Upon addition of Zn2+, both probes display an up to sevenfold enhancement in Eu3+ emission. Competition experiments demonstrated their specificity toward Zn2+ over other metal ions, while also revealing the nonspecificity of the derivatives lacking the DPA‐moiety, thus confirming the essential role of the DPA for the recognition of Zn2+. The induced emission changes of Eu3+ allow for precise quantitative analysis of Zn2+, establishing these lanthanide‐based complexes as viable chemosensors for biological applications.
Zeolite Nanocrystals Embedded in Microcellular Carbon Foam as a High‐Performance CO2 Capture Adsorbent with Energy‐Saving Regeneration Properties
Authors: Mazaj Matjaž , Bjelica Milan , Žagar Ema , Logar Nataša Zabukovec , Kovačič Sebastijan
Published: January 2020

Here, the facile synthesis of four‐length‐scaled (ultramicro‐micro‐meso‐macroporous) hierarchically structured porous carbon nanocomposite by an emulsion‐template strategy is reported. This previously unreported combination of zeolite nanocrystals embedded in the walls of microcellular carbon foams gives unique textural and structural properties, which result in their excellent ability to selectively capture CO2 owing to the presence of ultra‐micropores. The zeolite–microcellular carbon foam synergism delivers an adsorbent with a significantly enhanced CO2 capture capacity of up to 5 mmol g−1, CO2/N2 selectivity of up to 80, and an outstanding multi‐cycle capture performance under humid conditions (70 % performance retention after 30 regeneration cycles). More impressively, the electrically conductive carbon framework enables Joule heating and cooling, and thus fast and energy‐efficient regeneration is possible, with an estimated energy consumption of only about 12 kWh.
Molecular Design Strategy for High‐Redox‐Potential and Poorly Soluble n‐Type Phenazine Derivatives as Cathode Materials for Lithium Batteries
Authors: Miao Licheng , Liu Luojia , Zhang Kai , Chen Jun
Published: January 2020

The n‐type phenazine (PZ) derivatives represent an emerging class of cathode materials in lithium batteries for low‐cost and sustainable energy storage. However, their low redox potential (<2 V) and high solubility hinder their application to battery systems. To explore and solve such problems in lithium batteries, we investigate the redox characteristics of 13 n‐type PZ derivatives and their dissolution behavior in seven organic electrolytes systematically by using DFT calculations. Two decisive factors are observed to tune the redox potentials for these molecules: the first is the electron density around the N active sites and the second is the chelation on lithium by both the active N and the substituent group. Specific approaches that include the reduction of aromatic rings and the introduction of functional groups at β sites in n‐type PZ derivatives can improve the redox potential to approximately 3 V. In addition, we develop a new index denoted as Ediff to investigate the solubility of n‐type PZ derivatives. The most effective way to reduce the dissolution of electrodes in solvents is to improve intermolecular attraction between the electrode molecules by introducing π–π stacking and hydrogen bonds. Such all‐around guidelines should promote the application of n‐type PZ‐based organic cathodes with a high redox potential and low electrode solubility for lithium batteries.
Differentiated transmission services and optimization based on two‐dimensional forwarding for Internet traffic in the AS
Authors: Chen Wen‐Long , Zhou Yuan‐Yuan , Zhao Cheng‐An , Xiao Rong
Published: January 2020

Two‐dimensional routing (TD routing) implements flexible multipath transmission according to the inherent fields of IP packets. However, it may cause large overhead on routers' control plane and data plane. Focusing on autonomous systems with multiple exits, this paper proposes a differentiated transmission services and optimization based on two‐dimensional forwarding for Internet traffic in the autonomous system (AS) (DOTF). The optimal path from the access router to the border router is calculated by the border router. Then two‐dimensional routing information (TDRI) is advertised hop by hop along the reverse path of the optimal path to establish a TD transmission path. DOTF propagates routing information by extending the open shortest path first (OSPF). It compresses message content and optimizes the TDRI structure. TDRI is only released on the specific paths, which greatly reduces the resource consumption in the routers' control plane and data plane. We also analyze the merging of TD routing and one‐dimensional routing (OD routing), reducing the deployment of TD routing entries (TD‐REs). Our experiments on real routers demonstrate the performance of DOTF. The convergence characteristics of TD routing are also analyzed.
Diversity, structure, and synteny of the cutinase gene ofColletotrichumspecies
Authors: Villafana Ria T. , Rampersad Sephra N.
Published: January 2020

Colletotrichumspecies complexes are among the top 10 economically important fungal plant pathogens worldwide because they can infect climacteric and nonclimacteric fruit at the pre and/or postharvest stages.C. truncatumis the major pathogen responsible for anthracnose of green and red bell pepper fruit worldwide.C. brevisporumwas recently reported to be a minor pathogen of red bell pepper fruit in Trinidad, but has recently been reported as pathogenic to other host species in other countries. The ability of these phytopathogens to produce and secrete cutinase is required for dismantling the cuticle of the host plant and, therefore, crucial to the necrotrophic phase of their infection strategy. In vitro bioassays using different lipid substrates confirmed the ability ofC. truncatumandC. brevisporumisolates from green and red bell peppers to secrete cutinase. The diversity, structure and organization and synteny of the cutinase gene were determined among differentColletotrichumspecies. Cluster analysis indicated a low level of nucleotide variation amongC. truncatumsequences. Nucleotide sequences ofC. brevisporumwere more related toC. truncatumcutinase nucleotide sequences than toC. gloeosporioides. Cluster patterns coincided with haplotype and there was evidence of significant positive selection with no recombination signatures. The structure of the cutinase gene included two exons with one intervening intron and, therefore, one splice variant. Although amino acid sequences were highly conserved amongC. truncatumisolates, diversity “hot spots” were revealed when the 66‐amino acid coding region of 200 fungal species was compared. Twenty cutinaseorthologues were detected among different fungal species, whose common ancestor is Pezizomycotina and it is purported that theseorthologues arose through a single gene duplication event prior to speciation. The cutinase domain was retained both in structure and arrangement among 34 differentColletotrichumspecies. The order of aligned genomic blocks between species and the arrangement of flanking protein domains were also conserved and shared for those domains immediately located at the N‐ and C‐terminus of the cutinase domain. Among these were an RNA recognition motif, translation elongation factor, signal peptide, pentatricopeptide repeat, and Hsp70 family of chaperone proteins, all of which support the expression of the cutinase gene. The findings of this study are important to understanding the evolution of the cutinase gene inC. truncatumas a key component of the biotrophic–necrotrophic switch which may be useful in developing gene‐targeting strategies to decrease the pathogenic potential ofColletotrichumspecies.
The role of geography, environment, and genetic divergence on the distribution of pikas in the Himalaya
Authors: Dahal Nishma , Kumar Sunil , Noon Barry R. , Nayak Rajat , Lama Rinzin Phunjok , Ramakrishnan Uma
Published: January 2020

Pikas (Ochotona Link, 1795) are high‐altitude specialist species making them a useful bioindicator species to warming in high‐altitude ecosystem. The Himalayan Mountains are an important part of their range, supporting approximately 23%–25% of total pika species worldwide, yet we lack basic information on the distribution patterns. We combine field‐based surveys with genetics‐based identification and phylogeny to identify differences in species‐environment relationships. Further, we suggest putative evolutionary causes for the observed niche patterns.

Location

Himalayan high‐altitude region.

Methods

We sampled 11 altitudinal transects (ranging from ~2,000 to 5,000 m) in the Himalaya to establish occurrence records. We collected 223 species records using genetic analyses to confirm species' identity (based on some invasive and mostly noninvasive biological samples). Niche and geographic overlap were estimated using kernel density estimates.

Results

Most pikas in the Himalaya span wide elevation ranges and exhibit extensive spatial overlap with other species. However, even in areas of high species diversity, we found species to have a distinct environmental niche. Despite apparent overlapping distributions at broad spatial scales, in our field surveys, we encountered few cases of co‐occurrence of species in the sampled transects. Deeply diverged sister‐species pair had the least environmental niche overlap despite having the highest geographic range overlap. In contrast, sister‐species pair with shallow genetic divergence had a higher environmental niche overlap but was geographically isolated. We hypothesize that the extent of environmental niche divergence in pikas is a function of divergence time within the species complex. We assessed vulnerability of species to future climate change using environmental niche and geographic breadth sizes as a proxies. Our findings suggest that O. sikimaria may be the most vulnerable species. Ochotona roylii appears to have the most unique environmental niche space, with least niche overlap with other pika species from the study area.
The uplift of the Qinghai–Tibet Plateau and glacial oscillations triggered the diversification of Tetraogallus (Galliformes, Phasianidae)
Authors: Ding Li , Liao Jicheng , Liu Naifa
Published: January 2020

The Qinghai–Tibet Plateau (QTP) plays an important role in avian diversification. To reveal the relationship between the QTP uplift and avian diversification since the Late Cenozoic, here, we analyzed the phylogenetic relationship and biogeographical pattern of the genus Tetraogallus (Galliformes, Phasianidae) and the probable factors of speciation in the period of the QTP uplift inferred from concatenated data of four nuclear and five mitochondrial genes using the method of the Bayesian inference. Phylogenetic analysis indicated that T. himalayensis had a close relationship with T. altaicus and conflicted with the previous taxonomy of dark‐bellied and white‐bellied groups. The molecular clock showed that the speciation of Tetraogallus was profoundly affected by the uplift of the QTP and glacial oscillations. Biogeographic analysis suggested that the extant snowcocks originated from the QTP, and the QTP uplift and glacial oscillations triggered the diversification of Tetraogallus ancestor. Specifically, the uplift of the mountain provided a prerequisite for the colonization of snowcocks Tetraogallus as a result of the collision between the Indian and the Arab plates and the Eurasian plate, in which ecological isolation (the glacial and interglacial periods alternate) and geographical barrier had accelerated the Tetraogallus diversification process. Interestingly, we discovered hybrids between T. tibetanus and T. himalayensis for the first time and suggested that T. tibetanus and T. himalayensis hybridized after a second contact during the glacial period. Here, we proposed that the hybrid offspring was the ancestor of the T. altaicus. In conclusion, the uplift of QTP and glacial oscillations triggered the snowcocks colonization, and then, isolation and introgression hybridization promoted diversification.
Organization of Squamata (Reptilia) assemblages in Mediterranean archipelagos
Authors: Escoriza Daniel
Published: January 2020

Mediterranean islands have complex reptile assemblages, but little is known about the factors that determine their organization. In this study, the structure of assemblages of Squamata was evaluated based on their species richness and two measures of phylogenetic diversity (variability and clustering). I evaluated the composition of the assemblages comparing distinct biogeographic subregions within the Mediterranean: Adriatic, Aegean, Balearic, Corsica–Sardinia, Crete, Gulf of Gabés, Ionian Sea, Ligurian Sea, Malta, Sicily, and Tyrrhenian Sea. The effect of island environments and geographical isolation on the diversity metrics was assessed using generalized linear models. The analyses indicated that species richness was mostly influenced by island area and geographical isolation. Assemblages on smaller islands were poorer in species and phylogenetically dispersed, possibly as an effect of interspecific competition. The species composition of the assemblages was determined by similar environmental drivers within the biogeographic subregions, including island area, island elevation, geographical isolation, and aridity. In several subregions, significant patterns of phylogenetic attraction were found in species co‐occurrences, caused by the limits imposed by the island size on large predatory species.
Late diagnosis of Barth syndrome in a 39‐year‐old patient with non‐compaction cardiomyopathy and neutropenia
Authors: Seitz Andreas , Hinck Annely , Bekeredjian Raffi , Sechtem Udo
Published: January 2020

Barth syndrome is a rare X‐linked recessive disorder characterized by a broad spectrum of clinical features including cardiac and skeletal myopathy, neutropenia, exercise intolerance, and growth delay. Most affected patients are diagnosed during childhood, and mortality is highest in the first years of life. As a consequence, Barth syndrome is often considered a paediatric disease. Here, we report a case where the diagnosis was established in a 39‐year‐old patient with left ventricular non‐compaction and neutropenia. The clinical course of the patient presented here was relatively benign. This suggests that the prevalence of Barth syndrome in adults may be underestimated. Barth syndrome should be considered in the differential diagnosis of male patients with cardiomyopathy and neutropenia.
CT‐IGFBP‐4 as a novel prognostic biomarker in acute heart failure
Authors: Konev Alexey A. , Kharitonov Alexey V. , Rozov Fedor N. , Altshuler Evgeny P. , Serebryanaya Daria V. , Lassus Johan , Harjola Veli‐Pekka , Katrukha Alexey G. , Postnikov Alexander B.
Published: January 2020

Aims

Insulin‐like growth factor binding protein‐4 (IGFBP‐4) fragments have been shown to predict the risk of major adverse cardiovascular events, including segment‐elevation myocardial infarction, in patients with acute coronary syndrome. We evaluated the prognostic value of the carboxy‐terminal fragment of IGFBP‐4 (CT‐IGFBP‐4) for all‐cause mortality in emergency room patients with acute heart failure (AHF).

Methods and results

CT‐IGFBP‐4, N‐terminal pro brain natriuretic peptide (NT‐proBNP), and C‐reactive protein (CRP) were measured at admission from the lithium‐heparin plasma of 156 patients with AHF. All‐cause mortality was recorded for 1 year. Receiver operator characteristic (ROC) curves, Kaplan–Meier, and Cox proportional hazard ratio analyses were performed to evaluate the prognostic value of the various clinical variables, CT‐IGFBP‐4, NT‐proBNP, CRP, and their combinations. During 1 year of follow‐up, 52 (33.3%) patients died. CT‐IGFBP‐4 only weakly correlated with NT‐proBNP (Pearson correlation coefficient r = 0.16, P = 0.044) and did not correlate with CRP (r = 0.08, P = 0.35), emphasizing the different nature of these biomarkers. The receiver operator characteristic area under the curve (ROC AUC) of CT‐IGFBP‐4 for the prediction of all‐cause mortality (0.727) was significantly higher than that of NT‐proBNP (0.680, P = 0.045) and CRP (0.669, P = 0.016). The combination of CT‐IGFBP‐4, NT‐proBNP, and CRP predicted mortality significantly better (ROC AUC = 0.788) than any of the biomarkers alone (P < 0.01 for all). The addition of CT‐IGFBP‐4 to a clinical prediction model that included age, gender, systolic blood pressure, creatinine, and sodium levels, as well as the history of previous heart failure, coronary artery disease, and hypertension significantly improved the mortality risk prediction (ROC AUC 0.774 vs. 0.699, P = 0.025). Cox hazard analysis indicated that elevated CT‐IGFBP‐4 was independently associated with 1 year mortality (hazard ratio 3.26, P = 0.0008) after adjustment for age, gender, history of previous heart failure, coronary artery disease, hypertension, chronic kidney failure, history of diabetes, heart rate, haemoglobin, plasma sodium, NT‐proBNP, CRP, cystatin C, and elevated cardiac troponin I or T. Patients with increased levels of either two or three of the biomarkers CT‐IGFBP‐4, NT‐proBNP, and CRP had significantly higher mortality risk (adjusted hazard ratio 10.04, P < 0.0001) than patients with increased levels of one or none of the biomarkers.

Conclusions

CT‐IGFBP‐4 was independently associated with all‐cause mortality in patients with AHF. Compared with single biomarkers, the combination of CT‐IGFBP‐4, NT‐proBNP, and CRP improved the prediction of all‐cause mortality in patients with AHF.
Highly degraded RNA can still provide molecular information: An in vitro approach
Authors: Fattorini Paolo , Bonin Serena , Marrubini Giorgio , Bertoglio Barbara , Grignani Pierangela , Recchia Elisa , Pitacco Paola , Zupanič Pajnič Irena , Sorçaburu‐Ciglieri Solange , Previderè Carlo
Published: January 2020

The long‐term survival of RNA in postmortem tissues is a tricky topic. Many aged/forensic specimens show, in fact, high rates of null/inconclusive PCR‐based results, while reliable outcomes were sometimes achieved from archaeological samples. On the other hand, several data show that the RNA is a molecule that survives even to several physical–chemical stresses. In the present study, a simple protocol, which was already developed for the prolonged hydrolysis of DNA, was applied to a RNA sample extracted from blood. This protocol is based on the heat‐mediated (70°C) hydrolysis for up to 36 h using ultrapure water and di‐ethyl‐pyro‐carbonate‐water as hydrolysis medium. Measurable levels of depurination were not found even if microfluidic devices showed a progressive pattern of degradation. The reverse transcription/quantitative PCR analysis of two (60 bp long) housekeeping targets (glyceraldehyde‐3‐phosphate dehydrogenase and porphobilinogen deaminase) showed that the percentage of amplifiable target (%AT) decreased in relation to the duration of the damaging treatment (r2 > 0.973). The comparison of the %AT in the degraded RNA and in the DNA samples that underwent the same damaging treatment showed that the %AT is always higher in RNA, reaching up to three orders of magnitude. Lastly, even the end‐point PCR of blood‐specific markers gave reliable results, which is in agreement with the body fluid origin of the sample. In conclusion, all the PCR‐based results show that RNA maintains the ability to be retro‐transcribed in short cDNA fragments even after 36 h of incubation at 70°C in mildly acidic buffers. It is therefore likely that the long‐term survival of RNA samples depends mainly on the protection against RNAase attacks rather than on environmental factors (such as humidity and acidity) that are instead of great importance for the stability of DNA. As a final remark, our results suggest that the RNA analysis can be successfully performed even when DNA profiling failed.
A novel approach enables imaged capillary isoelectric focusing analysis of PEGylated proteins
Authors: Zhang Xin , Chemmalil Letha , Ding Julia , Li Zhengjian
Published: January 2020

PEGylation has been used as a strategy to enhance pharmacokinetic properties of therapeutic proteins by pharmaceutical industry. Imaged CIEF (iCIEF) is the current industry standard technology for pI determination and charge variant quantification of proteins and antibodies. However, the charge variants of PEGylated proteins merge into one broad peak during iCIEF, most likely due to masking of proteins by the surrounding PEG chain as well as the increased hydrodynamic volume due to PEGylation. Here, we report our novel matrix formula with a combination of glycine and taurine that significantly improved the separation of charge variants in PEGylated proteins. As a result, it is no longer necessary to conduct IEF of proteins prior to PEGylation, which does not reflect the changes caused by PEGylation and purification processes. The novel matrix (glycine and taurine) enables iCIEF analysis of PEGylated proteins in their real conjugated states.
Predicting the radial heat transfer in the wellbore of cryogenic nitrogen fracturing: Insights into stimulating underground reservoir
Authors: Song Weiqiang , Shi Xian , Wang Chunguang , Xu Jianchun , Chen Shaojie , Chen Zhongwei
Published: January 2020

Cryogenic nitrogen fracturing is an attractive method for stimulating underground reservoir, since it could favorably induce complex fracture due to the huge temperature difference with lower injection pressure and with the replacement of current water‐based fracturing fluid. However, the concern about whether cryogenic nitrogen would be overheated remains unrevealed in the engineering environment with large wellbore length. In addition, reservoir stimulation results are also related with the pressure state at bottom hole. Therefore, in this study, a mathematical model was proposed to predict the radial heat transfer and its influence on vertical pressure transmission in the wellbore with cryogenic nitrogen as fracturing fluid. The model fully couples the heat transfer, hydraulics, and the compressibility of nitrogen, and then, the calculation results were presented and analyzed through a case study. According to the results, the temperature of nitrogen increases too fast under conventional engineering conditions, and it changes into gaseous state at the depth lower than 100 m. Finally, the temperature difference between nitrogen and formation rock becomes too minimal to induce thermal stress at bottom hole. Due to the fast temperature increase, the density of nitrogen decreases too much, and the vertical pressure increasing rate by liquid nitrogen (1.66 MPa/km) is merely 18.2% that in carbon dioxide fracturing (9.13 MPa/km). The results indicate that utilization of special casing with much larger thermal resistance is an indispensable approach to realize the feasibility and advantages of cryogenic nitrogen fracturing.
Diagnostic yield of NanoString nCounter FusionPlex profiling in soft tissue tumors
Authors: Song Wangzhao , Platteel Inge , Suurmeijer Albert J. H. , van Kempen Léon C.
Published: January 2020

Diagnostic histopathology of soft tissue tumors can be troublesome as many entities are quite rare and have overlapping morphologic features. Many soft tissue tumors harbor tumor‐defining gene translocations, which may provide an important ancillary tool for tumor diagnosis. The NanoString nCounter platform enables multiplex detection of pre‐defined gene fusion transcripts in formalin‐fixed and paraffin‐embedded tissue. A cohort of 104 soft tissue tumors representing 20 different histological types was analyzed for the expression of 174 unique gene fusion transcripts. A tumor‐defining gene fusion transcript was detected in 60 cases (58%). Sensitivity and specificity of the NanoString assay calculated against the result of an alternative molecular method were 85% and 100%, respectively. Highest diagnostic coverage was obtained for Ewing sarcoma, synovial sarcoma, myxoid liposarcoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor. For these tumor types, the NanoString assay is a rapid, cost‐effective, sensitive, and specific ancillary screening tool for molecular diagnosis. For other sarcomas, additional molecular testing may be required when a translocation transcript is not identified with the current 174 gene fusion panel.
A process‐based approach to attribution of historical streamflow decline in a data‐scarce and human‐dominated watershed
Authors: Penny Gopal , Srinivasan Veena , Apoorva R. , Jeremiah Kirubaharan , Peschel Joshua , Young Sierra , Thompson Sally
Published: January 2020

Human activities have resulted in rapid hydrological change around the world, in many cases producing shifts in the dominant hydrological processes, confounding predictions, and complicating effective management and planning. Identifying and characterizing such changes in hydrological processes is therefore a globally relevant problem, one that is particularly challenging in sparsely monitored environments. We develop a novel, process‐based approach for attribution of hydrological change in such scenarios and apply the approach to the TG Halli watershed outside Bangalore, India, where streamflow has declined considerably over the last 50 years. The approach consists of (a) employing a range of field instrumentation and experiments to identify contemporary streamflow generation mechanisms, (b) using these observations to constrain our understanding and generate hypotheses pertaining to historical changes, and (c) evaluating these hypotheses with a range of evidence including proxies for historical hydrological processes. The body of evidence in the TG Halli watershed indicates the historical presence and subsequent loss of a shallow groundwater table that previously discharged to the stream, meaning that groundwater depletion is the most likely driver of streamflow decline. These findings present a viable path towards improved predictions of future water resources and sustainable water management within the watershed. Our process‐based approach to attribution has the potential to improve understanding of human‐driven hydrological change in regions with poor monitoring of hydrological systems.
Testing a theoretical resistance law for overland flow on a stony hillslope
Authors: Nicosia Alessio , Di Stefano Costanza , Pampalone Vincenzo , Palmeri Vincenzo , Ferro Vito , Nearing Mark A.
Published: January 2020

Overland flow, sediments, and nutrients transported in runoff are important processes involved in soil erosion and water pollution. Modelling transport of sediments and chemicals requires accurate estimates of hydraulic resistance, which is one of the key variables characterizing runoff water depth and velocity. In this paper, a new theoretical power–velocity profile, originally deduced neglecting the impact effect of rainfall, was initially modified for taking into account the effect of rainfall intensity. Then a theoretical flow resistance law was obtained by integration of the new flow velocity distribution. This flow resistance law was tested using field measurements by Nearing for the condition of overland flow under simulated rainfall. Measurements of the Darcy–Weisbach friction factor, corresponding to flow Reynolds number ranging from 48 to 194, were obtained for simulated rainfall with two different rainfall intensity values (59 and 178 mm hr−1). The database, including measurements of flow velocity, water depth, cross‐sectional area, wetted perimeter, and bed slope, allowed for calibration of the relationship between the velocity profile parameter Γ, the slope steepness s, and the flow Froude number F, taking also into account the influence of rainfall intensity i. Results yielded the following conclusions: (a) The proposed theoretical flow resistance equation accurately estimated the Darcy–Weisbach friction factor for overland flow under simulated rainfall, (b) the flow resistance increased with rainfall intensity for laminar overland flow, and (c) the mean flow velocity was quasi‐independent of the slope gradient.
Nonclinical safety assessment of repeated administration and biodistribution of ChAd3‐EBO‐Z Ebola candidate vaccine
Authors: Planty Camille , Chevalier Guillaume , Duclos Marie‐Ève , Chalmey Clémentine , Thirion‐Delalande Catherine , Sobry Cécile , Steff Ann‐Muriel , Destexhe Eric
Published: January 2020

ChAd3‐EBO‐Z is an investigational adenovirus‐based vaccine for the prevention of Ebola virus disease. Two nonclinical studies were performed to evaluate the biodistribution, local tolerance and potential local and systemic toxic effects of this vaccine. In the biodistribution study, rats received a single intramuscular injection of either ChAd3‐EBO‐Z or saline. Enlargement of the draining lymph nodes, starting on day 2, was noticed in ChAd3‐EBO‐Z‐treated rats, indicating that an immune response had taken place. Viral DNA was mainly found at the injection sites and in the draining lymph nodes, from where it progressively disappeared during the observation period, while it was found only transiently and occasionally in other organs. In the repeated‐dose toxicity study, either ChAd3‐EBO‐Z or saline was administered intramuscularly to rabbits on two occasions with a 2‐week interval. General health status, rectal temperature, local tolerance, ophthalmology, hematology, coagulation and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed. Treatment‐related changes included a transient increase in neutrophil count, C‐reactive protein and fibrinogen levels, and a transient decrease in platelet count. As expected, microscopic observations 3 days after the second injection were related to the elicited inflammatory reaction, and these inflammatory responses had almost completely disappeared 29 days after the second immunization. In conclusion, the vaccine was locally and systemically well‐tolerated and the viral vector was partially or totally cleared from the organs where it disseminated, supporting the clinical development of the vaccine.
Biomarkers in WNT1 and PLS3 Osteoporosis: Altered Concentrations of DKK1 and FGF23
Authors: Mäkitie Riikka E , Kämpe Anders , Costantini Alice , Alm Jessica J , Magnusson Per , Mäkitie Outi
Published: January 2020

Recent advancements in genetic research have uncovered new forms of monogenic osteoporosis, expanding our understanding of the molecular pathways regulating bone health. Despite active research, knowledge on the pathomechanisms, disease-specific biomarkers, and optimal treatment in these disorders is still limited. Mutations in WNT1, encoding a WNT/β-catenin pathway ligand WNT1, and PLS3, encoding X chromosomally inherited plastin 3 (PLS3), both result in early-onset osteoporosis with prevalent fractures and disrupted bone metabolism. However, despite marked skeletal pathology, conventional bone markers are usually normal in both diseases. Our study aimed to identify novel bone markers in PLS3 and WNT1 osteoporosis that could offer diagnostic potential and shed light on the mechanisms behind these skeletal pathologies. We measured several parameters of bone metabolism, including serum dickkopf-1 (DKK1), sclerostin, and intact and C-terminal fibroblast growth factor 23 (FGF23) concentrations in 17 WNT1 and 14 PLS3 mutation-positive subjects. Findings were compared with 34 healthy mutation-negative subjects from the same families. Results confirmed normal concentrations of conventional metabolic bone markers in both groups. DKK1 concentrations were significantly elevated in PLS3 mutation-positive subjects compared with WNT1 mutation-positive subjects (p < .001) or the mutation-negative subjects (p = .002). Similar differences were not seen in WNT1 subjects. Sclerostin concentrations did not differ between any groups. Both intact and C-terminal FGF23 were significantly elevated in WNT1 mutation-positive subjects (p = .039 and p = .027, respectively) and normal in PLS3 subjects. Our results indicate a link between PLS3 and DKK1 and WNT1 and FGF23 in bone metabolism. The normal sclerostin and DKK1 levels in patients with impaired WNT signaling suggest another parallel regulatory mechanism. These findings provide novel information on the molecular networks in bone. Extended studies are needed to investigate whether these biomarkers offer diagnostic value or potential as treatment targets in osteoporosis. © 2020 American Society for Bone and Mineral Research.
Neuroprotective efficacy of nano‐CoQ against propionic acid toxicity in rats: Role of BDNF and CREB protein expressions
Authors: Alhusaini Ahlam , Hasan Iman H. , Alrumayyan Bashayer , Alesikri Marwa , Alanazi Khansa , Almasoud Rawan , Almarshad Sarah
Published: January 2020

Propionic acid (PRA) is used as a food preservative. This study was aimed to investigate the neuroprotective effect of acetyl‐l‐carnitine (ALC) and nano‐Coenzyme Q (N‐CoQ) on brain intoxication induced by PRA in rats. Rats were divided into five groups: group I: control; group II: received PRA; group III: received ALC; group IV: received N‐CoQ; and group V: received ALC and N‐CoQ for 5 days. The antioxidants in question markedly ameliorated serum interleukin‐1β and tumor necrosis factor‐α, and brain NO, lipid peroxide, glutathione, and superoxide dismutase levels as well as protein expression of brain‐derived neurotrophic factor (BDNF) and P‐cyclic‐AMP response element‐binding protein (CREB) that were altered by a toxic dose of PRA, as well as histopathological alterations, including improvement of the cerebellum architecture. Interestingly, the combination therapy of ALC and N‐CoQ achieved the most neuroprotective effect compared with monotherapies. The current study established that N‐CoQ is considered as a useful tool to prevent brain injury induced by PRA. BDNF and CREB proteins are involved in both PRA neurotoxicity and treatment.