bluuebunny/crossref_metadata_2025 huggingface dataset:
Placenta‐on‐a‐Chip: In Vitro Study of Caffeine Transport across Placental Barrier Using Liquid Chromatography Mass Spectrometry
Authors: Pemathilaka Rajeendra L. , Caplin Jeremy D. , Aykar Saurabh S. , Montazami Reza , Hashemi Nicole N.
Published: February 2019

Due to the particular structure and functionality of the placenta, most current human placenta drug testing methods are limited to animal models, conventional cell testing, and cohort/controlled testing. Previous studies have produced inconsistent results due to physiological differences between humans and animals and limited availability of human and/or animal models for controlled testing. To overcome these challenges, a placenta‐on‐a‐chip system is developed for studying the exchange of substances to and from the placenta. Caffeine transport across the placental barrier is studied because caffeine is a xenobiotic widely consumed on a daily basis. Since a fetus does not carry the enzymes that inactivate caffeine, when it crosses a placental barrier, high caffeine intake may harm the fetus, so it is important to quantify the rate of caffeine transport across the placenta. In this study, a caffeine concentration of 0.25 mg mL−1 is introduced into the maternal channel, and the resulting changes are observed over a span of 7.5 h. A steady caffeine concentration of 0.1513 mg mL−1 is reached on the maternal side after 6.5 h, and a 0.0033 mg mL−1 concentration on the fetal side is achieved after 5 h.
PLA Easy Fil – White‐based membranes for CO2 separation
Authors: Iulianelli Adolfo , Russo Francesca , Galiano Francesco , Desiderio Giovanni , Basile Angelo , Figoli Alberto
Published: February 2019

Polymeric membrane technology applied to gas separation is seen as a valuable alternative to conventional systems due to its ease integrability with existing plant, its lower energy consumption, and its flexibility when scaling up. It constitutes a cheaper solution because, in accordance with the principles of process intensification strategy, realized with a reduced number of stages process. In this work, for the first time, a modified polylactic acid‐based polymer (PLA Easy Fil™ – White) was used to synthesize polymeric membranes for use in CO2 separation. This has the further advantage of adopting a biodegradable and non‐toxic material and environmental friendly. Dense symmetric PLA Easy Fil™ – White membranes (average thickness ∼ 27 μm) were prepared and characterized in terms of differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier‐transform infrared (FTIR) analyses and in single gas permeation tests to determine their perm‐selectivity at room temperature in the particular field of CO2/CH4 separation as an example of CO2 removal from raw natural gas or biogas. A CO2/CH4 ideal selectivity equal to 285 (corresponding to a CO2 permeability of 70 barrer) was obtained, overcoming the related Robeson's upper bound. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Feasibility and safety of needle‐assisted endoscopic thyroidectomy with lateral neck dissection for papillary thyroid carcinoma: a preliminary experience
Authors: Wang Bo , Weng Yu‐jing , Wang Si‐si , Zhao Wen‐xin , Yan Shou‐yi , Zhang Li‐yong , Wen Jia
Published: February 2019

Background

Endoscopic thyroidectomy is popular among patients with cosmetic requirements. However, when lateral neck dissection (LND) is required, endoscopic surgery may be challenging. Therefore, we introduced needle‐assisted endoscopic technique to achieve endoscopic LND procedure and evaluated its safety and feasibility in the present study.

Methods

Medical records of 37 patients who underwent needle‐assisted endoscopic thyroidectomy with LND were retrospectively reviewed.

Results

All of 37 patients had excellent cosmetic outcomes. The mean operative time was 338.2 ± 58.74 minutes. Mean number of lymph nodes retrieved in the lateral was 33.5 ± 11.69 and 15.9 ± 7.51 in the central neck. The rates of transient and permanent hypocalcemia were 32.4% and 2.7% and the rates of transient and permanent recurrent laryngeal nerve palsy were 8.1% and 0%, respectively.

Conclusions

Needle‐assisted endoscopic thyroidectomy with lateral neck dissection shows potential feasibility but further study is needed to better characterize its safety and applicability.
In vivo comparison of shape memory polymer foam‐coated and bare metal coils for aneurysm occlusion in the rabbit elastase model
Authors: Herting Scott M. , Ding Yonghong , Boyle Anthony J. , Dai Daying , Nash Landon D. , Asnafi Solmaz , Jakaitis Daniel R. , Johnson Collin R. , Graul Lance M. , Yeh Chung , Kallmes David F. , Kadirvel Ramanathan , Maitland Duncan J.
Published: February 2019

Shape memory polymer (SMP) foam‐coated coils (FCCs) are new embolic coils coated with porous SMP designed to expand for increased volume filling and enhanced healing after implantation. The purpose of this study was to compare chronic aneurysm healing after treatment with SMP FCCs to bare platinum coil (BPC) controls in the rabbit elastase aneurysm model. BPCs or SMP FCCs were implanted in rabbit elastase‐induced aneurysms for follow‐up at 30 days (n = 10), 90 days (n = 5), and 180 days (n = 12 for BPCs; n = 14 for SMP FCCs). Aneurysm occlusion and histologic healing, including a qualitative healing score, neointima thickness, collagen deposition, and inflammation were compared between the two groups. The mean neointima thickness was significantly greater in groups treated with SMP FCCs for all three time points. Histologic healing scores and collagen deposition quantification suggested that aneurysms treated with SMP FCCs experience more complete healing of the dome by 90 days, but the differences were not statistically significant. More progressive occlusion and recanalization were observed in aneurysms treated with SMP FCCs, but neither difference was statistically significant. Additionally, the SMP foam used in the FCCs was found to degrade faster in the rabbit elastase model than expected based on previous studies in a porcine sidewall aneurysm model. This study suggests that SMP FCCs can promote neointima formation along the aneurysm neck, and may lead to more complete healing of the dome and neck. These findings indicate potential benefits of this device for aneurysm occlusion procedures. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2466–2475, 2019.
Overexpression of UBR5 promotes tumor growth in gallbladder cancer via PTEN/PI3K/Akt signal pathway
Authors: Zhang Zhen , Zheng Xin , Li Jiaxin , Duan Jutao , Cui Lihua , Yang Lei , Zhang Lanqiu , Zhang Qi , Wang Ximo
Published: February 2019

As a key regulator of the ubiquitin‐proteasome system, ubiquitin protein ligase E3 component N‐recognin 5 (UBR5) plays an important role in various cancers. In this study, our results showed for the first time that UBR5 was overexpressed in gallbladder cancer (GBC) tumor tissues. UBR5 overexpression was significantly associated with tumor size, histological and tumor differentiation. UBR5 overexpression was also associated with poor prognosis in patients with GBC. The knockdown of UBR5 remarkably inhibited the cell proliferation and colony formation of GBC‐Shandong (SD) cells in vitro and in vivo. UBR5 potentially increases the level of protein kinase B phosphorylation via the degradation of phosphatase and tensin homolog, which contributes to tumor growth in GBC. UBR5 may be an important biomarker for predicting the prognosis of patients with GBC.
AMPKα1 overexpression improves postoperative cognitive dysfunction in aged rats through AMPK‐Sirt1 and autophagy signaling
Authors: Yan Wen‐Jun , Wang Da‐Bin , Ren Dong‐Qing , Wang Ling‐Kai , Hu Zhong‐Yuan , Ma Ya‐Bing , Huang Jin‐Wen , Ding Shao‐Li
Published: February 2019

Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients who undergo surgery involving anesthesia. Its underlying mechanisms remain unclear. Autophagy plays an important role in the damage and repair of the nervous system and is associated with the development of POCD. Using a rat model, adenosine monophosphate‐activated protein kinase α1 (AMPKα1), an important autophagy regulator, was found to be significantly downregulated in rats with POCD that was induced by sevoflurane anesthesia or by appendectomy. Overexpression of AMPKα1‐ameliorated POCD, as indicated by decreased escape latencies and increased target quadrant swimming times, swimming distances, and platform crossing times during Morris water maze tests. AMPKα1 overexpression activated autophagy signals by increasing the expression of light chain 3 II (LC3‐II) and Beclin1 and decreasing the expression of p62 in the hippocampus of rats with POCD. Moreover, blocking autophagy by 3‐methyladenine partly attenuated AMPKα1‐mediated POCD improvement. Furthermore, overexpression of AMPKα1 could upregulate the expression of p‐AMPK and Sirt1 in the hippocampus of rats with POCD. Intriguingly, inhibiting AMPK signals via Compound C effectively attenuated AMPKα1‐mediated POCD improvement, concomitant with the downregulation of p‐AMPK, Sirt1, LC3‐II, and Beclin1 and the upregulation of p62. We thus concluded that overexpression of AMPKα1 can improve POCD via the AMPK‐Sirt1 and autophagy signaling pathway.
Identification of DNA methylation signature to predict prognosis in gastric adenocarcinoma
Authors: Hu Sifeng , Yin Xiankun , Zhang Guangyong , Meng Fanmei
Published: February 2019

Gastric adenocarcinoma is an important death‐related cancer. To find factors related to survival and prognosis, and thus improve recovery prospects, a powerful signature is needed. DNA methylation plays an important role in gastric adenocarcinoma processes and development, and here we report on the search for a significant DNA methylation gene to aid with the earlier diagnosis of gastric adenocarcinoma patients. A Cox proportional risk regression analysis and random survival forest algorithm were used to analyze gastric adenocarcinoma patients’ DNA methylation data from The Cancer Genome Atlas, a public database. DNA methylation gene signature consisting of five genes (SERPINA3, AP000357.4, GZMA, AC004702.2, and GREB1L) were selected. As the most accurate predictor, the area under the curve in the training and test group were 0.72 and 0.61, respectively. The signature was able to sort patients into high‐ and low‐risk groups with meaningful overall survival rates (median: 18.36 vs 72.23 months, log‐rank test, P < 0.001) in the training group, which predictive ability was validated in a test data set (median: 25.56 vs 58.80 months, log‐rank test, P < 0.016). A multivariate Cox regression analysis showed the significant DNA methylation was an independent prediction prognostic factor for gastric adenocarcinoma patients. Functional analysis suggests that these signature genes may be related to pathways and biological processes associated with tumorigenesis. The significant DNA methylation gene could be a novel prediction and prognostic biomarker that both aids in the treatment and predicts the overall survival likelihoods of gastric adenocarcinoma patients.
Investigation of two‐dimensional hf‐based MXenes as the anode materials for li/na‐ion batteries: A DFT study
Authors: Yang Zhifang , Zheng Yanping , Li Wenliang , Zhang Jingping
Published: February 2019

Density functional theory calculations are performed to investigate electronic properties and Li/Na storage capability of Hf3C2 and its derivatives (uniform passivated: Hf3C2T2 [T = F, O, OH] and hybrid passivated: Hf3C2FxO2‐x and Hf3C2Ox(OH)2‐x [x = 1.0, 1.5]). For Hf3C2 monolayer, it has excellent performance, such as good conductivity, low diffusion energy barrier, low open circuit voltage, and high storage capacities (Li(1034.70 mAh g−1), Na(444.90 mAh g−1)), providing the most prospective as anode material. However, due to the unsaturated dangling bonds of surface Hf, so it is easily passivated. For the uniform passivated ones, Hf3C2T2, show higher diffusion barriers and lower storage capacities than bare monolayer Hf3C2. Nevertheless, compared with uniform passivated ones, the hybrid passivated derivative, Hf3C2F1.5O0.5 and Hf3C2OOH possess a lower energy barrier and a better storage capacity. Therefore, Hf3C2F1.5O0.5 and Hf3C2OOH are deemed to be a suitable candidate as anode electrode material for Li‐ion batteries. © 2019 Wiley Periodicals, Inc.
Synthesis, characterization, and antidiabetic activity of 6‐methoxyimidazo[1,2‐b]pyridazine derivatives
Authors: Kota Tata Veereswara Rao , Gandham Himabindu , Sanasi Paul Douglas
Published: February 2019

The present article describes the synthesis, characterization, and antidiabetic activity of 6‐methoxyimidazo[1,2‐b]pyridazine derivatives 7a‐l. The synthetic sequence for the preparation of these derivatives involves the following prominent reactions: (a) Step 1: involves the high‐pressure amination reaction; (b) Step 2: involves the Zinc oxide nanoparticle‐catalyzed cyclization reaction; (c) Step 3: involves the methoxylation; (d) Step 4: involves the bromination reaction; (e) Step 5: involves the Suzuki coupling reaction; (f) Step 6: involves the reduction of the –NO2 group; (g) Step 7: involves Boc protection of the 1o amino group (h) Step 8: involves diazotization of the amine group and finally the last of the synthesis (i) Step 9: involves the saponification of the ethyl ester group. Furthermore, the structures of the newly synthesized 6‐methoxyimidazo[1,2‐b]pyridazine derivatives 7a–l were determined using 1H NMR, 13C NMR, and Mass and IR spectroscopic analyses. These derivatives were evaluated for their antidiabetic property and the results revealed that most of the compounds exhibited significant potency. It is worth mentioning that compounds 7b (69.87%), 7f (69.0%), 7h (68.79%), and 7l (68.61%) with substitution R = para‐NH2, para‐COOH, meta‐NH2, and meta‐COOH, respectively, showed significant (good) hypoglycemic activity when compared to the standard drug insulin (50 mg/kg b.w) in reducing the blood glucose level.
Complex depression: The treatment of major depression and severe personality pathology
Authors: Clarkin John F. , Petrini Mark , Diamond Diana
Published: February 2019

The intensive treatment of a patient presenting with major depression, chronic suicidal ideation, and a borderline personality disorder with narcissistic features is described as it developed over an 18‐month treatment. The treatment approach is a transdiagnostic one with an emphasis on change in the patient's representation of self and others, identity and interpersonal functioning. The intended change is not only in the reduction of depression and suicidal ideation but also an improvement in interactions with others at work and intimate relations. The combination of rich clinical information from the therapist and independent research ratings of patient progress provide a complex picture of the treatment.
The crucial role of ZEB2: From development to epithelial‐to‐mesenchymal transition and cancer complexity
Authors: Fardi Masoumeh , Alivand Mohammadreza , Baradaran Behzad , Farshdousti Hagh Majid , Solali Saeed
Published: February 2019

Zinc finger E‐box binding homeobox 2 (ZEB2) is a DNA‐binding transcription factor, which is mainly involved in epithelial‐to‐mesenchymal transition (EMT). EMT is a conserved process during which mature and adherent epithelial‐like state is converted into a mobile mesenchymal state. Emerging data indicate that ZEB2 plays a pivotal role in EMT‐induced processes such as development, differentiation, and malignant mechanisms, for example, drug resistance, cancer stem cell‐like traits, apoptosis, survival, cell cycle arrest, tumor recurrence, and metastasis. In this regard, the understanding of mentioned subjects in the development of normal and cancerous cells could be helpful in cancer complexity of diagnosis and therapy. In this study, we review recent findings about the biological properties of ZEB2 in healthy and cancerous states to find new approaches for cancer treatment.
Pharmacokinetics, Pharmacodynamics, Immunogenicity, Safety, and Tolerability of JNJ‐61178104, a Novel Tumor Necrosis Factor‐Alpha and Interleukin‐17A Bispecific Antibody, in Healthy Subjects
Authors: Akpalu Derrick E. , Frederick Bart , Nnane Ivo P. , Yao Zhenling , Shen Fang , Ort Tatiana , Fink Damien , Dogmanits Shannon , Raible Donald , Sharma Amarnath , Xu Zhenhua
Published: February 2019

The safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of JNJ‑61178104, a novel anti–tumor necrosis factor‐alpha (TNFα) and anti–interleukin‐17A (IL‑17A) bispecific antibody, were investigated in a placebo‐controlled, first‐in‐human study. Healthy subjects (n = 54) received a single dose of JNJ‐61178104 by either intravenous infusion (0.1, 0.3, 1, 3, and 10 mg/kg) or subcutaneous injection (1 mg/kg). Blood samples for measurement of serum JNJ‐61178104 concentrations, total IL‐17A, total TNFα, and detection of antidrug antibodies were collected for up to 16 weeks after dosing and assessed using electrochemiluminescence immunoassays. PK parameters were calculated by noncompartmental analysis and estimated by nonlinear mixed‐effects modeling. JNJ‐61178104 was generally well tolerated in healthy subjects. For the intravenous cohorts, mean maximum concentration, and area under the concentration‐time curve values increased in a dose‐proportional manner. Mean clearance ranged from 6.73 to 9.99 mL/day/kg, mean volume of distribution at terminal phase after intravenous administration ranged from 51.0 to 91.9 mL/kg, and mean half‐life ranged from 4.3 to 9.7 days following intravenous administration. After a single subcutaneous dose of 1 mg/kg, median time to maximum concentration was 4.0 days, mean bioavailability was 52.0% and mean half‐life was 5.3 days. A linear 2‐compartment population model with first‐order elimination adequately characterized the pharmacokinetics with parameters consistent with noncompartmental analysis estimates. Body weight and antidrug antibodies were significant covariates on JNJ‐61178104 clearance. The time to reach mean maximum serum total TNFα and total IL‐17A concentrations appeared to be dose dependent across the 0.1 mg/kg to 10 mg/kg IV dose groups. All subjects who received active treatment were antidrug antibody positive after dosing with JNJ‐61178104.
Pepsin immobilization on biochar by adsorption and covalent binding, and its application for hydrolysis of bovine casein
Authors: Santos Mateus PF , Brito Mylena JP , Junior Evaldo CS , Bonomo Renata CF , Veloso Cristiane M
Published: February 2019

BACKGROUND

The objective of this research was to compare the efficiency of pepsin immobilization by adsorption and covalent binding on biochar obtained from pupunha palm processing residue, and to use the immobilized enzyme in the hydrolysis of bovine casein.

RESULTS

The surface modification of biochar with glutaraldehyde was effective, as shown by Fourier transform infrared analyses and the texture properties of the carbons. Both activated and functionalized biochar showed high immobilization efficiency (>95%) and high enzyme‐support binding capacity (>96 mg g–1). During the activity assays, the functionalized carbon showed a higher casein hydrolysis rate when compared to the enzyme immobilized by adsorption, with values of 39.17 U and 32.67 U, respectively, and c. 95% of the activity of the free enzyme, after 60 min.

CONCLUSION

The functionalization of the biochar led to a surface modification of biochar by the insertion of amine‐aldehyde groups, which was responsible for the formation of strong interactions between the support material and the enzyme, thus providing a greater proteolytic activity when compared to immobilization by adsorption. The immobilized enzymes were able to maintain their proteolytic activity for more than seven cycles of reuse. © 2019 Society of Chemical Industry
Sonochemical Preparation of Dipicolinamide Mn‐complexes and Their Application as Catalysts Towards Sono‐synthesis of Ketones
Authors: Arafa Wael A. A.
Published: February 2019

A series of non‐heme Mn‐complexes has been synthesized by the sonication of manganese (II)chloride and bis‐amides (condensation products of 2‐picolinic acid and o‐phenylenediamines). The Mn‐complexes effectively promote the oxidation of unactivated aliphatic and benzylic C─H and N‐bearing heterocycles substrates with low catalyst loading using eco‐friendly hydrogen peroxide in the presence of acetic acid as additive under ultrasonic irradiation. Chromatographic studies revealed that the corresponding ketones are the only detectable products. Noteworthy, the presence of electron donors in the catalyst structure significantly increased the reaction yields. The substantial lowering of the oxidation reaction yields by adding ionol (2,6‐di‐tert‐butyl‐4‐methylphenol) as a free radical trap suggesting a free radical reaction pathway.
Persistence on HIV preexposure prophylaxis medication over a 2‐year period among a national sample of 7148 PrEP users, United States, 2015 to 2017
Authors: Coy Kelsey C , Hazen Ronald J , Kirkham Heather S , Delpino Ambrose , Siegler Aaron J
Published: February 2019

Introduction

Persistence on preexposure prophylaxis for HIV prevention (PrEP) medication has rarely been reported for periods greater than one year, or in real‐world settings. This study used pharmacy fill records for PrEP users from a national chain pharmacy to describe persistence on PrEP medication over a two‐year period, and to explore correlates with PrEP medication persistence in a real‐world setting.

Methods

We analysed de‐identified pharmacy fill records of 7148 eligible individuals who initiated PrEP in 2015 at a national chain pharmacy. A standard algorithm was employed to identify TDF‐FTC use for PrEP indication. We considered three time periods for persistence, defined as maintaining refills in PrEP care: year 1 (zero to twelve months), year 2 (thirteen to twenty‐four months) and initiation to year 2 (zero to twenty‐four months). Individuals with 16 or more days of TDF‐FTC PrEP dispensed in a 1‐month period for at least three‐quarters of a given time period (e.g. nine of twelve months or eighteen of twenty‐four months) were classified as persistent on PrEP medication for the period.

Results

Persistence was 56% in year 1, 63% in year 2 and 41% from initiation to year 2. Individuals aged 18 to 24 had the lowest persistence, with 29% from initiation to year 2. Men had higher persistence than women, with 42% compared to 20% persistent from initiation to year 2. Individuals with commercial insurance and individuals who utilized a community‐based specialty pharmacy from the national chain also had higher persistence. Male gender, age >18 to 24 years, average monthly copay of $20 or less, commercial insurance, and utilization of a community‐based specialty pharmacy were positively associated in adjusted models with persistence in year 1 and from initiation to year 2; the same correlates, with the exception of utilization of a community‐based specialty pharmacy, were associated with higher persistence in year 2.

Conclusions

We found substantial non‐persistence on PrEP medication in both year 1 and year 2. Across the entire 2‐year period, only two out of every five users persisted on PrEP. Demographic, financial and pharmacy factors were associated with persistence. Further research is needed to explore how social, structural or individual factors may undermine or enhance persistence on PrEP, and to develop interventions to assist persistence on PrEP.
Danger signals in oral cavity-related diseases
Authors: Kay Jason G , Kramer Jill M , Visser Michelle B
Published: February 2019

The oral cavity is a unique environment containing teeth juxtaposed with soft tissues, all of which are constantly bathed in microbial products and host-derived factors. While microbial dysbiosis in the oral cavity clearly leads to oral inflammatory disease, recent advances find that endogenous danger-associated molecular patterns (DAMPs) released from oral and salivary tissue also contribute to the progression of inflammatory and autoimmune disease, respectively. In contrast, DAMPs produced during oral fungal infection actually promote the resolution of infection. Here, we present a review of the literature suggesting a role for signaling by DAMPs, which may intersect with pathogen-associated molecular pattern (PAMP) signaling, in diseases that manifest in the oral cavity, specifically periodontal disease, oropharyngeal candidiasis, and Sjögren’s syndrome.
Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B
Authors: Wei Mike T. , Le An K. , Chang Matthew S. , Hsu Holden , Nguyen Pauline , Zhang Jian Q. , Wong Chris , Wong Clifford , Cheung Ramsey , Nguyen Mindie H.
Published: February 2019

Background

Recent studies have suggested a potential increase in the incidence of osteoporosis for patients receiving tenofovir disoproxil fumarate (TDF), but this issue remains controversial.

Methods

The retrospective cohort study of 1224 Asian chronic hepatitis B (CHB) patients greater than 18 years without baseline osteopenia/osteoporosis seen at four US centers from 2008 to 2016. Patients were categorized into three groups—treatment‐naive patients who initiated therapy with TDF (1) or entecavir (ETV) (2), or untreated patients (3). Patients were followed until the development of osteopenia/osteoporosis or end of the study.

Results

Of the 1224 study patients, 276 were treated with TDF, 335 with ETV, and 613 were untreated. The prevalence of cirrhosis was lower for untreated patients (2.6% vs 16.3% for TDF and 17.6% for ETV; P < 0.001). The 8‐year cumulative incidence rate of osteopenia/osteoporosis was 13.17% for TDF, 15.09% for ETV, and 10.17% for untreated patients, with no statistically significant difference among the three groups (
P = 0.218). On multivariate Cox regression controlling for demographics, osteoporosis risk factors, albumin, and hepatitis B virus (HBV) DNA levels, neither TDF (adjusted hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.34 and 1.59) nor ETV (adjusted HR = 0.98; 95% CI: 0.51 and 1.90) were associated with increased osteopenia/osteoporosis risk compared with untreated patients.

Conclusions

Our retrospective study suggests that there is no significant increase in the incidence of osteopenia/osteoporosis for patients with CHB treated with TDF or ETV during a median follow‐up of about 4 to 5 years. However, further study with longer follow‐up is needed as an anti‐HBV therapy, which is often lifelong or long‐term and the development of osteopenia/osteoporosis can be a slow process.
Late Pleistocene to Holocene paleoenvironmental changes in the NW Black Sea
Authors: Briceag Andrei , Yanchilina Anastasia , Ryan William B. F. , Stoica Marius , Melinte‐Dobrinescu Mihaela C.
Published: February 2019

Two gravity cores that penetrated Upper Pleistocene to Upper Holocene sediments in the NW Black Sea have been studied lithologically and microfaunally. The investigations have been coupled with isotopic, calcium carbonate and radiocarbon dating. Six ecological intervals have been distinguished based on changes in microfossil assemblages, giving new insights on the sea‐level and paleoenvironmental changes that took place in the last 25 000 a BP. For the Last Glacial Maximum the ostracod community contains a homogeneous brackish assemblage dominated by Candonidae, suggesting a salinity around 5–8‰. The salinity decrease (to 0.5–5‰) that started concomitantly with the first Meltwater Pulse during Heinrich Stadial 1 is mirrored by increasing diversity and abundance of microfaunal assemblages. This microfaunal increase reached maximum values within the Bølling–Allerød warm period. The shift from Loxoconchidae to Candonidae towards the top of the Younger Dryas suggests a slight increase in salinity. The Preboreal warming period is marked by an abundance increase of ostracod assemblages. During the Late Holocene, stable marine conditions set in, reflected by assemblages similar to those of the present‐day. Based on these data, the first marine influx into the Black Sea before 9390 a BP is assumed.
Luminescence chronology of the Palaeolithic–Neolithic transition in the Yujiagou site at the Nihewan Basin, northern China
Authors: Rui Xue , Guo Yu‐Jie , Zhang Jia‐Fu , Hu Yue , Mei Hui‐Jie , Wang You‐Ping , Xie Fei , Li Bo
Published: February 2019

The relationship between the Palaeolithic–Neolithic cultural transition and environmental changes is important for understanding human history. However, the timing and nature of human behaviour at the transition, and their relationship to local environmental conditions, remain poorly understood. The Yujiagou archaeological site in the Nihewan Basin, northern China, provides valuable chronological and archaeological information about cultural changes in northern China due to its continuous archaeological sequence of cultural layers from the Palaeolithic to Neolithic. In this study, we apply post‐infrared infrared stimulated luminescence (pIRIR) dating on individual feldspar grains to date the Yujiagou deposits. We provide a revised chronology for the archaeological sequence at the site. We combine these results with multi‐proxy climatic indicators to gain insights into palaeoenvironmental changes in the region. The results show that the age of the artefact‐bearing deposits ranges from 13.5 to 9.7 ka. Polished stones and pottery begin to occur in the archaeological layer around 13 ka, corresponding to a transitional period when the local climate changed from cold to warm. This site provides evidence for understanding the process that led to the regional transition from hunter‐gathering to farming.
Late Holocene environmental changes reconstructed from stable isotope and geochemical records from a cushion‐plant peatland in the Chilean Central Andes (27°S)
Authors: Kock S. T. , Schittek K. , Mächtle B. , Wissel H. , Maldonado A. , Lücke A.
Published: February 2019

A Late Holocene paleoenvironmental record was obtained from the Lagunillas cushion peatland (LP, 27°12′S, 69°17′W), located in the dry Puna of the western Central Andes. Ten radiocarbon dates build the chronology for the last 1800 cal a BP. Analyses of stable isotopes on cellulose (δ18Ocell, δ13Ccell) and geochemical proxies on organic matter (δ13COM, δ15Nbulk, TOC, TN, LOI, T535) were conducted to identify major paleoenvironmental changes in this record. Simultaneously, ambient water (δ18O, δ2H) and plant samples of the dominant species Oxychloe andina (δ18Ocell, δ13Ccell) reveal insights into modern conditions. The record reveals distinct multi‐centennial oscillations of peat layer thickness and δ18Ocell. Decomposition, changes in the dominating plant species as well as in plant parts (leaves/roots) can be excluded as driving factors for these oscillations. Thus, δ18Ocell seems to be externally forced and reflects humidity changes. Around 470 cal a BP a distinct change towards increased humidity occurred, lasting during the Little Ice Age until about 70 cal a BP. Humid conditions prevailed between 1530 and 1270 cal a BP. Increasing δ18Ocell values since 30 cal a BP mark a trend towards again increased aridity.
The role of pepsin in epithelia‐mesenchymal transition in idiopathic subglottic stenosis
Authors: McCann Alec J. , Samuels Tina L. , Blumin Joel H. , Johnston Nikki
Published: February 2019

Objectives

Idiopathic subglottic stenosis (iSGS) is commonly characterized by laryngeal fibrosis thought to arise by epithelia‐mesenchymal transition (EMT) induced by chronic inflammation. Pepsin is a potent inducer of inflammation in the airways during chronic laryngopharyngeal reflux and has been observed in the subglottic mucosa of patients with iSGS, absent in normal mucosa. The aim of this study was to examine the effect of pepsin on mechanisms of EMT in laryngeal cells with implications for iSGS.

Study Design

In vitro translational research study.

Methods

Human laryngeal epithelial cell cultures were exposed to 0.1 mg/mL or 1.0 mg/mL pepsin at pH7 for 24 and 48 hours, or media pH5 ± 0.1 mg/mL pepsin for 10 minutes and harvested after 24 and 48 hours. EMT marker expression was measured by qPCR and enzyme‐linked immunosorbent assays. Wound‐healing scratch assay was performed on immortalized human vocal fold fibroblasts pretreated with media pH5 ± 0.1 mg/mL pepsin (10 minutes) or continuously treated with media pH7 ± 0.1 to 1 mg/mL pepsin for 24 hours.

Results

Pepsin yielded no effect on MMP1, MMP9, FN1, COL1A1, HAS2, or CDH1 gene expression or matrix metalloproteinase‐9 or fibronectin protein expression, either alone or in the presence of weak acid. Pepsin and/or acid produced no effect on fibroblast migration.

Conclusion

Whereas pepsin has been shown to be present in the subglottic mucosa of patients with iSGS, this in vitro acute exposure investigation does not provide evidence of a direct causal role for development of fibrosis in subglottic epithelial cell cultures.

Levels of Evidence

NA. Laryngoscope, 130:154–158, 2020
On para‐Kähler Lie algebroids and contravariant pseudo‐Hessian structures
Authors: Benayadi Saïd , Boucetta Mohamed
Published: February 2019

In this paper, we generalize all the results obtained on para‐Kähler Lie algebras in [3] to para‐Kähler Lie algebroids. In particular, we study exact para‐Kähler Lie algebroids as a generalization of exact para‐Kähler Lie algebras. This study leads to a natural generalization of pseudo‐Hessian manifolds, we call them contravariant pseudo‐Hessian manifolds. Contravariant pseudo‐Hessian manifolds have many similarities with Poisson manifolds. We explore these similarities which, among others, leads to a powerful machinery to build examples of non trivial pseudo‐Hessian structures. Namely, we will show that given a finite dimensional commutative and associative algebra, the orbits of the action Φ ofongiven byare pseudo‐Hessian manifolds, where. We illustrate this result by considering many examples of associative commutative algebras and show that the resulting pseudo‐Hessian manifolds are very interesting.
Optimal control problems constrained by the stochastic Navier–Stokes equations with multiplicative Lévy noise
Authors: Benner Peter , Trautwein Christoph
Published: February 2019

We consider the controlled stochastic Navier–Stokes equations in a bounded multidimensional domain, where the noise term allows jumps. In order to prove existence and uniqueness of an optimal control w.r.t. a given control problem, we first need to show the existence and uniqueness of a local mild solution of the considered controlled stochastic Navier–Stokes equations. We then discuss the control problem, where the related cost functional includes stopping times dependent on controls. Based on the continuity of the cost functional, we can apply existence and uniqueness results provided in [4], which enables us to show that a unique optimal control exists.
The Effect of Bending Rigidity on Polymers
Authors: Jia Jiying , Li Kunhe , Hofmann Andreas , Heermann Dieter W.
Published: February 2019

The conformations of chromatin are influenced by many factors. In the regulation of gene expression the bending rigidity of the chromatin polymer and its heterogeneity play an important role for the possible conformations. To elucidate this, the effect of bending rigidity as well as its heterogeneity on various polymer properties is investigated. In the context of chromatin organization, the contact probability is an important measure. It is analyzed whether there is any ambiguity in the definition of a contact. The results show that the contact probability does not depend on the range of contact in the limit of a large contour length between monomers. Further, the persistence length as a function of the bending rigidity is computed in the homogeneous and heterogeneous cases. The persistence length is systematically smaller in the heterogeneous case. Chromosomes are confined by each other in the nucleus and by looking at specific loci, the environment changes much more slowly than the local chromatin part. In conjunction with bending rigidity, polymers in rectangular confinements with several aspect ratios are simulated. Due to the spiraling behavior when the box size is small enough, an oscillation in the contact probability and the orientational correlation function is found.
Clinical heterogeneity of frontotemporal dementia and Parkinsonism linked to chromosome 17 caused by MAPT N279K mutation in relation to tau positron emission tomography features
Authors: Ikeda Aya , Shimada Hitoshi , Nishioka Kenya , Takanashi Masashi , Hayashida Arisa , Li Yuanzhe , Yoshino Hiroyo , Funayama Manabu , Ueno Yuji , Hatano Taku , Sahara Naruhiko , Suhara Tetsuya , Higuchi Makoto , Hattori Nobutaka
Published: February 2019

Background

While mechanistic links between tau abnormalities and neurodegeneration have been proven in frontotemporal dementia and parkinsonism linked to chromosome 17 caused by MAPT mutations, variability of the tau pathogenesis and its relation to clinical progressions in the same MAPT mutation carriers are yet to be clarified.

Objectives

The present study aimed to analyze clinical profiles, tau accumulations, and their correlations in 3 kindreds with frontotemporal dementia and parkinsonism linked to chromosome 17 attributed to the MAPT N279K mutation.

Methods

Four patients with N279K mutant frontotemporal dementia and parkinsonism linked to chromosome 17/MAPT underwent [11C]PBB3‐PET to estimate regional tau loads.

Results

Haplotype assays revealed that these kindreds originated from a single founder. Despite homogeneity of the disease‐causing MAPT allele, clinical progression was more rapid in 2 kindreds than in the other. The kindred with slow progression showed mild tau depositions, mostly confined to the midbrain and medial temporal areas. In contrast, kindreds with rapid progression showed profoundly increased [11C]PBB3 binding in widespread regions from an early disease stage.

Conclusions

[11C]PBB3‐PET can capture four‐repeat tau pathologies characteristic of N279K mutant frontotemporal dementia and parkinsonism linked to chromosome 17/MAPT. Our findings indicate that, in addition to the mutated MAPT allele, genetic and/or epigenetic modifiers of tau pathologies lead to heterogeneous clinicopathological features. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Wireless coils based on resonant and nonresonant coupled‐wire structure for small animal multinuclear imaging
Authors: Vergara Gomez Tania S. , Dubois Marc , Glybovski Stanislav , Larrat Benoit , de Rosny Julien , Rockstuhl Carsten , Bernard Monique , Abdeddaim Redha , Enoch Stefan , Kober Frank
Published: February 2019

Earlier work on RF metasurfaces for preclinical MRI has targeted applications such as whole‐body imaging and dual‐frequency coils. In these studies, a nonresonant loop was used to induce currents into a metasurface that was operated as a passive inductively powered resonator. However, as we show in this study, the strategy of using a resonant metasurface reduces the impact of the loop on the global performance of the assembled coil. To mitigate this deficiency, we developed a new approach that relies on the combination of a commercial surface coil and a coupled‐wire structure operated away from its resonance. This strategy enables the extension of the sensitive volume of the surface coil while maintaining its local high sensitivity without any hardware modification. A wireless coil based on a two parallel coupled‐wire structure was designed and electromagnetic field simulations were carried out with different levels of matching and coupling between both components of the coil. For experimental characterization, a prototype was built and tested at two frequencies, 300 MHz for 1H and 282.6 MHz for 19F at 7 T. Phantom and in vivo MRI experiments were conducted in different configurations to study signal and noise figures of the structure. The results showed that the proposed strategy improves the overall sensitive volume while simultaneously maintaining a high signal‐to‐noise ratio (SNR). Metasurfaces based on coupled wires are therefore shown here as promising and versatile elements in the MRI RF chain, as they allow customized adjustment of the sensitive volume as a function of SNR yield. In addition, they can be easily adapted to different Larmor frequencies without loss of performance.
Agreement between clinicoradiological signs at diagnosis and radiohistological analysis after neoadjuvant chemotherapy of suspected Wilms tumor rupture: Consequences on therapeutic choices
Authors: Le Rouzic Marie‐Amelyne , Mansuy Ludovic , Galloy Marie‐Agnès , Champigneulle Jacqueline , Bernier Valérie , Chastagner Pascal
Published: February 2019

Introduction

According to SIOP criteria, every patient presenting with preoperative Wilms tumor (WT) rupture must receive abdominal radiotherapy. Neoadjuvant chemotherapy reduces tumor volume and is responsible for the development of peritumoral capsule formation, which can mask tumor rupture on histological analysis, while it was clinically or radiologically obvious at diagnosis. Yet, there are no protocol recommendations for this particular presentation.

Objectives

Study the agreement between clinicoradiological signs and histological confirmation after neoadjuvant chemotherapy of suspected WT rupture and describe the therapeutic choices arising in consequence.

Methods

Descriptive retrospective study on a monocentric series of patients with WT between June 1991 and August 2017.

Results

Out of 71 patients, 28 presented with suspected tumor rupture. We observed good agreement between clinical and radiological signs of suspected rupture (κ coefficient: 0.67). However, we assessed poor agreement between these signs and histological conclusions after neoadjuvant chemotherapy (κ coefficient: 0.27). Only five patients with clinicoradiological signs were overtreated with radiotherapy while tumor rupture had been refuted after histological review. The notion of abdominal trauma and the presence of intraperitoneal effusion seemed to guide collegial decision to overtreat these patients. No statistical difference in survival between patients with and without suspicion of tumor rupture at diagnosis was observed.

Conclusion

This study highlights the need for recommendations in case of discrepancy between radiological and histological signs of rupture at diagnosis and after neoadjuvant chemotherapy. A study with stronger statistical power is necessary to define criteria that would lead to optimization of treatment in this context.
Cerebral oxygenation associated with INSURE versus LISA procedures in surfactant‐deficient newborn piglet RDS model
Authors: Rey‐Santano Carmen , Mielgo Victoria E. , Gomez‐Solaetxe Miguel A. , Salomone Fabrizio , Gastiasoro Elena , Loureiro Begoña
Published: February 2019

Background

Nasal continuous‐positive airway pressure (nCPAP) with the INSURE (INtubation‐SURfactant‐Extubation) or LISA (Less‐Invasive Surfactant Administration) procedures are increasingly being chosen as the initial treatment for neonates with surfactant deficiency. Our objective was to compare the effects on cerebral oxygenation of different methods for surfactant administration: INSURE and LISA, using a nasogastric tube (NT) or a LISAcath® catheter, in spontaneously breathing SF‐deficient newborn piglets.

Methods

Eighteen newborn piglets with SF‐deficient lung injury produced by repetitive bronchoalveolar lavages were randomly assigned to INSURE, LISA‐NT, or LISAcath® groups. We assessed pulmonary (gas exchange, lung mechanics, lung histology) and hemodynamic (mean arterial blood pressure, heart rate) changes, cerebral oxygenation (cTOI) and cerebral fractional tissue extraction (cFTOE), with near‐infrared spectroscopy, carotid blood flow and brain histology.

Results

SF‐deficient piglets developed respiratory distress (FiO2 = 1, pH <7.2, PaCO2 >70 mmHg, PaO2 <70 mmHg, Cdyn <0.5 mL/cmH2O/kg). Rapid improvements in pulmonary status were observed in all surfactant‐treated groups without hemodynamic alterations. In the INSURE group, a transient decrease in cTOI occurred during and immediately after surfactant administration, while cTOI only decreased during surfactant administration in the LISA‐NT group and did not change significantly in the LISAcath® group. Brain injury scores were low in all surfactant‐treated groups.

Conclusion

In spontaneously breathing SF‐deficient newborn piglets, short‐lasting decreases in cerebral oxygenation are associated with surfactant administration by the INSURE method or LISA using an NT, while no cerebral oxygenation changes occurred with LISA using a LISAcath®. Notably, none of treatments studied seems to have a negative impact on the neonatal brain.
Peripheral muscle strength is associated with lung function and functional capacity in patients with cystic fibrosis
Authors: Rovedder Paula Maria Eidt , Borba Gabrielle Costa , Anderle Mariluce , Flores Josani , Ziegler Bruna , Barreto Sérgio Saldanha Menna , Roth Dalcin Paulo de Tarso
Published: February 2019

Purpose

Cystic fibrosis (CF) is an inherited disease that causes important multisystemic impairments. The present study aimed to evaluate the association of peripheral muscle strength with lung function and functional capacity in adolescents and adults with CF.

Methods

Cross‐sectional study with prospective data of patients enrolled in the Program for Adults with CF at Hospital de Clínicas de Porto Alegre. The testing procedures included peripheral muscle strength testing, pulmonary function tests, and the 6‐minute walk test.

Results

The sample consisted of 41 subjects (27 women) with a mean age of 24.6. Upper extremity muscle strength was associated with forced vital capacity and forced expiratory volume in the first second, and lower extremity muscle strength was associated with the distance covered in the 6‐minute walk test, oxygen saturation, forced expiratory volume in the first second, and forced vital capacity.

Conclusions

Muscle strength was positively associated with lung function variable and functional capacity in patients with CF.
Experimental and theoretical investigation of the lower explosion limit of multiphase hybrid mixtures
Authors: Addai Emmanuel Kwasi , Ali Haider , Amyotte Paul , Krause Ulrich
Published: February 2019

This article reports on experimental and theoretical investigations of the lower explosion limits of two‐ and three‐phase mixtures such as gas‐dust, spray‐gas, dust‐spray, and dust‐gas‐spray. The materials used were lycopodium and brown coal as combustible dusts, methane, and hydrogen as combustible gases and ethanol and isopropanol as sprays (liquid solvent).

The experiments were performed in the standardized 20‐L spherical explosion chamber where modifications were done to allow the input of solvents and gases. The test protocol was in accordance with the European standard, EN 14034. The experimental results demonstrate significant enhancements in explosion likelihood brought about by gas or spray admixture with dust and vice versa. They also confirm that a hybrid mixture explosion is possible even when both dust and spray or gas concentrations are respectively lower than their minimum explosible concentration (MEC) and lower explosion limit (LEL). For example, the MEC of brown coal decreases from 250 to 60 g/m3, 60 and 100 g/m3 when small amounts of isopropanol spray, methane gas, and hydrogen gas respectively, were added (even though these concentrations of gases and solvents are all below the LEL of the individual substances).

Comparisons have been made between the lower explosible limit of the experimental data and classical models such as those developed by Bartknecht, Le Chatelier, and Jiang and coworkers. This research provides safety practitioners with a practical means to characterize material hazards without the need to perform a large number of tests. © 2019 American Institute of Chemical Engineers Process Saf Prog, 1–13: e12045 2019