bluuebunny/crossref_metadata_2025 huggingface dataset:
Paracrine recruitment and activation of fibroblasts by c‐Myc expressing breast epithelial cells through the IGFs/IGF‐1R axis
Authors: De Vincenzo Anna , Belli Stefania , Franco Paola , Telesca Marialucia , Iaccarino Ingram , Botti Gerardo , Carriero Maria V. , Ranson Marie , Stoppelli Maria Patrizia
Published: August 2019

Fibroblasts are among the most abundant stromal cells in the tumor microenvironment (TME), progressively differentiating into activated, motile, myofibroblast‐like, protumorigenic cells referred to as Cancer‐Associated Fibroblasts (CAFs). To investigate the mechanisms by which epithelial cells direct this transition, the early stages of tumorigenesis were exemplified by indirect cocultures of WI‐38 or human primary breast cancer fibroblasts with human mammary epithelial cells expressing an inducible c‐Myc oncogene (MCF10A‐MycER). After c‐Myc activation, the conditioned medium (CM) of MCF10A‐MycER cells significantly enhanced fibroblast activation and mobilization. As this was accompanied by decreased insulin‐like growth factor binding protein‐6 (IGFBP‐6) and increased insulin‐like growth factor‐1 and IGF‐II (IGF‐I, IGF‐II) in the CM, IGFs were investigated as key chemotactic factors. Silencing IGFBP‐6 or IGF‐I or IGF‐II expression in epithelial cells or blocking Insulin‐like growth factor 1 receptor (IGF‐1R) activity on fibroblasts significantly altered fibroblast mobilization. Exposure of WI‐38 fibroblasts to CM from induced MCF10A‐MycER cells or to IGF‐II upregulated FAK phosphorylation on Tyr397, as well as the expression of α‐smooth muscle actin (α‐SMA), features associated with CAF phenotype and increased cell migratory/invasive behavior. In three‐dimensional (3D)‐organotypic assays, WI‐38 or human primary fibroblasts, preactivated with either CM from MCF10A‐MycER cells or IGFs, resulted in a permissive TME that enabled nontransformed MCF10A matrix invasion. This effect was abolished by inhibiting IGF‐1R activity. Thus, breast epithelial cell oncogenic activation and stromal fibroblast transition to CAFs are linked through the IGFs/IGF‐1R axis, which directly promotes TME remodeling and increases tumor invasion.
Comparison of contingent and noncontingent access to therapy dogs during academic tasks in children with autism spectrum disorder
Authors: Protopopova Alexandra , Matter Ashley L. , Harris Breanna N. , Wiskow Katie M. , Donaldson Jeanne M.
Published: August 2019

This study compared contingent and noncontingent access to therapy dogs during educational tasks for children with autism spectrum disorder using a multielement design. The experimenters assessed whether initial preference for the dog predicted reinforcer efficacy and how preference changed across time. A higher response rate during contingent dog sessions than baseline sessions occurred for 4 out of 5 participants, suggesting that the dog functioned as a reinforcer. One participant engaged in a high rate of responding in both contingent and noncontingent dog conditions. Preference assessments revealed idiosyncrasies, suggesting that further research is needed into the predictive nature of initial preference assessments with animals as part of the stimulus array. The experimenters also analyzed salivary cortisol before and after sessions to determine if learning about the upcoming interaction with a dog reduced salivary cortisol in children. Cortisol was variable across participants, with only some deriving a potential physiological benefit from expecting to interact with the dog.
Bioactive glass and high‐intensity lasers as a promising treatment for dentin hypersensitivity: An in vitro study
Authors: Lee Ester M. R. , Borges Roger , Marchi Juliana , de Paula Eduardo Carlos , Marques Márcia M.
Published: August 2019

This in vitro study aimed to analyze the physical and chemical characteristics of the hypersensitive human dentin‐like surface after application of a bioactive glass (BG) paste (BG/Ac) irradiated or not with high‐power lasers. Dentin specimens were treated with 17% Ethylenediamine tetraacetic acid (EDTA) solution to mimic a hypersensitive dentin and then submitted to neodymium: yttrium–aluminum–garnet (Nd:YAG) laser or CO2 laser irradiation prior and after application of BG/Ac. Characterizations were performed by using X‐ray diffraction, Fourier transformed infrared spectroscopy, scanning electron microscopy, and energy dispersive X‐ray spectroscopy. The results suggested that application of BG/Ac by itself caused some obstructions of dentinal tubules. Nd:YAG laser irradiation reduced the opening of the dentinal tubules with no changes in the collagen structure. CO2 laser irradiation caused dentin melting and resolidification along with cracks and chemical changes in collagen fibers. However, when BG/Ac paste was irradiated with lasers, a sequence of surface reactions between glass and dentin interface led to the formation of an amorphous hydroxyapatite layer, similar to that of an inorganic component of the normal dentin. Moreover, BG/Ac was able to prevent the formation of cracks and degradation of collagen fibers caused by CO2 irradiation. Overall, this study supports that application of BG/Ac paste irradiated by high‐power laser could represent an effective and long‐lasting therapeutic approach for dentin hypersensitivity.
Effects of Upadacitinib Coadministration on the Pharmacokinetics of Sensitive Cytochrome P450 Probe Substrates: A Study With the Modified Cooperstown 5+1 Cocktail
Authors: Mohamed Mohamed‐Eslam F. , Feng Tian , Enejosa Jeffrey V. , Fisniku Ogert , Othman Ahmed A.
Published: August 2019

The aim of this study was to characterize the effects of upadacitinib, a Janus kinase 1 inhibitor, on in vivo activity of different cytochrome P450 (CYP) enzymes using a cocktail approach. Healthy subjects (n = 20) received single oral doses of the modified Cooperstown 5+1 cocktail drugs (midazolam [CYP3A], caffeine [CYP1A2], warfarin + vitamin K [CYP2C9], omeprazole [CYP2C19], and dextromethorphan [CYP2D6]) without upadacitinib and on day 11 (midazolam) or 12 (all other probes) of a 15‐day regimen of upadacitinib 30 mg once daily (extended‐release formulation). Serial blood samples and 12‐hour urine samples were collected for assays of the probe substrates and select metabolites. The ratio (90%CI) of area under the plasma concentration‐time curve from time 0 to infinity (AUCinf) central values when the cocktail drugs were administered with upadacitinib relative to when administered alone were 0.74 (0.68‐0.80) for midazolam, 1.22 (1.15‐1.29) for caffeine, 1.11 (1.07‐1.15) for S‐warfarin, 1.07 (0.95‐1.22) for dextromethorphan, and 0.82 (0.72‐0.94) for omeprazole. The ratio (90%CI) was 1.09 (1.00‐1.19) for 5‐hydroxy‐omeprazole to omeprazole AUCinf ratio and 1.17 (0.97‐1.41) for dextromethorphan to dextrorphan 12‐hour molar urinary ratio. Upadacitinib 30 mg once daily (a dose that is twice the optimal dose in rheumatoid arthritis based on phase 3 results) has a limited effect on CYP3A activity (26% decrease in exposure of midazolam, a sensitive CYP3A substrate) and no relevant effects on CYP1A2, CYP2C9, CYP2C19, or CYP2D6 activity in vivo. No clinically relevant changes in plasma exposures are expected for drugs that are substrates for the evaluated CYP enzymes when coadministered with upadacitinib.
Evaluation of the Effect of 5 QT‐Positive Drugs on the JTpeak Interval — An Analysis of ECGs From the IQ‐CSRC Study
Authors: Darpo Borje , Benson Charles , Brown Randy , Dota Corina , Ferber Georg , Ferry Jim , Jarugula Venkat , Keirns James , Ortemann‐Renon Catherine , Pham Thuan , Riley Steve , Sarapa Nenad , Ticktin Mark , Zareba Wojciech , Couderc Jean‐Philippe
Published: August 2019

The JTpeak interval has been proposed as a new biomarker to demonstrate mixed ion channel effects, potentially leading to reduced late‐stage electrocardiogram (ECG) monitoring for mildly QT‐prolonging drugs. ECG waveforms from the IQ‐CSRC study were used. Twenty healthy subjects were enrolled with 6 subjects on placebo and 9 subjects on each of 5 mildly QT‐prolonging drugs — moxifloxacin, dofetilide, ondansetron, dolasetron, and quinine — and 1 negative drug, levocetirizine. A vector magnitude lead was derived from 12‐lead ECGs, and measurements were made on a median beat from three 10‐second replicates. Data were analyzed using a linear concentration‐response model with QTcF and heart rate corrected JTpeak (JTpeak_c) as dependent variables. For moxifloxacin, dofetilide, and ondansetron, all pure hERG blockers, slopes of the concentration (C)‐QTcF and C‐JTpeak_c relationships were positive and statistically significant. With the prespecified linear model, the predicted effects on ΔΔQTcF and ΔΔJTpeak_c were 11.4 and 9.4 milliseconds for moxifloxacin at the geometric mean Cmax on day 1, 9.0 and 11.7 milliseconds for dofetilide and 11.5, and 7.9 milliseconds for ondansetron, respectively. In contrast, dolasetron and quinine, both with additional ion channel effects, prolonged QTcF with a positive C‐ΔQTcF slope and predicted ΔΔQTcF effect on day 1 of 6.2 and 11.4 milliseconds, whereas the C‐ΔJTpeak_c slope and the predicted ΔΔJTpeak on day 1 were negative (−0.3 and −7.5 milliseconds per ng/mL). Pure hERG‐blocking drugs prolonged both the QTc and the JTpeak_c intervals, whereas drugs with mixed ion channel effects, including peak sodium inhibition, prolonged QTcF but not the JTpeak_c interval.
Semi‐automatic combustion of environmental and biological samples on Oxidizer M307 and equivalents: New solutions for background reduction
Authors: Simion Corina A. , Mocanu Nicolae , Gaza Oana , Stanciu Iuliana M. , Sava Gabriela O. , Stefan Bianca M. , Sava Tiberiu B. , Pacesila Doru Gh. , Chiriloaei Francisca , Nechita Constantin
Published: August 2019

The aim is to introduce and characterize a new experimental demonstrative model contributing to the increase of measurement accuracy, in terms of minimum detectable activity (MDA) and background reduction, for the analysis of samples having low concentrations in tritium and radiocarbon on Quantulus 1220. The clue is related to the qualitative and quantitative differences between tritium and carbon‐14 inventories of the pulp used to manufacture the cups involved in noncatalytic combustion of samples by flame oxidation method. The quality of the experimental results depends on the temporal origin of the wood from which the pulp/cellulose was extracted/purified, the specific inventory contributing to the threshold level of the MDA for the beta‐emitting radionuclide to be investigated. Finally, the aim is to create and to use such a 100% old cellulose combustion cups for determining low concentrations of these radionuclides. It may be obtained by an adapted technology following the literature data and may be recommended for routine analyses of environmental samples coming from areas with no nuclear or minor nuclear influences, and also for low‐level biological samples. This first attempt resulted in improvement of measurement performances up to 400% for carbon‐14 and by approximately 50% for tritium.
The clinical profiles of female patients with Fabry disease in Latin America: A Fabry Registry analysis of natural history data from 169 patients based on enzyme replacement therapy status
Authors: Martins Ana M. , Cabrera Gustavo , Molt Fernando , Suárez‐Obando Fernando , Valdés Régulo A. , Varas Carmen , Yang Meng , Politei Juan M.
Published: August 2019

Background

Fabry disease is an X‐linked lysosomal storage disorder with heterogeneous clinical expression in female patients ranging from asymptomatic to severe clinical presentations as in classic males. We assessed clinical profiles and compared natural history data of female patients eventually initiated on enzyme replacement therapy (“ERT‐recipients”) with those remaining untreated (“ERT‐naïve”).

Methods

We analyzed Fabry Registry data from 93 ERT‐recipients, collected prior to ERT initiation, and 76 ERT‐naïve females with classic or unclassified phenotypes from four Latin American countries and evaluated Fabry symptoms, interventricular septum thickness, left ventricular posterior wall thickness, estimated glomerular filtration rate, and severe clinical events.

Results

For 169 patients with available data, median age of first Fabry symptom manifestation was 12.7 years with peripheral pain as predominant first symptom, and diagnostic delay of 10.3 years from the first reported symptom. Female patients had high symptomatic burden during natural history follow‐up, with 83% reporting peripheral pain, 69%‐79% cold/heat intolerance or abnormal sweating, and 32% gastrointestinal symptoms. ERT‐recipients reported similar age at first symptom as ERT‐naïve patients but they were older at diagnosis (median 39.2 vs 24.4 years, P < .01) and last follow‐up (median 43.4 vs 28.2 years, P < .01). Reported Fabry symptom frequencies and abnormal echocardiography findings were higher in ERT‐recipients. Functional renal assessments were normal and similar.

Conclusions

Female patients from Latin America have notable diagnostic delays and high symptomatic burden. ERT was prescribed late in females with advanced age at diagnosis and advanced disease. There remained many female patients who had been diagnosed at younger age, had substantial Fabry manifestations, but did not receive disease‐specific treatment.
Salivary cytomegalovirus excretion in children in daycare centers and home care facilities in Japan
Authors: Watanabe Masahiro , Torigoe Sadayoshi , Ito Masahiro , Negoro Manami , Suga Shigeru
Published: August 2019

Cytomegalovirus (CMV) is the most common cause of congenital viral infection in developed countries. The incidence of in utero infection is high in pregnant women who are CMV antibody negative. An important infection route is in contact with children who attend daycare centers (DCCs). However, there are few reports on CMV excretion in children at DCCs in Japan. Saliva samples were collected twice during a 6‐month interval from children attending one of two DCCs (DCC1 and DCC2 groups) and from those receiving home care (HC group). The samples were used to quantitatively evaluate CMV using real‐time polymerase chain reaction and to determine glycoprotein B (gB) genotypes. The percentage of subjects who demonstrated CMV excretion in either the first or second sample collection was higher in the DCC groups than in the HC group, with incidences in the DCC1, DCC2, and HC groups of 53.4% (n = 47 of 88), 23.9% (n = 16 of 67), and 12.7% (n = 7 of 55), respectively. Compared with the DCC2 group, the DDC1 group had a higher incidence of CMV excretion and included more subjects with a high number of viral copies. In both DCC groups, the incidence of CMV excretion was highest in children younger than 3 years of age. In all three groups, the predominant genotypes were gB1 and gB3. Based on the higher incidence of CMV excretion in the DCC groups compared with the HC group, it is considered that CMV infection is acquired mainly in DCCs in children under the age of 3.
Association Between Gait Kinetics and Symptomatic Progression in Persons With Patellofemoral With/Without Concurrent Tibiofemoral Osteoarthritis
Authors: Liao Tzu‐Chieh , Teng Hsiang‐Ling , Link Thomas M. , Majumdar Sharmila , Souza Richard B.
Published: August 2019

To identify the biomechanical risk factors associated with symptomatic progression at 1‐year follow‐up in persons with patellofemoral joint (PFJ) osteoarthritis (OA). Patients’ self‐reported Knee Injury and Osteoarthritis Outcome Score questionnaires, magnetic resonance (MR) imaging, and three‐dimensional gait analysis were obtained in 53 subjects with PFJ OA at baseline and after 1 year. Joint OA was diagnosed on knee MR images if cartilage lesions existed. Progression was defined by worsening of patients’ self‐reported symptoms from baseline to 1 year exceeding the minimal detectable change score. Analysis of covariance was used to compare peak knee flexion moment, knee flexion moment impulse, and vertical ground reaction force loading rate between progressors and non‐progressors. Seven (13.2%) subjects exhibited progression in self‐reported symptoms at 1‐year follow‐up. When comparing to non‐progressors, significantly higher peak knee flexion moment during first half of stance (p = 0.017) and higher moment impulse during the both halves of stance were observed among progressors (p = 0.020–0.040). Persons with symptomatic PFJ OA progression with or without concurrent tibiofemoral OA exhibited abnormal joint loading mechanics when compared with individuals who did not progress. Further work is needed to determine if modification to these loading variables results in a change in the symptomatic progression in these individuals. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2593–2600, 2019
The role of socioeconomic status and psychosocial factors on gingivitis in socially disadvantaged adolescents
Authors: Koga Reyce , Herkrath Ana Paula Correa de Queiroz , Vettore Mario Vianna , Herkrath Fernando José , Rebelo Vieira Janete Maria , Pereira Juliana Vianna , Rebelo Maria Augusta Bessa , Queiroz Adriana Corrêa de
Published: August 2019

Background

Evidence on the possible influence of social and psychosocial factors on gingival status in socially disadvantaged children is scarce. The aim of this study is to assess the relationships among socioeconomic status, pattern of dental visits, self‐esteem, oral health beliefs, toothbrushing frequency, oral hygiene effectiveness, and gingivitis in low social status adolescents.

Methods

A cross‐sectional study was performed involving 406 12‐year‐old students recruited in Manaus, Brazil. Socioeconomic status (family income, parent's schooling, number of goods, and household crowding), self‐esteem, oral health beliefs, and frequency of toothbrushing were collected through self‐completed questionnaires. Gingival status (bleeding on probing) and oral hygiene effectiveness (dental calculus) were evaluated by calibrated dentists through oral examinations. Structural equation modeling assessed the direct and indirect relationships between variables guided by a theoretical model.

Results

The prevalence of gingivitis was 77.6%. Worse socioeconomic status and poor oral hygiene effectiveness directly predicted gingival bleeding. Socioeconomic status was also linked to toothbrushing frequency. Positive oral health beliefs and higher self‐esteem predicted higher frequency of toothbrushing. The latter was directly linked to greater oral hygiene effectiveness. Oral health beliefs and self‐esteem indirectly predicted gingival bleeding via toothbrushing frequency and oral hygiene effectiveness.

Conclusion

The present findings suggest the importance of socioeconomic status and psychosocial factors on gingival status in underprivileged adolescents. Poor oral hygiene mediated the associations between psychosocial factors and gingival status.
A new late Pleistocene subfossil site (Tsaramody, Sambaina basin, central Madagascar) with implications for the chronology of habitat and megafaunal community change on Madagascar's Central Highlands
Authors: Samonds Karen E. , Crowley Brooke E. , Rasolofomanana Tojoarilala Rinasoa Nadia , Andriambelomanana Miora Christelle , Andrianavalona Harimalala Tsiory , Ramihangihajason Tolotra Niaina , Rakotozandry Ravoniaina , Nomenjanahary Zafindratsaravelo Bototsemily , Irwin Mitchell T. , Wells Neil A. , Godfrey Laurie R.
Published: August 2019

Madagascar is a complex ‘biodiversity hotspot’ with a rapidly dwindling biota. The Late Quaternary subfossil record includes many extinct species whose loss is attributed to natural climate change and human impacts. Investigation of the chronology of these events is challenging because few localities document pre‐Holocene communities not impacted by humans. Caves with extinct lemurs of large body size comprise some of Madagascar's richest subfossil sites, but provide only a limited window into the island's past. Open highland sites may have fewer primates, but may better document other megafauna, and allow the analysis of the role of the Central Highlands as refugia and as corridors for the dispersal of vertebrates before and after human arrival. Here we present a new subfossil site, Tsaramody (Sambaina basin, Central Madagascar), a high‐altitude wetland area that preserves a diverse late glacial and postglacial vertebrate community. Tsaramody bears testimony to fluctuations in the highland flora during the transition from glacial to postglacial conditions, and the composition of a highland vertebrate community before humans arrived. We compare its biota to those of other sites to begin to document the decline and disappearance of megafauna from some of Madagascar's open ecosystems – wetlands dominated by hippopotamuses and crocodylians. © 2019 John Wiley & Sons, Ltd.
Results of a Prospective Study to Evaluate the Impact of Point‐of‐Care Ultrasound in the Enhancement of Gastrointestinal Bleeding Risk Scores
Authors: Tung Chen Yale , Blancas Gómez‐Casero Rafael , Quintana Díaz Manuel , Villén Villegas Tomás , Cobo Mora Julio , Carballo Cardona César
Published: August 2019

Objectives

Gastrointestinal (GI) bleeding is a common illness seen in the emergency department. The prognosis varies from self‐limited to potentially life threatening. Currently available GI bleeding risk scores have only a modest predictive value, limiting their wide implementation. The aim of this study was to assess the association and capability of point‐of‐care ultrasound (POCUS) used by emergency physicians to improve common GI bleeding scores for predicting complications and long‐term outcomes of patients with GI bleeding, which to our knowledge have never been studied.

Methods

Between August 2015 and April 2017, 203 hemodynamically stable patients with acute GI bleeding admitted to the emergency department were prospectively investigated. Using ultrasound, we measured the inferior vena cava diameter, cardiac output with surrogate markers such as the velocity time integral before and after the passive leg‐raising test, and the presence of systolic obliteration of the left ventricle. The Rockall and Glasgow‐Blatchford scores were calculated for patients with upper GI bleeding and the Velayos score for lower GI bleeding. The patients had follow‐up during hospitalization and 30 days later to assess for early and late adverse events (AEs). Then we integrated the ultrasound findings of hypovolemia into the GI bleeding scores, assessing the capability to detect AEs.

Results

In our cohort, patients with upper GI bleeding who showed left ventricle kissing walls had a worse evolution, with a greater presence of late AEs (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.32–10.96; P = .01). Patients with lower GI bleeding who showed a collapse of the inferior vena cava (>50%) after passive leg raising had a greater presence of early AEs (OR, 3.6; 95% CI, 1.46–9.00; P = .004). The predictive performance of the Rockall score (receiver operating characteristic analysis: area under the curve [AUC], 77.6%; 95% CI, 66.3%–88.8%) increased with POCUS (AUC, 80.3%; 95% CI, 69.5%–91.1%); that of the Glasgow‐Blatchford score (AUC, 72.5%; 95% CI, 59.9%–85.2%) increased with POCUS (AUC, 73.2%; 95% CI, 61.1%–85.4%); and that of Velayos score (AUC, 55.7%; 95% CI, 42.5%–69.0%) also increased with POCUS (AUC, 72.2%; 95% CI, 61.1%–83.3%).

Conclusions

The use of POCUS in GI bleeding is feasible and enhances common GI bleeding risk scores, showing better predictive performance in detecting AEs.
The utility of intraoperative navigation of the temporal bone for otolaryngology resident training
Authors: Schwam Zachary G. , Kaul Vivian Z. , Cosetti Maura K. , Wanna George B.
Published: August 2019

Objectives

To determine whether image guidance improves dissection quality among residents in the temporal bone lab and to gauge their reactions to its use.

Methods

Prospective cohort study of nine otolaryngology residents who dissected cadaveric temporal bones with and without image guidance in the temporal bone laboratory. Quality of dissection was measured with the Welling scale. A survey was administered assessing their interactions with the navigation system.

Results

There was no significant difference in quality of dissection for the majority of structures or number of major errors with use of image guidance. Dissection quality of the tegmen (4.67 vs. 5.67, P = .034) and sinodural angle (0.83 vs. 1.56, P = .005) was superior in the non‐navigation specimens. The majority of residents reported increased confidence with locating several critical anatomic structures and found the system intuitive to use. Nearly all thought it would be helpful in revision cases or for aural atresia.

Conclusion

Image guidance did not improve quality of temporal bone dissection or number of major errors in this cohort of residents, but the majority found it intuitive and increased confidence in finding several structures. Navigation systems may play an important adjunctive role in resident education and further work is required to determine its optimal use.

Level of Evidence

NA

Laryngoscope, 130:E368–E371, 2020
Effects of NaCl, SO2, NH3, O3, and ultraviolet light on atmospheric corrosion of Zn
Authors: Onye Jermain , Frankel Gerald S.
Published: August 2019

The atmospheric corrosion behavior of Zn was studied in laboratory environments containing constituents that have not previously received much attention, in particular, humidity, SO2, NH
3, and O
3, along with ultraviolet (UV) light irradiation and a preloading of NaCl. After exposure, corrosion rates were measured using mass loss, and corrosion products were identified by X‐ray diffraction, Fourier transform‐infrared spectroscopy, and energy dispersive spectroscopy. In this study, UV light and O
3 did not significantly affect the Zn corrosion rate in the absence of Cl
−. However, when NaCl was present, UV light inhibited the Zn corrosion rate below 90% relative humidity (RH) and accelerated the Zn corrosion rate at 99% RH. The presence of UV light also increased the formation of zinc hydroxyl sulfate and gordaite when exposed to 120 parts per billion (ppb) SO
2 and NaCl. The combination of SO
2 and O
3 with the preloading of NaCl increased the corrosion rate of Zn compared with NaCl alone. NH
3 at a concentration of 550 ppb did not have a significant effect on the Zn corrosion rate.
Two‐dimensional elastic full‐waveform inversion of Love waves in shallow vertically transversely isotropic media: synthetic reconstruction tests
Authors: Krampe Valérie , Pan Yudi , Bohlen Thomas
Published: August 2019

In most shallow‐seismic applications of full‐waveform inversion, the subsurface is assumed to be isotropic, although near‐surface materials may exhibit strong seismic anisotropy. Ignoring anisotropy will lead to inexact solutions when simulating wave propagation or imaging the subsurface using full‐waveform inversion. For shallow structures, vertically transversely isotropic media provide a suitable approximation due to the fine horizontal layering of the sediments. We investigate the effects of anisotropy on surface waves and on shallow‐seismic full‐waveform inversion in vertically transversely isotropic media. The comparisons of seismograms calculated in isotropic and vertically transversely isotropic models show that the sensitivity of full‐waveform inversion towards anisotropy is significantly higher for Love waves than for Rayleigh waves. This observation indicates that it is more promising to perform full‐waveform inversion on Love waves rather than on Rayleigh waves to identify anisotropy of near‐surface materials. Therefore, we performed synthetic two‐dimensional reconstruction tests of anisotropic full‐waveform inversion using only shallow‐seismic Love waves. These tests revealed that the parameters describing vertical transverse isotropy can be accurately reconstructed by full‐waveform inversion. Although the inversion for density is still problematic, this does not affect the results for the seismic velocities in a significant way. The tests on synthetic data thus prove the general applicability and the benefits of an anisotropic inversion of shallow‐seismic Love waves, which can provide a more comprehensive subsurface characterization in shallow anisotropic media.
Overweight Patterns Between Childhood and Early Adulthood and Esophageal and Gastric Cardia Adenocarcinoma Risk
Authors: Petrick Jessica L. , Jensen Britt W. , Sørensen Thorkild I.A. , Cook Michael B. , Baker Jennifer L.
Published: August 2019

Objective

Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are among the most rapidly increasing cancers in Western countries. Elevated BMI in adulthood is a known risk factor, but associations in early life are unclear.

Methods

This study assessed weight change between childhood and early adulthood in relation to EA/GCA. Measured weights and heights during childhood (7‐13 years) and early adulthood (17‐26 years) were available for 64,695 young men from the Copenhagen School Health Records Register and the Danish Conscription Database. Individuals were categorized as having normal weight or overweight. Linkage with the Danish Cancer Registry identified 275 EA/GCA cases. Hazard ratios (HR) and 95% CI were estimated using Cox proportional hazards regression.

Results

The risk of EA/GCA was 2.5 times higher in men who were first classified as having overweight at age 7 (HR = 2.49; 95% CI: 1.50‐4.14) compared with men who were never classified as having overweight. Men who had persistent overweight at ages 7 and 13 and in early adulthood had an EA/GCA risk that was 3.2 times higher (HR = 3.18; 95% CI: 1.57‐6.44). However, there was little evidence of increased EA/GCA risk for men with overweight during childhood and subsequent remittance by early adulthood.

Conclusions

Persistent overweight in early life is associated with increased EA/GCA risk, which declines if body weight is reduced.
Agency Helps Rural Utilities Navigate Path to Infrastructure Funding
Authors: Dorava Joseph M.
Published: August 2019

Small systems face steep costs to rebuild and maintain drinking water and wastewater facilities. The US Department of Agriculture's Office of Rural Development helps communities with limited resources tackle the challenges involved with financing projects.
Adaptive hinged fiber reinforced plastics with tailored shape memory alloy hybrid yarn
Authors: Ashir Moniruddoza , Nocke Andreas , Hanke Uwe , Cherif Chokri
Published: August 2019

Currently, there is an urgent need to reduce the CO2 footprint and simultaneously improve resource efficiency. Hence, conventional construction materials are increasingly being replaced by fiber reinforced plastics, which can be used more efficiently by integration of actuator materials for the formation of adaptive fiber reinforced plastics. This paper presents the development of adaptive hinged fiber reinforced plastics based on shape memory alloys, which were structurally integrated into reinforcing fabrics by weaving technology. Prior to weaving, the SMA was converted into hybrid yarns in the form of core‐sheath structures by means of friction spinning technology. The produced functionalized fabrics were varied by the distance between two adjacent SMAs and their hinged width. Subsequently, the deformation behavior of adaptive fiber reinforced fabrics was tested, and results were evaluated in terms of quasi‐static and dynamic aspects. Results revealed that the maximum deformation of adaptive FRP was tripled by increasing the hinged width from 50 to 150 mm and doubled by reducing the distance between two adjacent SMAs from 20 to 10 mm.
Auxin Induces Widespread Proteome Remodeling in Arabidopsis Seedlings
Authors: Clark Natalie M. , Shen Zhouxin , Briggs Steven P. , Walley Justin W. , Kelley Dior R.
Published: August 2019

It is known that auxin induces rapid gene expression changes throughout plant development, but how these transcriptional responses relate to changes in protein abundance is not well characterized. This report identifies early auxin responsive proteins in whole Arabidopsis seedlings using an isobaric tags for relative and absolute quantification‐based quantitative proteomics approach. Approximately 25% of the detected proteins (1045 out of 4257 proteins) are auxin responsive, which is in line with the central role of auxin in the regulation of plant growth and development. Several well‐known auxin pathway proteins are identified as differentially expressed, validating this quantitative proteomics approach. Additionally, functional categorization of these auxin responsive proteins indicates that rapid and complex metabolic changes occur in seedlings in response to auxin, including lipid metabolism. Altogether, these data describe novel auxin‐regulated proteins and are an excellent resource for identifying new downstream signaling components related to auxin‐mediated plant growth and development.
A user centered design approach to development of an online self‐management program for cancer survivors: Springboard Beyond Cancer
Authors: Leach Corinne R. , Diefenbach Michael A. , Fleszar Sara , Alfano Catherine M. , Stephens Robert L. , Riehman Kara , Hudson Shawna V.
Published: August 2019

Objective

The American Cancer Society and the National Cancer Institute launched and evaluated a personalized online program leveraging behavioral science principles to help people self‐manage physical and emotional symptoms, improve communication skills, and lead healthier lives during and after a cancer diagnosis.

Methods

Cancer survivors were recruited from an academic medical and a community clinical setting (N = 40) to complete in‐person user testing of the Springboard Beyond Cancer website, which included action decks and content to promote self‐management. Action decks were printable or savable collections of information and action steps related to a cancer topic or treatment side effect. Participants performed structured tasks to evaluate the program's content and usability. Comments and reactions were recorded, and qualitative thematic analyses were conducted.

Results

Most participants successfully found information about fatigue (95%), pain (83%), sexual side effects (90%), and support groups (85%). Survivors, particularly those in treatment, found information on the site to be clear, concise, and meeting their needs. Use of action decks to create self‐management plans was inconsistent. Survivors reported needing more instruction and support within the program on how to best utilize enhanced functionality in action decks to prioritize their most pressing concerns.

Conclusions

Early stakeholder engagement throughout the multiple phases of prototyping and deployment are needed to fully maximize end user engagement. Providing actionable self‐management content and activating tools to cancer survivors via an eHealth program is a feasible and scalable approach to increasing access to self‐management tools and addressing cancer survivor needs.
Intraoperative validation of bone cut accuracy of a pinless smart touch‐screen navigation system device in total knee arthroplasty
Authors: Ulivi Michele , Orlandini Luca Claudio , Meroni Valentina , Castoldi Daniele , Lombardo Michele Davide Maria , Peretti Giuseppe M.
Published: August 2019

Purpose

Primary objective in most of the published literature on computer‐assisted total knee arthroplasty (TKA) has so far been the comparison of axial alignment and components position, obtained either through navigation systems or through conventional instrumentation. We have found no studies aimed at assessing the intraoperative reliability of a navigation system in relation to bone cuts height. Aim of our study was therefore to establish bone cut accuracy of a pinless navigation system.

Methods

From January 2014 to February 2016, 44 consecutive patients requiring total knee replacement (TKR) were enrolled in a prospective study. Primary end point of the study was to assess the accuracy of the DASH iPOD TOUCH Navigation System (Brainlab AG, Feldkirchen, Germany) by measuring the real thickness of both tibial and femoral osteotomies. We compared the data indicated by the navigation system with the intraoperative anatomical measurements done with the aid of a caliper. In addition, the radiographic alignment was compared with the data derived from the navigator.

Results

The device proved to be precise. Differences between the two methods of measurement are distributed over a millimeter range. Radiological measurements showed that 95.5% of tibial components were within the range of 3° varus/valgus; same results were obtained by the navigation system; instead, 90.1% of femoral components were within the range of 3° varus/valgus based on the radiological measurement, whereas according to the navigation system, 86.4% were in this range.

Conclusions

The DASH iPOD TOUCH Navigation System is a precise and reliable instrument to assist in TKA navigation.
A distributed leader‐following tracking controller using delayed control input information from neighbors
Authors: Zhu Bo , Chen Jingyang , Wang Jia
Published: August 2019

In this paper, we propose a simple, continuous, and distributed controller for the second‐order multiagent system to achieve leader‐following trajectory tracking, by exploiting the control input information of neighbors (CIIN) and using proportional‐derivative (PD) control in terms of local neighborhood synchronization error. A constant time delay is introduced in the CIIN as a design parameter to avoid the algebraic loop issue arising from the control input coupling. We develop an easily testable condition on the PD gains to ensure that the resulting neutral‐type error system is input‐to‐state stable for an arbitrary bounded delay, and prove that when the leader's acceleration is a Lipschitz continuous function with respect to time, the ultimate bound of tracking errors is strictly increasing with respect to the introduced time delay. Moreover, we analyze the robustness of the controller with respect to model uncertainties and show its potential advantages over two existing controllers in balancing the steady‐state tracking precision, the communication cost, and the continuity of controller signal. Finally, extensive simulations are conducted to show the effect of the delay on system stability, to verify the condition on PD gains, to confirm the robustness of the controller, and to demonstrate the detailed advantages.
Facile Synthesis of 3‐Hydroxy Oxindole by a Decarboxylative Aldol Reaction of β‐Ketoacid and Isatin in WERSA
Authors: Dwivedi Kartikey Dhar , Reddy Marri Sameer , Kumar Nandigama Satish , Chowhan L. Raju
Published: August 2019

Facile synthesis of bioactive 3‐hydroxy‐oxindole by decarboxylative aldol reaction via in‐situ generated methyl enolate of β‐ketoacid and isatin in Water Extract of Rice Straw Ash (WERSA) is described. This method provides clean, simple and useful alternative to synthesize 3‐hydroxy‐oxindole. The products were isolated in excellent yield without using column chromatography. The green chemistry matrices calculated, and it also shows green protocol used.
Enhancing Electroreduction of CO2 to Formate of Pd Catalysts Loaded on TiO2 Nanotubes Arrays by N, B‐Support Modification
Authors: Bai Bing , Chen Qingsong , Zhao Xiuhui , Zhuo Dehuang , Xu Zhongning , Wang Zhiqiao , Wu Mingyan , Tan Hongzi , Peng Siyan , Guo Guocong
Published: August 2019

Electrochemical reduction of CO2 to formate in aqueous electrolyte is a potentially effective route for energy storage and resource utilization of CO2. Pd is known as excellent catalyst for CO2 electrochemical reduction, however, the selectivity to formate on Pd catalysts was limited to narrow potential window which may restrict their applications. Herein, N, B‐doped TiO2 nanotube arrays (TNTA) were designed and synthesized to reveal the metal‐support interaction and its effects on the electrochemical reduction of CO2. The N, B doped TNTA supported Pd catalysts were found to highly enhance the activity with 3.7 and 4.6 times and the selectivity with 2 and 2.6 times comparing respectively to undoped one for CO2 electrochemical reduction to formate at −1.0 V vs SCE. The enhancement of formate production can be attributed to the modification of electron structure facilitating the stabilization of active Pd hydride phase and suppressing the CO formation. This study will shed light on strategies to improve the performance of catalysts via the functionalization of supports in field of CO2 selective electrochemical reduction.
Substituents Effects of Organic Linkers on Rotational Energy Barriers in Metal‐Organic Frameworks
Authors: Sinha Nilima , Deshpande Indraneel , Pakhira Srimanta
Published: August 2019

Metal‐organic frameworks (MOFs) are a new kind of solid porous materials built from metal cations and organic bridging linkers or ligands. We considered a model MOF system using various organic linkers with Zn2+ cations, and studied their equilibrium geometry, structure, potential energy curves (PECs), rotational dynamics, and rotational barriers of the linkers by employing first‐principles based DFT methods. We investigated the rotational and dynamical behaviors of the organic linkers in the MOFs. We found that the structural parameters and rotational barrier of the model MOF containing 1,4‐benzendicarboxylate (BDC) linker are in excellent agreement with previous experiments. The B3LYP rotational energy barrier of the model MOF containing 1,4‐naphthalenedicarboxylate (NDC) linker makes a replica of the previous experimental value. The present computation found that the rotational energy barriers differ considerably depending on the linkers and the substituent effects on them, oscillating from the largest barrier 56.5 kJ/mol (for BDC) to the lowest one 15.3 kJ/mol (for 2,3,5,6‐tetrafluoro‐1,4‐benzenedicarboxylate (TFBDC)). This study expands the opportunity of innovative reticular material chemistry to design novel flexible MOFs with ultrahigh working capacity and small rotational barrier to include linkers having the common acrylate connectivity. We envisage that this new class of MOFs with small rotational energy barrier will be beneficial in a variety of applications including H2‐storage, gas storage and separation, adsorption, sensors, and many others.
Green Optimization of the First Steps for the Synthesis of a Novel Surfactant: Towards the Elimination of CMR Solvents and the Drastic Reduction of the Used Solvent Volume
Authors: Giry Clément , Bertrand David , Cecutti Christine , Brossard Clarisse , Moreau Ella , Thiébaud‐Roux Sophie , Vaca‐Garcia Carlos , Vedrenne Emeline
Published: August 2019

In this report, the first steps of the synthesis of a novel surfactant have been described. Each stage has been optimized to abide by the principles of green chemistry. The replacement of CMR (Carcinogenic, Mutagenic, Reprotoxic) solvents by 4‐MTHP (4‐methyltetrahydropyran) led to the improvement of the overall yield and to the drastic reduction of the total organic solvent volume used in the process.
Total Synthesis of 2‐(2‐Ketoalkyl)‐piperidine Alkaloids (+)‐ Pelletierine, (+)‐Haloxynine and (‐)‐N‐Methyl‐pelletierine via Regioselective Wacker Oxidation
Authors: Mhaldar Shashank N. , Tilve Santosh G.
Published: August 2019

A practical synthesis of naturally occurring piperidine alkaloids (+)‐pelletierine, (+)‐haloxynine and (‐)‐N‐methyl‐pelletierine is described from (‐)‐pipecolinic acid using Wittig reaction and Wacker oxidation as the key steps. The protocol exploits the regioselective oxidation of the internal olefins.
Differential variation and expression analysis
Authors: Bar Haim , Schifano Elizabeth D.
Published: August 2019

We propose an empirical Bayes approach using a three‐component mixture model, the L2N model, that may be applied to detect both differential (mean) expression and variation. It consists of two log‐normal components (L2) for differentially expressed (dispersed) features: one component for underexpressed (dispersed) features and the other for overexpressed (dispersed) features, and a single normal component (N) for nondifferentially expressed (dispersed) features. Simulation results show that L2N can capture asymmetries in the numbers of overexpressed and underexpressed (dispersed) features (e.g., genes) when they exist and can provide a better fit to data in which the mixture component distributions are not well separated while also performing well under symmetry and separation. The L2N model is implemented in an R‐driven, user‐friendly, graphical interface called DVX, for differential variation and expression analysis, which does not require the user to have R programming knowledge. The interface also includes an implementation of differential expression analysis via the limma package, and a differential variation and expression analysis using a three‐way normal mixture model. It offers a set of diagnostics plots, data transformation tools, and report generation in Microsoft Excel‐ and Word‐compatible formats. The interface is available on the web at https://haim-bar.uconn.edu/software/DVX/.
Preclinical translation of exosomes derived from mesenchymal stem/stromal cells
Authors: Elahi Fanny M. , Farwell D. Gregory , Nolta Jan A. , Anderson Johnathon D.
Published: August 2019

Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell-autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane-associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome-based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC-derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC-derived exosome-based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC-exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation.
A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α
Authors: Monick Sarah , Mohanty Vineet , Khan Mariam , Yerneni Gowtham , Kumar Raj , Cantu Jorge , Ichi Shunsuke , Xi Guifa , Singh Bal Ram , Tomita Tadanori , Mayanil Chandra Shekhar
Published: August 2019

In a previous study, we showed that folate receptor-α (FRα) translocates to the nucleus where it acts as a transcription factor and upregulates Hes1, Oct4, Sox2, and Klf4 genes responsible for pluripotency. Here, we show that acetylation and phosphorylation of FRα favor its nuclear translocation in the presence of folate and can cause a phenotypic switch from differentiated glial cells to dedifferentiated cells. shRNA-FRα mediated knockdown of FRα was used to confirm the role of FRα in dedifferentiation. Ocimum sanctum hydrophilic fraction-1 treatment not only blocks the folate mediated dedifferentiation of glial cells but also promotes redifferentiation of dedifferentiated glial cells, possibly by reducing the nuclear translocation of ~38 kDa FRα and subsequent interaction with chromatin assembly factor-1. Stem Cells  2019;37:1441–1454