bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications
Authors: Zhou Wei , Ma Dongrui , Tan Eng-King
Published: September 2019

CHCHD2 mutations have been identified in various neurological diseases such as Parkinson’s disease (PD), frontotemporal dementia (FTD), and Alzheimer’s disease (AD). It is also the first mitochondrial gene whose mutations lead to PD. CHCHD10 is a homolog of CHCHD2; similar to CHCHD2, various mutations of CHCHD10 have been identified in a broad spectrum of neurological disorders, including FTD and AD, with a high frequency of CHCHD10 mutations found in motor neuron diseases. Functionally, CHCHD2 and CHCHD10 have been demonstrated to interact with each other in mitochondria. Recent studies link the biological functions of CHCHD2 to the MICOS complex (mitochondrial inner membrane organizing system). Multiple experimental models suggest that CHCHD2 maintains mitochondrial cristae and disease-associated CHCHD2 mutations function in a loss-of-function manner. However, both CHCHD2 and CHCHD10 knockout mouse models appear phenotypically normal, with no obvious mitochondrial defects. Strategies to maintain or enhance mitochondria cristae could provide opportunities to correct the associated cellular defects in disease state and unravel potential novel targets for CHCHD2-linked neurological conditions.
AAGAB Mutations in 18 Canadian Families With Punctate Palmoplantar Keratoderma and a Possible Link to Cancer
Authors: Elhaji Youssef , Hedlin Cherise , Nath Anu , Price Emma L. , Gallant Christopher , Northgrave Stacey , Hull Peter R.
Published: September 2019

Background:

Punctate palmoplantar keratoderma type 1 (PPPK1) presents in late childhood to adulthood with multiple small discrete hyperkeratotic papules on palms and soles. PPPK1 is an autosomal dominant skin disease caused by AAGAB mutations. It has been suggested that PPPK1 may be associated with an increased predisposition to systemic malignancies.

Objectives:

To evaluate the presence of AAGAB mutations in Canadian families with PPPK1 and the possible increased predisposition to systemic malignancies.

Methods:

Eighteen unrelated Canadian families with PPPK1 were recruited for this study. Genomic DNA was extracted from saliva and PCR amplification was performed for all AAGAB exons and exon/intron junctions. PCR products were sequenced and analyzed for mutations. A family history of malignancy was obtained from the index case and, when possible, from other family members.

Results:

We have identified 5 heterozygous AAGAB loss of function mutations in 11 families. The mutation c.370 C>T, p.Arg124* was the most prevalent and was identified in 6 families. A splice site mutation, c.451+3delAAGT, was identified in 2 families. The other mutations c.473delG, p.Gly158Glufs*0; c.550-551insAAT, p.Gly183*; and c.505-506 dupAA, p.Asn169Lysfs*6 were each identified in 1 family. Different cancers were reported in 11 families (Table 1 and Supplemental Figure S1).

Conclusions:

AAGAB mutations were found in 11 of 18 families with PPPK1. In some families there appears to be an association with cancer.
Understanding “expert” scientists: Implications for management and organization research
Authors: Dörfler Viktor , Eden Colin
Published: September 2019

This article contributes to the debate about rigor and relevance in management and organization research. The contribution derives from an empirical inquiry into the view of the research process of acknowledged experts in scientific research: Nobel Laureates. The research was conducted through loosely structured in-depth interviews with, and background information about, 19 of these expert researchers. The analysis of the interviews suggests emergent themes of the process of successful research that are likely to be relevant to the conduct of management and organization research. We focus on three themes from our interviews: the role of the “big leap” and its relationship to intuition; the significance of seeing both the “big picture” and the detail; and the ways of building and developing successful research teams. We set out our findings from the interviews in the context of the literature from history and philosophy of science and examine the implications for management and organization research.
Contextualising Relationships Between Mothers and Practitioners: Social Structures, Causal Factors, and Generative Mechanisms
Authors: Sims-Schouten Wendy , Barton Sarah
Published: September 2019

This study seeks to build an explanation of the sociological, psychological, and political processes and practices involved in relationships between mothers and practitioners, as generative and causal powers that underlie and shape this. Critical realist’s primacy of ontology forms the starting point, with grounded theory as the epistemological force providing critical realism’s method, contextualising research, and embedding this more firmly into practice. As such, this article offers critical realist grounded theory (CRGT) as a tool for contextualising parent–practitioner relationships, drawing on retroductive argumentation, which involves moving from the level of observation and lived experiences to making (non-linear) inferences about underlying structures/mechanisms that may account for the phenomena. Thirty-four participants participated in six in-depth focus group discussions; three were with early years practitioners and three with mothers of children aged between 2 years and 4 years. Focused coding led to themes reflecting the lived experiences of mothers and practitioners, namely being valued, relationships, what happens at home, child at the centre, and when I am not there. In line with CRGT, multiple causal mechanisms (including the interpretations of each situation made by individuals) were identified that were active in the situated contexts. To improve relationships between mothers and practitioners, attention needs to be paid to the psychological, social, and political forces at play, as generative, causal, and contextual powers, that have an impact on the status and relationships of the players within this triad (mothers, practitioners, and child).
H∞ loop-shaping control of azimuthal combustion instabilities in annular combustors
Authors: Feng Sheng , Li Jingxuan
Published: September 2019

Lean combustion technique and annular geometries are preferred in aero-engines and gas turbines, which however may lead to azimuthal combustion instabilities. Active control can be used to stabilize combustion instabilities. Due to its easy use, linear feedback controllers embedded with linear flame response models under weak perturbation amplitude are typically preferred. However, flame responses to oncoming disturbances are typically nonlinear; such controllers are not guaranteed to stabilize. Model-based control strategies generally focus on axisymmetric cases, even though symmetry breaking of azimuthal thermoacoustic modes often occurs in annular combustors. This work uses an improved thermoacoustic model to simulate combustion instabilities within annular combustors, providing a platform on which control strategies development can be performed. The improved model takes into account the nonlinear flame response and the symmetry breaking of azimuthal modes. Single-input single-output control strategies targeting on these nonlinear instabilities are developed in this work. Such controllers can achieve stability for linear and nonlinear fluctuations as well as in symmetric and non-axisymmetric cases. The controllers adopt the [Formula: see text] loop-shaping control strategy and a satisfactory robust performance is obtained.
The de Morton mobility index is a feasible and valid mobility assessment tool in hospitalized patients with an acute exacerbation of chronic obstructive pulmonary disease
Authors: Camp Pat G , Sima Carmen A , Kirkham Ashley , Inskip Jessica A , Parappilly Beena
Published: September 2019

There is no accepted standard for measuring mobility in hospitalized patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The objective of this study was to assess convergent, discriminant, and known-group validity and floor/ceiling effects of the de Morton Mobility Index (DEMMI) in hospitalized patients with AECOPD. Individuals with AECOPD ( n = 22) admitted to an acute care hospital medical ward were recruited. Data on the DEMMI, gait speed, daytime energy expenditure, step counts, 6-minute walk distance (6MWD), dyspnea, respiratory and heart rates, quality of life, and oxygen supplementation were collected on day 3 of admission. The DEMMI demonstrated convergent validity with the 6MWD and gait velocity measures (Spearman’s ρ 0.69 and 0.61, respectively; p < 0.003) but not with measures of physical activity or respiratory impairment. Discriminant validity was present, with no correlation between the DEMMI and quality of life and resting heart rate. Known-group validity (gait aids vs. no gait aids) was demonstrated ( p = 0.009). There was no floor effect but there was evidence of a possible ceiling effect (14% of participants received a perfect score). The DEMMI is feasible and showed moderate to strong validity with measures of observed physical function in hospitalized patients with AECOPD.
EEG Reactivity in Coma After Cardiac Arrest: Is it Enough to Wake Up the Dead?
Authors: Lee Jong Woo
Published: September 2019

[Box: see text]
Mindfulness in Surgery
Authors: Stephen Antonia E. , Mehta Darshan H.
Published: September 2019

In the past 20 years, interest in mindfulness and its cultivation through various meditative practices has increased astronomically. This is reflected in the popularity of mindfulness training programs, its ever-widening exposure in popular culture, and in the number of scientific articles published on the topic. With the recent focus on burnout in the medical profession and reports of high levels of anxiety and depression among residents and staff physicians, the potential applications of mindfulness are becoming increasingly apparent in the hospital setting. Mindfulness meditation may be particularly useful for surgeons because they are required to maintain their presence of mind and mental focus in the setting of challenging physical and mental tasks. Furthermore, personality traits such as perfectionism and intensity, which may have facilitated success in the competitive environment of medical school and residency training, may later manifest as intolerance and impatience, contributing to frustration and anger. A mindfulness meditation practice may help reduce the tendency to react to these emotions, yet still allow surgeons to remain motivated to excel. This article provides a definition of mindfulness and describes its introduction to Western culture. The connection of a regular meditation practice to improvements in focus and performance are reviewed. The potential benefits of mindfulness training to a surgical career are discussed, and an approach to introducing mindfulness and meditation to individual surgeons and surgical departments is outlined. We hypothesize that the introduction of department-wide training programs in mindfulness and meditation could benefit surgeons with regard to technical performance, empathy toward patients, academic productivity, and general life and career satisfaction.
Simulated robotic device malfunctions resembling malicious cyberattacks impact human perception of trust, satisfaction, and frustration
Authors: Abd Moaed A , Gonzalez Iker , Ades Craig , Nojoumian Mehrdad , Engeberg Erik D
Published: September 2019

Robot assistants and wearable devices are highly useful; however, these artificial systems are susceptible to hackers. In this article, two sets of experiments were conducted. The first part of this study simulated a malicious attack on a prosthetic arm system to adversely affect the operation of the prosthetic system, while the perception of 10 human subjects was surveyed. These 10 able-bodied subjects controlled the prosthetic arm and hand with electromyogram signals, while an artificial sensation of touch was conveyed to their arms as they operated the system, which enabled them to feel what the prosthetic hand was grasping as they were asked to transport an object from one location to another. This haptic feedback was provided in both the normal and abnormal operational modes but was disabled in the extremely abnormal mode. The electromyogram control signals for the arm were reversed in both the abnormal and extremely abnormal modes. Results from the simulated malicious attack on a prosthetic arm system showed that the subjects found the haptic feedback helpful in both the normal and abnormal modes of operation. Both the abnormal and extremely abnormal modes of operation negatively impacted the self-reported levels of trust, satisfaction, and frustration with the prosthetic system as the subjects grasped and transported an object. While these metrics were negatively impacted by system malfunctions resembling a malicious attack on the control functionality, it was possible to rebuild them to their former higher levels after the functionality of the prosthetic system was restored. A parallel study in this article involved simulating a malicious attack on a robot assistant to unfavorably affect the delivery operation modes, while the perception of 20 human subjects was surveyed. Results showed that the simulated malfunctions unfavorably impacted the perception of trust, satisfaction, and frustration, but it was possible to restore these metrics in two different ways as the device functionality was restored.
Trial by media: Why victims and activists seek a parallel justice forum for war crimes
Authors: Rae Maria
Published: September 2019

When the brutal Sri Lankan conflict ended, victims and activists launched global war crimes cases against the state alongside successful media campaigns. Although these justice claims never progressed to a court of law, they were heard, through the media, by the court of public opinion. This article considers to what extent a ‘trial by media’ might have the potential to provide a parallel justice forum. It questions how activists and victims view the role of the media in seeking justice. It finds they perceive the media’s key functions are to expose crimes, bear witness to crimes, name perpetrators, influence public opinion and apply pressure on legal and political institutions to respond to human rights abuses. However, victims and activists also recognise the media is limited in delivering justice. Therefore, this article argues a trial by media should be conceived of more as an accountability mechanism that has the capacity to draw attention to the shortcomings of official legal responses and processes.
Fistuloates A–C: New antioxidative aromatic compounds isolated from Cassia fistula
Authors: Aftab Zahida , Afzal Masood , Bushra  , Khan Hidayatullah , Badshah Syed , Khan Dilfaraz , Ullah Hamid , Khan Shafiullah
Published: September 2019

Three new aromatic compounds named fistuloates: A (3-butyl-6-ethylnonyl-3-(1-phenylethyl) benzoate), B (3-(6- tert-butyl-1-ethoxy-5-ethyl-4-methylnonyl)-5-ethylbenzoic acid isobutyl ester) and C (4,5-diethoxy-2-propylbenzoic acid 7-(6-pentyltetrahydropyran-2-yl)-heptyl ester) were isolated from the ethyl acetate soluble fraction of Cassia fistula Linn. The structural formulae of the isolated compounds A–C were established through interpretation of their spectral data. Compounds A–C exhibited significant antioxidant properties in 2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and superoxide anion radical scavenging assays that signifies that C. fistula carries potential anti-oxidant constituents and may assist to cure diseases associated with oxidative stress and others.
Versatile Synthetic Route for Resveratrol Modification via Amine Functionalization
Authors: Yanagi Masayoshi , Uchida Noriyuki , Hamada Hiroki
Published: September 2019

Resveratrol derivatives containing a primary amine functional group were synthesized by an introduction of N-Boc-bromoethylamine to resveratrol using Williamson ether synthesis and subsequent deprotection of the Boc group with trifluoroacetic acid. After conjugation of fluorescent NBD-F or rhodamine B with isothiocyanate (Rhd B-ITC) using the amine group, resveratrols modified with NBD or Rhd B (Resveratrol-NBD and Resveratrol-Rhd B, respectively) were successfully obtained.
Gentiopicroside Reduces Pain, Pruritus, and Corticosteroid Addictive Dermatitis
Authors: Zhou Chaoqun , Deng Weijian , Xiang Guanggang , Lin Xuhong , An Lei
Published: September 2019

Corticosteroid addictive dermatitis (CAD) has rapidly emerged as a health problem which is difficult to cure. The dermatitis control is general with the tacrolimus, pimecrolimus, and antihistamines, and these synthetic drugs are likely to have some side effects, and how to use the nonirritating natural product to reduce the CAD has been rarely reported. Strong evidence indicates that gentiopicroside (GPS) has been reported to have anti-inflammation and anticancer properties. In the present study, we invented a device to collect GPS to study the effect of GPS on pain, pruritus, and CAD repair in model animals. Our results showed that the data on antipain and antipruritus treated with GPS were better than those of control group, and the inflammation of rabbit skin upon 2,4-dinitrochlorobenzene exposure reduced by GPS. In conclusion, GPS could be a factor for antipain, antipruritus, and CAD repair; hence, these findings suggest that it can act as a protective factor for CAD.
Collagen-Covered Autologous Chondrocyte Implantation Versus Autologous Matrix-Induced Chondrogenesis: A Randomized Trial Comparing 2 Methods for Repair of Cartilage Defects of the Knee
Authors: Fossum Vegard , Hansen Ann Kristin , Wilsgaard Tom , Knutsen Gunnar
Published: September 2019

Background:

Autologous matrix-induced chondrogenesis (AMIC) is a single-stage alternative to autologous chondrocyte implantation for treatment of localized cartilage defects of the knee. To our knowledge, no randomized controlled trial exists comparing the 2 methods.

Purpose:

To evaluate any difference in the outcome of AMIC as compared with collagen-covered autologous chondrocyte implantation (ACI-C).

Study Design:

Randomized controlled trial; Level of evidence, 2.

Methods:

A prospective randomized controlled clinical trial was designed to assess any differences in the outcomes between ACI-C and AMIC for the treatment of ≥1 chondral or osteochondral defects of the distal femur and/or patella. The inclusion period was set to 3 years, and the aim was to include 80 patients (40 in each group). Patient inclusion was broad, with few exclusion criteria. The primary outcome was change in Knee injury and Osteoarthritis Outcome Score (KOOS) at 2 years as compared with baseline. The secondary outcomes were the number of failures in each group at 2 years and the change in KOOS subscale, Lysholm, and pain visual analog scale (VAS) scores at 2 years as compared with baseline. A 2-sample t test with a significance level of P < .05 was used to compare the change in score from baseline between groups.

Results:

A total of 41 patients over 3 years were included in the study: 21 in the ACI-C group and 20 in the AMIC group. All the patients had prior surgery to the index knee. At 2-year follow-up, the clinical scores for both groups improved significantly from baseline. No significant differences between groups were seen in the change from baseline for KOOS (AMIC, 18.1; ACI-C, 10.3), any of the KOOS subscales, the Lysholm score (AMIC, 19.7; ACI-C, 17.0), or the VAS pain score (AMIC, 30.6; ACI-C, 19.6). Two patients in the AMIC group had progressed to a total knee replacement by the 2-year follow-up as compared with none in the ACI-C group.

Conclusion:

At 2-year follow-up, no significant differences were found regarding outcomes between ACI-C and AMIC. Mid- and long-term results will be important.

Registration:

NCT01458782 ( ClinicalTrials.gov identifier).
Environmentality by the United Nations Framework Convention for Climate Change: Neoliberal ethos and the production of environmental subjects in Acre and Mozambique
Authors: Machaqueiro Raquel Rodrigues
Published: September 2019

As part of the transnational governance of the environment, platforms like the United Nations Framework Convention for Climate Change (UNFCCC) have created a regime that seeks to reinforce and reproduce the neoliberal ethos that informs current environmental conservation initiatives, as well as that seeks to produce environmental subjects. Such ethos is expressed through the preference for market-based solutions, principles of individual responsibility, or incentives to self-government. Drawing on ethnographic research in Acre (Brazil) and Mozambique, I explore some of the local elements of this neoliberal ethos. I use two public events about climate change to contend that such events constitute local instantiations of the UNFCCC's environmentality, by collectively performing and reproducing the neoliberal ethos that is encapsulated in the governance of the problem of climate change. These collective performances are important for the crystallization of a narrative that explains the reality and the terms of understanding future realities, thus contributing to processes of subjectification. The performances of these narratives are also important instances of mediation between the local and the transnational. I argue that although the production of environmental subjects promoted by the UNFCCC necessarily implies the erasure of localities, such subjectification depends on its indexation to local specificities. Ultimately, the reproduction of these environmental subjects—and the neoliberal ethos that undergirds their own constitution—has the potential to preclude the imagination of alternative models of development and of fighting climate change.
The 60-Minute MVP
Authors: Winkel Doan , Wilcox Justin , Teckchandani Atul
Published: September 2019

The 60-minute minimum viable product (MVP) exercise teaches critical aspects of the entrepreneurial mind-set and lean start-up methodology, namely, the iterative process of hypothesis testing through the creation of MVPs. In 60 minutes, with no prior technical expertise, students will work in teams to design a landing page, create a teaser video, and set up a way to gather information from prospective customers. The resulting low-fidelity MVP can subsequently be shared with prospective customers to gauge interest and be used as a starting point for the hypothesis testing process used in the lean start-up methodology. This is an immersive exercise that activates students, builds confidence, and teaches important entrepreneurial principles.
Assessing Theoretical Conclusions With Blinded Inference to Investigate a Potential Inference Crisis
Authors: Starns Jeffrey J. , Cataldo Andrea M. , Rotello Caren M. , Annis Jeffrey , Aschenbrenner Andrew , Bröder Arndt , Cox Gregory , Criss Amy , Curl Ryan A. , Dobbins Ian G. , Dunn John , Enam Tasnuva , Evans Nathan J. , Farrell Simon , Fraundorf Scott H. , Gronlund Scott D. , Heathcote Andrew , Heck Daniel W. , Hicks Jason L. , Huff Mark J. , Kellen David , Key Kylie N. , Kilic Asli , Klauer Karl Christoph , Kraemer Kyle R. , Leite Fábio P. , Lloyd Marianne E. , Malejka Simone , Mason Alice , McAdoo Ryan M. , McDonough Ian M. , Michael Robert B. , Mickes Laura , Mizrak Eda , Morgan David P. , Mueller Shane T. , Osth Adam , Reynolds Angus , Seale-Carlisle Travis M. , Singmann Henrik , Sloane Jennifer F. , Smith Andrew M. , Tillman Gabriel , van Ravenzwaaij Don , Weidemann Christoph T. , Wells Gary L. , White Corey N. , Wilson Jack
Published: September 2019

Scientific advances across a range of disciplines hinge on the ability to make inferences about unobservable theoretical entities on the basis of empirical data patterns. Accurate inferences rely on both discovering valid, replicable data patterns and accurately interpreting those patterns in terms of their implications for theoretical constructs. The replication crisis in science has led to widespread efforts to improve the reliability of research findings, but comparatively little attention has been devoted to the validity of inferences based on those findings. Using an example from cognitive psychology, we demonstrate a blinded-inference paradigm for assessing the quality of theoretical inferences from data. Our results reveal substantial variability in experts’ judgments on the very same data, hinting at a possible inference crisis.
Case Report of Endovascular Thrombectomy in Severe Acute Ischemic Stroke After Dabigatran Reversal with Idarucizumab
Authors: Nayani Sandeep , Chenna Rajesh Reddy , Sannareddy Rajesh Reddy , Bhapkar Sandeep , Kalra Sonesh , Jacob Nilan T.
Published: September 2019

Non-vitamin K antagonist oral anticoagulants have provided an optimization of management of patients in the prevention of stroke in nonvalvular atrial fibrillation. The lack of an effective reversal agent has remained a challenge to these agents’ widespread utilization. Idarucizumab, a specific reversal agent for dabigatran, is approved in many countries including India. However, there is limited data for its use for Indian patients. We are reporting one of the cases of its use in India where it successfully reversed dabigatran prior to mechanical thrombectomy in acute ischemic stroke.
The influence of heartwood, sapwood and density on moisture fluctuations and crack formations of coated Norway spruce in outdoor exposure
Authors: Sjökvist T. , Blom Å. , Wålinder M. E. P.
Published: September 2019

The moisture sorption behaviour of wood strongly influences the durability of exterior-coated wood. Wood characteristics are known to influence the water sorption of uncoated wood. Despite this, the majority of the research on coated wood has been focused on the coating properties. This study aims to investigate the impact of heartwood, sapwood and density on the moisture content (MC) and crack formation of coated Norway spruce (Picea abies (L.) Karst.). Boards with film-forming coatings or a non-film-forming coating were exposed outdoors during 3 years. Crack development and the mass of the boards were recorded during this period. Heartwood and sapwood samples showed no differences in MC. Thus, a coating seems to reduce the differences in water sorption behaviour that is present in uncoated heartwood and sapwood spruce. The reduction is probably related to wetting properties and different sorption mechanisms, involving free and bond water diffusion. However, the low-density samples had significantly higher MC levels than the high-density samples. The high-density samples with a non-film-forming coating showed a higher number of cracks than those with lower density. Furthermore, sapwood samples had a remarkably high number of cracks when compared to the corresponding heartwood samples, despite a similar density and MC.
Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes
Authors: Huang Jen-Hung , Chen Yao-Chang , Lu Yen-Yu , Lin Yung-Kuo , Chen Shih-Ann , Chen Yi-Jen
Published: September 2019

Background

Atrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. However, the role of AVP in HF-induced AF still remains unclear. Pulmonary veins (PVs) are central in the genesis of AF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms.

Methods

Patch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, Ca2+ homeostasis, and Ca2+ regulatory proteins in isolated rabbit single PV cardiomyocytes incubated with and without AVP (1 μM), OPC 21268 (0.1 μM, AVP V1 antagonist), or OPC 41061 (10 nM, AVP V2 antagonist) for 4–6 h.

Results

AVP (0.1 and 1 μM)-treated PV cardiomyocytes had a faster beating rate (108 to 152%) than the control cells. AVP (1 μM) treated PV cardiomyocytes had higher late sodium (Na+) and Na+/Ca2+ exchanger (NCX) currents than control PV cardiomyocytes. AVP (1 μM) treated PV cardiomyocytes had smaller Ca2+i transients, and sarcoplasmic reticulum (SR) Ca2+ content as well as higher Ca2+ leak. However, combined AVP (1 μM) and OPC 21268 (0.1 μM) treated PV cardiomyocytes had a slower PV beating rate, larger Ca2+i transients and SR Ca2+ content, smaller late Na+ and NCX currents than AVP (1 μM)-treated PV cardiomyocytes. Western blot experiments showed that AVP (1 μM) treated PV cardiomyocytes had higher expression of NCX and p-CaMKII, and a higher ratio of p-CaMKII/CaMKII.

Conclusions

AVP increases PV arrhythmogenesis with dysregulated Ca2+ homeostasis through vasopressin V1 signaling.
Staged complete revascularization or culprit-only percutaneous coronary intervention for multivessel coronary artery disease in patients with ST-segment elevation myocardial infarction and diabetes
Authors: Cui Kongyong , Lyu Shuzheng , Liu Hong , Song Xiantao , Yuan Fei , Xu Feng , Zhang Min , Wang Wei , Zhang Mingduo , Zhang Dongfeng , Tian Jinfan
Published: September 2019

Background

Recently, several randomized trials have noted improved outcomes with staged percutaneous coronary intervention (PCI) of nonculprit vessels in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, it remains unclear whether diabetes status affects the outcomes after different revascularization strategies. This study thus compared the impact of diabetes status on long-term outcomes after staged complete revascularization with that after culprit-only PCI.

Methods

From January 2006 to December 2015, 371 diabetic patients (staged PCI: 164, culprit-only PCI: 207) and 834 nondiabetic patients (staged PCI: 412, culprit-only PCI: 422) with STEMI and multivessel disease were enrolled. The primary endpoint was 5-year major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction (MI), stroke or unplanned revascularization.

Results

The rate of the 5-year composite primary endpoint for diabetic patients was close to that for nondiabetic patients (34.5% vs. 33.7%; adjusted hazard ratio [HR] 1.012, 95% confidence interval [CI] 0.815–1.255). In nondiabetic patients, the 5-year risks of MACCE (31.8% vs. 35.5%; adjusted HR 0.638, 95% CI 0.500–0.816), MI (4.6% vs. 9.2%; adjusted HR 0.358, 95% CI 0.200–0.641), unplanned revascularization (19.9% vs. 24.9%; adjusted HR 0.532, 95% CI 0.393–0.720), and the composite of cardiac death, MI or stroke (11.4% vs. 15.2%; adjusted HR 0.621, 95% CI 0.419–0.921) were significantly lower after staged PCI than after culprit-only PCI. In contrast, no significant difference was found between the two groups with respect to MACCE, MI, unplanned revascularization, and the composite of cardiac death, MI or stroke in diabetic patients. Significant interactions were found between diabetes status and revascularization assignment for the composite of cardiac death, MI or stroke (Pinteraction = 0.013), MI (Pinteraction = 0.005), and unplanned revascularization (Pinteraction = 0.013) at 5 years. In addition, the interaction tended to be significant for the primary endpoint of MACCE (Pinteraction = 0.053). Moreover, the results of propensity score-matching analysis were concordant with the overall analysis in both diabetic and nondiabetic population.

Conclusions

In patients with STEMI and multivessel disease, diabetes is not an independent predictor of adverse cardiovascular events at 5 years. In nondiabetic patients, an approach of staged complete revascularization is superior to culprit-only PCI, whereas the advantage of staged PCI is attenuated in diabetic patients.

Trial registrationThis study was not registered in an open access database
Nutrition among children of migrant construction workers in Ahmedabad, India
Authors: Ravindranath Divya , Trani Jean-Francois , Iannotti Lora
Published: September 2019

Background

Millions of poor households in India undertake short duration rural to urban migration along with their children to find work in the informal economy in the city. While literature has documented the precarity of such temporary jobs, typically characterized by low wages, insecure jobs, harsh recruitment regimes and economic vulnerability, little is known about its implications for children who migrate with their parents to the city. In this study, we draw attention to children of migrant construction workers and focus on their overall nutritional well-being, which remains under-studied. Our objectives were to categorize the current nutritional status of children under the age of five and determine the underlying causes of poor nutritional outcomes.

Methods

The field work for this study was undertaken between May 2017 and January 2018 at five construction sites in the city of Ahmedabad. We undertook anthropometric measurements of children under the age of five [N = 131; (male: 46%, female 53%); (mean age: 31.7 months)] and categorized their nutritional status. Using the UNICEF framework on undernutrition, we examined the underlying causes of poor nutritional outcomes among this group of children with the help of qualitative methods such as interviews, focused group discussions and participant observation at the field sites.

Results

Undernutrition was highly prevalent among the children (N = 131): stunted (40.5%); wasted (22.1%); and underweight (50.4%). We found common factors across parents interviewed such as similar misperceptions of malnutrition, long hours of work and lack of childcare provision at the worksite which resulted in disrupted quality of care. While socio-cultural beliefs and lack of information influenced breastfeeding, other factors such as inability to take breaks or lack of space further impaired infant feeding practices more broadly. Lack of dietary diversity at home, poor hygiene and sanitation, and economic inability to seek healthcare further affected child nutritional status.

Conclusions

Our study addresses a critical gap in migration literature in India by building a comprehensive narrative of migrant children’s experiences at construction sites. We find that parents’ informal work setting exposes children to a nutritionally challenging environment. Policies and programs seeking to address undernutrition, a critical challenge in India, must pay attention to the specific needs of migrant children.
Correction to: Optimizing conditions for labeling of mesenchymal stromal cells (MSCs) with gold nanoparticles: a prerequisite for in vivo tracking of MSCs
Authors: Nold Philipp , Hartmann Raimo , Feliu Neus , Kantner Karsten , Gamal Mahmoud , Pelaz Beatriz , Hühn Jonas , Sun Xing , Jungebluth Philipp , del Pino Pablo , Hackstein Holger , Macchiarini Paolo , Parak Wolfgang J. , Brendel Cornelia
Published: September 2019

The authors apologized for the unfortunate error in figure during publication of the article and they also explained that some of the solid grey graphs in Fig. 5 are intentionally based on the same data. For 8 different surface makers (CD14, CD73, CD34, CD105, CD19, CD90, CD45, HA-DR) in accordance to the guidelines of the manufacturer a panel of 4 different isotype controls were used, corresponding to 4 different fluorescence channels.
Hollow gold nanoshells-incorporated injectable genetically engineered hydrogel for sustained chemo-photothermal therapy of tumor
Authors: Jin RuiMei , Yang Jie , Zhao DongHui , Hou XiaoLin , Li ChaoQing , Chen Wei , Zhao YuanDi , Yin ZhongYuan , Liu Bo
Published: September 2019

Background

Combined therapy has demonstrated to be an effective strategy for cancer therapy. Herein, an injectable hydrogel based on the genetically engineered polypeptide and hollow gold nanoshells (HAuNS) has been developed for chemo-photothermal therapy of HepG2 tumor.

Methods

PC10A/DOX/HAuNS nanogel was prepared with layer-by-layer through the adsorption of DOX and PC10A successively. DOX with positive charge and PC10A with negative charge were coated step by step onto the surface of negatively charged HAuNS. The multifunctional hydrogel PC10A/DOX/HAuNS were prepared via dissolving hybrid PC10A/DOX/HAuNS nanogel in polypeptide PC10A. Chemotherapy drug DOX in the PC10A/DOX/HAuNS hydrogel was absorbed on the HAuNS and directly embedded in the PC10A hydrogel, which contributes to sequentially release of the drug. Specifically, DOX adsorbed on the HAuNS could be released slowly for sustainable chemotherapy.

Results

The PC10A/DOX/HAuNS hydrogel could pass 26-gauge needle without clogging, indicating that it is injectable. In addition, the PC10A/DOX/HAuNS hydrogel possessed outstanding photothermal effect and photothermal stability. In both in vitro cell and in vivo tumor-bearing mice experiments, a remarkably enhance tumor inhibition was observed by the combined therapy of chemo-photothermal therapy compared with photothermal therapy or chemotherapy alone.

Conclusions

The combined chemotherapy and photothermal therapy of PC10A/DOX/HAuNS hydrogels could significantly improve the therapeutic effect. Therefore, the multifunctional hydrogel PC10A/DOX/HAuNS is promising to provide a new strategy for sustained chemo-photothermal therapy.
Air pollution-induced placental alterations: an interplay of oxidative stress, epigenetics, and the aging phenotype?
Authors: Saenen N. D. , Martens D. S. , Neven K. Y. , Alfano R. , Bové H. , Janssen B. G. , Roels H. A. , Plusquin M. , Vrijens K. , Nawrot T. S.
Published: September 2019

According to the “Developmental Origins of Health and Disease” (DOHaD) concept, the early-life environment is a critical period for fetal programming. Given the epidemiological evidence that air pollution exposure during pregnancy adversely affects newborn outcomes such as birth weight and preterm birth, there is a need to pay attention to underlying modes of action to better understand not only these air pollution-induced early health effects but also its later-life consequences. In this review, we give an overview of air pollution-induced placental molecular alterations observed in the ENVIRONAGE birth cohort and evaluate the existing evidence. In general, we showed that prenatal exposure to air pollution is associated with nitrosative stress and epigenetic alterations in the placenta. Adversely affected CpG targets were involved in cellular processes including DNA repair, circadian rhythm, and energy metabolism. For miRNA expression, specific air pollution exposure windows were associated with altered miR-20a, miR-21, miR-146a, and miR-222 expression. Early-life aging markers including telomere length and mitochondrial DNA content are associated with air pollution exposure during pregnancy. Previously, we proposed the air pollution-induced telomere-mitochondrial aging hypothesis with a direct link between telomeres and mitochondria. Here, we extend this view with a potential co-interaction of different biological mechanisms on the level of placental oxidative stress, epigenetics, aging, and energy metabolism. Investigating the placenta is an opportunity for future research as it may help to understand the fundamental biology underpinning the DOHaD concept through the interactions between the underlying modes of action, prenatal environment, and disease risk in later life. To prevent lasting consequences from early-life exposures of air pollution, policy makers should get a basic understanding of biomolecular consequences and transgenerational risks.
Epigenetic downregulation of STAT6 increases HIF-1α expression via mTOR/S6K/S6, leading to enhanced hypoxic viability of glioma cells
Authors: Park Soo Jung , Kim Hyunmi , Kim Se Hyuk , Joe Eun-hye , Jou Ilo
Published: September 2019

Multifunctional signal transducer and activator of transcription (STAT) proteins play important roles in cancer. Here, we have shown that STAT6 is epigenetically silenced in some cases of malignant glioblastoma, which facilitates cancer cell survival in a hypoxic microenvironment. This downregulation results from hypermethylation of CpG islands within the STAT6 promoter by DNA methyltransferases. STAT6 interacts with Rheb under hypoxia and inhibits mTOR/S6K/S6 signaling, in turn, inducing increased HIF-1α translation. STAT6 silencing and consequent tumor-promoting effects are additionally observed in glioma stem-like cells (GSC). Despite recent advances in cancer treatment, survival rates have shown little improvement. This is particularly true in the case of glioma, where multimodal treatment and precision medicine is needed. Our study supports the application of epigenetic restoration of STAT6 with the aid of DNA methyltransferase inhibitors, such as 5-aza-2-deoxycytidine, for treatment of STAT6-silenced gliomas.
Microfluidic in vitro brain endothelial monolayer model to evaluate cell-penetrating peptides
Authors: Chung Bohye , Kim Jaehoon , Liu Hui-Wen , Nam Jiyoung , Kim Hyunho , Oh Hyun Jeong , Kim Yong Ho , Chung Seok
Published: September 2019

Blood vessels in central nervous system act as a great hurdle for drug delivery to the human brain. They only allow passage of water, some gases, lipid molecules, glucose and amino acid by selective transporter while restricting most of solutes and pathogens to protect brain. A lot of studies have tried to overcome this hurdle by discovering and optimizing brain deliverable drugs however the platforms used for preclinical stage are still limited. In this study, we constructed an in vitro 3-dimensional model for brain endothelial monolayer using hydrogel incorporated microfluidic device that provides an 3D extracellular matrix scaffold. We confirmed the stable endothelial barrier by staining a tight junction marker, VE-Cadherin, and strong block ability by comparing permeability with normal endothelial cells. Also, we succeed in verifying the strong permeability of angiopep-2 using our device that is known as a brain permeable peptide by utilizing receptor-mediated transcytosis. We propose our microfluidic device as an in vitro platform for evaluating various brain drugs or drug carrier candidates.
Numerical modeling of the geothermal hydrology of the Volcanic Island of Basse-Terre, Guadeloupe
Authors: Raguenel Margaux , Driesner Thomas , Bonneau François
Published: September 2019

This study investigates the thermo-hydraulic implications of three geologic scenarios for characterizing the geothermal hydrology of Basse-Terre Island, Guadeloupe. Despite newly acquired magnetotelluric, petrophysical, and geologic data, flow patterns and heat sources have remained elusive. Our simulations were performed in 2D, on a cross section going from La Soufrière volcano in the south to the operating Bouillante geothermal field near the west coast. Simulation results are compared to geologic constraints such as the temperature profile measured at Bouillante and the timing of volcanic activity in the area, which may be indicative of new heat sources at depth. The simulations indicate that during lateral flow from La Soufrière, geothermal fluids would cool too much to explain the temperature at Bouillante. Two other scenarios were found to explain the current thermal structure of the Bouillante geothermal system: a young (ca.  5000 years) and more local magmatic intrusion at depth, or vertical corridors of enhanced permeability that tap hot and porous formations at a few km depth. Without further geologic evidence, neither of these two scenarios can be preferred. The second magma chamber scenario would indicate a more complex magmatic history of the island than previously established. The study shows that geologically constrained scenarios of regional geothermal hydrology can be meaningfully tested with current numerical simulation techniques, providing further insights for geothermal exploration.
Using scaffold innovation-thinking frameworks to integrate food science and technology into the transdisciplinary engineering design classroom
Authors: Bosman Lisa , Eom Sangjun
Published: September 2019

Technology and innovation are essential for students to not only learn and understand the technical skills, but also identify a problem, discover a solution, and communicate the value proposition. In this study, innovation-thinking frameworks were integrated into undergraduate transdisciplinary engineering and technology classrooms with a topic of food science and technology, exploring design within the area of new product development. The qualitative analysis, conducted using NVivo, indicated that the food science and technology focused educational experiences had the potential of transforming student self-reported perspectives related to metacognitive reflection, connecting the topics to the real-world and communicating. The findings offer exciting insights into the benefit of integrating self-regulated learning, visualization, and communication technology into future food-related education programs.
Atypical RAS Mutations in Metastatic Colorectal Cancer
Authors: Pietrantonio Filippo , Yaeger Rona , Schrock Alexa B. , Randon Giovanni , Romero-Cordoba Sandra , Rossini Daniele , Fucà Giovanni , Ross Jeffrey S. , Kotani Daisuke , Madison Russell , Kim Seung Tae , Salvatore Lisa , Raimondi Alessandra , Pagani Filippo , Borelli Beatrice , Perrone Federica , Di Bartolomeo Maria , Miller Vincent A. , Ali Siraj M. , Lee Jeeyun , Yoshino Takayuki , de Braud Filippo , Falcone Alfredo , Hechtman Jaclyn F. , Cremolini Chiara
Published: September 2019

PURPOSE

To describe the clinical and molecular features of metastatic colorectal cancers (mCRCs) bearing uncommon atypical RAS (At- RAS) mutations at codons other than 12, 13, 59, 61, 117, and 146.

MATERIALS AND METHODS

By exploiting five next-generation sequencing sources (Italian collaboration, Memorial Sloan Kettering Cancer Center, Samsung Medical Center, the Biomarker Research for Anti-EGFR Monoclonal Antibodies by Comprehensive Cancer Genomics (BREAC) study, and the Foundation Medicine database), we retrieved 175 At- RAS mutated cases. Molecular data were obtained from 163 samples from Memorial Sloan Kettering Cancer Center and the Foundation Medicine database. Clinical data were available for 27 At- RAS–positive and 467 negative cases from the Italian collaboration, Memorial Sloan Kettering Cancer Center, Samsung Medical Center, and the BREAC study.

RESULTS

At- RAS mutations were identified in 163 (0.9%) of 18,270 mCRCs. Among 133 with evaluable microsatellite instability status, 11 (8%) were microsatellite instability high. POLE exonuclease domain mutations had higher frequency (7%) than expected and were found only in microsatellite-stable tumors with high tumor mutational burden (TMB). Overall, 17% (28 of 163) of At- RAS cases had TMB greater than 20 mutations/Mb. Co-occurring typical RAS/BRAF V600E mutations and NF1 mutations, presumed to cause RAS activation, were found in 30% and 12% of samples, respectively (up to 43% and 50%, respectively, in TMB-high samples). Patients with RAS/BRAF wild-type mCRC achieved a median overall survival (OS) of 42.1 months, whereas those harboring isolated At- RAS, typical RAS, or BRAF V600E mutations showed a median OS of 32.3, 30.0, and 17.9 months, respectively ( P < .001). No significant OS difference ( P = .240) was found between patients with At- RAS versus typical RAS-mutated mCRC. Only one of six patients evaluable for primary resistance to anti–epidermal growth factor receptors achieved tumor response.

CONCLUSION

At- RAS mutations may be a marker for RAS pathway activation and can be associated with high co-occurrence of POLE exonuclease domain mutations.