bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure Ulcer Risk Factors in Persons with Mobility-Related Disabilities
Authors: Sprigle Stephen , McNair Douglas , Sonenblum Sharon
Published: February 2020

OBJECTIVE

To assess pressure ulcer (PU) risk in persons with mobility impairments using a large data set to identify demographic, laboratory, hemodynamic, and pharmacologic risk factors.

METHODS

The cohort of interest was persons with disabilities who have mobility impairments and are diagnostically at risk of PUs. To define this cohort, diagnoses that qualify patients for skin protection wheelchair cushions were used. Data were obtained from the Cerner Health Facts data warehouse. Two cohorts were defined: persons with and without a history of PUs. Analysis included descriptive statistics and multivariate logistic regression modeling. Variables retained in the model were identified using LASSO, gradient boosting, and Bayesian model averaging.

MAIN RESULTS

The resulting cohorts included more than 87,000 persons with a history of PUs and more than 1.1 million persons who did not have a PU. The data revealed seven disability groups with the greatest prevalence of PUs: those with Alzheimer disease, cerebral palsy, hemiplegia, multiple sclerosis, paraplegia/quadriplegia, Parkinson disease, and spina bifida. Ulcers in the pelvic region accounted for 82% of PUs. Persons with disabilities who were male or black had a greater prevalence of PUs. Physiologic risk factors included the presence of kidney or renal disease, decreased serum albumin, and increased serum C-reactive protein.

CONCLUSIONS

The results indicate that, although persons with disabilities can exhibit a wide functional range, they remain at risk of PUs and should be evaluated for proper preventive measures, including support surfaces and wheelchair cushions.
Critical Illness Factors Associated With Long-Term Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock*
Authors: Zimmerman Jerry J. , Banks Russell , Berg Robert A. , Zuppa Athena , Newth Christopher J. , Wessel David , Pollack Murray M. , Meert Kathleen L. , Hall Mark W. , Quasney Michael , Sapru Anil , Carcillo Joseph A. , McQuillen Patrick S. , Mourani Peter M. , Wong Hector , Chima Ranjit S. , Holubkov Richard , Coleman Whitney , Sorenson Samuel , Varni James W. , McGalliard Julie , Haaland Wren , Whitlock Kathryn , Dean J. Michael , Reeder Ron W.
Published: February 2020

Objectives:

A companion article reports the trajectory of long-term mortality and significant health-related quality of life disability among children encountering septic shock. In this article, the investigators examine critical illness factors associated with these adverse outcomes.

Design:

Prospective, cohort-outcome study, conducted 2013–2017.

Setting:

Twelve United States academic PICUs.

Patients:

Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support.

Interventions:

Illness severity, organ dysfunction, and resource utilization data were collected during PICU admission. Change from baseline health-related quality of life at the month 3 follow-up was assessed by parent proxy-report employing the Pediatric Quality of Life Inventory or the Stein-Jessop Functional Status Scale.

Measurements and Main Results:

In univariable modeling, critical illness variables associated with death and/or persistent, serious health-related quality of life deterioration were candidates for multivariable modeling using Bayesian information criterion. The most clinically relevant multivariable models were selected among models with near-optimal statistical fit. Three months following septic shock, 346 of 389 subjects (88.9%) were alive and 43 of 389 had died (11.1%); 203 of 389 (52.2%) had completed paired health-related quality of life surveys. Pediatric Risk of Mortality, cumulative Pediatric Logistic Organ Dysfunction scores, PICU and hospital durations of stay, maximum and cumulative vasoactive-inotropic scores, duration of mechanical ventilation, need for renal replacement therapy, extracorporeal life support or cardiopulmonary resuscitation, and appearance of pathologic neurologic signs were associated with adverse outcomes in univariable models. In multivariable regression analysis (odds ratio [95% CI]), summation of daily Pediatric Logistic Organ Dysfunction scores, 1.01/per point (1.01–1.02), p < 0.001; highest vasoactive-inotropic score, 1.02/per point (1.00–1.04), p = 0.003; and any acute pathologic neurologic sign/event, 5.04 (2.15–12.01), p < 0.001 were independently associated with death or persistent, serious deterioration of health-related quality of life at month 3.

Conclusions and Relevance:

Biologically plausible factors related to sepsis-associated critical illness organ dysfunction and its treatment were associated with poor outcomes at month 3 follow-up among children encountering septic shock.
Trajectory of Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock*
Authors: Zimmerman Jerry J. , Banks Russell , Berg Robert A. , Zuppa Athena , Newth Christopher J. , Wessel David , Pollack Murray M. , Meert Kathleen L. , Hall Mark W. , Quasney Michael , Sapru Anil , Carcillo Joseph A. , McQuillen Patrick S. , Mourani Peter M. , Wong Hector , Chima Ranjit S. , Holubkov Richard , Coleman Whitney , Sorenson Samuel , Varni James W. , McGalliard Julie , Haaland Wren , Whitlock Kathryn , Dean J. Michael , Reeder Ron W.
Published: February 2020

Objectives:

In-hospital pediatric sepsis mortality has decreased substantially, but long-term mortality and morbidity among children initially surviving sepsis, is unknown. Accordingly, the Life After Pediatric Sepsis Evaluation investigation was conducted to describe the trajectory of mortality and health-related quality of life morbidity for children encountering community-acquired septic shock.

Design:

Prospective, cohort-outcome study, conducted 2013–2017.

Setting:

Twelve academic PICUs in the United States.

Patients:

Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support.

Interventions:

Demographic, infection, illness severity, organ dysfunction, and resource utilization data were collected daily during PICU admission. Serial parent proxy-report health-related quality of life assessments were obtained at baseline, 7 days, and 1, 3, 6, and 12 months following PICU admission utilizing the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale.

Measurements and Main Results:

Among 389 children enrolled, mean age was 7.4 ± 5.8 years; 46% were female; 18% were immunocompromised; and 51% demonstrated chronic comorbidities. Baseline Pediatric Overall Performance Category was normal in 38%. Median (Q1–Q3) Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores at PICU admission were 11.0 (6.0–17.0) and 9.0 (6.0–11.0); durations of vasoactive-inotropic and mechanical ventilation support were 3.0 days (2.0–6.0 d) and 8.0 days (5.0–14.0 d); and durations of PICU and hospital stay were 9.4 days (5.6–15.4 d) and 15.7 days (9.2–26.0 d). At 1, 3, 6, and 12 months following PICU admission for the septic shock event, 8%, 11%, 12%, and 13% of patients had died, while 50%, 37%, 30%, and 35% of surviving patients had not regained their baseline health-related quality of life.

Conclusions:

This investigation provides the first longitudinal description of long-term mortality and clinically relevant, health-related quality of life morbidity among children encountering community-acquired septic shock. Although in-hospital mortality was 9%, 35% of survivors demonstrated significant, health-related quality of life deterioration from baseline that persisted at least 1 year following hospitalization for septic shock.
The contribution of residential greenness to mortality among men with prostate cancer: a registry-based cohort study of Black and White men
Authors: Iyer Hari S. , Valeri Linda , James Peter , Chen Jarvis T. , Hart Jaime E. , Laden Francine , Holmes Michelle D. , Rebbeck Timothy R.
Published: February 2020

Background:

Black men with prostate cancer (CaP) experience excess mortality compared with White men. Residential greenness, a health promoting contextual factor, could explain racial disparities in mortality among men with CaP.

Methods:

We identified Pennsylvania Cancer Registry cases diagnosed between January 2000 and December 2015. Totally, 128,568 participants were followed until death or 1 January 2018, whichever occurred first. Residential exposure at diagnosis was characterized using the Normalized Difference Vegetation Index (NDVI) with 250 m resolution. We estimated hazard ratios (HRs) using Cox models, adjusting for area-level socioeconomic status, geographic healthcare access, and segregation. To determine whether increasing residential greenness could reduce racial disparities, we compared standardized 10-year mortality Black-White risk differences under a hypothetical intervention fixing NDVI to the 75th percentile of NDVI experienced by White men.

Results:

We observed 29,978 deaths over 916,590 person-years. Comparing men in the highest to lowest NDVI quintile, all-cause (adjusted HR [aHR]: 0.88, 95% confidence interval [CI]: 0.84, 0.92, P
trend < 0.0001), prostate-specific (aHR: 0.88, 95% CI: 0.80, 0.99, P
trend= 0.0021), and cardiovascular-specific (aHR: 0.82, 95% CI: 0.74, 0.90, P
trend < 0.0001) mortality were lower. Inverse associations between an interquartile range increase in NDVI and cardiovascular-specific mortality were observed in White (aHR: 0.90, 95% CI: 0.86, 0.93) but not Black men (aHR: 0.97, 95% CI: 0.89, 1.06; P
het = 0.067). Hypothetical interventions to increase NDVI led to nonsignificant reductions in all-cause (−5.3%) and prostate-specific (−23.2%), but not cardiovascular-specific mortality disparities (+50.5%).

Discussion:

Residential greenness was associated with lower mortality among men with CaP, but findings suggest that increasing residential greenness would have limited impact on racial disparities in mortality.
Effects of dose on acquisition and persistence of a new response for a remifentanil-associated stimulus
Authors: Robertson Stephen H. , Jutkiewicz Emily M.
Published: February 2020

Previous research demonstrated that a remifentanil-associated stimulus facilitated the acquisition of a previously unlearned response; however, it is unclear how long a remifentanil-associated stimulus maintains conditioned reinforcing properties under conditions of daily testing. To address this gap, we exposed adult male rats to response-independent stimulus presentations and deliveries of remifentanil (1.0, 3.2, or 10.0 μg/kg/infusion). Rats either received the stimulus presentations and remifentanil deliveries together (Paired Pavlovian conditioning) or according to separate clocks (Random control group). In the sessions following Pavlovian conditioning, we allowed rats to emit nose-poke responses for the presentation of the stimulus alone and measured the extent to which the stimulus facilitated and maintained a previously unlearned response. We tested responding for the stimulus presentations across 28 daily sessions to assess the Pavlovian extinction (degradation of the drug-stimulus association) of the conditioned reinforcing properties of the remifentanil-associated stimulus. We observed the highest and most persistent levels of responding in rats with a Paired Pavlovian conditioning history at 3.2 and 10.0 μg/kg/infusion. In addition, we included analyses of the variability in responding for each group, which revealed individual differences in the susceptibility of the remifentanil-associated stimulus acting as a conditioned reinforcer. These findings demonstrate that a remifentanil-associated stimulus has the ability to sustain drug-seeking behavior and underscores the importance of Pavlovian conditioning in promoting drug abuse.
The Victorian Institute of Sport Assessment Scale for Patellar Tendinopathy (VISA-P): A Reliability Generalization Meta-analysis
Authors: Palazón-Bru Antonio , Tomás Rodríguez María Isabel , Mares-García Emma , Hernández-Sánchez Sergio , Carbonell-Torregrosa María Ángeles , Gil-Guillén Vicente Francisco
Published: February 2020

Objective:

The Victorian Institute of Sport Assessment-Patella (VISA-P) is a questionnaire to assess the severity of patellar tendinopathies. Its use requires good reliability indicators: internal consistency, test-retest and parallel forms. Several studies have been published examining this question, but to date the reliability of this questionnaire (meta-analysis) has not been generalized. The aim of this study was to perform a meta-analysis to generalize the reliability of the VISA-P.

Data sources:

MEDLINE, EMBASE, and Scopus.

Study selection:

Studies included were those examining the reliability coefficients of the VISA-P: Cronbach alpha, intraclass correlation coefficient (ICC), and parallel-forms (correlation coefficients compared with other scales).

Data extraction:

All coefficients were extracted and the mean reliability was obtained using fixed- or random-effects models. Sensitivity (leave-one-out analysis) was analyzed. Quality assessment was performed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist.

Data Synthesis:

Of 364 scientific articles, 12 fulfilled meta-analysis criteria. The summary statistic was 0.86 [95% confidence interval (CI): 0.78-0.92] for Cronbach alpha and 0.94 (95% CI: 0.89-0.97) for the ICC. Parallel forms depended on the comparative test used, ranging from −0.83 to 0.68. The sensitivity analysis found an influential study for the parallel-forms reliability in the Blazina score. We were unable to analyze the asymmetry of funnel plots and meta-regression models because of the number of studies.

Conclusions:

The reliability of VISA-P for assessing the severity of patellar tendinopathies requires greater evaluation with more scientific evidence before it can be implemented in clinical practice.
Validation of the Chinese Version of the Somatic Symptom Disorder–B Criteria Scale for Detecting DSM-5 Somatic Symptom Disorders: A Multicenter Study
Authors: Li Tao , Wei Jing , Fritzsche Kurt , Toussaint Anne Christin , Jiang Yinan , Cao Jinya , Zhang Lan , Zhang Yaoyin , Chen Hua , Wu Heng , Ma Xiquan , Li Wentian , Ren Jie , Lu Wei , Müller Anne-Maria , Leonhart Rainer
Published: February 2020

Objective

This study aimed to validate the Chinese version of the Somatic Symptom Disorder–B Criteria Scale (SSD-12) in an outpatient sample from Chinese general hospitals and to determine the diagnostic performance of the SSD-12 as a screening tool for somatic symptom disorder (SSD).

Methods

The Chinese version of the SSD-12 was completed by 699 outpatients from nine general hospitals during a 16-month period (2016–2018). The SSD section of the Structured Clinical Interview for DSM Disorders, Fifth Edition, Research Version, was used to determine diagnostic accuracy (criterion validity). The construct validity of the SSD-12 was evaluated by examining correlations with the Whiteley Index-7, Patient Health Questionnaire-15, Patient Health Questionnaire-9, General Anxiety Disorder-7, World Health Organization Disability Assessment Schedule, and Medical Outcome Study 12-item Short Form Health Survey (SF-12).

Results

The SSD-12 had excellent internal consistency in this sample (Cronbach α = .95). Confirmatory factor analyses replicated a three-factor structure that reflects the cognitive, affective, and behavioral aspects (Comparative Fit Index = 0.963, Tucker-Lewis Index = 0.952, root mean square error of approximation = 0.08, 90% confidence interval = 0.08–0.09), but was also consistent with a general one-factor model of the SSD-12 (Comparative Fit Index = 0.957, Tucker-Lewis Index = 0.948, root mean square error of approximation = 0.09, 90% confidence interval = 0.08–0.10). The optimal cutoff point for the Structured Clinical Interview for DSM Disorders–based diagnosis of SSD was 16 (sensitivity = 0.76, specificity = 0.80). The SSD-12 sum score was significantly associated with somatic symptom burden (Patient Health Questionnaire-15: r = 0.52, p < .001), health anxiety (Whiteley Index-7: r = 0.82, p < .001), depressive symptoms (Patient Health Questionnaire-9: r = 0.63, p < .001), general anxiety (General Anxiety Disorder-7: r = 0.64, p < .001), health-related quality of life (physical component score of SF-12: r = −0.49, p < .001; mental component score of SF-12: r = −0.61, p < .001), and health-related disabilities (World Health Organization Disability Assessment Schedule: r = 0.56, p < .001).

Conclusions

Initial assessment indicates that the Chinese version of the SSD-12 has sufficient reliability and validity to warrant further testing in both research and clinical settings.
Cortical high-frequency oscillation loops initiate spasm seizures
Authors: Zhu Yu , Liu Chunyan , Sun Ying , Yu Tao , Xu Cuiping , Zhang Guojun , Wang Yuping
Published: February 2020

Some epileptic spasms are classified into focal-onset seizures. However, the cortical network underlying this kind of spasm seizure is not yet clear. Four patients with epileptic spasms who underwent intracranial electrode implantation and focal resection surgery were studied. All the patients had good outcomes, and three of them with intellectual disability showed improved intelligence after surgery. The power spectra characteristics of electrocorticography and the dynamic functional network changes of epileptic spasms were investigated. Electrocorticography power in the resected zone peaked 0.5 seconds before the clinical seizure onset and was especially prominent in the γ and ripple bands. The functional network analysis showed particular dynamic patterns of high-frequency activity among the resected zone, sensorimotor cortex, and the other region. In the gamma band, during the interictal segment, the information flow from the resected zone and the other region to the sensorimotor cortex was prominent. During the preictal segment, the information flow from the resected zone and sensorimotor cortex to the other region became stronger. In the ripple band, during the interictal segment, the information flow from the resected zone to the sensorimotor cortex and the other region was high. During the preictal segment, the information flow between the resected zone and sensorimotor cortex became stronger. Our results suggest that the sensorimotor cortex is a requisite for spasm seizure initiation, and the ripple activity loop between the resected zone and sensorimotor cortex may give rise to the seizure onset with the help of the gamma activity loop between the sensorimotor cortex and the other region for activation spreading.
Propagating wave activity in a tangential cortical slice
Authors: Lee Charles C.
Published: February 2020

Propagating neural waves in the cerebral cortex influence the integration of incoming sensory information with ongoing cortical activity. However, the neural circuit elements that support these cortical waves remain to be fully defined. Here, a novel tangential slice preparation was developed that exhibited propagating wave activity across the dorsal cortical sheet, as assessed using autofluorescence imaging following focal electrical stimulation. Analysis of functional connectivity in the slice preparation with laser-scanning photostimulation via glutamate uncaging revealed a lack of short-latency, presumed monosynaptic, long-range connections (>300 μm) in the slice preparation. These results establish a novel slice preparation for assessing cortical dynamics and support the proposition that interactions among local cortical elements are sufficient to enable widespread propagating wave activity.
Multiscale modelling of drug transport and metabolism in liver spheroids
Authors: Leedale Joseph A. , Kyffin Jonathan A. , Harding Amy L. , Colley Helen E. , Murdoch Craig , Sharma Parveen , Williams Dominic P. , Webb Steven D. , Bearon Rachel N.
Published: February 2020

In early preclinical drug development, potential candidates are tested in the laboratory using isolated cells. Thesein vitroexperiments traditionally involve cells cultured in a two-dimensional monolayer environment. However, cells cultured in three-dimensional spheroid systems have been shown to more closely resemble the functionality and morphology of cellsin vivo. While the increasing usage of hepatic spheroid cultures allows for more relevant experimentation in a more realistic biological environment, the underlying physical processes of drug transport, uptake and metabolism contributing to the spatial distribution of drugs in these spheroids remain poorly understood. The development of a multiscale mathematical modelling framework describing the spatio-temporal dynamics of drugs in multicellular environments enables mechanistic insight into the behaviour of these systems. Here, our analysis of cell membrane permeation and porosity throughout the spheroid reveals the impact of these properties on drug penetration, with maximal disparity between zonal metabolism rates occurring for drugs of intermediate lipophilicity. Our research shows how mathematical models can be used to simulate the activity and transport of drugs in hepatic spheroids and in principle any organoid, with the ultimate aim of better informing experimentalists on how to regulate dosing and culture conditions to more effectively optimize drug delivery.
Mathematical modelling of fluid flow and solute transport to define operating parameters forin vitroperfusion cell culture systems
Authors: Hyndman Lauren , McKee Sean , Mottram Nigel J. , Singh Bhumika , Webb Steven D. , McGinty Sean
Published: February 2020

In recent years, there has been a move away from the use of staticin vitrotwo-dimensional cell culture models for testing the chemical safety and efficacy of drugs. Such models are increasingly being replaced by more physiologically relevant cell culture systems featuring dynamic flow and/or three-dimensional structures of cells. While it is acknowledged that such systems provide a more realistic environment within which to test drugs, progress is being hindered by a lack of understanding of the physical and chemical environment that the cells are exposed to. Mathematical and computational modelling may be exploited in this regard to unravel the dependency of the cell response on spatio-temporal differences in chemical and mechanical cues, thereby assisting with the understanding and design of these systems. In this paper, we present a mathematical modelling framework that characterizes the fluid flow and solute transport in perfusion bioreactors featuring an inlet and an outlet. To demonstrate the utility of our model, we simulated the fluid dynamics and solute concentration profiles for a variety of different flow rates, inlet solute concentrations and cell types within a specific commercial bioreactor chamber. Our subsequent analysis has elucidated the basic relationship between inlet flow rate and cell surface flow speed, shear stress and solute concentrations, allowing us to derive simple but useful relationships that enable prediction of the behaviour of the system under a variety of experimental conditions, prior to experimentation. We describe how the model may used by experimentalists to define operating parameters for their particular perfusion cell culture systems and highlight some operating conditions that should be avoided. Finally, we critically comment on the limitations of mathematical and computational modelling in this field, and the challenges associated with the adoption of such methods.
Applications of novel bioreactor technology to enhance the viability and function of cultured cells and tissues
Authors: Hoyle H. W. , Smith L. A. , Williams R. J. , Przyborski S. A.
Published: February 2020

As the field of tissue engineering continues to advance rapidly, so too does the complexity of cell culture techniques used to generatein vitrotissue constructs, with the overall aim of mimicking thein vivomicroenvironment. This complexity typically comes at a cost with regards to the size of the equipment required and associated expenses. We have developed a small, low-cost bioreactor system which overcomes some of the issues of typical bioreactor systems while retaining a suitable scale for the formation of complex tissues. Herein, we have tested this system with three cell populations/tissues: the culture of hepatocellular carcinoma cells, where an improved structure and basic metabolic function is seen; the culture of human pluripotent stem cells, in which the cultures can form more heterogeneous tissues resembling thein vivoteratoma andex vivoliver tissue slices, in which improved maintenance of cellular viability is seen over the 3 days tested. This system has the flexibility to be used for a variety of further uses and has the potential to provide a more accessible alternative to current bioreactor technologies.
In vitro
and computational modelling of drug delivery across the outer blood–retinal barrier
Authors: Davies Alys E. , Williams Rachel L. , Lugano Gaia , Pop Serban R. , Kearns Victoria R.
Published: February 2020

The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate the development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion, due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer blood–retinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary
in vitro
and
in silico
models to study drug transport from silicone oil across the OBRB. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics software and validated using independent
in vitro
datasets. Computational simulations were able to predict dextran movement and ibuprofen release, with all of the features of the experimental release profiles being observed in the simulated data. Simulated values for peak concentrations of permeated dextran and ibuprofen released from silicone oil were within 18% of the
in vitro
results. This model could be used as a predictive tool for drug transport across this important tissue.
Synergism and antagonism of two distinct, but confused, Nrf1 factors in integral regulation of the nuclear-to-mitochondrial respiratory and antioxidant transcription networks
Authors: Zhang Shuwei , Deng Yangxu , Xiang Yuancai , Hu Shaofan , Qiu Lu , Zhang Yiguo
Published: February 2020

There is hitherto no literature available for explaining two distinct, but confused Nrf1 transcription factors, because they shared the same abbreviations from nuclear factor erythroid 2-related factor 1 (also called Nfe2l1) and nuclear respiratory factor (originally designated α-Pal). Thus, we have here identified that Nfe2l1Nrf1and α-PalNRF1exert synergistic and antagonistic roles in integrative regulation of the nuclear-to-mitochondrial respiratory and antioxidant transcription profiles. In mouse embryonic fibroblasts (MEFs), knockout ofNfe2l1–/–leads to substantial decreases in expression levels of α-PalNRF1and Nfe2l2, together with TFAM (mitochondrial transcription factor A) and other target genes. Similar inhibitory results were determined inNfe2l2–/–MEFs, with an exception thatGSTa1andAldh1a1were distinguishably up-regulated inNfe2l1–/–MEFs. Such synergistic contributions of Nfe2l1 and Nfe2l2 to the positive regulation of α-PalNRF1and TFAM were validated inKeap1–/–MEFs. However, human α-PalNRF1expression was unaltered byhNfe2l1α–/–,hNfe2l2–/–ΔTAor evenhNfe2l1α–/–+siNrf2, albeit TFAM was activated by Nfe2l1 but inhibited by Nfe2l2; such an antagonism occured in HepG2 cells. Conversely, almost all of mouse Nfe2l1, Nfe2l2 and co-target genes were down-expressed inα-PalNRF1+/–MEFs. On the contrary, up-regulation of human Nfe2l1, Nfe2l2 and relevant reporter genes took place after silencing of α-PalNRF1, but their down-regulation occurred upon ectopic expression of α-PalNRF1. Furtherly, Pitx2 (pituitary homeobox 2) was also identified as a direct upstream regulator of Nfe2l1 and TFAM, besides α-PalNRF1. Overall, these across-talks amongst Nfe2l1, Nfe2l2 and α-PalNRF1, along with Pitx2, are integrated from the endoplasmic reticulum to the nuclear-to-mitochondrial communication for targeting TFAM, in order to finely tune the cellular respiratory and antioxidant gene transcription networks, albeit they differ between the mouse and the human.
Suppressors of YpsA-mediated cell division inhibition inBacillus subtilis
Authors: Brzozowski Robert S. , Tomlinson Brooke R. , Sacco Michael D. , Chen Judy J. , Ali Anika N. , Chen Yu , Shaw Lindsey N. , Eswara Prahathees J.
Published: February 2020

Although many bacterial cell division factors have been uncovered over the years, evidence from recent studies points to the existence of yet to be discovered factors involved in cell division regulation. Thus, it is important to identify factors and conditions that regulate cell division to obtain a better understanding of this fundamental biological process. We recently reported that in the Gram-positive organismsBacillus subtilisandStaphylococcus aureus, increased production of YpsA resulted in cell division inhibition. In this study, we isolated spontaneous suppressor mutations to uncover critical residues of YpsA and the pathways through which YpsA may exert its function. Using this technique, we were able to isolate four unique intragenic suppressor mutations inypsA(E55D, P79L, R111P, G132E) that rendered the mutated YpsA non-toxic upon overproduction. We also isolated an extragenic suppressor mutation inyfhS, a gene that encodes a protein of unknown function. Subsequent analysis confirmed that cells lackingyfhSwere unable to undergo filamentation in response to YpsA overproduction. We also serendipitously discovered that YfhS may play a role in cell size regulation.

GRAPHICAL ABSTRACT

ABBREVIATED SUMMARY

InBacillus subtilis, we discovered that increased expression ofypsAresults in cell division inhibition and impairment of colony formation on solid medium. Colonies that do arise possess compensatory suppressor mutations. Analysis of one such suppressor mutation led us to a protein of unknown function, YfhS, which appears to play a role in regulating cell length and cell width.
Splice-site Strength Estimation: A simple yet powerful approach to analyse RNA splicing
Authors: Dent Craig , Singh Shilpi , Mishra Shikhar , Shamaya Nawar , Loo Kok Ping , Sarwade Rucha Dilip , Harrison Paul , Sureshkumar Sridevi , Powell David , Balasubramanian Sureshkumar
Published: February 2020

RNA splicing, and variations in this process referred to as alternative splicing, are critical aspects of gene regulation in eukaryotes. From environmental responses in plants to being a primary link between genetic variation and disease in humans, splicing differences confer extensive phenotypic changes across diverse organisms1–3. Current approaches for analysing splicing rely on quantifying variant transcripts (i.e., isoforms) or splicing events (i.e., intron retention, exon skipping etc)4, 5. However, regulation of splicing occurs at the level of selection of individual splice sites, which results in variation in the abundance of isoforms and/or splicing events. Here, we present a simple approach to quantify the strength of individual splice sites, which determines their selection in a splicing reaction. Splice-site strength, as a quantitative phenotype, allows us to analyse splicing precisely in unprecedented ways. We demonstrate the power of this approach in defining the genomic determinants of the strength of individual splice-sites through GWAS. Our pilot-GWAS with more than thousand splice sites hints thatcis-sequence divergence and competition between splice-sites and are among the primary determinants of variation in splicing among natural accessions ofArabidopsis thaliana.This approach allows deciphering the principles of splicing, which in turn has implications that range from agriculture to medicine.
Cell-specific cargo delivery using synthetic bacterial spores
Authors: Kong Minsuk , Updegrove Taylor B. , Constantino Maira Alves , Gallardo Devorah L. , Wu I-Lin , Fitzgerald David J. , Tanner Kandice , Ramamurthi Kumaran S.
Published: February 2020

SSHELs are synthetic bacterial spore-like particles wherein the spore’s cell surface is partially reconstituted around 1 µm-diameter silica beads coated with a lipid bilayer. Via a unique cysteine engineered in one of the surface proteins, the surface of SSHELs may be covalently decorated with molecules of interest. Here, we modified SSHELs with an affibody directed against HER2, a cell surface protein overexpressed in some breast and ovarian cancer cells, and loaded them with the chemotherapeutic agent doxorubicin. Drug-loaded SSHELs reduced tumor growth with lower toxicity in a mouse tumor xenograft model compared to free drug by specifically binding to HER2-positive cancer cells. We show that SSHELs bound to target cells are taken up and trafficked to acidic compartments, whereupon the cargo is released in a pH-dependent manner. Finally, we demonstrate that SHELLs can clear small tumor lesions in a complex tumor microenvironment in a zebrafish model of brain metastasis. We propose that SSHELs represent a versatile strategy for targeted drug delivery.
Factors Affecting Response to Recurrent Genomic Selection in Soybeans
Authors: Ramasubramanian Vishnu , Beavis William D
Published: February 2020

Herein we report the impacts of applying five selection methods across 40 cycles of recurrent selection and identify interactions among factors that affect genetic responses in sets of simulated families of recombinant inbred lines derived from 21 homozygous soybean lines. Our use of recurrence equation to model response from recurrent selection allowed us to estimate the half-lives, asymptotic limits to recurrent selection for purposes of assessing the rates of response and future genetic potential of populations under selection. The simulated factors include selection methods, training sets, and selection intensity that are under the control of the plant breeder as well as genetic architecture and heritability. A factorial design to examine and analyze the main and interaction effects of these factors showed that both the rates of genetic improvement in the early cycles and limits to genetic improvement in the later cycles are significantly affected by interactions among all factors. Some consistent trends are that genomic selection methods provide greater initial rates of genetic improvement (per cycle) than phenotypic selection, but phenotypic selection provides the greatest long term responses in these closed genotypic systems. Model updating with training sets consisting of data from prior cycles of selection significantly improved prediction accuracy and genetic response with three parametric genomic prediction models. Ridge Regression, if updated with training sets consisting of data from prior cycles, achieved better rates of response than BayesB and Bayes LASSO models. A Support Vector Machine method, with a radial basis kernel, had the worst estimated prediction accuracies and the least long term genetic response. Application of genomic selection in a closed breeding population of a self-pollinated crop such as soybean will need to consider the impact of these factors on trade-offs between short term gains and conserving useful genetic diversity in the context of the goals for the breeding program.
Crystal structure, Hirshfeld surface analysis and DFT studies of 1,3-bis[2-methoxy-4-(prop-2-en-1-yl)phenoxy]propane
Authors: Taia Abdelmaoujoud , Essaber Mohamed , Hökelek Tuncer , Aatif Abdeljalil , Mague Joel T. , Alsalme Ali , Al-Zaqri Nabil
Published: February 2020

The asymmetric unit of the title compound, C23H28O4, comprises two half-molecules, with the other half of each molecule being completed by the application of twofold rotation symmetry. The two completed molecules both have a V-shaped appearance but differ in their conformations. In the crystal, each independent molecule forms chains extending parallel to the b axis with its symmetry-related counterparts through C—H...π(ring) interactions. Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (65.4%), H...C/C...H (21.8%) and H...O/O...H (12.3%) interactions. Optimized structures using density functional theory (DFT) at the B3LYP/6–311 G(d,p) level are compared with the experimentally determined molecular structures in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.
The predictive value of strategic orientation for ESG performance over time
Authors: Chevrollier Nicolas , Zhang Jianhong , van Leeuwen Thijs , Nijhof André
Published: February 2020

Purpose

Despite the scholarly attention for the integration of sustainability within business strategy and processes, little is known about how strategic orientations of companies influence this integration. Drawing on stewardship theory, this paper aims to analyse the influence of strategic orientation of companies on their environmental, social and corporate governance (ESG) performance and the moderating effect of three different political models of economy (Rhine, British and American).

Design/methodology/approach

This paper creates a measurement for strategic orientations by using a coding scheme with a five-category evaluation matrix. The main empirical analysis is done by a fixed-effect model with a panel data set covering 179 publicly traded companies over the 2009-2016 period.

Findings

The conclusions of this paper present that – consistent over time – a stronger orientation on stewardship positively associates with higher ESG performance. Additionally, the political model of economy significantly alters the relationship indicating the effect of strategic orientation on ESG performance. The relationship is significantly stronger in the Rhine model and significantly weaker in the British model, when both compared to the American model.

Originality/value

The implications of this paper are vital to understanding corporate strategic orientation and its relationship to actual corporate behaviour and long-term performance. Implementing the elements of focus, motivation, commitment, support and communication linked to a stewardship orientation is fundamental to achieve higher levels of sustainability performance.
Influence of local institutional profile on global value chain participation
Authors: Hong Jin , Zhou Chongyang , Wang Ruicheng
Published: February 2020

Purpose

The emergence and rapid expansion of global value chains (GVCs) have profoundly changed and reshaped the global trade regime. Although many determinants of GVC participation of enterprises have been discussed extensively in extant literature, the important influence of local institutional profile on GVC participation is often neglected. The purpose of this paper is to investigate the influence of local institutional profile on GVC participation.

Design/methodology/approach

Taking the World Bank Enterprise Survey as the empirical sample, it is used an econometric method (propensity score matching technique) to test the relationship between local institutional profile and GVC participation.

Findings

Local institutional quality is positively related to GVC participation. Moreover, GVC participants display better innovation performance than non-participants. Innovation benefit from GVC participation is contingent upon the abilities of the participants, namely, absorptive capacity and research and development collaboration experience. GVC participants who only either export or import is compared with those who export and import; the findings show that the latter benefits more than the former.

Originality/value

This study offers researchers and practitioners a detailed view of local institutional profile and GVC participation.
Determinants of adoption and continuance intentions toward Internet-only banks
Authors: Lee Jin-Myong , Kim Hyo-Jung
Published: February 2020

Purpose

The purpose of this study is to investigate the determinants of consumers' intention to adopt or continue to use Internet-only banks based on the benefit–risk framework and network externality theory. It also examines the difference in the determinants between pre- and postadoption stages of innovation.

Design/methodology/approach

The proposed research model was tested by using online survey data collected from a South Korean sample, which was divided into two subgroups of 321 nonadopters and 351 existing users.

Findings

In both pre- and postadoption stages, the number of services provided and trust had a significant positive impact on consumers' behavioral intentions, while security risks had a negative impact. Critical mass in the preadoption stage and convenience and economic efficiency in the postadoption stage had positive effects on consumer's adoption intention and continuance intention, respectively.

Practical implications

Internet-only banks must reduce the security risks for consumers and increase their trust. In addition, to facilitate the adoption of nonadopters, focus should be on securing a critical mass; on the other hand, to promote the continued use of existing users, the focus should be on enhancing benefits such as convenience and economic efficiency.

Originality/value

The results of this study confirm the influence of network externalities on consumers' adoption and use of financial technology services and show differences in consumer decision-making according to the innovation diffusion process.
The effect of service improvisation competence on hotel performance
Authors: Secchi Enrico , Roth Aleda , Verma Rohit
Published: February 2020

Purpose

The development of a service improvisation competence (Serv-IC), operationally defined as “the systemic ability of a service firm’s employees to deviate from established service delivery processes and routines to respond in a timely manner to unforeseen events using available resources” (Secchiet al., 2019, p. 1329), has been proposed as an effective way to accommodate customer variability while increasing the quality of the service experience. However, empirical evidence of its impact on service performance is scant. This paper tests the effect of Serv-IC on performance in the hospitality industry.

Design/methodology/approach

This paper develops a conceptual typology of service delivery systems (hereafter service typology is used interchangeably) in the hotel industry based on the experiential content of the service and the amount of standardization of service delivery routines. Then, using a survey of hotel managers, the effect of Serv-IC on hotel performance is estimated within each service group in the typology.

Findings

Serv-IC is associated with increased occupancy in high-process-standardization and high-experience hotel operations but does not have a significant relationship with the average price per room. The results suggest that managers could invest in Serv-IC to increase loyalty and positive word of mouth but not to increase prices.

Originality/value

This paper provides evidence of the effectiveness of developing a service improvisation competence while also offering boundary conditions to its applicability. The proposed service typology disentangles the design of service processes from their execution, thereby shedding new light on the complex relationships among service design, employee behaviors and business outcomes.
Tourism distribution in small island destinations: the case of Fernando de Noronha, Brazil
Authors: Andrade Amalina , Smith Karen A.
Published: February 2020

Purpose

This paper investigates tourism distribution channels in a small island destination with capacity constraints and contributes to understanding distribution in an emerging economy. Using the case of Fernando de Noronha in Brazil, the structures and factors underlying channel choice behaviour of tourism suppliers and intermediaries were investigated.

Design/methodology/approach

41 in-depth interviews were conducted with the private sector (tourism suppliers based on Fernando de Noronha and intermediaries, based on the island as well as mainland Brazil) as well as governmental organisations. A stratified purposeful sample was taken to select suppliers and data were examined based on thematic analysis.

Findings

Both direct and indirect distribution channels are used, with limited airline tickets influencing the suppliers' choice of channels in this small island and capacity-constrained destination. Many suppliers focused on relationships with destination-based ground operators. These local intermediaries are important and extremely relevant to small island destinations building an effective business network to connect the destination to geographically distant markets and intermediaries.

Research limitations/implications

Limitations include the absence of air and cruise operators as interviewees.

Originality/value

The paper provides a comprehensive representation of the structures and analysis of tourism distribution channels in fragile small island destinations, specifically, in an emerging country context. This includes emphasising previously unexplored indirect channels of cruise ship operators and supplier's associations.
Innovation management processes and sustainable iterative circles: an applied integrative approach
Authors: Miller Christopher , Thomas Brychan Celfyn , Roeller Michael
Published: February 2020

Purpose

This study attempts to create new insights into innovation management through the integration of innovation management processes and sustainable, iterative circles. Through the exploration of the use of sustainable, iterative circles in a manufacturing environment, this paper explores their role in facilitating customer-focused innovation practices. Other supporting antecedences for innovative behavior are reviewed, and their combined effect upon delivering cost-effective product developments are assessed.

Design/methodology/approach

Data were collected through semi-structured interviews in manufacturing organizations from the automotive industry. Interviews were conducted with senior functional managers to interpret the application of sustainable, iterative development circles. Analysis of the data was undertaken via thematic analysis based upon pertinent and emergent themes.

Findings

Sustainable, iterative development circles overcame the inherent path-dependency of traditional linear development approaches, whereas, traditional approaches structure the involvement of key business functions, iterative circles facilitate more flexible approaches to product development that more closely met the requirements of the customer, especially when those requirements are in a state of flux.

Practical implications

This iterative, customer-centric approach to product development reflects the increasingly dynamic market environments in which manufacturing organizations operate. Using this approach helps to focus the organization’s attention upon customer requirements rather than the challenges of adhering to the rigid dogma of a chosen development methodology.

Originality/value

This study proposes a new approach toward the development of innovations in manufacturing organizations utilizing the sustainable, iterative circles, and therefore, contrasts with the traditional, linear development methodologies that are usually employed.