bluuebunny/crossref_metadata_2025 huggingface dataset:
WITHDRAWN: Genomic decoding of neuronal depolarization by stimulus-specific NPAS4 heterodimers
Authors: Stefano Brigidi G. , Hayes Michael G. B. , Hartzell Andrea L. , Texari Lorane , Lin Pei-Ann , Bartlett Anna , Ecker Joseph R , Benner Christopher , Heinz Sven , Bloodgood Brenda L.
Published: March 2019

WITHDRAWAL STATEMENT

This manuscript has been withdrawn after a formal request from The Office of Research Integrity of the U.S. Department of Health & Human Services, with the support of the corresponding author, Brenda Bloodgood. More information can be found athttps://ori.hhs.gov/content/case-summary-brigidi-gian-stefano.
Antitumor Activities and Cellular Changes Induced by TrkB Inhibition in Medulloblastoma
Authors: Thomaz Amanda , de Vargas Pinheiro Kelly , Souza Bárbara Kunzler , Gregianin Lauro , Brunetto Algemir L. , Brunetto André T. , de Farias Caroline Brunetto , da Cunha Jaeger Mariane , Ramaswamy Vijay , Nör Carolina , Taylor Michael D. , Roesler Rafael
Published: March 2019

Neurotrophins are critically involved in regulating in normal neural development and plasticity. Brain-derived neurotrophic factor (BDNF), a neurotrophin that acts by binding to the tropomyosin receptor kinase B (TrkB) receptor, has also been implicated in the progression of several types of cancer. However, its role in medulloblastoma (MB), the most common type of malignant brain tumor afflicting children, remains unclear. Here we show that selective TrkB inhibition with the small molecule compound ANA-12 impaired proliferation and viability of human UW228 and D283 MB cells. These effects were accompanied by increased apoptosis, reduced extracellular-regulated kinase (ERK) activity, increased expression of signal transducer and activator of transcription 3 (STAT3), and differential modulation of p21 expression dependent on the cell line. In addition, MB cells treated with ANA-12 showed morphological alterations consistent with differentiation, increased levels of the neural differentiation marker β-III Tubulin (TUBB3), and reduced expression of the stemness marker Nestin. Finally, TrkB inhibition was able to slow the growth of MB tumors xenografted into nude mice. These findings are consistent with the hypothesis that selective TrkB inhibition can display consistent anticancer effects in MB, possibly by modulating intracellular signaling and gene expression related to tumor progression, apoptosis, and differentiation.
A Complex Interplay of Anionic Phospholipid Binding Regulates 3’-Phosphoinositide-Dependent-Kinase-1 Homodimer Activation
Authors: de las Heras-Martínez Gloria , Calleja Véronique , Bailly Remy , Dessolin Jean , Larijani Banafshé , Requejo-Isidro Jose
Published: March 2019

3’-Phosphoinositide-dependent-Kinase-1 is a master regulator whereby its PI3-kinase-dependent dysregulation in human pathologies is well documented. Understanding the direct role for PtdIns(3,4,5)P3and other anionic phospholipids in the regulation of PDK1 conformational dynamics and its downstream activation remains incomplete.

Using advanced quantitative-time-resolved imaging, FCS and molecular modelling, we show an interplay of antagonistic binding effects of PtdIns(3,4,5)P3and other anionic phospholipids, regulating activated PDK1 homodimers. We demonstrate that phosphatidylserine maintains PDK1 in an inactive conformation. The dysregulation of the PI3K pathway affects the spatio-temporal and conformational dynamics of PDK1 and the activation of its downstream substrates.

We establish an anionic-phospholipid-dependent model for PDK1 regulation, depicting the conformational dynamics of multiple homodimer states. The dysregulation of the PI3K pathway perturbs equilibrium between the PDK1 homodimer conformations. Our findings indicate that the alteration of specific basic residues of PDK1-PH domain leads to its constitutive activation, a potential significance in different types of carcinomas.
Rho-dependent control of the Citron kinase, Sticky, drives midbody ring maturation
Authors: El-amine Nour , Carim Sabrya C. , Wernike Denise , Hickson Gilles R.X.
Published: March 2019

Rho-dependent proteins control assembly of the cytokinetic contractile ring (CR), yet it remains unclear how those proteins guide ring closure and how they promote subsequent formation of a stable midbody ring (MR). Citron kinase is one important component required for MR formation but its mechanisms of action and relationship with Rho are controversial. Here, we conduct a structure-function analysis of theDrosophilaCitron kinase, Sticky, in Schneider’s S2 cells. We define two separable and redundant RhoGEF/Pebble-dependent inputs into Sticky recruitment to the nascent MR and show that each input is subsequently required for retention at, and for the integrity of, the mature MR. The first input is via an actomyosin-independent interaction between Sticky and Anillin, a key scaffold also required for MR formation. The second input requires the Rho-binding domain of Sticky, whose boundaries we have defined. Collectively, these results show how MR biogenesis depends on the coordinated actions of Sticky, Anillin and Rho.
Ex vivo expansion of skeletal muscle stem cells with a novel small compound inhibitor of eIF2α dephosphorylation
Authors: Lean Graham , Halloran Matt , Mariscal Oceane , Jamet Solene , Lumb Jean-Phillip , Crist Colin
Published: March 2019

BACKGROUND

Regeneration of adult tissues requires the activity of rare, mitotically quiescent somatic stem cells. These features are illustrated by the muscle stem cell (MuSC), also known as the satellite cell for its satellite position underneath the basal lamina of the myofiber. Isolation of MuSCs results in their rapid activation of the myogenic program and their subsequent culture ex vivo leads to loss of stem cell regenerative capacity. These shortcomings make MuSCs difficult to study, manipulate and prevent cell based therapies. We have previously shown that muscle stem cells (MuSCs) require tightly regulated protein synthesis through the phosphorylation of eIF2α. Sal003, an analog of salubrinal that blocks eIF2α dephosphorylation, promotes ex vivo expansion of MuSCs retaining regenerative capacity after engraftment into the Dmdmdx mouse model of Duchenne muscular dystrophy.

METHODS

Since micromolar concentrations of sal003 (10μM) are required to expand MuSCs ex vivo, we undertook a structure relations study to identify novel sal003 analogs with efficacy at lower concentrations. We demonstrate ex vivo expansion of MuSCs isolated from wild-type and mdx mice using new compounds, and use CRISPR/Cas9 genome editing tools to restore dystrophin expression in cultured MuSCs.

RESULTS

Here, we have synthesized and screened chemical analogs of sal003 to identify a novel compound promoting the ex vivo expansion of MuSCs. The novel compound expands wild-type and mdx MuSCs more efficiently than sal003 and also prolongs culture of primary myoblasts from isolated MuSCs.

CONCLUSIONS

We identify a novel sal003 analog, C10, with increased potency at lower concentrations. Culture conditions including sal003 or C10 can extend culture of primary myoblasts from isolated MuSCs, which we predict will enable their further study, genetic manipulation and cell based therapies.
Circulating tumor DNA dynamics using patient-customized assays are associated with outcome in neoadjuvantly treated breast cancer
Authors: Butler Timothy M. , Boniface Christopher T. , Johnson-Camacho Katie , Tabatabaei Shaadi , Melendez Daira , Kelley Taylor , Gray Joe , Corless Christopher L. , Spellman Paul T.
Published: March 2019

Pathological complete response (pCR) is an accurate predictor of good outcome following neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. The presence of circulating-tumor DNA (ctDNA) has recently been reported to be strongly predictive of poor outcome in similar patient groups. We monitored ctDNA levels from 10 women undergoing NAC for locally advanced breast cancer using a patient-specific, hybrid-capture sequencing technique sensitive to the level of one altered allele in 10,000. Plasma was collected prior to the start of NAC, prior to each infusion of NAC, and during follow-up for between 350 and 1150 d after the start of NAC. Prior to the start of NAC, ctDNA was detectable in 3/3 triple negative, 3/3 HER2+, and 2/4 HER2−, ER+ breast cancer patients. Total cell-free DNA levels were considerably higher when patients were on NAC than at other times. ctDNA dynamics during NAC showed that patients with pCR experienced rapid declines in ctDNA levels, whereas patients without pCR typically showed evidence of residual ctDNA after initiation of treatment. Intriguingly, two of three patients that showed marked increases in ctDNA while on NAC experienced rapid recurrences (<2 yr following start of NAC). The third patient that had increases in ctDNA levels while on NAC had low-grade ER+ disease and showed residual ctDNA after surgery, which became undetectable after local radiation. Taken together, these results demonstrate the ability of our approach to sensitively serially monitor ctDNA during NAC, and identifies a need to further investigate the possibility of stratifying patients who need additional treatment or identify therapies that are ineffective.
Host country experience, institutional distance and location choice of Chinese MNEs
Authors: Quer Diego , Rienda Laura , Andreu Rosario , Miao Si
Published: March 2019

Purpose

The conventional wisdom suggests that the lack of prior host country-specific experience and a higher institutional distance deter multinational enterprises (MNEs) from entering a foreign country. However, past studies report that Chinese MNEs show an unconventional risk-taking behavior choosing foreign locations, where they have no prior experience or there is an increased institutional distance. Drawing on the institutional theory, the purpose of this paper is to argue that Chinese Government official visits to the host country may act as a risk-reduction device, thus providing an explanation for such an unconventional behavior.

Design/methodology/approach

The authors develop two hypotheses regarding how Chinese Government official visits moderate the impact of host country-specific experience and institutional distance on the location choice of Chinese MNEs. The authors test the hypotheses using a sample of investment location decisions by Chinese MNEs in Latin America.

Findings

The authors find that government official visits mitigate the lack of firm’s prior host country experience. However, only high-level government visits reduce institutional distance.

Originality/value

The authors contribute to the international business literature by analyzing how home country government diplomatic activities may pave the way of host country institutional environment for foreign MNEs from that home country. In addition, the authors provide an additional explanation for the unconventional risk-taking behavior of Chinese MNEs. Finally, the authors also contribute to a better understanding of the decision-making process of emerging-market MNEs entering other emerging economies.
The Gadamerian hermeneutics for a mesoeconomic analysis of Cultural Heritage
Authors: Settembre Blundo Davide , Maramotti Politi Anna Lucia , Fernández del Hoyo Alfonso Pedro , García Muiña Fernando Enrique
Published: March 2019

Purpose

The purpose of this paper is to explore the application of a hermeneutic-based approach as innovative way to study the Cultural Heritage management in a mesoeconomic space.

Design/methodology/approach

The paper builds a theoretical framework based on the analysis of relevant literature in the field of cultural economics, heritage economics and conservation and restoration techniques. Then, after having defined the conceptual hypothesis, a hermeneutical interpretative model is designed for the analysis of the processes of Cultural Heritage management with particular regard to the strategies of stakeholder engagement.

Findings

The research shows how the mesoeconomic space is that border area where it is possible to solve more easily the conflicts that arise as a result of the different expectations of stakeholders. Hermeneutical analysis, applied in iterative form, allows us to find common connections, points of contact and convergences between the interpretative horizons of the various stakeholders.

Practical implications

The application of the interpretative model allows the identification of the expectations of stakeholders, improving the knowledge of the tangible and intangible attributes of works of art, in order to design appropriate interventions of restoration, conservation and valorization.

Social implications

The new model of analysis, based on hermeneutic methodology, is designed to understand and describe the social and economic relations between the different stakeholders involved in the management of Cultural Heritage.

Originality/value

This paper examines for the first time the Cultural Heritage sector within the mesoeconomic area between the micro and the macroeconomy. In addition to this mesoeconomic analysis and conceptual approach, the authors introduce as methodology the economic hermeneutics that represents an innovative tool in the field of economic and business disciplines.
Work to be done? A survey of educational psychologists’ contribution to special schools for profound and multiple learning difficulties
Authors: Winter Sophie , Bunn Helena
Published: March 2019

This article explores the perspectives of educational psychologists across England with regard to their professional involvement, role and contribution to special schools for children and young people with profound and multiple learning difficulties (PMLD). An online survey was distributed to all educational psychology services in England and to private educational psychology practices. Data collected from 207 respondents were analysed using descriptive statistics and quantitative and qualitative content analysis. The findings suggest a complex national picture, including great variation in the frequency of educational psychology visits and indirect contact with the special schools. While the work carried out by educational psychologists in these special schools is primarily individual, statutory‐led casework, systemic work is considered to be the ‘ideal’ contribution. Educational psychologists’ views on their role in PMLD settings seem to feature limited ideas. The authors suggest that improving educational psychologists’ skills and knowledge of PMLD, building relationships with special schools and finding a niche in supporting, among other things, the emotional well‐being of the school’s community, might be ways forward for working in PMLD schools. The article concludes by emphasising the continued need for the profession to understand and market the specific role it can play in PMLD settings.
Do timely mental health services reduce re‐incarceration among prison releasees with severe mental illness?
Authors: Domino Marisa Elena , Gertner Alex , Grabert Brigid , Cuddeback Gary S. , Childers Trenita , Morrissey Joseph P.
Published: March 2019

Objective

To examine whether the receipt of timely mental health services is associated with changes in criminal justice interactions.

Data Sources

We used linked administrative data from Medicaid, mental health, and criminal justice settings in Washington State for persons with severe mental illness released from prison (n = 3086).

Study Design

We estimate local and average treatment effects to examine measures of criminal justice use in the year following release as a function of timely mental health services.

Data Extraction Methods

Measures of timely service and criminal justice use within 12 months postrelease were created from administrative data.

Principal Findings

Individuals receiving timely mental health services are more likely to experience prison re‐incarceration overall and specifically for technical violations 12 months postrelease. The effect of service receipt on incarceration for new charges was negative but not significant.

Conclusions

The finding that mental health services receipt is associated with increased risk of re‐incarceration due to technical violations speaks to the complexity of the relationship between mental health and criminal justice services for justice‐involved persons with severe mental illness. Further research should examine strategies at the interface of criminal justice and mental health that can improve mental health and criminal justice outcomes for this vulnerable population.
Fat and fat‐free mass of healthy Swedish children show tracking during early life, but there are differences
Authors: Forsum E , Eriksson B , Flinke E , Henriksson H , Henriksson P , Löf M
Published: March 2019

Aim

Obesity may start early in life. We investigated relationships between size and body composition variables in infancy and at 4 years of age using valid estimates of body composition. The results were compared to those obtained when body mass index (BMI) was used to estimate body fatness at 4 years.

Methods

Using air displacement plethysmography, size, fat mass and fat‐free mass were studied, between 2007 and 2015, in 253 full‐term healthy Swedish children at 1 week, 12 weeks and 4 years of age.

Results

Positive associations between variables in infancy and at 4 years were found at 1 and 12 weeks for weight, height, BMI, fat‐free mass and fat‐free mass index (p ≤ 0.002) and for fat mass, per cent body fat and fat mass index (p ≤ 0.04) at 12 weeks. Fat mass gained during infancy correlated positively (p ≤ 0.031) with per cent fat mass, fat mass index and BMI, all at 4 years. In girls, gains in fat‐free mass during infancy correlated with BMI (p = 0.0005) at 4 years.

Conclusion

The results provide information regarding body composition trajectories during early life and demonstrate limitations of BMI as a proxy for body fatness when relating early weight gain to variables, relevant for later obesity risk.
A latent growth curve analysis of precursor cognitive abilities and academic achievement
Authors: Moxley‐Paquette Elizabeth A. , Burkholder Gary J.
Published: March 2019

Background

Language‐based cognitive fitness describes the ability to carry out cognitive tasks with vigour and alertness, to learn, and to adapt.

Aims

The purpose of this research was to test the efficacy of a brain fitness training programme to better understand the role played by three precursor abilities for language‐based cognitive development—verbal reasoning, visual synthesis, and active analysis—and their impact on academic achievement.

Sample

The sample included 92 children from a private school designed to deliver a prescriptive educational model for the spectrum of challenged, average, and gifted students.

Method

Students completed cognitive tests at entry to the program and at the end of each academic year. Students completed daily brain‐based exercises. Associative latent variable growth curve modelling using Mplus was used to test growth in all variables. Bayesian estimation analysis was used for missing data imputation. Age and baseline cognitive ability were included as covariates.

Results

Model fit was excellent, χ2(104) = 115.98, p = .20, (χ2/df) = 1.11, CFI = 0.98, TLI = 0.98, RMSEA = 0.04, SRMR = 0.05. Students who started with the lowest ability levels initially grew faster than those students with higher initial two‐wave performance levels consistent with a closing of an ability gap. This had a lagged effect on achievement that accelerated in growth after the first 2 years.

Conclusions

Results provide evidence for the importance of interventions that focus on strengthening precursor cognitive abilities directly involved with language and mathematics achievement.
How we manage haemostasis during sepsis
Authors: Scully Marie , Levi Marcel
Published: March 2019

Sepsis may be associated with activation of the coagulation system and, in its most severe form, may result in disseminated intravascular coagulation (DIC). Initially, there is thrombosis primarily affecting small and medium sized vessels and contributing to organ dysfunction, but continued activation results in consumption of coagulation factors. This results in prolongation of global coagulation parameters. Often thrombocytopenia is the initial feature in sepsis, which may be followed by prolongation of global coagulation assays, and in severe cases, associated with hypofibrinogenaemia, with overactivation of the fibrinolytic path. The end result is a bleeding phenotype. Scoring systems can be used to help identify patients at risk of DIC and aid in confirming a diagnosis of DIC utilising routine laboratory parameters. Discussion includes medical and blood product support of haemostasis, from thrombotic to bleeding states, in relation to sepsis trigger.
The role of FOXP3+ regulatory T cells in human autoimmune and inflammatory diseases
Authors: Mohr A , Atif M , Balderas R , Gorochov G , Miyara M
Published: March 2019

CD4+ regulatory T cells (Treg) expressing the forkhead box protein 3 (FOXP3) transcription factor (Tregs) are instrumental for the prevention of autoimmune diseases. There is increasing evidence that the human T regulatory population is highly heterogeneous in phenotype and function. Numerous studies conducted in human autoimmune diseases have shown that Treg cells are impaired either in their suppressive function, in number, or both. However, the contribution of the FOXP3+ Treg subpopulations to the development of autoimmunity has not been delineated in detail. Rare genetic disorders that involve deficits in Treg function can be studied to develop a global idea of the impact of partial or complete deficiency in a specific molecular mechanism involved in Treg function. In patients with reduced Treg numbers (but no functional deficiency), the expansion of autologous Treg cells could be a suitable therapeutic approach: either infusion of in-vitro autologous expanded cells, infusion of interleukin (IL)-2/anti-IL-2 complex, or both. Treg biology-based therapies may not be suitable in patients with deficits of Treg function, unless their deficit can be corrected in vivo/in vitro. Finally, it is critical to consider the appropriate stage of autoimmune diseases at which administration of Treg cellular therapy can be most effective. We discuss conflicting data regarding whether Treg cells are more effectual at preventing the initiation of autoimmunity, ameliorating disease progression or curing autoimmunity itself.
Clonal highlights: Clonal seborrheic keratoses often demonstrates p16 expression
Authors: Omman Reeba A. , Speiser Jodi , Robinson Shamika , Lapadat Razvan , Mudaliar Kumaran
Published: March 2019

Background

At times, distinguishing Bowen disease (BD) and benign seborrheic keratosis (SK) is histologically challenging, especially when SK shows clonal features (clonal seborrheic keratosis [CSK]). While p16 is often reported as positive in BD and negative in SK, p16 expression in CSK is rarely studied. Here we investigate p16 immunohistochemistry in CSK, SK, and BD.

Methods

p16 immunohistochemistry with pattern of expression was noted for 14 CSK, 12 SK, and 18 BD. The degree of inflammation among lesions with respect to p16 expression was also noted.

Results

When examining p16 staining in clonal nests of CSK, 57% showed diffuse or patchy/diffuse positivity, 21% showed patchy positivity, and 21% showed clusters of single positive cells. 67% of BD showed diffuse positivity, 11% showed patchy/diffuse positivity, 17% showed patchy positivity, and 6% were negative. 25% of SK showed focal areas of patchy to full thickness positivity, 25% showed moderate number of positive single cells with or without patchy staining, and 50% showed negative/scattered single cell positivity.

Conclusion

Our findings support that p16 positivity limited to clonal nests in CSK is normal. p16 positivity in clonal nests of CSK in isolation without concurrent atypical histologic features should not be used to support a diagnosis of BD.
Attention and executive functioning in infancy: Links to childhood executive function and reading achievement
Authors: Blankenship Tashauna L. , Slough Madeline A. , Calkins Susan D. , Deater‐Deckard Kirby , Kim‐Spoon Jungmeen , Bell Martha Ann
Published: March 2019

This study provides the first analyses connecting individual differences in infant attention to reading achievement through the development of executive functioning (EF) in infancy and early childhood. Five‐month‐old infants observed a video, and peak look duration and shift rate were video coded and assessed. At 10 months, as well as 3, 4, and 6 years, children completed age‐appropriate EF tasks (A‐not‐B task, hand game, forward digit span, backwards digit span, and number Stroop). Children also completed a standardized reading assessment and a measure of verbal intelligence (IQ) at age 6. Path analyses on 157 participants showed that infant attention had a direct statistical predictive effect on EF at 10 months, with EF showing a continuous pattern of development from 10 months to 6 years. EF and verbal IQ at 6 years had a direct effect on reading achievement. Furthermore, EF at all time points mediated the relation between 5‐month attention and reading achievement. These findings may inform reading interventions by suggesting earlier intervention time points and specific cognitive processes (i.e. 5‐month attention).
Drier tropical forests are susceptible to functional changes in response to a long‐term drought
Authors: Aguirre‐Gutiérrez Jesús , Oliveras Imma , Rifai Sami , Fauset Sophie , Adu‐Bredu Stephen , Affum‐Baffoe Kofi , Baker Timothy R. , Feldpausch Ted R. , Gvozdevaite Agne , Hubau Wannes , Kraft Nathan J. B. , Lewis Simon L. , Moore Sam , Niinemets Ülo , Peprah Theresa , Phillips Oliver L. , Ziemińska Kasia , Enquist Brian , Malhi Yadvinder
Published: March 2019

Climatic changes have profound effects on the distribution of biodiversity, but untangling the links between climatic change and ecosystem functioning is challenging, particularly in high diversity systems such as tropical forests. Tropical forests may also show different responses to a changing climate, with baseline climatic conditions potentially inducing differences in the strength and timing of responses to droughts. Trait‐based approaches provide an opportunity to link functional composition, ecosystem function and environmental changes. We demonstrate the power of such approaches by presenting a novel analysis of long‐term responses of different tropical forest to climatic changes along a rainfall gradient. We explore how key ecosystem's biogeochemical properties have shifted over time as a consequence of multi‐decadal drying. Notably, we find that drier tropical forests have increased their deciduous species abundance and generally changed more functionally than forests growing in wetter conditions, suggesting an enhanced ability to adapt ecologically to a drying environment.
Schizophrenia is a later‐onset feature ofPCDH19Girls Clustering Epilepsy
Authors: Vlaskamp Danique R. M. , Bassett Anne S. , Sullivan Joseph E. , Robblee Jennifer , Sadleir Lynette G. , Scheffer Ingrid E. , Andrade Danielle M.
Published: March 2019

Objective

To investigate the occurrence of psychosis and serious behavioral problems in females with protocadherin 19 gene (PCDH19) pathogenic variants.

Methods

We evaluated whether psychosis and serious behavioral problems had occurred in 60 females (age 2‐75 years) withPCDH19pathogenic variants belonging to 35 families. Patients were identified from epilepsy genetics databases in Australia, New Zealand, theUnited States,and Canada. Neurologic and psychiatric disorders were diagnosed using standard methods.

Results

Eight of 60 females (13%) from 7 families developed a psychotic disorder: schizophrenia (6), schizoaffective disorder (1), or an unspecified psychotic disorder (1). Median age at onset of psychotic symptoms was 21 years (range 11‐28 years). In our cohort of 39 females aged 11 years or older, 8 (21%) developed a psychotic disorder. Seven had ongoing seizures at onset of psychosis, with 2 continuing to have seizures when psychosis recurred. Psychotic disorders occurred in the setting of mild (4), moderate (2), or severe (1) intellectual disability, or normal intellect (1). Preexisting behavioral problems occurred in 4 patients, and autism spectrum disorder in 3. Two additional females (3%) had psychotic features with other conditions: an adolescent had recurrent episodes of postictal psychosis, and a 75‐year‐old woman had major depression with psychotic features. A further 3 adolescents (5%) with moderate to severe intellectual disability had onset of severe behavioral disturbance, or significant worsening.

Significance

We identify that psychotic disorders, including schizophrenia, are a later‐onset manifestation ofPCDH19Girls Clustering Epilepsy. Affected girls and women should be carefully monitored for later‐onset psychiatric disorders.
Residential Satisfaction among College Students: Examining High‐End Amenity Student Housing
Authors: Moore Haley Pierce , Carswell Andrew T. , Worthy Sheri , Nielsen Robert
Published: March 2019

Compared to previous generations of students, today's college‐bound students have found that their housing situation offers demonstrably more amenities. These amenities can be offered either through university‐provided housing or through private student housing providers specializing in high‐amenity housing. This study is based on research on residential satisfaction, housing adjustment theory, and housing careers to help understand the effects that these amenities have on the students’ overall well‐being. The sample is extracted from a database collected by a private student housing provider covering multiple university settings across the United States. The results of data analysis suggest that while amenities such as resort‐style pools and fast Internet speed increase housing satisfaction, other amenities such as computer rooms and coffee shops have a negative effect. However, several variables measuring quality of customer service have positive effects on housing satisfaction. The results suggest that the students’ experiences in these environments may help form their housing norms as they leave college.
RAF dimers control vascular permeability and cytoskeletal rearrangements at endothelial cell‐cell junctions
Authors: Dorard Coralie , Cseh Botond , Ehrenreiter Karin , Wimmer Reiner , Varga Andrea , Hirschmugl Tatjana , Maier Barbara , Kramer Karina , Fürlinger Sabine , Doma Eszter , Baccarini Manuela
Published: March 2019

The endothelium functions as a semipermeable barrier regulating fluid homeostasis, nutrient, and gas supply to the tissue. Endothelial permeability is increased in several pathological conditions including inflammation and tumors; despite its clinical relevance, however, there are no specific therapies preventing vascular leakage. Here, we show that endothelial cell‐restricted ablation of BRAF, a kinase frequently activated in cancer, prevents vascular leaking as well metastatic spread. BRAF regulates endothelial permeability by promoting the cytoskeletal rearrangements necessary for the remodeling of VE‐Cadherin‐containing endothelial cell–cell junctions and the formation of intercellular gaps. BRAF kinase activity and the ability to form complexes with RAS/RAP1 and dimers with its paralog RAF1 are required for proper permeability control, achieved mechanistically by modulating the interaction between RAF1 and the RHO effector ROKα. Thus, RAF dimerization impinges on RHO pathways to regulate cytoskeletal rearrangements, junctional plasticity, and endothelial permeability. The data advocate the development of RAF dimerization inhibitors, which would combine tumor cell autonomous effect with stabilization of the vasculature and antimetastatic spread.
Efficacy of aloe vera mouthwash versus chlorhexidine on plaque and gingivitis: A systematic review
Authors: Al‐Maweri Sadeq A. , Nassani Mohammad Zakaria , Alaizari Nader , Kalakonda Butchibabu , Al‐Shamiri Hashem M. , Alhajj Mohammed N. , Al‐Soneidar Walid A. , Alahmary Ahmed W.
Published: March 2019

Objectives

The present systematic review assessed the efficacy of aloe vera mouthrinse on plaque and gingival inflammation.

Methods

A comprehensive search of PubMed, EMBASE, Scopus and Web of Science was conducted in February 2018 to identify all relevant studies using the following keywords: aloe vera, gingivitis, gingival inflammation, plaque‐induced gingivitis, periodontal health and plaque control. The eligibility criteria were all randomized clinical trials that assessed the efficacy of aloe vera mouthrinse in comparison to chlorhexidine on plaque and gingivitis. The risk of bias of the included studies was assessed using the Cochrane risk of bias assessment tool.

Results

Six randomized clinical trials comprising 1358 subjects were included in this systematic review. All included studies showed that aloe vera was effective in reducing plaque and gingival inflammation. Four studies found aloe vera as effective as chlorhexidine in reducing plaque scores, while two studies found chlorhexidine significantly more effective than aloe vera. With regard to gingival inflammation, three studies showed comparable results between aloe vera and chlorhexidine, while one study showed better results with chlorhexidine. Moreover, the results showed that aloe vera had no or very minimal side effects compared to chlorhexidine, which showed significant side effects including stains and altered taste sensation.

Conclusion

The available evidence remains inconclusive but suggests that aloe vera mouthwash is comparable to chlorhexidine in reducing gingival inflammation but inferior to chlorhexidine in reducing plaque. These findings are preliminary and further high‐quality studies with adequate sample sizes are highly recommended.
Effect of aqueous‐based mechanical polishing on the nanoindentation response of borosilicate glasses
Authors: Hackett Benjamin L. , Wereszczak Andrew A. , Pharr George M.
Published: March 2019

When attempting to measure material properties by sampling near‐surface volumes with techniques like nanoindentation, careful consideration of the state of the surface compared to the bulk is paramount for valid characterization. The process of surface planarization of glass in preparation for analysis is no exception. Water's general reactivity with silicate glasses has been well‐established, but under the typical conditions for mechanical polishing, the usual practical assumption is that the potential effects on measured mechanical properties are insignificant due to the short period of glass‐water interaction and the non‐extreme corrosive environment. On the contrary, in this study, it is shown that the act of polishing certain borosilicate glass compositions in an aqueous environment directly affects the nanomechanical response to several micrometers, reducing the measured elastic modulus and hardness by ~20% and ~35%, respectively. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) are used to confirm the formation of an altered, hydrated surface layer.
Evaluation of an immunochromatographic test for alpha thalassaemia screening in a multi‐ethnic population
Authors: Nelson Anna Clare , Motum Penelope Irene , Emeto Theophilus I.
Published: March 2019

Introduction

The standard screening method for alpha thalassaemia is the examination of HbH preparation. It is labour intensive and poorly standardized. The development of a rapid strip immunochromatographic test (ICT) for haemoglobin Barts offers a fast, user friendly and cost‐effective alternative screening tool.

Method

A total of 180 subjects with results of the thalassaemia screen and genetic testing were included. Results of the ICT and HbH preparation were correlated with genetic results to determine the performance characteristics of the tests and the effect of mean sample age on results.

Results

Of 180 subjects, 111 carried alpha thalassaemia mutations and 69 participants had normal genetic results. The ICT had a sensitivity of 63.06% for all alpha gene mutations and 100% for both heterozygous alpha0 and HbH disease, with a specificity of 91.30%. Examination of HbH preparation had a sensitivity of 34.23% overall, detecting 89% of heterozygous alpha0 and 100% of HbH disease with a specificity of 98.55%. Sample age did not affect overall results.

Conclusions

The ICT is a sensitive screening method for significant alpha mutations and detects the majority of homozygous alpha+ and nondeletional mutations. It demonstrates greater correlation with genetic testing than HbH preparation and could replace HbH preparation in the screening algorithm for alpha thalassaemia.
“Taking to Bed”: A Simple, and Important, Clinical Indicator
Authors: Kutner Jean S.
Published: March 2019

This editorial comments on the article by Thomas Gill et al. in this issue.
Factors Considered by Interprofessional Team for Treatment Decision in Hip Fracture with Dementia
Authors: Baker Alice C. , Ambrose Catherine G. , Knudson Paula L. , Saraykar Smita S. , Piller Linda B. , McCurdy Sheryl A. , Rianon Nahid J.
Published: March 2019

Objectives

Patients with dementia are at high risk for hip fractures and often have poor outcomes when a fracture is sustained. Despite this poor prognosis, little data are available on what factors should be prioritized to guide surgical decision making in these cases. We aimed to understand the decision‐making process for older dementia patients hospitalized after hip fractures.

Design

We performed a qualitative analysis of in‐depth elite interviews conducted with a clinical care team involved in management of patients with dementia after hospitalization for hip fractures.

Setting

Interviews were conducted with an interprofessional team involved in the care of patients with dementia after being hospitalized for hip fractures.

Participants

Interviewees included nine orthopaedic surgeons, three hospitalists, three geriatricians, five nurses, three occupational therapists, three physical therapists, and two clinical ethicists.

Measurements

Verbatim transcripts of the interviews were analyzed and coded using QSR International's NVivo 10 qualitative database management software.

Results

The three main themes that most interviewees discussed were pain control, functional status, and medical comorbidities. Interviewees brought up many factors related to restoring functional status including baseline functional status, rehabilitation potential, social support, and the importance of mobility. Dementia and its impact on rehabilitation potential were mentioned by all geriatricians.

Conclusion

Although frailty, prognosis, and life expectancy were largely absent from the responses, the emphasis on dementia, advanced directives, and involving family or caregivers by the three geriatricians indicates the importance of including geriatricians in the decision‐making team for these patients.
Correlates of Rural, Appalachian, and Community Identity in the CITIES Cohort
Authors: Paskett Electra D. , Young Gregory S. , Bernardo Brittany M. , Washington Chasity , DeGraffinreid Cecilia , Fisher James L. , Huerta Timothy R.
Published: March 2019

Purpose: To determine correlates of rural, Appalachian, and community identity among a cohort of participants in the Community Initiative Towards Improving Equity and Health Status (CITIES) project.

Methods: Mixed linear and logistic regression effects models were utilized to determine correlates of 3 outcomes: 1) community identity, 2) rural identity, and 3) Appalachian identity among participants in the Ohio CITIES project.

Findings: Distinct demographic characteristics were found to be associated with each of the outcomes. For community identity, while no differences were found for rural or urban participants, those who were single or never married (P < .0001) as well as those who graduated from college (P = .0005) reported significantly lower community identity scores than married individuals with less than a college education. Those who resided in an Appalachian county reported higher community identity scores (P = .0009) than non‐Appalachian residents. For rural identity, those who did not identify as Christian (P = .018) as well as those who identified as Democrat (P = .027) reported significantly lower rural identity scores than others. Lastly, for Appalachian identity, county‐level percentage of families in poverty (P = .06), as well as gender (P = .05), were associated with self‐reported Appalachian identity, but these effects were only marginally significant.

Conclusions: Although community, rural, and Appalachian identity may be viewed as similar due to their measure of attachment to a place, results from this study suggest that there are distinct individual and area‐level correlates associated with community, rural, and Appalachian identity.
Rural and Urban Differences in the Adoption of New Health Information and Medical Technologies
Authors: Haggstrom David A. , Lee Joy L. , Dickinson Stephanie L. , Kianersi Sina , Roberts Jamie L. , Teal Evgenia , Baker Layla B. , Rawl Susan M.
Published: March 2019

Background

This statewide survey sought to understand the adoption level of new health information and medical technologies, and whether these patterns differed between urban and rural populations.

Methods

A random sample of 7,979 people aged 18‐75 years, stratified by rural status and race, who lived in 1 of 34 Indiana counties with high cancer mortality rates and were seen at least once in the past year in a statewide health system were surveyed.

Results

Completed surveys were returned by 970 participants. Rural patients were less likely than urban to use electronic health record messaging systems (28.3% vs 34.5%,P= .045) or any communication technology (43.0% vs 50.8%,P= .017). Rural patients were less likely to look for personal health information for someone else's medical record (11.0% vs 16.3%,P= .022), look‐up test results (29.5% vs 38.3%,P= .005), or use any form of electronic medical record (EMR) access (57.5% vs 67.1%,P= .003). Rural differences in any use of communication technology or EMRs were no longer significant in adjusted models, while education and income were significantly associated. There was a trend in the higher use of low‐dose computed tomography (CT) scan among rural patients (19.1% vs 14.4%,P= .057). No significant difference was present between rural and urban patients in the use of the human papilloma virus test (27.1% vs 26.6%,P= .880).

Conclusions

Differences in health information technology use between rural and urban populations may be moderated by social determinants. Lower adoption of new health information technologies (HITs) than medical technologies among rural, compared to urban, individuals may be due to lower levels of evidence supporting HITs.
Clinical presentation, diagnosis and staging of cholangiocarcinoma
Authors: Forner Alejandro , Vidili Gianpaolo , Rengo Marco , Bujanda Luis , Ponz‐Sarvisé Mariano , Lamarca Angela
Published: March 2019

Cholangiocarcinoma (CCA) is a heterogeneous group of tumours, derived from cells of the biliary tree, which represent the second most frequent primary liver tumour. According to the most recent classifications, CCA can be subdivided into intrahepatic (iCCA) and extrahepatic (eCCA) which include perihilar (pCCA) and distal (dCCA) CCA. CCA are usually identified at advanced stages, when the primary tumour grows enough to produce a large liver mass or when jaundice has developed because of biliary tree obstruction. The ongoing challenges in the identification of risk factors and definition of a specific population at higher risk of developing CCA are the main challenges for the development of screening programs. Therefore, late diagnosis remains an unresolved issue in CCA. Imaging plays an important role in the detection and characterization of CCA, helping with radiological diagnosis, guiding biopsy procedures and allowing staging of the tumour. This review focuses on clinical presentations and diagnosis and staging techniques of CCA.
Fine‐grained material associated with a large sulfide returned from Comet 81P/Wild 2
Authors: Gainsforth Z. , Westphal A. J. , Butterworth A. L. , Jilly‐Rehak C. E. , Brownlee D. E. , Joswiak D. J. , Ogliore R. C. , Zolensky M. E. , Bechtel H. A. , Ebel D. S. , Huss G. R. , Sandford S. A. , White A. J.
Published: March 2019

In a consortium analysis of a large particle captured from the coma of comet 81P/Wild 2 by the Stardust spacecraft, we report the discovery of a field of fine‐grained material (FGM) in contact with a large sulfide particle. The FGM was partially located in an embayment in the sulfide. As a consequence, some of the FGM appears to have been protected from damage during hypervelocity capture in aerogel. Some of the FGM particles are indistinguishable in their characteristics from common components of chondritic‐porous interplanetary dust particles, including glass with embedded metals and sulfides and equilibrated aggregates. The sulfide exhibits surprising Ni‐rich lamellae, which may indicate that this particle experienced a long‐duration heating event after its formation but before incorporation into Wild 2.
Challenging assumptions of innateness – leave nothing unturned
Authors: Han Jason J , Vapiwala Neha
Published: March 2019

The authors describe the potential to enrich medical curricula by overthrowing assumptions that certain skills or characteristics are innate instead of requiring deliberate teaching.
Postmortem late phase histopathology after pulmonary vein isolation using a cryoballoon: A case report
Authors: Ukita Kohei , Nakamura Hitoshi , Matsuhiro Yutaka , Yasumoto Koji , Yasumura Keisuke , Tanaka Akihiro , Matsunaga‐Lee Yasuharu , Nakamura Daisuke , Yano Masamichi , Yamato Masaki , Egami Yasuyuki , Shutta Ryu , Nishino Masami , Tanouchi Jun
Published: March 2019

We report the autopsy case of 68‐year‐old woman who received cryoballoon (CB) ablation for paroxysmal atrial fibrillation 7 months before death. Both macroscopic and microscopic findings revealed no thrombus formation around pulmonary veins. Previous experimental studies have shown the lower risk of thrombus formation in CB ablation as compared to radiofrequency ablation. Our findings in the human autopsy case may support this merit of CB ablation. To confirm this benefit of CB ablation, further studies regarding histopathology of CB ablation should be performed.
Maximizing biventricular pacing in patients with rate‐controlled atrial fibrillation using ventricular sense response
Authors: Montemezzo Mauricio , AlTurki Ahmed , Essebag Vidal
Published: March 2019

In patients with atrial fibrillation (AF), cardiac resynchronization therapy (CRT) is challenging because the ventricular rate of conducted AF exceeds the biventricular pacing rate. In the current report, we present a patient who received a CRT device that was programmed to ventricular sense response (VSR) on with VVI 40 beats per minute to allow the AF to be paced as fusion beats. We found that the pacing configuration resulting in the narrowest QRS in this patient was VVI 40 with VSR biventricular fusion pacing during AF. VSR mode allows for CRT delivery without the need to artificially increase heart rate.
Hookworm‐related cutaneous larva migrans of the penis successfully treated with topical ivermectin
Authors: Gelmetti Carlo , Brena Michela , Veraldi Stefano
Published: March 2019

Hookworm‐related cutaneous larva migrans is an infestation of the skin caused by nematodes. Involvement of genitals is extremely rare. We report the case of a child with this infestation on the penis who cleared rapidly with topical ivermectin.