bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainability of community-based interventions for people affected by dementia: a protocol for the SCI-Dem realist review
Authors: Morton Thomas , Atkinson Teresa , Brooker Dawn , Wong Geoffrey , Evans Shirley , Kennard Clive
Published: July 2019

Introduction

With numbers set to increase globally, finding ways to better support people with dementia and their families is a matter of growing concern. Community-based interventions can play a key role in supporting people with early to moderate stage dementia postdiagnosis, helping delay decline and hospitalisation. However, provision of such interventions is fragmented, with significant gaps and no reliable funding model, hence innovative groups and schemes catering for a genuine need can struggle long term and frequently fold.

Methods and analysis

This realist review aims to expand our understanding of how best to implement and facilitate community-based interventions to run sustainably, focusing on contextually relevant explanations. We will gather and synthesise literature using a realist approach designed to accommodate and account for the complexity of ‘real life’ programmes, as implemented under different conditions in different settings, aiming to draw transferable conclusions about their sustainability that explain how and why context can influence outcomes. Our review will iteratively progress through five steps: (1) locate existing theories; (2) search for evidence (using Academic Search, AMED, CINAHL, EMBASE, MEDLINE, ProQuest, PsycINFO, PubMed, Scopus and Social Care Online, between May and September 2019); (3) article selection; (4) extracting and organising data; (5) synthesising the evidence and drawing conclusions. Data analysis will use a realist logic to explain what works, for whom, in what circumstances, in what respects, how and why. A stakeholder group will provide guidance and feedback throughout.

Ethics and dissemination

Ethical approval was not required. Recommendations drawn from results are likely to be of interest to a range of stakeholders including those commissioning, planning, running, supporting or attending such interventions, as well as policymakers, healthcare professionals and researchers. We will draw on the expertise of our stakeholder group regarding tailoring dissemination to each audience using a variety of materials, formats and channels.
The panoramic dental radiograph for emergency physicians
Authors: Sklavos Anton , Beteramia Daniel , Delpachitra Seth Navinda , Kumar Ricky
Published: July 2019

Dental emergencies are common reasons for presenting to hospital emergency departments. Here, we discuss the panoramic radiograph (orthopantomogram (OPG, OPT) as a diagnostic tool for the assessment of mandibular trauma and odontogenic infections. In this article, we review the radiographic principles of image acquisition, and how to conduct a systematic interpretation of represented maxillofacial anatomy. The aim is to equip the emergency physician with the skills to use the OPG radiograph when available, and to rapidly assess the image to expedite patient management. Included is a discussion of a number of cases seen in the emergency setting and some common errors in diagnosis.
Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy
Authors: Bégué Céline , Mörner Stellan , Brito Dulce , Hengstenberg Christian , Cleland John G F , Arbustini Eloisa , Galve Enrique , Wichter Thomas , Richter Anette , Golmard Jean-Louis , Bernard Maguy , Dubourg Olivier , Komajda Michel , Charron Philippe , Isnard Richard
Published: July 2019

Objectives

N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM.

Methods

We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion.

Results

Of 357 patients enrolled, the median age was 52 (IQR: 36–65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10–4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1–2 vs 3–4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001).

Conclusions

MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.
Frequency, predictors, and outcomes of readmission to index versus non-index hospitals after mechanical thrombectomy in patients with ischemic stroke
Authors: Shkirkova Kristina , Connor Michelle , Lamorie-Foote Krista , Patel Arati , Liu Qinghai , Ding Li , Amar Arun , Sanossian Nerses , Attenello Frank , Mack William
Published: July 2019

Background

Stroke systems of care employ a hub-and-spoke model, with fewer centers performing mechanical thrombectomy (MT) compared with stroke-receiving centers, where a higher number offer high-level, centralized treatment to a large number of patients.

Objective

To characterize rates and outcomes of readmission to index and non-index hospitals for patients with ischemic stroke who underwent MT.

Methods

This study leveraged a population-based, nationally representative sample of patients with stroke undergoing MT from the Nationwide Readmissions Database between 2010 and 2014. Descriptive, logistic regression analyses, and univariate and multivariate logistic regression models were carried out to determine patient- and hospital-level factors, mortality, complications, and subsequent readmissions associated with index and non-index hospitals' 90-day readmissions.

Results

In the study, 2111 patients with a stroke were treated with MT, of whom 534 were readmitted within 90 days. The most common reasons for readmission were: septicemia (5.9%), atrial fibrillation (4.8%), and cerebral artery occlusion with infarct (4.8%). Among readmitted patients, 387 (74%) were readmitted to index and 136 (26%) to non-index hospitals. On multivariable logistic regression analysis, non-index hospital readmission was not independently associated with major complications (p=0.09), mortality (p=0.34), neurological complications (p=0.47), or second readmission (p=0.92).

Conclusion

One-quarter of patients with a stroke treated with MT were readmitted within 90 days, and one quarter of these patients were readmitted to non-index hospitals. Readmission to a non-index hospital was not associated with mortality or increased complication rates. In a hub-and-spoke model it is important that follow-up care for a specialized procedure can be performed effectively at a vast number of non-index hospitals covering a large geographic area.
When and why? Timing of post-migration HIV acquisition among sub-Saharan migrants in France
Authors: Gosselin Anne , Ravalihasy Andrainolo , Pannetier Julie , Lert France , Desgrées du Loû Annabel
Published: July 2019

Objective

Recent studies highlighted that many HIV-positive migrants in Europe acquired their infections post-migration. However, the timing of these infections is not always known. This study aims to estimate the timing of post-migration HIV acquisition among sub-Saharan migrants in France and to understand the correlates of post-migration infection.

Methods

Within the PARCOURS retrospective survey conducted in 2012–2013 in 74 healthcare facilities in the Paris region, life-event data were collected among a random sample of 926 patients living with HIV in HIV services and 763 patients undiagnosed with HIV in primary care centres born in sub-Saharan Africa (reference group). Based on previous analysis, we considered the first 6 years in France after migration as a settlement period. Among the persons who acquired HIV after migration, we estimated the proportion of persons infected during settlement (0–6 years after migration) and after settlement (>6 years after migration) by using an algorithm that combines life-event data and a modelisation of CD4
+
T-cell count decline. We then assessed the determinants of HIV acquisition during settlement and after settlement using bivariate logistic regression models.

Results

Overall, 58% of sub-Saharan migrants who acquired HIV after migration were infected during the first 6 years in France. HIV acquisition during settlement was found to be linked to short/transactional partnerships and lack of a resident permit. 42% of migrants had contracted HIV after settlement. After settlement, HIV acquisition was associated with short/transactional but also with concurrent partnerships and not with social hardship.

Conclusion

Two profiles of HIV post-migration acquisition emerged. The majority of HIV post-migration acquisition occurs during the settlement period: comprehensive combination prevention programmes among recently arrived migrants are needed. However, long-term migrants are also at risk for HIV through multiple partnerships. Prevention programmes should address the different profiles of migrants at risk for post-migration HIV acquisition.
Understanding Zika virus as an STI: findings from a qualitative study of pregnant women in the Bronx
Authors: Rodriguez Miguel , Lord Ayla , Sanabia Carolina C , Silverio Abigail , Chuang Meleen , Dolan Siobhan M
Published: July 2019

Objectives

Pregnant women in the Bronx were at risk for travel-related Zika exposure in the USA between 2016 and 2017. This qualitative study explored the experiences of 13 pregnant women to learn about their knowledge of Zika and prevention measures.

Methods

In the summer of 2017, pregnant women at risk of travel-related Zika exposure were interviewed in either Spanish or English to learn about their experiences and transcripts were analysed using a grounded theory approach.

Results

Most participants were Latinas living in the Bronx, median age of 29 years and median household income between $26 000 and $50 000. Participants displayed a strong understanding of Zika transmission via mosquito bites yet lacked knowledge about its sexual transmission. Interviews revealed three key themes: (1) Zika as a new disease, (2) denial as a coping mechanism and (3) the recommendation to treat Zika as an STI. Women observed Zika as a brand new disease with early messages emphasising mosquito-borne transmission. They lacked awareness of newer messaging about sexual transmission. Furthermore, if women did read about risk of sexual transmission, many stated being in denial and struggling with recommendations to prevent sexual transmission. Barriers included problems changing travel plans and rejection of condom use. Women unanimously suggested labelling Zika as an STI and adding it to existing lists of STIs for messaging and outreach in community-based and clinical prevention.

Conclusion

Many pregnant women were unaware that Zika virus can be sexually transmitted due to: (1) novelty of Zika, (2) denial as a coping mechanism and (3) Zika not being listed along with well-known STIs. Overcoming these barriers via community-based as well as clinical education for pregnant women in the Bronx would be helpful in 2019 and beyond when the risk of travel-related Zika exposure remains a public health threat to optimal pregnancy outcomes.
UK tobacco price increases: driven by industry or public health?
Authors: Hiscock Rosemary , Branston J Robert , Partos Timea R , McNeill Ann , Hitchman Sara C , Gilmore Anna B
Published: July 2019

Background

Tobacco companies claim that higher taxes will force smokers into buying illicit tobacco, but if they were truly concerned about increasing illicit sales with higher prices they would only increase retail prices in line with changes in taxation. In this paper, we explore UK pricing of both factory-made cigarettes (FM) and roll-your-own tobacco (RYO) to explore the extent to which price increases were due to government tax rises or industry strategies to increase profit per pack.

Method

Nielsen commercial data on UK tobacco sales data (2010–2015) were combined with official UK data on inflation and tax rates, to identify the source of real price increases.

Results

Between 2010 and 2012, when there were unexpected large tax increases, industry driven price changes were small (16% of the price rise in FM and 20% in RYO), and changes were similar between market segments. Between 2013 and 2015, when tax increases were smaller and expected, industry behaviour generally accounted for a larger share of price rises (33% FM, 48% RYO), but changes varied considerably by segment.

Conclusion

The industry has increased its prices beyond that required by tax changes, even when tax rises were larger and unexpected, although were notably smaller in such conditions. This suggests (1) that the industry is not actually concerned by the threat of illicit, especially since RYO had the highest levels of industry driven price increases despite higher levels of illicit, and (2) there remains scope for further tax increases, which should be relatively large and unexpected.
Learners’ perspectives onStop the Bleed: a course to improve survival during mass casualty events
Authors: Zhao Karen L , Herrenkohl Madeline , Paulsen Maria , Bulger Eileen M , Vavilala Monica S , Moore Megan , Pham Tam N
Published: July 2019

Background

In response to increasing mass casualty events nationwide, the American College of Surgeons Committee on Trauma developed a bleeding control course (Stop the Bleed) to teach hemorrhage control techniques to laypeople. There is a high level of public interest in learning about injury mitigation, but no study evaluating learners’ perspectives after bleeding control training. We sought to evaluate the didactic value of the bleeding control course by analyzing learners’ feedback within the framework of adult learning theory.

Study design

We analyzed a total of 720 open-ended surveys from 20 regional bleeding control courses taught by a level I trauma center team during a 9-month period. Major themes expressed by learners were organized into a categorical code structure. Keywords identified from free text responses were used to code comments into subthemes. These themes were organized into categories within the framework of adult learning theory.

Results

The two primary themes identified from learners’ feedback were empowerment and practicality. Respondents reported an overwhelmingly positive experience; 97% of participants would recommend the course to others. The course design (lecture, didactics and hands-on activities) was cited as a positive element of the course. Participants felt empowered and prepared to act and help others during mass emergency events. Actionable items for future course improvement were identified.

Conclusion

Themes from learners’ feedback fit within the framework of adult learning theory. These findings highlight the bleeding control course as an empowering experience and a practical and engaging approach to teaching hemorrhage mitigation to the public.

Level of evidence

Level V, qualitative analysis.
Unveiling cosmography from the dark energy equation of state
Authors: Escamilla-Rivera Celia , Capozziello Salvatore
Published: July 2019

Constraining the dark energy equation of state, [Formula: see text], is one of the main issues of current and future cosmological surveys. In practice, this requires making assumptions about the evolution of [Formula: see text] with redshift [Formula: see text], which can be manifested in a choice of a specific parametric form where the number of cosmological parameters play an important role in the observed cosmic acceleration. Since any attempt to constrain the EoS requires some prior fixing in one form or the other, settling a method to constrain cosmological parameters is of great importance. In this paper, we provide a straightforward approach to show how cosmological tests can be improved via a parametric methodology based on cosmography. Using Supernovae Type IA samplers, we show how by performing a statistical analysis of a specific dark energy parametrization can give directly the cosmographic parameters values.
PRICING DOUBLE BARRIER OPTIONS ON HOMOGENEOUS DIFFUSIONS: A NEUMANN SERIES OF BESSEL FUNCTIONS REPRESENTATION
Authors: KRAVCHENKO IGOR V. , KRAVCHENKO VLADISLAV V. , TORBA SERGII M. , DIAS JOSÉ CARLOS
Published: July 2019

This paper develops a novel analytically tractable Neumann series of Bessel functions representation for pricing (and hedging) European-style double barrier knock-out options, which can be applied to the whole class of one-dimensional time-homogeneous diffusions, even for the cases where the corresponding transition density is not known. The proposed numerical method is shown to be efficient and simple to implement. To illustrate the flexibility and computational power of the algorithm, we develop an extended jump to default model that is able to capture several empirical regularities commonly observed in the literature.
Automorphisms of the total graph over upper triangular matrices
Authors: Wang Long , Fang Xianwen , Tian Fenglei
Published: July 2019

Let [Formula: see text] be a finite field, [Formula: see text] the ring of all [Formula: see text] upper triangular matrices over [Formula: see text], [Formula: see text] the set of all zero-divisors of [Formula: see text], i.e. [Formula: see text] consists of all [Formula: see text] upper triangular singular matrices over [Formula: see text]. The total graph of [Formula: see text], denoted by [Formula: see text], is a graph with all elements of [Formula: see text] as vertices, and two distinct vertices [Formula: see text] are adjacent if and only if [Formula: see text]. In this paper, we determine all automorphisms of the total graph [Formula: see text] of [Formula: see text].
Effect of scaling and root planing on level of immunoglobulin E and immunoglobulin G4in children with gingivitis and house-dust mite allergy: A pilot randomised controlled trial
Authors: Nelwan Sindy Cornelia , Nugraha Ricardo Adrian , Endaryanto Anang , Dewi Frisma , Nuraini Prawati , Tedjosasongko Udijanto , Utomo Daniel Haryono
Published: July 2019

Background and Objective: There is a pressing need for developing innovative strategies to prevent allergic diseases among children. As house-dust mite (HDM) allergy is often seen in children with gingivitis, strategies should be derived from a conceptual framework of allergen elimination and pathogen eradication; one such strategy is dental scaling and root planing (SRP) to remove dental plaque and periodontal pathogens. The study aimed to evaluate the beneficial effects of comprehensive 6-months dental SRP to reduce the level of immunoglobulin E (IgE) and immunoglobulin G4(IgG4) in children with gingivitis and HDM allergy. IgE and IgG4, whose production is controlled mainly by Th-2 cells and B cells, are proven biomarkers for atopic inflammatory responses.

Methods: The present study conducted a non-blinded randomised controlled trial with superiority design. A total of 10 subjects (age range 6–16 years) with gingivitis and positive skin-prick test to HDM from Pediatric Allergy Outpatient Clinic, Dr. Soetomo General Hospital were enrolled in the present study. Of the 10 subjects, only five received dental SRP. We further evaluated total serum IgE and IgG4level before and 6 months after treatment.

Results and Discussion: Subjects in the standard treatment group showed a slight decrease in the IgE level ([Formula: see text]) but no change in the IgG4level ([Formula: see text]), while subjects in the intervention group showed a significant decrease in IgE ([Formula: see text]) and IgG4levels ([Formula: see text]).

Conclusion: The study results suggest that 6-month comprehensive dental scaling combined with root planing may help to reduce IgE and IgG4levels in children with gingivitis and HDM allergy. Furthermore, untreated or undertreated gingivitis is often associated with worsening allergic manifestation and thus should be avoided.

Trial Registration: ISRCTN31416107, retrospectively registered on 17 April 2018.
THE INVESTMENT CERTIFICATES IN THE ITALIAN MARKET: A COMPARISON OF QUOTED AND ESTIMATED PRICES
Authors: VIGANÒ BRANDO , VITALI SEBASTIANO , MORIGGIA VITTORIO , ZANOTTI GIOVANNA
Published: July 2019

Investment certificates are securitized derivatives built as a combination of financial instruments. The financial engineering process aims to create new payoff profiles that allow investors to diversify or to hedge the risk of their portfolios. Such instruments are relatively challenging to price, as highlighted in the recent publications for other European markets. The aim of this paper is to analyze whether in the Italian market there are also differences between the quoted price and the estimated price obtained applying a standard pricing approach well known in the literature. In particular, we analyze three representative certificates, belonging to the classes of target coupon certificates and autocallable certificates, that have been most appreciated by the investors during the last years. To evaluate the price, we propose a Monte Carlo approach that computes directly the payoff of the certificates on a set of scenarios for the evolution of the underlying asset. Moreover, studying the payoff profile of the certificates, we investigate and comment on the recent regulatory debate on “complexity”. We show that complexity, the new parameter behind return and risk, should not be necessarily associated with the engineering level of the financial products and that, sometimes, complexity is not associated with risk.
Energy Efficient Chip-to-Chip Wireless Interconnection for Heterogeneous Architectures
Authors: Gade Sri Harsha , Ahmed M. Meraj , Deb Sujay , Ganguly Amlan
Published: July 2019

Heterogeneous multichip architectures have gained significant interest in high-performance computing clusters to cater to a wide range of applications. In particular, heterogeneous systems with multiple multicore CPUs, GPUs, and memory have become common to meet application requirements. The shared resources like interconnection network in such systems pose significant challenges due to the diverse traffic requirements of CPUs and GPUs. Especially, the performance and energy consumption of inter-chip communication have remained a major bottleneck due to limitations imposed by off-chip wired links. To overcome these challenges, we propose a wireless interconnection network to provide energy-efficient, high-performance communication in heterogeneous multi-chip systems. Interference-free communication between GPUs and memory modules is achieved through directional wireless links, while omnidirectional wireless interfaces connect cores in the CPUs with other components in the system. Besides providing low-energy, high-bandwidth inter-chip communication, the wireless interconnection scales efficiently with system size to provide high performance across multiple chips. The proposed inter-chip wireless interconnection is evaluated on two system sizes with multiple CPU and multiple GPU chips, along with main memory modules. On a system with 4 CPU and 4 GPU chips, application runtime is sped up by 3.94×, packet energy is reduced by 94.4%, and packet latency is reduced by 58.34% as compared to baseline system with wired inter-chip interconnection.
Speculative Symbolic Graph Execution of Imperative Deep Learning Programs
Authors: Jeong Eunji , Cho Sungwoo , Yu Gyeong-In , Jeong Joo Seong , Shin Dong-Jin , Kim Taebum , Chun Byung-Gon
Published: July 2019

The rapid evolution of deep neural networks is demanding deep learning (DL) frameworks not only to satisfy the requirement of quickly executing large computations, but also to support straightforward programming models for quickly implementing and experimenting with complex network structures. However, existing frameworks fail to excel in both departments simultaneously, leading to diverged efforts for optimizing performance and improving usability.

This paper presents JANUS, a system that combines the advantages from both sides by transparently converting an imperative DL program written in Python, a de-facto scripting language for DL, into an efficiently executable symbolic dataflow graph. JANUS can convert various dynamic features of Python, including dynamic control flow, dynamic types, and impure functions, into elements of a symbolic dataflow graph. Our experiments show that JANUS can achieve fast DL training by exploiting the techniques imposed by symbolic graph-based DL frameworks, while maintaining the simple and flexible programmability of imperative DL frameworks at the same time.
Smoking, Helicobacter Pylori Serology, and Gastric Cancer Risk in Prospective Studies from China, Japan, and Korea
Authors: Butt Julia , Varga Matthew G. , Wang Tianyi , Tsugane Shoichiro , Shimazu Taichi , Zheng Wei , Abnet Christian C. , Yoo Keun-Young , Park Sue K. , Kim Jeongseon , Jee Sun Ha , Qiao You-lin , Shu Xiao-Ou , Waterboer Tim , Pawlita Michael , Epplein Meira
Published: July 2019

Smoking is an established risk factor for gastric cancer development. In this study, we aimed to assess prospectively the association of smoking with gastric cancer risk in 1,446 non-cardia gastric cancer cases and 1,796 controls from China, Japan, and Korea with consideration of Helicobacter pylori infection as a potential effect modifier. Applying logistic regression models stratified by study and adjusted for age and sex we found that current, but not former, smoking was significantly associated with gastric cancer risk [OR = 1.33; 95% confidence interval (CI), 1.07–1.65]. However, the association was significant only in H. pylori sero-positive individuals determined by 3 different sero-markers: overall sero-positivity, sero-positivity to the onco-protein CagA, and sero-positivity to the gastric cancer associated sero-marker HP0305 and HP1564. Specifically, a significant interaction was found when stratifying by HP0305/HP1564 (Pinteraction = 0.01) with a 46% increased risk of gastric cancer among HP0305/HP1564 sero-positive current smokers (95% CI, 1.10–1.93) as opposed to no increased gastric cancer risk among HP0305/HP1564 sero-negative current smokers (OR = 0.93; 95% CI, 0.65–1.33). We confirmed that current smoking is associated with an increased gastric cancer risk, however, only among individuals that are simultaneously sero-positive for the leading causal factor for gastric cancer, H. pylori.
The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC
Authors: Hollstein Pablo E. , Eichner Lillian J. , Brun Sonja N. , Kamireddy Anwesh , Svensson Robert U. , Vera Liliana I. , Ross Debbie S. , Rymoff T.J. , Hutchins Amanda , Galvez Hector M. , Williams April E. , Shokhirev Maxim N. , Screaton Robert A. , Berdeaux Rebecca , Shaw Reuben J.
Published: July 2019

Mutations in the LKB1 (also known as STK11) tumor suppressor are the third most frequent genetic alteration in non–small cell lung cancer (NSCLC). LKB1 encodes a serine/threonine kinase that directly phosphorylates and activates 14 AMPK family kinases (“AMPKRs”). The function of many of the AMPKRs remains obscure, and which are most critical to the tumor-suppressive function of LKB1 remains unknown. Here, we combine CRISPR and genetic analysis of the AMPKR family in NSCLC cell lines and mouse models, revealing a surprising critical role for the SIK subfamily. Conditional genetic loss of Sik1 revealed increased tumor growth in mouse models of Kras-dependent lung cancer, which was further enhanced by loss of the related kinase Sik3. As most known substrates of the SIKs control transcription, gene-expression analysis was performed, revealing upregulation of AP1 and IL6 signaling in common between LKB1- and SIK1/3-deficient tumors. The SIK substrate CRTC2 was required for this effect, as well as for proliferation benefits from SIK loss.

Significance:

The tumor suppressor LKB1/STK11 encodes a serine/threonine kinase frequently inactivated in NSCLC. LKB1 activates 14 downstream kinases in the AMPK family controlling growth and metabolism, although which kinases are critical for LKB1 tumor-suppressor function has remained an enigma. Here we unexpectedly found that two understudied kinases, SIK1 and SIK3, are critical targets in lung cancer.

This article is highlighted in the In This Issue feature, p. 1469
Alpha Globin Gene Mutation: A Major Determinant of Hydroxyurea Response in Transfusion-Dependent HbE-β-Thalassaemia
Authors: Biswas Sujana , Ray Rudra , Roy Kaushik , Bandyopadhyay Anish , Ghosh Kanjaksha , Bhattacharyya Maitreyee
Published: July 2019

Thalassaemias are the most common inherited autosomal recessive single gene disorders characterised by chronic hereditary haemolytic anaemia due to absence or reduced synthesis of one or more of the globin chains. Haemoglobin E (HbE)-β-thalassaemia is the genotype responsible for approximately one-half of all cases of severe β-thalassaemia worldwide. This study proposes to evaluate response of hydroxyurea in reducing transfusion requirements of severe HbE-β-thalassaemia patients, and its correlation with foetal haemoglobin (HbF) level and α-mutation. Hydroxyurea was started at a baseline dose in 82 transfusion-dependent HbE-β-thalassaemia patients. HbF levels and %F-cells were measured. β-Thalassaemia mutations and α-globin gene deletions and triplications were detected by amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) and Gap-PCR, respectively. Patients were categorised as good (41.5%), moderate (31.7%), and poor responders (26.8%) based on their decrease in transfusion requirements. Nine patients were excellent responders who became transfusion independent. The mean increase in HbF levels and %F-cells after therapy was correlated with decrease in transfusion requirements. Patients having a deletion of the α-globin gene were better responders. The response was proportional to the number of α-globin gene deletions. We conclude that hydroxyurea treatment decreases transfusion requirements, and the response correlates with α-globin gene deletions.
Dabrafenib and Trametinib for BRAF-Mutated Conjunctival Melanoma
Authors: Kim Jenna May , Weiss Sarah , Sinard John H. , Pointdujour-Lim Renelle
Published: July 2019

Background: Conjunctival melanoma is a potentially lethal malignancy of the ocular surface. There have been no therapeutic advancements made in the past several decades despite increasing prevalence of the disease. Methods: The authors report the case of a 52-year-old Caucasian male with unresectable, recurrent conjunctival melanoma with V600 BRAF mutation who was treated with systemic BRAF/MEK inhibition. Results: There was complete regression of local disease within the first 9 months. The patient remains without local recurrence or systemic metastasis at 1 year. Conclusion: This is the first reported case of conjunctival melanoma with complete response to BRAF/MEK inhibition. As long as targeted therapy remains an option, patients with conjunctival melanoma should undergo mutational profiling of their tumor.
Assessment of Central Drive to the Diaphragm by Twitch Interpolation: Normal Values, Theoretical Considerations, and Future Directions
Authors: Spiesshoefer Jens , Henke Carolin , Herkenrath Simon , Randerath Winfried , Brix Tobias , Young Peter , Boentert Matthias
Published: July 2019

Background: The twitch interpolation technique is a promising tool for assessing central drive to the diaphragm. It is used to quantify the degree of voluntary diaphragm activation during predefined breathing maneuvers. Objectives: This study was designed to (a) determine reference values for the level of voluntary activation of the diaphragm using the twitch occlusion technique in healthy adults and (b) explore the association between central drive to the diaphragm and volitional tests of respiratory muscle strength. Methods: Twenty-seven healthy volunteers aged 26 ± 14 years (18 male) were enrolled. Twitch transdiaphragmatic pressure (Pdi) was determined at relaxed functional residual capacity in response to cervical magnetic stimulation (CMS) of the phrenic nerves. The subjects were then instructed to gradually increase voluntary activation of the diaphragm, and the effects of superimposed magnetic stimuli on voluntary Pdi were assessed. Results: The twitch Pdi amplitude following CMS linearly decreased with increasing inspiratory effort. The resulting diaphragm voluntary activation index (DVAI) during maximal voluntary contraction was 75 ± 15% irrespective of gender or age. Twitch duration, half relaxation time, and area under the curve of superimposed Pdi deflections did not show a linear but an exponential association with increasing voluntary activation of the diaphragm. More than 2/3 of the decrease in the above values was evident after 1/3 of voluntary diaphragm contraction. Forced vital capacity (FVC) was inversely correlated with the DVAI. Conclusions: Twitch interpolation allows for assessment of central drive to the diaphragm. The maximum DVAI is independent of gender or age, and significantly related to FVC but not to maximum inspiratory pressure or Pdi as direct measures of diaphragm strength.
Fibroblast Growth Factors: A Controlling Mechanism of Skin Aging
Authors: de Araújo Rousilândia , Lôbo Myla , Trindade Kelvis , Silva Darizy Flávia , Pereira Neila
Published: July 2019

Cutaneous aging is a complex and continuous biological process characterized by cellular and molecular alterations, with progressive reduction of the body’s capacity to maintain the homeostasis, senescence, and/or apoptosis of the dermal cells. Fibroblast growth factors (FGF) have elicited studies to evaluate their role of repair and remodeling of the dermis during the skin anti-aging process, since they are regulatory proteins that mediate important signaling pathways and act on cell regeneration and repair processes. FGF acts primarily through binding to tyrosine kinase receptors through the autophosphorylation of their residues, promoting the phosphorylation of serine, threonine, and tyrosine residues of specific target proteins such as Raf-1, MAPK/Erk kinase, and extracellular signal-regulated kinase-1, which are part of the cascade of MAP kinases (mitogen-activated protein kinase). Then, FGF initiate signaling cascades inside the cell, where each kinase activates the following by phosphorylation, resulting in alterations of cellular functions. In addition, the FGF has a relevant role in anti-aging therapy because it is related to collagen and elastin synthesis activation responsible for skin resistance and elasticity, characteristics that are diminished with skin aging. Thus, the present article aims to review several scientific studies that demonstrated the cell signaling involved with the action of FGF on skin aging.
Development of Lichen Planopilaris-Like Alopecia following Occupational Exposure to Trichloroethylene and Tetrachloroethylene
Authors: Marks Dustin H. , Hagigeorges Dina , Manatis-Lornell Athena J. , Foreman Ruth K. , Senna Maryanne M.
Published: July 2019

Background: We report a case of acute and severe lichen planopilaris (LPP)-like alopecia in a 35-year-old male construction worker following occupational exposure to trichloroethylene (TCE) and tetrachloroethylene (PCE). Case Report: Two weeks after initiating ground-intrusive construction at a previous dry-cleaning facility site, the patient developed sudden scalp pruritus and associated patchy hair loss. As subsequent scalp biopsies revealed LPP, he was started on hydroxychloroquine at 200 mg twice daily and clobetasol solution once daily. Despite treatment, the patient’s hair loss rapidly progressed to involve >95% of his scalp within 3 years. An official “work clean” policy report revealed high-concentration exposure to TCE and PCE. Conclusion: Although causation cannot be proven, the close temporal relationship and rapid progression of LPP-like alopecia in an atypical patient demographic support a strong correlation between chemical exposure to TCE/PCE and scarring hair loss.
Assessment of Preoperative Liver Function for Surgical Decision Making in Patients with Hepatocellular Carcinoma
Authors: Kokudo Takashi , Hasegawa Kiyoshi , Shirata Chikara , Tanimoto Meguri , Ishizawa Takeaki , Kaneko Junichi , Akamatsu Nobuhisa , Arita Junichi , Demartines Nicolas , Uldry Emilie , Kokudo Norihiro , Halkic Nermin
Published: July 2019

Background: Most patients with hepatocellular carcinoma (HCC) have underlying liver disease and a preoperative liver function evaluation is important to avoid postoperative liver failure and death. In Western guidelines, portal hypertension (PH) is listed as a contraindication for liver resection. On the other hand, the indocyanine green retention rate at 15 min (ICG R15) has been widely used in Asian countries for surgical decision making. However, these criteria are based on reports published in the 20th century that included only a small number of patients and were developed empirically. Summary: The number of published case series concerning liver resection in HCC patients with PH has been rapidly increasing since 2011, indicating that liver resection in HCC patients with PH is now routinely performed in specialized centers worldwide. Although PH certainly has an impact and should be considered as a contraindication for major liver resection, it is no longer considered to be a contraindication for minor liver resection, especially laparoscopic liver resection. In addition, new biomarkers and imaging tools to assess preoperative liver function have been extensively reported. The combination of these new factors to well-known risk factors, such as PH and ICG R15, might strengthen the ability to stratify the risk of postoperative liver failure. Key Messages: The present review covers recent topics regarding the assessment of preoperative liver function for surgical decision making in patients with HCC.
Reduction of Ocular Surface Damage and Bacterial Survival Using 0.05% Povidone-Iodine Ocular Surface Irrigation before Cataract Surgery
Authors: Fan Fang , Zhao Zhihua , Zhao Xiaobin , Ma Qingmin , Li Kejun , Fu Wei , Jia Zhiyang
Published: July 2019

Background: To investigate the effects of 0.05% povidone-iodine (PI) irrigation on the ocular surface structure and bacterial survival rate in patients with cataract. Methods: Ninety eyes of 90 patients with cataract were included. Before surgery, the operative field was irrigated with 0.05% PI and divided into 30-s, 1-, and 2-min groups. Anterior chamber fluid was cultured bacteriologically. Tear film breakup time (BUT), corneal fluorescein staining (CFS), lacrimal river height (LRH), and Schirmer test I (STI) were conducted to assess ocular surface. Results: In all groups, the patients had significantly shorter postoperative BUT at 1 day, 3 days, and 1 week postoperatively than preoperatively. In addition, there was still lower BUT at 1 month postoperatively in the 1- and 2-min groups. STI and LRH were all decreased postoperatively at different time points (1 day, 3 days, 1 week), while CFS was increased. With the extension of time preoperatively (1 and 3 months), the ocular surface indicators returned to the preoperative level. The bacterial cultures after eye irrigating were negative in all groups. Conclusion: 0.05% PI irrigating the conjunctival sac for 30 s can achieve a low bacterial contamination rate. Importantly, it reduced the damage of ocular surface, which is beneficial to the recovery of ocular surface function.
Rapid Regression of B-Cell Non-Hodgkin’s Lymphoma after Eradication of Hepatitis C Virus by Direct Antiviral Agents
Authors: Hirose Shunji , Yamaji Yoko , Tsuruya Kota , Ogawa Yoshiaki , Miyaoka Masashi , Kagawa Tatehiro
Published: July 2019

A 47-year-old woman visited Tokai University Hospital complaining of left cervical lymph node swelling in 2007. The laboratory data were almost normal except for slight anemia (Hgb 10.5 g/dL), elevation of serum soluble interleukin (IL)-2 receptor levels (645 U/mL [normal range 220–530 U/mL]), and positive hepatitis C virus (HCV) antibody. Serum transaminase and lactated dehydrogenase levels were normal. Contrast-enhanced computed tomography (CT) showed lymph node swelling with a diameter of 3 cm at the left supraclavicular fossa and mild splenomegaly, and 18F-fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT) revealed abnormal uptake in the left supraclavicular fossa. The patient was diagnosed as having indolent nodal marginal zone B-cell lymphoma by lymph node biopsy. After 9 years with no progression of lymphoma, the patient received 12-week ledipasvir/sofosbuvir therapy for HCV infection and achieved sustained virologic response without any adverse effects. The left supraclavicular mass disappeared in the FDG-PET/CT performed 5 months after antiviral therapy indicating complete response. The serum soluble IL-2 receptor concentration decreased to 244 U/mL. Thereafter, her lymphoma was in remission for 3 years.
Kann eine Online-Intervention für Depressionen emotionale Probleme und Schmerzen lindern? Eine randomisiert-kontrollierte Studie
Authors: Miegel Franziska , Gehlenborg Josefine , Bücker Lara , Lion Despina , Moritz Steffen
Published: July 2019

Hintergrund: Personen mit Schmerzsymptomen leiden häufig unter komorbider Depression. Die Gate-Control-Theorie nimmt an, dass die Schmerzwahrnehmung durch psychosoziale Einflüsse moduliert wird und dass die Linderung von Depressionen entsprechend auch Schmerzen verringern kann. Da Schmerzpatienten oft immobil sind und die psychotherapeutische Versorgung unzureichend ist, stellen Online-Interventionen eine vielversprechende Alternativbehandlung dar. Die vorliegende randomisiert-kontrollierte Studie untersucht die Wirksamkeit der Online-Intervention novego – Depressionen bewältigen bei Schmerzpatienten mit depressiven Symptomen. Patienten und Methoden: Von den re­krutierten Teilnehmern mit Schmerzen und depressiven Symptomen wurden je 71 Personen randomisiert der Interventionsgruppe oder der Wartekontrollgruppe zugeteilt. Der Interventionszeitraum betrug 12 Wochen. Zum Baseline- und Postzeitpunkt wurden depressive (BDI-II; primärer Endpunktparameter) sowie Schmerzsymptome (VAS, DSF; sekundäre Endpunktparameter) erfasst. Ergebnisse: Die Teilnehmer der novego-Gruppe zeigten einen signifikanten Rückgang im BDI-II mit einer kleinen bis mittleren Effektgröße von ηp2 = 0,043 in der Intention-to-treat-Analyse und ηp2 = 0,057 in der Per-protocol-Analyse. Die Schmerzsymptome gingen in beiden Gruppen gleichermaßen ohne signifikante Unterschiede zurück. Explorative Moderationsanalysen zeigten jedoch, dass Patienten mit Schmerzen in den Händen oder im oberen Rücken signifikant von novego bezüglich der Schmerzsymptomatik profitierten. Die Zufriedenheit mit der Intervention war hoch. Schlussfolgerung: Die Online-Intervention novego ist geeignet, um depressive Symptome bei Teilnehmern mit unterschiedlicher Schmerz­symptomatik zu reduzieren. Patienten mit Schmerzen in den Händen oder im oberen Rücken können besonders davon profitieren.
Cytogenetic Analysis and Chromosomal Mapping of Repetitive DNA in Melipona Species (Hymenoptera, Meliponini)
Authors: Travenzoli Natália M. , Lima Bárbara A. , Cardoso Danon C. , Dergam Jorge A. , Fernandes-Salomão Tânia M. , Lopes Denilce M.
Published: July 2019

Stingless bees of the genus Melipona are subdivided into 4 subgenera called Eomelipona, Melikerria, Melipona sensu stricto, and Michmelia according to species morphology. Cytogenetically, the species of the genus Melipona show variation in the amount and distribution of heterochromatin along their chromosomes and can be separated into 2 groups: the first with low content of heterochromatin and the second with high content of heterochromatin. These heterochromatin patterns and the number of chromosomes are characteristics exclusive to Melipona karyotypes that distinguish them from the other genera of the Meliponini. To better understand the karyotype organization in Melipona and the relationship among the subgenera, we mapped repetitive sequences and analyzed previously reported cytogenetic data with the aim to identify cytogenetic markers to be used for investigating the phylogenetic relationships and chromosome evolution in the genus. In general, Melipona species have 2n = 18 chromosomes, and the species of each subgenus share the same characteristics in relation to heterochromatin regions, DAPI/CMA3 fluorophores, and the number and distribution of 18S rDNA sites. Microsatellites were observed only in euchromatin regions, whereas the (TTAGG)6 repeats were found at telomeric sites in both groups. Our data indicate that in addition to the chromosome number, the karyotypes in Melipona could be separated into 2 groups that are characterized by conserved cytogenetic features and patterns that generally are shared by species within each subgenus, which may reflect evolutionary constraints. Our results agree with the morphological separation of the Melipona into 4 subgenera, suggesting that they must be independent evolutionary lineages.
Distribution and habitats of Paphiopedilum Pfitzer (Orchidaceae) known to occur in Bhutan
Authors: Gurung Dhan Bahadur , Gyeltshen Nima , Tobgay Kezang , Dalström Stig , Wangdi Jangchuk , Ghalley Bhakta Bahadur , Chaida Lekey , Phuntsho Phuntsho , Gyeltshen Ngawang , Dawa Kelzang , Wangchuk Tandin , Pradhan Rebecca , Hoijer Thomas Axel Ivan , Gyeltshen Choki
Published: July 2019

Paphiopedilum fairrieanum, P. spicerianum, and P. venustum (Orchidaceae: Cypripedioideae) are reported to occur in Bhutan, of which the former is known to be Critically Endangered and the latter two are Endangered.  Based on numerous field trips conducted over the last decade, populations of P. fairrieanum and P. venustum were located in Bhutan.  No individual of P. spicerianum, however, was found despite many search attempts.  Its occurrence in Bhutan may have been originally erroneous.  Based on the accessibility of the habitats, six 10m × 10m quadrats were defined to enumerate the plant species found in the Paphiopedilum habitats.  Vegetation analyses and cluster dendrograms of the plant species composition indicated the presence of three forest types with distinct species compositions.  Paphiopedilum fairrieanum was found growing mainly as a lithophyte on seasonally dry limestone cliffs or on limestone outcrops with a comparatively open forest canopy.  These populations were mostly located on southwest- or northwest-facing slopes with soil pH ranging from 7.1 to 7.8.  Paphiopedilum venustum, in contrast, was a ground-dwelling species restricted to relatively dense forests with soil pH ranging from 7.1 to 7.5.