bluuebunny/crossref_metadata_2025 huggingface dataset:
Health for all by all-pursuing multi-sectoral action on health for SDGs in the WHO Eastern Mediterranean Region
Authors: Al-Mandhari Ahmed , El-Adawy Maha , Khan Wasiq , Ghaffar Abdul
Published: December 2019

The WHO Eastern Mediterranean Region is endowed with deep intellectual tradition, interesting cultural diversity, and a strong societal fabric; components of a vibrant platform for promoting health and wellbeing. Health has a central place in the Sustainable Development Goals (SDGs) for at least three reasons: Firstly, health is shaped by factors outside of the health sector. Secondly, health can be singled out among several SDGs as it provides a clear lens for examining the progress of the entire development process. Thirdly, in addition to being an outcome, health is also a contributor to achieving sustainable development. Realizing this central role of health in SDGs and the significance of collaboration among diverse sectors, the WHO is taking action. In its most recent General Program of Work 2019–2023 (GPW 13), the WHO has set a target of promoting the health of one billion more people by addressing social and other determinants of health through multi-sectoral collaboration. The WHO Regional Office for the Eastern Mediterranean Region, through Vision 2023, aims at addressing these determinants by adopting an equity-driven, leaving no one behind approach. Advocating for Health in All Policies, multi-sectoral action, community engagement, and strategic partnerships are the cornerstone for this approach. The focus areas include addressing the social and economic determinants of health across the life course, especially maternal and child health, communicable diseases, non-communicable diseases, and injuries. The aspirations are noteworthy – however, recent work in progress in countries has also highlighted some areas for improvement. Joint work among different ministries and departments at country level is essential to achieve the agenda of sustainable development. For collaboration, not only the ministries and departments need to be engaged, but the partnerships with other stakeholders such as civil society and private sector are a necessity and not a choice to effectively pursue achievement of SDGs.
Contradictions within the SDGs: are sin taxes for health improvement at odds with employment and economic growth in Zambia
Authors: Hangoma Peter , Surgey Gavin
Published: December 2019

Background

A recurring discussion in the literature relates to the possible contradictions among the Sustainable Development Goals (SDGs). The focus has been on economic goals, such as economic growth and goals related to climate change. We explore the possible contradictions that may arise between economic goals and health goals, specifically, the goal on Non-Communicable Diseases (NCDs) — SDG3.4. As a way to achieve SDG3.4, countries have been urged to introduce sin taxes, such as those on sugar. Yet others have argued that such taxes may affect employment (SDG 8.5), economic growth (SDG 8.1), and increase poverty (SDG1). However, there is limited or no reliable evidence, using actual experience, on the effect of sugar tax on health and economic outcomes. This makes it hard to assess the possible contradictions in SDGs that sugar taxes may generate.

Main body

Using a conceptual framework on SDGs that views relationships among SDGs as either contradictory, reinforcing, or neutral, we carefully consider whether there are contradictions between SDG 3.4 on one hand and SDG 1, SDG 8.1, and SDG 8.5 on the other hand. We illustrate this using Zambia which recently introduced an equivalent 3% tax on non-alcoholic beverages, implicitly targeted at sugar-sweetened beverages (SSBs), given the stated goal of reducing NCDs. Concerns are that such a tax would be detrimental to the Zambia sugar value chain which contributes about 6% to GDP, in which case the achievement of SDG 3.4 (health) would be at odds with, or contradict, SDG 1, SDG 8.1, and SDG 8.5 (poverty eradication, economic growth, and creation of employment). We discuss that the existence of contradictions depend on a number of contextual factors, which allows us to make two conclusions about sugar taxation in Zambia. First, the current tax rate of 3% is likely neutral (no contradictions or reinforcing relationships) because it is too low to have any health or employment effects. However, the revenue raised can be reinvested to improve livelihoods. Secondly, the tax rate should be increased but care has to be exercised to ensure that the rate is not too high to generate contradictions. There will be need to carefully assess important parameters such as elasticities and explore alternative economic livelihoods.

Conclusion

Without paying due consideration to important contextual factors, Zambia and many LMIC risk experiencing contradictions among SDGs.
Pulsatile arterial blood pressure mimicking aortic valve opening during continuous-flow LVAD support: a case report
Authors: Paprotny Matthias , Ruschitzka Frank , Lüders Bernd , Wilhelm Markus J. , Aser Raed , Bettex Dominique , Flammer Andreas J. , Rudiger Alain , Winnik Stephan
Published: December 2019

Background

Left ventricular assist devices (LVAD) have become a common treatment option in advanced heart failure. Lack of aortic valve opening during left ventricular unloading is a common complication and associated with a worse outcome. Maintaining a minimum pulse pressure is an important goal during the early postoperative period after LVAD implantation since it is commonly seen as secure sign of aortic valve opening.

Aims/objective

We report a case of an LVAD-supported patient with early permanent closure of the aortic valve despite a pulse pressure > 15 mmHg at all times following LVAD implantation. We demonstrate how careful assessment of the invasive arterial blood pressure curve can indicate aortic valve closure irrespective of pulsatile blood flow.

Method

A 69-year old male patient with terminal ischemic cardiomyopathy was referred for long-term mechanical circulatory support. Due to mild aortic regurgitation both an aortic bioprosthesis and a continuous-flow left ventricular assist device were implanted. Postoperative echocardiography documented a patent aortic bioprosthesis and an acceptable residual systolic left ventricular contractility. During invasive arterial blood pressure monitoring repetitive transient slight blood pressure decreases followed by slight blood pressure increases coincided with programmed LVAD flushing cycles. Permanent pulsatile flow with a pulse pressure of ≥15 mmHg conveyed systolic opening of the aortic valve. Echocardiography, however, proved early permanent aortic valve closure. In retrospect, transformation of the automated LVAD flushing cycles into visible changes of the arterial blood pressure curve during invasive blood pressure monitoring is indicative of ejection of the complete cardiac output through LVAD itself, and therefore an early clinical sign of aortic valve closure.

Discussion/conclusion

We present this interesting didactic case to highlight caveats during the early postoperative period after LVAD implantation. Moreover, this case demonstrates that careful and differentiated observation of the arterial blood pressure waveform provides crucial information in this unique and growing patient population of continuous-flow LVAD support.
Huang-Lian Jie-Du decoction: a review on phytochemical, pharmacological and pharmacokinetic investigations
Authors: Qi Yiyu , Zhang Qichun , Zhu Huaxu
Published: December 2019

Huang-Lian Jie-Du decoction (HLJDD), a famous traditional Chinese prescription constituted byRhizoma Coptidis,Radix Scutellariae,Cortex PhellodendriandFructus Gradeniae, has notable characteristics of dissipating heat and detoxification, interfering with tumors, hepatic diseases, metabolic disorders, inflammatory or allergic processes, cerebral diseases and microbial infections. Based on the wide clinical applications, accumulating investigations about HLJDD focused on several aspects: (1) chemical analysis to explore the underlying substrates responsible for the therapeutic effects; (2) further determination of pharmacological actions and the possible mechanisms of the whole prescription and of those representative ingredients to provide scientific evidence for traditional clinical applications and to demonstrate the intriguing molecular targets for specific pathological processes; (3) pharmacokinetic feature studies of single or all components of HLJDD to reveal the chemical basis and synergistic actions contributing to the pharmacological and clinically therapeutic effects. In this review, we summarized the main achievements of phytochemical, pharmacological and pharmacokinetic profiles of HLJDD and its herbal or pharmacologically active chemicals, as well as our understanding which further reveals the significance of HLJDD clinically.
Insecticide resistance in Culex quinquefasciatus Say, 1823 in Brazil: a review
Authors: Lopes Ramon Pereira , Lima José Bento Pereira , Martins Ademir Jesus
Published: December 2019

Culex quinquefasciatusis a successful invasive species broadly distributed in subtropical regions, including Brazil. It is an extremely annoying mosquito due to its nocturnal biting behavior, in high-density populations and it is a potential bridge between sylvatic arbovirus from birds to man in urban territories. Herein, we present a review concerning the methods of chemical control employed againstCx. quinquefasciatusin Brazil since the 1950’s and insecticide resistance data registered in the literature. As there is no specific national programme forCx. quinquefasciatuscontrol in Brazil, the selection of insecticide resistance is likely due in part to the well-designed chemical campaigns againstAedes aegyptiand the elevated employment of insecticides by households and private companies. There are very few publications about insecticide resistance inCx. quinquefasciatusfrom Brazil when compared toAe. aegypti. Nevertheless, resistance to organophosphates, carbamate, DDT, pyrethroids and biolarvicides has been registered inCx. quinquefasciatuspopulations from distinct localities of the country. Concerning physiological mechanisms selected for resistance, distinct patterns of esterases, as well as mutations in the acetylcholinesterase (ace-1) and voltage-gated sodium channel (NaV) genes, have been identified in natural populations. Given environmental changes and socioeconomical issues in the cities, in recent years we have been experiencing an increase in the number of disease cases caused by arboviruses, which may involveCx. quinquefasciatusparticipation as a key vector. It is urgent to better understand the efficiency and susceptibility status to insecticides, as well as the genetic background of known resistant mechanisms already present inCx. quinquefasciatuspopulations for an effective and rapid chemical control when eventually required.
MethylToSNP: identifying SNPs in Illumina DNA methylation array data
Authors: LaBarre Brenna A. , Goncearenco Alexander , Petrykowska Hanna M. , Jaratlerdsiri Weerachai , Bornman M. S. Riana , Hayes Vanessa M. , Elnitski Laura
Published: December 2019

Background

Current array-based methods for the measurement of DNA methylation rely on the process of sodium bisulfite conversion to differentiate between methylated and unmethylated cytosine bases in DNA. In the absence of genotype data this process can lead to ambiguity in data interpretation when a sample has polymorphisms at a methylation probe site. A common way to minimize this problem is to exclude such potentially problematic sites, with some methods removing as much as 60% of array probes from consideration before data analysis.

Results

Here, we present an algorithm implemented in an R Bioconductor package, MethylToSNP, which detects a characteristic data pattern to infer sites likely to be confounded by polymorphisms. Additionally, the tool provides a stringent reliability score to allow thresholding on SNP predictions. We calibrated parameters and thresholds used by the algorithm on simulated and real methylation data sets. We illustrate findings using methylation data from YRI (Yoruba in Ibadan, Nigeria), CEPH (European descent) and KhoeSan (southern African) populations. Our polymorphism predictions made using MethylToSNP have been validated through SNP databases and bisulfite and genomic sequencing.

Conclusions

The benefits of this method are threefold. First, it prevents extensive data loss by considering only SNPs specific to the individuals in the study. Second, it offers the possibility to identify new polymorphisms in samples for which there is little known about the genetic landscape. Third, it identifies variants as they exist in functional regions of a genome, such as in CTCF (transcriptional repressor) sites and enhancers, that may be common alleles or personal mutations with potential to deleteriously affect genomic regulatory activities. We demonstrate that MethylToSNP is applicable to the Illumina 450K and Illumina 850K EPIC array data and is also backwards compatible to the 27K methylation arrays. Going forward, this kind of nuanced approach can increase the amount of information derived from precious data sets by considering samples of the project individually to enable more informed decisions about data cleaning.
Reflecting trends in the academic landscape of sustainable energy using probabilistic topic modeling
Authors: Bickel Manuel W.
Published: December 2019

Background

Facing planetary boundaries, we need a sustainable energy system providing its life support function for society in the long-term within environmental limits. Since science plays an important role in decision-making, this study examines the thematic landscape of research on sustainable energy, which may contribute to a sustainability transformation. Understanding the structure of the research field allows for critical reflections and the identification of blind spots for advancing this field.

Methods

The study applies a text mining approach on 26533 Scopus-indexed abstracts published from 1990 to 2016 based on a latent Dirichlet allocation topic model. Models with up 1100 topics were created. Based on coherence scores and manual inspection, the model with 300 topics was selected. These statistical methods served for highlighting timely topic trends, differing thematic fields, and emerging communities in the topic network. The study critically reflects the quantitative results from a sustainability perspective.

Results

The study identifies a focus on establishing and optimizing the energy infrastructure towards 100% renewable energies through key modern technology areas: materials science, (biological) process engineering, and (digital) monitoring and control systems. Energy storage, photonic materials, nanomaterials, or biofuels belong to the topics with the strongest trends. The study identifies decreasing trends for general aspects regarding sustainable development and related economic, environmental, and political issues.

Conclusions

The discourse is latently adopting a technology-oriented paradigm focusing on renewable energy generation and is moving away from the multi-faceted concept of sustainability. The field has the potential to contribute to climate change mitigation by optimizing renewable energy systems. However, given the complexity of these systems, horizontal integration of the various valuable vertical research strands is required. Furthermore, the holistic ecological perspective considering the global scale that has originally motivated research on sustainable energy might be re-strengthened, e.g., by an integrated energy and materials perspective. Beyond considering the physical dimensions of energy systems, existing links from the currently technology-oriented discourse to the social sciences might be strengthened. For establishing sustainable energy systems, future research will not only have to target the technical energy infrastructure but put a stronger focus on issues perceivable from a holistic second-order perspective.
A prospective clinical study on implant impression accuracy
Authors: Osman Motaz , Ziada Hassan , Suliman Ahmed , Abubakr Neamat Hassan
Published: December 2019

Background

An accurate impression is crucial to the long-term success of dental implants. This investigation evaluated the accuracy of the open and closed implant impression techniques in partially edentulous patients who received two adjacent implants.

Material and methods

Forty patients received Osstem Implants (Osstem Implant System, Seoul, Korea). Two impressions were made for each patient, one using an open tray and a second with a closed tray technique. The horizontal distances between two impression copings were measured and compared to similar measurements on the master casts. Also, under a stereomicroscope (AmScop14370, Myford Road, #150, Irvine, CA 92606 USA) at a 50-fold magnification, the presence or absence of the marginal discrepancies was evaluated.

Results

There were no statistically significant differences regarding horizontal measurements and in the marginal relationship for the two impression techniques, except between the anterior and posterior regions, for the closed tray technique. There were also no statistically significant differences in the impression accuracy between maxillary and the mandibular arches. In addition, there were no statistically significant differences for the intraoral horizontal distances, compared to similar horizontal measurements on master casts, between the open and closed tray techniques.

Conclusions

Within the limitations of the present study, there were generally no differences in the impression accuracy between the open and closed tray techniques in partially edentulous patients with two adjacent implants.
Acid-specific formaldehyde donor is a potential, dual targeting cancer chemotherapeutic/chemo preventive drug for FANC/BRCA-mutant cancer
Authors: Ridpath John R. , Nakamura Jun
Published: December 2019

Background

Development of chemotherapeutic/preventive drugs that selectively kill cancer - the Holy Grail of cancer research - is a major challenge. A particular difficulty arises when chemotherapeutics and radiation are found to be rather ineffective against quiescent cancer cells in solid tumors. In the limited oxygen condition within a solid tumor, glycolysis induces an acidic environment. In such an environment the compound hexamethylenetetramine (HMTA) will act as a formaldehyde donor. HMTA has been characterized a non-carcinogen in experimental animals and causes no major adverse side-effects in humans. We previously reported that both a chicken B-lymphocyte cell line transformed with an avian leucosis virus and human colon cancer cells deficient in the FANC/BRCA pathway are hypersensitive to formaldehyde. Thus, we assessed the potential usage of HMTA as a chemotherapeutic agent.

Results

The differential cytotoxicity of HMTA was tested using chicken DT40 cells deficient in DNA repair under neutral and acidic conditions. While HMTA is not efficiently hydrolyzed under neutral conditions, all HR-deficient DT40 cells tested were hypersensitive to HMTA at pH 7.3. In contrast, HMTA clearly increased cell toxicity in FANCD2-, BRCA1- and BRCA2- deficient cells under acidic conditions.

Conclusion

Here we show that in vitro experiments showed that at low pH HMTA causes drastic cytotoxicity specifically in cells deficient in the FANC/BRCA pathway. These results strongly suggest that HMTA may be an attractive, dual-targeting chemotherapeutic/preventive drug for the selective delivery of formaldehyde to solid tumors and causes cell death in FANC/BRCA-deficient cells without major adverse effects.
Responses of earliness and lateness genes for heading to different photoperiods, and specific response of a gene or a pair of genes to short day length in rice
Authors: Rana Birendra Bahadur , Kamimukai Misa , Bhattarai Mukunda , Koide Yohei , Murai Masayuki
Published: December 2019

Background

Heading time is an important trait for regional and seasonal adaptabilities in rice, and is controlled by genetic factors in relation with environmental factors, mainly day length and temperature. The following genes controlling heading were examined for their responses to six different environmental conditions involving different day lengths using five early near-isogenic lines (NILs) of T65-R and three late NILs of T65wx: two earliness genes,Ef1andEfxcontrolling basic vegetative phase (BVG), andm-Ef1, the enhancer to the former gene; and two lateness genes,Se1-pat(t) andse-patcontrolling photo-sensitivity and BVG, respectively. T65-R and T65-T were different accessions of Taichung 65. T65wx is a NIL of T65-T carryingwx.

Results

The five early NILs of T65-R were in the order of ER50 (Ef1,Efx,m-Ef1) < ER40 (Ef1,m-Ef1) ≤ ER20 (Ef1,Efx) < ER1 (Ef1) ≤ ER21 (Efx) < T65-R regarding days to heading (DTH) under two spring-sowing and one summer-sowing paddy field (PF) conditions. The three late NILs of T65wx were in the order of LF3 (Se1-pat(t)) ≤ LF2 (Se1-pat(t),se-pat) ≤ T65wx < LF1 (se-pat) under two short-day conditions (10-h photoperiod condition with artificial-light and natural short-day condition from autumn to winter). The NILs and T65wx were in the order of T65wx < LF3 < LF1 < LF2 under the two spring-sowing PF (long day) conditions. T65-R (Ac-ef1) was 2.8 or 5.1 days earlier in DTH than T65-T (ac-ef1) under the two spring-sowing PF conditions. However, T65-R was 19 and 10 days earlier than T65-T under the two short-day conditions.

Conclusions

Earliness gene(s) and their combinations reduced DTH regardless of photoperiod lengths.Se1-pat(t) increased DTH under long-day conditions but decreased it under short-day conditions, whilese-patelongated DTH under both short-day and long-day conditions indicating thatse-patis responsible for BVG. These-patincreased DTH by adding its effect over that ofSe1-pat(t) under long-day conditions. However, this increasing effect of DTH byse-patwas almost completely masked when it coexisted withSe1-pat(t) under the short-day conditions. Notably, the response ofAc-ef1to day length was found to delay heading under the short-day conditions.
Examining the episodic context account: does retrieval practice enhance memory for context?
Authors: Hong Min Kyung , Polyn Sean M. , Fazio Lisa K.
Published: December 2019

Retrieval practice, such as filling in blanks or taking quizzes, is firmly established as an effective study strategy. However, the underlying mechanism of how retrieval practice benefits memory is still unclear. One current theory, the episodic context account, proposes that retrieval enhances memory by reinstating a prior learning context. This retrieved context is then strengthened and updated to include context at the time of recall, which later serves as an effective retrieval cue. However, few studies have directly tested this hypothesis. We did so by examining participants’ memory for the initial study context. Across three experiments, participants encoded cue-target pairs presented in different colors and either restudied or practiced retrieving the targets. If retrieval practice benefits memory by reinstating the prior episodic context, participants who successfully retrieved the items during practice should have enhanced memory for context details (i.e. font color) compared to participants who restudied the pairs. Contrary to this prediction, memory for font colors did not differ between the restudy condition and the retrieval practice condition. Even when font color was actively attended to and integrated with the to-be-remembered items, retrieval practice did not increase memory for this aspect of context. Our results suggest that the context reinstated during retrieval practice is limited in nature. Aspects of the context that are not essential to retrieval of the item are not strengthened by retrieval practice.
Domperidone treatment advances onset of puberty in the viviparous mosquitofish Gambusia affinis
Authors: Bhat Shilpa K. , Ganesh C. B.
Published: December 2019

Background

Although dopamine (DA) exerts modulatory effect on reproduction in the majority of fishes, its role is not clearly understood in viviparous species. The aim of this investigation was to determine the influence of DA antagonist domperidone (DOM) on puberty in the viviparous speciesGambusia affinis.

Results

Treatment of 1.5 or 4 mg DOM to 25 days post-hatching (DPH) juveniles for a period of 35 days resulted in dense aggregations of gonadotropin-releasing hormone (GnRH)-immunoreactive fibres in the proximal pars distalis (PPD) region of the pituitary gland in contrast to faintly seen fibres in treatment controls. In the ovary, the follicles belonging to stages I–IV did not differ significantly among different experimental groups. However, stage V (vitellogenic) follicles were completely absent in treatment controls in contrast to their presence in 1.5 or 4 mg DOM-treated fish. Besides, the diameter of stage V follicles was significantly higher in 1.5 mg DOM-treated fish compared with 4 mg DOM-treated fish.

Conclusions

The results suggest that DOM treatment triggers the follicular development and promotes the early onset of puberty, possibly by attenuating the dopaminergic inhibition on GnRH fibres, for the first time in a viviparous species.
Recommendations from the Brazilian society of rheumatology for the diagnosis of Sjögren’s syndrome (Part I): glandular manifestations (systematic review)
Authors: Trevisani Virginia Fernandes Moça , Pasoto Sandra Gofinet , Fernandes Marilena Leal Mesquita Silvestre , Lopes Maria Lúcia Lemos , de Magalhães Souza Fialho Sonia Cristina , Pinheiro Aysa César , dos Santos Laura Caldas , Appenzeller Simone , Fidelix Tania , Ribeiro Sandra Lúcia Euzébio , de Brito Danielle Christinne Soares Egypto , Libório Tatiana , Santos Maria Carmen Lopes Ferreira Silva , Tanure Leandro , Gennari Juliana D Agostino , Civile Vinicius Tassoni , Pinto Ana Carolina Pereira Nunes , Oliveira Fabíola Reis , de Sousa Jaqueline Martins , Miyamoto Samira Tatiyama , Valim Valeria
Published: December 2019

Background

Primary Sjögren’s syndrome (pSS) is a systemic immune-mediated disease whose main characteristic is exocrine gland inflammation and, subsequent reduction in tear and saliva production. A delayed diagnosis is common due to the nonspecific clinical manifestations of disease. The aim of the present study was to develop recommendations for the diagnosis of glandular manifestations of pSS based on evidence and expert opinion.

Main body of the abstract

We conducted a systematic literature review to retrieve the best evidence available on the accuracy of diagnostic tests for pSS. We also held two in-person meetings with experts (rheumatologists, pathologists, ophthalmologists and dentists) to establish their level of agreement using the Delphi method. Ultimately, we generated 18 recommendations that aim to facilitate the diagnosis of the glandular manifestations of pSS.

Conclusion

The diagnosis of glandular manifestations of pSS is complex and multidisciplinary. It requires specific knowledge in the field of ophthalmology, immunology, pathology and imaging, making it compulsory for the rheumatologist to work with professionals from these different areas in order to improve accuracy and early diagnosis. Glandular dysfunction tests, ANA, RF, Anti-Ro, protein electrophoresis, urinalysis, blood count, C-Reactive protein, complement, testing for syphilis and viruses (HCV, HIV) and SGUS should be investigated when dryness or systemic manifestation are present. Minor salivary gland biopsy is recommended for all anti-Ro negative or incomplete criteria cases.
The use of a dedicated neurological triage system improves process times and resource utilization: a prospective observational study from an interdisciplinary emergency department
Authors: Hoyer Carolin , Stein Patrick , Rausch Hans-Werner , Alonso Angelika , Nagel Simon , Platten Michael , Szabo Kristina
Published: December 2019

Background

Patients with neurological symptoms have been contributing to the increasing rates of emergency department (ED) utilization in recent years. Existing triage systems represent neurological symptoms rather crudely, neglecting subtler but relevant aspects like temporal evolution or associated symptoms. A designated neurological triage system could positively impact patient safety by identifying patients with urgent need for medical attention and prevent inadequate utilization of ED and hospital resources.

Methods

We compared basic demographic information, chief complaint/presenting symptom, door-to-doctor time and length of stay (LOS) as well as utilization of ED resources of patients presenting with neurological symptoms or complaints during a one-month period before as well as after the introduction of the Heidelberg Neurological Triage System (HEINTS) in our interdisciplinary ED. In a second step, we compared diagnostic and treatment processes for both time periods according to assigned acuity.

Results

During the two assessment periods, 299 and 300 patients were evaluated by a neurologist, respectively. While demographic features were similar for both groups, overall LOS (p < 0.001) was significantly shorter, while CT (p = 0.023), laboratory examinations (p = 0.006), ECG (p = 0.011) and consultations (p = 0.004) were performed significantly less often when assessing with HEINTS. When considering acuity, an epileptic seizure was less frequently evaluated as acute with HEINTS than in the pre-HEINTS phase (p = 0.002), while vertigo patients were significantly more often rated as acute with HEINTS (p < 0.001). In all cases rated as acute, door-to-doctor-time (DDT) decreased from 41.0 min to 17.7 min (p < 0.001), and treatment duration decreased from 304.3 min to 149.4 min (p < 0.001) after introduction of HEINTS triage.

Conclusion

A dedicated triage system for patients with neurological complaints reduces DDT, LOS and ED resource utilization, thereby improving ED diagnostic and treatment processes.
α-Fetoprotein (AFP)-L3% and transforming growth factor B1 (TGFB1) in prognosis of hepatocellular carcinoma after radiofrequency
Authors: Shawky Elsawabi Ahmed , Abdel wahab Khaled , Ibrahim Wesam , Saleh Shereen , Massoud Yasmine , Abdelbary Mohamed , Nabih Ahmed
Published: December 2019

Background

Numerous hepatocellular carcinoma (HCC) biomarkers have been assessed in the diagnosis and prognosis of HCC. The aim of this study was to assess the value of α-fetoprotein (AFP)-L3% and transforming growth factor B1 (TGFB1) as prognostic markers in hepatocellular carcinoma after radiofrequency ablation (RFA). This observational cohort study included 40 patients with HCC diagnosed by triphasic computed tomography criteria indicated for radiofrequency ablation. Serum AFP, AFP-L3%, and TGFB1 were measured in all patients before and 3 months after radiofrequency ablation.

Results

Statistically significant lower levels of TGFB1, AFP, and AFP-L3% were noted in the HCC patients after radiofrequency ablation. Significant lower levels of TGFB1, AFP, and AFP-L3% were found in the no recurrence group in comparison to the recurrence group. The cutoff value of TGFB1 > 56.87 ng/mL, AFP > 74.9 ng/mL, and AFP-L3% > 8.5% was the best in the discrimination of tumor recurrence with sensitivity of 85.7%, 57.1%, and 100%; specificity of 54.6%, 84.9%, and 100%; and diagnostic accuracy of 64.5%, 69%, and 100%, respectively.

Conclusion

TGFB1 and AFP-L3% are good prognostic markers for HCC. They could be used to monitor the response of HCC to treatment.
Impact of Conditioning Intensity of Allogeneic Transplantation for Acute Myeloid Leukemia With Genomic Evidence of Residual Disease
Authors: Hourigan Christopher S. , Dillon Laura W. , Gui Gege , Logan Brent R. , Fei Mingwei , Ghannam Jack , Li Yuesheng , Licon Abel , Alyea Edwin P. , Bashey Asad , Deeg H. Joachim , Devine Steven M. , Fernandez Hugo F. , Giralt Sergio , Hamadani Mehdi , Howard Alan , Maziarz Richard T. , Porter David L. , Scott Bart L. , Warlick Erica D. , Pasquini Marcelo C. , Horwitz Mitchell E.
Published: December 2019

PURPOSE

Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown.

METHODS

Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC).

RESULTS

No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive.

CONCLUSION

This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.
The Foot of the Lake
Authors: Dinkin Aaron J.
Published: December 2019

In 2013, Dinkin reported an unexpectedly sharp dialect boundary in northern New York between the communities of Ogdensburg and Canton in St. Lawrence County: Ogdensburg exhibited the Northern Cities Vowel Shift (NCS) and very little evidence of the low back merger, while Canton showed low back merger nearing completion and no NCS. This article investigates the nature of this dialect boundary via new sociolinguistic interview data from eight neighboring communities: four along the St. Lawrence River and four 25 miles south of it. An east-west division is observed in merger incidence: the four communities to the west, including Ogdensburg, show relatively robust lot-thought distinction, though apparent-time trends toward merger exist; east of Ogdensburg, the merger is much more advanced. A similar sharp boundary may hold for the NCS raising of trap (though the data are spottier due to the NCS’s obsolescence). The geographical sharpness of this boundary suggests that it is not due merely to socioeconomic differences between communities. It may be due to historical patterns of transportation: in the nineteenth century, Ogdensburg was the easternmost navigable point of the upper St. Lawrence River, meaning communities east of Ogdensburg were not directly accessible to the Great Lakes shipping network.
The Myth of Section 7(a): Worker Militancy, Progressive Labor Legislation, and the Coal Miners
Authors: Goldfield Michael , Melcher Cody R.
Published: December 2019

In this article, the authors look at the supposed causal role of progressive labor legislation on union organizing. As an extension of the Wagner Act debates of the late 1980s and early 1990s, the authors argue—contrary to the accepted wisdom of virtually all established scholarship—that “progressive” labor legislation is not generally the impetus for worker organization, a necessary prerequisite without which mass unionization would be impossible. Rather, this legislation is often consciously cooptive, with the explicit goal of diffusing worker militancy, denuding and undermining radical leadership while simultaneously placating popular discontent. The theoretical and methodological shortcomings of the former position are analyzed in the context of the passage of Section 7(a) of the National Industrial Recovery Act (NIRA). The authors argue that if the unionization of coal miners—the supposed primary beneficiaries of the stimulus attributed to the legislation—occurred prior to the passage of the NIRA, Section 7(a) could not have acted as a catalyst to unionization in the coalfields. The authors show, using archival and secondary accounts, that nearly all the nation’s coal miners were organized before the passage of the NIRA. In light of this empirical data, the authors propose an alternative model of union growth that rejects the methodological individualist assumptions that tacitly undergird the existing literature.
Short term cyclical stretch phosphorylates p38 and ERK1/2 MAPKs in cultured fibroblasts from the hearts of rainbow trout, Oncorhynchus mykiss
Authors: Johnston Elizabeth F. , Gillis Todd E.
Published: December 2019

The form and function of the rainbow trout heart can remodel in response to various stressors including changes in environmental temperature and anaemia. Previous studies have hypothesized that changes in biomechanical forces experienced by the trout myocardium as result of such physiological stressors could play a role in triggering the remodeling response. However, there has been no work examining the influence of biomechanical forces on the trout myocardium or of the cellular signals that would translate such a stimuli into a biological response. In this study, we test the hypothesis that the application of biomechanical forces to trout cardiac fibroblasts activate the cell signalling pathways associated with cardiac remodeling. This was done by cyclically stretching cardiac fibroblasts to 10% equibiaxial deformation at 0.33 Hz and quantifying the activation of the p38-JNK-ERK mitogen activated protein kinase (MAPK) pathway. After 20 min, p38 MAPK phosphorylation was elevated by 4.2-fold compared to control cells (P<0.05) and after 24h of stretch, p38 MAPK phosphorylation remained elevated and extracellular-regulated kinase 1/2 was phosphorylated by 2.4-fold compared to control (P<0.05). Together, these results indicate that mechanotransducive pathways are active in cardiac fibroblasts, and lead to the activation of cell signalling pathways involved in cardiac remodeling.
Positional information and tissue scaling during development and regeneration
Authors: Čapek Daniel , Müller Patrick
Published: December 2019

In order to contribute to the appropriate tissues during development, cells need to know their position within the embryo. This positional information is conveyed by gradients of signaling molecules, termed morphogens, that are produced in specific regions of the embryo and induce concentration-dependent responses in target tissues. Positional information is remarkably robust, and embryos often develop with the correct proportions even if large parts of the embryo are removed. In this Review, we discuss classical embryological experiments and modern quantitative analyses that have led to mechanistic insights into how morphogen gradients adapt, scale and properly pattern differently sized domains. We analyze these experimental findings in the context of mathematical models and synthesize general principles that apply to multiple systems across species and developmental stages.
The Drosophila NCAM homolog Fas2 signals independently of adhesion
Authors: Neuert Helen , Deing Petra , Krukkert Karin , Naffin Elke , Steffes Georg , Risse Benjamin , Silies Marion , Klämbt Christian
Published: December 2019

The development of tissues and organs requires close interaction of cells. To achieve this, cells express adhesion proteins such as the neural cell adhesion molecule (NCAM) or its Drosophila ortholog Fasciclin 2 (Fas2). Both are members of the Ig-domain superfamily of proteins that mediate homophilic adhesion. These proteins are expressed as isoforms differing in their membrane anchorage and their cytoplasmic domains. To study the function of single isoforms, we have conducted a comprehensive genetic analysis of Fas2. We reveal the expression pattern of all major Fas2 isoforms, two of which are GPI anchored. The remaining five isoforms carry transmembrane domains with variable cytoplasmic tails. We generated Fas2 mutants expressing only single isoforms. In contrast to the null mutation, which causes embryonic lethality, these mutants are viable, indicating redundancy among the different isoforms. Cell type-specific rescue experiments showed that glial-secreted Fas2 can rescue the Fas2 mutant phenotype to viability. This demonstrates that cytoplasmic Fas2 domains have no apparent essential functions and indicate that Fas2 has function(s) other than homophilic adhesion. In conclusion, our data suggest novel mechanistic aspects of a long-studied adhesion protein.
Oral administration of a synthetic vinyl-ether plasmalogen normalizes open field activity in a mouse model of rhizomelic chondrodysplasia punctata
Authors: Fallatah Wedad , Smith Tara , Cui Wei , Jayasinghe Dushmanthi , Di Pietro Erminia , Ritchie Shawn A. , Braverman Nancy
Published: December 2019

Rhizomelic chondrodysplasia punctata (RCDP) is a rare genetic disorder caused by mutations in peroxisomal genes essential for plasmalogen biosynthesis. Plasmalogens are a class of membrane glycerophospholipids containing a vinyl-ether-linked fatty alcohol at the sn-1 position that affect functions including vesicular transport, membrane protein function and free radical scavenging. A logical rationale for the treatment of RCDP is therefore the therapeutic augmentation of plasmalogens. The objective of this work was to provide a preliminary characterization of a novel vinyl-ether synthetic plasmalogen, PPI-1040, in support of its potential utility as an oral therapeutic option for RCDP. First, wild-type mice were treated with 13C6-labeled PPI-1040, which showed that the sn-1 vinyl-ether and the sn-3 phosphoethanolamine groups remained intact during digestion and absorption. Next, a 4-week treatment of adult plasmalogen-deficient Pex7hypo/null mice with PPI-1040 showed normalization of plasmalogen levels in plasma, and variable increases in plasmalogen levels in erythrocytes and peripheral tissues (liver, small intestine, skeletal muscle and heart). Augmentation was not observed in brain, lung and kidney. Functionally, PPI-1040 treatment normalized the hyperactive behavior observed in the Pex7hypo/null mice as determined by open field test, with a significant inverse correlation between activity and plasma plasmalogen levels. Parallel treatment with an equal amount of ether plasmalogen precursor, PPI-1011, did not effectively augment plasmalogen levels or reduce hyperactivity. Our findings show, for the first time, that a synthetic vinyl-ether plasmalogen is orally bioavailable and can improve plasmalogen levels in an RCDP mouse model. Further exploration of its clinical utility is warranted.

This article has an associated First Person interview with the joint first authors of the paper.
Plasmodium falciparum GCN5 acetyltransferase follows a novel proteolytic processing pathway that is essential for its function
Authors: Bhowmick Krishanu , Tehlan Ankita , Sunita  , Sudhakar Renu , Kaur Inderjeet , Sijwali Puran Singh , Krishnamachari Annangarachari , Dhar Suman Kumar
Published: December 2019

The pathogenesis of human malarial parasite Plasmodium falciparum is interlinked with its timely control of gene expression during its complex life cycle. In this organism, gene expression is partially controlled through epigenetic mechanisms, the regulation of which is, hence, of paramount importance to the parasite. The P. falciparum (Pf)-GCN5 histone acetyltransferase (HAT), an essential enzyme, acetylates histone 3 and regulates global gene expression in the parasite. Here, we show the existence of a novel proteolytic processing for PfGCN5 that is crucial for its activity in vivo. We find that a cysteine protease-like enzyme is required for the processing of PfGCN5 protein. Immunofluorescence and immuno-electron microscopy analysis suggest that the processing event occurs in the vicinity of the digestive vacuole of the parasite following its trafficking through the classical ER-Golgi secretory pathway, before it subsequently reaches the nucleus. Furthermore, blocking of PfGCN5 processing leads to the concomitant reduction of its occupancy at the gene promoters and a reduced H3K9 acetylation level at these promoters, highlighting the important correlation between the processing event and PfGCN5 activity. Altogether, our study reveals a unique processing event for a nuclear protein PfGCN5 with unforeseen role of a food vacuolar cysteine protease. This leads to a possibility of the development of new antimalarials against these targets.

This article has an associated First Person interview with the first author of the paper.
Pneumothorax rates in CT-Guided lung biopsies: a comprehensive systematic review and meta-analysis of risk factors
Authors: Huo Ya Ruth , Chan Michael Vinchill , Habib Al-Rahim , Lui Isaac , Ridley Lloyd
Published: December 2019

Objective:

This systematic review and meta-analysis investigated risk factors for pneumothorax following CT-guided percutaneous transthoracic lung biopsy.

Methods:

A systematic search of nine literature databases between inception to September 2019 for eligible studies was performed.

Results:

36 articles were included with 23,104 patients. The overall pooled incidence for pneumothorax was 25.9% and chest drain insertion was 6.9%. Pneumothorax risk was significantly reduced in the lateral decubitus position where the biopsied lung was dependent compared to a prone or supine position [odds ratio (OR):3.15]. In contrast, pneumothorax rates were significantly increased in the lateral decubitus position where the biopsied lung was non-dependent compared to supine (OR:2.28) or prone position (OR:3.20). Other risk factors for pneumothorax included puncture site up compared to down through a purpose-built biopsy window in the CT table (OR:4.79), larger calibre guide/needles (≤18G vs >18G: OR 1.55), fissure crossed (OR:3.75), bulla crossed (OR:6.13), multiple pleural punctures (>1 vs 1: OR:2.43), multiple non-coaxial tissue sample (>1 vs 1: OR 1.99), emphysematous lungs (OR:3.33), smaller lesions (<4 cm vs 4 cm: OR:2.09), lesions without pleural contact (OR:1.73) and deeper lesions (≥3 cm vs <3cm: OR:2.38).

Conclusion:

This meta-analysis quantifies factors that alter pneumothorax rates, particularly with patient positioning, when planning and performing a CT-guided lung biopsy to reduce pneumothorax rates.

Advances in knowledge:

Positioning patients in lateral decubitus with the biopsied lung dependent, puncture site down with a biopsy window in the CT table, using smaller calibre needles and using coaxial technique if multiple samples are needed are associated with a reduced incidence of pneumothorax.
Κίνητρα και αντικίνητρα διεκδίκησης θέσης διοικητικής ευθύνης: Στάσεις και απόψεις των αιρετών της πρωτοβάθμιας εκπαίδευσης
Authors: Σπυριάδου Κωνσταντία , Κουτούζης Μανώλης
Published: December 2019

Το παρόν άρθρο επιχειρεί να αναδείξει τις απόψεις των αιρετών εκπροσώπων των εκπαιδευτικών σχετικά με τα κίνητρα και αντικίνητρα των εκπαιδευτικών ως προς τη διεκδίκηση διευθυντικής θέσης. Ειδικότερα, πραγματοποιήθηκε πρωτογενής ποιοτική έρευνα με τηλεφωνικές συνεντεύξεις σε 30 αιρετούς από τα 3 υπηρεσιακά συμβούλια πρωτοβάθμιας εκπαίδευσης, αλλά και τις 13 περιφερειακές διευθύνσεις εκπαίδευσης. Σύμφωνα με τα ερευνητικά ευρήματα, οι αιρετοί θεωρούν ότι οι εκπαιδευτικοί που διεκδικούν διευθυντική θέση έχουν κυρίως εξωτερικά κίνητρα όπως το επίδομα θέσης ευθύνης, τις μειωμένες ώρες διδασκαλίας και την κοινωνική αναγνώριση, παρά εσωτερικά κίνητρα, όπως την υλοποίηση  οράματος και την ανάπτυξη κοινωνικών και διοικητικών δεξιοτήτων. Συνεπώς, τα αναμενόμενα πλεονεκτήματα της διευθυντικής θέσης λειτουργούν ως κίνητρα που ενισχύουν την κατασκευή και εκδήλωση Ηγετικής Ταυτότητας. Κατά την άποψη των αιρετών, οι εκπαιδευτικοί που εσωτερικεύουν Ταυτότητα Ακόλουθου έχουν κυρίως εσωτερικά εμπόδια, καθώς προσπαθούν να προστατευθούν από τους κινδύνους που συνδέονται με τις διοικητικές ευθύνες.